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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1541-1548.)
© 1999 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effects of Lovastatin Therapy on Susceptibility of LDL to Oxidation During -Tocopherol Supplementation

Ari Palomäki; Kimmo Malminiemi; Outi Malminiemi; Tiina Solakivi

From the Department of Internal Medicine, Kanta-Häme Central Hospital, Hämeenlinna (A.P.), and the Departments of Internal Medicine (K.M.) and of Clinical Chemistry (O.M., T.S.), Tampere University Hospital, Tampere, Finland.

Correspondence to Ari Palomäki, MD, Kanta-Häme Central Hospital, Department of Internal Medicine, FIN-13530 Hämeenlinna, Finland.

Abstract—A randomized, double-masked, crossover clinical trial was carried out to evaluate whether lovastatin therapy (60 mg daily) affects the initiation of oxidation of low density lipoprotein (LDL) in cardiac patients on -tocopherol supplementation therapy (450 IU daily). Twenty-eight men with verified coronary heart disease and hypercholesterolemia received -tocopherol with lovastatin or with dummy tablets in random order. The two 6-week, active-treatment periods were preceded by a washout period of at least 8 weeks. The oxidizability of LDL was determined by 2 methods ex vivo. The depletion times for LDL ubiquinol and LDL -tocopherol were determined in timed samples taken during oxidation induced by 2,2-azobis(2,4-dimethylvaleronitrile). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated-diene formation. -Tocopherol supplementation led to a 1.9-fold concentration of reduced -tocopherol in LDL (P<0.0001) and to a 2.0-fold longer depletion time (P<0.0001) of -tocopherol compared with determinations after the washout period. A 43% prolongation (P<0.0001) was seen in the lag time of conjugated-diene formation. Lovastatin decreased the depletion time of reduced -tocopherol in metal ion–independent oxidation by 44% and shortened the lag time of conjugated-diene formation in metal ion–dependent oxidation by 7%. In conclusion, -tocopherol supplementation significantly increased the antioxidative capacity of LDL when measured ex vivo, which was partially abolished by concomitant lovastatin therapy.

Key Words: -tocopherol • clinical trials • lipid oxidation • lovastatin • ubiquinol

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