The effect of statin therapy on plasma high-density lipoprotein cholesterol levels is modified by paraoxonase-1 in patients with familial hypercholesterolaemia.

Abstract

OBJECTIVES. Statins reduce low-density lipoprotein cholesterol (LDL-C) and can raise high-density lipoprotein cholesterol (HDL-C). HDL-bound paraoxonase-1 (PON1) is associated with variations in plasma HDL-C, and may, therefore, contribute to changes of HDL-C during statin therapy. DESIGN. The effects of baseline PON1 status to HDL-C changes because of statin therapy were investigated. PON1 status was determined with (i) PON1 -107C>T and 192Q>R genotype, (ii) PON1 levels and (iii) PON1 paraoxonase, diazoxonase and arylesterase activity. SETTING. Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. SUBJECTS. A total of 134 familial hypercholesterolaemia (FH) patients undergoing atorvastatin or simvastatin therapy. RESULTS. PON1 levels and activities significantly modified the HDL-C increment (P=0.002 for PON1 levels and arylesterase activity and P=0.001 for diazoxonase activity). The effects were even more evident amongst subgroup classifications based on PON1 status and baseline HDL-C concentrations: the HDL-C increment was more pronounced in subgroups of -107CT/TT or 192QR/RR genotype combined with low baseline HDL-C (+13.9%, P<0.001, respectively+15.4%, P<0.001). In contrast, the -107CC or 192QQ genotype in combination with high baseline HDL-C, did not show a significant increase of HDL-C. CONCLUSIONS. PON1 status in conjunction with baseline HDL-C levels predicts HDL-C increment during statin therapy in FH patients.