Dose-Dependent Effects of Rosuvastatin on the Plasma Sphingolipidome and Phospholipidome in the Metabolic Syndrome

Context: Statins are effective cholesterol-lowering agents that reduce cardiovascular disease risk but also have pleiotropic effects that may extend to other lipid classes. Objective: The purpose of this article was to investigate, in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma sphingolipids and phospholipids in men with the metabolic syndrome. Methods: Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization–tandem mass spectrometry. Results: Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P < .001 unless stated otherwise) lowered plasma cholesterol (−34% and −42% [% change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (−49% and −57%) and triglyceride (−24%, P =.03 and −42%) concentrations. Co...