Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease.
BACKGROUND
Lp(a) lipoprotein binds proinflammatory oxidized phospholipids. We investigated whether levels of oxidized low-density lipoprotein (LDL) measured with use of monoclonal antibody E06 reflect the presence and extent of obstructive coronary artery disease, defined as a stenosis of more than 50 percent of the luminal diameter.


METHODS
Levels of oxidized LDL and Lp(a) lipoprotein were measured in a total of 504 patients immediately before coronary angiography. Levels of oxidized LDL are reported as the oxidized phospholipid content per particle of apolipoprotein B-100 (oxidized phospholipid:apo B-100 ratio).


RESULTS
Measurements of the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels were skewed toward lower values, and the values for the oxidized phospholipid:apo B-100 ratio correlated strongly with those for Lp(a) lipoprotein (r=0.83, P<0.001). In the entire cohort, the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels showed a strong and graded association with the presence and extent of coronary artery disease (i.e., the number of vessels with a stenosis of more than 50 percent of the luminal diameter) (P<0.001). Among patients 60 years of age or younger, those in the highest quartiles for the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels had odds ratios for coronary artery disease of 3.12 (P<0.001) and 3.64 (P<0.001), respectively, as compared with patients in the lowest quartile. The combined effect of hypercholesterolemia and being in the highest quartiles of the oxidized phospholipid:apo B-100 ratio (odds ratio, 16.8; P<0.001) and Lp(a) lipoprotein levels (odds ratio, 14.2; P<0.001) significantly increased the probability of coronary artery disease among patients 60 years of age or younger. In the entire study group, the association of the oxidized phospholipid:apo B-100 ratio with obstructive coronary artery disease was independent of all clinical and lipid measures except one, Lp(a) lipoprotein. However, among patients 60 years of age or younger, the oxidized phospholipid:apo B-100 ratio remained an independent predictor of coronary artery disease.


CONCLUSIONS
Circulating levels of oxidized LDL are strongly associated with angiographically documented coronary artery disease, particularly in patients 60 years of age or younger. These data suggest that the atherogenicity of Lp(a) lipoprotein may be mediated in part by associated proinflammatory oxidized phospholipids.
Division of Cardiovascular Diseases, University of California, San Diego, La Jolla, CA 92093-0682, USA. stsimikas@ucsd.edu
Sotirios
S
Tsimikas
Emmanouil S
ES
Brilakis
Elizabeth R
ER
Miller
Joseph P
JP
McConnell
Ryan J
RJ
Lennon
Kenneth S
KS
Kornman
Joseph L
JL
Witztum
Peter B
PB
Berger
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D023921:Coronary Stenosis / Q000175:diagnosis; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D017270:Lipoprotein(a) / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood*; D014280:Triglycerides / Q000097:blood
D000911:Antibodies, Monoclonal; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D017270:Lipoprotein(a); D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol