Update on Women and Cardiovascular

Disease Amy Rawl Epps, M.D.

Columbia Cardiology2/5/09

Financial Relationships“As it pertains to CME, I have no

relevant financial relationships with any commercial interest to disclose.”

Why is it so critical to recognize and diagnose CAD in women?

Circulation 2005

Although US men have experienced a decline in CAD deaths, the number of coronary deaths in women, >240 000 annually, has increased

CAD is a substantial cause of morbidity and disability for US women.

Women, in particular young women (<55 years), have a worse prognosis from acute MI than their male counterparts, with a greater recurrence of MI and higher mortality.

Up to 40% of initial cardiac events in women are fatal

* Number of deaths are rounded to the nearest thousand. COPD = chronic obstructive pulmonary disease. National Heart, Lung, and Blood Institute. The Healthy Heart Handbook for Women. 2003.

Cause of Death

Nu

mb

er

of

Death

s*

0

50,000

100,000

150,000

200,000

250,000

300,000

350,000

400,000 Heart Disease 366,000

BreastCancer42,000

COPD62,000

LungCancer65,000

Stroke103,000

• CHD mortality rate

•10 X that from breast cancer

•50% > all forms of cancer combined

• 38% one-year morality post-MI

• 46% six-year disability rate from CHF

Mortality Rates for Women

United States 2001

CVD Mortality Trends for Males and Females: US 1979–2002

American Heart Association. Heart Disease and Stroke Statistics — 2005 Update. Dallas, Tex: American Heart Association; 2005. ©2005, American Heart Association.

Years

Males Females

400

440

480

520

0

1979 81 83 85 87 89 91 93 95 97 99 01 02

Dea

ths

(tho

usan

ds)

NCEP I NCEP II NCEP III

NCEP = National Cholesterol Education Program.

Compared with Men: 38% of women and 25% of men will die within one year of a first

recognized heart attack. 35% of women and 18% of men heart attack survivors will have another

heart attack within six years. 46% of women and 22% of men heart attack survivors will be disabled

with heart failure within six years. Women are almost twice as likely as men to die after bypass surgery. Women are less likely than men to receive beta-blockers, ACE

inhibitors or even aspirin after a heart attack. More women than men die of heart disease each year, yet women

receive only: 33% of angioplasties, stents and bypass surgeries 28% of inplantable defibrillators and 36% of open-heart surgeries

Women comprise only 25% of participants in all heart-related research studies.

Similar risk profile for men and women

Circulation. 2004;109:573-579

Why Women Don’t Women Take Action Against Heart Disease Stereotype of only men getting heart disease More concerned about ‘other’ diseases Think they’re not old enough to be at risk More accustomed to the role of caregiver They don’t put their health as a top priority Too busy to deal with it…do it later Already feeling tired & stressed out

Risk Stratification:How much risk

am I at?

Risk Stratification: Major Risk Factors:

Age > 55 years Smoking Hypertension (whether or not controlled with medication) HDL cholesterol < 40mg/dL; LDL (>130-160)

(HDL cholesterol ≥ 60mg/dL is a negative risk factor) Family history of premature CVD (Defined as CVD in a female first degree

relative < 65 years old, or a first degree male relative < 55 years old) Obesity/Sedentary Lifestyle

‘CHD equivalent’ (automatically places in “high-risk” category) Diabetes Established atherosclerotic disease (carotid, peripheral) +/- kidney disease

Source: Mosca 2004, ATP III 2002

Key Tests for Heart Disease Risk

Risk Stratification Blood pressure Blood cholesterol Fasting plasma glucose (diabetes test) Body mass index (BMI)

Testing Electrocardiogram Stress test Other

Coronary Disease Mortality and Diabetes in Women

Mort

alit

y (

per

10

00

wom

en

)

Relative Risk of Coronary Events for Smokers Compared to Non-Smokers

3.12

5.48

1

0

1

2

3

4

5

6

Never Smoked 1-14 Cigarettes perday

15 Cigarettes perday

Relative Risk

Source: Adapted from Stampfer 2000

>

Obesity & Heart Disease

<1.0

Body Weight & CHD Mortality Among Women

7.4

2.6

0

1

2

3

4

5

6

7

8

Wt Gain 10-19kg Wt Gain 20kg

Weight Gain Since Age 18

Relative Risk of CHD

Mortality

P for trend < 0.001

≥

Source: Adapted from Manson 1995

Noninvasive diagnostic and prognostic testing offers the potential to identify women at increased CAD risk and establish the basis for instituting preventive and therapeutic interventions.

PITFALLS in Diagnosing Heart Disease in WomenSome diagnostic tests and procedures may not be as

accurate in women, so physicians may avoid using them.

(For example, the exercise stress test may be less accurate in women and giving a false positive result.)

That means the disease process resulting in a heart attack or stroke may not be detected in women until later, with more serious consequences.

More precise noninvasive and less invasive diagnostic tests tend to cost more. These include nuclear or echocardiographic stress tests and cardiac CT/MRI.

Evaluating for Ischemic Heart Disease is Difficult to do in Women Symptoms are more likely to be atypical and

therefore difficult to recognize Higher rate of functional disability (due to co-

morbidities) Lower prevalence of obstructive CAD by

coronary angiography as compared to men-therefore diagnostic accuracy of testing is variable and confusing

Questions to ask yourself before ordering a test……

What is the patient's pretest risk of disease? How does the sensitivity and specificity of

the alternative tests compare? What are the costs and effects on health

outcomes of each test? Do special considerations make one test more

suitable than another in a specific patient?

Benefits of the Stress ECG

Valuable prognostic information can be learned!!

Chronotropic and hemodynamic responses to exercise

Duke Treadmill Score can predict significant coronary stenosis

Women who exercise <5 metabolic equivalents (METs) are at increased risk of death

Prognostic value of functional capacity in asymptomatic (n = 8,715) and symptomatic (n = 8,214) women as synthesized from published reports

Disparity even after Stress Testing Several researchers have found that a positive exercise test

in women is often not followed up with subsequent testing. This finding has been cited as the reason for lower rates of catheterization and coronary bypass surgery in women and for the higher mortality of women after cardiac surgery. (Annals of Int Med 1990;112:561-7)

Other researchers have suggested that differences between the sexes in rates of treatment derive from the overtreatment of men at low risk of disease or death and an appropriately conservative level of care for women. (Annals of Int Med 1992;116: 791-7)

In men and women with a similar prevalence of abnormal results on initial stress tests for the diagnosis of coronary heart disease,additional studies were performed in only 38% of women, as compared with 62.3% of men. Follow-up revealed a higher incidence of coronary events in the women, regardless of initial stress-test results (1.6% for women with normal test results vs. 0.8 % for men; 14.3% for women with abnormal test results vs. 6.0% for men).

Cardiac CT Angiography

Coronary Angiography

SYMPTOMS OF A HEART ATTACK

JAMA. 2000;283:3223-3229

Atypical Warning Signs in Women

Early Warning Symptoms in Women

Circulation. 2003;108:2619

Stable Angina

Women describe their angina using a more emotional presentation, calling the pain “hot-burning” or “tender” and rating it as more intense

More women than men suffer from chronic stable angina The female stable angina patient is usually older than the

male stable angina patient and female Syndrome X patients, and more often has diabetes and high hs-CRP levels

Compared with men, women with stable angina tend to receive fewer diagnostic tests, fewer prescriptions for recommended medications, and fewer interventional procedures

Women have a worse prognosis than men in terms of relief from angina pain after treatment

Clotting factors, BNP, and hs-CRP have been found to be predictive of adverse events after treatment for angina

Acute Coronary Syndrome/Unstable Angina

UA/NSTEMI is the most common cause of cardiac hospital admissions

Women presenting with UA/NSTEMI have worse clinical profiles, but less extensive CAD compared with men

Women with ACS are more likely to present with UA than MI

UA and NSTEMI are differentiated based on the presence of biomarkers of myocardial injury

Women with UA/NSTEMI are more likely to present with atypical symptoms than men

Acute Coronary Syndrome

The most common cause of UA/NSTEMI is the development of non-occlusive thrombus on a disrupted atherosclerotic plaque

All patients without contraindications should be given aspirin, nitroglycerin, beta blockers, and heparin

It is unclear whether female ACS patients managed medically benefit from the use of GP IIb/IIIa inhibitors

High-risk patients including women benefit from an early invasive strategy

It is unclear whether a routine invasive strategy is beneficial in women and/or lower-risk patients

The prognosis of women with UA/NSTEMI is as good as or better than that of men

Acute Myocardial Infarction

Female AMI patients are generally 5 to 10 years older and have more co-morbidities

Common acute symptoms of AMI in women include dyspnea, weakness, fatigue, nausea/vomiting, palpitations, and indigestion

Women <50 years old are more prone to coronary thrombosis due to plaque erosion than postmenopausal women

Younger female AMI patients have a higher in-hospital mortality than men of the same age and older female AMI patients

Women often have higher short-term mortality rates than men largely due to their older age and increased co-morbidities

Women are often under prescribed AMI discharge medications, including aspirin and beta blockers

Lifestyle InterventionsSmoking cessationPhysical activity (cardiac rehabilitation)Weight reduction/maintenanceHeart healthy dietOmega 3 fatty acids Psychosocial factors

Source: Mosca 2004

Women Receive Less Interventions to Prevent and Treat Heart DiseaseLess cholesterol screeningLess lipid-lowering therapiesLess use of heparin, beta-blockers

and aspirin during myocardial infarction

Fewer referrals to cardiac rehabilitation

Source: Chandra 1998, Nohria 1998, Scott 2004, O’Meara 2004, Hendrix 2005

Lifestyle Approaches to Hypertension in Women

Source: JNC VII 2004, Sacks 2001

Maintain ideal body weight Weight loss of as little as 10 lbs reduces blood pressure

DASH eating plan Even without weight loss, a diet rich in fruits, vegetables, and low

fat dairy products can reduce blood pressure

Sodium restriction to 2400 mg/d Further restriction to 1500 mg/d may be beneficial, especially in

African American patients

Increase physical activity

Limit alcohol to one drink per day Alcohol raises blood pressure One drink = 12 oz beer, 5 oz wine, or 1.5 oz liquor

Guidelines at a GlanceParameter ATP III + Update1 Women2

1. ATP lll. JAMA. 2001;285:2486-2497. 2. Mosca L et al. Circulation. 2004;109:672-693. 3. American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S68-S71. 4. Grundy SM et al. Circulation. 2004;110:227-239..

ADA Position3

Optimal LDL-C <100 mg/dL <100 mg/dL <100 mg/dLVery high risk(2004 Update)4

<70 mg/dL

Optimal TG <150 mg/dL <150 mg/dL <150 mg/dL

Optimal HDL-C <40 mg/dL* >50 mg/dL >40 mg/dL men>50 mg/dL women

LDL-C goal for CHDor equivalents <100 mg/dL <100 mg/dL <100 mg/dL

Non–HDL-C goal <130 mg/dL <130 mg/dL

*Defined as high risk.

Framingham CHD Risk:HDL-C Predicts Risk at All LDL-C Levels*

0.0

1.0

2.0

3.0

100 160 220 8565

4525

LDL-C (mg/dL)

HDL-C (mg/dL)

Adapted from Castelli WP. Can J Cardiol. 1988;4(suppl A):5A-10A.

RR

for

CH

D A

fter

4 y

*Data represent men age 50-70 y from the Framingham Study.

Patient 1:LDL-C: 100 mg/dLHDL-C: 25 mg/dL

Patient 2:LDL-C: 220 mg/dLHDL-C: 45 mg/dL

Jupiter Trial Trial stopped earlyLooked at significance of elevated hsCRP

levels in 15,000 low risk patients without CV disease and low or normal LDL

Patients randomized to either Crestor 20mg or placebo

Showed decreased cardiovascular morbidity and mortality in Crestor group

Abdominal obesity

Glucose intolerance/ Insulin resistance

Hypertension

Atherogenic dyslipidemia

Proinflammatory/Prothrombotic state

Characteristics of the Metabolic Characteristics of the Metabolic Syndrome: NCEP-ATP IIISyndrome: NCEP-ATP III

National Cholesterol Educational Program (NCEP), Adult Treatment Panel (ATP) III; 2001.

DiabetesDiabetesDiabetesDiabetes CVDCVDCVDCVD

Daily Aspirin

High risk women75-162 mg daily (clopidogrel if intolerant to

aspirin) Unless contraindicated (bleeding, allergy)

Intermediate risk womenConsider aspirin therapy (75-162 mg)

if benefit is likely to outweigh riskLower risk women

Many women, especially those >65 yo, may benefit from taking low-dose aspirin every other day to prevent MI or stroke The use of low dose aspirin should be balanced

against the risk of increased internal bleeding

Hormone Replacement TherapyRisk vs. Benefit

BenefitsVasomotor SymptomsOsteoporosisVaginal AtrophyColon CancerSkin PreservationDepression

RisksDVT/PEGallbladder DiseaseBreast CancerBreast/Bleeding Side EffectsCHDStrokeDementiaPancreatitis?Ovarian Cancer

Source: ACOG Task Force for Hormone Therapy 2004

Women’s Health Initiative: Estrogen Alone in Postmenopausal Women

0.61

0.77

0.91

1.04

1.08

1.39

0 0.5 1 1.5 2

Stroke

Colorectal Cancer

Total Mortality

CHD

Breast Cancer

Hip Fracture

Relative Risk Compared to Placebo

*

* P < .05*

Favors Treatment Favors Placebo

Menopausal Hormone Therapy 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

Source: Hulley 1998, Rossouw 2002, Anderson 2004

Excess CHD events: 7/10,000 woman-years

Excess stroke events : 8/10,000 woman-years

Excess pulmonary emboli: 8/10,000 woman-years

Excess invasive breast cancer: 8/10,000 woman-years

Women’s Health Initiative Estrogen and Progestin Arm: Absolute Benefits Fewer colorectal cancers: 6/10,000 woman-years

Fewer hip fractures: 5/10,000 woman-years

Antioxidants, etc.

Antioxidants, Antibiotics, & ChelationVitamins A, C, E, & homocysteineAntibiotics (azithromycin)Chelation therapy

No cardiovascular benefit in randomized trials of primary and secondary prevention

Depression and CHD: Results from the Women’s Health Initiative StudyDepression is an independent predictor of

CHD death among women with no history of CHD

Source: Wassertheil-Smoller 2004

CHD Risk Equivalents

High Risk > 20% 10-yr risk for CHD eventsEstablished coronary artery diseaseCarotid artery stenosisPeripheral arterial diseaseAbdominal aortic aneurysmDiabetesIncludes many patients with chronic renal disease,

especially ESRD

Source: Mosca 2004

Intermediate Risk 10-20% 10-yr risk for CHD eventsMay include women with metabolic syndrome,

especially women over the age of 60 or with individual factors that are markedly elevated or severe

Often includes women with multiple risk factors, a single markedly elevated risk factor, or a 1st degree relative with premature CVD

May include women with subclinical cardiovascular disease (elevated coronary calcium score)- this is not included in Framingham risk calculations

Source: Mosca 2004

Low Risk <10% 10-yr risk for CHD eventswomen with one or more risk factorswomen with defined metabolic syndrome, if

no individual factor is severe or markedly elevated

women with no risk factors, but non-optimal lifestyle factors, such as lack of regular exercise or a high fat diet

Optimal Risk <10% 10-yr risk for CHD eventsOptimal levels of risk factorsHeart healthy lifestyle

Source: Mosca 2004