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Epidemiology of Coronary Heart Disease in Women
The major cause of mortality and morbidity among Americans, both males and females is heart disease (1). In 1992, final cardiovascular mortality among males was 444,180 (48.1% of deaths from cardiovascular disease) and among females it was 479,236 (51.9% of deaths from cardiovascular disease). There is an increase in the risk of cardiovascular disease following the menopause for women. One third of American women between age 50 and 75 have cardiovascular disease and half will die as a result. Despite these statistics, coronary heart disease continues to be under diagnosed and under treated in women when compared to men. This is due partly to the myth that coronary artery disease is more benign in women than in men.
Unique Gender-specific Cardiac Issues
a. Syndrome X Chest pain with normal coronary arteries, ischemic ECG responses to exercise, and reduced myocardial blood flow reserve is characteristic. The diagnosis of syndrome X requires exclusion of coronary and other cardiac and extra cardiac causes of chest pain and is usually made after costly investigation in search of obstructive coronary artery disease. The majority of patients are female (75%) and approximately 60% are postmenopausal. A substantial number (45%) have undergone hysterectomy at an average of 8 years before the onset of chest pain. Chest pain usually has a gradual onset, is mainly retrostemal and typically radiates to the left arm. Episodes of chest pain occur frequently, are often prolonged and occasionally last more than 30 minutes.
b. Arrhythmias and Gender. Recently, new concerns have been addressed regarding the presentation of women with cardiac arrhythmias and the dire consequences of antiarrhythmic treatment in women. Lessons from the Cardiac Arrhythmia Suppression Trial (CAST) indicate 2 factors increase the hazard rates for arrhythmic death: 1) female gender (p<0.05) and 2) ECG events including VT, proarrhythmia, heart block and bradycardia (p<0.005). Of further alarm is the formal investigation confirming clinical and anecdotal reports that women are more prone than men to experience cardiovascular drug-related torsades de pointes.
A retrospective review from 1980 to 1992 disclosed that 70% of 332 cases of cardiac drug related torsades de pointes occurred in women and that female prevalence exceeded 50% in 25 separate reports. Female prevalence occurred regardless of hypokalemia, hypomagnesemia, digoxin use, bradycardia, or underlying left ventricular dysfunction. Noteworthy is the finding that drugs that affect refractoriness and the K+ channel including procainamide, disopyramide, amiodarone, sotalol and bepridil are responsible for 44 to 50% of reported cases.
c. Heart Failure and Women. A recent study challenges previous research findings suggesting that the survival advantage of women with heart failure over that of men might be due to differences between men and women in the type of treatment they receive and the length of time they had the disease. Adams and associates reported that a woman has a survival advantage even if her heart failure is as severe as a man's and she has had the disease for the same duration. In short, the authors found than found that women with advanced congestive heart failure.
Risk Factors for Coronary Heart Disease in Women
The risk factors that contribute to the development of a cardiovascular disease include hypertension, diabetes, smoking, family history, age, and hyperlipidemia. Almost 500,000 women die annually from some form of heart disease, and about 250,000 will die of coronary artery disease and myocardial infarction. Among women, the age-adjusted death rates vary and race is an important determinant of risk. For example, the 1991-93 deaths (per 100,00) for white women were 99.3, for Hispanic/Latina were 70.3, but for African-American women they were 164.4.
Hormonal Replacement and Coronary Heart Disease
A number of epidemiologic studies indicate that hormonal replacement therapy in the menopause is beneficial in reducing primary cardiovascular risk by about 50% and the risk for hip fracture by about 25%, but there is considerable debate about the mechanism of action for this benefit. By reducing the chance of heart attack and hip fracture, estrogen therapy is generally believed to increase the length and quality of life. In women with a uterus, however, the risk for developing endometrial cancer increases (3% without estrogen to 18% with estrogen). Addition of progestin maintains hip fracture risk reduction, removes the increased risk for endometrial cancer, but has uncertain effects on risks for breast cancer and cardiovascular disease. Use of hormonal replacement therapy is expected to increase life expectancy by 10 months to two years, depending on the presence of risk factors, a gain similar to that achieved by treatment of hypertension.
Estrogen Quandary. The question of whether women with known heart disease should begin hormone therapy for the purpose of secondary prevention of heart disease, is often raised as the benefits of secondary prevention may be considerable. The Heart and Estrogen/progestin Replacement Study, (HERS) was conducted to determine if estrogen plus progestin therapy.
Effect of Hormones on Cholesterol
Most previous literature on the risk of cardiovascular disease and stroke associated with hormonal replacement has concentrated of exogenous estrogen therapy. The Postmenopausal Estrogen/Progestin Intervention (PEPI) (20) has provided reliable information about the effects of adding progesterone to the estrogen regimen. The major finding of PEPI is that the beneficial effect on cholesterol persists whether estrogen or estrogen combined with progesterone is used during the menopause. The regimens used in PEPI were: 1) 0.625 mg/day of estrogen monotherapy; 2) 0.625 mg/day of estrogen plus cyclic medroxy progesterone; 3) 0.625 mg/day of estrogen plus continuous medroxy progesterone; 4) 0.625 mg/day of estrogen plus cyclic micronized progesterone; or 5) placebo.
Breast Cancer Risk after Estrogen.
There have been relatively few controlled studies of the effects on breast cancer risk when progesterone is added to the estrogen regimen. The Nurses' Health Study, a longitudinal study using a questionnaire format, recently reported on the use of hormones and breast cancer risk. This analysis showed a significant increase in the risk of breast cancer and mortality among postmenopausal women over the age to 55 who used hormone therapy for more than five years. The addition of progesterone to estrogen had no significant effect on breast cancer risk.