Phenotype-dependent and -independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia


      This randomised, double-blind, placebo-controlled crossover study evaluated the effects of rosuvastatin (40 mg/day for 8 weeks) on atherogenic apolipoprotein B-containing lipoprotein subfractions. Subjects, recruited based on raised plasma triglyceride (TG) or low-density lipoprotein cholesterol (LDL-C), were divided into normotriglyceridaemic (NTG, n=13; TG<2.0 mmol/l) and hypertriglyceridaemic (HTG, n=16; TG≥2.0 mmol/l) groups. Similar reductions on rosuvastatin were observed for both groups in LDL-C (NTG −60%; HTG −56%), apoB (both −49%), intermediate-density lipoprotein (NTG −57%; HTG −54%) and LDL circulating mass (NTG −52%, HTG −58%) (all P<0.001 versus placebo), i.e., these changes were phenotype independent. Phenotype dependency in response was observed in HTG relative to NTG in concentration of small dense LDL (LDL-III) (NTG −44%, P=NS; HTG −69%, P<0.001), very-low-density lipoprotein1 (NTG −18%, P=NS; HTG 46%, P<0.01), and remnant-like particle cholesterol (NTG −31%, P=NS; HTG −48%, P<0.05). Rosuvastatin reduced cholesteryl ester transfer protein (CETP) by 33% in NTG and 37% in HTG (both P<0.001); a reduction in cholesteryl ester transfer activity (−59%, P<0.001) was observed in HTG only. Rosuvastatin therefore, in addition to lowering LDL and apoB-concentrations, largely corrected the TG and LDL abnormalities in subjects who had the propensity to develop the atherogenic lipoprotein phenotype.


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