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BACKGROUND: Lipoprotein(a) (Lp(a)) levels predict the risk of myocardial infarction (MI) in populations of European ancestry; however, little data are available for other ethnic groups. Furthermore, differences in isoform size distribution and the associated Lp(a) concentrations have not fully been characterized between ethnic groups. METHODS: We studied 6,086 cases of first MI and 6,857 controls from the INTERHEART study that were stratified by ethnicity and adjusted for age and sex. A total of 775 Africans, 4,443 Chinese, 1,352 Arabs, 1,856 Europeans, 1,469 Latin Americans, 1,829 South Asians, and 1,221 Southeast Asians were included in the study. Lp(a) concentration was measured in each participant using an assay that was insensitive to isoform size, with isoform size being assessed by western blot in a subset of 4,219 participants. RESULTS: Variations in Lp(a) concentrations and isoform size distributions were observed between populations, with Africans having the highest Lp(a) concentration (median=27.2 mg/dL) and smallest isoform size (median=24 KIV repeats). Chinese samples had the lowest concentration (median=7.8 mg/dL) and largest isoform sizes (median=28). Overall, high Lp(a) concentrations (>50 mg/dL) were associated with an increased risk of myocardial infarction (OR, 1.48; 95% CI, 1.32-1.67; p<0.001). The association was independent of established MI risk factors, including diabetes, smoking, high blood pressure, ApoB and ApoA ratio. An inverse association was observed between isoform size and Lp(a) concentration, which was consistent across ethnic groups. Larger isoforms tended to be associated with a lower risk of MI, but this relationship was not present after adjustment for concentration. Consistent with variations in Lp(a) concentration across populations, the population attributable risk of high Lp(a) for MI varied from 0% in Africans to 9.5% in South Asians. CONCLUSIONS: Lp(a) concentration and isoform size varied markedly between ethnic groups. Higher Lp(a) concentrations were associated with an increased risk of MI and carried an especially high population burden in South Asians and Latin Americans. Isoform size was inversely associated with Lp(a) concentration, but did not significantly contribute to risk.

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Apo(a), Lipoprotein(a), biomarkers, disease risk prediction, myocardial infarction