Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity

Objective: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. Besides, potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range. Methods: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness(cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. HDL functions were measured in a subgroup (n=101). Results: Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI. CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely associated with HDL-mediated inhibition of platelet aggregation and CEC, but surprisingly it was directly associated with the antioxidant activity. Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. Conclusion: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.