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High Levels of Inflammatory Biomarkers Are Associated with Increased Allele-Specific Apolipoprotein(a) Levels in African-Americans

Department of Medicine (E.A., A.C., L.B.), University of California, Davis, Sacramento, California 95817; Department of Medicine (J.R.), Columbia University, New York, New York 10027; Department of Pathology (R.P.T.), University of Vermont, Burlington, Vermont 05405; Department of Community and Preventive Medicine (T.A.P.), University of Rochester, Rochester, New York 14627; and VA Northern California Health Care System (L.B.), Sacramento, California 95655

Address all correspondence and requests for reprints to: Lars Berglund, M.D., Department of Medicine, University of California, Davis, UCD Medical Center, Clinical and Translation Science Center, 2921 Stockton Boulevard, Suite 1400, Sacramento, California 95817. E-mail: lars.berglund{at}ucdmc.ucdavis.edu.

Background: A role of inflammation for cardiovascular disease (CVD) is established. Lipoprotein(a) [Lp(a)] is an independent CVD risk factor where plasma levels are determined by the apolipoprotein(a) [apo(a)] gene, which contains inflammatory response elements.

Design: We investigated the effect of inflammation on allele-specific apo(a) levels in African-Americans and Caucasians. We determined Lp(a) levels, apo(a) sizes, allele-specific apo(a) levels, fibrinogen and C-reactive protein (CRP) levels in 167 African-Americans and 259 Caucasians.

Results: Lp(a) levels were increased among African-Americans with higher vs. lower levels of CRP [<3 vs. 3 mg/liter (143 vs. 108 nmol/liter), P = 0.009] or fibrinogen (<340 vs. 340 mg/liter, P = 0.002). We next analyzed allele-specific apo(a) levels for different apo(a) sizes. No differences in allele-specific apo(a) levels across CRP or fibrinogen groups were seen among African-Americans or Caucasians for small apo(a) sizes (<22 kringle 4 repeats). Allele-specific apo(a) levels for medium apo(a) sizes (22–30 kringle 4 repeats) were significantly higher among African-Americans, with high levels of CRP or fibrinogen compared with those with low levels (88 vs. 67 nmol/liter, P = 0.014, and 91 vs. 59 nmol/liter, P < 0.0001, respectively). No difference was found for Caucasians.

Conclusions: Increased levels of CRP or fibrinogen are associated with higher allele-specific medium-sized apo(a) levels in African-Americans but not in Caucasians. These findings indicate that proinflammatory conditions result in a selective increase in medium-sized apo(a) levels in African-Americans and suggest that inflammation-associated events may contribute to the interethnic difference in Lp(a) levels between African-Americans and Caucasians.