2
Coronary Artery Disease in Women
by Wael Almahmeed MD, FCCP, FRCPC, FRCPE, FACP, FACC, FESC
Clinical Associate Professor of Medicine, UAE University
Consultant Cardiologist at
Cleveland Clinic, Abu Dhabi
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Objectives
1. Coronary Artery Disease in women in the West.
2. Coronary Artery Disease in women in the Gulf States.
3. Summary
Age-adjusted prevalence of obesity in adults 20 to 74 years of age by sex and survey year (National Health Examination Survey: 1960–1962; National Health and Nutrition Examination
Survey: 1971–1974, 1976–1980, 1988–1994, 1999–2002, 2003-2006, and 2009–2012).
Mozaffarian D et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.
Prevalence of cardiovascular disease in adults ≥20 years of age by age and sex (National Health and Nutrition Examination Survey: 2009–2012).
Mozaffarian D et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.
Cardiovascular disease and other major causes of death for all males and females (United States: 2011).
Mozaffarian D et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.
Cardiovascular disease (CVD) mortality trends for males and females (United States: 1979–2011).
Mozaffarian D et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.
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Prevalence of CAD in Women
• Coronary Artery Disease is the leading cause of death in Women.
• CAD mortality is higher in Women than Men.
• Impact of obesity is greater in Women than in Men.
• Incidence of CAD lags 10 years behind Men.
• Consequences of CAD are worse in Women than in Men.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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• Pathophysiology of CAD is different in Women.
• Women have smaller Coronary Arteries.
• Less obstructive CAD.
• Disorders of the micro vasculative and Endothelial dysfunction have been implicated in Women.
• Women have a greater frequency of plaque erosion and distal embolization.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Risk Assessment
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Risk Assessment
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Risk Assessment
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Diagnosis of Myocardial Ischemia in Women
A negative exercise test is a good negative predictor of CAD in Women.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Management of Obstructive CAD in Women
Why is mortality due ACS in Women higher than in Women?
1. Women are treated less aggressively than men.
2. Receive less EB medicine.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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With regards to surgery: CABG Female sex is an independent risk factor for morbidity and mortality.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Management of Non-Obstructive CAD
Women with myocardial ischemia and non-obstructive CAD, the prognosis was felt to be benign in the past.
More recent data has shown that the prognosis is not benign and the risk of CV events is higher than for asymptomatic women.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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In the WISE Study:- Symptomatic women with non-obstructive CAD had an event rate of 16% vs 7.9% in Symptomatic women with no CAD and event rate was 2.4% in asymptomatic controls.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Treatment of Non-Obstructive CAD
1. Improve Endothelial function with Statins and ACE Inhibitors.
2. Symptoms with Beta Blockers and Imipranine and L arginine.
3. Ranolazine is promising.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
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Undertreatment of CAD • Women are still less likely to receive
preventive recommendations, such as lipid lowering, ASA, life style modification.
• Hypertensive women are less likely to have their BP at goal.
• Dyslipidemic women are less likely to reach their LDL goals, (particularly diabetic women).
• Women receive less cardiac rehabilitation.
Sharma K, et al; Global Heart; Vol. 8 No. 2, 2013
Allam et al (JAMA 2009;302(19) )
Coronary Artery Disease in Women of the Middle East is not new. It has recently been identified in Egyptian Mummies.
Gulf RACE I
6 months prospective multi center Registry of ACS in 6 Gulf States. 8,169 consecutive patients were recruited from 64 hospitals with diagnosis of ACS, including unstable angina, STEMI and NSTEMI.
Am J Cardiol 2009;104:1018-1022.
The Distribution of Men and Women in relation to
Citizenship
CitizensExpatriates
82%
48%
Men Women
p<0.001
Citizens
Expatriates
6 Middle-eastern Countries
Clinical Characteristics
Variable Men
(n=6,183)
Women
(n=1,983)
p
Value
Age (years) 53 (16) 62 (17)
Previous angina pectoris 2,295 (37%) 1,017 (51%) 0.001
Previous MI 1,531 (25%) 463 (23%) 0.225
Previous CABG 329 (5%) 132 (7%) 0.028
Diabetes Mellitus 2,226 (36%) 1,085 (55%) 0.001
Hypertension 2,665 (43%) 1,390 (70%) 0.001
Clinical Characteristics (cont.)
Variable Men
(n=6,183)
Women
(n=1,983)
p
Value
Dyslipidemia 1,736 (28%) 872 (44%) 0.001
Current smokers 2,886 (47%) 101 (5%) 0.001
Renal impairment 807 (14%) 277 (15%) 0.22
COPD 281 (5%) 154 (8%) 0.001
Stroke 225 (4%) 153 (8%) 0.001
PVD 127 (2%) 68 (3%) 0.001
Age
6 Middle-eastern Countries
Clinical Characteristics (cont.) Variable Men
(n=6,183)
Women
(n=1,983)
p
Value
BMI (kg/m2) 26.3 (5.4) 28.3 (8.4)
Heart Rate (beats/min) 80 (26) 88 (24)
Systolic BP (mm Hg) 136 (38) 140 (40)
Killip class > I 1,206 (20%) 568 (29%) 0.001
Ischemic Chest Pain 5,084 (82%) 1,400 (71%) 0.001
Atypical Chest pain 379 (6%) 158 (8%) 0.005
Dyspnea 499 (8%) 300 (15%) 0.001
Clinical Characteristics (cont.)
Variable Men
(n=6,183)
Women
(n=1,983)
p
Value
GRACE risk score 0.000
Low 1,073 (46%) 84 (25%)
Medium 702 (30%) 102 (29%)
High 585 (25%) 161 (46%)
WOMEN
9 years older than men more diabetes more HTN more obesity more dyslipidemia less smoking more co-morbidities
Variability
Variable Men Women p
Value
STEMI at discharge 2,749 443
Presentation > 12 hrs 731 (28%) 173 (42%) 0.001
Door-to-needle time 35 (40) 40 (50)
Eligible for reperfusion 1,929 (73%) 244 (59%) 0.001
Shortfall 153 (8%) 37 (15%) 0.001
Variability (cont.) Variable Men Women p Value
Thrombolysis 1,613 (84%)* 195 (80%)* 0.172
Primary PCI 163 (8%) 12 (5%) 0.074
Asprin 2,617 (96%) 408 (98%) 0.474
Beta Blockers 1,682 (63%) 234 (56%) 0.006
ACE inhibitors/ARBs 1,824 (69%) 272 (65%) 0.211
Clopidogrel 1,588 (60%) 229 (55%) 0.073
Heparin 2,438 (92%) 383 (92%) 0.971
Glycoprotein inhibitors 239 (9%) 9 (2%) 0.003
Statins 2,238 (81%) 354 (80%) 0.35
0
10
20
30
40
50
60
70
80
90
100
MenWomen
Lytics Pri PCI Aspirin -blockers Clopidogrel
84%*
80%*
96% 98%
63%
56% 60%
55%
5% 8%
P=NS
P=07
P=NS
P=.006 P=.07
* Of patients eligible for thrombolysis.
6 Middle-eastern Countries
Variability (cont.) Variable Men Women p Value
Death 137 (5%) 62 (14%) 0.0000
Heart failure 420 (15%) 128 (29%) 0.0000
Cardiogenic shock 204 (7%) 91 (21%) 0.0000
Reinfarction 77 (3%) 21 (5%) 0.02
Recurrent ischemia 241 (9%) 69 (16%) 0.000
Stroke 23 (1%) 13 (3%) 0.002
Major bleeding 28 (1%) 7 (2%) 0.38
Hospital stay 5 (3) 6 (4)
0
5
10
15
20
25
30
Death CHF Shock Re-MI Stroke
MenWomen
Hospital Outcome
5%
14% 15%
29%
7%
21%
3%
5%
1%
3%
P<0.001
P<0.001
P<0.001
P=0.02
P=0.002
6 Middle-eastern Countries
0
2
4
6
8
10
12
14
STEMI NSTEMI U.Angina
MenWomen
Mortality Rate Stratified According to type of ACS and Gender
5%
14%
2%
4%
1% 1.2%
P=0.001
P=0.007
P=0.68
6 Middle-eastern Countries
WOMEN
presented more often after 12 hrs STEMI missed in women compared to men
(6% vs 3%) HR high BP high presented with more dyspnea and atypical
chest pain. heart failure was more prevalent in women
Women
Less likely to receive thrombolysis, primary PCI
and have a prolonged door- -to-needle time.
WOMEN: Received less EB medicines verses the men. Had high GRACE scores Higher morbidity High in Hospital mortality Higher :- heart failure
cardiogenic shock recurrent ischemia stroke
Multivariate Analysis Predictor OR 95% CI p Value
Female gender 1.75 1.10 - 2.781 0.01
PCI 0.50 0.15 - 1.73 0.27
Asprin 0.25 0.12 - 0.70 0.008
Clopidogrel 0.96 0.64 - 1.46 0.87
Glycoprotein IIb/IIIb 0.51 0.18 - 1.39 0.18
Beta blockers 0.37 0.23 - 0.59 0.000
ACE Inhibitors 0.43 0.28 - 0.65 0.000
Thrombolysis 0.52 0.34 - 0.81 0.003
After adjustment for Age, HR, DM, HTM, GRACE Risk Score: Female gender comes associated with increased in hospital mortality. Under use of EB therapies was also associated with increased mortality.
This is the 1st study from the Middle East to show that Women with ACS had a high mortality rate
compared to men, after adjustment of all co-founders.
It confirms previous studies that women have different risk profiles :-
Present late Atypical symptoms Longer door-to-needle times Less perfusion therapies
Recognition of gender differences will lead to a number of quality
improvement projects to improve the process of care.
Physician and public awareness
programs are important to improve the management of women with ACS.
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Gender Differences in Gulf RACE2
Females comprised 21.3% of the ACS population.
Baseline characteristics:
Females were; Older
Higher BMI
More NSTEMI, UA
more HTN
Diabetes
Dyslipidemia
More atypical chest pain
Shehab A, et al; Plos One, 2013; Vol 8.
47
Gender Differences in Gulf RACE2
Medical treatment:
Males received more: Beta Blockers
Clopidogrel
Females received more: CCB
ARBs
Insulin and OHA
Men had more PCI vs Women: 15.6% vs 10.5%
Men had more reperfusion 20.2% vs 6.9
therapy
Shehab A, et al; Plos One, 2013; Vol 8.
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Gender Differences in Gulf RACE2
At discharge:
Men got more: ASA
Plavix
Beta Blockers
ACE
Statins
Shehab A, et al; Plos One, 2013; Vol 8.
Figure 1. Proportion of patients dying in-hospital and within one year from hospital discharge (n = 6132).
Shehab A, Al-Dabbagh B, AlHabib KF, Alsheikh-Ali AA, et al. (2013) Gender Disparities in the Presentation, Management and Outcomes of Acute Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). PLoS ONE 8(2): e55508. doi:10.1371/journal.pone.0055508 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055508
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Clinical Outcomes & Mortality
Recurrent ischemia
CHF
Ventilation
Shock
In Hospital Death
Death at 1 month
Death at 1 year
Were all higher in Women.
Shehab A, et al; Plos One, 2013; Vol 8.
Figure 2. Association of gender (female) and mortality derived from multivariate-adjusted analyses (n = 7930).
Shehab A, Al-Dabbagh B, AlHabib KF, Alsheikh-Ali AA, et al. (2013) Gender Disparities in the Presentation, Management and Outcomes of Acute
Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). PLoS ONE 8(2): e55508.
doi:10.1371/journal.pone.0055508
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055508
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Clinical Outcomes & Mortality
When adjusting for:
Age BMI presenting Symptoms
Country Killip class medical history
Diagnosis Tobacco invasive procedures
Medications
There is no difference in the 1 year mortality between genders
Shehab A, et al; Plos One, 2013; Vol 8.
Table 3. In-hospital outcomes and 1-month and 1-year post discharge mortality of the study cohort by gender (n = 7930).
Shehab A, Al-Dabbagh B, AlHabib KF, Alsheikh-Ali AA, et al. (2013) Gender Disparities in the Presentation, Management and Outcomes of Acute
Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). PLoS ONE 8(2): e55508.
doi:10.1371/journal.pone.0055508
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055508
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Gulf RACE II
Women presented with more NSTEMI/UA
70.2% vs 50.2%
While Men presented with STEMI
49.8% vs 29.8%
Women had more HTN
DM
Dyslipidemia
Shehab A, et al; Plos One, 2013; Vol 8.
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Gulf RACE II
Women are treated more conservatively. This may have been due to the following:
1. More co-morbidities
2. Atypical presentation
3. Patient preference
4. Physicians preference or Fear
Shehab A, et al; Plos One, 2013; Vol 8.
56
Gulf RACE II
In this Study, in contrast to Gulf RACE I, the Multivariate Regression Models indicated that most of the differences in mortality can be explained by the confounding baseline variables and the differences in management.
Greater awareness of CAD in Women may eliminate the gender gap.
Shehab A, et al; Plos One, 2013; Vol 8.
Summary of Statin Initiation Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults (See Figures 3, 4, and 5 for More Detailed Management Information).
Stone N J et al. Circulation. 2014;129:S1-S45
Copyright © American Heart Association, Inc. All rights reserved.
Summary of Statin Initiation Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults (See Figures 3, 4, and 5 for More Detailed Management Information).
Stone N J et al. Circulation. 2014;129:S1-S45
Copyright © American Heart Association, Inc. All rights reserved.
Menopausal Hormone Therapy, SERMs and CVD: Summary of Major Randomized Trials
Use of estrogen plus progestin associated with a small but significant risk of CHD and stroke
Use of estrogen without progestin associated with a small but significant risk of stroke
Use of all hormone preparations should be limited to short term menopausal symptom relief
Use of a selective estrogen receptor modulator (raloxifene) does not affect risk of CHD or stroke, but is associated with an increased risk of fatal stroke
Source: Hulley 1998, Rossouw 2002, Anderson 2004, Barrett-Connor 2006
Interventions that are not useful/effective and may be harmful for the prevention of heart disease
Hormone therapy and selective estrogen-receptor modulators (SERMs) should not be used for the primary or secondary prevention of CVD
Source: Mosca 2007
HEART DISEASE IN WOMEN Summary
1. Less obstructive CAD. 2. More chest pain without obstructive CAD. 3. Symptoms do not correlate with severity of
stenoses. 4. Young and middle aged women show high
rates of adverse outcomes after MI.
Vaccarino, Circ Cardiovasc Quality Outcomes, 2010
Women do worse than men when they have an STEMI.
Sex differences are found in younger women with MI.
These women have a higher rate of risk factors and co-morbidities compared to men.
Sex differences in EB medications are significant.
There are larger differences in reperfusion therapy.
Also differences in catheterization and revascularization.
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Summary 1. Introduction
2. Coronary Artery Disease in women in the West.
3. Coronary Artery Disease in women in the Gulf States.