Women with diabetes mellitus are at markedly increased risk of cardiovascular disease and cardiovascular mortality. Among participants in the Nurses' Health Study, a prospective study of 121,700 female nurses, women with diabetes had a six- to seven-fold increased risk of coronary heart disease(CHD) and more than a five-fold increased risk of ischemic stroke as compared with non-diabetic women (13). Moreover, diabetes appears to essentially eliminate the advantage in cardiovascular risk generally conferred by female gender; indeed, absolute cardiovascular mortality rates among diabetic women in the Framingham Heart Study (11) and the Rancho Bernardo Study (1) were comparable to those of diabetic men.
Several explanations have been proposed for the increased cardiovascular risks associated with diabetes mellitus. For one, diabetes mellitus is strongly associated with other coronary risk factors, including hypertension, dyslipidemia, and, in the case of non-insulin-dependent diabetes mellitus, obesity and increasing age (11,13); however, the association between diabetes mellitus and cardiovascular disease persists after adjustment for these and other potential confounders. Diabetes, particularly non-insulin-dependent diabetes mellitus, is also associated with insulin resistance, which likewise appears to be associated with increased risk of coronary heart disease (5). Glycosylation of lipoproteins and tissue proteins in the setting of hyperglycemia may additionally contribute to accelerated atherosclerosis(3). Furthermore, diabetes mellitus is associated with abnormalities of platelet function and thromboxane generation which may predispose to thrombosis (16).
While the association of other coronary risk factors with diabetes mellitus does not completely explain the increased risks associated with this condition, coexistence of these risk factors with diabetes increases absolute rates of CHD well above those seen in the setting of diabetes mellitus alone. Diabetic women in the Nurses' Health Study who were current smokers, were obese (body mass index ≥ 6 kg·m-2), or had hypertension or hypercholesterolemia were much more likely to experience non-fatal myocardial infarction or fatal CHD than diabetic women without these coronary risk factors (12). In addition, low levels of HDL and high levels of VLDL were strongly associated with CHD mortality rates in diabetic women in a smaller population-based study (8).
Factors that may reduce cardiovascular risks associated with diabetes in women, however, have been little studied. Certainly, any intervention that might reduce the risk of developing diabetes would substantially reduce absolute rates of cardiovascular disease in women. In the Nurses' Health Study, regular physical activity was associated with a reduced risk of developing non-insulin-dependent diabetes mellitus (14). Obesity and weight gain are associated with increased risks of developing non-insulin-dependent diabetes mellitus (4); importantly, however, a significant inverse association between physical activity level and diabetes persists, even after adjustment for body mass index(14). In addition, a report of increased risk of non-insulin-dependent diabetes mellitus among current cigarette smokers in the Nurses' Health Study (17) suggests that smoking may be another modifiable risk factor for this disorder.
Among women who already have diabetes, CHD risk may be reduced in the setting of various factors known to be associated with reduced risks of CHD in generally non-diabetic populations. Consistent with observations that current cigarette smoking and severe obesity are associated with increased CHD risks in women with diabetes mellitus, avoidance (or cessation) of smoking and maintenance of a non-obese body habitus are associated with reduced risks of CHD in this population (13).
Regular physical activity also appears to be associated with a reduced risk of CHD in individuals with diabetes, as is true in non-diabetics(2). Even independent of body mass index, diabetic participants in the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-Up Study who reported the highest non-leisure time physical activity levels had a significantly lower risk of CHD mortality than those who were inactive (7), with risk reductions comparable to those observed among non-diabetic participants. While women were not assessed separately from men in the NHANES Study, data from the Nurses' Health Study likewise suggest reduced rates of CHD among diabetic women who engage in regular vigorous physical activity (unpublished data). Regular physical activity may facilitate weight reduction or weight maintenance, and may result in lower blood pressure, improved lipid profile, and improved insulin sensitivity, all of which may particularly benefit individuals with diabetes (10).
Pharmacologic therapies may also have a role in reducing risk of CHD in women with diabetes mellitus. Among participants in the Nurses' Health Study, regular aspirin use (i.e., 1-6 aspirin·wk-1) was associated with reduced risk of CHD, including the subset of women with diabetes(15). Consistent with results of interventional studies in generally non-diabetic men (9), a large interventional study in women and men with diabetic retinopathy also suggested that regular aspirin use may reduce risk of CHD, although risk reductions among women examined separately were not statistically significant(6). Preliminary analyses from the Nurses' Health Study also suggest that postmenopausal estrogen replacement, which has been associated with a 40% to 50% reduction in CHD risk in generally non-diabetic populations (18), may also be associated with risk reductions in diabetic women (unpublished data).
Better understanding of the role of these and other factors in modifying risk of cardiovascular disease in diabetic women awaits further study. Current observational data support further investigation in randomized trials of the effects of lifestyle and pharmacologic interventions in reducing the high risk of cardiovascular disease associated with diabetes in women.
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18. Stampfer, M. J. and G. A. Colditz. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev. Med.
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.