Probably the biggest challenge to taking care of women with coronary heart disease is getting tuned in to the possibility that they have it.

Coronary heart disease (CHD) is the number one cause of death in American women, with almost 250,000 deaths per year, yet many physicians do not take heart disease risk and symptoms seriously in women. The Framingham study revealed that many women get non-specific chest pain, an observation that was seemingly taken to imply that chest pain or angina in women did not represent serious coronary heart disease.

Now that methods for pinpointing pain of coronary origin have improved --by the anatomical delineation of the coronary angiogram, by dynamic imaging, and by provocative studies--we are much better able to make a secure diagnosis of coronary heart disease in women. But three longstanding misconceptions appear to have prevented these methods from becoming widely used in doctors's offices:

• Women don't get coronary heart disease.
• Chest pain in women is not coronary heart disease.
• Coronary chest pain (angina) in women does not carry a serious prognosis.

For this conference I interviewed Debra R. Judelson, MD, FACC, FACP, the incoming President of the American Medical Women's Association (AMWA), Senior Partner, Cardiovascular Medical Group of Southern California and Director, Women's Cardiovascular Institute of Southern California. She has also been the Chair, Subcommittee on Cardiovascular Disease in Women for AMWA and in 1994 directed the formation of the Education Project in Coronary Heart Disease in Women.

The most important concept we would like to convey in this conference is that women do get coronary heart disease, but not in exactly the same manner as men. For example, women get CHD about 10-15 years later than men. Therefore, when your 50-year-old men are getting heart attacks, in women of the same age group, the most serious illness is likely to be breast cancer.

Armed with a few crisp facts about women and coronary heart disease, you can increase your sophistication and improve your management of your women patients. We will address four areas:

1. Coronary risk factors in women
2. Symptoms in women
3. Diagnostic studies in women
4. Outcomes in women

Coronary Heart Disease Risk Factors in Women

The Big Five identified by the Framingham Study (family history, smoking, diabetes, high cholesterol, and high blood pressure) are operative in women, just as they are in men. Low HDL cholesterol, obesity, and the sedentary life style also carry risks for women. Then there are specific risks in women from estrogen withdrawal. Here are a few points of interest about the Big Five regarding women.

Family History

We define early CHD in women at an older age than early in a man. A female relative with a heart attack before the age of 65 conveys a risk equivalent to a male relative with a heart attack below the age of 55.

Smoking in Women

One of the tragedies of our times is the high incidence of smoking in adolescent women that carries over into an equal or greater incidence of female to male smokers in adulthood. Current women smokers have 3.6 times the risk of MI as nonsmoking women. This increased risk disappears within two to three years after smoking cessation.(1) Compared to nonsmokers, the first myocardial infarction occurs 19 years earlier in female smokers compared to seven years earlier in male smokers.(2) Two prominent factors to keep in mind about women smokers are the fear of gaining weight and the use of nicotine as an antidote to depression and anxiety. [A detailed discussion on women smokers and getting them to quit will be the subject of a future women's health conference.]

Diabetes

This illness is a powerful risk factor for CHD in women.(3) Women with diabetes have the same risk of developing CHD as nondiabetic men at a similar age. Whether tight control would reverse this effect is a question yet to be answered.

Cholesterol and Lipids

The National Cholesterol Education Project (NCEP II) guidelines define an HDL of less than 35mg/dL as a risk factor for CHD; while appropriate for men, this value is too low for women and an HDL below 50mg/dL should be used instead.(4) The NCEP II guidelines focus on the high LDL cholesterol conferring risk. In women, the level of HDL is the most important consideration, and there are some differences from men in the risk-associated levels in women. Similarly, in NCEP II, an HDL greater than 60 will nullify one coronary risk factor in men, but we believe this value is too low for women, who have an average HDL around 55mg/dL. In women, an HDL of greater than 75 will nullify one CHD risk factor.(5) An elevated triglyceride level is also considered a risk factor in women.

High Blood Pressure

Hypertension is common in women, especially as they age. It increases dramatically after menopause, while post-menopausal hormone replacement therapy actually lowers blood pressure. Oral contraceptives are associated with an increase in blood pressure, especially higher dose formulations, and are a greater risk in women over the age of 35.(6) Nearly half of women over age 55 have hypertension; 72% of women over 75 years, compared to 60% of men who develop high blood pressure. Isolated systolic hypertension, more common in older women than in men, is now recognized as an independent risk factor for CHD, along with the traditional combined systolic and diastolic hypertension.(7) There has been a reluctance by many physicians to treat isolated systolic hypertension in older women. Medications are well tolerated and are associated with a significant reduction in cardiac complications, so treatment should not be withheld.

Additional Risk Factors Specific to Women: Menopausal Status

Early physiological menopause or surgical menopause (usually hysterectomy with oophorectomy) must be taken into account when assessing coronary risk in women. A women who is 10 years post menopause without hormone replacement therapy (HRT) now has risk equivalent to a man. Conversely, HRT reduces the CHD risk by 1/3 to 2/3, with the greatest benefit seen in women who already have CHD. Both unopposed estrogen and estrogen in combination with progesterone have this effect.(8)

Symptoms of Coronary Heart Disease in Women

One observation has been that the classical angina, anterior chest pain with left arm radiation, is not as common in women as it is in men. When it does occur, the woman is likely to be younger, nondiabetic, or a smoker. In women who are older, have diabetes or high blood pressure, coronary ischemic symptoms may be perceived as a generalized feeling of weakness, breathlessness, or discomfort in other parts of the body, such as the abdomen, the shoulder, or the jaw. In older women, who are not physically active, the first anginal symptom may occur at rest, denoting a more serious level of heart disease. It is important to assess the degree of physical activity of the patient in order to put symptoms into perspective.(9)

Diagnostic Studies in Women

The Stress Test

The standard stress test, or exercise tolerance test (ETT), using the electrocardiogram is less reliable in women because they have a higher incidence of nonspecific S-T changes resulting in false positives. Another problem is that many women in the coronary age group are in poor physical condition and cannot achieve the maximal heart rate that assures the clinician that no ischemia is present. Without achieving maximal stimulation, a negative stress test may be a false negative.

Nuclear Imaging Studies

Thallium, and the newer agent, technetium sestamibi, are both excellent for determining the presence of CHD in women. They may give more information about the extent of CHD, even at somewhat less than maximal exercise levels. The one drawback in women is that the left breast may interpose sufficient tissue between the heart and the camera to create the impression that there is a perfusion defect in the heart. With technetium sestamibi, there may be a lower false positive rate because of less scattering by the interposed tissue.

Echocardiogram

The stress echocardiogram detects changes in wall motion that indicate underperfused cardiac tissue. If the maximal stimulus is achieved, this test is very accurate in detecting the presence of CHD.

Pharmacologic Agents Used in Stress Tests

When physical conditioning does not permit achievement of maximal heart rate by exercise, pharmacologic agents can bring out evidence of ischemia by increasing heart rate and/or contractility. Dipyridamole and adenosine increase the blood flow to the heart muscle and are most helpful with the nuclear imaging studies. Dolbutamine increases cardiac contractility and is best used in stress ECHO.

Angiography

This is of course the gold standard for confirming a fixed coronary lesion. In contrast to the exercise stress studies, it is important to remember that delineating the anatomical form of the coronaries does not necessarily tell you that what you see on the x-ray is responsible for the patient's symptoms. We have to keep reminding ourselves that relating symptoms to test findings is crucial, because our ultimate therapeutic goal is to relieve symptoms and improve function.

For women cardiovascular patients the most important therapeutic step occurs after they describe their symptoms to their doctor -- too many studies have shown that the appropriate diagnostic study does not take place.(10)

Treatment Outcomes in Women with CHD

A number of studies have confirmed poorer results of treatment in women with coronary heart disease compared to men.(11) In percutaneous transluminal coronary angioplasty (PTCA), there is a lower primary success rate. The coronary artery bypass graft (CABG) operative complication rate is higher.(12) The CABG operative mortality is higher. There are higher rates of graft failure. Short-term post-op survival rates are poorer.

There is a lot of speculation about the reasons for these statistics. These women are older and have more co-morbidities. But the haunting question for many of us is, how much are these statistics due to the limitations on treatment of the older age group with other medical problems? Alternatively, how much is due to missing the diagnosis at an early stage because of the preconceived notions discussed at the beginning of this piece:

• Women don't get coronary heart disease.
• Chest pain in women is not due to coronary heart disease.
• Angina, or coronary pain, in women is not serious.

We hope you will be able to use this information to sharpen your evaluation of women patients. With the new attention to research on women and coronary heart disease, more information about the risks and outcomes of this disease in women will be available.