Pleiotropic Effects of Atorvastatin and Fenofibrate in Metabolic Syndrome and Different Types of Pre-Diabetes

OBJECTIVE - To compare extra-lipid effects of statins and fibrates in relation to the baseline metabolic status of patients. RESEARCH DESIGN AND METHODS - The study involved a group of 242 metabolic syndrome patients with or without pre-diabetes and randomized to atorvastatin, fenofibrate, or placebo. RESULTS - Compared with matched healthy subjects, metabolic syndrome patients exhibited higher plasma levels/activities of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, factor VII, plasminogen activator inhibitor 1, and enhanced monocyte cytokine release. These abnormalities were alleviated by both atorvastatin and fenofibrate treatment. CRP-lowering and monocyte-suppressing actions were more pronounced for atorvastatin in subjects with impaired fasting glucose and for fenofibrate in patients with impaired glucose tolerance. CONCLUSIONS - The presence of pre-diabetes potentiates metabolic syndrome induced abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Both atorvastatin and fenofibrate exhibit multidirectional pleiotropic effects in subjects with metabolic syndrome, the strength of which seem to be partially determined by the type of pre-diabetes.