Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men

Obesity is related to cardiovascular disease (CVD) morbidity and mortality, however, the mechanisms for the development of obesity-induced CVD risk re main unclear. Hyperinsulinemia and insulin resistance are considered key co mponents in the metabolic cardiovascular syndrome and as independent risk f actors for CVD. Plasma leptin and tumor necrosis factor-alpha (TNF-a), two adipocyte products, are also proposed to be associated with the development of CVD risk. The purpose of this study is to evaluate the association of P lasma leptin, soluble TNF receptors (sTNF-R), and insulin levels as possibl e mediators of the effect of obesity on atherogenic and thrombogenic CVD ri sk factors among men. From the Health Professionals Follow-up Study (HPFS), we selected 268 men, aged 47-83 years, who were free of CVD, diabetes, and cancer (except non-melanoma skin cancer), and who had provided a fasting b lood sample in 1994. We measured plasma insulin and leptin levels by radioi mmunoassay and sTNF-R levels by ELISA. Men in the highest quintile of body mass index (BMI, mean = 30.5 kg/m(2)) were less physically active and had a more adverse cardiovascular lipid and homeostatic profile, as indicated by levels of insulin, triglyceride (TG), tissue plasminogen activator (t-PA) antigen levels, and apolipoprotein Al (Apo-Al). In a multivariate regressio n model controlling for age, smoking, alcohol intake, physical activity and diet, BMI was inversely associated with HDL-cholesterol (HDL-C) and Apo-Al and positively associated with TG, Apo-B and t-PA antigen levels. The asso ciations between BMI and these CVD risk factors were only slightly changed after adjusting for leptin and/or sTNF-R; but were substantially attenuated after controlling for insulin levels. These data suggest that the associat ion between obesity and biological predictors of CVD may be mediated throug h changes in plasma insulin, rather than leptin or sTNF-R levels. However, plasma leptin may still play a role in CVD through independent effects on l ipid metabolism. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .