(Circulation. 1997;95:840-845.)
© 1997 American Heart Association, Inc.
Articles |
Lipoprotein Oxidation and Progression of Carotid Atherosclerosis
the Research Institute of Public Health (J.T.S., K.N., R.S., E.P.-S., T.-P.T.), University of Kuopio, Finland, and Karolinska Institute (U.D., I.B.), Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Huddinge University Hospital, Stockholm, Sweden.
Correspondence to Prof Jukka T. Salonen, Research Institute of Public Health, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland.
Background Epidemiological studies and animal experiments have provided evidence supporting the role of lipid peroxidation in atherogenesis and cardiovascular diseases. Direct evidence linking lipid oxidation to atherosclerotic progression in humans, however, has been lacking. We investigated the association of lipid oxidation products with the progression of early carotid atherosclerosis in hypercholesterolemic men from eastern Finland.
Methods and Results Twenty subjects with a fast progression and 20 with no progression of carotid atherosclerosis in 3 years were selected from >400 participants in the Kuopio Atherosclerosis Prevention Study. Progression of carotid atherosclerosis was assessed by high-resolution B-mode ultrasonography. Serum 7ß-hydroxycholesterol, a major oxidation product of cholesterol in membranes and lipoproteins, and seven other cholesterol oxidation products were measured by isotope dilution–mass spectrometry, lipid hydroperoxides in LDL fluorometrically as thiobarbituric acid–reactive substances (TBARS) and oxidation susceptibility of LDL and VLDL kinetically. High concentrations of serum 7ß-hydroxycholesterol (ß=.47, P=.0005), cigarette smoking (ß=.35, P=.0167), and LDL TBARS (ß=.23, P=.0862) and an increased oxidation susceptibility of VLDL+LDL (ß=.22, P=.1114) were the strongest predictors of a 3-year increase in carotid wall thickness of more than 30 variables tested in step-up least-squares regression models. A 10-variable model explained 60% of the atherosclerotic progression. In a multivariate logistic model, the risk of experiencing a fast progression increased by 80% (P=.013) per unit (µg/L) of 7ß-hydroxycholesterol.
Conclusions The findings of this study provide further evidence to support an association between lipid oxidation and atherogenesis in humans.
Key Words: arteriosclerosis • carotid arteries • cholesterol • oxysterols
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