© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
High Levels of Lp(a) With a Small Apo(a) Isoform Are Associated With Coronary Artery Disease in African American and White Men
From the Department of Medicine (F.P., C.H.T., J.R., L.B.), Columbia University, New York, NY; Bassett Research Institute (T.A.P., H.F.C.W., M.M., H.F.M., E.F.P., R.G.R.), Cooperstown, NY; University of Rochester (T.A.P.), Rochester, NY; and Harlem Hospital (C.K.F.), New York, NY.
Correspondence to Lars Berglund, MD, Department of Medicine, Room P&S 9-510, Columbia University, 630 West 168th St, New York, NY 10032. E-mail LFB9{at}columbia.edu
Abstract—Elevated
levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms
of apolipoprotein(a) [apo(a)] have been associated with
coronary artery disease (CAD) in whites but not in
African Americans. Because of marked race/ethnicity differences in the
distribution of Lp(a) levels across apo(a) sizes, we tested the
hypothesis that apo(a) isoform size determines the association between
Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels
of Lp(a) associated with different apo(a) isoforms to the presence of
CAD (
50% stenosis) in 576 white and African American men and
women. Only in white men were Lp(a) levels significantly higher among
patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL,
respectively; P=0.004), and only in this group was the
presence of small apo(a) isoforms (<22 kringle 4 repeats) associated
with CAD (P=0.043). Elevated Lp(a) levels (30 mg/dL)
were found in 26% of whites and 68% of African Americans, and of
those, 80% of whites but only 26% of African Americans had a small
apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were
significantly associated with CAD (P<0.01) in African
American and white men but not in women. This association remained
significant after adjusting for age, diabetes mellitus, smoking,
hypertension, HDL cholesterol, LDL cholesterol,
and triglycerides. We conclude that elevated levels of
Lp(a) with small apo(a) isoforms independently predict risk for CAD in
African American and white men. Our study, by determining the
predictive power of Lp(a) levels combined with apo(a) isoform size,
provides an explanation for the apparent lack of association of either
measure alone with CAD in African Americans. Furthermore, our results
suggest that small apo(a) size confers atherogenicity to
Lp(a).
Key Words: lipoprotein(a) • coronary artery disease • African Americans • angiography • genetic variation
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