Abstract 1094: Inflammation Results In Increased Allele-specific Apo(a) Levels In African Americans: Potential Explanation For Inter-ethnic Difference?

Abstract

Background: The role of inflammation in the pathogenesis of cardiovascular disease (CVD) is well recognized. Lipoprotein(a), Lp(a), is an independent CVD risk factor where plasma levels are largely determined by apo(a) gene size. Allele-specific apo(a) levels are higher among African Americans (AA) compared to Caucasians (C), and the most pronounced inter-ethnic difference is seen for medium-sized apo(a) alleles. This difference remains unexplained. The apo(a) gene contains response elements for inflammatory factors. However, the effect of inflammation on Lp(a) level, particularly on allele-specific apo(a) levels is unknown. Objective: We investigated the effect of inflammation measured by two acute-phase reactants (CRP and fibrinogen) on allele-specific apo(a) levels in AA and C. Methods: We determined Lp(a) levels, apo(a) sizes, allele-specific apo(a) levels, fibrinogen and CRP levels in 167 AA and 259 C. Results: Lp(a) levels were increased among AA with higher vs. lower CRP (>3 mg/dl) or fibrinogen (>340 mg/dl) levels (143 vs. 108 nmol/l, P =0.009, and 146 vs. 105 nmol/l, P =0.002, respectively). We next analyzed allele-specific apo(a) levels for different apo(a) sizes. No differences in allele-specific apo(a) levels across CRP (>3 vs. ≤3 mg/dl) or fibrinogen (>340 vs. ≤340 mg/dl) groups were seen among AA or C for small apo(a) sizes (<22 K4). Allele specific apo(a) levels for medium apo(a) sizes (23–30 K4) were significantly higher among AA with high levels of CRP or fibrinogen compared to those with low levels (88 vs. 67 nmol/l, P =0.014 and 91 vs. 59 nmol/l, P< 0.0001, respectively). In contrast, there were no significant differences in allele-specific apo(a) levels across CRP or fibrinogen groups among C with medium sized apo(a) alleles. Conclusion: Increased levels of CRP or fibrinogen are associated with higher allele-specific medium-sized apo(a) levels in AA, but not in C. Our results implicate that a pro-inflammatory stimulus may result in a selective increase in Lp(a) levels among AA carrying medium-sized apo(a). These findings provide a potential explanation for differences in Lp(a) levels between African Americans and Caucasians and suggest that inflammation-associated events may contribute to this inter-ethnic difference.