Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Shaista Malik, MD, PhD, MPH, FACC Associate Professor Medical Director, Preventive Cardiology and Cardiac Rehab Program Director, Women’s Heart Disease Program University of California, Irvine None Gender differences in clinical presentation, risk profiles, and outcomes Guideline/position statements that address gender differences in prevention and diagnosis of heart disease Gaps in literature/future research efforts At Every Age, More Women Die of Heart Disease Than Breast Cancer Coronary Artery Disease Stroke Lung Cancer Breast Cancer Colon Cancer Endometrial Cancer 6500 Death Rate per 100,000 4500 2500 1600 1200 800 400 0 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Age (years) National Center for Health Statistics. 1999:164-167. by Increased Mortality in Younger Women Vaccarino et al., NEJM 1999;34:217-225 Gupta el al, JACC 2014; 64:337-45 100.0% 20.0% 90.0% 18.0% 3.4% (n=5,229) p<0.0001 80.0% 16.0% 14.0% Percent of cases Percent of cases 70.0% 60.0% 50.0% 40.0% 6.4% (n=4,565) p<0.0001 30.0% 7.3% (n=331) p<0.0001 12.0% 10.0% 3.8% (n=200) p<0.0001 8.0% 6.0% 20.0% 4.0% 68.1% (n=151,630) p<0.0001 31.9% (n=71,030) p<0.0001 10.0% 0.0% 6.4% (n=4,565) p<0.0001 2.0% 3.4% (n=5,229) p<0.0001 0.0% Women Men Women Men Complications in patients who underwent PCI Mortality in patients who experienced complications Total patients who underwent PCI Complications in patients who underwent PCI Agarwal M, Kim M, Erande A, Amin A, Patel P, Malik S, JACC supplement March 2014 Women Have a Two-fold Increase in “Normal” Coronary Arteries during a Heart Attack: Open Artery Heart Attack Stable Angina ~50% ~17% Bugiardini, JAMA 2005;293:477-84 9 Risk Factors with greater relative risk in women Diabetes, Hypertension, Triglycerides Biological Differences: Greater prevalence of nonobstructive disease, greater prevalence of vascular dysfunction coronary microvascular dysfunction Awareness/Treatment Bias Undertreatment of women (primary and secondary prevention) ▪ ▪ ▪ ▪ ▪ ▪ Less cholesterol screening Fewer lipid-lowering therapies Less use of heparin, beta-blockers and aspirin during myocardial infarction Less antiplatelet therapy for secondary prevention Fewer referrals to cardiac rehabilitation Fewer implantable cardioverter-defibrillators compared to men with the same recognized indications Lack of evidence based guidance for treatment of CHD in women Recognition of risk factors specific to women (pregnancy related, autoimmune disease) Response to lack of risk prediction by FRS, lowering of score required to be high risk Risk categories: Ideal, At risk, High risk IDEAL Mosca, Circulation, 2011 AT RISK CVD Mortality per 100,000 Women HTN – Hypertension GDM – Gestational Diabetes PCOS – Polycystic Ovary Syndrome Source: Adapted from “CVD Prevention and the Primary Care Partnership”, Deborah Ehrenthal, MD, FACP 13 GENDER GAP 50% higher RR for CHD in women vs. men with DM (Huxley et al meta-analysis), even after adjustment of other RF. Age gap of 10 years in CVD presentation between women and men is completely attenuated in women with DM 27% higher RR for Stroke in women vs. men with DM (Peters et al) Etiology for this gap could be sex hormones or lifestyle factors Huxley et al, BMJ, 2006 Peters et al, Lancet 2014; Malik, Nature Rev Endocrin, 2014 Raloxifene Use for the Heart (RUTH) trial 10,101 post-menopausal women selected for high CHD risk Negative trail, Raloxifene offered no protection against CHD 3672 with DM without known CHD and 3265 with history of CHD without known DM DM was CHD risk equivalent in women for fatal (not nonfatal) CHD Daniels, Circ Cardiov Outcomes 2013 Women have impaired glucose tolerance in OGTT, doesn’t get picked up on fasting glucose testing 19% of women, 27% of men with CAD had normal OGTT in the Euro Heart Survey on diabetes A1c maybe a better measure of prevalence of glycemic abnormalities in women Anthropometric measures maybe more abnormal in women compared to men with diabetes, no other differences in co-existing RF between men and women Higher adiposity equals higher inflammation Peters et al, Lancet 2014, Dotevall Eur Heart J, 20007, Barrett-Connor, Global Heart 2013 Women's Ischemia Syndrome Evaluation (WISE) study Women with significant myocardial ischemia and “open” arteries Tested for function of the endothelium 50% of women with normal angiograms to have microvascular coronary dysfunction (MCD) or small vessel disease 17 WISE Study Male Pattern Plaque: Focal Female Pattern Plaque: Diffuse Burke et al, Circulation 1998 Khuddus, et al. J Int Cardiology, Dec 2010 Shaw et al, Circ Cardiov Imaging, 2010 Obstructive Coronary Disease More prevalent in men Small Vessel Disease /Microvascular Coronary Dysfunction More prevalent in women? Slide courtesy of Noel Bairey-Merz, MD adapted from New York Times NY Times Patients hospitalized for chest pain or heart attack Get a diagnostic angiogram Results of the angiogram lead to treatment Increased deaths in those that do not follow male pattern of heart disease Merz C N B Eur Heart J 2011;32:1313-1315 540 patients with signs and symptoms of ischemia and <50% CAD on angiogram (WISE cohort) Compared to 1000 age and race-matched controls (WTH) 2.5%/year Gulati et al., Arch Intern Med 2009;169:843-850 Confers a 2 fold increased risk Johnson et al., European Heart J 2006;27:1408-1415 Normal Coronar y Arteries HR 1.52 (1.27-1.83) p<0.001 Jespersen et al., European Heart J 2012;33:734-744 Symptoms of angina (typical and atypical) Objective evidence of ischemia by traditional stress testing No obstructive CAD by coronary angiogram Microvascular Coronary Dysfunction (MCD) is believed to be the high risk subset of Syndrome X patients and represents true pathology of the small vessels of the heart Pathophysiologic Definition: Disordered function of the smaller (<100-200 um) coronary resistance vessels Functional Definition (coronary flow reserve): Increase in coronary blood flow to maximal hyperemic stimuli (eg, adenosine) < 2.5 fold from baseline Coronary flow reserve is the increase in blood flow in response to metabolic/pharma stimuli Abnormal coronary microvascular that is clinically evident as inappropriate coronary blood flow response Primary MCD in the absence of obstructive CAD or structural disease Secondary To obstructive CAD To myocardial diseases (anatomical restriction of the vascular cross-section) ▪ HCM ▪ RCM ▪ LVH (hypertension, aortic stenosis) Iatrogenic (distal embolization during PTCA and vasoconstriction due to recanalization) Camici P, et al. NEJM 2007;356:830-840 Secondary MCD Primary MCD Secondary MCD Kothawade et al., Curr Prob Cardiol 2011;36:291-318 Shaw et al., JACC 2009;54:1561-75 Diagnosis of MCD/Small Vessel Disease Exertional angina or ACS presentation Abnormal stress testing (nuclear stress test, Adenosine MRI) Endothelial function testing (EndoPAT-RHI 1.67) Abnormal coronary flow reserve (<2.5, <50%) May have diffuse atherosclerosis by IVUS 30 Circulation 1999;99:1774 Endo-PAT Test Procedure 5 - 10 min Cuff inflation Confidential 5 min Occlusion 5 - 10 min Cuff deflation 31 Control arm Automatic data analysis Occluded period Test arm Reactive hyperemia Endothelial Dysfunction Normal Endothelial Function 5/25/2017 Endothelial Dysfunction 33 CMRI validated for evaluation of: 1) subendocardial perfusion 2) myocardial flow reserve 3) fibrosis and microinfarction 4) assess LV function and mass Pilz et al. J Cardiovasc Magn Reson 2008;10:8 Panting et al. NEJM 2002;346:1948-53 Measure both pressure and flow Hasdai et al., Int J Cardiology 1996;53:203-208 >2.5 Endothelial Independent : Adenosine >50% Endothelial Dependent : Acetylcholine Pulse wave doppler to measure blood flow velocity Coronary blood flow measured by change in diameter of vessle and change in velocity Macrovascular dysfunction Endothelial dependent Endothelial Independent Microvascular dysfunction Abnormal vasoreactivity to Acetylcholine Reduced coronary blood flow in response to Acetylcholine Abnormal vasoreactivity to Nitroglycerin Reduced coronary flow reserve in response to Adenosine Recent clinical trail data show that medical management is safe for those with stable heart disease Clinical and prognostic significance of nonobstructive CAD detected by IVUS or CCTA Myocardial ischemia is associated with higher mortality in women than in men Symptoms in women are correlated with coronary vascular dysfunction in the setting of nonobstructive disease In both women and men, the most common presentation of ischemia is CP However women have different pattern and distribution of non-chest related pain symptoms Epigastric discomfort with nausea Radiation to arms, neck, back Dyspnea and fatigue More often precipitated by mental or emotional stress and less frequently by exertion Significant overlap between men and women when it comes to symptoms Women with stress test abnormalities and nonobstructive CAD are NO LONGER defined as having a false-positive test Test needs to be classified as ABNORMAL and they are noted to be at elevated risk High Risk Equivalents: DM, CKD, PVD, COPD, TIA/CVA, Functional Disability Diagnostic Testing Strategy now includes CCTA and Stress MRI Prior studies focused on men with underrepresentation or exclusion of women Studies of women: WISE, Nurses’ Health Study, WHI, have not included a male comparison group Newer data shows some contradictions Min et al, JACC 2011; Mieres 2014 Liepsic et al, Radiology July 15 2014, epub When matched for age, CAD risk factors, angina typicality, and nonobstructive CAD extent, women and men experience comparable rates of incident mortality and myocardial infarction. In multivariable analysis, nonobstructive CAD was associated with similarly increased MACE for both women (hazard ratio: 1.96 [95% confidence interval [CI: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI: 1.07, 2.93], P = .03). “Our data strengthen the WISE conclusions that extent and distribution of epicardial nonobstructive CAD may not be a significant contributor to sex-based differences in adverse clinical outcomes” 405 men, 813 women at Mass General referred for suspected CAD for PET myocardial perfusion imaging Coronary flow reserve (CFR) was quantified to assess presence of CMD, CFR <2 considered abnormal. Murthy et al, Circulation 2014; 129: 2518-2527 Confirms WISE study findings and extends them to men Mental stress–induced myocardial ischemia (MSIMI) diagnosed as either worsening of WMA or decrease in EF while doing 1 of 3 mental stress tasks (mental math, mirror trace, and anger recall). Showed that MSIMI is much greater in prevalence than previously thought. Of 310 patients in the study only 18 were women, of these women 57% had MSIMI compared to 41% of men Men had greater hypertensive response in blood pressure to stress Women also had increased platelet aggregation in reponse to collagen compared to men (increased aggregation with all agonists but power limitations). 34 yo female no cardiac risk factors Severe central chest pressure with exertion or rest 1 episode of 10/10 pain with associated symptoms, Tn 4.1 Normal EF, No WMA Normal Angiogram Additional testing: A1c, CRP? EndoPAT testing Additional testing: A1c, CRP? EndoPAT testing Abnormal Additional testing: A1c, CRP? Adenosine MRI 18% reversible circumferential subendocardial ischemia, inferolateral wall Underwent CRT Normal coronary arteries Abnormal response to adenosine of 1.8 (normal >2.5) Abnormal response to Ach of 13% (normal >50%), with visual vasoconstriction Normal response to NTG, no spasm noted Diagnosis: MCD For her chest pain and ischemia B-blocker add on therapy with Ranolazine if needed For endothelial dysfunction Statin ACEI Gaps in knowledge “Paradoxical sex differences” have been noted in which, compared with men, women have less obstructive coronary disease, but higher rates of angina and death Microvascular and endothelial dysfunction has been postulated to play a significant role in presentation and pathogenesis of Personalized approach to women with symptoms suspicious of heart disease Abnormal stress test and normal angiogram= abnormal test Test for microvascular dysfunction (stress MRI, CRT in cath lab, endothelial function tests) UC Irvine’s Women’s Heart practice is a unique, integrative program dedicated to comprehensive clinical service, innovative research, and outstanding education for clinicians and patients alike, with the common goal of diagnosing and treating women’s heart disease. • • Only Academic Program in OC focusing on Women’s Heart Care Specializing : ❤Coronary Heart Disease ❤Cardiac Arrhythmia ❤Preventive Heart disease and Cardiac Rehab ❤Heart Failure ❤Cardiac Imaging ❤Adult Congenital Heart Disease ❤Cardiac Research UC Irvine: OurProgram Women’s UCIHeal: Women’s Heart Heart Program Clinical Services We are the one academic-based women’s heart practice in Orange County with the largest number of physicians and researchers dedicated to women’s heart health. Members include: • • • • • • Shaista Malik MD PhD—preventive cardiology and cardiac rehab Jin Kyung Kim MD PhD—role of hormones and heart disease and Echo Dawn Lombardo DO—heart failure program and Echo Jeannette Lin MD—adult congenital heart disease Afshan Hameed MD—high risk pregnancy and heart disease Pranav M. Patel, MD—interventional cardiology 55 y/o female with HTN and dyslipidemia, has had CP, pressure like sensation, not related to physical exertion. Had TMST two years ago at outside facility with no ischemic changes. She presents to preventive program for weight loss 34 y/o female with h/o migrane and TIA presents to clinic c/o CP radiating to her jaw. CP is not exertional and is worse at night. Stress echo was negative Pt continued to have CP, EndoPAT test ordered. Abnormal EndoPAT, Adenosine MRI ordered