As background for this Roundtable addressing preventive coronary interventions for women, my initial task is to define the scope of coronary heart disease as a problem for women in the U.S., next to provide an overview of the risk factor status of U.S. women, and finally to address two risk factors that will not be reviewed by the other essayists.
CORONARY HEART DISEASE IN U.S. WOMEN
Coronary heart disease is the leading cause of death for women in our country, responsible for about one quarter of a million deaths yearly(24). There is a significant age-dependency of coronary disease among women in that one in nine women aged 45-64 yr had clinical evidence of coronary disease, whereas this increases to one in every three women older than 65 yr of age.
Further, comparing the common medical problems affecting women, the lifetime risk among postmenopausal women for coronary heart disease is about 31%, as contrasted with 2.8% for hip fracture, 2.8% for breast cancer, and 0.7% for endometrial cancer. The emphasis that coronary disease is the most prevalent illness affecting older women requires wider dissemination: unless women in the United States perceive coronary disease as part of their illness experience, they are unlikely to heed coronary preventive messages at younger age or to respond to symptoms of coronary disease when older.
The concern for coronary prevention is highlighted by the more adverse outcome for women than for men once coronary heart disease becomes clinically manifest (21). In prior years, the ominous prognosis for women with clinical evidence of coronary heart disease was not adequately appreciated in that data from the Framingham Heart Study initially defined angina as a relatively benign problem for women. The symptom designated as angina in the Framingham Heart Study should more correctly have been termed chest pain, in that there was no objective test confirmation available at that time to document evidence for myocardial ischemia. In the Framingham Heart Study, one man in four considered to have angina developed myocardial infarction within the ensuing 5 yr, whereas 86% of women with angina in the Framingham cohort never incurred myocardial infarction. The flaw in the Framingham analysis became evident with publication of data from the Coronary Artery Surgery Study (CASS) Registry (14), a listing of men and women referred to participating institutions by their treating physicians because of chest pain syndromes of sufficient severity to warrant evaluation by coronary arteriography for coronary artery bypass surgery. Among this population, 50% of the women had little or no obstructive disease in their epicardial coronary arteries as compared with 17% of men. Essentially, this means that many women with chest pain syndromes that mimic angina pectoris have another cause for this symptom. However, if such was the case in Framingham, it may explain why 86% of women in this population never developed myocardial infarction; half of them probably had a noncoronary etiology for their chest pain. However, even among Framingham women, there was a small overlooked subset, the oldest of the women, aged 60-69 yr, who had the same adverse prognosis as did the men, again emphasizing the important age-dependency of coronary heart disease in women.
The mortality from myocardial infarction is greater for women than for men. In Framingham, initial myocardial infarction entailed a 39% mortality among women as compared with 31% for men; although the contemporary mortality from myocardial infarction has been substantially reduced by newer therapies, recent data from the Myocardial Infarction Triage and Intervention Registry showed that women had a 16% mortality rate with myocardial infarction as compared with 11% for men. Whereas the percentage varies somewhat from one series to the next, the ratios remain uniform among all reported series. It is not yet known whether this excess mortality for women is attributable to gender per se, or whether it reflects the host characteristics including older age and greater comorbidity, potential differences in access to care, time to arrival at hospital, or a number of other variables, including potential suboptimal use of medical therapies. Data from Framingham also documented that women were more likely to have had unrecognized or silent myocardial infarction; today, these findings would not be surprising in that individuals of both genders of older age, and with concomitant diabetes and hypertension, are more likely to have silent or unrecognized infarction, and, indeed, these were the characteristics of the women in the Framingham cohort.
Not only do women have less favorable outcomes with myocardial infarction, but women also have greater morbidity and mortality with myocardial revascularization procedures. Although women both with chest pain syndromes and following myocardial infarction are more likely to be evaluated for myocardial revascularization procedures than was the case a decade ago, women have almost double the mortality rate of men with coronary artery bypass graft surgery. Even among survivors, there is less graft patency and less symptomatic relief, although long-term survival among women discharged from the hospital following coronary artery bypass graft surgery is comparable to that for men. Although percutaneous transluminal coronary angioplasty has comparable procedural success by gender, the newer procedures, particularly atherectomy, have a lesser success rate and a higher complication rate among women. Again, as with myocardial revascularization procedures, it is uncertain whether the less favorable outcome relates specifically to gender, or whether it is a reflection of older age, greater comorbidity, a number of other variables including body size and therefore coronary artery size, or the greater urgency or emergency of the revascularization procedures.
CORONARY RISK FACTORS IN WOMEN: AN OVERVIEW
Let me next provide an overview of coronary risk factors among women, based on the data available in mid 1994. In recent years, the decreases in both total cardiovascular mortality and total coronary mortality have been less pronounced for women than for men; concomitantly, during the past two or three decades, the decrease in coronary risk factors has been less pronounced among women than in their male counterparts (3). Limitations of these data relate to the traditional exclusion of women and of elderly persons of both genders from many research studies; these problems limit the reliability of the ascertainment both of coronary risk attributes in these populations and of the efficacy of risk interventions. As I have previously stated, women and elderly persons constitute the understudied majority(5,22,23).
Coronary risk factors are highly prevalent in elderly women, and even when recognized at older age, warrant intervention; however, the emphasis of this Roundtable is on preventive interventions for women across the lifespan. Based on 1991 data from the National Center for Health Statistics(16), reflecting information derived from women aged 20-74 yr, one-fourth of women in the U.S. have an elevated serum cholesterol level, defined as a total cholesterol concentration greater than 240 mg·dl-1. One-third of U.S. women have hypertension, using as definition of hypertension a systolic blood pressure in excess of 140 mm Hg, a diastolic blood pressure in excess of 90 mm Hg, or those using anti-hypertensive medications. More than one-fourth of U.S. women are cigarette smokers, more than one-fourth are overweight (using the definition of overweight as more than 20% in excess of desirable weight levels), and about one-fourth of all women are sedentary. Worthy of citation is the preponderance of risk factors among women with less favorable socioeconomic circumstances, and in particular those with lower educational levels, both of which often coexist.
The importance of prevention is highlighted by several observations(10,20). First is that 40% of all coronary events in women are fatal; hence, prevention assumes obvious importance. Next is that 67% of all sudden deaths in women involve those not previously known to have coronary disease; sudden death is their initial disease manifestation. Not only the mortality, but also the morbidity, is problematic; in the age group 55-64 yr, 36% of women with clinically manifest coronary disease are disabled by their illness, and this percentage rises to 55% in women with defined coronary disease older than 75 yr of age.
Thus, the importance of education, of the dissemination of the messages from this Roundtable, is to dissuade women in the U.S. from the view that coronary disease is predominantly a disease of men, and to emphasize that preventive coronary care is part of the health care for women of all ages. Examining the relative importance of risk factors for coronary disease by gender, based on followup data from the NHANES I Study, the relative risk and confidence intervals for women and men are essentially the same for hypertension, and the risk of elevated total cholesterol level is only slightly greater for men than for women, but diabetes imparts a far more ominous relative risk for women. There is comparable risk of overweight by gender and the smoking risk is slightly greater among women than for men(1).
CIGARETTE SMOKING/SMOKING CESSATION
Because smoking cessation will not be addressed separately at this Roundtable, it is important to define the current equal prevalence of cigarette smoking among men and women in the U.S., owing to the far greater smoking cessation among men than among women during the past decades(16). This is despite the fact that, between 1955 and 1990, there has been a 30% and 36% respective decrease in cigarette smoking among white and black women. Even with this decrease, 23% of women in the U.S. older than 18 yr of age still smoke cigarettes in the 1990s. Added to these absolute numbers is the fact that, among women who smoke, there is currently a greater intensity of smoking (based on the daily number of cigarettes) and an earlier onset of smoking behavior. Cigarette smoking triples the risk of myocardial infarction, even among premenopausal women. An additional mechanism by which smoking may engender coronary risk is that smoking women undergo menopause at younger age, and their longer time in menopausal status may contribute to increased coronary risk (6,17).
The number of cigarettes smoked correlates with the occurrence of fatal coronary heart disease, nonfatal myocardial infarction, and cardiac catheterization-documented angina pectoris. Importantly, this is not simply an independent risk factor, but rather an interactive one, in that smoking imparts the greatest risk for women already at high risk due to older age, a parental history of myocardial infarction, overweight, hypertension, hypercholesterolemia, and diabetes. Smoking cessation should be encouraged by the favorable observation that former smokers, within 2 yr of quitting, decrease their cardiovascular mortality risk by about one-fourth, almost assuming the low risk status of women who never smoked cigarettes(13,25).
The challenge in smoking cessation is that this is more likely to occur in men, in those with a more favorable socioeconomic status, among white and married individuals, but interestingly also among those aged 65-75 yr(2,4,18,19). The latter is almost counterintuitive, but possibly relates to the development of overt coronary disease as a stimulus for smoking cessation at older age. It is unfortunate that often only a clinical coronary event serves as the impetus for smoking cessation for some individuals. Worthy of emphasis, again, is that former smokers, after 2 yr, have comparable rates of myocardial infarction and fatal coronary disease as women who never smoked cigarettes. Smoking cessation improves survival and decreases reinfarction, not only following myocardial infarction, but also following coronary artery bypass surgery. Based on data from the Coronary Artery Surgery Study (CASS) Registry, the benefit of smoking cessation did not decrease with older age (8): stated another way, older individuals benefit equally from smoking cessation in decreasing cardiovascular risk.
OBESITY AND BODY FAT DISTRIBUTION
In recent years there has been an increased prevalence of obesity in the U.S. among both genders. However, obesity is most prominent among black women. Hispanic women, and Native American women; as with other risk attributes, it is most prevalent among populations with a lower education, lower income, and lower socioeconomic status. Based on 1988 data from the National Center for Health Statistics (16), 50% of black women and 30% of white women were of 20% or greater than desirable weight. Obesity, in the Framingham population, was a significant independent predictor of cardiovascular risk, especially among women; whether the risk is obesityper se or the associated increased total cholesterol, triglyceride, and LDL cholesterol levels, and the lower HDL cholesterol levels, as well as insulin resistance, hyperuricemia, and hypertension has not been well identified (9,11,15). Weight control can improve the cardiovascular risk profile.
Upper body obesity increases coronary risk in older women and the upper body obesity pattern is common among older women. Again, it is uncertain whether the obesity pattern per se or the concomitant greater prevalence of diabetes mellitus, elevated triglyceride levels, elevated insulin levels, and hypertension imparts risk. Neither has the optimal approach to weight control been defined nor is it known whether benefits of weight control differ when this is accomplished with diet, with exercise, or with a combination of these interventions (7,12).
In summary, coronary heart disease is an equal opportunity killer for women and thus requires the equal application of preventive interventions. Areas to be highlighted include intensive coronary risk reduction for diabetic women of all ages, because these are women at high risk. Smoking cessation has high priority both for healthy women and for women with defined coronary disease. Emphasis should also be placed on weight reduction in overweight women as a means of lessening hypertension, glucose intolerance, hyperlipidemia, and the like. Hypertension control likely imparts greater stroke than coronary benefit for women, based on available data.
There is substantial evidence that moderate-intensity leisure exercise, as a means of imparting physical fitness, has widespread and powerful survival benefits. The efficacy of lipid-lowering interventions has been less extensively documented in the literature, although the extent of cholesterol lowering and resultant decline in rates of coronary heart disease were often comparable for women and men. Finally, postmenopausal hormone therapy appears a promising approach to addressing a risk attribute unique to women; however, definitive recommendations must await the result of ongoing clinical trials, both in healthy women and in women with coronary heart disease.
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Exercise and Cardiovascular Disease Risk in Women: Interaction with Selected Endocrine Factors
Nanette K. Wenger: Preventive Coronary Interventions for Women
Udho Thadani: Hypertension and Cardiovascular Disease Risk in Women
Steven N. Blair: Physical Inactivity and Cardiovascular Disease Risk in Women
Ronald T. Burkman: Oral Contraceptive Use and Coronary and Cardiovascular Risk
Margo A. Denke: Lipids, Estrogen Status, and Coronary Heart Disease Risk in Women
Caren Solomon: Diabetes Mellitus and Risk of Cardiovascular Disease in Women
Murray Freedman: Postmenopausal Hormone Replacement Therapy and Cardiovascular Disease Risk
This mongraph is based on the proceedings of an ACSM Roundtable entitled“Exercise and Cardiovascular Disease Risk in Women: Interaction with Selected Endocrine Factors,” held June 21-22, 1994, in Indianapolis, Indiana.
The Exercise and Cardiovascular Disease Risk in Women: Interaction with Selected Endocrine Factors Roundtable was funded through a grant from Wyeth-Ayerst Laboratories.