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1: N Engl J Med. 2005 Jul 7;353(1):46-57. Related Articles, Cited in PMC,
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Comment in:
N Engl J Med. 2005 Jul 7;353(1):9-11.

Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease.

Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS,
Witztum JL, Berger PB.

Division of Cardiovascular Diseases, University of California, San Diego, La
Jolla, CA 92093-0682, USA. stsimikas@ucsd.edu

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. Copyright 2005
Massachusetts Medical Society.

PMID: 16000355 [PubMed - indexed for MEDLINE]