Effects of Ezetimibe Add-on to Statin Therapy on Adipokine Production in Patients With Metabolic Syndrome and Stable Vascular Disease

The aim of this study was to determine whether the addition of ezetimibe to ongoing statin therapy in patients with atherosclerosis and metabolic syndrome would favorably affect levels of inflammatory markers and adipokines. Individuals with the metabolic syndrome exhibit higher levels of inflammatory biomarkers and adipokines, which have been implicated in the pathobiology of cardiovascular risk. The impact of the addition of ezetimibe to statin therapy on these proinflammatory mediators is unclear. Fifty patients with metabolic syndrome and concomitant vascular disease receiving stable statin monotherapy, with low-density lipoprotein cholesterol (LDL-C) levels > 77.4 mg/dL (> 2.0 mM), were treated with ezetimibe 10 mg per day for 12 weeks. The primary study end point was the % change in adiponectin levels from baseline to 12 weeks. Secondary study end points included % changes in the levels of other circulating inflammatory markers, adipokines, and plasma lipids. The addition of ezetimibe to statin therapy resulted in a significant reduction in total cholesterol and LDL-C and the ratio of total cholesterol to high-density lipoprotein cholesterol. However, ezetimibe add-on treatment had no effect on the primary outcome of plasma adiponectin or on any of the secondary outcomes, including leptin, hsCRP, tumor necrosis factor-alpha, or interleukin-6 concentrations. These observations remained unchanged after adjusting for body mass index and for background statin used. The addition of ezetimibe to stable statin therapy in patients with vascular disease and metabolic syndrome, who were not at guideline recommended LDL-C levels, did not alter adipokine levels after 12 weeks. Short-term add-on with ezetimibe may not be associated with additional inflammatory benefits beyond improvements in cholesterol homeostasis.