AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Elevated Lipoprotein(a) and Cardiovascular Outcomes in Adults with Hypercholesterolemia: A Comparative Observational Study
By Khan ZZ, Sajid A, Khan FZ et al.
BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease and calcific aortic stenosis. However, real-world data quantifying its association with a broad range of cardiovascular outcomes in patients with hypercholesterolemia remain limited. Hypothesis: Among adults with hypercholesterolemia, elevated Lp(a) is associated with higher 3-year risk of atherosclerotic and valvular cardiovascular outcomes compared with non-elevated Lp(a). Methods: We performed a retrospective propensity score-matched cohort study using the TriNetX US Collaborative Network (65 healthcare organizations). Adults with hypercholesterolemia and elevated Lp(a), defined as 50 mg/dL or higher or 125 nmol/L or higher, were compared with adults with non-elevated Lp(a). Cohorts were matched 1:1 on demographics, comorbidities, lipid-lowering and cardiovascular medications, and lipid values. Outcomes were assessed over 1,095 days. Risk ratios (RRs) were calculated from event proportions, and hazard ratios (HRs) were estimated using Cox models with log-rank P values.RESULTS: After matching, 15,925 patients were included in each cohort, and all standardized mean differences were below 0.10. Elevated Lp(a) was associated with higher risk of calcific aortic stenosis (1.6% vs 1.1%; RR 1.52, 95% CI 1.25-1.84; HR 1.49, 95% CI 1.23-1.80; P<0.001), coronary revascularization (1.1% vs 0.7%; RR 1.49, 95% CI 1.17-1.90; HR 1.47, 95% CI 1.15-1.86; P=0.002), acute myocardial infarction (1.0% vs 0.7%; RR 1.45, 95% CI 1.13-1.85; HR 1.41, 95% CI 1.10-1.80; P=0.006), acute limb ischemia or peripheral revascularization (0.3% vs 0.2%; RR 1.69, 95% CI 1.04-2.75; HR 1.65, 95% CI 1.02-2.68; P=0.041), new coronary artery disease (7.4% vs 6.1%; RR 1.21, 95% CI 1.10-1.32; HR 1.20, 95% CI 1.10-1.32; P<0.001), and peripheral artery disease (2.9% vs 2.4%; RR 1.19, 95% CI 1.04-1.36; HR 1.17, 95% CI 1.02-1.34; P=0.023). Ischemic stroke was significant by RR but not by survival analysis (0.9% vs 0.7%; RR 1.29, 95% CI 1.01-1.67; P=0.044; HR 1.25, 95% CI 0.97-1.62; log-rank P=0.079). Differences were not statistically significant for 3-point major adverse cardiovascular events (RR 1.18; P=0.061), all-cause mortality (RR 1.21; P=0.145), or aortic valve replacement (RR 1.47; P=0.250). CONCLUSIONS: In propensity-matched adults with hypercholesterolemia, elevated Lp(a) was associated with higher 3-year risk of myocardial infarction, coronary and peripheral atherosclerotic disease, and calcific aortic stenosis. These findings support Lp(a) measurement for cardiovascular risk stratification and reinforce the rationale for trials of targeted Lp(a)-lowering therapies.