Coronary Artery Disease - ATHERO.ORG · 2019-06-03 · 2 Coronary Artery Disease in Women by Wael...

transcript

Coronary Artery Disease

in Women

by Wael AlmahmeedMD, FCCP, FRCPC, FRCPE, FACP, FACC, FESC

Clinical Associate Professor of Medicine, UAE University

Consultant Cardiologist at

Cleveland Clinic, Abu Dhabi

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

Prevalence of cardiovascular disease in adults ≥20 years of age by age and sex (National Health and Nutrition Examination Survey: 2009–2012).

Cardiovascular disease and other major causes of death for all males and females (United States: 2011).

Cardiovascular disease (CVD) mortality trends for males and females (United States: 1979–2011).

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

• 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.

Risk Assessment

Diagnosis of Myocardial

Ischemia in Women

A negative exercise test is a good negative predictor of CAD in Women.

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.

With regards to surgery: CABG Female sex is an independent risk factor for morbidity and mortality.

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.

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.

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.

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.

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

Citizens

Expatriates

MenWomen

p<0.001

Citizens

Expatriates

6 Middle-eastern Countries

Clinical Characteristics

Variable Men

(n=6,183)

(n=1,983)

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)

(n=1,983)

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

Variable Men

(n=6,183)

(n=1,983)

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

Variable Men

(n=6,183)

(n=1,983)

GRACE risk score 0.000

Low 1,073 (46%) 84 (25%)

Medium 702 (30%) 102 (29%)

High 585 (25%) 161 (46%)

9 years older than men

more diabetes

more HTN

more obesity

more dyslipidemia

less smoking

more co-morbidities

Variability

Variable Men Women p

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

Lytics Pri PCI Aspirin -blockers Clopidogrel

96% 98%

56%60%

P=.006P=.07

* Of patients eligible for thrombolysis.

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)

Death CHF Shock Re-MI Stroke

Hospital Outcome

14%15%

P<0.001

P=0.02

P=0.002

STEMI NSTEMI U.Angina

Mortality Rate Stratified According to type of ACS and Gender

1% 1.2%

P=0.001

P=0.007

P=0.68

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

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.

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.

Gender Differences

in Gulf RACE2

Medical treatment:

Males received more: Beta Blockers

Clopidogrel

Females received more: CCB

Insulin and OHA

Men had more PCI vs Women: 15.6% vs 10.5%

Men had more reperfusion 20.2% vs 6.9

therapy

Gender Differences

in Gulf RACE2

At discharge:

Men got more: ASA

Plavix

Beta Blockers

Statins

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

Clinical Outcomes & Mortality

Recurrent ischemia

Ventilation

In Hospital Death

Death at 1 month

Death at 1 year

Were all higher in Women.

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

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

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

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

Dyslipidemia

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

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.

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

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

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

Sex differences in EB medications are

significant.

There are larger differences in

reperfusion therapy.

Also differences in catheterization and

revascularization.

Summary

1. Introduction

2. Coronary Artery Disease in women in the West.

3. Coronary Artery Disease in women in the Gulf States.

Coronary Artery Disease - ATHERO.ORG · 2019-06-03 · 2 Coronary Artery Disease in Women by Wael...

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