OBJECTIVE -The excess risk of macrovascular disease and death associated with diabetes seems higher in women than in men. The pathogenesis for this risk difference has not been fully elucidated. We investigated whether female sex was associated with macrovascular disease and death, independently of known risk factors related to type 2 diabetes, nephropathy, or retinopathy in normotensive patients with type 2 diabetes and microalbuminuria.RESEARCH DESIGN AND METHODS -We conducted a prospective, prolonged follow-up study of a subgroup of 67 diabetic patients (46 men and 21 women) without established cardiovascular disease who participated in a larger clinical trial. Data were collected on current and past health, medication use, blood pressure, renal function, and HbA 1c during the follow-up period of 4.7 Ϯ 0.8 (means Ϯ SE) years. The end point was a composite of death, cardiovascular disease, cerebrovascular events, and peripheral artery disease.RESULTS -Of the women, eight (38.1%) met the end point compared with six (13.4%) of the men (P ϭ 0.02 for difference in event-free survival). The hazard ratio of women relative to men was 3.19 (95% CI 1.11-9.21), which further increased after adjusting for age, systolic blood pressure, BMI, smoking, total-to-HDL cholesterol ratio, urinary albumin excretion, and retinopathy.CONCLUSIONS -In our study population of normotensive patients with type 2 diabetes and microalbuminuria, female sex was associated with increased risk of fatal and nonfatal cardiovascular disease, independent of the classical cardiovascular risk factors, the severity of nephropathy or presence of retinopathy, or health care utilization.
Diabetes Care 29:1851-1855, 2006T ype 2 diabetes, with its rapidly growing prevalence, has become a major public health problem (1). It associates with an increased risk of coronary heart disease, cerebrovascular disease, and peripheral vascular disease (2,3). Strikingly, this excess risk for cardiovascular disease seems relatively higher for female than for male diabetic patients (3-6). Type 2 diabetes substantially contributes to the 500,000 women dying annually of cardiovascular disease in the U.S. It is unclear whether the difference in cardiovascular risk between the sexes is caused by known cardiovascular risk factors (like duration of diabetes and systolic blood pressure) or by lower health care utilization by women compared with men (7,8).In the present study, we extended the prospective follow-up of normotensive patients with type 2 diabetes and microalbuminuria who participated in a double-blind, randomized, placebo-controlled trial (9). The original study excluded patients with a history of cardiovascular disease, and the prolonged follow-up study removed differences in health care utilization among the participants.In this study, we investigated whether female sex was associated with cardiovascular disease, cerebrovascular disease, peripheral artery disease, and death, independently of the classical cardiovascular risk factors related to type 2 diabetes, neph...