SlideShare a Scribd company logo

Heart Disease in Women by M.D. Nanda, Navin C

•
•
L
Lucky Gods

🫀 Listen up, ladies! It's time to take charge of your heart health! Forget what you think you know about heart disease – this ain't just a "man's problem" anymore. ‍♀️ In "Heart Disease in Women: 1st Edition," Dr. Nanda, Navin C. cracks the code on women's unique cardiac risks and empowers you to fight for a healthy, vibrant life.

Healthcare
1 of 541
Download to read offline
🌟Welcome to Your Journey of Ultimate Wellness! 🌈💖 Thank you for choosing our ebook/magazine! 📘✨To enhance your health and beauty experience, we've curated some phenomenal products that promise to elevate your well-being. 🌺🌟 Skincare Saviors: Hydrossential - Unique Beauty Serum: 💦One Simple Way To Maintain A Flawless Skin. Link: https://mas.so/hydrossential Sun-Kissed Confidence: Totally Bangin' Tan by Turbo Babe: ☀️Go From “Pale Princess” to “Golden Goddess” with this Anti-Aging Sunless Tanning. Link: https://mas.so/bangin Hairraisingly Healthy: FoliPrime - The Natural Egyptian Hair Balm: 💆‍♀️Supports Hair Health. Link: https://mas.so/foliprime Men's Wellness Wonders: Endo Pump - Male Enhancement MONSTER: 💪U.S. Scientists Discover Secret For Stamina & Virility At Any Age. Link: https://mas.so/endopump African “Sex Monkeys” Unveil How To Reverse Erectile Dysfunction So You Can Have A Rock Hard Erection Again And Last At Least 30 Minute In Bed! (Note: Due to the potentially offensive language, I recommend considering revising this title and description.) Link: https://mas.so/edprotocol Conquer Health Concerns: MenoRescue: 🧘‍♀️Support healthy hormone levels with MenoRescue™. Formulated using the latest Ivy League research. Link: https://mas.so/menorescue GlucoFence - Blood Sugar Support: 🛡️#1 Most Hated By Big Pharma , Rogue Doctor Fixes Type 2 Diabetes. Link: https://mas.so/glucofence Bonus Goodies: NEW '23: Archangel Health Prayers for 400 Diseases, Weight Loss... Link: https://mas.so/archangels Natural Therapy With Killer VSL & Captivating Hook That Converts Like Crazy For Both Health & PD Niches! Powerful Therapy Based On Acupuncture. New Non- Invasive Alternative. To Electro-Acupuncture, Producing Astounding Results… Self- Application Is Easy, Rapid Response. Link: https://mas.so/naturaltherapy Every Morning This Ancient Amazonian “Drip Method” Is Being Used To Support Healthy Weight Loss. Link: https://mas.so/ignite The "Hidden Survival Muscle" In Your Body Missed By Modern Physicians That Keep Millions Of Men And Women Defeated By Pain, Frustrated With Belly Fat, And Struggling To Feel Energized Every Day… Link: https://mas.so/hipflexors Meditation - "InnaPeace Meditation Program" : The InnaPeace Program for Anxiety Sufferers, Discover why thousands are flocking to what experts are calling “the most advanced self-development method known to human kind”. Link: https://mas.so/innapeace Don't miss out on these amazing products! Click the links above and start your journey to a healthier, happier you! Don't let shortened links with mas.so send shivers down your spine! 🥶It's just a friendly URL shrinker, like a superhero packing superpowers into a tiny suit. 💪👀Fear not, visit https://mas.so and see what mas.so is. ✨Then, click with confidence and discover your favorite products! 🗺️Trust needs to be built on the first click. Thanks!💎
Heart Disease in Women
Heart Disease in Women Editors Navin C Nanda MD DSc(Hon) Distinguished Professor of Medicine and Cardiovascular Disease Division of Cardiovascular Disease and Director, Heart Station/Echocardiography Laboratories University of Alabama at Birmingham and the University of Alabama Health Services Foundation The Kirklin Clinic, Birmingham, Alabama, USA President, International Society of Cardiovascular Ultrasound Nurgül Keser MD Professor of Cardiology Sakarya University Medical Faculty Sakarya, Turkey Foreword Prof (Dr) Muzaffer Elmas New Delhi | London | Philadelphia | Panama The Health Sciences Publisher
Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd. 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 E-mail: jaypee@jaypeebrothers.com Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com Heart Disease in Women First Edition: 2015 ISBN: 978-93-5152-294-2 Printed at Overseas Offices J.P. Medical Ltd. 83, Victoria Street, London SW1H 0HW (UK) Phone: +44-20 3170 8910 Fax: +44(0)20 3008 6180 E-mail: info@jpmedpub.com Jaypee-Highlights Medical Publishers Inc. City of Knowledge, Bld. 237, Clayton Panama City, Panama Phone: +1 507-301-0496 Fax: +1 507-301-0499 E-mail: cservice@jphmedical.com Jaypee Medical Inc. The Bourse 111, South Independence Mall East Suite 835, Philadelphia, PA 19106, USA Phone: +1 267-519-9789 E-mail: jpmed.us@gmail.com Jaypee Brothers Medical Publishers (P) Ltd. 17/1-B, Babar Road, Block-B, Shaymali Mohammadpur, Dhaka-1207 Bangladesh Mobile: +08801912003485 E-mail: jaypeedhaka@gmail.com Jaypee Brothers Medical Publishers (P) Ltd. Bhotahity, Kathmandu, Nepal Phone: +977-9741283608 E-mail: kathmandu@jaypeebrothers.com Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2015, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photo­ copying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contra­ indications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity.
Dedicated to My late parents Balwant Rai Nanda MD and Mrs Maya Vati Nanda My wife Kanta Nanda MD Our children Nitin Nanda, Anita Nanda Wasan MD and Anil Nanda MD Their spouses Sanjeev Wasan MD and Seema Tailor Nanda, and our grandchildren Vinay and Rajesh Wasan, and Nayna and Ria Nanda Navin C Nanda MD DSc(Hon) My mother and father Zehra Keser and Mehmet Keser who made all things possible Nurgül Keser MD
Contributors Sahar S Abdelmoneim MBBCH MS MSc Cardiovascular Ultrasound Imaging and Hemodynamic Laboratory Mayo Clinic Rochester, Minnesota, USA Division of Cardiovascular Diseases Assiut University Assiut, Egypt Kul Aggarwal MD Professor of Clinical Medicine, University of Missouri Chief, Cardiology Section, Harry S Truman Veterans Hospital Columbia, Missouri, USA Michelle A Albert MD MPH Howard University College of Medicine and Division of Cardiovascular Medicine, Department of Medicine, Howard University Hospital Washington DC, USA Ezra A Amsterdam MD Distinguished Professor of Medicine Department of Internal Medicine Associate Chief (academic affairs) Division of Cardiovascular Medicine Master Clinician Educator University of California Davis Medical Center Sacramento, California, USA Zinzi Bailey MSPH Department of Social and Behavioral Sciences, Harvard School of Public Health Boston, Massachusetts, USA Kunal Bhagatwala MBBS University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Joseph R Biggio Jr MD Professor Director, Division of Maternal Fetal Medicine Medical Director, Obstetric Services University of Alabama at Birmingham Department of Obstetrics & Gynecology Birmingham, Alabama, USA Lori A Blauwet MD Assistant Professor of Medicine Division of Cardiovascular Diseases Mayo Clinic Rochester, Minnesota, USA Peter C Block MD FACC FSCAI Emory University Hospital Emory University School of Medicine Atlanta, Georgia, USA Uğur Canpolat MD Türkiye Yüksek İhtisas Training and Research Hospital Cardiology Clinic Ankara, Turkey Sibel Catirli Enar MD *Associate Professor of Cardiology Turkey Hospital/Memorial Hospital Istanbul, Turkey Kelli Chaviano DO Philadelphia College of Osteopathic Medicine Atlanta, Georgia, USA Reema Chugh MD FACC Cardiologist Specialist in Adult Congenital Heart Disease and Heart Disease in Pregnancy Department of Internal Medicine Kaiser Permanente Medical Center Panorama City, California, USA Anne B Curtis MD FACC FHRS FACP FAHA Charles and Mary Bauer Professor and Chair University at Buffalo Distinguished Professor Department of Medicine University at Buffalo Buffalo, New York, USA Mackram F Eleid MD Assistant Professor of Medicine Mayo Clinic College of Medicine Interventional Cardiology Fellow Mayo Clinic Rochester, Minnesota, USA Stephanie El-Hajj MD Department of Internal Medicine Louisiana State University Health Sciences Center, Baton Rouge Louisiana, USA Cevdet Erdöl MD Professor of Cardiology Member of the Grand National Assembly of Turkey Ankara, Turkey Keith C Ferdinand MD FACC FAHA Professor of Clinical Medicine Division of Cardiology Tulane University School of Medicine New Orleans, Louisiana, USA Charu Gandotra MD Assistant Professor Division of Cardiology Department of Internal Medicine Howard University Hospital Washington, DC, USA Gopal Ghimire MD DM MRCP University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA
viii Heart Disease in Women Fadi G Hage MD FASH FACC Division of Cardiovascular Diseases Department of Medicine University of Alabama at Birmingham Birmingham, Alabama, USA Rachel R Huxley DPhil School of Population Health University of Queensland Brisbane, Queensland, Australia Aryana Jacobs BA Howard University College of Medicine and Division of Cardiovascular Medicine Department of Medicine, Howard University Hospital Washington DC, USA Nidhi Karia MBBS University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Tugba Kemaloglu Oz MD University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Nese Keser MD Fatih Sultan Mehmet Research and Training Hospital Department of Neurosurgery Istanbul, Turkey Nurgül Keser MD Professor of Cardiology Sakarya University Medical Faculty Sakarya, Turkey Anant Kharod MD University of Alabama at Birmingham Department of Internal Medicine Birmingham, Alabama Jennifer Kiessling MD University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Juliana M Kling MD MPH Department of General Internal Medicine Mayo Clinic Scottsdale, Arizona, USA Anand Kulkarni MD FACC Robert Wood Johnson Physician Enterprise Somerset, New Jersey, USA Rachana Kulkarni MD FACC Medicor Cardiology and Chairman of Department of Medicine Somerset Medical Center Somerset, New Jersey, USA Rebecca D Levit MD Emory University School of Medicine Department of Medicine, Division of Cardiology Atlanta, Georgia, USA Rekha Mankad MD FACC Instructor of Medicine Mayo Clinic College of Medicine Mayo Clinic Rochester, Minnesota, USA Francesca Mantovani MD Division of Cardiovascular Diseases Cardiovascular Ultrasound Imaging and Hemodynamic Laboratory Mayo Clinic Rochester, Minnesota, USA Luis D Meggo Quiroz MD Third Post-graduate Year, Department of Internal Medicine University of Alabama at Birmingham Birmingham, Alabama USA Ankit Mehra MD Cardiovascular Fellow, University of Missouri and Harry S Truman Veterans Hospital, Columbia, Missouri, USA Virginia M Miller PhD Departments of Surgery and Physiology and Biomedical Engineering Mayo Clinic Rochester, Minnesota, USA Sobia Mujtaba MD Medical Resident Jacobi Medical Center Albert Einstein College of Medicine Bronx, New York, USA Sharon L Mulvagh MD FACC FAHA FASE     FRCP(C) Professor of Medicine Director Women’s Heart Clinic Mayo Clinic College of Medicine Mayo Clinic Rochester, Minnesota, USA Deepika Narasimha MD PGY-3, Internal Medicine Department of Medicine University at Buffalo Buffalo, New York, USA Chitra Narasimhan MD FICPC Assistant Professor of Clinical Pediatric Cardiology Sri Jayadeva Institute of Cardiovascular Sciences and Research Bengaluru, India Samar A Nasser PhD MPH PA-C Director of Research Partnership UM-Dearborn/Oakwood Healthcare Research Partnership The University of Michigan-Dearborn School of Education Dearborn, Michigan, USA Navin C Nanda MD DSc(Hon) Distinguished Professor of Medicine and Cardiovascular Disease Division of Cardiovascular Disease and Director, Heart Station/Echocardiography Laboratories University of Alabama at Birmingham and the University of Alabama Health Services Foundation, The Kirklin Clinic Birmingham, Alabama, USA President, International Society of Cardiovascular Ultrasound Sanne AE Peters PhD Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The Netherlands The George Institute for Global Health University of Sydney Sydney, Australia Ileana L Piña MD MPH Associate Chief of Academic Affairs Division of Cardiology Montefiore Medical Center Professor of Medicine Professor of Epidemiology and Population Health Albert Einstein College of Medicine Bronx, New York, USA
ix Contributors Amy West Pollak MD MS Department of Internal Medicine Division of Cardiovascular Diseases Women’s Heart Clinic Mayo Clinic, Rochester, Minnesota, USA Julie J Ramos MD Attending Cardiologist Montefiore Medical Center Assistant Professor of Clinical Medicine Albert Einstein College of Medicine Bronx, New York, USA Mary L Rosser MD PhD Assistant Professor and Attending Physician Department of Obstetrics and Gynecology and Women’s Health Albert Einstein College of Medicine Montefiore Medical Center Bronx, New York, USA Kumar Sanam MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA Anita Saxena MD DM FACC FAMS Department of Cardiology All India Institute of Medical Sciences New Delhi, India Anurag Singh MD Fellow, Electrophysiology Department of Cardiology Mount Sinai Medical Center New York, New York, USA Necati Sirmaci MD Professor of Cardiology Turkish Heart and Research Foundation Istanbul, Turkey Akila Subramaniam MD MPH Maternal-Fetal Medicine/ Medical Genetics Fellow University of Alabama at Birmingham Birmingham, Alabama, USA Aylin Sungur MD University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Manish Tandon MD Hartford Hospital Hartford, Connecticut, USA Suman Tandon MD Yale University School of Medicine New Haven, Connecticut, USA Cynthia C Taub MD Director, Non-Invasive Cardiology Einstein Division Montefiore Medical Center Associate Professor of Clinical Medicine Albert Einstein College of Medicine Bronx, New York, USA Jane S Titterington MD PhD Emory University School of Medicine Department of Medicine, Division of Cardiology Atlanta, Georgia, USA Lale Tokgozoglu MD FACC FESC Professor Department of Cardiology Hacettepe University Faculty of Medicine Ankara, Turkey Yvonne T van der Schouw PhD Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht, The Netherlands IB Vijayalakshmi MD DM FICC FIAMS        FIAE FICP FCSI FAMS DSc Professor of Pediatric Cardiology Sri Jayadeva Institute of Cardiovascular Sciences and Research Bengaluru, India Nanette K Wenger MD Emory University School of Medicine Department of Medicine, Division of Cardiology Atlanta, Georgia, USA Mark Woodward PhD The George Institute for Global Health University of Sydney Sydney, Australia Department of Epidemiology Johns Hopkins University Baltimore, Maryland, USA Victoria Zysek DO MBA Division of Cardiovascular Diseases Women’s Heart Clinic Mayo Clinic Rochester, Minnesota, USA
Foreword The Sakarya University, founded in 1970, has become a world class institution with several schools, institutes and as many as 14 centers performing research in various scientific fields. During the past few years, it has been recognized for "excellence" and has won several awards including the European Commission and National Quality Awards. Last year, it received the "sustainability in excellence" award as well as an award for innovations and supporting innovative studies. The University is also sensitive to national and international problems and issues and one of its missions is to collaborate actively with other international organizations towards solving them on a global scale. During the International Congress on Women and Health organized by the Sakarya University in Sakarya, Turkey in 2010 with Dr Nurgül Keser as the Director and Dr Navin C Nanda as the International Director, it became clear that there was a need to publish an up-to-date book on heart disease in women taking into account the fact there was hardly any book on this subject. On our recommendation, Dr Nanda and Dr Keser undertook this difficult task and have come up with a book that will emphasize and focus attention on various aspects of heart disease in women and how they are underdiagnosed and undertreated compared to men. This will increase awareness and may spur efforts by various government agencies to tackle these mostly unrecognized issues affecting women throughout the world. Our heartfelt thanks to Dr Nanda and all the national and international contributors of this book for taking time off from their busy schedule to collaborate on this very important project. Prof (Dr) Muzaffer Elmas President, Sakarya University Sakarya, Turkey
Preface Cardiovascular disease represents the most common cause of death in women in both developed and developing countries affecting high, middle and low income social strata. According to some data, more women die from cardiovascular disease than men. Despite these impressive statistics published by the World Health Organization, misperceptions are prevalent among both the lay public and medical professionals that cardiovascular disease is an uncommon entity in women. This unawareness coupled with the fact that women may present with atypical symptoms results in reduced surveillance, misdiagnosis or delayed diagnosis and consequently under treatment of cardiovascular disease, especially ischemic heart disease, in women. These issues were highlighted during an international conference on women and health organized by the Sakarya University and the International Society of Cardiovascular Ultrasound in Sakarya, Turkey in 2010. During this conference, it became clear to us that a book focusing on all aspects of heart disease in women could prove invaluable to medical and paramedical professionals given the paucity of such books on this subject. With this in mind we contacted several nationally and internationally renowned physicians, scientists and cardiologists who readily agreed to contribute and we are most grateful to them for sharing their expertise by writing excellent chapters for this book. This book consists of a total of 34 chapters organized into 8 sections. The first two chapters by Rachana and Anand Kulkarni deal in a succinct manner the myths and facts about cardiovascular disease in women and the important topic of cardiovascular disease prevention. Both modifiable and non-modifiable risk factors and guidelines for prevention are discussed, with special reference to women. The third chapter by Sanne Peters and associates emphasizes sex differences in the effects of leading and most prevalent risk factors in women. This is followed by a chapter on dyslipidemia by Lale Tokgozoglu from Ankara, Turkey. Gopal Ghimire in the next chapter discusses various aspects of familial hypercholesterolemia with special focus on women and highlights the guidelines proposed by the National Lipid Association.MetabolicsyndromeisnextcoveredbySibelCatirliEnarandcolleagues.Theepidemiology,pathophysiology and management of hypertension in women are elegantly summarized by Keith Ferdinand and Samar Nasser in the following chapter (Chapter 7). They also cover the important topics of resistant and refractory hypertension. Cardiac and non-cardiac causes of stroke in women are detailed in the next chapter by Nese Keser from Istanbul, Turkey. The relationship of oral contraceptive pills and hormone replacement therapy to stroke as well as risk factors for stroke during pregnancy are also discussed. Professors Nurgül Keser and Cevdet Erdöl in the next chapter discuss the deleterious effects of smoking in women, especially younger women in whom the prevalence of smoking is alarmingly increasing in many parts of the world. A special mention is made of the increasing use of waterpipe tobacco smoking in several countries of Europe and the Middle East. Measures taken by government agencies to curb smoking are also mentioned. Job stress, strain, burnout, unemployment and biomarkers and their relationship to some of these factors are delineated in Chapter 10 by Aryanna Jacobs and colleagues. The following chapter by Mackram Eleid and associates from the Mayo Clinic in Rochester describe the role of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid antibody syndrome in atherosclerotic plaque formation in the next chapter. The last chapter in this section by Juliana Kling and associates is also from the Mayo Clinic and explains the effect of pregnancy and menopause on cardiovascular function and points to the controversial relationship of menopausal hormone therapy to progression of cardiovascular disease. The second section of the book pertains to with coronary heart disease. The first chapter by Ezra Amsterdam provides a perspective and overview of coronary heart disease in women. The second chapter (Chapter 14) by Kumar Sanam and colleagues outlines the approach to assessment of chest pain in a woman presenting to the Emergency Department. The clinical presentation, diagnostic testing, the use of biomarkers and differential diagnosis are given in detail. The third chapter, from the group of Nanette Wenger, a renowned expert in heart disease in women, details all aspects of stable ischemic heart disease in women including pathophysiology of gender differences in women, different terminologies used, the scope of the burden, challenges in diagnosis and treatment strategies. The last chapter in this section, by Ankit Mehra and Kul Aggarwal, explains different aspects of acute coronary syndromes including the pathophysiology of
xiv Heart Disease in Women atherosclerotic plaque rupture and erosion and different modalities of treatment with special reference to management in a pregnant woman. Section 3 of the book deals with noninvasive testing. Jennifer Kiessling and colleagues from the University of Alabama at Birmingham outline the use of echocardiography in the diagnosis of various acquired and congenital structural heart lesions in women. In particular, the use of stress echocardiography in the assessment of coronary artery disease is highlighted. Echocardiography in the pregnant woman and its usefulness in the assessment and management of fetal cardiac anomalies are also delineated. The next chapter in this section (Chapter 18) by Francesca Mantovani and associates outline factors affecting the accuracy of diagnostic testing in women and the advantages and disadvantages of various modalities used for noninvasive stress testing including contrast stress echocardiography. The last chapter in this section by Suman and Manish Tandon focuses in detail on the use of radionuclide stress imaging techniques in the evaluation of ischemic heart disease. Radiation considerations are also mentioned. The fourth section of this book relates to heart failure, cardiomyopathy and pericarditis in women. Cynthia Taub and colleagues from Ileana Piña’s group provide a comprehensive review of the etiology, pathophysiology, diagnostic assessment and management issues of heart failure in women in the first chapter of this section. Heart failure in pregnancy is also covered. In the next chapter (Chapter 21), Anant Kharod reviews myocarditis and pericarditis with particular emphasis in women. The etiology, clinical manifestations, diagnosis and treatment options are discussed. The last chapter of this section by Keli Chaviano and colleagues covers all aspects of Takotsubo cardiomyopathy which is characteristically seen in postmenopausal women. Section 5 of the book deals with arrhythmias in women. Deepika Narasimha and Anne Curtis describe in great detail sex-based differences in the epidemiology, prevalence, clinical manifestation, and management of various types of arrhythmias including atrial fibrillation and ventricular tachycardia. This chapter is followed by another one (Chapter 24) by Anurag Singh which specifically discusses ventricular arrhythmias and sudden death in women. The next section (Section 6) consists of chapters on rheumatic heart disease and valvular heart disease in women. The first chapter by Anita Saxsena from New Delhi, India, highlights the problem of rheumatic heart disease in the developing countries and the fact that rheumatic mitral stenosis is much more prevalent in women than men. Various sequele of rheumatic heart disease including its management in pregnancy are given in this chapter. The next chapter by Vijayalakshmi and Chitra Narasimhan provide a detailed review of valvular heart disease in women and this is supplemented by a large number of illustrations depicting various pathological findings. Prosthetic valves are also covered in this chapter. The last chapter in this section (Chapter 27) by Peter Block deals with gender differences in the outcome of the relatively recently developed technique of transcatheter aortic valve replacement. Section 7 of the book describes heart diseases in pregnancy and congenital cardiac lesions frequently seen in women. The first chapter by Akila Subramaniam and Joseph Biggio mentions various physiological changes in the cardiovascular system that occur during pregnancy as well as evaluation and management of acquired and congenital cardiac diseases during pregnancy. A different perspective on the same subject is provided by Reema Chugh in the next chapter (Chapter 29). Next, Lori Blauwet elegantly discusses all aspects of the important topic of peripartum cardiomyopathy. The last chapter in this section, also by Reema Chugh, deals with congenital heart lesions in women. It represents a detailed review of issues pertaining to acyanotic and cyanotic women with congenital heart disease. The last section (Section 8) of the book covers miscellaneous topics. Peripheral arterial disease in women is reviewed by Amy Pollak and Sharon Mulvagh. Diagnostic testing including the use of ankle-brachial index, gender differences in its values and guidelines used in the management are provided in this chapter. Charu Gandotra, in the next chapter, discusses cardiovascular implications of cancer in women. He focusses on commonly used chemotherapeutic agents with potential for cardiac toxicity and various strategies employed for its identification and management. The last chapter of this section and book (Chapter 34) by Stephanie El-Hajj, Navin C Nanda and Fadi G Hage provides a summary of recently published literature on heart disease in women. Because of the large number of contributors, some overlap of content and chapters is inevitable and does exist in the book. However, deliberately, no attempt was made by us to correct this as it was felt that some of it could provide a different perspective to the reader and would serve to reinforce important concepts and issues in the assessment of heart disease in women. Navin C Nanda Nurgül Keser
AsmentionedinthePreface,wearemostgratefultoallthecontributorswhoprovidedexcellentchaptersforthisbook. We also appreciate the encouragement provided by the Sakarya University and the International Society of Cardiovascular Ultrasound in the preparation of this book. Special thanks to Shree Jitendar P Vij, CEO and Group Chairman of Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India and Mr Ankit Vij (Managing Director) for their help in publishing this book and all their associates especially Ms Chetna Malhotra Vohra (Senior Manager–Business Development) and Ms Saima Rashid (Development Editor). We also deeply appreciate the help of Lindy Chapman (Administrative Associate) and Kanta Nanda. Acknowledgments
Contents Section 1: Prevention and Risk Factors 1. Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic 3 Rachana Kulkarni, Anand Kulkarni 2. Prevention of Heart Disease in Women 10 Rachana Kulkarni, Anand Kulkarni • • Unmodifiable Risk Factors 10 • • Modifiable Risk Factors 11 • • Lifestyle Risk Factors 12 • • Guidelines for Prevention of CVD in Women 12 3. Sex Differences in the Effects of Leading and Most Prevalent Modifiable Risk Factors 17 Sanne AE Peters, Yvonne T van der Schouw, Mark Woodward, Rachel R Huxley 4. Dyslipidemia in Women 30 Lale Tokgozoglu, Uğur Canpolat • • Evaluation and Treatment of Women with Hyperlipidemia 30 • • Management of Dyslipidemia in Women: Translating Evidence from Clinical Trials into Practice 30 • • Management 33 5. Familial Hypercholesterolemia in Women: Its Identification and Management 36 Gopal Ghimire, Navin C Nanda • • Identification of FH 37 • • Management of FH 40 6. Cardiovascular Dysfunction in Women with Metabolic Syndrome 47 Sibel Catirli Enar, Anant Kharod, Navin C Nanda • • Prevalence of Metabolic Syndrome 47 • • Metabolic Syndrome in Coronary Artery Disease and Acute Coronary Syndrome 48 • • Congestive Heart Failure 48 • • Left Ventricular Dysfunction 48 • • Diastolic Dysfunction 48 • • Right Ventricular Dysfunction 49 • • Left Atrial Dysfunction 49 • • Atrial Flutter and Fibrillation 49 • • Carotid Atherosclerosis 49 • • Endothelial Dysfunction 50 • • Hypertension 50
xviii Heart Disease in Women • • Hypothyroidism 51 • • Polycystic Ovarian Syndrome 51 • • Obstructive Sleep Apnea 51 7. Hypertension in Women 57 Keith C Ferdinand, Samar A Nasser • • Epidemiology Hypertension: Focus on Women 57 • • Pathophysiology of Hypertension in Women 57 • • Dietary Considerations 58 • • Pharmacotherapy of Hypertension in Women 59 • • Current Aspects of Resistant Hypertension: Definitions, Prevalence, and Outcomes 60 • • Recognition of Refractory Hypertension: A Newer Concept and Call-to-Action 61 8. Stroke and Women 64 Nese Keser, Necati Sirmaci, Luis D Meggo Quiroz, Navin C Nanda • • Hormonal Effects 64 • • Pregnancy and Stroke 65 • • Oral Contraceptive Pills and Hormone Replacement Therapy 66 • • Prevention of Stroke in Women 66 • • Coronary Artery Disease and Aspirin 66 • • Atrial Fibrillation and Stroke 66 9. Women and Smoking 70 Nurgül Keser, Cevdet Erdöl, Luis D Meggo Quiroz, Navin C Nanda • • Smoking: A Global Burden 70 • • Pathophysiology 70 • • Gender and Age Differences 71 • • Clinical Implications 71 • • Associated Exposures 72 • • Public Policy 72 10. Job Burnout, Job Strain (Stress), and Cardiovascular Disease: Selected Review 75 Aryana Jacobs, Zinzi Bailey, Michelle A Albert • • Common Theoretical Frameworks and Definitions Related to Job Stress and Job Burnout 75 • • Job Burnout and CVD Studies 76 • • Job Strain and CVD 77 • • Influence of Psychological Status and Social Support on Job Strain and CVD Risk 78 • • Unemployment and CVD Outcomes 78 • • Job Strain and Select CVD Risk Equivalents 79 11. Atherosclerosis and Autoimmune Disease: Mechanisms and Emerging Treatments 83 Mackram F Eleid, Sharon L Mulvagh, Rekha Mankad 12. Hormonal Transitions and the Cardiovascular System in Women 93 Juliana M Kling, Virginia M Miller, Sharon L Mulvagh • • Regulatory Mechanisms Contributing to Sex Differences in Cardiovascular Physiology 93 • • Sex-Specific Conditions Affecting Cardiovascular Disease in Women 94
xix Contents • • Guidelines and Recommendations 96 • • Phenotypic Expression of Cardiovascular Disease in Women 96 Section 2: Coronary Heart Disease 13. A Perspective on Women and Coronary Heart Disease 105 Ezra A Amsterdam • • Epidemiology 105 • • Management 105 • • Risk Factors for CHD 106 • • Clinical Presentation 106 • • Stress Testing 107 • • Pathophysiology of Myocardial Ischemia 107 14. Chest Pain Evaluation in Women Presenting to the Emergency Department 110 Kumar Sanam, Kelli Chaviano, Navin C Nanda • • Clinical Presentation 110 • • Diagnostic Tests 111 • • Imaging Studies 113 • • Differential Diagnosis 116 15. Stable Ischemic Heart Disease in Women 118 Rebecca D Levit, Jane S Titterington, Nanette K Wenger • • Pathophysiology of Gender Differences in Stable Ischemic Heart Disease 118 • • Terminology 120 • • Epidemiology—Scope of the Problem 120 • • Diagnostic Testing for SIHD 121 • • Treatment of SIHD 122 • • Burden of Angina 128 16. Acute Coronary Syndromes in Women 134 Ankit Mehra, Kul Aggarwal • • Pathophysiology 137 • • Plaque Disruption 137 • • Clinical Presentation 139 • • Management 139 • • Treatment 140 • • Antiplatelet Agents 140 • • Fibrinolytic Therapy 142 • • Anticoagulants 142 • • Oral Medications 143 • • Coronary Angiography and PCI 143 • • Outcomes 144 • • Pregnancy and ACS 145 • • Conditions Mimicking ACS 146 • • Spontaneous Coronary Artery Dissection 146 • • Aortic Dissection 147 • • Pulmonary Embolism 148
xx Heart Disease in Women Section 3: Noninvasive Testing 17. Echocardiography in Women 155 Jennifer Kiessling, Nurgül Keser, Navin C Nanda, Tugba Kemaloglu Oz, Aylin Sungur, Kunal Bhagatwala, Nidhi Karia • • Ischemic Heart Disease/Stress Echocardiography/Polycystic Ovarian Syndrome 155 • • Takotsubo Cardiomyopathy 160 • • Echocardiography in Pregnancy, Peripartum Cardiomyopathy, and Fetal Echocardiography 162 • • Congenital Heart Disease 168 • • Pulmonary Hypertension 170 • • Structural Heart Disease: MVP, Mitral Stenosis, and Mitral Annular Calcification 170 • • Differences in Echocardiographic Measurements and Technical Considerations 176 • • Other Echo Examples of Pathological Conditions Seen in Women 181 18. Noninvasive Stress Testing in Women 192 Francesca Mantovani, Sahar S Abdelmoneim, Victoria Zysek, Sharon L Mulvagh • • Exercise Electrocardiography 193 • • Imaging Techniques during Stress Testing 195 • • Stress Echocardiography 195 • • Stress Gated Myocardial Perfusion SPECT 199 • • Cardiac PET 199 • • MPI vs SE 200 • • Emerging Stress Test Imaging Modalities in Women with Suspected Coronary Artery Disease: MRI 200 • • Recommendations for Noninvasive Testing in Women with Suspected Coronary Artery Disease 200 19. Stress Myocardial Perfusion Imaging—Diagnosis and Risk Assessment in Women 206 Suman Tandon, Manish Tandon • • Evaluating Clinical Risk 206 • • Exercise Treadmill Test in the Diagnosis and Risk Assessment of Suspected CAD 207 • • SPECT Myocardial Perfusion Imaging 209 • • PET Myocardial Perfusion Imaging 211 • • Flow Quantification with PET 212 • • Radiation Considerations 213 Section 4: Heart Failure. Cardiomyopathy. Pericarditis 20. Women and Heart Failure 221 Cynthia C Taub, Julie J Ramos, Mary L Rosser, Sobia Mujtaba, Ileana L Piña • • Sex Differences in the Manifestation and Outcome of Cardiovascular Disease: Experimental Evidence from Animal Models 222 • • Conditions that Contribute to Heart Failure 223 • • Assessment of Heart Failure 228 • • Management of Heart Failure 229 • • Transition of Care 240 • • Implications from Clinical Trials 241
xxi Contents 21. Myocarditis and Pericarditis in Women 252 Anant Kharod, Navin C Nanda • • Defining Sex and Gender 252 • • History And Epidemiology of Myocarditis 252 • • Sex Differences in Normal Cardiac Physiology 253 • • Sex Hormones and the Immune System 254 • • Myocarditis, What We Know 254 • • Clinical Manifestations, Diagnosis, and Treatment 255 • • Pericarditis in Women 257 • • Pericarditis: Symptoms and Diagnosis 257 • • Pericarditis: Treatment 257 22. Takotsubo Cardiomyopathy in Women 262 Kelli Chaviano, Kumar Sanam, Navin C Nanda • • Variants 262 • • Epidemiology 263 • • Etiology 263 • • Precipitating Events and Risks 264 • • Presentation 265 • • Diagnosis 265 • • Treatment 266 • • Prognosis 266 Section 5: Arrhythmias 23. Arrhythmias and Implantable Devices in Women 271 Deepika Narasimha, Anne B Curtis • • Cardiac Electrophysiology 271 • • Diagnostic Testing 272 • • Specific Arrhythmias 273 • • Pharmacotherapy 280 • • Implantable Device Therapy 281 • • Arrhythmias in Pregnancy 283 24. Ventricular Arrhythmia in Women 288 Anurag Singh, Navin C Nanda • • Gender Differences in Mechanism of Ventricular Arrhythmias 289 • • Coronary Artery Disease 289 • • Dilated Cardiomyopathy 289 • • Long QT Syndromes 289 • • Hypertrophic Cardiomyopathy 290 • • Arrhythmogenic Right Ventricular Cardiomyopathy 290 • • Brugada Syndrome 291 • • Catecholaminergic Polymorphic Ventricular Tachycardia 291 • • Idiopathic Ventricular Tachycardia 291 • • Special Considerations in Management of Female Patients 291
xxii Heart Disease in Women Section 6:Valvular Heart Disease 25. Rheumatic Heart Disease in Women 295 Anita Saxena • • Burden of the Disease 295 • • Gender Differences 295 • • Etiopathogenesis 296 • • Clinical Features 296 • • Mitral Stenosis 296 • • Mitral Regurgitation 297 • • Aortic Regurgitation 297 • • Aortic Stenosis 298 • • Tricuspid Valve Disease 298 • • Multivalvular Disease 298 • • Diagnostic Evaluation 298 • • Echocardiography in Rheumatic Heart Disease 300 • • Cardiac Catheterization 305 • • Management of Women with Rheumatic Heart Disease 305 • • Gender and Prognosis 306 • • Pregnancy and Rheumatic Heart Disease 306 • • Risk Assessment 307 • • General Principles of Management 307 • • Pregnancy with Mitral Stenosis 307 • • Other Valvular Lesions during Pregnancy 308 • • Pregnancy with Prosthetic Heart Valves 308 26. Native Valvular Heart Disease in Women 311 IB Vijayalakshmi, Chitra Narasimhan • • Mitral Stenosis 312 • • Mitral Regurgitation 316 • • Aortic Stenosis 318 • • Aortic Regurgitation 323 • • Tricuspid Stenosis 324 • • Tricuspid Regurgitation 325 • • Pulmonic Stenosis 326 • • Pulmonic Regurgitation 326 • • VHD in Pregnancy 326 • • General Management of Women with VHD 329 • • Infective Endocarditis 337 27. Gender Differences in Outcomes after Transcatheter Aortic Valve Replacement 344 Peter C Block • • Gender Differences in Cardiac Surgery 344 • • Transcatheter Aortic Valve Replacement 344 • • Possible Mechanisms 346
xxiii Contents Section 7: Pregnancy. Congenital Heart Disease 28. Pregnancy and Heart Disease 351 Akila Subramaniam, Joseph R Biggio • • Physiologic Changes in the Cardiovascular System during Pregnancy 351 • • General Evaluation and Management of Cardiac Disease in Pregnancy 352 • • Congenital Heart Disease 355 • • Pulmonary Hypertension 357 • • Valvular Heart Disease 357 • • Cardiomyopathy 358 • • Idiopathic Hypertrophic Cardiomyopathy 359 • • Ischemic Heart Disease and Coronary Artery Disease 359 • • Cardiac Transplantation 360 • • Arrhythmia 360 • • Genetic Causes of Cardiovascular Disease 360 • • Infective Endocarditis and Prophylaxis in Pregnancy 361 • • Artificial Heart Valves and Pregnancy 361 29. Management of Heart Disease in Pregnancy: A Clinician's Approach 368 Reema Chugh • • Common Cardiovascular Management Issues in Pregnancy 369 • • Hypertension in Pregnancy 369 • • Deep Venous Thrombosis 372 • • Anticoagulation 373 • • Endocarditis 374 • • Heart Failure 374 • • Arrhythmias 379 • • Aortic Root Dilation 387 • • Pulmonary Hypertension 389 • • Common Heart Diseases/Defects during Pregnancy 390 • • Valvular Heart Disease 391 • • Coronary Artery Disease 393 • • Cardiac Surgery in Pregnancy 396 • • Cardiopulmonary Resuscitation in Pregnancy 397 • • Preconception Assessment and Counseling 397 • • Maternal Risk Assessment 397 • • Fetal Risk Assessment 398 • • Antenatal Cardiac Assessment and Management 398 • • Labor and Delivery 400 30. Peripartum Cardiomyopathy 407 Lori A Blauwet • • Epidemiology 407 • • Risk Factors 408 • • Genetics 408
xxiv Heart Disease in Women • • Proposed Etiologies and Pathophysiological Mechanisms 409 • • Clinical Presentation 410 • • Diagnosis 412 • • Natural History 414 • • Treatment 414 • • Labor and Delivery 419 • • Breastfeeding 420 • • Contraception 420 • • Prognosis 420 • • Subsequent Pregnancy 421 31. Congenital Heart Disease in Women 427 Reema Chugh • • Transitional Issues in Females with CHD 427 • • Medical Records 428 • • Gynecological Health and Contraception in Women with CHD 429 • • Pregnancy in CHD 430 • • Common Medical Issues in CHD 430 • • Exercise Counseling 430 • • Congenital Heart Defects 430 • • Shunt Lesions 431 • • Congenital Valvular Heart Defects 438 • • Complex Congenital Heart Defects 450 • • Cyanotic Congenital Heart Disease 465 Section 8: Miscellaneous 32. Peripheral Arterial Disease in Women: The Unmet Challenge 479 Amy West Pollak, Sharon L Mulvagh • • How is Peripheral Arterial Disease Diagnosed? 479 • • Who Should Be Screened for PAD with an ABI? 479 • • Cardiovascular Risk Factor Modification in PAD 480 • • Treatment of Symptomatic PAD 481 • • Is There a Sex-Based Difference in the Burden of PAD? 481 • • Why are Sex-Based Differences Important? 482 • • What are the Critical Steps Needed to Raise Awareness about PAD in Women? 482 33. Cardiovascular Implications of Cancer in Women 485 Charu Gandotra • • Incidence and Mortality of Cancer in Women 485 • • Disparities in Cancer Epidemiology 485 • • Common Risk Factors for Cancer and Cardiovascular Disease 485 • • Cancer Chemotherapy Cardiotoxicity: Spectrum of Cardiovascular Effects 487 • • Breast Cancer Chemotherapy 488 • • Colorectal Cancer Chemotherapy 491 • • Lung Cancer 492 • • Thoracic Radiation Therapy 492
xxv Contents • • Monitoring and Diagnosis of Chemotherapy-Induced Cardiotoxicity 493 • • Prevention and Treatment of Chemotherapy-Related Cardiotoxicity 494 • • Cancer Survivors 494 34. Heart Disease in Women: An Update on Recently Published Literature 499 Stephanie El-Hajj, Navin C Nanda, Fadi G Hage • • Risk Factors 499 • • Pregnancy 503 • • Awareness 503 • • Symptoms 503 • • Stress Testing 504 • • Noninvasive Management 505 • • Invasive Management 506 Index 515
1 S E C T I O N Prevention and Risk Factors
Rachana Kulkarni, Anand Kulkarni Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic 1 C H A P T E R INTRODUCTION Cardiovascular disease (CVD), particularly, ischemic heart disease, is the leading cause of death among women in the United States and around the globe. As the average life span is increasing in the developed countries, so is the prevalence of heart disease. In the United States, because of an aging population, the absolute number of deaths due to CVD in women is actually increasing.1 As the risk of CVD increases linearly with age, CVD is the leading cause of hospital admissions as well, and has significant financial implications. Because of the sheer magnitude of this problem, there is a need for increased awareness of the importance of CVD as a major public health issue for women across the world. Let us start by examining some statistics about heart disease in women in the United States. Each year on an average 43 million American women are affected by heart disease. It roughly translates into heart disease killing one woman per minute. Center for Disease Control (CDC) data indicate that heart disease is the leading cause of death among women in the United States, killing 292,188 women in 2009—i.e. one in every four female deaths. Since the last scientific statement on this topic in 1993, when the gender gap in various aspects of CVD was brought to light, a lot of attention has been given to a better appreciation of the influence of gender on heart disease and its management. In spite of that effort, however, important gaps in knowledge remain. Heart disease in women presents a decade later as compared with men. But as women have a higher likeli­ hood to survive longer, the death rates in women due to CVD tends to be equal or higher as compared with the men.1 Also, as indicated by the Framingham Heart study, two- thirds of the women who had sudden cardiac death had no previous symptoms. Since majority of the women never make it to the hospital, presumably because of the lack of awareness of their heart symptoms, raising awareness of heart disease in women and directing the focus on primary prevention seem to be the best approach. Cardiovascular disease has been the leading cause of death among women worldwide. It has been shown very well in the data presented by World Health Organization (WHO) in 2011. The organization studied the 10 leading causes of death among women in the countries with different income levels. The results are outlined below (Figs. 1A to E). It is evident from the above-mentioned data that heart disease is the leading cause of death in women around the globe, regardless of the level of income. Because of the worldwide extent of this health problem and its implications on the world health economics, in 2010, the WHO launched a worldwide effort to draw urgent attention to the number one killer for women. WHO Assis­ tant Director-General Dr. Catherine Le Gales-Camus poin­ ted out that. “Although most women fear cancer, particularly breast cancer, they do not make the same efforts to safeguard themselves from heart disease, which is eminently preven­ table.” As Dr. Le Gales-Camus has stated, heart disease is the most common cause of fatality in women everywhere. However, in spite of clear evidence, most women still con­ sider breast cancer as their number one threat. We, as physicians, know that the anatomy and physio­ logy of the heart is the same in men and women. Then, we wonder, why would there be a difference in heart disease
4 Section 1 Prevention and Risk Factors Figs. 1A to E: WHO Media center—Women’s health, Fact Sheet N0 334, September 2013, Data source for charts: Cause specific mortality: regional estimates for 2000-2011. A C E B D in men and women at every step from the diagnosis to prognosis. The differences in heart disease in men and women are due to the differences in the perception and presentation of the disease which then leads to the differences in the treatment and follow ups. These in turn ultimately result in the differences in prognosis and survival. Let us examine some of the common myths that women and communities harbor about heart disease. Myth—Heart disease is a man’s disease.
5 Chapter 1 Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic Fact—Heart disease kills more women than men. Since 1984, each year more women have died of heart disease than men (Fig. 2). Since 1984, women have outnumbered men in cardio­ vascular mortality, and the gap continues to widen each year. Yet only one in five women thinks that heart disease is a real threat to them.1 Despite increased awareness over the past decade, only 54% of women recognize that heart disease is their number one killer2 (Fig. 3). Myth—Breast cancer kills more women than heart disease. Fact—Most women perceive breast cancer as their biggest threat and are diligent about their yearly breast examination and mammograms. However, the fact is that heartdiseasekillsmorewomenthanallcancerscombined. Studies show that on an average one in 25 women will die of cancer and one in two women will die of heart disease.1 Myth—Heart disease is a disease of old men. Fact—Increased incidence of smoking and use of birth control pills have increased the incidence of heart disease in women under 55 years of age. More than 50% of myocardial infarction (MI) in women is attributable to smoking. Althoughtheprevalenceofsmokinghasbeendeclining in the United States, the rate of smoking cessation is lower in women than men;1 and after 2000, smoking rates have been higher in women (23%) than men (20%).3 The increased prevalence of smoking and the increas­ ing trend of smoking particularly in young women have definitely contributed to the higher rates of CVD and cardiac deaths in women. Deaths of young women have significant implications on the families and economics alike. Smoking also increases their risk for hypertension. A Norwegian study conducted by Meyer et al.4 demons­ trated that smoking significantly increases cardiovascular and stroke risks in all the age groups in the 54,000 patients studied over three decades. However, it also showed that women who smoked had a higher incidence of cardio­ vascular mortality and morbidity as compared with the men who smoked.4 The longitudinal study showed that two-thirds of the men who smoked had CVD, whereas half of the women who smoked suffered with cardiovascular disease (Fig. 4). Another variable known to have increased the risk of heart disease in women is the lack of physical activity leading to the increased incidence of obesity. The preva­ lence of obesity has increased steadily in women over the last two decades; and according to the 2007 estimates from the National Center for Health Statistics of the Center for Disease Control and Prevention, 60% of the adult women in the United States are overweight. Just over one-thirds of the overweight adult women are obese.5 In the last decade, approximately 34 million American women are classified as obese. Obesity, particularly abdominal obesity, is an important risk factor for CVD in women.6,7 The figure below (Fig. 5) illustrates the CDC data on obesity trends among the adults in the United States in 2011–2012.8 Age-adjusted prevalence of obesity, by sex and age group, among adults at the age of 20 years and over: United States, 2011–2012. Fig. 2: AHA Statistical Update. Heart Disease and Stroke Statis- tics—2011 Update. A Report from the AHA. Circulation. 2011;123: 4e18-e209. Source: Adapted from Rosamond 2008 and Roger 2011. Fig. 3: National Center of Heart Statistics and the American Heart Association. Mosca et al. Circulation. 1997;96:2468-2482.
6 Section 1 Prevention and Risk Factors Increased prevalence of obesity has translated into increased risk of type two diabetes, which then increases the risk of heart disease, several folds.9 Diabetes is asso­ ciated with a threefold to sevenfold elevation in coronary heart disease risk among women, compared with a twofold to threefold elevation among men; this gender-based difference may be because of a particularly deleterious effect of diabetes on lipids and blood pressure in women.5 Approximately 50% of the deaths in patients with type two diabetes is usually due to ischemic heart disease.10 In addition to the above-mentioned misperceptions, the symptoms of heart disease in women could be atypical. In addition to the traditional symptom of chest pain, women present with shortness of breath as a common presenting symptom. Other common symptoms are jaw or shoulder pain, dizziness, nausea, unexplained fatigue, or flu like symptoms.11 Obviously these symptoms are vague and so a lot of women tend to ignore them and do not seek medical attention. Because of the ambiguous and atypical nature of the symptoms, they are likely to be ignored by the healthcare professionals as well. So, it comes as no surprise that the Framingham Heart Study revealed that two-thirds of the sudden cardiac deaths occurred in women with no “known” previous symptoms as compared with only half of the sudden deaths in men.1 The 2012 statistical report from the American Heart Association (AHA) confirms the same finding.12 As for physicians, most of our practice guidelines and textbooks use data obtained in major clinical trials. Since women were involved in less than 25% of clinical trials, the data derived from them comprised of symptoms mostly of men, which then became the basis of traditional medical teaching and practice guidelines. As a result of that, physicians also did not identify and associate the above- mentioned symptoms with heart disease. This gap in acknowledging symptoms of heart disease by patients and physicians has led to delays in diagnosis and seeking and delivering care by patients and physicians alike. So, it is no wonder that more women than men have cardiac arrest as their presenting symptom. It may explain why treatment is less likely to reduce death rate in women as most of them never reach a hospital.13 However, a recent review of literature about the evaluation of chest pain in women suggests that it is advisable to stratify patients in low-, intermediate-, and high-risk categories based on their cardiovascular risk factors, which will then guide the physician to seek appropriate diagnostic measures in a cost-effective manner.14 The 2011 updated effectiveness- based guidelines for primary and secondary prevention of CVD in women provide a very helpful algorithm for the workup to evaluate cardiovascular risk in women. This flow diagram is illustrated in the chapter by the same authors about the prevention of heart disease in women.15 Fig. 4: Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med. 2000 Jul 6;343(1):16-22. Source: Adapted from Stampfer 2000. Fig. 5: CDC data—Age-adjusted prevalence of obesity, by sex and age group, among adults aged 20 and over: United States, 2011-2012. 1 Crude estimate 35.1%. 2 Significant difference from the age of 20 to 39 years. 3 Significant difference from the age of 40 to 59 years. Note: Estimates are age adjusted for all adults of the age 20 years and over by the direct method to the 2000 U.S. census population using the age groups 20–39, 40–59, and 60 and over. Source: CDC/NCHS, National Health and Nutrition Examination Survey, 2011–2012.
7 Chapter 1 Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic Heart disease in women presents a decade later as compared with men. As a result, women have more com­ orbidities such as hypertension, diabetes, and hyper­ lipidemia among others. This puts them at a higher risk for having a more complex clinical picture at the time of presentation and makes them more likely to have com­ plications. Sometimes, the advanced and diffuse nature of the disease at presentation can limit the treatment options for the physicians. The NIH study performed in 2012 shows a clear gender gap in the treatment of heart disease. The study indicates that for a variety of reasons women get less invasive treatment as compared with men.16 They are less likely to be offered with less-invasive therapy, and when offered, they are also more likely to decline the invasive treatment. If they undergo invasive procedures, they are more likely to have complications. After cardiac surgery, they are less likely to opt for rehab and are less likely to follow up. These findings were almost replicated in a French study by Leurent17 of the Centre Hospitalier Universitaire in Rennes, France. Compared with men, women had a significantly higher rate of intrahospital mortality from MI at 9% versus 4.4% (P <0.0001). The study further identified the lack of timely aggressive treatment in women. Women also had a significantly longer median delay between onset of MI symptoms and calling for medical assistance (60 versus 44 min, P <0.0001). Female patients also had significantly more STEMI (S-T elevation myocardial infarc­ tion) complications than men, including atrial fibrillation (7% versus 3%, P <0.0001). Leurent et al.17 also found that women were less likely to be discharged on recommended therapies than men:17 • Aspirin: 95% versus 98%, P <0.0001 • Clopidogrel/prasugrel: 93% versus 95%, P <0.0001 • Beta-blockers: 88% versus 91%, P = 0.001 • Angiotensin converting enzyme (ACE) inhibitors: 62% versus 67%, P <0.0001 • Statins: 89% versus 95%, P <0.0001 • Cardiovascular rehabilitation: 27% versus 47%, P <0.0001. All of these factors translate into worse prognosis for women. They have higher fatality rate than men with the first MI. It is very interesting to see how the gender gap continues through the course. In the Framingham study and the more recent Multicenter Investigation of the limitation of Infarct Size study, women have been shown to have higher in-house mortality rate (13%) as compared with men (7%). By the first year after MI, the mortality was 44% in women as compared with 23% in men. By the second year, the gap continues, as mortality in women was 36% as compared with 21% in men.18 Women were also more likely to have subsequent cardiac events as compared with men.19 The data from the Myocardial Infarction Triage and Intervention registry also indicate that the gender gap in mortality in patients presenting with acute MI can be attributable to women receiving less-acute coro­ nary interventions.20,21 Similar findings were noted in a community study—Atherosclerotic Risk in Communities study.22 A national survey shows that women are also less likely to enrol in cardiac rehabilitation after MI (6.9% versus 13.3%) and coronary artery bypass surgery (20.2% versus 24.6%) than men.23 In addition to lower attendance rate, dropout rates from cardiac rehabilitation are also higher in women than men.24 World Health Organization and the Indian Council of Medical Research collaborated to study heart disease in women.3 The study showed that urbanization in deve­ loping countries has added several new variables to the traditional risk factors. As more women are entering the office work force, it has led to a lack of physical activity and an increased consumption of fast food and restaurant cooked food, which tends to have higher caloric content, which can translate into weight gain. Other factors that may increase cardiovascular risks are increased prevalence of smoking, rise in the use of birth control measures, and consumption of alcohol. All of these factors have contributed to the increased risk of heart disease in the urban women population in the developing countries. In 1997, the AHA commissioned a survey to study the awareness of heart disease in women and the health­ care community. The study identified and recognized a significant gap and lack of awareness about heart disease in women in the general population and healthcare providers alike.25 “This is a missed opportunity,” said Lori Mosca, MD, MPH, PhD, lead author of the study. “Habits established in younger women can have lifelong rewards. We need to speak to the new generation, and help them understand that living heart healthy is going to help them feel better, not just help them live longer. So often the message is focused on how many women are dying from heart disease, but we need to be talking about how women are going to live—and live healthier.” As a result of this gap, in 2003, AHA started the “Go Red for Women” initiative. The purpose was to raise awareness of heart disease in women, physicians, and communities.
8 Section 1 Prevention and Risk Factors The “Red Dress,” which is a symbol of the “Go Red for Women” initiative, is meant to be a red alert for women to be aware of the risks of heart disease in them and to take action to protect them. Fortunately, this initiative has been a great success. It has helped to bring this issue at the forefront of scientific discussions and has captured the attention of news media. A comparative analysis of the awareness in women about the aforementioned issue in 1997 and 2012 shows that in 1997, only 30% of women identified heart disease as the leading cause of death. By 2012, however, the percentage of women acknowledging the same rose to 56%. In 1997, 35% women listed breast cancer as their biggest threat and by 2012 that number had dropped to 24%. The number of women who identified heart disease as a leading cause of death in women has doubled in the last 10 years. With WHO recognizing the impact of heart disease in womenasapreventableglobalissue,manyothercountries have started taking measures to evaluate this problem at their national level. Heart disease is a threat to women and their families across the globe. As is evident from the data presented here, it is mostly preventable. Because of the enormous social and economic implications of heart disease in women, more countries need to dedicate resources to raise awareness of heart disease in women and physicians alike, so that measures can be taken to stop this silent epidemic. ACKNOWLEDGMENTS We are thankful for the support and guidance of Dr. Navin Nanda. We appreciate the assistance of Mr. Aditya Kulkarni BA, MPH. REFERENCES 1. American Heart Association. 1997 Heart and Stroke Facts: Statistical Update. Dallas, Tex: American Heart Association; 1996. 2. Mosca L, Mochari-Greenberger H, Dolor RJ, et al. Twelve- year follow-up of American women’s awareness of cardio­ vascular disease risk and barriers to heart health. Circ Cardiovasc Qual Outcomes. 2010;3:120-127. 3. Surveillance for selected tobacco-use behaviors—United States, 1900–1994. Morb Mortal Week Rep. 1994;43(SS-3): 1-43. 4. Meyer H. Tremendous impact of smoking on mortality and cardiovascular disease,. Europian Society of Cardio­ logy University of Oslo and Norwegian Institute of Public Health; 2009. 5. Pate RR, Pratt M, Blair SN, et al. Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. JAMA. 1995;273:402-07. 6. Manson JE, Stampfer MJ, Colditz GA, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med. 1990;322:882-9. 7. Folsom AR, Daye SS, Sellers TA, et al. Body fat distri­ bution and 5-year risk of death in older women. JAMA. 1993;269:483-7. 8. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. Obes Res. 1998;6 suppl 2:51s-209s. 9. Manson JE, Spelsberg A. Risk modification in the diabetic patient. In: Manson JE, Ridker PM, Gaziano JM, Hennekens CH (Eds). Prevention of Myocardial Infarction. New York, NY: Oxford University Press; 1996.pp. 241-73. 10. Geiss LS, Herman WH, Smith PJ. Mortality in non-insulin- dependent diabetes. Diabetes in America. National Insti­ tutes of Health, National Institute of Diabetes and Digestive and Kidney Disease; 1995. pp. 249-50. 11. National Heart, Lung and Blood Institute. What are the signs and symptoms of heart disease? [online]Available from: www.nhlbi.nih.gov/health/health-topics/hdw/signs. html. [Accessed July, 2013]. 12. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-220. 13. Kochanek KD, Xu JQ, Murphy SL, et al. Deaths: final data for 2009 [PDF-2M]. National Vital Statistics Reports. 2011; 60(3). 14. Douglas PS, Ginsburg GS. The evaluation of chest pain in women. N Engl J Med. 1996;344:1311-15. 15. Mosca et al. Circulation. 2011;123:1243-62. 16. Claassen M, Sybrandy KC, Appelman YE, et al. World J Cardiol. 2012;4(2):36-47. 17. Leurent, G, Garlantézec R, Auffret V, et al. Gender differ­ ences in presentation, management and in hospital out­ come in patients with ST-segment elevation myocardial infarction: data from 5,000 patients included in the ORBI prospective French regional registry. Arch Cardiovasc Dis. 2014;107(5):291-8. 18. Kannel WB, Wilson PW. Risk factors that attenuate the female coronary disease advantage. Arch Intern Med. 1995; 155:57-61. 19. Tofler GH, Stone PH, Muller JE, et al. Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women. J Am Coll Cardiol. 1987;9:473-82. 20. Kudenchuk P, Maynard C, Martin J, et al. Comparison of presentation, treatment, and outcome of acute myocardial infarction in men versus women (the Myocardial Infarc­ tion Triage and Intervention Registry). Am J Cardiol. 1996; 78:9-14.
9 Chapter 1 Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic 21. Douglas PS, Ginsburg GS. The evaluation of chest pain in women. N Engl J Med. 1996;344:1311-15. 22. Weitzman S, Cooper L, Chambless L, et al. Gender, racial, and geographic differences in the performance of cardiac diagnostic and therapeutic procedures for hospitalized acute myocardial infarction in four states. Am J Cardiol. 1997;79:722-26. 23. Thomas RJ, Miller NH, Lamendola C, et al. National survey on gender differences in cardiac rehabilitation prog­ rams: patient characteristics and enrollment patterns. J Cardio­ pulm Rehabil. 1996;16:402-12. 24. Cannistra LB, Balady GJ, O’Malley CJ, et al. Comparison of the clinical profile and outcome of women and men in cardiac rehabilitation. Am J Cardiol. 1992;69:1274-79. 25. Allender S, Lacey B, Webster P, et al. Level of urbanization and noncommunicable disease risk factors in Tamil Nadu, India. Bull WHO. 2010;88:297-304.
Rachana Kulkarni, Anand Kulkarni Prevention of Heart Disease in Women 2 C H A P T E R An apple a day, keeps the doctor away. But does it prevent heart disease? Is it true that increased consumption of fruits can prevent heart disease? What about antioxidants then? What works? And does it matter? Isn’t heart disease a disease of men and women who need not worry about it? There are many myths about heart disease in women. Let us try to get some clarity on this. Cardiovascular disease (CVD) is the number one killer of women. CVD kills more women than stroke, lung cancer, breast cancer, and chronic obstructive pulmonary disease (COPD) combined.1 Statistics state that every third death is from CVD. One in six deaths results from coronary artery disease (CAD). A great deal of progress has been made since 1999 in the prevention and treatment of heart disease in women.2 The good news is that age-adjusted mortality from heart disease decreased from 1980 to 2002 in men (52%) and women (49%). The badnewsis thatwe areseeing a reversal in that trend. Heart disease death rate among the women of 35–54 years of age in the United States is now increasing. This may be because of the changes in several risk factors leading to CAD.3 Women all over the world are now entering the work force. More sedentary life style is being adopted, leading to obesity and diabetes. Smoking rates are on the rise. A lot needs to be done to reverse this trend. To decrease CVD related mortality, it is not enough to work only on prevention. Along with the measures to be taken to prevent heart disease in women, it is also necessary to increase awareness of this leading cause of death. In the United States, for example, public awareness of CVD as the leading cause of death has increased to 54% in 2009. It was only 30% in 1997.4 It is important that women should call for help at the onset of cardiac symptoms to improve survival from cardiac events. In a recent survey by the American Heart Association (AHA), only 53% of women said that the first thing they would do if they thought they were having a heart attack was to call 911.4 Women need to be aware of high prevalence of heart disease, symptoms of heart disease, and of the need to seek immediate help at the onset of symptoms. Prevention of heart disease hinges on understanding the risk factors and then efforts to modulate them. These risk factors are commonly divided into those that can be modified to decrease the risk and those that cannot be modified. UNMODIFIABLE RISK FACTORS Age Prevalence of heart disease increases with age. This is true in men as well as in women. It is seen that the first presentation of CAD occurs approximately 10 years later in women than in men. The INTERHEART study performed in 42 countries around the world shows that a difference of 8–10 years in age at the onset is seen widely around the world (Table 1).5 It is thought that before menopause, women are protec­ ted from development of atherosclerotic cardio­ vascular disease (ASCVD) because of the presence of estrogen. This explanation is very attractive but it should be remembered that in clinical practice, the replacement of estrogen after menopause does not prevent cardio­ vascular events and is a Class 3 indication according to the Effectiveness Based Guidelines for Prevention of Cardiovascular Disease in Women.6-10
11 Chapter 2 Prevention of Heart Disease in Women Family History Genetic contribution to heart disease is well-known and it is well documented that CAD and death from CVD have a hereditary component. The genetic transmission in families is rarely monogenic with a Mendelian pattern. More commonly, it is complex reflecting multiple genes, each contributing modestly to a predisposition to atherosclerosis and atherothrombotic events. The statistical association of gene variants with coronary disease differs in men and women, suggesting that different pathways may operate in the manifestation of CVD between men and women. In women, stromely­ sin 1 (a member of matrix metalloproteinase family of enzymes) and plasminogen activator inhibitor (PAI-1) are thought to be important. In men, two different genes are associated with MI—the gap junction protein Connexin 37 and p22(phox), a component of NAD(P)H redox system.11 The different manifestations may be because of the presence of circulating estrogens or presence or absence of the Y chromosome. Only limited work has explored sex differences in gene expression, proteomics, or metabolomics. Further work in these areas may provide important insights into the development, diagnosis, and tailored treatment of CVD in the two sexes.12 MODIFIABLE RISK FACTORS Hypertension High blood pressure (BP) is long known to be associated with risk of development of CVD and CAD. In a meta- analysis of 61 prospective studies published in the journal Lancet in 2002, more than one million healthy adults were studied between the age of 49 and 89 years. CAD risk was slightly higher in women than men. Hypertension (HTN) is increasing in the United States in both sexes but more so in women who have 15% higher prevalence than men.13,14 Under the age of 35 years, HTN was more prevalent in men than in women. The prevalence of HTN increases with age in both sexes, but from the age of 45 to 54 years, the rate of rise was greater in women than in men. After the age of 65 years, a higher percentage of women than men have HTN and the gap increases with continued age.15 The difference in prevalence reaches statistical significance at 75 years of age. The problem does not stop there. Not only the preva­ lence increases with age, women are more likely to be undertreated. In the National Health and Nutrition Exami­ nation Survey (NHANES) over time (1988–1994 and follow up survey 1999–2000), in men, the treatment rate increased by 9.8% and control rate by 15.3%. In women, the treatment rate increased by a mere 1.9% and control rate by only 0.5%.16 This lack of improvement is really concerning. Diabetes Mellitus Diabetes mellitus (DM) increases the risk of CVD in women. Diabetes is a risk factor for the development and severity of CAD in both men and women but carries a greater risk in women that completely eliminates “the female advantage.”17,18 CVD is twice as common in women with DM compared with those without DM. Diabetic women are four times as likely to be hospitalized as com­ pared with nondiabetics. Prevalence of DM is increasing rapidly in the United States. Between 1990 and 2001, it rose by 61%.1 In 2006, out of 17 million patients with known DM, 9.5 million were Table 1: Comparison of age at first myocardial infarction Region Median age women Median age men Western Europe 68 61 Central and Eastern Europe 68 59 North America 64 58 South America and Mexico 65 59 Australia and New Zealand 66 58 Middle East 57 50 Africa 56 52 South Asia 60 52 China 67 60 Southeast Asia and Japan 63 55 Ethnic origin European 68 59 Chinese 67 60 South Asian 60 50 Other Asian 63 55 Arab 57 52 Latin American 64 58 Black African 54 52 Colored African 58 52 Other 63 53 Overall 65 56 Source: Modified from Yusuf S et al, the INTERHEART Study.5
12 Section 1 Prevention and Risk Factors women (more than 50%). It is also seen that women are less likely to be treated to HbA1c goal than men are.1 Hyperlipidemia Hyperlipidemia, a known risk factor for the development of CAD, is not much more common in women at a young age. According to a statistic from the AHA, 47% of the women have total serum cholesterol of 200 mg/dL or more and 31.7% have low-density lipoprotein (LDL) cholesterol level of 130 mg/dL or more. This is similar to the general population. Only 6.7% of women have high-density lipoprotein (HDL) of less than 40 when compared with 15.5% of overall Americans. Things begin to change around menopause. Total chol­ esterol and LDL cholesterol increase on an average by about 10% from levels at 6 months before menopause. Menopause affects HDL cholesterol less dramatically. HDL concentration declines gradually in the two years before menopause and then levels off after menopause. The postmenopausal increase in CVD risk may result partly from these lipid profile changes. LIFESTYLE RISK FACTORS Obesity and Sedentary Lifestyle Obesity, described as body mass index (BMI) greater than 30 kg/sq meter, has been rapidly increasing. Prevalence of obesity increased from 12.2% in 1991 to 20.8% in 2001.19 It increased further to 35.3% in the 2005–2006 NHANES. There is an epidemic of obesity in the United States. Vigorous physical exercise is needed to modify several riskfactorsandtodecreaseriskofheartdisease.Prevalence of physical exercise is very low in women. National Center for Health interview survey reported in 2007 that 66.3% women never performed vigorous physical activity and only 9.8% engaged in vigorous physical activity, 5 days or more per week. Objective accelerometer data from NHANES were even more concerning with only 2.5%–3.2% women doing 30 minutes of exercise at least 5 days per week.20 Smoking Smoking is a strong independent risk factor for CAD in both men and women. Estimated prevalence of smoking in women 18 years of age or older was 18%–23% in 2006.1 Although smoking rates in the United States are falling overall, they are increasing in women.21 This risk is not improved by low nicotine cigarettes and is present even with minimal exposure.22 Women using contraceptive pills and smoking are at particularly high risk especially after the age of 35 years.23 Women find it harder to quit smoking than men, probably because of the weight gain seen with stopping smoking. Smoking can also lead to earlier menopause, a risk factor that is unique to women.23 GUIDELINES FOR PREVENTION OF CVD IN WOMEN Identifying the fact that heart disease in women presents differently, behaves differently, and requires a different consideration for prevention is an important step. In 2004, AHA along with several other organizations sponsored the “Evidence Based Guidelines for Cardiovascular Disease Prevention in Women.” Initially, the guidelines challenged the conventional thinking that women should be treated the same as men. Concerns were also raised about lack of representation of women in clinical trials. Since then, over time, more women have participated in clinical trials and more gender-specific analysis has become available. Considering the health implications and economic costs associated with CVD in women, sustained efforts are needed to apply evidence-based therapies that work. In2007,theguidelineswereupdated.10 Anewalgorithm for risk classification in women was adopted. This was revised when 2011 AHA guidelines were published.24 Three risk categories were identified—(1) at high risk, (2) at risk, and (3) at optimal risk (ideal cardiovascular health). Among the high risk, the rate of MI, CHD death, and stroke was 19%, at risk 5.5%, and at optimal risk 2.2% per 10 years. A major difference from prior guidelines to 2011 updates is that instead of limiting recommendations to evidence based (benefits observed in clinical research), effectiveness-based (benefits and risks observed in clinical practice) recommendations were considered.24 The American College of Cardiology (ACC) and AHA in 2013 came up with a new tool to calculate 10 year and lifetime risk for ASCVD.25 Along with traditional risk factors of age, DM, hyperlipidemia and hypertension, various other parameters like race, and sex were also introduced into the calculations to get to this prediction and determine the need for further work up as well treatment. New recommendations from ACC/AHA guide­ lines for lipid management came in November 2013.26 Eighth Joint National Committee (JNC8) guidelines for HTN management came online in December 2013 and
13 Chapter 2 Prevention of Heart Disease in Women print published in 2014.27 It is expected that these will be incorporated in the next AHA update for guidelines for prevention of CVD in women. Major Risk Factor Interventions Hypertension Treatment of HTN can go a long way in helping prevent CVD as well as stroke. JNC8 recommendations set some- what different targets for BP levels.27 • For patients less than 60 years of age, drug therapy should be considered for systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. The goal is <140/90 mm Hg. • For patients 60 years or older, drug therapy should be considered for systolic BP ≥150 mm Hg or diastolic BP ≥90 mm Hg. The goal is <150/90 mm Hg. If pharmacologic treatment for high BP results in systolic BP <140 mm Hg and treatment is well tolerated and without adverse effects, there is no need to adjust therapy. • For patients with diabetes and patients with chronic kidney disease (CKD), the threshold to initiate drug therapy is 140/90 mm Hg. The goal is <140/90 mm Hg. • In nonblack patients, including those with DM initial drug-classchoicesarethiazide-typediuretics,calcium- channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin-receptor bloc­kers (ARBs). • In black patients, including those with DM, acceptable initial drug-class choices are thiazide-type diuretics or CCBs. • Patients with CKD generally should receive ACE inhi­ bitors or ARBs. This is true for all patients with CKD, regardless of race or presence of DM. Diabetes Mellitus Lifestyle modifications and pharmacotherapy are recom­ mended in women to achieve HbA1c <7, if this can be achieved without significant hypoglycemia. A lot of litera­ ture is available in medical and endocrine journals on this issue. At this point, achieving HbA1c below 6 does not seem to confer extra protection. Hyperlipidemia Pharmacotherapy is recommended for LDL-C lowering in high risk women. While prior recommendations set specific levels as targets, new 2013 ACC/AHA guidelines usedtheintensityofstatintherapyasthegoaloftreatment.26 Four groups of individuals were identified for whom an extensive body of evidence from randomized controlled trials demonstrated a reduction in ASCVD events with a good margin of safety from moderate- or high-intensity statin therapy: • Individuals with clinical ASCVD • Individuals with primary elevations of LDL-C ≥190 mg/dL • Individuals 40–75 years of age with DM and LDL-C 70–189 mg/dL without clinical • ASCVD • Individuals without clinical ASCVD or DM who are 40–75 years of age with LDL-C 70–189 mg/dL and have an estimated 10-year ASCVD risk of 7.5% or higher. High-intensity statin therapy reduces LDL-C by appro­ ximately 50% and includes Atorvastatin 40–80 mg and Rosuvastatin 20–40 mg. Moderate-intensity statin therapy lowers LDL-C by approximately 30%–50%. Low-intensity statin therapy lowers LDL-C on average by 30%. Although high-intensity statin therapy reduces ASCVD events more than moderate-intensity statin therapy, lower-intensity statin therapy has also been shown to reduce ASCVD events, although to a lesser degree. Therefore, individuals that merit guideline-recommended statin therapy should be treated with the maximum appropriate intensity of a statin that does not cause adverse effects. Because evidence from randomized controlled trials shows that the absolute benefit of statin treatment is proportional to baseline ASCVD risk, treatment decisions for women should be based on the level of ASCVD risk. This conclusion is a departure from previous approaches that focused on LDL-C levels to guide treatment decisions. Statin treatment based on estimated 10-year ASCVD risk avoids the overtreatment of lower-risk groups such as younger, non-Hispanic White women who, despite moderate elevations in LDL-C, are typically not at significantly increased risk for ASCVD in the next 10 years in the absence of substantial risk-factor burden. However, ignoring the increased ASCVD risk in African American women might result in the under treatment of some individuals who are at significantly higher ASCVD risk at the same LDL-C level. Thus, this guideline recommends statin therapy for individuals in whom it is most likely to provide ASCVD risk reduction based on the estimated 10-year risk of ASCVD.
14 Section 1 Prevention and Risk Factors Non-statin therapy for hyperlipidemia, with or without statin, may sometimes need to be considered. Use of nia­ cin, bile acid sequestrates, fibrates, omega 3 fatty acids, and agents like Ezetimibe that inhibit cholesterol absorp­ tion may be monitored as carefully as in men. Cigarette Smoking Smoking cessation is one of the most effective and cer­ tainly the least expensive approach to disease prevention. It does not cost anything and may in fact save money. Women should be advised not to smoke and to avoid second hand smoke as well. After smoking cessation, the risk for MI quickly declined and the risk for CAD became similar to nonsmokers at about 3 years. Despite this, not many women who smoke are advised to quit by the health care providers. Data from Centers for Disease Control indicate that only close to 50% smokers who had at least one visit to their health care provider were advised to quit.28 It has been estimated that each year an additional 1 million smokers could be helped to quit smoking if they got a brief counseling.29 Brief counseling should include determining whether a patient smokes, advising any patient who smokes to quit, assisting the patient in quitting, for example, by setting a quit date and providing self-help material and scheduling follow-up visits to reinforce adherence.30,31 Providers should counsel women at each encounter, advise behavioral program or formal smoking cessation program, nicotine replacement, and other pharmacotherapy. Physical Activity Physicalactivityandvigorousregularexerciseisamainstay of staying healthy. Women should be advised to achieve at least 150 min/week of moderate exercise and 75 min/week of vigorous exercise. More benefit is obtained by increasing moderate intensity aerobic physical activity to 5 h per week, 2.5 h of vigorous intensity exercise, or an equivalent combination of both.24 Women should also be advised to do muscle strengthening exercises 2 or more days of the week. Women who need to lose weight should be advised to do a minimum of 60–90 min of at least moderate intensity exercises on most and preferably all days of the week.24 Prudent exercise programs are cost effective and have a low potential for adverse effects.32 Exercise should be individualized to accommodate the patient’s level of physical fitness, cardiac status, and preferred activities. Weight Maintenance/Loss Women should be advised to maintain or lose weight through a combination of lower caloric intake, physical activity, and formal behavioral programs to achieve an appropriate body weight (e.g. BMI <25 kg/sq meter).24 Dietary Intake Women should consume a diet rich in fruits and vegetables and to choose whole grain high fiber foods (Table 2). They should be advised to eat fish, especially oily fish at least twice a week. They should limit intake of saturated fat, cholesterol, alcohol, salt, sugar, and avoid trans-fatty acids. Effectiveness-based guidelines in the 2011 update have excellent recommendations24 What Does Not Work/May Be Harmful The effectiveness-based guidelines also came up with recommendations on the things that do not work (Class 3 indication).24 Menopausal therapy: Hormone therapy should not be used for primary or secondary prevention of CVD. Antioxidant supplements: Vitamin C, E, and beta caro­ tene should not be used for primary or secondary preven­ tion of CVD. Folic acid with or without B6 and B12 supplements should not be used for primary or secondary prevention of CVD. Aspirin for MI in women <65 years of age: Routine use of Aspirin is not recommended for prevention of MI in healthy women less than 65 years of age. A very helpful approach to primary and secondary prevention is outlined below as recommended in 2011 update to effectiveness-based guidelines for prevention of CVD in women (Flow chart 1). Thus, an apple a day may not keep the doctor away but a diet rich in fruits and vegetables and nuts is definitely recommended to prevent heart disease in women. Anti­ oxidants, despite the hype in the last few years, are not. Aspirin, while routinely recommended in the past, is not recommended in women younger than 65 years of age. As the epidemic of obesity is increasing in the United States and as CVD is increasing in some age groups in women, a prevention strategy involving dietary intervention and increasing physical exercise is essential to combat this growing threat.
15 Chapter 2 Prevention of Heart Disease in Women ACKNOWLEDGMENTS We appreciate the guidance and support of Dr Navin C Nanda. We are grateful for the support provided by Aditya Kulkarni MPH. REFERENCES 1. Lloyd-Jones D, Adams R, Carnethon M et al. Heart dis- ease and stroke statistics—2009 update: A report from the American Heart Association Statistics Committee and Stroke-Statistics Subcommittee. Circulation. 2009;119:w21. 2. Mosca L, Grundy SM, Judelson D, et al. Guide to preventive cardiology for women: AHA/ACC Scientific Statement Consensus panel statement. Circulation. 1999;99:2480. Table 2: Dietary intake recommendations for women Nutrient Serving Serving size Fruits and Vegetables >4.5 cups /day 1 cup raw leafy vegetables, ½ cup cut-up raw or cooked vegetables, ½ cup vegetable juice, 1 medium fruit, ¼ cup dried fruit, ½ cup fresh frozen or canned fruit, ½ cup fruit juice Fish 2/wk 3.5 oz, cooked (preferably oily types of fish Fiber 30g/d(1.1g/10g carbohydrate) Bran cereal, berries, avocado, and so on Whole grains 3/day 1 slice bread, 1 oz dry cereal, 1/2 cup cooked rice, pasta, or cereal (all whole-grain products) Sugar <5/wk (450 kcal/wk from sugar- sweetened beverages 1 tablespoon sugar, 1 table- spoon jelly or jam, 1/2 cup sorbet, 1 cup lemonade Nuts, Leg- umes, Seeds >4/wk 1/3 cup or 1 1/2 oz nuts (avoid macadamia nuts and salted nuts), 2 tablespoons peanut butter, 2 tablespoon or 1/2 oz seeds, 1/2 cup cooked legumes (dry beans and peas) Saturated fat <7% total energy intake Found in fried foods, fat on meat or chicken skin, packaged desserts, butter, cheese, sour cream, and so on Cholesterol <150 mg/day Found in animal meats, organ meats, eggs, and so on Alcohol One drink or less 4 oz wine, 12 oz beer, 1.5 oz of 80 proof sprits or 1 oz of 100 proof sprits Sodium <1500 mg Trans-fatty acids 0 Mosca L et al. Circulation, 2011; 123:1243-1262. Flow chart 1: Prevention of CAD in women24
16 Section 1 Prevention and Risk Factors 3. Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med. 2007;356:2388-98. 4. Mosca L, Mochari-Greenberger H, Dolor RJ, et al. Twelve- year follow-up of American women’s awareness of cardio­ vascular disease risk and barriers to heart health. Circ Cardiovasc Qual Outcomes. 2010;3:120-7. 5. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarc­ tion in 52 countries (the INTERHEART study): Case Control Study. Lancet. 2004;364:937. 6. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coro­ nary heart disease in postmenopausal women. JAMA. 1998; 280:605. 7. Grady D, Herrington D, Brenner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progestin Replacement Study follow-up (HERS II). JAMA. 2002;288:49. 8. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523. 9. Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health initiative rando­ mized controlled trial. JAMA. 2004;291:1701. 10. Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 Update. Circulation. 2007;115:1481. 11. Yamanda Y, Izawa H, Ichihara s, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002;347:1916. 12. Newby LK, Douglas PS. Cardiovascular Disease in Women, Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 9th edition. Philadelphia, PA: Elsevier Saunders; 2012. p. 1757. 13. Fields LE, Burt VL, Cutler JA, et al. The burden of adult hypertension in the United States 199 to 200: A rising tide. Hypertension. 2004;44:398. 14. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: A meta- analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903 15. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123:e18. 16. Hajjar, I, Kotchen TA. Trends in prevalence, awareness, treatment and control of hypertension in the United States, 1988–2000. JAMA. 2003;290:199. 17. Wang XL, Tam C, McCredie RM, et al. Determinants of severity of coronary artery disease in Australian men and women. Circulation. 1994;89:1974. 18. Spelsberg A, Ridker PM, Manson JE. Carbohydrate meta­ bolism, obesity and diabetes. In: Douglas PS (Ed). Cardio­ vascular Health and Disease in Women. Philadelphia: WB Saunders Company; 1993. p. 191 19. Mokdad AH, Ford ES, Bowman, BA, et al. Prevalence of obesity, diabetes and obesity related health risk factors, 2001. JAMA. 2003;289:76. 20. Troiano RP, Berrigan D, Dodd KW, et al. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc. 2008;40:181. 21. Fried LP, Becker DM. Smoking and cardiovascular disease. In: Douglas PS (Ed). Cardiovascular Health and Disease in Women. Philadelphia: WB Saunders Company; 1993. p. 217. 22. Colditz GA, Bonita R, Stampfer MJ, et al. Cigarette smoking and risk of stroke in middle aged women. N Engl J Med. 1988;318:937. 23. Shapiro S, Sloane D, Rosenberg L, et al. Oral contracep­ tive use in relation to myocardial infarction. Lancet. 1979; 1:743 24. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update, a guideline from the American Heart Association. Circulation. 2011;123:1243. 25. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/ AHA guide­ line on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2935-59. 26. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce athero­ sclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Asso­ ciation Task Force on Practice Guideline. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934. 27. James PA, Oparil S, Carter B, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the Eighth Joint National Committee (JNC8). JAMA. 2014; 311(5):507. 28. Physician and other health-care professional counselling of smokers to quit—United States, 1991. MMWR. 1993; 42:854. 29. Public Health service: Healthy People 2000: National health Promotion and disease prevention objectives—full report, with commentary. (DHHS publication no PHS 91-50212. Washington DC: US Department of Health and Human Services. Public Health Service, 1991. 30. Glynn TJ, Manley MW. How to help your patients stop smoking: A national cancer Institute manual for physicians. (DHHS publication no. PHS 92- 3064. Bethesda, MD: US. Department of Health and Human Services, National institute of Health, National cancer Institute 1992. 31. Farmer JA, Gotto AM. Dyslipidemia and Other Risk Factors for Coronary Artery Disease. Braunwald’s Heart Disease. Philadelphia, PA: WB Saunders Company; 1997. 32. Levine GN, Balady GJ. The benefits and risks of exercise training: The exercise prescription. Adv Intern Med. 1993; 38:57.
Sanne AE Peters, Yvonne T van der Schouw, Mark Woodward, Rachel R Huxley Sex Differences in the Effects of Leading and Most Prevalent Modifiable Risk Factors 3 C H A P T E R Despite substantial progress in the awareness, treatment and prevention of cardiovascular disease (CVD) over the past decades, CVD remains the world’s leading, and argu- ably the most preventable, cause of death and disability.1 Moreover, despite considerable efforts to raise awareness of CVD and its symptoms, there is still a widespread per- ception, particularly in lower and middle-income coun- tries, that CVD is a disease that predominantly affects men.2 However, as women have a greater life expectancy than men, the cardiovascular burden in absolute terms, is actually greater in women than in men; in 2004, almost 32% of all deaths in women were due to cardiovascu- lar causes compared with 27% in men.3 These estimates, and the notable sex difference in cardiovascular burden, are likely to increase further due to population aging, a higher life expectancy and the decade delay in the development of symptomatic CVD in women relative to men.4-7 Sex differences can be identified throughout the entire life course of CVD. Compared with men, women are less likely to receive pharmacological treatment for the management of cardiovascular risk factors;8,9 coronary ischemic attacks present differently in men and women, such that women are more likely to delay seeking medical attention than men;10-12 women are less likely to be referred for diagnostic and therapeutic procedures;13 and the prognosis for women with CVD is usually worse than it is for men.14-16 Moreover, despite the significant anatomical, physiological and behavioral differences between men and women, it is commonly assumed in medicine that the effects of risk factors on disease outcomes are the same in women as in men. This assumption largely stemmed from the historical fact that (with the rare exception) most of the early cohort studies and randomized trials that were initiated in the mid-20th century were comprised solely of men.17-20 However, since the initiation in the 1980s and more recently, of large prospective cohorts comprising both men and women,21,22 or solely women,23-26 we are now in a position to better test the hypothesis of an equivalency of risk factor effects on cardiovascular and other outcomes between the sexes. Determining reliably, whether there are clinically meaningful sex differences in risk factor–disease asso­ ciations is important, not solely to better understand the etiology of CVD, but also from a population and public health vantage. Convincing evidence of whether sex differences exist in the effect of the most prevalent and modifiable risk factors, including elevated blood pressure, cigarette smoking, diabetes mellitus, excess weight and raised cholesterol, is necessary since these risk factors are among the leading causes of CVD.3 Current estimates of the burden of CVD, which are used to inform public health policy, assume that these risk factors effect cardiovascular risk similarly in women as in men.1,3 However, if this assumption is proven to be invalid, then it would neces­ sitate the revision of the estimates to more accurately reflect the true nature of the relationships in women and men. Moreover, just as possible racial differences in the relationships between risk factors and diseases are considered when tailoring specific interventions for different communities, so could information on important sex differences be used to provide an added impetus for targeted interventions aimed at the treatment and management of these risk factors in both sexes. The objectives of the present review are two-fold. First, we aim to provide an overview of the most current evidence on sex differences in the prevalence of major CVD risk factors. Second, we examine the evidence pertaining
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C
Heart Disease in Women by M.D. Nanda, Navin C

Recommended

Intentional Health Detoxify, Nourish, and Rejuvenate Your Body into Balance
Intentional Health Detoxify, Nourish, and Rejuvenate Your Body into BalanceIntentional Health Detoxify, Nourish, and Rejuvenate Your Body into Balance
Intentional Health Detoxify, Nourish, and Rejuvenate Your Body into BalanceLucky Gods
 
Prevent, Halt & Reverse Heart Disease: 109 Things You Can Do
Prevent, Halt & Reverse Heart Disease: 109 Things You Can DoPrevent, Halt & Reverse Heart Disease: 109 Things You Can Do
Prevent, Halt & Reverse Heart Disease: 109 Things You Can DoLucky Gods
 
Ciottone's Disaster Medicine 3rd Edition
Ciottone's Disaster Medicine 3rd EditionCiottone's Disaster Medicine 3rd Edition
Ciottone's Disaster Medicine 3rd EditionLucky Gods
 
The Beginner's Guide to Foods That Fight Inflammation - 2023
The Beginner's Guide to Foods That Fight Inflammation - 2023The Beginner's Guide to Foods That Fight Inflammation - 2023
The Beginner's Guide to Foods That Fight Inflammation - 2023Lucky Gods
 
Complete Guide To The Human Body - 1st Edition, 2023
Complete Guide To The Human Body - 1st Edition, 2023Complete Guide To The Human Body - 1st Edition, 2023
Complete Guide To The Human Body - 1st Edition, 2023Lucky Gods
 
The Anti-Inflammatory Plan - 6th Edition, 2024
The Anti-Inflammatory Plan - 6th Edition, 2024The Anti-Inflammatory Plan - 6th Edition, 2024
The Anti-Inflammatory Plan - 6th Edition, 2024Lucky Gods
 
Men's Health - UK - June 2023
Men's Health - UK - June 2023Men's Health - UK - June 2023
Men's Health - UK - June 2023Lucky Gods
 
Men's Health - UK - March 2023
Men's Health - UK - March 2023Men's Health - UK - March 2023
Men's Health - UK - March 2023Lucky Gods
 

Recommended

Intentional Health Detoxify, Nourish, and Rejuvenate Your Body into Balance
Intentional Health Detoxify, Nourish, and Rejuvenate Your Body into BalanceIntentional Health Detoxify, Nourish, and Rejuvenate Your Body into Balance
Intentional Health Detoxify, Nourish, and Rejuvenate Your Body into BalanceLucky Gods
 
Prevent, Halt & Reverse Heart Disease: 109 Things You Can Do
Prevent, Halt & Reverse Heart Disease: 109 Things You Can DoPrevent, Halt & Reverse Heart Disease: 109 Things You Can Do
Prevent, Halt & Reverse Heart Disease: 109 Things You Can DoLucky Gods
 
Ciottone's Disaster Medicine 3rd Edition
Ciottone's Disaster Medicine 3rd EditionCiottone's Disaster Medicine 3rd Edition
Ciottone's Disaster Medicine 3rd EditionLucky Gods
 
The Beginner's Guide to Foods That Fight Inflammation - 2023
The Beginner's Guide to Foods That Fight Inflammation - 2023The Beginner's Guide to Foods That Fight Inflammation - 2023
The Beginner's Guide to Foods That Fight Inflammation - 2023Lucky Gods
 
Complete Guide To The Human Body - 1st Edition, 2023
Complete Guide To The Human Body - 1st Edition, 2023Complete Guide To The Human Body - 1st Edition, 2023
Complete Guide To The Human Body - 1st Edition, 2023Lucky Gods
 
The Anti-Inflammatory Plan - 6th Edition, 2024
The Anti-Inflammatory Plan - 6th Edition, 2024The Anti-Inflammatory Plan - 6th Edition, 2024
The Anti-Inflammatory Plan - 6th Edition, 2024Lucky Gods
 
Men's Health - UK - June 2023
Men's Health - UK - June 2023Men's Health - UK - June 2023
Men's Health - UK - June 2023Lucky Gods
 
Men's Health - UK - March 2023
Men's Health - UK - March 2023Men's Health - UK - March 2023
Men's Health - UK - March 2023Lucky Gods
 
Men's Health - UK - May 2023
Men's Health - UK - May 2023Men's Health - UK - May 2023
Men's Health - UK - May 2023Lucky Gods
 
Men's Health - UK - July Aug 2023
Men's Health - UK - July Aug 2023Men's Health - UK - July Aug 2023
Men's Health - UK - July Aug 2023Lucky Gods
 
Cooking Light - Winter 2023
Cooking Light - Winter 2023Cooking Light - Winter 2023
Cooking Light - Winter 2023Lucky Gods
 
Cooking Light - Fall 2023
Cooking Light - Fall 2023Cooking Light - Fall 2023
Cooking Light - Fall 2023Lucky Gods
 
Cooking Light - Spring 2023
Cooking Light - Spring 2023Cooking Light - Spring 2023
Cooking Light - Spring 2023Lucky Gods
 
Cooking Light - Summer 2023
Cooking Light - Summer 2023Cooking Light - Summer 2023
Cooking Light - Summer 2023Lucky Gods
 
Aesthetic Medicine - April 2023
Aesthetic Medicine - April 2023Aesthetic Medicine - April 2023
Aesthetic Medicine - April 2023Lucky Gods
 
Aesthetic Medicine - September 2023
Aesthetic Medicine - September 2023Aesthetic Medicine - September 2023
Aesthetic Medicine - September 2023Lucky Gods
 
Aesthetic Medicine - February 2023
Aesthetic Medicine - February 2023Aesthetic Medicine - February 2023
Aesthetic Medicine - February 2023Lucky Gods
 
Aesthetic Medicine - October 2023
Aesthetic Medicine - October 2023Aesthetic Medicine - October 2023
Aesthetic Medicine - October 2023Lucky Gods
 
Aesthetic Medicine - March 2023
Aesthetic Medicine - March 2023Aesthetic Medicine - March 2023
Aesthetic Medicine - March 2023Lucky Gods
 
Aesthetic Medicine - June 2023
Aesthetic Medicine - June 2023Aesthetic Medicine - June 2023
Aesthetic Medicine - June 2023Lucky Gods
 
How It Works – Understanding Human Anatomy, 1st Edition, 2023
How It Works – Understanding Human Anatomy, 1st Edition, 2023How It Works – Understanding Human Anatomy, 1st Edition, 2023
How It Works – Understanding Human Anatomy, 1st Edition, 2023Lucky Gods
 
Ancient and Traditional Foods, Plants, Herbs and Spices used in Diabetes
Ancient and Traditional Foods, Plants, Herbs and Spices used in DiabetesAncient and Traditional Foods, Plants, Herbs and Spices used in Diabetes
Ancient and Traditional Foods, Plants, Herbs and Spices used in DiabetesLucky Gods
 
Best Health - August & September 2023
Best Health - August & September 2023Best Health - August & September 2023
Best Health - August & September 2023Lucky Gods
 
Foods to Fight Cancer: What to Eat to Reduce Your Risk
Foods to Fight Cancer: What to Eat to Reduce Your RiskFoods to Fight Cancer: What to Eat to Reduce Your Risk
Foods to Fight Cancer: What to Eat to Reduce Your RiskLucky Gods
 
The Art of Deception: Unraveling Logical Fallacies
The Art of Deception: Unraveling Logical FallaciesThe Art of Deception: Unraveling Logical Fallacies
The Art of Deception: Unraveling Logical FallaciesLucky Gods
 
Automotive Technician Training: Theory 2nd Edition
Automotive Technician Training: Theory 2nd EditionAutomotive Technician Training: Theory 2nd Edition
Automotive Technician Training: Theory 2nd EditionLucky Gods
 
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...Lucky Gods
 
The Benefits of Remote Working: The Freedom of Working from Anywhere
The Benefits of Remote Working: The Freedom of Working from AnywhereThe Benefits of Remote Working: The Freedom of Working from Anywhere
The Benefits of Remote Working: The Freedom of Working from AnywhereLucky Gods
 
Medical Presentations: A Prescription for Success 1st Edition
Medical Presentations: A Prescription for Success 1st EditionMedical Presentations: A Prescription for Success 1st Edition
Medical Presentations: A Prescription for Success 1st EditionLucky Gods
 
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...Lucky Gods
 

More Related Content

Similar to Heart Disease in Women by M.D. Nanda, Navin C

Men's Health - UK - May 2023
Men's Health - UK - May 2023Men's Health - UK - May 2023
Men's Health - UK - May 2023Lucky Gods
 
Men's Health - UK - July Aug 2023
Men's Health - UK - July Aug 2023Men's Health - UK - July Aug 2023
Men's Health - UK - July Aug 2023Lucky Gods
 
Cooking Light - Winter 2023
Cooking Light - Winter 2023Cooking Light - Winter 2023
Cooking Light - Winter 2023Lucky Gods
 
Cooking Light - Fall 2023
Cooking Light - Fall 2023Cooking Light - Fall 2023
Cooking Light - Fall 2023Lucky Gods
 
Cooking Light - Spring 2023
Cooking Light - Spring 2023Cooking Light - Spring 2023
Cooking Light - Spring 2023Lucky Gods
 
Cooking Light - Summer 2023
Cooking Light - Summer 2023Cooking Light - Summer 2023
Cooking Light - Summer 2023Lucky Gods
 
Aesthetic Medicine - April 2023
Aesthetic Medicine - April 2023Aesthetic Medicine - April 2023
Aesthetic Medicine - April 2023Lucky Gods
 
Aesthetic Medicine - September 2023
Aesthetic Medicine - September 2023Aesthetic Medicine - September 2023
Aesthetic Medicine - September 2023Lucky Gods
 
Aesthetic Medicine - February 2023
Aesthetic Medicine - February 2023Aesthetic Medicine - February 2023
Aesthetic Medicine - February 2023Lucky Gods
 
Aesthetic Medicine - October 2023
Aesthetic Medicine - October 2023Aesthetic Medicine - October 2023
Aesthetic Medicine - October 2023Lucky Gods
 
Aesthetic Medicine - March 2023
Aesthetic Medicine - March 2023Aesthetic Medicine - March 2023
Aesthetic Medicine - March 2023Lucky Gods
 
Aesthetic Medicine - June 2023
Aesthetic Medicine - June 2023Aesthetic Medicine - June 2023
Aesthetic Medicine - June 2023Lucky Gods
 
How It Works – Understanding Human Anatomy, 1st Edition, 2023
How It Works – Understanding Human Anatomy, 1st Edition, 2023How It Works – Understanding Human Anatomy, 1st Edition, 2023
How It Works – Understanding Human Anatomy, 1st Edition, 2023Lucky Gods
 
Ancient and Traditional Foods, Plants, Herbs and Spices used in Diabetes
Ancient and Traditional Foods, Plants, Herbs and Spices used in DiabetesAncient and Traditional Foods, Plants, Herbs and Spices used in Diabetes
Ancient and Traditional Foods, Plants, Herbs and Spices used in DiabetesLucky Gods
 
Best Health - August & September 2023
Best Health - August & September 2023Best Health - August & September 2023
Best Health - August & September 2023Lucky Gods
 

Similar to Heart Disease in Women by M.D. Nanda, Navin C (15)

Men's Health - UK - May 2023
Men's Health - UK - May 2023Men's Health - UK - May 2023
Men's Health - UK - May 2023
 
Men's Health - UK - July Aug 2023
Men's Health - UK - July Aug 2023Men's Health - UK - July Aug 2023
Men's Health - UK - July Aug 2023
 
Cooking Light - Winter 2023
Cooking Light - Winter 2023Cooking Light - Winter 2023
Cooking Light - Winter 2023
 
Cooking Light - Fall 2023
Cooking Light - Fall 2023Cooking Light - Fall 2023
Cooking Light - Fall 2023
 
Cooking Light - Spring 2023
Cooking Light - Spring 2023Cooking Light - Spring 2023
Cooking Light - Spring 2023
 
Cooking Light - Summer 2023
Cooking Light - Summer 2023Cooking Light - Summer 2023
Cooking Light - Summer 2023
 
Aesthetic Medicine - April 2023
Aesthetic Medicine - April 2023Aesthetic Medicine - April 2023
Aesthetic Medicine - April 2023
 
Aesthetic Medicine - September 2023
Aesthetic Medicine - September 2023Aesthetic Medicine - September 2023
Aesthetic Medicine - September 2023
 
Aesthetic Medicine - February 2023
Aesthetic Medicine - February 2023Aesthetic Medicine - February 2023
Aesthetic Medicine - February 2023
 
Aesthetic Medicine - October 2023
Aesthetic Medicine - October 2023Aesthetic Medicine - October 2023
Aesthetic Medicine - October 2023
 
Aesthetic Medicine - March 2023
Aesthetic Medicine - March 2023Aesthetic Medicine - March 2023
Aesthetic Medicine - March 2023
 
Aesthetic Medicine - June 2023
Aesthetic Medicine - June 2023Aesthetic Medicine - June 2023
Aesthetic Medicine - June 2023
 
How It Works – Understanding Human Anatomy, 1st Edition, 2023
How It Works – Understanding Human Anatomy, 1st Edition, 2023How It Works – Understanding Human Anatomy, 1st Edition, 2023
How It Works – Understanding Human Anatomy, 1st Edition, 2023
 
Ancient and Traditional Foods, Plants, Herbs and Spices used in Diabetes
Ancient and Traditional Foods, Plants, Herbs and Spices used in DiabetesAncient and Traditional Foods, Plants, Herbs and Spices used in Diabetes
Ancient and Traditional Foods, Plants, Herbs and Spices used in Diabetes
 
Best Health - August & September 2023
Best Health - August & September 2023Best Health - August & September 2023
Best Health - August & September 2023
 

More from Lucky Gods

Foods to Fight Cancer: What to Eat to Reduce Your Risk
Foods to Fight Cancer: What to Eat to Reduce Your RiskFoods to Fight Cancer: What to Eat to Reduce Your Risk
Foods to Fight Cancer: What to Eat to Reduce Your RiskLucky Gods
 
The Art of Deception: Unraveling Logical Fallacies
The Art of Deception: Unraveling Logical FallaciesThe Art of Deception: Unraveling Logical Fallacies
The Art of Deception: Unraveling Logical FallaciesLucky Gods
 
Automotive Technician Training: Theory 2nd Edition
Automotive Technician Training: Theory 2nd EditionAutomotive Technician Training: Theory 2nd Edition
Automotive Technician Training: Theory 2nd EditionLucky Gods
 
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...Lucky Gods
 
The Benefits of Remote Working: The Freedom of Working from Anywhere
The Benefits of Remote Working: The Freedom of Working from AnywhereThe Benefits of Remote Working: The Freedom of Working from Anywhere
The Benefits of Remote Working: The Freedom of Working from AnywhereLucky Gods
 
Medical Presentations: A Prescription for Success 1st Edition
Medical Presentations: A Prescription for Success 1st EditionMedical Presentations: A Prescription for Success 1st Edition
Medical Presentations: A Prescription for Success 1st EditionLucky Gods
 
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...Lucky Gods
 
Textbook of Contraception, Sexual and Reproductive Health
Textbook of Contraception, Sexual and Reproductive HealthTextbook of Contraception, Sexual and Reproductive Health
Textbook of Contraception, Sexual and Reproductive HealthLucky Gods
 
DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...
DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...
DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...Lucky Gods
 
ChatGPT - The AI Rich Dad: Fire Prompts And Grow Rich
ChatGPT - The AI Rich Dad: Fire Prompts And Grow RichChatGPT - The AI Rich Dad: Fire Prompts And Grow Rich
ChatGPT - The AI Rich Dad: Fire Prompts And Grow RichLucky Gods
 
Earth Knowledge Genius! (DK Knowledge Genius)
Earth Knowledge Genius! (DK Knowledge Genius)Earth Knowledge Genius! (DK Knowledge Genius)
Earth Knowledge Genius! (DK Knowledge Genius)Lucky Gods
 
Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...
Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...
Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...Lucky Gods
 
Fit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s Guide
Fit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s GuideFit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s Guide
Fit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s GuideLucky Gods
 
Digital Business and E-Commerce Management 7th Edition
Digital Business and E-Commerce Management 7th EditionDigital Business and E-Commerce Management 7th Edition
Digital Business and E-Commerce Management 7th EditionLucky Gods
 
Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...
Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...
Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...Lucky Gods
 
Palm Reading (The Psychic Arts)
Palm Reading (The Psychic Arts)Palm Reading (The Psychic Arts)
Palm Reading (The Psychic Arts)Lucky Gods
 
Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...
Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...
Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...Lucky Gods
 
Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...
Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...
Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...Lucky Gods
 
Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...
Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...
Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...Lucky Gods
 
Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...
Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...
Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...Lucky Gods
 

More from Lucky Gods (20)

Foods to Fight Cancer: What to Eat to Reduce Your Risk
Foods to Fight Cancer: What to Eat to Reduce Your RiskFoods to Fight Cancer: What to Eat to Reduce Your Risk
Foods to Fight Cancer: What to Eat to Reduce Your Risk
 
The Art of Deception: Unraveling Logical Fallacies
The Art of Deception: Unraveling Logical FallaciesThe Art of Deception: Unraveling Logical Fallacies
The Art of Deception: Unraveling Logical Fallacies
 
Automotive Technician Training: Theory 2nd Edition
Automotive Technician Training: Theory 2nd EditionAutomotive Technician Training: Theory 2nd Edition
Automotive Technician Training: Theory 2nd Edition
 
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...
How Not to Get Eaten: More than 75 Incredible Animal Defenses (Wonders of Wil...
 
The Benefits of Remote Working: The Freedom of Working from Anywhere
The Benefits of Remote Working: The Freedom of Working from AnywhereThe Benefits of Remote Working: The Freedom of Working from Anywhere
The Benefits of Remote Working: The Freedom of Working from Anywhere
 
Medical Presentations: A Prescription for Success 1st Edition
Medical Presentations: A Prescription for Success 1st EditionMedical Presentations: A Prescription for Success 1st Edition
Medical Presentations: A Prescription for Success 1st Edition
 
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...
The Artificial Intelligence Handbook for Real Estate Brokers: "Future-Proof Y...
 
Textbook of Contraception, Sexual and Reproductive Health
Textbook of Contraception, Sexual and Reproductive HealthTextbook of Contraception, Sexual and Reproductive Health
Textbook of Contraception, Sexual and Reproductive Health
 
DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...
DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...
DIGITAL GOLD RUSH: A Guide to Cryptocurrency Mining Optimization for Wealth C...
 
ChatGPT - The AI Rich Dad: Fire Prompts And Grow Rich
ChatGPT - The AI Rich Dad: Fire Prompts And Grow RichChatGPT - The AI Rich Dad: Fire Prompts And Grow Rich
ChatGPT - The AI Rich Dad: Fire Prompts And Grow Rich
 
Earth Knowledge Genius! (DK Knowledge Genius)
Earth Knowledge Genius! (DK Knowledge Genius)Earth Knowledge Genius! (DK Knowledge Genius)
Earth Knowledge Genius! (DK Knowledge Genius)
 
Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...
Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...
Animal Knowledge Genius: A Quiz Encyclopedia to Boost Your Brain (DK Knowledg...
 
Fit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s Guide
Fit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s GuideFit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s Guide
Fit @ Any Age Fitness tips from a 92 year old runner A Practitioner’s Guide
 
Digital Business and E-Commerce Management 7th Edition
Digital Business and E-Commerce Management 7th EditionDigital Business and E-Commerce Management 7th Edition
Digital Business and E-Commerce Management 7th Edition
 
Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...
Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...
Build Autonomous Mobile Robot from Scratch using ROS: Simulation and Hardware...
 
Palm Reading (The Psychic Arts)
Palm Reading (The Psychic Arts)Palm Reading (The Psychic Arts)
Palm Reading (The Psychic Arts)
 
Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...
Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...
Pathfinders: Extraordinary Stories of People Like You on the Quest for Financ...
 
Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...
Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...
Overcoming Debt, Achieving Financial Freedom: 8 Pillars to Build Wealth 1st E...
 
Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...
Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...
Broken Money: Why Our Financial System Is Failing Us and How We Can Make It B...
 
Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...
Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...
Business Wealth Without Risk: How to Create a Lifetime of Income & Wealth Eve...
 

Recently uploaded

Call Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar Suman
Call Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar SumanCall Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar Suman
Call Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar SumanCall Girls Service Chandigarh Ayushi
 
Udaipur Call Girls 📲 9999965857 Call Girl in Udaipur
Udaipur Call Girls 📲 9999965857 Call Girl in UdaipurUdaipur Call Girls 📲 9999965857 Call Girl in Udaipur
Udaipur Call Girls 📲 9999965857 Call Girl in Udaipurseemahedar019
 
💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋Sheetaleventcompany
 
Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...
Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...
Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...Sheetaleventcompany
 
Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...
Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...
Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...gurkirankumar98700
 
💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋Sheetaleventcompany
 
Hot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In Chandigarh
Hot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In ChandigarhHot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In Chandigarh
Hot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In ChandigarhVip call girls In Chandigarh
 
Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...
Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...
Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...Niamh verma
 
No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...
No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...
No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...Vip call girls In Chandigarh
 
Dehradun Call Girls Service 08854095900 Real Russian Girls Looking Models
Dehradun Call Girls Service 08854095900 Real Russian Girls Looking ModelsDehradun Call Girls Service 08854095900 Real Russian Girls Looking Models
Dehradun Call Girls Service 08854095900 Real Russian Girls Looking Modelsindiancallgirl4rent
 
Russian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in Lucknow
Russian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in LucknowRussian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in Lucknow
Russian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in Lucknowgragteena
 
VIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near Me
VIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near MeVIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near Me
VIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near Memriyagarg453
 
Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.
Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.
Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.ktanvi103
 
VIP Kolkata Call Girl New Town 👉 8250192130 Available With Room
VIP Kolkata Call Girl New Town 👉 8250192130 Available With RoomVIP Kolkata Call Girl New Town 👉 8250192130 Available With Room
VIP Kolkata Call Girl New Town 👉 8250192130 Available With Roomdivyansh0kumar0
 
Basics of Anatomy- Language of Anatomy.pptx
Basics of Anatomy- Language of Anatomy.pptxBasics of Anatomy- Language of Anatomy.pptx
Basics of Anatomy- Language of Anatomy.pptxAyush Gupta
 
Call Girls Thane Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Thane Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Thane Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Thane Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
Call Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In Raipur
Call Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In RaipurCall Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In Raipur
Call Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In Raipurgragmanisha42
 
indian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana Tulsi
indian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana Tulsiindian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana Tulsi
indian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana TulsiHigh Profile Call Girls Chandigarh Aarushi
 
❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...
❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...
❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...Gfnyt.com
 
Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅
Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅
Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅gragmanisha42
 

Recently uploaded (20)

Call Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar Suman
Call Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar SumanCall Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar Suman
Call Girl Price Amritsar ❤️🍑 9053900678 Call Girls in Amritsar Suman
 
Udaipur Call Girls 📲 9999965857 Call Girl in Udaipur
Udaipur Call Girls 📲 9999965857 Call Girl in UdaipurUdaipur Call Girls 📲 9999965857 Call Girl in Udaipur
Udaipur Call Girls 📲 9999965857 Call Girl in Udaipur
 
💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Chandigarh Escort Service Call Girls, ₹5000 To 25K With AC💚😋
 
Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...
Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...
Call Girl In Zirakpur ❤️♀️@ 9988299661 Zirakpur Call Girls Near Me ❤️♀️@ Sexy...
 
Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...
Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...
Russian Call Girls Lucknow ₹7.5k Pick Up & Drop With Cash Payment 8923113531 ...
 
💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋
💚😋Kolkata Escort Service Call Girls, ₹5000 To 25K With AC💚😋
 
Hot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In Chandigarh
Hot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In ChandigarhHot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In Chandigarh
Hot Call Girl In Chandigarh 👅🥵 9053'900678 Call Girls Service In Chandigarh
 
Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...
Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...
Call Girls Service Chandigarh Gori WhatsApp ❤7710465962 VIP Call Girls Chandi...
 
No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...
No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...
No Advance 9053900678 Chandigarh Call Girls , Indian Call Girls For Full Ni...
 
Dehradun Call Girls Service 08854095900 Real Russian Girls Looking Models
Dehradun Call Girls Service 08854095900 Real Russian Girls Looking ModelsDehradun Call Girls Service 08854095900 Real Russian Girls Looking Models
Dehradun Call Girls Service 08854095900 Real Russian Girls Looking Models
 
Russian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in Lucknow
Russian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in LucknowRussian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in Lucknow
Russian Escorts Aishbagh Road * 9548273370 Naughty Call Girls Service in Lucknow
 
VIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near Me
VIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near MeVIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near Me
VIP Call Girls Noida Jhanvi 9711199171 Best VIP Call Girls Near Me
 
Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.
Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.
Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.
 
VIP Kolkata Call Girl New Town 👉 8250192130 Available With Room
VIP Kolkata Call Girl New Town 👉 8250192130 Available With RoomVIP Kolkata Call Girl New Town 👉 8250192130 Available With Room
VIP Kolkata Call Girl New Town 👉 8250192130 Available With Room
 
Basics of Anatomy- Language of Anatomy.pptx
Basics of Anatomy- Language of Anatomy.pptxBasics of Anatomy- Language of Anatomy.pptx
Basics of Anatomy- Language of Anatomy.pptx
 
Call Girls Thane Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Thane Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Thane Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Thane Just Call 9907093804 Top Class Call Girl Service Available
 
Call Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In Raipur
Call Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In RaipurCall Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In Raipur
Call Girl Raipur 📲 9999965857 ヅ10k NiGhT Call Girls In Raipur
 
indian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana Tulsi
indian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana Tulsiindian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana Tulsi
indian Call Girl Panchkula ❤️🍑 9907093804 Low Rate Call Girls Ludhiana Tulsi
 
❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...
❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...
❤️♀️@ Jaipur Call Girls ❤️♀️@ Meghna Jaipur Call Girls Number CRTHNR Call G...
 
Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅
Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅
Russian Call Girls Kota * 8250192130 Service starts from just ₹9999 ✅
 

Heart Disease in Women by M.D. Nanda, Navin C

  • 1.
  • 2. 🌟Welcome to Your Journey of Ultimate Wellness! 🌈💖 Thank you for choosing our ebook/magazine! 📘✨To enhance your health and beauty experience, we've curated some phenomenal products that promise to elevate your well-being. 🌺🌟 Skincare Saviors: Hydrossential - Unique Beauty Serum: 💦One Simple Way To Maintain A Flawless Skin. Link: https://mas.so/hydrossential Sun-Kissed Confidence: Totally Bangin' Tan by Turbo Babe: ☀️Go From “Pale Princess” to “Golden Goddess” with this Anti-Aging Sunless Tanning. Link: https://mas.so/bangin Hairraisingly Healthy: FoliPrime - The Natural Egyptian Hair Balm: 💆‍♀️Supports Hair Health. Link: https://mas.so/foliprime Men's Wellness Wonders: Endo Pump - Male Enhancement MONSTER: 💪U.S. Scientists Discover Secret For Stamina & Virility At Any Age. Link: https://mas.so/endopump African “Sex Monkeys” Unveil How To Reverse Erectile Dysfunction So You Can Have A Rock Hard Erection Again And Last At Least 30 Minute In Bed! (Note: Due to the potentially offensive language, I recommend considering revising this title and description.) Link: https://mas.so/edprotocol Conquer Health Concerns: MenoRescue: 🧘‍♀️Support healthy hormone levels with MenoRescue™. Formulated using the latest Ivy League research. Link: https://mas.so/menorescue GlucoFence - Blood Sugar Support: 🛡️#1 Most Hated By Big Pharma , Rogue Doctor Fixes Type 2 Diabetes. Link: https://mas.so/glucofence Bonus Goodies: NEW '23: Archangel Health Prayers for 400 Diseases, Weight Loss... Link: https://mas.so/archangels Natural Therapy With Killer VSL & Captivating Hook That Converts Like Crazy For Both Health & PD Niches! Powerful Therapy Based On Acupuncture. New Non- Invasive Alternative. To Electro-Acupuncture, Producing Astounding Results… Self- Application Is Easy, Rapid Response. Link: https://mas.so/naturaltherapy Every Morning This Ancient Amazonian “Drip Method” Is Being Used To Support Healthy Weight Loss. Link: https://mas.so/ignite The "Hidden Survival Muscle" In Your Body Missed By Modern Physicians That Keep Millions Of Men And Women Defeated By Pain, Frustrated With Belly Fat, And Struggling To Feel Energized Every Day… Link: https://mas.so/hipflexors Meditation - "InnaPeace Meditation Program" : The InnaPeace Program for Anxiety Sufferers, Discover why thousands are flocking to what experts are calling “the most advanced self-development method known to human kind”. Link: https://mas.so/innapeace Don't miss out on these amazing products! Click the links above and start your journey to a healthier, happier you! Don't let shortened links with mas.so send shivers down your spine! 🥶It's just a friendly URL shrinker, like a superhero packing superpowers into a tiny suit. 💪👀Fear not, visit https://mas.so and see what mas.so is. ✨Then, click with confidence and discover your favorite products! 🗺️Trust needs to be built on the first click. Thanks!💎
  • 4.
  • 5. Heart Disease in Women Editors Navin C Nanda MD DSc(Hon) Distinguished Professor of Medicine and Cardiovascular Disease Division of Cardiovascular Disease and Director, Heart Station/Echocardiography Laboratories University of Alabama at Birmingham and the University of Alabama Health Services Foundation The Kirklin Clinic, Birmingham, Alabama, USA President, International Society of Cardiovascular Ultrasound Nurgül Keser MD Professor of Cardiology Sakarya University Medical Faculty Sakarya, Turkey Foreword Prof (Dr) Muzaffer Elmas New Delhi | London | Philadelphia | Panama The Health Sciences Publisher
  • 6. Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd. 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 E-mail: jaypee@jaypeebrothers.com Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com Heart Disease in Women First Edition: 2015 ISBN: 978-93-5152-294-2 Printed at Overseas Offices J.P. Medical Ltd. 83, Victoria Street, London SW1H 0HW (UK) Phone: +44-20 3170 8910 Fax: +44(0)20 3008 6180 E-mail: info@jpmedpub.com Jaypee-Highlights Medical Publishers Inc. City of Knowledge, Bld. 237, Clayton Panama City, Panama Phone: +1 507-301-0496 Fax: +1 507-301-0499 E-mail: cservice@jphmedical.com Jaypee Medical Inc. The Bourse 111, South Independence Mall East Suite 835, Philadelphia, PA 19106, USA Phone: +1 267-519-9789 E-mail: jpmed.us@gmail.com Jaypee Brothers Medical Publishers (P) Ltd. 17/1-B, Babar Road, Block-B, Shaymali Mohammadpur, Dhaka-1207 Bangladesh Mobile: +08801912003485 E-mail: jaypeedhaka@gmail.com Jaypee Brothers Medical Publishers (P) Ltd. Bhotahity, Kathmandu, Nepal Phone: +977-9741283608 E-mail: kathmandu@jaypeebrothers.com Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2015, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photo­ copying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contra­ indications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity.
  • 7. Dedicated to My late parents Balwant Rai Nanda MD and Mrs Maya Vati Nanda My wife Kanta Nanda MD Our children Nitin Nanda, Anita Nanda Wasan MD and Anil Nanda MD Their spouses Sanjeev Wasan MD and Seema Tailor Nanda, and our grandchildren Vinay and Rajesh Wasan, and Nayna and Ria Nanda Navin C Nanda MD DSc(Hon) My mother and father Zehra Keser and Mehmet Keser who made all things possible Nurgül Keser MD
  • 8.
  • 9. Contributors Sahar S Abdelmoneim MBBCH MS MSc Cardiovascular Ultrasound Imaging and Hemodynamic Laboratory Mayo Clinic Rochester, Minnesota, USA Division of Cardiovascular Diseases Assiut University Assiut, Egypt Kul Aggarwal MD Professor of Clinical Medicine, University of Missouri Chief, Cardiology Section, Harry S Truman Veterans Hospital Columbia, Missouri, USA Michelle A Albert MD MPH Howard University College of Medicine and Division of Cardiovascular Medicine, Department of Medicine, Howard University Hospital Washington DC, USA Ezra A Amsterdam MD Distinguished Professor of Medicine Department of Internal Medicine Associate Chief (academic affairs) Division of Cardiovascular Medicine Master Clinician Educator University of California Davis Medical Center Sacramento, California, USA Zinzi Bailey MSPH Department of Social and Behavioral Sciences, Harvard School of Public Health Boston, Massachusetts, USA Kunal Bhagatwala MBBS University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Joseph R Biggio Jr MD Professor Director, Division of Maternal Fetal Medicine Medical Director, Obstetric Services University of Alabama at Birmingham Department of Obstetrics & Gynecology Birmingham, Alabama, USA Lori A Blauwet MD Assistant Professor of Medicine Division of Cardiovascular Diseases Mayo Clinic Rochester, Minnesota, USA Peter C Block MD FACC FSCAI Emory University Hospital Emory University School of Medicine Atlanta, Georgia, USA Uğur Canpolat MD Türkiye Yüksek İhtisas Training and Research Hospital Cardiology Clinic Ankara, Turkey Sibel Catirli Enar MD *Associate Professor of Cardiology Turkey Hospital/Memorial Hospital Istanbul, Turkey Kelli Chaviano DO Philadelphia College of Osteopathic Medicine Atlanta, Georgia, USA Reema Chugh MD FACC Cardiologist Specialist in Adult Congenital Heart Disease and Heart Disease in Pregnancy Department of Internal Medicine Kaiser Permanente Medical Center Panorama City, California, USA Anne B Curtis MD FACC FHRS FACP FAHA Charles and Mary Bauer Professor and Chair University at Buffalo Distinguished Professor Department of Medicine University at Buffalo Buffalo, New York, USA Mackram F Eleid MD Assistant Professor of Medicine Mayo Clinic College of Medicine Interventional Cardiology Fellow Mayo Clinic Rochester, Minnesota, USA Stephanie El-Hajj MD Department of Internal Medicine Louisiana State University Health Sciences Center, Baton Rouge Louisiana, USA Cevdet Erdöl MD Professor of Cardiology Member of the Grand National Assembly of Turkey Ankara, Turkey Keith C Ferdinand MD FACC FAHA Professor of Clinical Medicine Division of Cardiology Tulane University School of Medicine New Orleans, Louisiana, USA Charu Gandotra MD Assistant Professor Division of Cardiology Department of Internal Medicine Howard University Hospital Washington, DC, USA Gopal Ghimire MD DM MRCP University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA
  • 10. viii Heart Disease in Women Fadi G Hage MD FASH FACC Division of Cardiovascular Diseases Department of Medicine University of Alabama at Birmingham Birmingham, Alabama, USA Rachel R Huxley DPhil School of Population Health University of Queensland Brisbane, Queensland, Australia Aryana Jacobs BA Howard University College of Medicine and Division of Cardiovascular Medicine Department of Medicine, Howard University Hospital Washington DC, USA Nidhi Karia MBBS University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Tugba Kemaloglu Oz MD University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Nese Keser MD Fatih Sultan Mehmet Research and Training Hospital Department of Neurosurgery Istanbul, Turkey Nurgül Keser MD Professor of Cardiology Sakarya University Medical Faculty Sakarya, Turkey Anant Kharod MD University of Alabama at Birmingham Department of Internal Medicine Birmingham, Alabama Jennifer Kiessling MD University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Juliana M Kling MD MPH Department of General Internal Medicine Mayo Clinic Scottsdale, Arizona, USA Anand Kulkarni MD FACC Robert Wood Johnson Physician Enterprise Somerset, New Jersey, USA Rachana Kulkarni MD FACC Medicor Cardiology and Chairman of Department of Medicine Somerset Medical Center Somerset, New Jersey, USA Rebecca D Levit MD Emory University School of Medicine Department of Medicine, Division of Cardiology Atlanta, Georgia, USA Rekha Mankad MD FACC Instructor of Medicine Mayo Clinic College of Medicine Mayo Clinic Rochester, Minnesota, USA Francesca Mantovani MD Division of Cardiovascular Diseases Cardiovascular Ultrasound Imaging and Hemodynamic Laboratory Mayo Clinic Rochester, Minnesota, USA Luis D Meggo Quiroz MD Third Post-graduate Year, Department of Internal Medicine University of Alabama at Birmingham Birmingham, Alabama USA Ankit Mehra MD Cardiovascular Fellow, University of Missouri and Harry S Truman Veterans Hospital, Columbia, Missouri, USA Virginia M Miller PhD Departments of Surgery and Physiology and Biomedical Engineering Mayo Clinic Rochester, Minnesota, USA Sobia Mujtaba MD Medical Resident Jacobi Medical Center Albert Einstein College of Medicine Bronx, New York, USA Sharon L Mulvagh MD FACC FAHA FASE     FRCP(C) Professor of Medicine Director Women’s Heart Clinic Mayo Clinic College of Medicine Mayo Clinic Rochester, Minnesota, USA Deepika Narasimha MD PGY-3, Internal Medicine Department of Medicine University at Buffalo Buffalo, New York, USA Chitra Narasimhan MD FICPC Assistant Professor of Clinical Pediatric Cardiology Sri Jayadeva Institute of Cardiovascular Sciences and Research Bengaluru, India Samar A Nasser PhD MPH PA-C Director of Research Partnership UM-Dearborn/Oakwood Healthcare Research Partnership The University of Michigan-Dearborn School of Education Dearborn, Michigan, USA Navin C Nanda MD DSc(Hon) Distinguished Professor of Medicine and Cardiovascular Disease Division of Cardiovascular Disease and Director, Heart Station/Echocardiography Laboratories University of Alabama at Birmingham and the University of Alabama Health Services Foundation, The Kirklin Clinic Birmingham, Alabama, USA President, International Society of Cardiovascular Ultrasound Sanne AE Peters PhD Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The Netherlands The George Institute for Global Health University of Sydney Sydney, Australia Ileana L Piña MD MPH Associate Chief of Academic Affairs Division of Cardiology Montefiore Medical Center Professor of Medicine Professor of Epidemiology and Population Health Albert Einstein College of Medicine Bronx, New York, USA
  • 11. ix Contributors Amy West Pollak MD MS Department of Internal Medicine Division of Cardiovascular Diseases Women’s Heart Clinic Mayo Clinic, Rochester, Minnesota, USA Julie J Ramos MD Attending Cardiologist Montefiore Medical Center Assistant Professor of Clinical Medicine Albert Einstein College of Medicine Bronx, New York, USA Mary L Rosser MD PhD Assistant Professor and Attending Physician Department of Obstetrics and Gynecology and Women’s Health Albert Einstein College of Medicine Montefiore Medical Center Bronx, New York, USA Kumar Sanam MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA Anita Saxena MD DM FACC FAMS Department of Cardiology All India Institute of Medical Sciences New Delhi, India Anurag Singh MD Fellow, Electrophysiology Department of Cardiology Mount Sinai Medical Center New York, New York, USA Necati Sirmaci MD Professor of Cardiology Turkish Heart and Research Foundation Istanbul, Turkey Akila Subramaniam MD MPH Maternal-Fetal Medicine/ Medical Genetics Fellow University of Alabama at Birmingham Birmingham, Alabama, USA Aylin Sungur MD University of Alabama at Birmingham Division of Cardiovascular Disease Birmingham, Alabama, USA Manish Tandon MD Hartford Hospital Hartford, Connecticut, USA Suman Tandon MD Yale University School of Medicine New Haven, Connecticut, USA Cynthia C Taub MD Director, Non-Invasive Cardiology Einstein Division Montefiore Medical Center Associate Professor of Clinical Medicine Albert Einstein College of Medicine Bronx, New York, USA Jane S Titterington MD PhD Emory University School of Medicine Department of Medicine, Division of Cardiology Atlanta, Georgia, USA Lale Tokgozoglu MD FACC FESC Professor Department of Cardiology Hacettepe University Faculty of Medicine Ankara, Turkey Yvonne T van der Schouw PhD Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht, The Netherlands IB Vijayalakshmi MD DM FICC FIAMS        FIAE FICP FCSI FAMS DSc Professor of Pediatric Cardiology Sri Jayadeva Institute of Cardiovascular Sciences and Research Bengaluru, India Nanette K Wenger MD Emory University School of Medicine Department of Medicine, Division of Cardiology Atlanta, Georgia, USA Mark Woodward PhD The George Institute for Global Health University of Sydney Sydney, Australia Department of Epidemiology Johns Hopkins University Baltimore, Maryland, USA Victoria Zysek DO MBA Division of Cardiovascular Diseases Women’s Heart Clinic Mayo Clinic Rochester, Minnesota, USA
  • 12.
  • 13. Foreword The Sakarya University, founded in 1970, has become a world class institution with several schools, institutes and as many as 14 centers performing research in various scientific fields. During the past few years, it has been recognized for "excellence" and has won several awards including the European Commission and National Quality Awards. Last year, it received the "sustainability in excellence" award as well as an award for innovations and supporting innovative studies. The University is also sensitive to national and international problems and issues and one of its missions is to collaborate actively with other international organizations towards solving them on a global scale. During the International Congress on Women and Health organized by the Sakarya University in Sakarya, Turkey in 2010 with Dr Nurgül Keser as the Director and Dr Navin C Nanda as the International Director, it became clear that there was a need to publish an up-to-date book on heart disease in women taking into account the fact there was hardly any book on this subject. On our recommendation, Dr Nanda and Dr Keser undertook this difficult task and have come up with a book that will emphasize and focus attention on various aspects of heart disease in women and how they are underdiagnosed and undertreated compared to men. This will increase awareness and may spur efforts by various government agencies to tackle these mostly unrecognized issues affecting women throughout the world. Our heartfelt thanks to Dr Nanda and all the national and international contributors of this book for taking time off from their busy schedule to collaborate on this very important project. Prof (Dr) Muzaffer Elmas President, Sakarya University Sakarya, Turkey
  • 14.
  • 15. Preface Cardiovascular disease represents the most common cause of death in women in both developed and developing countries affecting high, middle and low income social strata. According to some data, more women die from cardiovascular disease than men. Despite these impressive statistics published by the World Health Organization, misperceptions are prevalent among both the lay public and medical professionals that cardiovascular disease is an uncommon entity in women. This unawareness coupled with the fact that women may present with atypical symptoms results in reduced surveillance, misdiagnosis or delayed diagnosis and consequently under treatment of cardiovascular disease, especially ischemic heart disease, in women. These issues were highlighted during an international conference on women and health organized by the Sakarya University and the International Society of Cardiovascular Ultrasound in Sakarya, Turkey in 2010. During this conference, it became clear to us that a book focusing on all aspects of heart disease in women could prove invaluable to medical and paramedical professionals given the paucity of such books on this subject. With this in mind we contacted several nationally and internationally renowned physicians, scientists and cardiologists who readily agreed to contribute and we are most grateful to them for sharing their expertise by writing excellent chapters for this book. This book consists of a total of 34 chapters organized into 8 sections. The first two chapters by Rachana and Anand Kulkarni deal in a succinct manner the myths and facts about cardiovascular disease in women and the important topic of cardiovascular disease prevention. Both modifiable and non-modifiable risk factors and guidelines for prevention are discussed, with special reference to women. The third chapter by Sanne Peters and associates emphasizes sex differences in the effects of leading and most prevalent risk factors in women. This is followed by a chapter on dyslipidemia by Lale Tokgozoglu from Ankara, Turkey. Gopal Ghimire in the next chapter discusses various aspects of familial hypercholesterolemia with special focus on women and highlights the guidelines proposed by the National Lipid Association.MetabolicsyndromeisnextcoveredbySibelCatirliEnarandcolleagues.Theepidemiology,pathophysiology and management of hypertension in women are elegantly summarized by Keith Ferdinand and Samar Nasser in the following chapter (Chapter 7). They also cover the important topics of resistant and refractory hypertension. Cardiac and non-cardiac causes of stroke in women are detailed in the next chapter by Nese Keser from Istanbul, Turkey. The relationship of oral contraceptive pills and hormone replacement therapy to stroke as well as risk factors for stroke during pregnancy are also discussed. Professors Nurgül Keser and Cevdet Erdöl in the next chapter discuss the deleterious effects of smoking in women, especially younger women in whom the prevalence of smoking is alarmingly increasing in many parts of the world. A special mention is made of the increasing use of waterpipe tobacco smoking in several countries of Europe and the Middle East. Measures taken by government agencies to curb smoking are also mentioned. Job stress, strain, burnout, unemployment and biomarkers and their relationship to some of these factors are delineated in Chapter 10 by Aryanna Jacobs and colleagues. The following chapter by Mackram Eleid and associates from the Mayo Clinic in Rochester describe the role of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid antibody syndrome in atherosclerotic plaque formation in the next chapter. The last chapter in this section by Juliana Kling and associates is also from the Mayo Clinic and explains the effect of pregnancy and menopause on cardiovascular function and points to the controversial relationship of menopausal hormone therapy to progression of cardiovascular disease. The second section of the book pertains to with coronary heart disease. The first chapter by Ezra Amsterdam provides a perspective and overview of coronary heart disease in women. The second chapter (Chapter 14) by Kumar Sanam and colleagues outlines the approach to assessment of chest pain in a woman presenting to the Emergency Department. The clinical presentation, diagnostic testing, the use of biomarkers and differential diagnosis are given in detail. The third chapter, from the group of Nanette Wenger, a renowned expert in heart disease in women, details all aspects of stable ischemic heart disease in women including pathophysiology of gender differences in women, different terminologies used, the scope of the burden, challenges in diagnosis and treatment strategies. The last chapter in this section, by Ankit Mehra and Kul Aggarwal, explains different aspects of acute coronary syndromes including the pathophysiology of
  • 16. xiv Heart Disease in Women atherosclerotic plaque rupture and erosion and different modalities of treatment with special reference to management in a pregnant woman. Section 3 of the book deals with noninvasive testing. Jennifer Kiessling and colleagues from the University of Alabama at Birmingham outline the use of echocardiography in the diagnosis of various acquired and congenital structural heart lesions in women. In particular, the use of stress echocardiography in the assessment of coronary artery disease is highlighted. Echocardiography in the pregnant woman and its usefulness in the assessment and management of fetal cardiac anomalies are also delineated. The next chapter in this section (Chapter 18) by Francesca Mantovani and associates outline factors affecting the accuracy of diagnostic testing in women and the advantages and disadvantages of various modalities used for noninvasive stress testing including contrast stress echocardiography. The last chapter in this section by Suman and Manish Tandon focuses in detail on the use of radionuclide stress imaging techniques in the evaluation of ischemic heart disease. Radiation considerations are also mentioned. The fourth section of this book relates to heart failure, cardiomyopathy and pericarditis in women. Cynthia Taub and colleagues from Ileana Piña’s group provide a comprehensive review of the etiology, pathophysiology, diagnostic assessment and management issues of heart failure in women in the first chapter of this section. Heart failure in pregnancy is also covered. In the next chapter (Chapter 21), Anant Kharod reviews myocarditis and pericarditis with particular emphasis in women. The etiology, clinical manifestations, diagnosis and treatment options are discussed. The last chapter of this section by Keli Chaviano and colleagues covers all aspects of Takotsubo cardiomyopathy which is characteristically seen in postmenopausal women. Section 5 of the book deals with arrhythmias in women. Deepika Narasimha and Anne Curtis describe in great detail sex-based differences in the epidemiology, prevalence, clinical manifestation, and management of various types of arrhythmias including atrial fibrillation and ventricular tachycardia. This chapter is followed by another one (Chapter 24) by Anurag Singh which specifically discusses ventricular arrhythmias and sudden death in women. The next section (Section 6) consists of chapters on rheumatic heart disease and valvular heart disease in women. The first chapter by Anita Saxsena from New Delhi, India, highlights the problem of rheumatic heart disease in the developing countries and the fact that rheumatic mitral stenosis is much more prevalent in women than men. Various sequele of rheumatic heart disease including its management in pregnancy are given in this chapter. The next chapter by Vijayalakshmi and Chitra Narasimhan provide a detailed review of valvular heart disease in women and this is supplemented by a large number of illustrations depicting various pathological findings. Prosthetic valves are also covered in this chapter. The last chapter in this section (Chapter 27) by Peter Block deals with gender differences in the outcome of the relatively recently developed technique of transcatheter aortic valve replacement. Section 7 of the book describes heart diseases in pregnancy and congenital cardiac lesions frequently seen in women. The first chapter by Akila Subramaniam and Joseph Biggio mentions various physiological changes in the cardiovascular system that occur during pregnancy as well as evaluation and management of acquired and congenital cardiac diseases during pregnancy. A different perspective on the same subject is provided by Reema Chugh in the next chapter (Chapter 29). Next, Lori Blauwet elegantly discusses all aspects of the important topic of peripartum cardiomyopathy. The last chapter in this section, also by Reema Chugh, deals with congenital heart lesions in women. It represents a detailed review of issues pertaining to acyanotic and cyanotic women with congenital heart disease. The last section (Section 8) of the book covers miscellaneous topics. Peripheral arterial disease in women is reviewed by Amy Pollak and Sharon Mulvagh. Diagnostic testing including the use of ankle-brachial index, gender differences in its values and guidelines used in the management are provided in this chapter. Charu Gandotra, in the next chapter, discusses cardiovascular implications of cancer in women. He focusses on commonly used chemotherapeutic agents with potential for cardiac toxicity and various strategies employed for its identification and management. The last chapter of this section and book (Chapter 34) by Stephanie El-Hajj, Navin C Nanda and Fadi G Hage provides a summary of recently published literature on heart disease in women. Because of the large number of contributors, some overlap of content and chapters is inevitable and does exist in the book. However, deliberately, no attempt was made by us to correct this as it was felt that some of it could provide a different perspective to the reader and would serve to reinforce important concepts and issues in the assessment of heart disease in women. Navin C Nanda Nurgül Keser
  • 17. AsmentionedinthePreface,wearemostgratefultoallthecontributorswhoprovidedexcellentchaptersforthisbook. We also appreciate the encouragement provided by the Sakarya University and the International Society of Cardiovascular Ultrasound in the preparation of this book. Special thanks to Shree Jitendar P Vij, CEO and Group Chairman of Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India and Mr Ankit Vij (Managing Director) for their help in publishing this book and all their associates especially Ms Chetna Malhotra Vohra (Senior Manager–Business Development) and Ms Saima Rashid (Development Editor). We also deeply appreciate the help of Lindy Chapman (Administrative Associate) and Kanta Nanda. Acknowledgments
  • 18.
  • 19. Contents Section 1: Prevention and Risk Factors 1. Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic 3 Rachana Kulkarni, Anand Kulkarni 2. Prevention of Heart Disease in Women 10 Rachana Kulkarni, Anand Kulkarni • • Unmodifiable Risk Factors 10 • • Modifiable Risk Factors 11 • • Lifestyle Risk Factors 12 • • Guidelines for Prevention of CVD in Women 12 3. Sex Differences in the Effects of Leading and Most Prevalent Modifiable Risk Factors 17 Sanne AE Peters, Yvonne T van der Schouw, Mark Woodward, Rachel R Huxley 4. Dyslipidemia in Women 30 Lale Tokgozoglu, Uğur Canpolat • • Evaluation and Treatment of Women with Hyperlipidemia 30 • • Management of Dyslipidemia in Women: Translating Evidence from Clinical Trials into Practice 30 • • Management 33 5. Familial Hypercholesterolemia in Women: Its Identification and Management 36 Gopal Ghimire, Navin C Nanda • • Identification of FH 37 • • Management of FH 40 6. Cardiovascular Dysfunction in Women with Metabolic Syndrome 47 Sibel Catirli Enar, Anant Kharod, Navin C Nanda • • Prevalence of Metabolic Syndrome 47 • • Metabolic Syndrome in Coronary Artery Disease and Acute Coronary Syndrome 48 • • Congestive Heart Failure 48 • • Left Ventricular Dysfunction 48 • • Diastolic Dysfunction 48 • • Right Ventricular Dysfunction 49 • • Left Atrial Dysfunction 49 • • Atrial Flutter and Fibrillation 49 • • Carotid Atherosclerosis 49 • • Endothelial Dysfunction 50 • • Hypertension 50
  • 20. xviii Heart Disease in Women • • Hypothyroidism 51 • • Polycystic Ovarian Syndrome 51 • • Obstructive Sleep Apnea 51 7. Hypertension in Women 57 Keith C Ferdinand, Samar A Nasser • • Epidemiology Hypertension: Focus on Women 57 • • Pathophysiology of Hypertension in Women 57 • • Dietary Considerations 58 • • Pharmacotherapy of Hypertension in Women 59 • • Current Aspects of Resistant Hypertension: Definitions, Prevalence, and Outcomes 60 • • Recognition of Refractory Hypertension: A Newer Concept and Call-to-Action 61 8. Stroke and Women 64 Nese Keser, Necati Sirmaci, Luis D Meggo Quiroz, Navin C Nanda • • Hormonal Effects 64 • • Pregnancy and Stroke 65 • • Oral Contraceptive Pills and Hormone Replacement Therapy 66 • • Prevention of Stroke in Women 66 • • Coronary Artery Disease and Aspirin 66 • • Atrial Fibrillation and Stroke 66 9. Women and Smoking 70 Nurgül Keser, Cevdet Erdöl, Luis D Meggo Quiroz, Navin C Nanda • • Smoking: A Global Burden 70 • • Pathophysiology 70 • • Gender and Age Differences 71 • • Clinical Implications 71 • • Associated Exposures 72 • • Public Policy 72 10. Job Burnout, Job Strain (Stress), and Cardiovascular Disease: Selected Review 75 Aryana Jacobs, Zinzi Bailey, Michelle A Albert • • Common Theoretical Frameworks and Definitions Related to Job Stress and Job Burnout 75 • • Job Burnout and CVD Studies 76 • • Job Strain and CVD 77 • • Influence of Psychological Status and Social Support on Job Strain and CVD Risk 78 • • Unemployment and CVD Outcomes 78 • • Job Strain and Select CVD Risk Equivalents 79 11. Atherosclerosis and Autoimmune Disease: Mechanisms and Emerging Treatments 83 Mackram F Eleid, Sharon L Mulvagh, Rekha Mankad 12. Hormonal Transitions and the Cardiovascular System in Women 93 Juliana M Kling, Virginia M Miller, Sharon L Mulvagh • • Regulatory Mechanisms Contributing to Sex Differences in Cardiovascular Physiology 93 • • Sex-Specific Conditions Affecting Cardiovascular Disease in Women 94
  • 21. xix Contents • • Guidelines and Recommendations 96 • • Phenotypic Expression of Cardiovascular Disease in Women 96 Section 2: Coronary Heart Disease 13. A Perspective on Women and Coronary Heart Disease 105 Ezra A Amsterdam • • Epidemiology 105 • • Management 105 • • Risk Factors for CHD 106 • • Clinical Presentation 106 • • Stress Testing 107 • • Pathophysiology of Myocardial Ischemia 107 14. Chest Pain Evaluation in Women Presenting to the Emergency Department 110 Kumar Sanam, Kelli Chaviano, Navin C Nanda • • Clinical Presentation 110 • • Diagnostic Tests 111 • • Imaging Studies 113 • • Differential Diagnosis 116 15. Stable Ischemic Heart Disease in Women 118 Rebecca D Levit, Jane S Titterington, Nanette K Wenger • • Pathophysiology of Gender Differences in Stable Ischemic Heart Disease 118 • • Terminology 120 • • Epidemiology—Scope of the Problem 120 • • Diagnostic Testing for SIHD 121 • • Treatment of SIHD 122 • • Burden of Angina 128 16. Acute Coronary Syndromes in Women 134 Ankit Mehra, Kul Aggarwal • • Pathophysiology 137 • • Plaque Disruption 137 • • Clinical Presentation 139 • • Management 139 • • Treatment 140 • • Antiplatelet Agents 140 • • Fibrinolytic Therapy 142 • • Anticoagulants 142 • • Oral Medications 143 • • Coronary Angiography and PCI 143 • • Outcomes 144 • • Pregnancy and ACS 145 • • Conditions Mimicking ACS 146 • • Spontaneous Coronary Artery Dissection 146 • • Aortic Dissection 147 • • Pulmonary Embolism 148
  • 22. xx Heart Disease in Women Section 3: Noninvasive Testing 17. Echocardiography in Women 155 Jennifer Kiessling, Nurgül Keser, Navin C Nanda, Tugba Kemaloglu Oz, Aylin Sungur, Kunal Bhagatwala, Nidhi Karia • • Ischemic Heart Disease/Stress Echocardiography/Polycystic Ovarian Syndrome 155 • • Takotsubo Cardiomyopathy 160 • • Echocardiography in Pregnancy, Peripartum Cardiomyopathy, and Fetal Echocardiography 162 • • Congenital Heart Disease 168 • • Pulmonary Hypertension 170 • • Structural Heart Disease: MVP, Mitral Stenosis, and Mitral Annular Calcification 170 • • Differences in Echocardiographic Measurements and Technical Considerations 176 • • Other Echo Examples of Pathological Conditions Seen in Women 181 18. Noninvasive Stress Testing in Women 192 Francesca Mantovani, Sahar S Abdelmoneim, Victoria Zysek, Sharon L Mulvagh • • Exercise Electrocardiography 193 • • Imaging Techniques during Stress Testing 195 • • Stress Echocardiography 195 • • Stress Gated Myocardial Perfusion SPECT 199 • • Cardiac PET 199 • • MPI vs SE 200 • • Emerging Stress Test Imaging Modalities in Women with Suspected Coronary Artery Disease: MRI 200 • • Recommendations for Noninvasive Testing in Women with Suspected Coronary Artery Disease 200 19. Stress Myocardial Perfusion Imaging—Diagnosis and Risk Assessment in Women 206 Suman Tandon, Manish Tandon • • Evaluating Clinical Risk 206 • • Exercise Treadmill Test in the Diagnosis and Risk Assessment of Suspected CAD 207 • • SPECT Myocardial Perfusion Imaging 209 • • PET Myocardial Perfusion Imaging 211 • • Flow Quantification with PET 212 • • Radiation Considerations 213 Section 4: Heart Failure. Cardiomyopathy. Pericarditis 20. Women and Heart Failure 221 Cynthia C Taub, Julie J Ramos, Mary L Rosser, Sobia Mujtaba, Ileana L Piña • • Sex Differences in the Manifestation and Outcome of Cardiovascular Disease: Experimental Evidence from Animal Models 222 • • Conditions that Contribute to Heart Failure 223 • • Assessment of Heart Failure 228 • • Management of Heart Failure 229 • • Transition of Care 240 • • Implications from Clinical Trials 241
  • 23. xxi Contents 21. Myocarditis and Pericarditis in Women 252 Anant Kharod, Navin C Nanda • • Defining Sex and Gender 252 • • History And Epidemiology of Myocarditis 252 • • Sex Differences in Normal Cardiac Physiology 253 • • Sex Hormones and the Immune System 254 • • Myocarditis, What We Know 254 • • Clinical Manifestations, Diagnosis, and Treatment 255 • • Pericarditis in Women 257 • • Pericarditis: Symptoms and Diagnosis 257 • • Pericarditis: Treatment 257 22. Takotsubo Cardiomyopathy in Women 262 Kelli Chaviano, Kumar Sanam, Navin C Nanda • • Variants 262 • • Epidemiology 263 • • Etiology 263 • • Precipitating Events and Risks 264 • • Presentation 265 • • Diagnosis 265 • • Treatment 266 • • Prognosis 266 Section 5: Arrhythmias 23. Arrhythmias and Implantable Devices in Women 271 Deepika Narasimha, Anne B Curtis • • Cardiac Electrophysiology 271 • • Diagnostic Testing 272 • • Specific Arrhythmias 273 • • Pharmacotherapy 280 • • Implantable Device Therapy 281 • • Arrhythmias in Pregnancy 283 24. Ventricular Arrhythmia in Women 288 Anurag Singh, Navin C Nanda • • Gender Differences in Mechanism of Ventricular Arrhythmias 289 • • Coronary Artery Disease 289 • • Dilated Cardiomyopathy 289 • • Long QT Syndromes 289 • • Hypertrophic Cardiomyopathy 290 • • Arrhythmogenic Right Ventricular Cardiomyopathy 290 • • Brugada Syndrome 291 • • Catecholaminergic Polymorphic Ventricular Tachycardia 291 • • Idiopathic Ventricular Tachycardia 291 • • Special Considerations in Management of Female Patients 291
  • 24. xxii Heart Disease in Women Section 6:Valvular Heart Disease 25. Rheumatic Heart Disease in Women 295 Anita Saxena • • Burden of the Disease 295 • • Gender Differences 295 • • Etiopathogenesis 296 • • Clinical Features 296 • • Mitral Stenosis 296 • • Mitral Regurgitation 297 • • Aortic Regurgitation 297 • • Aortic Stenosis 298 • • Tricuspid Valve Disease 298 • • Multivalvular Disease 298 • • Diagnostic Evaluation 298 • • Echocardiography in Rheumatic Heart Disease 300 • • Cardiac Catheterization 305 • • Management of Women with Rheumatic Heart Disease 305 • • Gender and Prognosis 306 • • Pregnancy and Rheumatic Heart Disease 306 • • Risk Assessment 307 • • General Principles of Management 307 • • Pregnancy with Mitral Stenosis 307 • • Other Valvular Lesions during Pregnancy 308 • • Pregnancy with Prosthetic Heart Valves 308 26. Native Valvular Heart Disease in Women 311 IB Vijayalakshmi, Chitra Narasimhan • • Mitral Stenosis 312 • • Mitral Regurgitation 316 • • Aortic Stenosis 318 • • Aortic Regurgitation 323 • • Tricuspid Stenosis 324 • • Tricuspid Regurgitation 325 • • Pulmonic Stenosis 326 • • Pulmonic Regurgitation 326 • • VHD in Pregnancy 326 • • General Management of Women with VHD 329 • • Infective Endocarditis 337 27. Gender Differences in Outcomes after Transcatheter Aortic Valve Replacement 344 Peter C Block • • Gender Differences in Cardiac Surgery 344 • • Transcatheter Aortic Valve Replacement 344 • • Possible Mechanisms 346
  • 25. xxiii Contents Section 7: Pregnancy. Congenital Heart Disease 28. Pregnancy and Heart Disease 351 Akila Subramaniam, Joseph R Biggio • • Physiologic Changes in the Cardiovascular System during Pregnancy 351 • • General Evaluation and Management of Cardiac Disease in Pregnancy 352 • • Congenital Heart Disease 355 • • Pulmonary Hypertension 357 • • Valvular Heart Disease 357 • • Cardiomyopathy 358 • • Idiopathic Hypertrophic Cardiomyopathy 359 • • Ischemic Heart Disease and Coronary Artery Disease 359 • • Cardiac Transplantation 360 • • Arrhythmia 360 • • Genetic Causes of Cardiovascular Disease 360 • • Infective Endocarditis and Prophylaxis in Pregnancy 361 • • Artificial Heart Valves and Pregnancy 361 29. Management of Heart Disease in Pregnancy: A Clinician's Approach 368 Reema Chugh • • Common Cardiovascular Management Issues in Pregnancy 369 • • Hypertension in Pregnancy 369 • • Deep Venous Thrombosis 372 • • Anticoagulation 373 • • Endocarditis 374 • • Heart Failure 374 • • Arrhythmias 379 • • Aortic Root Dilation 387 • • Pulmonary Hypertension 389 • • Common Heart Diseases/Defects during Pregnancy 390 • • Valvular Heart Disease 391 • • Coronary Artery Disease 393 • • Cardiac Surgery in Pregnancy 396 • • Cardiopulmonary Resuscitation in Pregnancy 397 • • Preconception Assessment and Counseling 397 • • Maternal Risk Assessment 397 • • Fetal Risk Assessment 398 • • Antenatal Cardiac Assessment and Management 398 • • Labor and Delivery 400 30. Peripartum Cardiomyopathy 407 Lori A Blauwet • • Epidemiology 407 • • Risk Factors 408 • • Genetics 408
  • 26. xxiv Heart Disease in Women • • Proposed Etiologies and Pathophysiological Mechanisms 409 • • Clinical Presentation 410 • • Diagnosis 412 • • Natural History 414 • • Treatment 414 • • Labor and Delivery 419 • • Breastfeeding 420 • • Contraception 420 • • Prognosis 420 • • Subsequent Pregnancy 421 31. Congenital Heart Disease in Women 427 Reema Chugh • • Transitional Issues in Females with CHD 427 • • Medical Records 428 • • Gynecological Health and Contraception in Women with CHD 429 • • Pregnancy in CHD 430 • • Common Medical Issues in CHD 430 • • Exercise Counseling 430 • • Congenital Heart Defects 430 • • Shunt Lesions 431 • • Congenital Valvular Heart Defects 438 • • Complex Congenital Heart Defects 450 • • Cyanotic Congenital Heart Disease 465 Section 8: Miscellaneous 32. Peripheral Arterial Disease in Women: The Unmet Challenge 479 Amy West Pollak, Sharon L Mulvagh • • How is Peripheral Arterial Disease Diagnosed? 479 • • Who Should Be Screened for PAD with an ABI? 479 • • Cardiovascular Risk Factor Modification in PAD 480 • • Treatment of Symptomatic PAD 481 • • Is There a Sex-Based Difference in the Burden of PAD? 481 • • Why are Sex-Based Differences Important? 482 • • What are the Critical Steps Needed to Raise Awareness about PAD in Women? 482 33. Cardiovascular Implications of Cancer in Women 485 Charu Gandotra • • Incidence and Mortality of Cancer in Women 485 • • Disparities in Cancer Epidemiology 485 • • Common Risk Factors for Cancer and Cardiovascular Disease 485 • • Cancer Chemotherapy Cardiotoxicity: Spectrum of Cardiovascular Effects 487 • • Breast Cancer Chemotherapy 488 • • Colorectal Cancer Chemotherapy 491 • • Lung Cancer 492 • • Thoracic Radiation Therapy 492
  • 27. xxv Contents • • Monitoring and Diagnosis of Chemotherapy-Induced Cardiotoxicity 493 • • Prevention and Treatment of Chemotherapy-Related Cardiotoxicity 494 • • Cancer Survivors 494 34. Heart Disease in Women: An Update on Recently Published Literature 499 Stephanie El-Hajj, Navin C Nanda, Fadi G Hage • • Risk Factors 499 • • Pregnancy 503 • • Awareness 503 • • Symptoms 503 • • Stress Testing 504 • • Noninvasive Management 505 • • Invasive Management 506 Index 515
  • 28. 1 S E C T I O N Prevention and Risk Factors
  • 29.
  • 30. Rachana Kulkarni, Anand Kulkarni Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic 1 C H A P T E R INTRODUCTION Cardiovascular disease (CVD), particularly, ischemic heart disease, is the leading cause of death among women in the United States and around the globe. As the average life span is increasing in the developed countries, so is the prevalence of heart disease. In the United States, because of an aging population, the absolute number of deaths due to CVD in women is actually increasing.1 As the risk of CVD increases linearly with age, CVD is the leading cause of hospital admissions as well, and has significant financial implications. Because of the sheer magnitude of this problem, there is a need for increased awareness of the importance of CVD as a major public health issue for women across the world. Let us start by examining some statistics about heart disease in women in the United States. Each year on an average 43 million American women are affected by heart disease. It roughly translates into heart disease killing one woman per minute. Center for Disease Control (CDC) data indicate that heart disease is the leading cause of death among women in the United States, killing 292,188 women in 2009—i.e. one in every four female deaths. Since the last scientific statement on this topic in 1993, when the gender gap in various aspects of CVD was brought to light, a lot of attention has been given to a better appreciation of the influence of gender on heart disease and its management. In spite of that effort, however, important gaps in knowledge remain. Heart disease in women presents a decade later as compared with men. But as women have a higher likeli­ hood to survive longer, the death rates in women due to CVD tends to be equal or higher as compared with the men.1 Also, as indicated by the Framingham Heart study, two- thirds of the women who had sudden cardiac death had no previous symptoms. Since majority of the women never make it to the hospital, presumably because of the lack of awareness of their heart symptoms, raising awareness of heart disease in women and directing the focus on primary prevention seem to be the best approach. Cardiovascular disease has been the leading cause of death among women worldwide. It has been shown very well in the data presented by World Health Organization (WHO) in 2011. The organization studied the 10 leading causes of death among women in the countries with different income levels. The results are outlined below (Figs. 1A to E). It is evident from the above-mentioned data that heart disease is the leading cause of death in women around the globe, regardless of the level of income. Because of the worldwide extent of this health problem and its implications on the world health economics, in 2010, the WHO launched a worldwide effort to draw urgent attention to the number one killer for women. WHO Assis­ tant Director-General Dr. Catherine Le Gales-Camus poin­ ted out that. “Although most women fear cancer, particularly breast cancer, they do not make the same efforts to safeguard themselves from heart disease, which is eminently preven­ table.” As Dr. Le Gales-Camus has stated, heart disease is the most common cause of fatality in women everywhere. However, in spite of clear evidence, most women still con­ sider breast cancer as their number one threat. We, as physicians, know that the anatomy and physio­ logy of the heart is the same in men and women. Then, we wonder, why would there be a difference in heart disease
  • 31. 4 Section 1 Prevention and Risk Factors Figs. 1A to E: WHO Media center—Women’s health, Fact Sheet N0 334, September 2013, Data source for charts: Cause specific mortality: regional estimates for 2000-2011. A C E B D in men and women at every step from the diagnosis to prognosis. The differences in heart disease in men and women are due to the differences in the perception and presentation of the disease which then leads to the differences in the treatment and follow ups. These in turn ultimately result in the differences in prognosis and survival. Let us examine some of the common myths that women and communities harbor about heart disease. Myth—Heart disease is a man’s disease.
  • 32. 5 Chapter 1 Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic Fact—Heart disease kills more women than men. Since 1984, each year more women have died of heart disease than men (Fig. 2). Since 1984, women have outnumbered men in cardio­ vascular mortality, and the gap continues to widen each year. Yet only one in five women thinks that heart disease is a real threat to them.1 Despite increased awareness over the past decade, only 54% of women recognize that heart disease is their number one killer2 (Fig. 3). Myth—Breast cancer kills more women than heart disease. Fact—Most women perceive breast cancer as their biggest threat and are diligent about their yearly breast examination and mammograms. However, the fact is that heartdiseasekillsmorewomenthanallcancerscombined. Studies show that on an average one in 25 women will die of cancer and one in two women will die of heart disease.1 Myth—Heart disease is a disease of old men. Fact—Increased incidence of smoking and use of birth control pills have increased the incidence of heart disease in women under 55 years of age. More than 50% of myocardial infarction (MI) in women is attributable to smoking. Althoughtheprevalenceofsmokinghasbeendeclining in the United States, the rate of smoking cessation is lower in women than men;1 and after 2000, smoking rates have been higher in women (23%) than men (20%).3 The increased prevalence of smoking and the increas­ ing trend of smoking particularly in young women have definitely contributed to the higher rates of CVD and cardiac deaths in women. Deaths of young women have significant implications on the families and economics alike. Smoking also increases their risk for hypertension. A Norwegian study conducted by Meyer et al.4 demons­ trated that smoking significantly increases cardiovascular and stroke risks in all the age groups in the 54,000 patients studied over three decades. However, it also showed that women who smoked had a higher incidence of cardio­ vascular mortality and morbidity as compared with the men who smoked.4 The longitudinal study showed that two-thirds of the men who smoked had CVD, whereas half of the women who smoked suffered with cardiovascular disease (Fig. 4). Another variable known to have increased the risk of heart disease in women is the lack of physical activity leading to the increased incidence of obesity. The preva­ lence of obesity has increased steadily in women over the last two decades; and according to the 2007 estimates from the National Center for Health Statistics of the Center for Disease Control and Prevention, 60% of the adult women in the United States are overweight. Just over one-thirds of the overweight adult women are obese.5 In the last decade, approximately 34 million American women are classified as obese. Obesity, particularly abdominal obesity, is an important risk factor for CVD in women.6,7 The figure below (Fig. 5) illustrates the CDC data on obesity trends among the adults in the United States in 2011–2012.8 Age-adjusted prevalence of obesity, by sex and age group, among adults at the age of 20 years and over: United States, 2011–2012. Fig. 2: AHA Statistical Update. Heart Disease and Stroke Statis- tics—2011 Update. A Report from the AHA. Circulation. 2011;123: 4e18-e209. Source: Adapted from Rosamond 2008 and Roger 2011. Fig. 3: National Center of Heart Statistics and the American Heart Association. Mosca et al. Circulation. 1997;96:2468-2482.
  • 33. 6 Section 1 Prevention and Risk Factors Increased prevalence of obesity has translated into increased risk of type two diabetes, which then increases the risk of heart disease, several folds.9 Diabetes is asso­ ciated with a threefold to sevenfold elevation in coronary heart disease risk among women, compared with a twofold to threefold elevation among men; this gender-based difference may be because of a particularly deleterious effect of diabetes on lipids and blood pressure in women.5 Approximately 50% of the deaths in patients with type two diabetes is usually due to ischemic heart disease.10 In addition to the above-mentioned misperceptions, the symptoms of heart disease in women could be atypical. In addition to the traditional symptom of chest pain, women present with shortness of breath as a common presenting symptom. Other common symptoms are jaw or shoulder pain, dizziness, nausea, unexplained fatigue, or flu like symptoms.11 Obviously these symptoms are vague and so a lot of women tend to ignore them and do not seek medical attention. Because of the ambiguous and atypical nature of the symptoms, they are likely to be ignored by the healthcare professionals as well. So, it comes as no surprise that the Framingham Heart Study revealed that two-thirds of the sudden cardiac deaths occurred in women with no “known” previous symptoms as compared with only half of the sudden deaths in men.1 The 2012 statistical report from the American Heart Association (AHA) confirms the same finding.12 As for physicians, most of our practice guidelines and textbooks use data obtained in major clinical trials. Since women were involved in less than 25% of clinical trials, the data derived from them comprised of symptoms mostly of men, which then became the basis of traditional medical teaching and practice guidelines. As a result of that, physicians also did not identify and associate the above- mentioned symptoms with heart disease. This gap in acknowledging symptoms of heart disease by patients and physicians has led to delays in diagnosis and seeking and delivering care by patients and physicians alike. So, it is no wonder that more women than men have cardiac arrest as their presenting symptom. It may explain why treatment is less likely to reduce death rate in women as most of them never reach a hospital.13 However, a recent review of literature about the evaluation of chest pain in women suggests that it is advisable to stratify patients in low-, intermediate-, and high-risk categories based on their cardiovascular risk factors, which will then guide the physician to seek appropriate diagnostic measures in a cost-effective manner.14 The 2011 updated effectiveness- based guidelines for primary and secondary prevention of CVD in women provide a very helpful algorithm for the workup to evaluate cardiovascular risk in women. This flow diagram is illustrated in the chapter by the same authors about the prevention of heart disease in women.15 Fig. 4: Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med. 2000 Jul 6;343(1):16-22. Source: Adapted from Stampfer 2000. Fig. 5: CDC data—Age-adjusted prevalence of obesity, by sex and age group, among adults aged 20 and over: United States, 2011-2012. 1 Crude estimate 35.1%. 2 Significant difference from the age of 20 to 39 years. 3 Significant difference from the age of 40 to 59 years. Note: Estimates are age adjusted for all adults of the age 20 years and over by the direct method to the 2000 U.S. census population using the age groups 20–39, 40–59, and 60 and over. Source: CDC/NCHS, National Health and Nutrition Examination Survey, 2011–2012.
  • 34. 7 Chapter 1 Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic Heart disease in women presents a decade later as compared with men. As a result, women have more com­ orbidities such as hypertension, diabetes, and hyper­ lipidemia among others. This puts them at a higher risk for having a more complex clinical picture at the time of presentation and makes them more likely to have com­ plications. Sometimes, the advanced and diffuse nature of the disease at presentation can limit the treatment options for the physicians. The NIH study performed in 2012 shows a clear gender gap in the treatment of heart disease. The study indicates that for a variety of reasons women get less invasive treatment as compared with men.16 They are less likely to be offered with less-invasive therapy, and when offered, they are also more likely to decline the invasive treatment. If they undergo invasive procedures, they are more likely to have complications. After cardiac surgery, they are less likely to opt for rehab and are less likely to follow up. These findings were almost replicated in a French study by Leurent17 of the Centre Hospitalier Universitaire in Rennes, France. Compared with men, women had a significantly higher rate of intrahospital mortality from MI at 9% versus 4.4% (P <0.0001). The study further identified the lack of timely aggressive treatment in women. Women also had a significantly longer median delay between onset of MI symptoms and calling for medical assistance (60 versus 44 min, P <0.0001). Female patients also had significantly more STEMI (S-T elevation myocardial infarc­ tion) complications than men, including atrial fibrillation (7% versus 3%, P <0.0001). Leurent et al.17 also found that women were less likely to be discharged on recommended therapies than men:17 • Aspirin: 95% versus 98%, P <0.0001 • Clopidogrel/prasugrel: 93% versus 95%, P <0.0001 • Beta-blockers: 88% versus 91%, P = 0.001 • Angiotensin converting enzyme (ACE) inhibitors: 62% versus 67%, P <0.0001 • Statins: 89% versus 95%, P <0.0001 • Cardiovascular rehabilitation: 27% versus 47%, P <0.0001. All of these factors translate into worse prognosis for women. They have higher fatality rate than men with the first MI. It is very interesting to see how the gender gap continues through the course. In the Framingham study and the more recent Multicenter Investigation of the limitation of Infarct Size study, women have been shown to have higher in-house mortality rate (13%) as compared with men (7%). By the first year after MI, the mortality was 44% in women as compared with 23% in men. By the second year, the gap continues, as mortality in women was 36% as compared with 21% in men.18 Women were also more likely to have subsequent cardiac events as compared with men.19 The data from the Myocardial Infarction Triage and Intervention registry also indicate that the gender gap in mortality in patients presenting with acute MI can be attributable to women receiving less-acute coro­ nary interventions.20,21 Similar findings were noted in a community study—Atherosclerotic Risk in Communities study.22 A national survey shows that women are also less likely to enrol in cardiac rehabilitation after MI (6.9% versus 13.3%) and coronary artery bypass surgery (20.2% versus 24.6%) than men.23 In addition to lower attendance rate, dropout rates from cardiac rehabilitation are also higher in women than men.24 World Health Organization and the Indian Council of Medical Research collaborated to study heart disease in women.3 The study showed that urbanization in deve­ loping countries has added several new variables to the traditional risk factors. As more women are entering the office work force, it has led to a lack of physical activity and an increased consumption of fast food and restaurant cooked food, which tends to have higher caloric content, which can translate into weight gain. Other factors that may increase cardiovascular risks are increased prevalence of smoking, rise in the use of birth control measures, and consumption of alcohol. All of these factors have contributed to the increased risk of heart disease in the urban women population in the developing countries. In 1997, the AHA commissioned a survey to study the awareness of heart disease in women and the health­ care community. The study identified and recognized a significant gap and lack of awareness about heart disease in women in the general population and healthcare providers alike.25 “This is a missed opportunity,” said Lori Mosca, MD, MPH, PhD, lead author of the study. “Habits established in younger women can have lifelong rewards. We need to speak to the new generation, and help them understand that living heart healthy is going to help them feel better, not just help them live longer. So often the message is focused on how many women are dying from heart disease, but we need to be talking about how women are going to live—and live healthier.” As a result of this gap, in 2003, AHA started the “Go Red for Women” initiative. The purpose was to raise awareness of heart disease in women, physicians, and communities.
  • 35. 8 Section 1 Prevention and Risk Factors The “Red Dress,” which is a symbol of the “Go Red for Women” initiative, is meant to be a red alert for women to be aware of the risks of heart disease in them and to take action to protect them. Fortunately, this initiative has been a great success. It has helped to bring this issue at the forefront of scientific discussions and has captured the attention of news media. A comparative analysis of the awareness in women about the aforementioned issue in 1997 and 2012 shows that in 1997, only 30% of women identified heart disease as the leading cause of death. By 2012, however, the percentage of women acknowledging the same rose to 56%. In 1997, 35% women listed breast cancer as their biggest threat and by 2012 that number had dropped to 24%. The number of women who identified heart disease as a leading cause of death in women has doubled in the last 10 years. With WHO recognizing the impact of heart disease in womenasapreventableglobalissue,manyothercountries have started taking measures to evaluate this problem at their national level. Heart disease is a threat to women and their families across the globe. As is evident from the data presented here, it is mostly preventable. Because of the enormous social and economic implications of heart disease in women, more countries need to dedicate resources to raise awareness of heart disease in women and physicians alike, so that measures can be taken to stop this silent epidemic. ACKNOWLEDGMENTS We are thankful for the support and guidance of Dr. Navin Nanda. We appreciate the assistance of Mr. Aditya Kulkarni BA, MPH. REFERENCES 1. American Heart Association. 1997 Heart and Stroke Facts: Statistical Update. Dallas, Tex: American Heart Association; 1996. 2. Mosca L, Mochari-Greenberger H, Dolor RJ, et al. Twelve- year follow-up of American women’s awareness of cardio­ vascular disease risk and barriers to heart health. Circ Cardiovasc Qual Outcomes. 2010;3:120-127. 3. Surveillance for selected tobacco-use behaviors—United States, 1900–1994. Morb Mortal Week Rep. 1994;43(SS-3): 1-43. 4. Meyer H. Tremendous impact of smoking on mortality and cardiovascular disease,. Europian Society of Cardio­ logy University of Oslo and Norwegian Institute of Public Health; 2009. 5. Pate RR, Pratt M, Blair SN, et al. Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. JAMA. 1995;273:402-07. 6. Manson JE, Stampfer MJ, Colditz GA, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med. 1990;322:882-9. 7. Folsom AR, Daye SS, Sellers TA, et al. Body fat distri­ bution and 5-year risk of death in older women. JAMA. 1993;269:483-7. 8. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. Obes Res. 1998;6 suppl 2:51s-209s. 9. Manson JE, Spelsberg A. Risk modification in the diabetic patient. In: Manson JE, Ridker PM, Gaziano JM, Hennekens CH (Eds). Prevention of Myocardial Infarction. New York, NY: Oxford University Press; 1996.pp. 241-73. 10. Geiss LS, Herman WH, Smith PJ. Mortality in non-insulin- dependent diabetes. Diabetes in America. National Insti­ tutes of Health, National Institute of Diabetes and Digestive and Kidney Disease; 1995. pp. 249-50. 11. National Heart, Lung and Blood Institute. What are the signs and symptoms of heart disease? [online]Available from: www.nhlbi.nih.gov/health/health-topics/hdw/signs. html. [Accessed July, 2013]. 12. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-220. 13. Kochanek KD, Xu JQ, Murphy SL, et al. Deaths: final data for 2009 [PDF-2M]. National Vital Statistics Reports. 2011; 60(3). 14. Douglas PS, Ginsburg GS. The evaluation of chest pain in women. N Engl J Med. 1996;344:1311-15. 15. Mosca et al. Circulation. 2011;123:1243-62. 16. Claassen M, Sybrandy KC, Appelman YE, et al. World J Cardiol. 2012;4(2):36-47. 17. Leurent, G, Garlantézec R, Auffret V, et al. Gender differ­ ences in presentation, management and in hospital out­ come in patients with ST-segment elevation myocardial infarction: data from 5,000 patients included in the ORBI prospective French regional registry. Arch Cardiovasc Dis. 2014;107(5):291-8. 18. Kannel WB, Wilson PW. Risk factors that attenuate the female coronary disease advantage. Arch Intern Med. 1995; 155:57-61. 19. Tofler GH, Stone PH, Muller JE, et al. Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women. J Am Coll Cardiol. 1987;9:473-82. 20. Kudenchuk P, Maynard C, Martin J, et al. Comparison of presentation, treatment, and outcome of acute myocardial infarction in men versus women (the Myocardial Infarc­ tion Triage and Intervention Registry). Am J Cardiol. 1996; 78:9-14.
  • 36. 9 Chapter 1 Cardiovascular Disease in Women: Myths and Facts about a Silent Epidemic 21. Douglas PS, Ginsburg GS. The evaluation of chest pain in women. N Engl J Med. 1996;344:1311-15. 22. Weitzman S, Cooper L, Chambless L, et al. Gender, racial, and geographic differences in the performance of cardiac diagnostic and therapeutic procedures for hospitalized acute myocardial infarction in four states. Am J Cardiol. 1997;79:722-26. 23. Thomas RJ, Miller NH, Lamendola C, et al. National survey on gender differences in cardiac rehabilitation prog­ rams: patient characteristics and enrollment patterns. J Cardio­ pulm Rehabil. 1996;16:402-12. 24. Cannistra LB, Balady GJ, O’Malley CJ, et al. Comparison of the clinical profile and outcome of women and men in cardiac rehabilitation. Am J Cardiol. 1992;69:1274-79. 25. Allender S, Lacey B, Webster P, et al. Level of urbanization and noncommunicable disease risk factors in Tamil Nadu, India. Bull WHO. 2010;88:297-304.
  • 37. Rachana Kulkarni, Anand Kulkarni Prevention of Heart Disease in Women 2 C H A P T E R An apple a day, keeps the doctor away. But does it prevent heart disease? Is it true that increased consumption of fruits can prevent heart disease? What about antioxidants then? What works? And does it matter? Isn’t heart disease a disease of men and women who need not worry about it? There are many myths about heart disease in women. Let us try to get some clarity on this. Cardiovascular disease (CVD) is the number one killer of women. CVD kills more women than stroke, lung cancer, breast cancer, and chronic obstructive pulmonary disease (COPD) combined.1 Statistics state that every third death is from CVD. One in six deaths results from coronary artery disease (CAD). A great deal of progress has been made since 1999 in the prevention and treatment of heart disease in women.2 The good news is that age-adjusted mortality from heart disease decreased from 1980 to 2002 in men (52%) and women (49%). The badnewsis thatwe areseeing a reversal in that trend. Heart disease death rate among the women of 35–54 years of age in the United States is now increasing. This may be because of the changes in several risk factors leading to CAD.3 Women all over the world are now entering the work force. More sedentary life style is being adopted, leading to obesity and diabetes. Smoking rates are on the rise. A lot needs to be done to reverse this trend. To decrease CVD related mortality, it is not enough to work only on prevention. Along with the measures to be taken to prevent heart disease in women, it is also necessary to increase awareness of this leading cause of death. In the United States, for example, public awareness of CVD as the leading cause of death has increased to 54% in 2009. It was only 30% in 1997.4 It is important that women should call for help at the onset of cardiac symptoms to improve survival from cardiac events. In a recent survey by the American Heart Association (AHA), only 53% of women said that the first thing they would do if they thought they were having a heart attack was to call 911.4 Women need to be aware of high prevalence of heart disease, symptoms of heart disease, and of the need to seek immediate help at the onset of symptoms. Prevention of heart disease hinges on understanding the risk factors and then efforts to modulate them. These risk factors are commonly divided into those that can be modified to decrease the risk and those that cannot be modified. UNMODIFIABLE RISK FACTORS Age Prevalence of heart disease increases with age. This is true in men as well as in women. It is seen that the first presentation of CAD occurs approximately 10 years later in women than in men. The INTERHEART study performed in 42 countries around the world shows that a difference of 8–10 years in age at the onset is seen widely around the world (Table 1).5 It is thought that before menopause, women are protec­ ted from development of atherosclerotic cardio­ vascular disease (ASCVD) because of the presence of estrogen. This explanation is very attractive but it should be remembered that in clinical practice, the replacement of estrogen after menopause does not prevent cardio­ vascular events and is a Class 3 indication according to the Effectiveness Based Guidelines for Prevention of Cardiovascular Disease in Women.6-10
  • 38. 11 Chapter 2 Prevention of Heart Disease in Women Family History Genetic contribution to heart disease is well-known and it is well documented that CAD and death from CVD have a hereditary component. The genetic transmission in families is rarely monogenic with a Mendelian pattern. More commonly, it is complex reflecting multiple genes, each contributing modestly to a predisposition to atherosclerosis and atherothrombotic events. The statistical association of gene variants with coronary disease differs in men and women, suggesting that different pathways may operate in the manifestation of CVD between men and women. In women, stromely­ sin 1 (a member of matrix metalloproteinase family of enzymes) and plasminogen activator inhibitor (PAI-1) are thought to be important. In men, two different genes are associated with MI—the gap junction protein Connexin 37 and p22(phox), a component of NAD(P)H redox system.11 The different manifestations may be because of the presence of circulating estrogens or presence or absence of the Y chromosome. Only limited work has explored sex differences in gene expression, proteomics, or metabolomics. Further work in these areas may provide important insights into the development, diagnosis, and tailored treatment of CVD in the two sexes.12 MODIFIABLE RISK FACTORS Hypertension High blood pressure (BP) is long known to be associated with risk of development of CVD and CAD. In a meta- analysis of 61 prospective studies published in the journal Lancet in 2002, more than one million healthy adults were studied between the age of 49 and 89 years. CAD risk was slightly higher in women than men. Hypertension (HTN) is increasing in the United States in both sexes but more so in women who have 15% higher prevalence than men.13,14 Under the age of 35 years, HTN was more prevalent in men than in women. The prevalence of HTN increases with age in both sexes, but from the age of 45 to 54 years, the rate of rise was greater in women than in men. After the age of 65 years, a higher percentage of women than men have HTN and the gap increases with continued age.15 The difference in prevalence reaches statistical significance at 75 years of age. The problem does not stop there. Not only the preva­ lence increases with age, women are more likely to be undertreated. In the National Health and Nutrition Exami­ nation Survey (NHANES) over time (1988–1994 and follow up survey 1999–2000), in men, the treatment rate increased by 9.8% and control rate by 15.3%. In women, the treatment rate increased by a mere 1.9% and control rate by only 0.5%.16 This lack of improvement is really concerning. Diabetes Mellitus Diabetes mellitus (DM) increases the risk of CVD in women. Diabetes is a risk factor for the development and severity of CAD in both men and women but carries a greater risk in women that completely eliminates “the female advantage.”17,18 CVD is twice as common in women with DM compared with those without DM. Diabetic women are four times as likely to be hospitalized as com­ pared with nondiabetics. Prevalence of DM is increasing rapidly in the United States. Between 1990 and 2001, it rose by 61%.1 In 2006, out of 17 million patients with known DM, 9.5 million were Table 1: Comparison of age at first myocardial infarction Region Median age women Median age men Western Europe 68 61 Central and Eastern Europe 68 59 North America 64 58 South America and Mexico 65 59 Australia and New Zealand 66 58 Middle East 57 50 Africa 56 52 South Asia 60 52 China 67 60 Southeast Asia and Japan 63 55 Ethnic origin European 68 59 Chinese 67 60 South Asian 60 50 Other Asian 63 55 Arab 57 52 Latin American 64 58 Black African 54 52 Colored African 58 52 Other 63 53 Overall 65 56 Source: Modified from Yusuf S et al, the INTERHEART Study.5
  • 39. 12 Section 1 Prevention and Risk Factors women (more than 50%). It is also seen that women are less likely to be treated to HbA1c goal than men are.1 Hyperlipidemia Hyperlipidemia, a known risk factor for the development of CAD, is not much more common in women at a young age. According to a statistic from the AHA, 47% of the women have total serum cholesterol of 200 mg/dL or more and 31.7% have low-density lipoprotein (LDL) cholesterol level of 130 mg/dL or more. This is similar to the general population. Only 6.7% of women have high-density lipoprotein (HDL) of less than 40 when compared with 15.5% of overall Americans. Things begin to change around menopause. Total chol­ esterol and LDL cholesterol increase on an average by about 10% from levels at 6 months before menopause. Menopause affects HDL cholesterol less dramatically. HDL concentration declines gradually in the two years before menopause and then levels off after menopause. The postmenopausal increase in CVD risk may result partly from these lipid profile changes. LIFESTYLE RISK FACTORS Obesity and Sedentary Lifestyle Obesity, described as body mass index (BMI) greater than 30 kg/sq meter, has been rapidly increasing. Prevalence of obesity increased from 12.2% in 1991 to 20.8% in 2001.19 It increased further to 35.3% in the 2005–2006 NHANES. There is an epidemic of obesity in the United States. Vigorous physical exercise is needed to modify several riskfactorsandtodecreaseriskofheartdisease.Prevalence of physical exercise is very low in women. National Center for Health interview survey reported in 2007 that 66.3% women never performed vigorous physical activity and only 9.8% engaged in vigorous physical activity, 5 days or more per week. Objective accelerometer data from NHANES were even more concerning with only 2.5%–3.2% women doing 30 minutes of exercise at least 5 days per week.20 Smoking Smoking is a strong independent risk factor for CAD in both men and women. Estimated prevalence of smoking in women 18 years of age or older was 18%–23% in 2006.1 Although smoking rates in the United States are falling overall, they are increasing in women.21 This risk is not improved by low nicotine cigarettes and is present even with minimal exposure.22 Women using contraceptive pills and smoking are at particularly high risk especially after the age of 35 years.23 Women find it harder to quit smoking than men, probably because of the weight gain seen with stopping smoking. Smoking can also lead to earlier menopause, a risk factor that is unique to women.23 GUIDELINES FOR PREVENTION OF CVD IN WOMEN Identifying the fact that heart disease in women presents differently, behaves differently, and requires a different consideration for prevention is an important step. In 2004, AHA along with several other organizations sponsored the “Evidence Based Guidelines for Cardiovascular Disease Prevention in Women.” Initially, the guidelines challenged the conventional thinking that women should be treated the same as men. Concerns were also raised about lack of representation of women in clinical trials. Since then, over time, more women have participated in clinical trials and more gender-specific analysis has become available. Considering the health implications and economic costs associated with CVD in women, sustained efforts are needed to apply evidence-based therapies that work. In2007,theguidelineswereupdated.10 Anewalgorithm for risk classification in women was adopted. This was revised when 2011 AHA guidelines were published.24 Three risk categories were identified—(1) at high risk, (2) at risk, and (3) at optimal risk (ideal cardiovascular health). Among the high risk, the rate of MI, CHD death, and stroke was 19%, at risk 5.5%, and at optimal risk 2.2% per 10 years. A major difference from prior guidelines to 2011 updates is that instead of limiting recommendations to evidence based (benefits observed in clinical research), effectiveness-based (benefits and risks observed in clinical practice) recommendations were considered.24 The American College of Cardiology (ACC) and AHA in 2013 came up with a new tool to calculate 10 year and lifetime risk for ASCVD.25 Along with traditional risk factors of age, DM, hyperlipidemia and hypertension, various other parameters like race, and sex were also introduced into the calculations to get to this prediction and determine the need for further work up as well treatment. New recommendations from ACC/AHA guide­ lines for lipid management came in November 2013.26 Eighth Joint National Committee (JNC8) guidelines for HTN management came online in December 2013 and
  • 40. 13 Chapter 2 Prevention of Heart Disease in Women print published in 2014.27 It is expected that these will be incorporated in the next AHA update for guidelines for prevention of CVD in women. Major Risk Factor Interventions Hypertension Treatment of HTN can go a long way in helping prevent CVD as well as stroke. JNC8 recommendations set some- what different targets for BP levels.27 • For patients less than 60 years of age, drug therapy should be considered for systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. The goal is <140/90 mm Hg. • For patients 60 years or older, drug therapy should be considered for systolic BP ≥150 mm Hg or diastolic BP ≥90 mm Hg. The goal is <150/90 mm Hg. If pharmacologic treatment for high BP results in systolic BP <140 mm Hg and treatment is well tolerated and without adverse effects, there is no need to adjust therapy. • For patients with diabetes and patients with chronic kidney disease (CKD), the threshold to initiate drug therapy is 140/90 mm Hg. The goal is <140/90 mm Hg. • In nonblack patients, including those with DM initial drug-classchoicesarethiazide-typediuretics,calcium- channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin-receptor bloc­kers (ARBs). • In black patients, including those with DM, acceptable initial drug-class choices are thiazide-type diuretics or CCBs. • Patients with CKD generally should receive ACE inhi­ bitors or ARBs. This is true for all patients with CKD, regardless of race or presence of DM. Diabetes Mellitus Lifestyle modifications and pharmacotherapy are recom­ mended in women to achieve HbA1c <7, if this can be achieved without significant hypoglycemia. A lot of litera­ ture is available in medical and endocrine journals on this issue. At this point, achieving HbA1c below 6 does not seem to confer extra protection. Hyperlipidemia Pharmacotherapy is recommended for LDL-C lowering in high risk women. While prior recommendations set specific levels as targets, new 2013 ACC/AHA guidelines usedtheintensityofstatintherapyasthegoaloftreatment.26 Four groups of individuals were identified for whom an extensive body of evidence from randomized controlled trials demonstrated a reduction in ASCVD events with a good margin of safety from moderate- or high-intensity statin therapy: • Individuals with clinical ASCVD • Individuals with primary elevations of LDL-C ≥190 mg/dL • Individuals 40–75 years of age with DM and LDL-C 70–189 mg/dL without clinical • ASCVD • Individuals without clinical ASCVD or DM who are 40–75 years of age with LDL-C 70–189 mg/dL and have an estimated 10-year ASCVD risk of 7.5% or higher. High-intensity statin therapy reduces LDL-C by appro­ ximately 50% and includes Atorvastatin 40–80 mg and Rosuvastatin 20–40 mg. Moderate-intensity statin therapy lowers LDL-C by approximately 30%–50%. Low-intensity statin therapy lowers LDL-C on average by 30%. Although high-intensity statin therapy reduces ASCVD events more than moderate-intensity statin therapy, lower-intensity statin therapy has also been shown to reduce ASCVD events, although to a lesser degree. Therefore, individuals that merit guideline-recommended statin therapy should be treated with the maximum appropriate intensity of a statin that does not cause adverse effects. Because evidence from randomized controlled trials shows that the absolute benefit of statin treatment is proportional to baseline ASCVD risk, treatment decisions for women should be based on the level of ASCVD risk. This conclusion is a departure from previous approaches that focused on LDL-C levels to guide treatment decisions. Statin treatment based on estimated 10-year ASCVD risk avoids the overtreatment of lower-risk groups such as younger, non-Hispanic White women who, despite moderate elevations in LDL-C, are typically not at significantly increased risk for ASCVD in the next 10 years in the absence of substantial risk-factor burden. However, ignoring the increased ASCVD risk in African American women might result in the under treatment of some individuals who are at significantly higher ASCVD risk at the same LDL-C level. Thus, this guideline recommends statin therapy for individuals in whom it is most likely to provide ASCVD risk reduction based on the estimated 10-year risk of ASCVD.
  • 41. 14 Section 1 Prevention and Risk Factors Non-statin therapy for hyperlipidemia, with or without statin, may sometimes need to be considered. Use of nia­ cin, bile acid sequestrates, fibrates, omega 3 fatty acids, and agents like Ezetimibe that inhibit cholesterol absorp­ tion may be monitored as carefully as in men. Cigarette Smoking Smoking cessation is one of the most effective and cer­ tainly the least expensive approach to disease prevention. It does not cost anything and may in fact save money. Women should be advised not to smoke and to avoid second hand smoke as well. After smoking cessation, the risk for MI quickly declined and the risk for CAD became similar to nonsmokers at about 3 years. Despite this, not many women who smoke are advised to quit by the health care providers. Data from Centers for Disease Control indicate that only close to 50% smokers who had at least one visit to their health care provider were advised to quit.28 It has been estimated that each year an additional 1 million smokers could be helped to quit smoking if they got a brief counseling.29 Brief counseling should include determining whether a patient smokes, advising any patient who smokes to quit, assisting the patient in quitting, for example, by setting a quit date and providing self-help material and scheduling follow-up visits to reinforce adherence.30,31 Providers should counsel women at each encounter, advise behavioral program or formal smoking cessation program, nicotine replacement, and other pharmacotherapy. Physical Activity Physicalactivityandvigorousregularexerciseisamainstay of staying healthy. Women should be advised to achieve at least 150 min/week of moderate exercise and 75 min/week of vigorous exercise. More benefit is obtained by increasing moderate intensity aerobic physical activity to 5 h per week, 2.5 h of vigorous intensity exercise, or an equivalent combination of both.24 Women should also be advised to do muscle strengthening exercises 2 or more days of the week. Women who need to lose weight should be advised to do a minimum of 60–90 min of at least moderate intensity exercises on most and preferably all days of the week.24 Prudent exercise programs are cost effective and have a low potential for adverse effects.32 Exercise should be individualized to accommodate the patient’s level of physical fitness, cardiac status, and preferred activities. Weight Maintenance/Loss Women should be advised to maintain or lose weight through a combination of lower caloric intake, physical activity, and formal behavioral programs to achieve an appropriate body weight (e.g. BMI <25 kg/sq meter).24 Dietary Intake Women should consume a diet rich in fruits and vegetables and to choose whole grain high fiber foods (Table 2). They should be advised to eat fish, especially oily fish at least twice a week. They should limit intake of saturated fat, cholesterol, alcohol, salt, sugar, and avoid trans-fatty acids. Effectiveness-based guidelines in the 2011 update have excellent recommendations24 What Does Not Work/May Be Harmful The effectiveness-based guidelines also came up with recommendations on the things that do not work (Class 3 indication).24 Menopausal therapy: Hormone therapy should not be used for primary or secondary prevention of CVD. Antioxidant supplements: Vitamin C, E, and beta caro­ tene should not be used for primary or secondary preven­ tion of CVD. Folic acid with or without B6 and B12 supplements should not be used for primary or secondary prevention of CVD. Aspirin for MI in women <65 years of age: Routine use of Aspirin is not recommended for prevention of MI in healthy women less than 65 years of age. A very helpful approach to primary and secondary prevention is outlined below as recommended in 2011 update to effectiveness-based guidelines for prevention of CVD in women (Flow chart 1). Thus, an apple a day may not keep the doctor away but a diet rich in fruits and vegetables and nuts is definitely recommended to prevent heart disease in women. Anti­ oxidants, despite the hype in the last few years, are not. Aspirin, while routinely recommended in the past, is not recommended in women younger than 65 years of age. As the epidemic of obesity is increasing in the United States and as CVD is increasing in some age groups in women, a prevention strategy involving dietary intervention and increasing physical exercise is essential to combat this growing threat.
  • 42. 15 Chapter 2 Prevention of Heart Disease in Women ACKNOWLEDGMENTS We appreciate the guidance and support of Dr Navin C Nanda. We are grateful for the support provided by Aditya Kulkarni MPH. REFERENCES 1. Lloyd-Jones D, Adams R, Carnethon M et al. Heart dis- ease and stroke statistics—2009 update: A report from the American Heart Association Statistics Committee and Stroke-Statistics Subcommittee. Circulation. 2009;119:w21. 2. Mosca L, Grundy SM, Judelson D, et al. Guide to preventive cardiology for women: AHA/ACC Scientific Statement Consensus panel statement. Circulation. 1999;99:2480. Table 2: Dietary intake recommendations for women Nutrient Serving Serving size Fruits and Vegetables >4.5 cups /day 1 cup raw leafy vegetables, ½ cup cut-up raw or cooked vegetables, ½ cup vegetable juice, 1 medium fruit, ¼ cup dried fruit, ½ cup fresh frozen or canned fruit, ½ cup fruit juice Fish 2/wk 3.5 oz, cooked (preferably oily types of fish Fiber 30g/d(1.1g/10g carbohydrate) Bran cereal, berries, avocado, and so on Whole grains 3/day 1 slice bread, 1 oz dry cereal, 1/2 cup cooked rice, pasta, or cereal (all whole-grain products) Sugar <5/wk (450 kcal/wk from sugar- sweetened beverages 1 tablespoon sugar, 1 table- spoon jelly or jam, 1/2 cup sorbet, 1 cup lemonade Nuts, Leg- umes, Seeds >4/wk 1/3 cup or 1 1/2 oz nuts (avoid macadamia nuts and salted nuts), 2 tablespoons peanut butter, 2 tablespoon or 1/2 oz seeds, 1/2 cup cooked legumes (dry beans and peas) Saturated fat <7% total energy intake Found in fried foods, fat on meat or chicken skin, packaged desserts, butter, cheese, sour cream, and so on Cholesterol <150 mg/day Found in animal meats, organ meats, eggs, and so on Alcohol One drink or less 4 oz wine, 12 oz beer, 1.5 oz of 80 proof sprits or 1 oz of 100 proof sprits Sodium <1500 mg Trans-fatty acids 0 Mosca L et al. Circulation, 2011; 123:1243-1262. Flow chart 1: Prevention of CAD in women24
  • 43. 16 Section 1 Prevention and Risk Factors 3. Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med. 2007;356:2388-98. 4. Mosca L, Mochari-Greenberger H, Dolor RJ, et al. Twelve- year follow-up of American women’s awareness of cardio­ vascular disease risk and barriers to heart health. Circ Cardiovasc Qual Outcomes. 2010;3:120-7. 5. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarc­ tion in 52 countries (the INTERHEART study): Case Control Study. Lancet. 2004;364:937. 6. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coro­ nary heart disease in postmenopausal women. JAMA. 1998; 280:605. 7. Grady D, Herrington D, Brenner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progestin Replacement Study follow-up (HERS II). JAMA. 2002;288:49. 8. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523. 9. Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health initiative rando­ mized controlled trial. JAMA. 2004;291:1701. 10. Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 Update. Circulation. 2007;115:1481. 11. Yamanda Y, Izawa H, Ichihara s, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002;347:1916. 12. Newby LK, Douglas PS. Cardiovascular Disease in Women, Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 9th edition. Philadelphia, PA: Elsevier Saunders; 2012. p. 1757. 13. Fields LE, Burt VL, Cutler JA, et al. The burden of adult hypertension in the United States 199 to 200: A rising tide. Hypertension. 2004;44:398. 14. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: A meta- analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903 15. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123:e18. 16. Hajjar, I, Kotchen TA. Trends in prevalence, awareness, treatment and control of hypertension in the United States, 1988–2000. JAMA. 2003;290:199. 17. Wang XL, Tam C, McCredie RM, et al. Determinants of severity of coronary artery disease in Australian men and women. Circulation. 1994;89:1974. 18. Spelsberg A, Ridker PM, Manson JE. Carbohydrate meta­ bolism, obesity and diabetes. In: Douglas PS (Ed). Cardio­ vascular Health and Disease in Women. Philadelphia: WB Saunders Company; 1993. p. 191 19. Mokdad AH, Ford ES, Bowman, BA, et al. Prevalence of obesity, diabetes and obesity related health risk factors, 2001. JAMA. 2003;289:76. 20. Troiano RP, Berrigan D, Dodd KW, et al. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc. 2008;40:181. 21. Fried LP, Becker DM. Smoking and cardiovascular disease. In: Douglas PS (Ed). Cardiovascular Health and Disease in Women. Philadelphia: WB Saunders Company; 1993. p. 217. 22. Colditz GA, Bonita R, Stampfer MJ, et al. Cigarette smoking and risk of stroke in middle aged women. N Engl J Med. 1988;318:937. 23. Shapiro S, Sloane D, Rosenberg L, et al. Oral contracep­ tive use in relation to myocardial infarction. Lancet. 1979; 1:743 24. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update, a guideline from the American Heart Association. Circulation. 2011;123:1243. 25. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/ AHA guide­ line on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2935-59. 26. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce athero­ sclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Asso­ ciation Task Force on Practice Guideline. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934. 27. James PA, Oparil S, Carter B, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the Eighth Joint National Committee (JNC8). JAMA. 2014; 311(5):507. 28. Physician and other health-care professional counselling of smokers to quit—United States, 1991. MMWR. 1993; 42:854. 29. Public Health service: Healthy People 2000: National health Promotion and disease prevention objectives—full report, with commentary. (DHHS publication no PHS 91-50212. Washington DC: US Department of Health and Human Services. Public Health Service, 1991. 30. Glynn TJ, Manley MW. How to help your patients stop smoking: A national cancer Institute manual for physicians. (DHHS publication no. PHS 92- 3064. Bethesda, MD: US. Department of Health and Human Services, National institute of Health, National cancer Institute 1992. 31. Farmer JA, Gotto AM. Dyslipidemia and Other Risk Factors for Coronary Artery Disease. Braunwald’s Heart Disease. Philadelphia, PA: WB Saunders Company; 1997. 32. Levine GN, Balady GJ. The benefits and risks of exercise training: The exercise prescription. Adv Intern Med. 1993; 38:57.
  • 44. Sanne AE Peters, Yvonne T van der Schouw, Mark Woodward, Rachel R Huxley Sex Differences in the Effects of Leading and Most Prevalent Modifiable Risk Factors 3 C H A P T E R Despite substantial progress in the awareness, treatment and prevention of cardiovascular disease (CVD) over the past decades, CVD remains the world’s leading, and argu- ably the most preventable, cause of death and disability.1 Moreover, despite considerable efforts to raise awareness of CVD and its symptoms, there is still a widespread per- ception, particularly in lower and middle-income coun- tries, that CVD is a disease that predominantly affects men.2 However, as women have a greater life expectancy than men, the cardiovascular burden in absolute terms, is actually greater in women than in men; in 2004, almost 32% of all deaths in women were due to cardiovascu- lar causes compared with 27% in men.3 These estimates, and the notable sex difference in cardiovascular burden, are likely to increase further due to population aging, a higher life expectancy and the decade delay in the development of symptomatic CVD in women relative to men.4-7 Sex differences can be identified throughout the entire life course of CVD. Compared with men, women are less likely to receive pharmacological treatment for the management of cardiovascular risk factors;8,9 coronary ischemic attacks present differently in men and women, such that women are more likely to delay seeking medical attention than men;10-12 women are less likely to be referred for diagnostic and therapeutic procedures;13 and the prognosis for women with CVD is usually worse than it is for men.14-16 Moreover, despite the significant anatomical, physiological and behavioral differences between men and women, it is commonly assumed in medicine that the effects of risk factors on disease outcomes are the same in women as in men. This assumption largely stemmed from the historical fact that (with the rare exception) most of the early cohort studies and randomized trials that were initiated in the mid-20th century were comprised solely of men.17-20 However, since the initiation in the 1980s and more recently, of large prospective cohorts comprising both men and women,21,22 or solely women,23-26 we are now in a position to better test the hypothesis of an equivalency of risk factor effects on cardiovascular and other outcomes between the sexes. Determining reliably, whether there are clinically meaningful sex differences in risk factor–disease asso­ ciations is important, not solely to better understand the etiology of CVD, but also from a population and public health vantage. Convincing evidence of whether sex differences exist in the effect of the most prevalent and modifiable risk factors, including elevated blood pressure, cigarette smoking, diabetes mellitus, excess weight and raised cholesterol, is necessary since these risk factors are among the leading causes of CVD.3 Current estimates of the burden of CVD, which are used to inform public health policy, assume that these risk factors effect cardiovascular risk similarly in women as in men.1,3 However, if this assumption is proven to be invalid, then it would neces­ sitate the revision of the estimates to more accurately reflect the true nature of the relationships in women and men. Moreover, just as possible racial differences in the relationships between risk factors and diseases are considered when tailoring specific interventions for different communities, so could information on important sex differences be used to provide an added impetus for targeted interventions aimed at the treatment and management of these risk factors in both sexes. The objectives of the present review are two-fold. First, we aim to provide an overview of the most current evidence on sex differences in the prevalence of major CVD risk factors. Second, we examine the evidence pertaining