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(Circulation. 2009;119:1711-1719.)
© 2009 American Heart Association, Inc.

Epidemiology

Relationship of Oxidized Phospholipids on Apolipoprotein B-100 Particles to Race/Ethnicity, Apolipoprotein(a) Isoform Size, and Cardiovascular Risk Factors

Results From the Dallas Heart Study

Sotirios Tsimikas, MD; Paul Clopton, MS; Emmanouil S. Brilakis, MD; Santica M. Marcovina, PhD; Amit Khera, MD, MSc; Elizabeth R. Miller, BS; James A. de Lemos, MD; Joseph L. Witztum, MD

From the Department of Medicine (S.T., E.R.M., P.C., J.L.W.), University of California San Diego, La Jolla; Department of Medicine (S.M.M.), University of Washington, Seattle; and Dallas VA Medical Center (E.S.B.) and Donald W. Reynolds Cardiovascular Clinical Research Center (E.S.B., A.K., J.A.d.L.), University of Texas Southwestern Medical Center, Dallas.

Correspondence to Sotirios Tsimikas, Vascular Medicine Program, University of California San Diego, 9500 Gilman Dr, BSB 1080, La Jolla, CA 92093–0682. E-mail stsimikas{at}ucsd.edu

Received November 21, 2008; accepted January 30, 2009.

Background— Elevated levels of oxidized phospholipids (OxPLs) on apolipoprotein B-100 particles (OxPL/apoB) are associated with cardiovascular disease and predict new cardiovascular events. Elevated lipoprotein (a) [Lp(a)] levels are a risk factor for cardiovascular disease in whites and also in blacks if they carry small apolipoprotein(a) [apo(a)] isoforms. The relationship of OxPL/apoB levels to race/ethnicity, cardiovascular risk factors, and apo(a) isoforms is not established.

Methods and Results— OxPL/apoB levels were measured in 3481 subjects (1831 black, 1047 white, and 603 Hispanic subjects) in the Dallas Heart Study and correlated with age, sex, cardiovascular risk factors, and Lp(a) and apo(a) isoforms. Significant differences in OxPL/apoB levels were noted among racial/ethnic subgroups, with blacks having the highest levels compared with whites and Hispanics (P<0.001 for each comparison). OxPL/apoB levels generally did not correlate with age, sex, or risk factors. In the overall cohort, OxPL/apoB levels strongly correlated with Lp(a) (r=0.85, P<0.001), with the shape of the relationship demonstrating a "reverse L" shape for log-transformed values. The highest correlation was present in blacks, followed by whites and Hispanics; was dependent on apo(a) isoform size; and became progressively weaker with larger isoforms. The size of the major apo(a) isoform (number of kringle type IV repeats) was negatively associated with OxPL/apoB (r=–0.49, P<0.001) and Lp(a) (r=–0.61, P<0.001) regardless of racial/ethnic group. After adjustment for apo(a) isoform size, the relationship between OxPL/apoB and Lp(a) remained significant (r=0.67, P<0.001).

Conclusions— OxPL/apoB levels vary according to race/ethnicity, are largely independent of cardiovascular risk factors, and are inversely associated with apo(a) isoform size. The association of OxPL with small apo(a) isoforms, in which a similar relationship is present among all racial/ethnic subgroups despite differences in Lp(a) levels, may be a key determinant of cardiovascular risk.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2009 119: 1691-1693. [Extract] [Full Text]

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