Lipoprotein oxidation and progression of carotid atherosclerosis.
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.


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 7 beta-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 7 beta-hydroxycholesterol (beta = 47, P = .0005), cigarette smoking (beta = .35, P = .0167), and LDL TBARS (beta = .23, P = .0862) and an increased oxidation susceptibility of VLDL + LDL (beta = .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 (microgram/L) of 7 beta-hydroxycholesterol.


CONCLUSIONS
The findings of this study provide further evidence to support an association between lipid oxidation and atherogenesis in humans.
Salonen
J T
JT
Research Institute of Public Health, University of Kuopio, Finland.
Nyyssönen
K
K
Salonen
R
R
Porkkala-Sarataho
E
E
Tuomainen
T P
TP
Diczfalusy
U
U
Björkhem
I
I
D001161:Arteriosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015415:Biomarkers; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018450:Disease Progression; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011336:Probability; D012307:Risk Factors; D012907:Smoking; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography
D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006888:Hydroxycholesterols; D008074:Lipoproteins; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; C011724:cholest-5-en-3 beta,7 alpha-diol