Circulating lipid hydroperoxides predict cardiovascular events in patients with stable coronary artery disease: the PREVENT study.
OBJECTIVE
This study was designed to determine the predictive value of lipid hydroperoxide (LOOH) levels for adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD).


BACKGROUND
Oxidative modification of circulating lipids contributes to inflammation and endothelial dysfunction, which are hallmark features of atherosclerosis. A serum biomarker of oxidation is LOOH, which is a primary product of fatty acid peroxidation.


METHODS
Serum LOOH levels were measured and correlated with clinical events over a 3-year period in 634 patients with angiographic evidence of CAD.


RESULTS
Baseline LOOH levels in the highest quartile were associated with hazard ratios of 3.24 (95% confidence interval [CI] 1.86 to 5.65; p = 0.0001) for nonfatal vascular events (n = 149), 1.80 (95% CI 1.13 to 2.88; p = 0.014) for major vascular procedures (n = 139), and 2.23 (95% CI 1.44 to 3.44; p = 0.0003) for all vascular events and procedures. Baseline LOOH levels correlated with serum levels of soluble intercellular adhesion molecule-1 (p = 0.001) and thiobarbituric acid reactive substances (p = 0.001) as well as the mean percent change in stenosis for large segments >50% stenosed (p = 0.048). A multivariate proportional hazards model, adjusted for traditional risk factors and inflammatory markers, showed an independent effect of LOOH on nonfatal vascular events, vascular procedures, and all events or procedures. Amlodipine treatment was associated with reduced cardiovascular events and changes in LOOH levels compared with placebo.


CONCLUSIONS
Elevated LOOH levels were predictive of nonfatal vascular events and procedures in patients with stable CAD, independent of traditional risk factors and inflammatory markers.
Walter
Mary F
MF
Elucida Research, Beverly, Massachusetts, USA.
Jacob
Robert F
RF
Bjork
Rebekah E
RE
Jeffers
Barrett
B
Buch
Jan
J
Mizuno
Yoshiko
Y
Mason
R Preston
RP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors
D008054:Lipid Peroxides; D006861:Hydrogen Peroxide