Coronary Heart Disease in Women (Dr. Karol E. Watson)

Coronary Heart Disease in WomenKarol E. Watson, MD, PhD

Assistant Professor of Medicine/ Division of Cardiology

Co-director, UCLA Program in Preventive Cardiology

David Geffen School of Medicine at UCLA

Statistics

• Heart Disease and Stroke – First and third leading causes of death in US– Accounts for more than 40% of all deaths

• About 95,000 Americans die of heart disease or stroke each year– Amounts to one death every 33 seconds

• Heart Disease is the leading cause of disability among working adults

Cardiovascular Disease Mortality Cardiovascular Disease Mortality Trends for Males and Females Trends for Males and Females United States: 1979-2003United States: 1979-2003

Source: CDC/NCHS.

400

420

440

460

480

500

520

79 80 85 90 95 00 03

Years

Dea

ths

in T

hous

ands

Males Females

0

Hospital Discharges for Heart Failure by Sex - United States: 1979-2003

Source: National Hospital Discharge Survey, CDC/NCHS and NHLBI.

0

100

200

300

400

500

600

700

79 80 85 90 95 00 03

Years

Dis

ch

arg

es

in

Th

ou

sa

nd

s

Male Female

Source: NCHS and NHLBI. These data include coronary heart disease, heart failure, stroke and hypertension.

14.8

39.1

71.3

9.4

39.5

75.183.0

92.0

0.0

20.0

40.0

60.0

80.0

100.0

20-39 40-59 60-79 80+

Per

cent

of

Pop

ulat

ion

Males Females

Prevalence of cardiovascular diseases in adults by age and sex (NHANES: 1999-2004).

10.1

21.4

34.6

59.2

4.28.9

40.2

74.4

20.0

65.2

010

2030

4050

6070

80

45-54 55-64 65-74 75-84 85-94

Age

Pe

r 1

,00

0 P

ers

on

Ye

ars

Men Women

Source: FHS, 1980-2003. NHLBI.

Incidence of cardiovascular disease by age and sex

0

2

4

6

8

10

12

14

35-44 45-54 55-64 65-74

Ages

Per

1,0

00 P

erso

ns White Men

Black Men

White Women

Black Women

Source: NHLBI’s ARIC surveillance study, 1987-2000.Source: NHLBI’s ARIC surveillance study, 1987-2000.

Annual rate of first heart attacks by age, sex and race (ARIC: 1987-2000).

Note: Hospital discharges include people discharged alive, dead and status unknown..

Source: NHDS, NCHS and NHLBI.

Hospital discharges for heart failure by sex(United States: 1979-2004).

Women and Heart Disease

Heart Disease is the #1 Killer of Women

• Coronary heart disease is the single leading cause of death and a significant cause of morbidity among American women.

• In 1997 CHD claimed the lives of 502,938 women (men had less deaths)

• Since 1984, CVD has killed more American women than men each year.

“Breast Cancer is the REAL issue!”

• Who cares about heart disease doc…I am more concerned about:

BREAST CANCER and lung cancer!”

• In a recent survey, 75% of women identified cancer as their leading cause of death…

In perspective:

• 1 in 2 women will die of heart disease.

• 1 in 25 women will die of breast cancer.

CHD Mortality in Younger Women

2.94.1

5.7

8.2

10.7

14.4

18.4

21.8

25.3

6.17.4

9.5

11.1

13.4

16.6

19.1

21.5

24.2

0

5

10

15

20

25

30

< 50 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89

Dea

th d

urin

g H

ospi

taliz

atio

n (%

) Men

Women

Figure 1. Rates of death during hospitalization for Myocardial Infarction among w omen and men, according to age. The interaction betw een sex and age w as signif icant (P<0.001).

Women Women underunder 65 suffer the highest relative sex-specific CHD mortality 65 suffer the highest relative sex-specific CHD mortality

Coronary Heart Disease in Women

• Presentation and differences from men

• 2/3 of women who die suddenly have no previously recognized symptoms.

• Women are more prone to non-cardiac chest pain…..

• In fact they may experience little or no squeezing chest pain in the center of the chest, lightheadedness, fainting, or shortness of breath with an MI

Source: Milner Am J Cardiol 1999;84:396

Nationally: The Problem – AWARENESS

• Perception• 67% knowledgeable

that chest pain can be heart disease

• <10% knowledgeable that SOB, nausea, indigestion can be heart disease

• Reality• chest pain is the

presenting symptom in <50% of women

• Almost half of MIs in women present with SOB, nausea, indigestion, fatigue and shoulder pain

Causes of Confusion:

• Women may experience more dizziness, nausea, indigestion, and fatigue than men.

• Women are more likely to have neck, arms, back and shoulder pain.

Women and Heart Disease

Risk Factors

Source: NCHS and NHLBI. Source: NCHS and NHLBI.

163

171 170

165

174

155

163161

172

166163

166168

164

156

161

145

150

155

160

165

170

175

180

White Males Black Males White Females Black Females

Mea

n T

ota

l Blo

od

Ch

ole

ster

ol

1976-80 1988-94 1999-02 2003-04

Trends in total cholesterol among adolescents ages 12-17 by race and sex

(NHES: 1966-70; NHANES: 1971-74 and 1988-94).

Non-modifiable Risk Factors

• Age > 55

– CAD rates are 2-3x’s higher in postmenopausal women

• Family history

– CHD in primary 1st degree relative male<55 or female<65

The #1 Preventable Risk- Smoking

• A. 50% of heart attacks among women are due to smoking. Smokers tend to have their first heart attack 10 years earlier than nonsmokers.

• B. If you smoke, you are 4-6x’s more likely to suffer a heart attack and increase your risk of a stroke.

• C. Women who smoke and take OCP’s increase their risk of heart disease 30x’s.

SMOKING:

• Stop!!!!! (avg. attempt = 8 times)• Women who have other smokers in

their household have a 2.5 X's greater likelihood of relapse. Circulation 2002:106

• Smoking cessation was associated with a 36% reduction in mortality among patients with CHD.

JAMA 2003:290

Hypertension

• 65% of all hypertension remains either undetected or inadequately treated.

• People who are normotensive at 55 have a 90% lifetime risk of developing HTN.

• Prevalence increases with age and women live longer- hypertension is more common in females.

• HTN is more common with OCP and obesity.

Women and HTN—JNC VII

• The relationship bet. BP and CV events is continuous, consistent and independent of other risk factors.

• The higher the BP the greater the chance of MI, CHF, stroke, and kidney disease.

• Can try to achieve good BP through lifestyle changes.

Risk Factors: Diabetes • Diabetes increases the risk of CHD 3-7 X

in women versus 2-3 X in men.

• Diabetic women who smoke have a 84% higher risk of developing stroke than nonsmokers.

• 2 of 3 people with diabetes die from CHD or stroke.

Cholesterol

• More than 55 million women (45million men) have TC>200.

• Check cholesterol at least once q 5yr’s starting at age 20.

• 36 Million people in the US should be taking a statin according to guidelines, but only 11 million are.

Lifestyle Modification for HTN

Modification Recommendation Expected systolic reduction

Weight reduction Goal of BMI 18-25

Waist <35inches5-20 mm Hg per 10kg wt loss

DASH Fruits, veges, low-fat dairy products, less fat

8-14 mm Hg

Sodium restriction <2.4 g every day 2-8 mm Hg

Physical activity 30 mins of aerobic 4x’s a week

4-9 mm Hg

Reduced EtOH

(1/2 for women)

2-12 oz beer, 1 10oz wine, 3 oz 80proof whiskey in men

2-4 mm Hg

Cholesterol

• Women at high risk should be considered for statin therapy regardless of cholesterol-LDL levels.

• Statins have surpassed all other classes of agents in reducing the incidence of the major adverse outcomes of death, MI, and stroke.

NEJM 350:15 April 8, 2004

How we’ve changed our thinking about Primary Prevention in Women

• Hormone Therapy

• Risk Factors

• Preventive Medications

• Lifestyle Interventions

HERS: Combined HT Does Not Decrease All-Cause Mortality

Hulley S, et al. JAMA. 1998;280:605–613.

Inci

den

ce

(%

)

Follow-up, y (no. at risk)

0

5

10

15

0(2763)

1(2720)

2(2666)

3(2595)

4(1590)

5(130)

Estrogen-Progestin

Placebo

Coronary Heart DiseaseHR = 1.2995% nCI. 1.02–1.6395% aCI. 0.85–1.97

Estrogen + Progestin

Placebo

0.03

0.01

0.02

0

Cu

mu

lati

ve

H

aza

rdC

um

ula

tive

H

aza

rd

0.03

0.01

0.02

0

StrokeHR = 1.4195% nCI. 1.07–1.8595% aCI. 0.86–2.31

Invasive Breast CancerHR = 1.2695% nCI. 1.00–1.5995% aCI. 0.83–1.92

Pulmonary EmbolismHR = 2.1395% nCI. 1.39–3.2595% aCI. 0.99–4.56

Cu

mu

lati

ve

Ha

zard

0.03

0.01

0.02

0

Hip FractureHR = 0.6695% nCI. 0.45–0.9895% aCI. 0.33–1.33

Colorectal CancerHR = 0.6395% nCI. 0.43–0.9295% aCI. 0.32–1.24

0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7Time (y)Time (y)

Estrogen + Progestin and Disease in WHI*

24% Increase Breast Cancer

Also: DVTs

Fracture Reduction (Hip 23%)

STOPPED Early, Clear Harm

24% Increase CHD31% Increase

Stroke

RisksBenefits

JAMA. 2002;288:321-333

Stopped 3.3 yrs early

111% Increase Pulmonary Emboli

39% Reduction Colorectal Cancer

WHI E+P Trial Findings, July 2002 (avg 5.2 y)

105% Increase Dementia

Summary of WHI Estrogen-Alone Results

Event Relative Hazard 95% CI

Inv. Breast Cancer 0.77 0.59-1.01CHD 0.91 0.75-1.12Hip Fracture 0.61 0.41-0.91*All Fractures 0.70 0.63-0.70*Colorectal Cancer 1.08 0.75-1.15_____________________________________________*p<.05JAMA, 4/14/04

Also: DVTs

Fracture Reduction (Hip 39%)

STOPPED Early, suggestion of harm

Neutral for CHDNeutral for breast cancer

39% Increase Stroke

Risks

Benefits

JAMA 2004;291:2947-58

Stopped 1.7 yrs early

34% Increase Pulmonary Emboli

WHI E Alone Trial Findings, 2004 (avg 6.8 y)

49% Increase Dementia

• Analysis of 24,317 women 50-79 years old in WHI– whose age at menopause could be defined– stratified into 3 groups: 50-59/ 60-60 /70-79 y.o.

• CHD, stroke & mortality rates analyzed• Stroke was increased in all women, regardless of age at

menopause or E vs. E + P • CHD was decreased in women who took E alone vs. E + P

(0.95 vs. 1.23 p=0.02)• In hormone users

– HR for CHD if < 10 years from menopause = 0.76– HR for CHD if 10-20 from menopause = 1.10– HR for CHD if >20 years from menopause = 1.28

Estrogen in the early menopausal years

Rossouw, J. E. et al. JAMA 2007;297:1465-1477.

Current research centers around the question: Does estrogen mean

different things in different vessels?

How we’ve changed our thinking

• Hormone Therapy– WHI - Combined hormone therapy increases

cardiovascular risk overall * (but may be safe/?beneficial in the early menopausal years)

– WHI - Estrogen only therapy is neutral on CHD

• Risk Factors • Preventive Medications• Lifestyle Interventions

NHANES III: Age-Adjusted Prevalence of ≥3 Risk Factors for the Metabolic Syndrome*

*Criteria based on ATP III; diabetics were included in diagnosis;

overall unadjusted prevalence 21.8%. Ford ES et al. JAMA. 2002;287:356-359.

24.8

16.4

28.3

22.8

25.7

35.6

Pre

vale

nce

( %

)

0

5

10

15

20

25

30

35

40

White African American Mexican American

Men

Women

Elevated Triglycerides Increase CHD Risk

Rela

tive R

isk f

or

CH

D

Men

Women

For every increase in serum TG level of 89 mg/dL, risk of CHD increases 30% in men and 69% in women13.14

Framingham Heart Study

Meta-Analysis of 17

Prospective Studies

*.001<P<.01; †P<.05; ‡For diabetic patient relative to nondiabetic patient aged 35–64 years.Wilson et al. In: Ruderman et al, eds. Hyperglycemia, Diabetes, and Vascular Disease. 1992:21-29.

CVD Events in Patients With Diabetes: Framingham Heart Study 30-Year Follow-Up

Rel

ativ

e R

isk

Rat

io‡

Women

Total CVD

**

CHD

*

*

Cardiac Failure

*

*

Intermittent Claudication

*

*

Stroke

†

0

2

4

6

8

10

12 Men

Risk of Stroke With Metabolic Syndrome, Stratified by Gender

0.0001 0.0001 1.4-3.5 1.4-3.5 2.2 2.2 Women Women

NS NS 0.5-1.7 0.5-1.7 0.9 0.9 Men Men

p p 95% CI 95% CI Hazard Hazard ratio ratio

Gender Gender

Boden-Albala BM et al. American Academy of Neurology Annual Meeting. Mar 29-Apr 5, 2003: Honolulu, HI.

• Hormone Therapy

• Risk Factors – Triglycerides, diabetes, and the metabolic

syndrome are greater risks for women as compared to men




Meta-analysis from CholesterolClinical Trialists (CCT) Collaboration

Cholesterol Clinical Trialists Collaboration. Lancet. 2005;366:1267.

Groups

Post MI

Other CHD

None

Sex

Male

Female

1681 (11.7%)

568 (8.7%)

1088 (4.5%)

2207 (15.4%)

744 (11.4%)

1469 (6.1%)

3630 (10.6%)

790 (7.3%)

2686 (7.8%)

651 (6.1%)

Events

Treatment Control45,002 45,054 RR

Heterogeneity/trend test

0.78 (0.74-0.84)

0.77 (0.68-0.87)

0.72 (0.66-0.80)

0.76 (0.72-0.80)

0.82 (0.73-0.93)

0.5 1.0 1.5

Control better

Treatment better

P=0.2

P=0.1

Aspirin Evidence: Primary Prevention in MenAspirin Evidence: Primary Prevention in Men

Physicians’ Health Study (PHS)22,071 men randomized to aspirin (325mg QOD) followed for 5 years

Aspirin significantly reduces the risk of MI in men

End point Relative Risk (95% CI) P value Myocardial infarction Fatal 0.34 (0.15-0.75) 0.007 Nonfatal 0.59 (0.47-0.74) <0.00001 Total 0.56 (0.45-0.70) <0.00001 Stroke Fatal 1.51 (0.54-4.28) 0.43 Nonfatal 1.20 (0.91-1.59) 0.20 Total 1.22 (0.93-1.60) 0.15

Physicians’ Health Study Research Group. NEJM 1989;321:129-35

CI=Confidence interval, MI=Myocardial infarction

End points (mean, 10.1 yrs):● Combined end point of nonfatal MI, nonfatal stroke, or total cardiovascular death

● Incidence of total malignant neoplasms of epithelial cell origin

Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial

Ridker PM. Presented at: 54th Annual Scientific Session of the American Collegeof Cardiology; March 7, 2005; Orlando, Fla. Ridker PM, et al. N Engl J Med. 2005;352.

39,876 initially healthy† women, aged 45 yrsRandomized, blinded, factorial

Low-Dose Aspirin100 mg on alternate days

n=19,934

Placebo

n=19,942

† No history of coronary heart disease, cerebrovascular disease, cancer (except nonmelanoma skin cancer), or other major chronic illness; no history of side effects to any of the study medications; not taking aspirin or nonsteroidal anti-inflammatory medications (NSAIDs) more than once a week (or were willing to forgo their use during the trial); not taking anticoagulants or corticosteroids; and not taking individual supplements of vitamin A, E, or beta carotene more than once a week.

Aspirin : Primary Prevention in WomenAspirin : Primary Prevention in Women

Womens’ Health Study (WHS)

0.00

0.01

0.02

0 2 4 6 8 10

Cum

ulat

ive

Inci

denc

e of

MI

Placebo

Aspirin

P=0.83

Ridker P et al. NEJM 2005;352:1293-304

MI=Myocardial infarction

Years

39,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years

Aspirin does not reduce the risk of MI in low risk women

Conclusions

• In this large, primary-prevention trial among women, aspirin (50 mg/d) lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes. In the subgroup of women > 65 years old both stroke and MI were significantly decreased

Aspirin Evidence: Primary PreventionAspirin Evidence: Primary PreventionBDT, 1988

Combined

PPP, 2001

HOT, 1998

TPT, 1998

PHS, 1989

RR of MI in Men

1.0 2.0 5.00.50.2

RR = 0.68 (0.54-0.86)P=0.001

1.0 2.0 5.00.50.2

RR = 1.13 (0.96-1.33)P=0.15

HOT, 1998

Combined

WHS, 2005

PPP, 2001

1.0 2.0 5.00.50.2

Aspirin Better Placebo Better

RR = 0.99 (0.83-1.19)P=0.95

1.0 2.0 5.00.50.2

Aspirin Better Placebo Better

RR = 0.81 (0.69-0.96)P=0.01

RR of CVA in Men

RR of MI in Women

RR of CVA in Women

Ridker P et al. NEJM 2005;352:1293-304

CVA=Cerebrovascular accident, MI=Myocardial infarction, RR=Relative risk

• Hormone Therapy• Risk Factors • Preventive Medications

– Statins reduce CHD in both men and women, however the NNT in women is greater

– ASA (50 mg/d) reduces the risk of stroke, but not MI in low risk women under the age of 65. For men, low dose ASA has shown the opposite



Women’s Health Initiative StudyReducing Total Fat Intake

• Study the effect of low-fat, high fruit, vegetable, and grain diet on breast cancer, colorectal cancer and heart disease in postmenopausal women

• Diet NOT designed for weight loss• Women followed 8.1 years• 48,000 postmenopausal woman

– No intervention – 60% of participants– Intervention (dietary change) – 40% of participants

WHI – Heart Disease: RESULTS

• No reduction in risk of MI or CHD death

• Small but significant improvements in risk factors including:–Body weight–LDL –Diastolic blood pressure–Factor VII C (a blood clotting factor)

WHI : What went wrong?

• Dietary pattern reduced ALL types of fat

• Diet designed for heart disease would focus on reducing saturated and trans fat

• Relied on food frequency questionnaires which rely heavily on memory*

• Participants started the study late in life*

Trans Fatty Acids and CHD Risk in Women

Sun et. al. Circulation 2007: 115

• Blood samples from 32,836 NHS subjects• 6 yr F/U 166 CHD events• Nested case/control• RBC trans fatty acid content divided into

quartiles• Multivariable relative risks

– Q1 vs. Q2 = 1.6– Q1 vs. Q3 = 1.6– Q1 vs. Q4 = 3.3

• Hormone Therapy

• Risk Factors


• Lifestyle Interventions– Diets that lower only total fat intake, and are

started later in life may not decrease CHD– Trans fat intake is strongly associated with

increased CHD in women


Documents

Coronary Heart Disease in Women (Dr. Karol E. Watson)