Insulin resistance, subclinical left ventricular remodeling, and the obesity paradox: MESA (Multi-Ethnic Study of Atherosclerosis)

Objectives: This study assessed whether impaired fasting glucose (IFG), insulin resistance, and waist-to-hip ratio (WHR) had effects on cardiac remodeling, independent of obesity, in the MESA (Multi-Ethnic Study of Atherosclerosis) trial. Background: Recent studies have suggested that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI). Methods: We investigated 4,364 subjects without diabetes in the MESA trial. IFG (100 to 125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance [HOMA-IR]) and WHR were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on left ventricular (LV) remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging. Results: Individuals with IFG were more likely to be older and hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, subjects with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p < 0.05 for all). HOMA-IR (p < 0.0001), WHR (p < 0.0001), and the presence of IFG (p = 0.04), but not BMI (p = 0.24), were independently associated with LV mass-to-volume ratio after adjustment for age, sex, hypertension, race, and dyslipidemia. Conclusions: Insulin resistance and WHR were associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI.