Evolving Knowledge of Women and Heart Disease Jo-Ann Eastwood PhD, RN, CCNS, ACNP-BC, FAHA
Magnitude of the Problem • Leading cause of death, mostly due to ischemic heart disease and stroke • Angina is a more common presentation of coronary heart disease in women than in men • Ischemic heart disease in women versus men • Present at older age • Less likely to be diagnosed and treated • Higher cardiovascular mortality • Estimated annual cost for cardiovascular disease in men and women: $400 billion
CVD & Other Causes of Death More than 1 in 4 women will die of heart disease 1 in 30 women will die of breast cancer
Women are getting the message What is the leading cause of death in women? We know the answer: Heart Disease! In 1997, only 30% (less than 1 out of 3) women knew the right answer. In 2010, 57% of women knew the right answer. This realization was shared by fewer Black & Hispanic Majority of women believed they couldreduce their risk with multivits, antioxidants or ASA Only 53% said they would call 911 if they had symptoms Mosca, L Circ. CardiovascQual Outcomes 2010;3(2):120-7
Cardiovascular Disease Deathsin the United States (1980-2009) Women Deaths (in thousands) Men 1980 1985 1990 1995 2000 2005 2009 Go AS, et al. Circulation. 2013;127:e6-e-245.
Gender Differences in Sudden Cardiac Death, Symptoms, and Quality of Life • Sudden cardiac death before arrival at a hospital • Women: 42% • Men: 25% • Symptomatic women versus men • More often have recurrent symptoms requiring hospitalizations • Lower ratings of general well-being and limitations in ability to perform activities of daily living Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1571.
Aftermath of CHD • Survivors of ACS have 1.5 – 15 x greater risk of illness and death than general population • Within 6 years of MI: % Men % Women • Recurrent MI: 18 35 • SCD 6 7 • HF 22 46 • Stroke 8 11
ACC National Cardiovascular Data Registry: In-Hospital Mortality Chest Pain Women Men P=0.89 P<0.0001 In-Hospital Mortality Rate (%) P=0.23 P=0.14 White (n=338,252) Asian (n=7823) Black (n=24,998) Hispanic (n=3562) Native American (n=1251) In-hospital mortality after coronary angiography. Among patients with stable chest pain, white women with 1- to 3-vessel CAD had 1.67- to 2.02-fold higher in-hospital mortality than white men (P=0.013). .
In light of these epidemiologic data, common misunderstandings and a growing awareness of potentially relevant sex differences, the AHA has updated CVD Prevention Guidelines for Women. SEX Matters
VIRGO Study: Gender Differences in Symptom Presentation and Perception Symptoms at MI Presentation • Younger patients with MI from 104 US hospitals, 2008-2012 (n=2990) • Age: 18 to 55 years • 2:1 female to male enrollment • 90% of men and 87% of women presented with chest pain, pressure, tightness, or discomfort • Women presented more additional symptoms • More women waited >1 day to seek care than men (55% versus 49%; P<0.05) • At time of hospitalization • 24% of women said health care provider did not think symptoms were heart related compared with 12% of men (P<0.001) Chest Pain/ Discomfort Radiating Pain Indigestion/ Nausea Shortness of Breath Weakness/ Fatigue Palpitations * † † † * Women (n=2012) Men (n=978) † Patients (%) *P<0.05 and †P<0.01 versus men. Lichtman JH, et al. Circulation. 2012;126(suppl). Abstract 17831.
Women’s Ischemia Syndrome Evaluation (WISE) Study • NHLBI-sponsored 4-center study • Women (>18 years of age) undergoing clinically ordered coronary angiography for suspected myocardial ischemia (n=936) • Myocardial ischemia at non-invasive testing • Exclusion criteria • Emergency referral, pregnancy, cardiomyopathy, NYHA class IV CHF, recent acute MI or unstable angina, recent coronary revascularization, significant valvular or congenital heart disease, any contraindication to provocative myocardial stress testing, and any condition likely to affect study retention • Objectives • Optimize symptom evaluation and diagnostic testing for ischemic heart disease • Explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenoses • Evaluate the influence of reproductive hormones on symptoms and diagnostic test response Merz CN, et al. J Am Coll Cardiol. 1999;33:1453-1461.
WISE Study: Estimated Lifetime Costs for Women With Angina Direct Cardiovascular Costs/Patient $1,051,302 $1,008,780 $1,001,493 $767,288 Projected Lifetime Costs (US$) Nonobstructive CAD 3 Vessel CAD 1 Vessel CAD 2 Vessel CAD Shaw LJ, et al. Circulation. 2006;114:894-904.
Evolving Understanding of Angina in Women • Typical versus atypical angina diagnosis by gender • 3225 patients referred to Duke University for evaluation of chest pain with median of 5 episodes of chest pain weekly • Angina equivalents • Fatigue • Lightheadedness • Weakness • Diaphoresis • Coronary patients with angina rate their quality of life lower than those without angina • Shortness of breath • Nausea • Indigestion *P<0.05 for comparison across gender. No angina: males (11%) and females (19%). Abrams J. N Engl J Med. 2005;352:2524-2533; Alexander KP, et al. J Am Coll Cardiol. 1998;32:1657-1664; Fang JC. Braunwald’s Heart Disease. 9th Edition. 2012. Bandu I, et al. Chest. 1994;105:1009-1012; Stern S. Circulation. 2002;106:1906-1908; Marquis P, et al. Eur Heart J. 1995;16:1554-1560.
Novel Risk Factors in Women • Traditional risk factors and the Framingham risk score may underestimate risk in women • Novel risk markers may improve risk detection • Abdominal obesity • Metabolic syndrome • Low estrogen levels • Elevated testosterone levels and polycystic ovary syndrome • Elevated C-reactive protein • Postmenopause • Clustering of risk factors is common (obesity, hypertension, dyslipidemia) • These risk factors also predict early menopause Shaw LJ, et al. J Am Coll Cardiol. 2006;47(suppl):4S-20S. Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1575. SWAN Study. http://www.swanstudy.org. Greenland P, et al. J Am Coll Cardiol. 2010;56:e50-e103.
Reclassification of Risk in Women Using the Reynolds Risk Score Ridker PM, et al. JAMA. 2007;297:611-619. Reynolds Risk Score calculator: http://www.reynoldsriskscore.org/.
Assessment of Myocardial Ischemia and Obstructive Coronary Disease in Women • Symptoms suggestive of myocardial ischemia • Women have lower rates of obstructive CAD at angiography • Early work by Diamond and Forrester • Women with typical or atypical chest pain symptoms have calculated obstructive CAD probabilities substantially less than men • Typical exertional angina in a 55-year-old man has a probability of obstructive CAD of approximately 90% as compared with wide range from 55% to 90% for a 55-year-old woman • This does not address angina equivalents • Chest pain symptoms are less accurate and less precise predictors of obstructive CAD in women Shaw LJ, et al. J Am Coll Cardiol. 2006;47(suppl):4S-20S. Diamond GA, et al. N Engl J Med. 1979;300:1350-1358.
Smaller size Increased stiffness (fibrosis, remodeling, etc) More diffuse disease More plaque erosion versus rupture Microemboli, rarefaction (drop out), disarray, etc Gender Differences in Ischemic Heart Disease in Women Structural Features (macro- and microvessels) Functional Features (macro- and micro -vessels) • Endothelial dysfunction • Smooth muscle dysfunction (Raynaud’s, migraine, coronary artery spasm) • Inflammation • Plasma markers • Vasculitis (Takayasu’s, rheumatoid, SLE, CNSV, giant cell, etc) Wenger NK. Curr Cardiol Rep. 2010;12:307:314. Kramer MC, et al. J Am Coll Cardiol. 2010;55:122-132. Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1575.
Model of Microvascular Angina in Women Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1571.
Overarching Working Model of Ischemic Heart Disease Pathophysiology in Women Shaw LJ, et al. J Am Coll Cardiol. 2009;54:1561-1571.
Plaque Erosion and Outward (Positive) Remodeling • Plaque erosion and thrombus formation 2x likely in women (men have more plaque rupture) • Outward (positive) remodeling- atherosclerotic lesion protrudes outward than impinging on the lumen Lumen Thrombus Formation Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585
AHA Impact Goal For All Americans • 20% by 2020 : • Improvement CV health • Reduction in CVD/stroke deaths • Primordial prevention (at all levels of risk) • CVD & associated risk factors develop early in life • Health promotion & disease prevention require all approaches: • Population-level • Individual high risk
Focus on Women • “..defining a women’s risk status and then improving adherence to preventive lifestyle behaviors is the most effective way to lower CVD in women.” Wenger, NK. ClinCardilol. 2011
Targeting Education - Awareness AND. . . • Prevention • Prevention • Prevention • Prevention
CVD Risk in Women Mosca, Circulation 123:1243, 2011
Female – Specific Issues • Gender differences in CVD risk factors • Tobacco • Diabetes and Met Syn • Dyslipidemia • HTN • Fitness • Autoimmune diseases with ↑ CVD risk • Rheumatoid Arthritis • SLE • Female specific issues • Pregnancy induced HTN • Pre-eclampsia • Gestational diabetes • PCOS • Other Issues for Women • Breast cancer therapy effects, • Chest radiation
Counseling All Women: Recommended Lifestyle Changes For all women: • Smoking cessation and avoidance of secondhand smoke • Physical activity • Moderate activity at least 6-7 days a week • Strength training x2/week • DASH-like low-sodium diet • Weight Management
2011 Guidelines: Evidence-based toEffectiveness-based • Benefits and risks observed in clinical practice • Therapies that may have potential benefit Ex. Screening for depression- indirectly may impact CVD risk through adherence to prevention therapies or other mechanisms. Acknowledgement that 10 year risk is not efficacious in women
Premenopausal • Initial assessment: Detailed medical and pregnancy-complications hx • Pregnancy: • Early “stress test”? Unique opportunity to assess lifetime CVD risk • “Metabolic syndrome of pregnancy” • Preeclampsia • Postpartum referral for CVD risk assessment
Pregnancy: A Stress Test for Life Pregnancy stresses maternal carbohydrate, lipid, inflammatory pathways, vascular function ● Unmasks underlying metabolic, vascular disease •? Pregnancy a screen for later hypertension, diabetes •? Preeclampsia induces damage to vascular endothelium; ? pathway for microvascular dysfunction •? Preeclampsia triggers inflammatory, autoimmune responses •? How can/should preeclampsia, hypertensive disorders of pregnancy (HDP) be incorporated into CV risk assessment for women Williams, CurrOpinObstetGynec 15:465, 2003 Ness, Ann Epidemiol 15:726, 2005 Mosca, Circulation 123:1243, 2011
HDP and Subsequent CV Disease Compelling evidence for association HDP and future CVD Hypertension Ischemic heart disease Ischemic stroke Thromboembolic disease Heart failure Chronic kidney disease Diabetes mellitus Arrhythmias Hypertension in adolescent life in offspring Mannisto, Circulation 127:681, 2013 8
Contemporary Recommendations • Pregnancy history integral component of CV risk evaluation for women • Women with prior preeclampsia, hypertensive disorders of pregnancy → early, intensive coronary risk intervention Counsel re ↑ CVD risk • Counsel re effectiveness of CV risk assessment, reduction in primary prevention CV disease • ? Screen as early as 1 year postpartum • Guidelines needed for structured follow-up, CV risk management after HDP • Smith, Am J ObstetGynecol 200:58.e1, 2009 • Mosca, Circulation 123:1243, 2011
Perimenopausal • Decrease in exercise > decrease in calorie intake • Weight gain, waist circumference, increase BP • Decreased social interaction d/t: • Mood disorders • Sleep disturbance • Vasomotor symptoms • Changes in work patterns /stress • Alterations in lipid profiles (ESHRE Capri Workshop Group 2011)
Postmenopausal • Dyslipidemia • Hypertension • Metabolic Syndrome • Lack of exercise • Psychosocial function • Social support • Dysphorias • Higher prevalence of stroke
Dispelling Myths: Confusion Among Women Remains • Observational studies reported HRT effective for symptoms & diseases ie CV and osteoporosis for menopausal women • 2 large RCTS HERS and WHI reported no benefits prevention of CVD. WHI found increases Breast CA incidence & CV events in healthy women • Million Women Study- increase in Breast CA with HRT
Dispelling Myths: Confusion Among Women Remains • Hormone therapy should not be used for primary or secondary prevention of CVD • Supplements not useful in preventing CVD • Vitamins E and C • Beta carotene • Folic acid • Aspirin not recommended for healthy women < 65 yrs
Health Disparities • Higher prevalence of risk factors in racial/ethnic groups • HTN → Black women • Diabetes →Hispanic women • Additional socio-economic factors • Inadequate access to healthcare • Reduced access to fresh food/easy availability of fast food • Community characteristics
Challenges: Real World • “I want to eat 5 fruits a day but once I dole out the fruit to the kids there is nothing left” • “It’s not safe in my neighborhood to walk besides I can’t leave the kids” • “I have to use the money I have for healthy groceries to give to the kids to pay for lunch. If they stand in the free lunch line they are teased and embarrassed all day!”
Successes! • “This is the first time my husband’s blood pressure has been down to 120/80 since the 6th grade” (N’s husband was admitted for a BP of 210/100 last November) • “My daughter (14 yo and overweight) watched me choosing good foods to eat and said I want to eat what you’re eating Mommy” • “My BP is 138/88 and my doctor says lose 20 lbs! Then I got your message about getting to goal <120/80. I am going back!”
Lessons from the Field • Women may be the key to changing health habits in minority communities • A message that resonates: “Take care of yourself so you can take care of your family” • If you treat the woman, the family changes • Women need social support • Go where the women are: • Churches, community organizations
Thank-you for your attention! AHA : Clinical Research Grant Award & to the many LA women who have committed themselves to not becoming a statistic!
Additional References • AHA. http://www.americanheart.org/downloadable/heart/1136818052118Females06.pdf. • Go AS, et al. Circulation. 2013;127:e6-e-245. • Wenger NK. Prog Cardiovasc Dis. 2003;46:199-229. • Hemingway H, et al. JAMA. 2006;295:1404-1411. • Daly C, et al. Circulation. 2006;113:490-498 • Merz CN, Kelsey SF, Pepine CJ, et al. The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999;33:1453-1461 • Shaw LJ, et al. J Am Coll Cardiol. 2008;117:1787-1801