High Dose Alpha Tocopherol therapy does not affect subfractions of High Density Lipoproteins in patients with Coronary Artery Disease on Statin therapy

Abstract

Low levels of High density lipoprotein (HDL) are predictive of coronary heart disease (CHD). However, subfractions of HDL are implicated as better indicators of the disease process. The large HDL particles (HDL2) are inversely correlated to the severity of coronary artery disease (CAD). Alpha tocopherol (AT) is the main lipid soluble antioxidant in plasma and is anti-inflammatory. Previously, a small study (n=44) showed that the combination of an antioxidant cocktail (800 IU/d RRR-AT plus 1g Vitamin C, 25 mg β-carotene and 100 ug Se) with simvatstatin –niacin (S-N) therapy attenuated the protective increase in HDL2 seen with S-N alone. Thus, we tested the effect of high dose RRR-AT (1200 IU/d for 2 yrs) supplementation on HDL subfractions in a prospective randomized placebo-controlled study in a larger population of patients (n=90) with stable CAD on AT / placebo at 5 different time points (baseline, 6 months, 1 year, 1½ and 2 years). Importantly, 94% of the patients were on statin therapy. HDL subfractions were analyzed by NMR spectroscopy and divided into large (8.8 to 13.0nm), medium (8.2 to 8.8 nm), and small (7.3 to 8.2 nm) HDL particles. AT levels significantly increased (p<0.05) following therapy compared to placebo. There were no differences in the plasma total cholesterol, TG or LDL-C. AT therapy over 2 years had no significant effect on total (p=0.5), large (p=0.6), medium (p=0.8) and small (p=0.9) HDL particles compared to baseline or placebo. We conclude that high dose RRR-AT therapy over 2 years, in patients with CAD on statin therapy, does not negatively affect HDL subclasses. Thus the negative interaction previously proposed between antioxidant cocktail and statin therapy cannot be ascribed to AT. NIH RO1