Normotensive Women With Type 2 Diabetes and Microalbuminuria Are at High Risk for Macrovascular Disease

Abstract

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...

MECHANISMS IN ENDOCRINOLOGY: Cardiovascular risk in women with type 2 diabetes mellitus and prediabetes: is it indeed higher than men?

“…This risk was 3.19 times higher in women in unadjusted analysis and, after adjusting for established CVD risk factors (such as age, systolic BP, BMI, total-to-HDL cholesterol (HDLC) ratio, smoking and urinary albumin excretion or retinopathy), it was still increased to over twofold. Nevertheless, the limitations of this study were that it included a relatively small number of patients (46 men and 21 women) and it was confined to normotensive patients with microalbuminuria (26). Studies reporting an absolute risk of CVD death in diabetic sexes (most of them adjusted for CVD risk factors) are summarised in Table 3.…”

Exploring differences in Canadian adult men and women with Diabetes management: results from the Canadian Community Health Survey

“…Heart disease remains the leading cause of mortality in people with diabetes. Previous research has shown that women with diabetes may be at higher risk for developing cardiovascular disease [27,28] than men and that mortality from both coronary heart disease [29,30] and stroke [31] is also higher in women with diabetes than men. While mortality was not assessed, our study did provide further evidence of higher odds of women having hypertension and yet, less likely to have heart disease than men with diabetes, a finding consistent in the literature [32,33].…”

“…A number of studies have looked at differences in diabetes complications and diabetes management among men and women. For examples, studies have shown that the relative risk of cardiovascular disease (CVD), coronary artery disease and stroke is higher among women with diabetes than among men with diabetes [9][10][11][12][13][14][15]. Another study showed that women with diabetes may not reach the recommended therapeutic targets for lipid profile, blood pressure (BP) levels and Hemoglobin A1C (A1C), a measure of glycemic control, as a result of less aggressive management of diabetes compared to men with diabetes [16].…”

Exploring differences in Canadian adult men and women with Diabetes management: results from the Canadian Community Health Survey

“…Previous research has shown that women with diabetes may be at higher risk for developing cardiovascular disease [27,28] than men and that mortality from both coronary heart disease [29,30] and stroke [31] is also higher in women with diabetes than men. While mortality was not assessed, our study did provide further evidence of higher odds of women having hypertension and yet, less likely to have heart disease than men with diabetes, a finding consistent in the literature [32,33].…”