Abstract 18: Apo(a) Isoform Size Is Associated with Myocardial Infarction in a Study of an Admixed Population from the Central Valley of Costa Rica

Objective: Lipoprotein(a) [Lp(a)] particles contain a single apolipoprotein(a) [apo(a)] molecule. Both plasma Lp(a) levels and apo(a) isoform size are associated with myocardial infarction (MI). We asked whether Lp(a) level and apo(a) isoform size are independently associated with MI in an admixed population (African, Amer-indian, Southern European) from the Central Valley of Costa Rica. Methods: Apo(a) isoform size is determined by the number of kringle IV type 2 (KIV-2) repeats in the protein, and when two different alleles are expressed, the smaller isoform is typically expressed at higher levels. We assessed isoform size by Western blot and Lp(a) levels by immunoturbidometric assay in randomly selected MI cases and population-based controls from a study of 4186 Central Valley Costa Ricans. Association with MI was assessed using logistic regression models that included Lp(a) level and the size of the smaller isoform as explanatory variables. A model including adjustment for local ethnicity determined by principal component analysis of 41 SNPs within 410 kilobases of the gene encoding apo(a) [LPA] was performed on a subset of subjects with genotypes for all 41 SNPs. Results: For 433 subjects, for whom one or both apo(a) isoform sizes were determined by Western blot, we found that both size of the smaller expressed apo(a) isoform and Lp(a) level were associated with MI: OR=1.48 (p= 0.021) per decrease of 5 KIV-2 repeats and OR=1.27 (p=2.8x10-5) per 10 mg/dL increase in Lp(a). In multivariable analysis, the size of the smaller apo(a) isoform was associated with MI after adjustment for Lp(a) levels (OR=1.29; p= 0.034). Similarly, Lp(a) levels remained associated with MI after adjustment for the size of the smaller apo(a) isoform (OR=1.19; p=0.005). Further adjustment for local ethnicity did not appreciably change the association of the smaller apo(a) isoform with MI (OR= 1.38;p= 0.056) or the association of Lp(a) levels with MI (OR=1.11, p=0.18). Apo(a) isoform size was strongly associated with Lp(a) levels (9.6 mg/dL increase in Lp(a) per decrease of 5 KIV-2 repeats (p=1.7x10-24). Conclusion: Apo(a) isoform size is associated with MI after adjustment for Lp(a) in a population from the Central Valley of Costa Rica. The hypothesis that apo(a) isoform size is associated with MI independent of Lp(a) levels appears worthy of further study.