Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women

Abstract

Background-Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors. Methods and Results-We identified 15 288 women from the Women's Health Initiative Biomarkers studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993)(1994)(1995)(1996)(1997)(1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-highdensity lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin resistance was associated with CVD risk after adjusting for age and race/ethnicity with hazard ratios (

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“…However, evidence accumulated from systematic reviews, cross-sectional and prospective cohort studies point in favour of an increased risk of developing CVD among subjects without diabetes presenting insulin resistance, despite some discrepancies between studies. 26 27 Indeed, partly corroborating our findings, Schmiegelow et al demonstrated a significant association in a univariable analysis between CVD risk estimated using the Framingham equation and insulin resistance assessed by the HOMA-IR index in a population of 15 288 postmenopausal US women; but this association became non-significant in multivariable analysis after adjusting for HDL-C. 28 Moreover, Howard et al did not find a significant relationship between insulin resistance and atherosclerosis in African Americans, which on the contrary was significant among Euro-Americans. 29 …”

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“…It is a disease commonly found in women after menopause, where the disease symptoms worsen by estrogen deficiency. 144 Generally, an excessive number of pro-inflammatory type 1 macrophages over anti-inflammatory type 2 macrophages were found in the hearts of diabetic mice. Additionally, an increase in the cell apoptosis, fibrosis, reactive oxygen species production, and cardiac hypertrophy had observed in the hearts of ovariectomized diabetic mice.…”