Measures of Insulin Resistance in Postmenopausal Women: Limited Incremental Prognostic Value | Journal Scan

Study Questions:

Does insulin resistance improve cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors?


This was an analysis of data from the Women’s Health Initiative, a large multiethnic cohort of postmenopausal women aged 50-79 years at baseline, between 1993 and 1998. All women with available measures of insulin resistance were included. The primary endpoint was time to first major CVD event defined as nonfatal myocardial infarction (MI), fatal coronary heart disease (CHD), and nonfatal and fatal ischemic stroke within 10 years of enrollment. The authors assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol (TG/HDL-C) ratio, or impaired fasting glucose to traditional risk factors. HOMA-IR was defined as insulin levels (pmol/L) x glucose levels (mg/dl) / (6.945 x 405). Incremental prognostic value was assessed with risk discrimination and reclassification.


The analytic sample was comprised of 15,288 postmenopausal women. Over a mean follow-up of 9.2 years, there were 894 first CVD events (5.8%). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased CVD risk after adjusting for most CVD risk factors, none remained significant after adjusting for HDL-C. The c-index for a model including age, race/ethnicity, and HDL-C was 0.669; with measures of insulin resistance, the change in c-indices were between 0.001 and 0.002, with all 95% confidence intervals contained in the interval (-0.001 to 0.005).


The authors concluded that select measures of insulin resistance were not associated with CVD risk in models that adjusted for HDL-C.


The limitations of this analysis of postmenopausal women aside, the authors provide a useful contribution in which they establish that the incremental prognostic value of markers of insulin resistance to predicting cardiovascular events is limited when compared to traditional risk factors (and HDL-C, in particular). As the authors summarize well, ‘Although insulin resistance may be important in the pathophysiology of atherosclerosis, the information provided by measures of insulin resistance appeared to be captured in traditional cardiovascular risk factors in healthy, postmenopausal women.’

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet

Keywords: Atherosclerosis, Cardiovascular Diseases, Cholesterol, Coronary Disease, Dyslipidemias, Fasting, Glucose, Homeostasis, Insulin, Insulin Resistance, Lipoproteins, HDL, Myocardial Infarction, Postmenopause, Primary Prevention, Risk Factors, Stroke, Women's Health

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