This is about the epidemiology, unique presentation, clinical features, diagnosis and management of CAD in women

1. CAD IN WOMEN

2. Overview
 The Scope of the problem.
 Impact of CAD on women
 Risk assessment
 Sex specific characteristics
 Management strategies specific to women.

3. 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.

4. Prevalence of CHD by age and sex
Dariush Mozaffarian et al. Circulation. 2016;133:e38-

5. Annual number of adults per 1000 having diagnosed
heart attack or fatal CHD by age and sex
Dariush Mozaffarian et al. Circulation. 2016;133:e38-

6. Incidence of Heart attack or fatal CHD by age, sex, and
race
Dariush Mozaffarian et al. Circulation. 2016;133:e38-

7. Incidence of angina pectoris by age and sex
Dariush Mozaffarian et al. Circulation.

8. CAD IN INDIAN WOMEN
 Prevalence of CAD - men 4.8 %, women 2.6 %.
 19 crore Indian women have CAD.
M. N. Krishnan et al. BMC Cardiovascular Disorders
2016

9. 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

10. 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

11. 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 2015
2.Vaccarino V et al. N Engl J Med 1999
3.Wilson PW et al, Arch Intern Med 2002

12. 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

13. 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 2001
3.WISE study. Eur Heart J 2006
4.WISE study. Circulation 2006

14. 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)

15. What are the symptoms?

16. 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

17. Symptoms in women with MI
 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
Canto JG et al. JAMA 2012;307:813

18. Symptoms in women with MI
These women who presented without CP were sicker
and has worse outcomes :
 More had DM
 Later presentation
 More Killip III/IV
 More NSTEMI
 Less timely therapies
 Less antiplatelet meds, heparin, BB
Canto JG et al. JAMA 2012;307:813

19. Which risk factors are more predictive in
women?
 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)
Huxley R et al.BMJ 2006
Njolstad I et al. Circulation 1996;93(3):450;
Prescott E et al. BMJ 1998;316(7137):1043

20. Which risk factors are more predictive in
women?
 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 # Lerner D J eta l.Am Heart J 1986
Rich-Edwards, JW et al. NEJM 1995; 332:1758;
Miller VT. Atherosclerosis 1994; 108 Suppl:S73;
Orth-Gomer K. Circulation 1997;95:329
Hokanson JE et al. J Cardiovasc Risk 1996.

21.  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.

22. 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)

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

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

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

26. 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.

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

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

29. Under treatment 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
2005
Abuful A, et al. Physicians’ attitudes toward preventive therapy for coronary artery disease: is there a gender bias? Clin Cardiol
2005

30. 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.

31. ACS in Pregnancy
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. Pregnancy associated AMI: a review of contemporary experience in 150 cases between 2006 and 2011.
Circulation. 2014.

32. 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.

33. 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.

34. Diagnostic value of stress tests in women
Kohli P et al. Circulation 2010

35. 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

36. Non obstructive CAD in women
 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 cardio
vascular MRI. N Engl J Med 2002

37. Non obstructive CAD in women
 In a small substudy from the WISE cohort, women with non
obstructive CAD with an abnormal stress-induced CMR had an
increase in adverse cardiovascular events.
Johnson BD et al. Circulation 2004

38. 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.

39. 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 RBC
transfusion.

40. Conclusion: women were less likely to receive early aspirin 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

41. Conclusion- Invasive strategy was more beneficial in women with
positive bio markers in contrast to women with negative biomarkers.
Such a difference was not seen in men
JAMA 2008

42.  With raised biomarkers, women receive a risk reduction with
GP IIb/IIIa inhibitors.
(Boersma E et al. Lancet 2002)

43. 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. 1993 ,2Gottlieb 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

44. 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

45. 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 2000
Edwards FH et al.Ann Thorac Surg 1998
Puskas JD et al.Ann Thorac Surg 2007

46. CABG in women
 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;

47. 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 1995
3. 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 2009
4. 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

48.  Focus of treatment- Symptoms relief and improving vascular
function.
 ACEIs 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.

49. 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 1998
4.Thomas RJ et al. National Survey on Gender Differences in Cardiac Rehabilitation Programs. Patient
characteristics and enrollment patterns. J Cardiopulm Rehabil 1996

50. 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

51. Take home message
 Awareness is still less than it needs to be.
 Prevention Can reduce risk.
 Screening programs should be encouraged.

53. Thank you