INTERHEART China Study finds dual apo(a) isoforms smaller than 23 increase acute myocardial infarction risk (Am J Cardiol 2026)

There are limited effective methods or biomarkers for assessing the risk of acute myocardial infarction (AMI). This study evaluated the distribution characteristics of plasma lipoprotein(a) [Lp(a)] concentrations and apolipoprotein(a) [apo(a)] isoform sizes. Then, we investigated their independent and interactive associations with the risk of AMI. Based on the INTERHEART China case-control study, 1,908 participants (963 patients with first-time AMI and 945 age and sex matched controls) were enrolled. Risk factors, including lifestyle, metabolic markers, and psychosocial factors were collected using standardized questionnaires. Lp(a) concentrations were measured using an isoform-insensitive immunoassay, and apo(a) isoform sizes were quantified in all participants via Western blotting. Multivariate logistic regression models were used to analyze risk associations; restricted cubic splines were applied to assess dose-response relationships, and interactions were tested. High Lp(a) concentrations were significantly associated with an increased risk of AMI. Overall, a consistent negative correlation was observed between apo(a) isoform size and Lp(a) concentration. Further, In the single isoform subgroup, smaller apo(a) size was associated with a higher AMI risk in the unadjusted model, but this association became non-significant after adjusting for Lp(a) levels. However, in the dual isoform subgroup, carrying smaller isoforms (< 23) was associated with a significantly higher AMI risk (OR, 1.83;95% CI, 1.12-3.04), while larger isoform sizes (>29) showed a trend towards higher risk of MI. In conclusion, our findings suggest that current cardiovascular risk stratification might be optimized by integrating both Lp(a) mass and isoform genotyping, offering a new perspective on the precise risk stratification of AMI patients.