21% Heart Disease in Women:The Magnitude of the Problem. U.S. women who think heart disease is their greatest health threat (7% in 1997)

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1 Heart Disease in Women:The Magnitude of the Problem Sharonne N. Hayes MD, FACC, FAHA Founder, Women s Heart Clinic Mayo Clinic Rochester, MN 21% U.S. women who think heart disease is their greatest health threat (7% in 1997) 48% believe it is cancer (61%, 1997) 2006 AHA Survey: Christian, J Women Health 2007 CP CP Cause of Death in Women Cancer COPD Influenza Diabetes Heart disease Breast Cancer Cerebrovascular disease Deaths (000s) Cardiovascular Deaths Females Males Other Deaths (thousands) AHA Statistical Update, 2007 CP Years AHA Statistical Update: Circulation 121, Perceived Leading Cause of Death in Women Misconceptions % White Black Hispanic X Missed opportunity for. Risk factor intervention Inclusion in research trials 0 Breast cancer Cancer (any) AHA Survey, Mosca: Circulation, 2004 Heart disease Unsure CP CP

Gender and Participation in CV Clinical Trials Only 20-25% female participants in CV trials Historically due to trial design (excluded, age)

Early diagnosis by women and MDs Getting the best treatment CP992570-12 Risks for Missed Diagnosis of Heart Attack Normal/non-diagnostic ECG

Misdiagnosis Less likely to be transferred Lower use of best, proven treatments (angiography, revascularization, aspirin, blockers, statins,

control Lower adherence to proven guidelines (ACC/AHA, NCEP, JNC VII, etc) Mortality Sex Based Treatment and Research Issues Physiologic sex

2 Gender and Participation in CV Clinical Trials Only 20-25% female participants in CV trials Historically due to trial design (excluded, age) Men much more willing to volunteer CP Misconceptions X Missed opportunity for Risk factor intervention Inclusion in research trials Early diagnosis by women and MDs Getting the best treatment CP Risks for Missed Diagnosis of Heart Attack Normal/non-diagnostic ECG Shortness of breath Non-white Woman <55 years old Challenges for Women with Heart Disease Delays in symptom recognition and treatment Misdiagnosis Less likely to be transferred Lower use of best, proven treatments (angiography, revascularization, aspirin, blockers, statins, ACE-I) Pope et al: NEJM, 2000 CP CP Challenges for Women with Heart Disease Less counseling, cardiac rehab and risk factor control Lower adherence to proven guidelines (ACC/AHA, NCEP, JNC VII, etc) Mortality Sex Based Treatment and Research Issues Physiologic sex differences Under-treatment ( Guideline Gap ) Diagnostic testing questions Optimal treatment issues Under-representation and under reporting in research CP

Gender-Specific Guidelines Guidelines Are Good for Women Non gender-specific guidelines often ignored/not on radar screen of womenonly

preventive care 237,225 pts, CAD admit (2002-07) (ASA, β-b, ACE-I, LLT, tobacco) CP1170099-8 Lewis, W. R. et al.

Sex and Gender Differences in Heart Disease Natural history Symptoms Accuracy of diagnostic tests Risk factors Hormones

risks and symptoms Access to care Accurate diagnosis Appropriate treatment and referral Optimal use of proven therapy (guidelines) Lack of

3 Gender-Specific Guidelines Guidelines Are Good for Women Non gender-specific guidelines often ignored/not on radar screen of womenonly providers Most, but not all, interventions that work in men also work in women, but the evidence is often weak Gender disparities in preventive care 237,225 pts, CAD admit ( ) (ASA, β-b, ACE-I, LLT, tobacco) CP Lewis, W. R. et al. Circ Cardiovasc Qual Outcomes 2009;2: How are Women Different? Sex and Gender Differences in Heart Disease Natural history Symptoms Accuracy of diagnostic tests Risk factors Hormones Behavioral/psychosocial factors Quality of life/personal priorities Communication style Heart Disease in Women Challenges Awareness of risks and symptoms Access to care Accurate diagnosis Appropriate treatment and referral Optimal use of proven therapy (guidelines) Lack of support CP Sex-Based Cardiology: What Now? Eliminate disparities: proven effective interventions are underutilized in women Address sex differences in research trials (power, recruitment) and report results by sex Support women with heart disease CP

4 Solutions to Heart Disease in Women Society Women Government Physicians WomenHeart.org CP Society Government Women Physicians Women s Solutions to Heart Disease Empower yourself Assume primary responsibility for your health Know warning signs of heart attack and have action plan Know personal risk factors and take action to control them CP Heart Disease in Women:The Basics Sharonne N. Hayes MD, FACC, FAHA Founder, Women s Heart Clinic Mayo Clinic Rochester, MN CP Understanding Heart Diseae in Women Heart Disease Myocardium - heart muscle Coronary arteries Heart valves Electrical system Great vessels Pericardium 4

5 Aorta PA Aorta RA RA Right Ventricle Left Ventricle RA PA LA Right Ventricle Left Ventricle Diastole Systole CP Keys to Understanding Coronary Arteries Heart Disease Myocardium - heart muscle Coronary arteries Heart valves Electrical system Great vessels Pericardium CP

Normal Coronary Arteries What Are We Talking About?

abnormalities of the coronary arteries, muscle, valves, or rhythm, (inc.

Coronary heart disease (CHD) CAD plus complications-heart attacks, symptoms

$Dysfunction (LVD) Reduced LV function/ejection fraction Keys to Understanding$

6 Normal Coronary Arteries What Are We Talking About? Cardiovascular Disease (CVD) all heart disease and stroke Heart Disease any and all abnormalities of the coronary arteries, muscle, valves, or rhythm, (inc. congenital) CP What Are We Talking About? What Are We Talking About? Coronary artery disease (CAD) atherosclerosis (blockages) in the coronary arteries Coronary heart disease (CHD) CAD plus complications-heart attacks, symptoms (angina) Congestive Heart Failure (CHF) Clinical diagnosis; inability of the heart to pump enough blood to meet the needs of the rest of the body Left Ventricular Dysfunction (LVD) Reduced LV function/ejection fraction Keys to Understanding Artery narrowed by atherosclerosis Atherosclerosis Myocardial infarction Ischemia Angina artery wall blood fatty deposit cross section of artery 6

7 Artery narrowed by atherosclerosis blood artery wall fatty deposit Longitudinal section of artery Thrombus (clot) on plaque CP Vulnerable Plaque Heart Attack 7

Time is the Muscle Shortening door-to-balloon time from 90 minutes to 30 minutes What About Women s Symptoms?

Women have MORE Sx (anatomic, physiologic, biologic, psychologic explanations) May vary with menstrual cycle Little prospective or

Diagnosis, Treatment Typical Signs of Heart Attack Pressure, fullness, squeezing or pain in chest that lasts for several minutes Radiation

8 Time is the Muscle Shortening door-to-balloon time from 90 minutes to 30 minutes What About Women s Symptoms? Are Symptoms Different in Women? Women have MORE Sx (anatomic, physiologic, biologic, psychologic explanations) May vary with menstrual cycle Little prospective or sex-specific data Questions used in research may not apply to women Prodrome, pre-hospital Sx unknown All this contributes to delayed Diagnosis, Treatment Typical Signs of Heart Attack Pressure, fullness, squeezing or pain in chest that lasts for several minutes Radiation to shoulders, back, or arms Other symptoms which may accompany Syncope (fainting) Sweating Nausea Dyspnea (shortness of breath) Women often have more non-chest symptoms Neck, jaw or shoulder pain Abdominal pain Nausea/vomiting Shortness of breath Prolonged chest discomfort Non-exertional 8

Pathophysiology of CHD New Paradigm in Women Diffuse

dysfunction Small vessel disease (Syndrome X,

heart, tako-tsubo cardiomyopathy, stress

Unstable angina Vasospastic (variant, Prinzmetal s)

Pressure Diffuse atherosclerosis Pressure Gould KL,

Disease Prinzmetal s Vasospastic Coronary syndrome X

9 Pathophysiology of CHD New Paradigm in Women Diffuse atherosclerosis Coronary vasospasm Endothelial dysfunction Small vessel disease (Syndrome X, microvascular disease) Apical Ballooning ( broken heart, tako-tsubo cardiomyopathy, stress cardiomyopathy) Types of Angina Chronic stable angina Unstable angina Vasospastic (variant, Prinzmetal s) Microvascular (coronary syndrome X) Focal stenosis Pressure Diffuse atherosclerosis Pressure Gould KL, Coronary Vasospasm Microvascular Disease Prinzmetal s Vasospastic Coronary syndrome X Endothelial dysfunction Microvascular dysfunction Apical ballooning syndrome (broken heart) Variant CP

10 Apical Ballooning Epicardial vs Microvascular CVD NY Times 4/17/06 ST-segment elevation,t-wave inversion LV wall motion abnormality at the apex No significant coronary artery stenosis LV wall motion abnormality recovers within several weeks LV Gram with MA Echo-5 weeks later SCAD I d like some of that preventive medicine I ve heard so much about. CP

38% Women whose doctor discussed heart disease prevention *MD s

men When it Comes to the Heart All risks are not created equal 2003

Personal Risk Factors Smoking High cholesterol Diabetes Stress

Family history Age Menopause CP992570-35 Obesity Smoking

Oxidative stress Conventional Risk Factors Homocysteine Diabetes

Hx/genetics Infection Thrombotic factors Fibrinogen TpA PAI-1

11 38% Women whose doctor discussed heart disease prevention *MD s systematically underestimate CVD risk and in women vs. men When it Comes to the Heart All risks are not created equal 2003 AHA Survey; Mosca, Circulation 2005 CP CP Personal Risk Factors Smoking High cholesterol Diabetes Stress Depression High fat diet Hypertension Obesity Physical inactivity Family history Age Menopause CP Obesity Smoking Hypertension Psychosocial factors Depression Environmental stress Oxidative stress Conventional Risk Factors Homocysteine Diabetes Hyperlipidemia Inflammation CRP Physical inactivity Family Hx/genetics Infection Thrombotic factors Fibrinogen TpA PAI-1 Nonconventional Risk Markers Iron load Vitamin deficiency CP Before After Percutaneous Balloon Angioplasty PTCA CP

Intracoronary Stent CP1016817-70 CP1082360-17

restoration of blood flow during heart attack

improve heart function (in cases where muscle

Prolong life Provide long term benefits without

12 Intracoronary Stent CP CP Benefits of Stenting & CABG Provides urgent restoration of blood flow during heart attack (PCI) Relieves angina, symptoms of ischemia May improve heart function (in cases where muscle not getting blood at rest) CP Stenting & CABG do NOT. The Heart as a Pump Prevent heart attacks Prolong life Provide long term benefits without concurrent medicine and lifestyle intervention = Normal Ejection Fraction> 50-55% CP

Keys to Understanding Congestive heart failure - CHF Dyspnea Orthopnea Edema Cardiomyopathy Dilated,

Function AKA: diastolic dysfunction More common in women Hypertension is main risk factor Less well

cells for cardiac repair Getting Cells to the Heart Beeres, S. L M A et al.

13 Keys to Understanding Congestive heart failure - CHF Dyspnea Orthopnea Edema Cardiomyopathy Dilated, ischemic, hypertrophic, idiopathic, peripartum Ejection Fraction Heart Failure with Normal Systolic Function AKA: diastolic dysfunction More common in women Hypertension is main risk factor Less well researched than systolic heart failure Prevention of heart failure Heart muscle regeneration Sources of cells for cardiac repair Getting Cells to the Heart Beeres, S. L M A et al. Heart 2008;94: Copyright 2008 BMJ Publishing Group Ltd. Beeres, S. L M A et al. Heart 2008;94: Copyright 2008 BMJ Publishing Group Ltd. 13

Current cardiotherapies do not repair The future?

Limited capacity for selfrenewal Angioplasty Blood

(short axis) at baseline and at 12 months from a

inducible ischemia in the inferolateral wall (arrow).

Heart 2008;94:1214-1226 Copyright 2008 BMJ Publishing

Keys to Understanding Heart Disease Myocardium - heart

Great vessels Pericardium Tricuspid Valve Pulmonary

14 Current cardiotherapies do not repair The future??? Cell Therapy Heart attack Obstructed blood vessel Limited capacity for selfrenewal Angioplasty Blood vessel reopened Stress and rest Tc-99m SPECT images (short axis) at baseline and at 12 months from a representative patient showing relief of stress inducible ischemia in the inferolateral wall (arrow). Beeres, S. L M A et al. Heart 2008;94: Copyright 2008 BMJ Publishing Group Ltd. Keys to Understanding Heart Disease Myocardium - heart muscle Coronary arteries Heart valves Electrical system Great vessels Pericardium Tricuspid Valve Pulmonary Valve PA Aorta Mitral Valve Aortic Valve Cardiac Valves Aortic Mitral Tricuspid Pulmonary Cardiac Valves Stenosis Regurgitation Prolapse Rheumatic heart disease Endocarditis 14

15 Prosthetic Valves Percutaneous Prosthetic Valves The Kinds of Lines Women Really Should be Worrying About NY Times, 10/13/93 CP Sinus node AV node Bundle branches Arrhythmias Palpitations Sinus rhythm Tachycardia Bradycardia Bundle branch block (LBBB/ RBBB) Heart block or AV block Sinus node AV node Arrhythmias Bundle branches VPC s, PVC s APC s, SVPC s SVT-supraventricular tachycardia 15

Arrhythmias Atrial Fibrillation Sinus node AV node Bundle branches Atrial fibrillation Atrial flutter CP1048413-15 Sinus node AV node Arrhythmias Bundle branches VT- Ventricular Tachycardia VF -

16 Arrhythmias Atrial Fibrillation Sinus node AV node Bundle branches Atrial fibrillation Atrial flutter CP Sinus node AV node Arrhythmias Bundle branches VT- Ventricular Tachycardia VF - Ventricular Fibrillation RA ASD Right Ventricle Aorta PA VSD LA Left Ventricle Congenital Heart Disease Bicuspid aortic valve Atrial septal defect (ASD) Patent foramen ovale (PFO) Ventricular septal defect (VSD) CP

17 CP

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