Effects of atorvastatin treatment on the oxidatively modified low density lipoprotein in hyperlipidemic patients

Atorvastatin is an established HMG-CoA reductase inhibitor which effectivel y reduces the plasma low density lipoprotein (LDL)-cholesterol level in hyp erlipidemic patients. The present study was designed to investigate whether atorvastatin treatment can modify the biochemical content of oxidized LDL in hyperlipidemic patients and the ability of oxidized LDL to impair the en dothelium-dependent relaxation of blood vessels. With atorvastatin (10 mg/d ay) treatment for 4 weeks in 19 type IIa hyperlipidemic patients, total cho lesterol level was lowered by 23%, LDL-cholesterol was lowered by 32% and t riacylglycerol was lowered by 19% as compared with dietary therapy alone. H igh density lipoprotein levels increased by approximatly 9%. The ability of oxidized LDL from hyperlipidemic patients after atorvastatin treatment to impair the endothelium-dependent relaxation was significantly reduced as co mpared with dietary intervention alone. Analysis of the biochemical content s of oxidized LDL from this group revealed that there was an 11% reduction in lysophosphatidylcholine (LPC) as compared with the group that received o nly dietary counseling. A decrease in the C16:0 moiety with a corresponding increase in the C18:0 moiety of LPC in the oxidized LDL was also observed in the atorvastatin treated group. We propose that the observed reduction a nd the change in composition of acyl groups in LPC in the oxidized LDL of t he atorvastatin-treated group results from a combination of the continued d ietary treatment as well as drug therapy. In view of an observation that bo th C16:0 and C18:0 LPC species are equally potent in the impairment of endo thelium-dependent relaxation of the aortic rings, we feel that the reduced level of LPC in the oxidized LDL produced by atorvastatin treatment is part ially responsible for the improvement in endothelium control of vascular to ne.