Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia

Most described modifications of low-density lipoprotein (LDL) cholesterol share an increase in its negative electric charge; in fact, an electronegative form of LDL can be identified and isolated from plasma. Although the exact nature of the chemical modification of electronegative LDL is still controversial, its toxicity on endothelial cells has been demonstrated. Statins have protective effects against cardiovascular disease that are independent of their lipid-lowering action and which could be due, at least in part, to the prevention of LDL modification. We evaluated the effect of 6 months of simvastatin therapy (40 mg/day) on electronegative LDL proportion and LDL susceptibility to in vitro induced oxidation in 21 patients with heterozygous familial hypercholesterolemia (FH). Eleven normolipemic subjects were analyzed as a control group. Total cholesterol as well as LDL and very low density lipoprotein cholesterol, triglycerides, and apoprotein B decreased 30% after the first month of therapy, with no further decreases thereafter. LDL susceptibility to oxidation was similar in FH patients and controls and did not change throughout the treatment. Electronegative LDL proportion was 35.1 ± 9.9% in FH patients and 9.1 ± 2.4% in control subjects (p <0.0001) but, in contrast to total LDL cholesterol and the rest of lipid parameters, it decreased to 28.6 ± 9.1% in the third month and to 21.2 ± 7.7% in the sixth month of therapy. The decrease in these cytotoxic particles may be a relevant mechanism by which simvastatin protects against cardiovascular disease.