AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Higher Lipoprotein(a) Identifies Residual Cardiovascular Risk Despite Achieving LDL-C Targets After Myocardial Infarction
By Elesawy M, Alkhateeb M, Mohamed Siraj H et al.
Background: Intensive LDL-C lowering after myocardial infarction (MI) reduces recurrent cardiovascular risk, but most LDL-C lowering therapies do not specifically target Lp(a). As new guidelines emphasize more aggressive lowering of LDL-C to <55mg/dL after MI, it remains poorly understood the impact of elevated Lp(a) in this high-risk population. We sought to evaluate whether elevated Lp(a) is associated with residual cardiovascular risk among post-MI patients who achieved guideline-recommended LDL-C thresholds. Methods: We performed a retrospective observational analysis using the TriNetX US Collaborative Network database. Adults aged ≥18 years with prior MI, documented Lp(a) measurement, and subsequent achievement of LDL-C <70 mg/dL or <55 mg/dL were included. Patients were stratified into higher and lower Lp(a) groups using a threshold of 125 nmol/L or 50 mg/dL, depending on the reported assay unit. Cohorts were propensity-matched for demographics, major cardiometabolic comorbidities, baseline lipid profile, body mass index, glycemic control, kidney disease, and use of lipid-lowering, antiplatelet, anticoagulant, and other cardiovascular medications. Kaplan-Meier (KM) analysis and Cox proportional hazards models were used to assess clinical outcomes. Results: After propensity matching, 5,225 patients were included in each Lp(a) group for the LDL-C <70 mg/dL analysis, and 3,827 patients were included in each group for the LDL-C <55 mg/dL analysis. Baseline characteristics were well balanced between cohorts. In both LDL-C strata, higher Lp(a) was associated with significantly greater residual risk of recurrent MI, ischemic stroke, peripheral artery disease, and aortic stenosis. For the LDL-C <70 mg/dL and LDL-C <55 mg/dL groups, respectively, hazard ratios were 1.09 and 1.12 for recurrent MI, 1.33 and 1.34 for ischemic stroke, 1.17 and 1.20 for peripheral artery disease, and 1.35 and 1.39 for aortic stenosis. In the LDL-C <55 mg/dL cohort, KM cumulative incidence curves demonstrated early and sustained separation between higher and lower Lp(a) groups across all outcomes, with significant log-rank differences. Conclusion: Among post-MI patients who achieved guideline-recommended LDL-C thresholds, higher Lp(a) remained associated with greater residual recurrent atherosclerotic events and aortic stenosis. Among ASCVD outcomes, the strongest association was observed for ischemic stroke. These findings enforce the role of Lp(a) in residual risk stratification beyond LDL-C and highlight the need for Lp(a)-directed therapeutic strategies