coronary artery disease in women by dr abhishek rathore

D R A B H I S H E K R A T H O R E

S R I J A Y A D E V A I N S T I T U T E O F C A R D I O V A S C U L A R S C I E N C E , B A N G A L O R E

CAD IN WOMEN

OVERVIEW

• The Scope of the problem.• Impact of CAD on women• Risk assesment• Sex specific characteristics• Management strategies specific to women.

BURDEN OF CAD IN WOMEN

• CAD is a leading cause of death of women and men worldwide.

• Heart disease and stroke claim nearly 400,000 women’s lives each year in U.S.

• 1 in 3 women die of heart disease.

• Nearly 1 women is dying every 80 seconds.

• Awareness regarding prevention, diagnosis and management of CAD in women is a major concern.

PREVALENCE OF CHD BY AGE AND SEX

Dariush Mozaffarian et al. Circulation. 2016;133:e38-e360

ANNUAL NUMBER OF ADULTS PER 1000 HAVING DIAGNOSED HEART ATTACK OR FATAL CHD BY AGE AND

SEX


INCIDENCE OF HEART ATTACK OR FATAL CHD BY AGE, SEX, AND RACE


INCIDENCE OF ANGINA PECTORIS BY AGE AND SEX


CAD IN INDIAN WOMEN

• Prevalence of CAD - men 4.8 %, women 2.6 %.

• 19 crore Indian women have CAD.

1.M. N. Krishnan et al. BMC Cardiovascular Disorders 2016

CAD IN INDIAN WOMEN

• In 1,565 patients of ACS (STEMI 52%)in the DEMAT registry , 21% were women, who were older than men, had more HTN and DM, but had similar incidence of dyslipidaemia or stroke1.

• In 6867 patients of CAD from Ahmedabad(17%females), females had higher prevalence of HTN, DM and obesity.

• CABG and PCI were used less often to treat females, and medical therapy was the preferred option2.

1.Pagidipati NJ et al. Association between Gender, Process of Care Measures, and Outcomes in ACS in India: Results from the Detection and Management of Coronary Heart Disease (DEMAT) Registry. PLoS ONE. 2013 2.Bhatt P et al. Unique Aspects of Coronary Artery Disease in Indian Women. Cardiovasc Drugs Ther. 2015 May 26

SCOPE OF THE PROBLEM

• Average age at first MI is 64.5 years for men and 70.3 years for women

• Women have more comorbidities when they present.

• Women present late to medical attention.

• Women are referred less often for appropriate testing or treatment.

Stangl V, et al. Eur Heart J 2008;29:707;Dariush Mozaffarian et al, Circulation 2015

Mosca L et al. Circulation 2005;111:499; Wenger NK. Circulation 2004;109:558;

Alter DA et al. JACC 2002;39:1909

IMPACT OF CAD IN WOMEN

• Women with MI are more likely to have complications and increased mortality1.

• Young females with MI have worse prognosis than men2.

• #Obesity- Prevalence same in men and women, but risk of CAD is 64% in women and 46% in men3.

• Fewer women have been included in studies, so there’s less data.

1.Dariush Mozaffarian et al, Circulation 20152.Vaccarino V et al. N Engl J Med 19993.Wilson PW et al, Arch Intern Med 2002

IMPACT OF CAD IN WOMEN

• Among individuals with premature MI (under age 50),women experience a 2 fold higher mortality than men.

(Vaccarino et al, NEJM 1999)

• Between 45-64 yrs , women are more likely to develop heart failure within 5 years of MI.

Wilson PW et al, Arch Intern Med 2002

HOW PATHOPHYSIOLOGY OF CAD IN WOMEN DIFFERS?

• It appears that the pathophysiology of CAD varies between women and men.

• On cardiac CT, women had smaller coronary artery diameters than men do.

• Women are less likely than men to have obstructive CAD. • Despite the lack of obstructive CAD ,the prognosis in

women is not benign.

• >50% of symptomatic women without obstructive CAD continue to have S/S of ischemia and to undergo repeat hospitalization and CAG. 1.Dickerson JA et al, Clin Cardiol 2010

2.WISE Study,Am J Cardiol 20013.WISE study. Eur Heart J 20064.WISE study. Circulation 2006

HOW PATHOPHYSIOLOGY OF CAD IN WOMEN DIFFERS?

• Men have higher degrees of atheroma and endothelial dysfunction, whereas women have more disease of the microvasculature. (Han SH et al. Eur Heart J 2008)

• Retinal artery narrowing has been shown to be a marker for microvascular disease in women. This relationship was not seen in men. (ARIC Study. JAMA 2002)

WHAT ARE THE SYMPTOMS?

Chest pain or discomfort

Unusual upper body discomfort

Shortness of breath

Breaking out in a cold sweat

Unusual or unexplained

fatigue (tiredness)

Light-headedness or sudden dizziness

Nausea (feeling sick to the stomach)

SYMPTOMS IN WOMEN WITH MI

• Study of 515 women with MI• Chest pain absent in 43%• Most common symptom:

• Dyspnea in 58%• Weakness in 55%• Fatigue in 43%

• Prodrome:• Fatigue in 71%• Sleep disturbance (48%)• dyspnea (42%)

McSweeney JC, et al. Circulation 2003;108:2619

SYMPTOMS IN WOMEN WITH MI CONT…

Canto JG et al. JAMA 2012;307:813

• Over 1,000,000 men and women in NRMI registry, 1994-2006 (4,81,581 women)

• 42% of women presented without CP (vs. 31% of men)

• Higher in-hospital mortality in women (14.6%) than in men (10.3%)

• Younger women without chest pain were at the highest risk

SYMPTOMS IN WOMEN WITH MI CONT…

Canto JG et al. JAMA 2012;307:813

• These women who presented without CP were sicker and fared worse:• More had DM• Later presentation• More Killip III/IV• More NSTEMI• Less timely therapies• Less antiplatelet meds, heparin, BB

WHICH RISK FACTORS ARE MORE PREDICTIVE IN WOMEN?

Huxley R et al.BMJ 2006Njolstad I et al. Circulation 1996;93(3):450; Prescott E et al. BMJ 1998;316(7137):1043

• Diabetes: Increase a woman’s risk of CAD by 3- to 7-fold, with only a 2- to 3-fold increase in diabetic men.

• Smoking: • associated with 50% of all coronary events in women• Risk elevated even with minimal use• Women who smoke have a six-fold increased risk of

MI (vs. 3x in men)

WHICH RISK FACTORS ARE MORE PREDICTIVE IN WOMEN?

# Lerner D J eta l.Am Heart J 1986Rich-Edwards, JW et al. NEJM 1995; 332:1758; Miller VT. Atherosclerosis 1994; 108 Suppl:S73;

Orth-Gomer K. Circulation 1997;95:329Hokanson JE et al. J Cardiovasc Risk 1996.

• After the 5th decade of life, women have higher cholesterol levels than men do#.

• Low HDL is more predictive than high LDL

• Lp (a) can be more predictive in younger women

• TG can be more predictive in older women, especially if >400 mg/dL

• Premature CAD in a first-degree female relative is a relatively more potent risk factor than is premature CAD in male relatives

• (Scheuner MT et al.The Multi-Ethnic Study of Atherosclerosis. Genet Med 2008)

• St. James Women Take Heart Project (CIRCULATION 2003)

Asymptomatic women who were unable to achieve 5 METS on a Bruce protocol have a 3-fold increased risk of death compared with women who achieved >8 MET, even after controlling for traditional risk factors.

AUTOIMMUNE DISEASES AND CAD IN WOMEN

• Framingham offspring study-(Am J Epidemiol 1997)

• Women with 34 to 44 years with SLE were 50 fold more likely to have an acute MI than were women of the same age without SLE

• SLE with presence of myocardial perfusion defects was independently associated with an increased risk of CAD.

(Nikpour M et al. J Rheumatol 2009)

• Women with lupus, serial carotid ultrasounds demonstrated that 28% had progressive atherosclerosis over a 34-month follow-up period, averaging approximately a 10% progression per year

(Roman MJ et al. Arthritis Rheum 2007)

RISK ASSESMENT FOR CAD IN WOMEN

Risk Status Criteria

High risk (≥1 high-risk states)

Clinically manifest CHDClinically manifest cerebrovascular disease

Clinically manifest peripheral arterial diseaseAbdominal aortic aneurysmEnd-stage or chronic kidney diseaseDiabetes mellitus10-y Predicted CVD risk ≥10%

Lori Mosca et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the AHA. Circulation 2011

At risk (≥1 major risk factor[s])

Cigarette smokingSBP ≥120 mm Hg, DBP ≥80 mm Hg, or treated hypertensionTC ≥200 mg/dL, HDL-C <50 mg/dL, or treated for dyslipidemia

Obesity, particularly central adiposityPoor dietPhysical inactivityF/H/O premature CVD occurring in first-degree relatives in men <55 y of age or in women <65 YRS.Metabolic syndromeEvidence of advanced subclinical atherosclerosis (eg, coronary calcification, carotid plaque, or thickened IMT)

Poor exercise capacity on TMT and/or abnormal HRR after stopping exercise

Systemic autoimmune collagen-vascular disease (eg, lupus or RA

History of preeclampsia, gestational diabetes, or pregnancy-induced hypertension


Ideal cardiovascular health (all of these)

Total cholesterol <200 mg/dL (untreated)BP <120/<80 mm Hg (untreated)Fasting blood glucose <100 mg/dL (untreated)Body mass index <25 kg/m2

Abstinence from smokingPhysical activity at goal for adults >20 y of age: ≥150 min/wk moderate intensity, ≥75 min/wk vigorous intensity, or combination

Healthy (DASH-like) diet


HORMONAL EFFECTS• PCOS have an increased prevalence of impaired GTT, metabolic

syndrome, and DM.

• Functional hypothalamic amenorrhea, also associated with premature coronary atherosclerosis.

• Early age at menarche <12 yrs is also associated with increased risk of CAD , CAD mortality, and overall mortality in women.

• Pre-eclampsia double the risk of subsequent IHD, stroke, and venous thromboembolic events over the 5 to 10 years following pregnancy.

• Gestational diabetes increases the risk for future diabetes thereby increasing the risk for future CAD

• OCPs and Menopause.

AWARENESS IS LACKING

• ~2500 women > 25 y.o. surveyed• Between 1997-2012, awareness among whole study

population nearly doubled: 30%56%Mosca L, et al. Fifteen-year trends in awareness of heart disease in

women. Circulation 2013; 127.

AWARENESS

Mosca L, et al. Fifteen-year trends in awareness of heart disease in women. Circulation 2013; 127.

UNDERTREATMENT OF CAD IN WOMEN

• Awareness is now increasing.

• Fewer than 1 in 5 physicians recognized that more women than men die each year from CAD.

• Women are less likely to receive preventive recommendations, such as lipid-lowering therapy, aspirin, and lifestyle advice.

• Hypertensive women are less likely to have their BP at goal.

• Women are less likely to be treated to reach goal for LDL-C.

Mosca L et al. National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation 2005Abuful A, et al. Physicians’ attitudes toward preventive therapy for coronary artery disease: is there a gender bias? Clin Cardiol 2005Chou AF et al.Gender disparities in the quality of cardiovascular disease care in private managed care plans.Womens Health Issues 2007

ACS IN PREGNANCY

• Incidence was 6.2 in 100,000 pregnancies.

• The risk of MI was increased 3 to 4 fold compared to nonpregnant women.

• Most cases occur in the third trimester and six-week postpartum period.

• Risk factors – Same• Other risk factors- Thrombophilia, and APLA syndrome,

and pregnancy related complications such as blood transfusion and postpartum infection.

A study of 150 cases1:• Coronary dissection - 43% • Coronary atherosclerosis - 27%.• Thrombus in a normal coronary artery - 17% • Coronary artery spasm - 2%• Normal coronary anatomy - 11%

1.Elkayam U et al. Pregnancyassociated AMI: a review of contemporary experience in 150 cases between 2006 and 2011. Circulation. 2014.

MANAGEMENT OF AMI IN PREGNANCY

• Principles same as general population.

• A high co-ordination among emergency, obstetric, and cardiovascular teams needed.

• Heparin, Low dose aspirin, beta blockers, and nitrates is used.

• Fibrinolytic therapy is relatively contraindicated.

• ACE inhibitors, ARBs and statins are contraindicated.

DIAGNOSIS OF MYOCARDIAL ISCHEMIA IN WOMEN

• In women, ST depression on exercise stress testing is less accurate than in men.

• Also the sensitivity and specificity of ST-segment depression is lower than in men.

• But negative predictive value is high in both men and women.

• Duke treadmill score is particularly useful in women and performs better in women than in men for predicting significant CAD.

DIAGNOSTIC VALUE OF STRESS TESTS IN WOMEN

Stress Testing Modality

Sensitivity, %

Specificity, %

Negative PredictiveValue

Positive PredictiveValue

Exercise ECG 31- 71 66- 78 78 47

Exercise Echo 80- 88 79- 86 98 74

Exercise SPECT 78- 88 64- 91 99 87

Pharmacological Echo

76- 90 85- 94 68 94

Pharmacological SPECT

80- 91 65- 86 90 64

Kohli P et al. Circulation 2010

ACS WITH NON OBSTRUCTIVE CAD IN WOMEN

Women with ACS and normal coronary arteries who underwent CMR , abnormalities on late gadolinium enhancement consistent with ischemia is frequently noted.

Reynolds HR et al. Circulation 2011

• A study of predominantly female patients with chest pain and nonobstructive CAD who underwent adenosine CMR found that subendocardial ischemia was frequently present when compared with images of control subjects.

• Panting JR et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med 2002

• In a small substudy from the WISE cohort, women with nonobstructive CAD with an abnormal stress-induced CMR had an increase in adverse cardiovascular events.

• Johnson BD et al. Circulation 2004

MANAGEMENT OF OBSTRUCTIVE CAD IN WOMEN

• Why is mortality due to ACS higher in women than in men???

• Undertreatment and less aggressive management.

• CRUSADE initiative- women were less likely to• receive heparin and GP IIb/IIIa inhibitors and less likely to

undergo cardiac catheterization and revascularization.

• Women with ACS have also been shown to be less likely to receive early aspirin, beta-blockers, reperfusion, and timely reperfusion.

Conclusion- Women were less likely to receive heparin, ACE Inhibitor, and GP IIb/IIIa inhibitors and less commonly received aspirin, and statins at discharge. Use of cardiac catheterization and revascularization was higher in men. Women were at higher risk for in-hospital death, reinfarction, heart failure, stroke , and RBCtransfusion. Women with NSTE ACS are treated less aggressively than men.

Conclusion: women were less likely to receive early aspirin treatment , early BB treatment , reperfusion therapy , or timely reperfusion . Women also experienced lower use of cardiac catheterization and revascularization Procedures. Women with STEMI had higher adjusted mortality rates than men.

Circulation 2008

Conclusion- Invasive strategy was more beneficial in women with positive biomarkers in contrast to women with negative biomarkers.

Such a difference was not seen in men

JAMA 2008

• With raised biomarkers, women receive a risk reduction with GP IIb/IIIa inhibitors.

• (Boersma E et al. Lancet 2002)

FIBRINOLYSIS IN WOMEN

• Women are less likely to receive fibrinolysis, even if eligible, and had a greater delay in being treated.

• Women receiving fibrinolysis have a higher rate of mortality and morbidity compared to men1-5.

• These differences are primarily due to worse baseline characteristics, such as older age and significantly higher rates of diabetes mellitus, hypertension, and prior heart failure.

• Women have a modestly increased risk of bleeding, including hemorrhagic stroke, after fibrinolysis

1White HD et al.The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Study. Circulation. 19932Gottlieb S et al. Circulation. 2000;102:2484. 3Vaccarino V et al. N Engl J Med. 1999. 4Stone GW et al.Am J Cardiol. 1995. 5Woodfield SL et al. J Am Coll Cardiol. 1997

PCI IN WOMEN

• After PCI, women have a higher mortality in STEMI and NSTEMI.

• (Lansky AJ. Prog Cardiovasc Dis 2004)

• DES placement in men and women have found similar outcomes.1,2

1.Solinas E et al. Gender-specific outcomes after sirolimus-eluting stent implantation. J Am Coll Cardiol 2007

2.Lansky AJ, et al, for the TAXUS-IV Investigators.Gender-based outcomes after paclitaxel-eluting stent implantation in patients with coronary artery disease. J Am Coll Cardiol 2005

CABG IN WOMEN

• Female sex is an independent risk factor for morbidity and mortality.

• Less relief from angina than do men after CABG.

• In contrast to the short-term findings, long-term survival after CABG in women is comparable to, or better than, that for men.

Abramov D et al. Ann Thorac Surg 2000Edwards FH et al.Ann Thorac Surg 1998Puskas JD et al.Ann Thorac Surg 2007

• In the BARI trial in 1829 patients, 27% were women.

• Crude mortality rates at 5.4 years were similar for women and men (12.8 and 12.0%).

• However, women were older and had more heart failure, hypertension, and diabetes;

MANAGEMENT OF NON-OBSTRUCTIVE CAD IN WOMEN

• Prognosis was initially felt to be benign1,2.

• More recent data have shown that the prognosis is not benign and the risk of cardiovascular events is higher than it is for asymptomatic women3,4.

• Symptomatic women in the WISE study with nonobstructive CAD (lesions 1% to 49%) had a CAD event rate of 16% versus only 7.9% in women with no CAD and only 2.4% in asymptomatic age- and race-matched controls.4

1.Kemp HG et al. CASS registry study. J Am Coll Cardiol 1986.2.Kaski JC et al.Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol 19953. Gulati M et al. Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the WISE Study and the St. James Women Take Heart Project. Arch InternMed 20094. Shaw LJ et al, for the WISE Investigators. The economic burden of angina in women with suspected IHD results from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation. Circulation 2006

• Focus of treatment- Symptoms relief and improving vascular function.

• ACE Θ and Statins

• Effects of BB and Ranolazine are promising in improving angina.

• RCT data on women with chest pain and non obstructive CAD are currently lacking.

• Cardiac rehabilitation after MI is underused, particularly in women1-4.

1.Witt BJ et al. Cardiac rehabilitation after MI in the community. J Am Coll Cardiol 2004.2.Suaya JA et al. Use of cardiac rehabilitation by Medicare beneficiaries after myocardial infarction or coronary bypass surgery. Circulation 2007.3.Evenson KR et al. Predictors of outpatient cardiac rehabilitation utilization: the Minnesota Heart Surgery Registry. J Cardiopulm Rehabil 19984.Thomas RJ et al. National Survey on Gender Differences in Cardiac Rehabilitation Programs. Patient characteristics and enrollment patterns. J Cardiopulm Rehabil 1996

TAKE HOME MESSAGE• CAD is the biggest health risks for women.

• Women can present differently, and do worse when they do.

• Most risk factors are the same for men and women, but women are at particularly high risk if they have DM, Gender specific risks like menopause and intake of birth control pills.

• Women present late and referred less often for appropriate testing and treatment.

• Women can have more complications from treatment, but still do better than without Rx.

TAKE HOME MESSAGE

• Awareness is still less than it needs to be.

• Prevention Can reduce risk.

• Screening programs should be encouraged.

THANK YOU

coronary artery disease in women by dr abhishek rathore

Health & Medicine