Reduction of charge-modified LDL by statin therapy in patients with CHD or CHD risk factors and elevated LDL-C levels: The SPECIAL Study

Abstract Various forms of atherogenic modified low-density lipoprotein (LDL) including oxidized LDL and small, dense LDL have increased negative charge as compared to normal LDL. Charge-modified LDL (electronegative LDL) and normal LDL subfractions in plasma are analyzed by capillary isotachophoresis (cITP) as fast-migrating LDL (fLDL) and slow-migrating LDL (sLDL). We examined the effects of pravastatin and simvastatin on charge-based LDL subfractions as determined by cITP in patients with hypercholesterolemia. Patients ( n = 72) with CHD or CHD risk factors and elevated LDL cholesterol (LDL-C) levels were randomly assigned to receive pravastatin or simvastatin. After treatment with statins for 3 and 6 months, both cITP fLDL and sLDL were reduced ( p < 0.05) from the baseline, but the effects did not differ between treatment with pravastatin and simvastatin. At baseline and after treatment for 3 months, cITP sLDL was correlated with LDL-C, but fLDL was correlated with inflammatory markers, high-sensitive C-reactive protein and LDL-associated platelet-activating factor acetylhydrolase, and atherogenic lipoproteins, remnant-like particle cholesterol and small, dense LDL cholesterol. In conclusion, cITP fLDL was related to inflammatory markers and atherogenic lipoproteins and was reduced by treatment with statins. Charge-modified LDL subfraction could be a potential marker for atherosclerosis and a target for therapy.