Effects of Atorvastatin and Simvastatin on Low-Density Lipoprotein Subtraction Profile, Low-Density Lipoprotein Oxidizability, and Antibodies to Oxidized Low-Density Lipoprotein in Relation to Carotid Intima Media Thickness in Familial Hypercholesterolemia

Abstract

Background Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression. Methods In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose atorvastatin (80 mg) and conventional-dose simvastatin (40 mg) on LDL subtraction profile ( n = 289), LDL oxidizability ( n = 121), and circulating autoantibodies to oxidized LDL ( n = 220). Progression of atherosclerosis was measured by carotid intima media thickness (IMT) ( n = 325). Results At baseline, the patients showed an intermediate LDL subtraction profile composed of three LDL subtractions (LDL1, LDL2, LDL3), with LDL2 as the predominant subtraction. A strong negative correlation was found between plasma triglycerides and the LDL subtraction profile ( r = - .64, p = .000). Both plasma levels of triglycerides and small dense LDL3 correlated weakly with baseline IMT ( r = .11, p = .04 and r = .15, p = .01, respectively; n = 289). No association was found between baseline IMT and oxidation parameters or circulating antibodies to oxidized LDL. Atorvastatin reduced triglycerides, LDL cholesterol, and all LDL subtractions to a greater extent than did simvastatin and led to regression of carotid IMT. However, LDL subtraction pattern and plasma levels of autoantibodies to oxidized LDL remained unchanged in both treatment groups, and LDL oxidizability increased minimally to a similar extent in both groups. Significant treatment differences were found for the rate of in vitro oxidation of LDL and the amount of dienes formed during in vitro oxidation of LDL, which both decreased more following atorvastatin than after simvastatin. Conclusion Change of IMT after statin treatment was associated with baseline IMT ( r = .41), LDL cholesterol ( r = -.20), and the amount of dienes formed during in vitro oxidation of LDL ( r = .28) but not with plasma levels of antibodies to oxidized LDL, in vitro LDL oxidizability, and LDL subtraction profile.