CARDIO VASCULAR DISEASE IN WOMEN ALPESH SHAH MD, FACC, FSCAI THE METHODIST DEBAKEY HEART AND VASCULAR AP, WEI LL CORNELL MEDICAL COLLEGE AP, BAYLOR COLLEGE OF MEDI CINE DI RECTOR, BRHS CARDI AC CATH LAB CENTER FINANCIAL DISCLOSURE • Medical Advisory Board: Abbott Vascular • Consultant: Medtronic Inc • Research grants: Abbott Vascular, Medtronic Inc, GE imaging CVD IS # 1 KILLER IN WOMEN • Rates increasing in women between 30 and 54 years of age • Obesity increasing (2 out of every 3 women >20 years overweight or obese) GENDER BASED MORTALITY DIFFERENCE Cardiovascular mortality among US women has decreased dramatically each year since 2000; the 2007 cardiovascular mortality rate in women represents a 43% reduction from the 1997 rate WOMEN ARE UNAWARE OF THE PROBLEM STROKES • Women have more strokes than men and more strokes than CHD • Hormone replacement, pregnancy etc. contribute • Women have more hypertension than men at older age MEDICAL CHALLENGES • Risk factors are similar, outcomes however are worse in women • Late referrals and delayed presentation • Physicians not aggressive • Atypical presentation • more advanced CAD, older patients with more co morbidities • Metabolic/ anatomical differences • more urgent/emergent procedures • Women comprise only 25% of participants in all heart-related research studies. • More women than men die of heart disease each year, yet women receive only: • 33% of angioplasties/stents • 28% of implantable defibrillators • 36% of open-heart surgeries RISK STRATIFICATION NCEP ATP III guidelines: Age HTN Dyslipidemia DM Family history smoking • Classifies individuals into low, intermediate (?indeterminate), high risk • Uses Framingham risk score • 2011 update recognized potential value of hsCRP, CC score, CIMT NON HDL-C/ TG • LDL-C, VLDL-C, IDL-C, Lp(a)cholesterol • Non-HDL-C = Total cholesterol- HDL cholesterol • Non HDL-C goal is < 30mg above LDL-C goal • TG <150 mg HDL-C Current HDL-C Cut points • NCEP ATP III: 40 mg/dL • Metabolic syndrome criteria (ATP III, IDF) – Men <40 mg/dL – Women <50 mg/dL • AHA Women’s Cardiovascular Health Guidelines: 50 mg/dL • No treatment target for HDL-C as for LDL-C TREATMENT FOR LIPIDS • Women with CHD, goals of treatment LDLC<100 mg/dL, HDL-C >50 mg/dL, triglycerides<150 mg/dL, and non-HDL-C <130 mg/dL; • similar goals in women with other CVD or DM • Aggressive control in women with recent ACS or mulitple CV risk factors with CHD may require LDL-C < 70. • Drugs: Statins Fibrates Niacin Omega-3 fatty acids Ezetimibe Bile acid resins HORMONES CV risk is very low for women until after menopause Estrogen levels decrease at menopause Lipoprotein profile deteriorates after menopause HDL decreases LDL increases HRT improves lipoprotein profile HRT lowers fibrinogen (surrogate marker for CVD HERS observational studies had found lower rates of CHD in women who take postmenopausal estrogen 2,763 postmenopausal women average age 67 treated for approximately 4 years estrogen/progestin combination or placebo LDL cholesterol was reduced by 11% HDL cholesterol was increased by 10% HERS the use of estrogen plus progestin in postmenopausal women with heart disease did not prevent further heart attacks or death from CHD HRT regimen was associated with increased the risk of DVT & PE the results suggested an early acceleration of CV risk from HRT in these older postmenopausal women with established CHD The authors speculated that the HERS results may be explained by differences in the effect of therapy over time When they examined the results by year, they found that there was a trend towards a higher risk for CHD events such as MI during the 1st year of therapy but that this trend was reversed during the final two years. By the end of the study, there was no significant difference in CHD risk between the two groups CURRENT HRT RECOMMENDATION • Hormone therapy after menopause does not reduce the risk of CHD and should not be used for primary or secondary CHD Prevention Hormone therapy after menopause increases rates of stroke and venous thromboembolism screening for stroke risk factors is advised before initiating hormones in all postmenopausal women. CHD events are increased by estrogen plus progestin treatment in women with an intact uterus the CV risk within the first 10 years after menopause is minimal so one could consider HRT for postmenopausal vasomotor symptoms, at the lowest effective dose for the least amount of time METABOLIC SYNDROME GENDER DIFFERENCES IN METABOLIC DISEASE. Central adiposity • Prevalence of extreme obesity is increased in women compared with men • Increased waist circumference in women increases risk of metabolic syndrome to a greater degree than in men Dyslipidemia • Associated with a greater risk for coronary artery disease in women than in men • Elevated triglyceride levels have a greater impact on coronary artery disease risk in women than in men, especially when combined with low HDL levels Hypertension • Congestive heart failure is more commonly seen as a consequence of hypertension in women than in men • 'White coat hypertension' is more commonly reported in women than in men Hyperglycemia • Glucose levels after a glucose load are more commonly elevated than fasting blood glucose in women; the opposite is found in men EFFECTS OF HTN SECONDARY HTN DRUGS INDUCED HTN TREATMENT OF BLOOD PRESSURE • Therapy is indicated when BP ≥ 140/90 or ≥ 130/80 in the setting of CKD and DM • Initial therapy should include thiazide diuretics unless special populations indicate special therapies (Class I, Level of evidence A) • *ACEI contraindicated in women who are pregnant or may become pregnant RENAL ARTERY SYMPATHETIC DENERVATION FOR REFRACTORY HTN CONTROL (SIMPLICITY) Radiofrequency ablation BP change 10 0 Systolic Diastolic -18-11 -23-10 -23-11 -25-12 -27-13 -10 -20 -30 -40 1 3 6 9 12 month months months months months (n=70) (n=64) (n=56) (n=40) (n=34) ASPIRIN • Aspirin (75 mg to 325 mg) in women with CHD • Aspirin (75 mg to 325 mg) in women with DM • Can be used in women ≥ 65 yrs (81 mg daily or 100 mg every other day) if BP is controlled for ischemic stroke and MI prevention (as long as benefit outweighs risk of GI bleed or hemorrhagic stroke) and may be reasonable for stroke prevention (but not MI) in women < 65 yrs PREGNANCY: CONTRAINDICATIONS Pulmonary hypertension ~25% mortality Severe ventricular dysfunction SVEF <30%, NYHA III/IV; residual PPCM Severe Left Heart Obstruction Symptomatic AS, MS, coarc Dilated aortic root Marfan (equivalents) AAo > 45 mm BAV with Aao >50 mm (27/m2) * Cyanotic heart disease: 85/90 Rule NONINVASIVE TESTING OPTIONS Stress ECG Stress MPI/PET EBCT/CTA Stress ECHO MRI DIAGNOSTIC ACCURACY OF EXERCISE ECG TESTING IN WOMEN • Altered prevalence of disease1,2 • Reduced predictive accuracy in younger women2 • Potential factors affecting diagnostic accuracy1: • Hormonal influences • Reduced functional capacity • Resting ST-T wave abnormalities • Comorbidities 1. Isaac D, et al. Can J Cardiol. 2001;17(suppl D):38D-48D. 2. Shaw LJ, et al. In: Charney P, ed. Coronary Artery Disease in Women: What All Physicians Need to Know. Philadelphia, Pa: American College of Physicians. 1999:327-350. STRESS ECHO Ultrasound performed both at rest and during peak stress Exercise or other stress Ischemia defined by development of wall-motion abnormalities Courtesy of Howard Lewin, MD, of San Vicente Cardiac Imaging Center. NUCLEAR STRESS TEST Exercise or pharmacologic stress vs rest Stress Rest Myocardial accumulation of radioactivity in proportion to blood flow Stress Rest Stress Ischemia defined by diminished perfusion during stress vs rest Rest Stress Rest Courtesy of Jennifer H. Mieres, MD, NYU Medical Center. HOW IS CARDIOVASCULAR DISEASE PRESENTATION DIFFERENT IN WOMEN? Typical Heart Attack Warning Signs • Chest tightness, pressure, burning and squeezing of the chest • Discomfort in one or both arms, shoulders, neck, jaw, stomach or back • Shortness of breath • Fatigue, cold sweats, nausea, weakness Less Typical Symptoms Of Heart Disease In Women • Pain in upper back, jaw or neck • Shortness of breath • Flu- like symptoms, nausea or vomiting, cold sweats • Fatigue or weakness • Feeling of anxiety, loss of appetite, discomfort GAPS IN DIAGNOSIS AND TREATMENT Prevalence of Coronary Heart Disease (CHD) M 52%: W 48% Diagnostic Procedures (Diag. catheterizations & Non-invasive Tests) M 55%: W 45% CABG M 73%: W 27% PCI M 61%: W 39% Medical Management Only M 47%: W 53% PCI / STENTS Expandable metal mesh tubes that buttresses the dilated segment, limit restenosis. Drug eluting stents: further reduce cellular proliferation in response to the injury of dilatation. STENT Bare metal stent Drug eluting stent 32 STENT FEATURE MATRIX Bare-Metal Stents Reduced DualAntiplatelet Therapy No neointimal hyperplasia Restoration of Vasomotion Material (Biocompatible) Drug-eluting Stent Bioabsorbable drug- eluting Stent PCI • Only 33% of PCI are performed in women annually • Delayed treatment with PCI in women is common • Often >24 hours after presentation • Women continue to be underrepresented in clinical trials of percutaneous coronary intervention • They don’t meet inclusion criteria!!! • Get there late • More risk factors: older, worse renal function • Sicker on presentation Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lee et al. JAMA. 2001;286:708-713, Harris DJ et al. N Engl J Med 2000;343(7):475-480, Simon V. Science 2005;308(5728):1517. PCI PROCEDURE RELATED CHALLENGE • Higher bleeding complication , especially access site • Contemporary subacute or late thrombosis rates are similar between genders, 1.3% vs 1.2%, p=NS • Women are 61% more likely to present with in-stent restenosis following stents, particularly diffuse in-stent restenosis • 1.9x more women will return to the ER within 30 days of their intervention  even after successful interventions • 38% of women and 25% of men will die within one year of a first recognized heart attack. • Complex anatomy, small vessels • More recent data suggests no difference in death, MI, and emergent CABG but continued increased risk of morbidity, particularly bleeding • Improved PCI mortality over time in both men and women CLINICAL OUTCOMES DURING PCI BY GENDER (ACUITY TRIAL) Women Men P-value (N=2091) (N=5698) 30-Day Major Bleeding 1-Year Composite Ischemia 1-Year Mortality 10.7% 4.2% <0.0001 19.6% 18.5% 0.27 3.5% 3.1% 0.31 PERCUTANEOUS ACCESS (FEMORAL, RADIAL, BRACHIAL) 37 RADIAL APPROACH IS STILL ASSOCIATED WITH MORE BLEEDING IN WOMEN • 1348 ACS patients pretreated with ASA, clopidogrel → radial PCI using 70 u/kg uFH and abciximab (EASY trial of early discharge) Women Men p value Sheath size – 5F – 6F 57% 43% 44% 55% 0.0003 Hb drop 1.7% 0.4% 0.059 Hematoma 22% 5.8% 0.001 Final ACT (sec) 322 308 0.003 AHJ 2009; 157:740 TREATMENT OF WOMEN WITH ACUTE CORONARY SYNDROME • Less likely to have an ECG done within 10 minutes of presentation • Less likely to be cared for by a cardiologist during their inpatient admission • Less likely to acutely be given appropriate pharmacotherapy such as heparin, aspirin, statins, ACEI • longer DTB times in STEMI cases LESS OFTEN RECEIVE GUIDELINE RECOMMENDED THERAPY BUT WOULD SIGNIFICANTLY BENEFIT FROM AN EARLY AGGRESSIVE INVASIVE STRATEGY AMI in Women: Later Presentation and Delay in Treatment - CADILLAC Primary PCI Trial- Men N P Women Value 1520 562 - Chest pain to ER (hrs) 2.6 ± 2.5 3.0 ± 2.6 < 0.001 ER to procedure (hrs) 1.9 ± 2.2 2.1 ± 2.3 < 0.001 Stent use 57% 57% NS Abciximab use 54% 51% NS PRIMARY PCI IS SUPERIOR TO LYTICS IN WOMEN META-ANALYSIS - 23 RANDOMIZED TRIALS (PCAT-2) 16 Lytic Primary PCI 14.4 30-Day Mortality 14 12 10 8 9.6 7.7 8.5 7.1 5.3 6 4.9 3.5 4 2 0 ≤ 2 hrs Women > 2 hrs ≤ 2 hrs > 2 hrs Men PCI MORTALITY COMPARISONS BY ERA AND GENDER Group 30-d mortality, 30-d mortality, 1979–1995 (%) 1996–2004 (%) Women 4.4 2.9 0.002 Men 2.8 2.2 0.04 Singh M et al. J Am Coll Cardiol 2008; 51:2313-2320. P value ABSORB III EXCEL (LEFT MAIN STENT VS. CABG) Demonstrating in subjects with ULMCA disease (either isolated to the left main trunk or associated with disease in other coronary arteries) that compared to CABG, treatment of the left main stenosis other significant coronary lesions with the XIENCE PRIME or XIENCE V stent will result in non-inferior or superior rates of the composite measure of all-cause mortality, MI or stroke at an anticipated median follow-up duration of 3 years MANY WOMEN WITH ANGINA HAVE NON-OBSTRUCTIVE CAD • 57% of women presenting with chest pain or suspected myocardial ischemia had nonobstructive CAD (<50% stenosis) • An analysis of 673 WISE patients showed 46% with nonobstructive CAD had persistent chest pain (PChP) at 1 year follow-up • More intense symptoms at baseline • Younger (mean 54 years) • Lower functional capacity • More comorbidities • Depression and lower QOL % of Patients with Persistent Chest Pain (PChP) at 1 Year WHAT IS MICROVASCULAR DISEASE? • Dysfunction in small coronary arterioles <500 microns in diameter • Main determinants of vascular resistance • Major etiological factor for ischemic heart disease in women • Potential precursor of obstructive CAD • 2-3 million women with microvascular coronary dysfunction in the U.S. • ~90,000 new cases annually INDICATIONS FOR SURGERY (GENERAL) • Left main disease • three-vessel disease • two-vessel disease with proximal LAD lesion • significant left ventricular impairment with multi-vessel disease • Diabetes? • Failure of medical/PTCA management WOMEN AND CABG • Increased transfusion rate • Increased need for urgent surgical intervention • Older age at operation • Diffuse disease process? • More advanced symptoms of CHF • More postop admissions for CHF and unstable angina SURGICAL OPTIONS ALOHA: SAY FAREWELL TO HEART DISEASE AHA Guidelines: CV Prevention in Women Assess and stratify women into high, intermediate, lower, or optimal risk categories. Lifestyle approaches (smoking cessation, regular exercise, weight management, and heart-healthy diet) to prevent CVD—should be recommended for all women and a top priority in clinical practice. Other CVD risk-reducing interventions should be prioritized on the basis of strength of recommendation. Lifestyle, which is a top priority for all women. Highest priority for risk intervention in clinical practice is based on risk stratification (high risk > intermediate risk > lower risk > optimal risk). Avoid interventions designated as Class III: antioxidants, hormone replacement, and aspirin for women at low risk. Mosca et al. Circulation. 2004;109:158-160. “NO DIFFERENCE? R U KIDDING ME?” CARDIO VASCULAR DISEASE IN WOMEN ALPESH SHAH MD, FACC, FSCAI THE METHODIST DEBAKEY HEART AND VASCULAR AP, WEI LL CORNELL MEDICAL COLLEGE AP, BAYLOR COLLEGE OF MEDI CINE DI RECTOR, BRHS CARDI AC CATH LAB CENTER