Myocardial collagen turnover in normotensive obese patients:: relation to insulin resistance

OBJECTIVES: The present study was undertaken to assess the differential impact of insulin resistance, leptin and body composition on myocardial mass and serum markers of cardiac fibrosis in obese subjects, within a small range of elevated BMI (30-40 kg/m(2)), without pulmonary disease, cardiovascular disease, hypertension, cardiac hypertrophy or other cardiovascular disease. BACKGROUND: Obesity is an independent predictor of left ventricular mass (LVM) and is associated with disturbances in cardiac structure. The extent of the interstitial fibrosis in obese patients is not known, especially in the absence of cardiac hypertrophy. METHODS AND RESULTS: We included 160 obese subjects. The LVM was obtained using the Devereux formula. Body composition was estimated from a total body scan. Insulin sensitivity was assessed by homeostasis model assessment (HOMA), and cardiac collagen turnover by measurement of procollagen type III aminopeptide (PIIINP). PIIINP was correlated to the E/A ratio (r = 0.24; P = 0.012), a marker of ventricular function. PIIINP was independently correlated with glucose concentration (r = 0.27; P = 0.004), indexes of insulin resistance (HOMA (r = 0.27; P = 0.003), insulin (r = 0.24; P = 0.008)), and parameters associated with the insulin-resistance syndrome (HDL-cholesterol r = -0.27; P = 0.004) and fat trunk/fat leg ratio (r = 0.24; P = 0.053)). The variable most correlated with PIIINP was HDL-cholesterol, followed by HOMA (r(2) = 0.13). When HOMA was substituted for blood glucose concentration and insulinemia (Model 2), HDL-cholesterol was strongly related to lower PIIINP levels, followed by higher glucose concentration (r(2) = 0.21). Regression analyses showed that LVM had the strongest independent positive correlation with fat-free mass (FFM) (r = 0.39; P = 0.0002), followed by systolic blood pressure (r = 0.19; P = 0.034). Neither adipose mass nor height independently added information to multivariate models. The ratio leptin/fat mass was correlated with LVM (r = -0.27; P = 0.004), but not independently of the FFM. Markers for fibrosis were not significantly correlated with LVM. As a result, FFM was the most predictive factor of LVM in obese subjects. CONCLUSION: We found that serum levels of markers of cardiac collagen synthesis were significantly associated with insulin resistance in normotensive, nondiabetic obese subjects, and not related to the LVM. As a result, PIIINP could be a very early marker of ventricular dysfunction in these patients. Furthermore, we suggest that, for better detection of left ventricle hypertrophy in obese subjects, LVM should be indexed to FFM rather than to body surface area, or height.