Epidemiology
Each 50 mg/dL rise in Lp(a) raises premature ASCVD risk by 30% in a pooled 27,756-person, multi-ethnic US cohort (Am J Prev Cardiol 2025)
Original title: Lipoprotein(a), family history, and incidence of premature ASCVD events in a pooled US cohort
This analysis pooled 27,756 individuals without baseline ASCVD from five US prospective cohort studies to examine Lp(a)'s association with premature ASCVD (men under 55, women under 65) versus later-onset events, and how this varies by sex, race and family history. Among 5,276 incident ASCVD events over a mean 21.1-year follow-up, 773 (14.7%) were premature; premature ASCVD cases were disproportionately women (65.2% vs. 38.3%) and Black individuals (45.8% vs. 27.7%) compared with non-premature cases. Each 50 mg/dL increase in Lp(a) raised premature ASCVD risk by 30% (HR 1.30, 95% CI 1.28-1.51) versus 24% for non-premature events (HR 1.24, 95% CI 1.14-1.33), and Lp(a) at or above the 90th percentile carried adjusted hazard ratios of 1.39 for both premature and non-premature events. The association with premature ASCVD trended stronger in those with a family history of ASCVD and in White individuals, underscoring Lp(a)'s relevance to early-onset disease across a diverse population.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is an independent, genetic, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited data on its impact on premature ASCVD, including in diverse populations and with family history. We examined Lp(a) in relation to premature ASCVD (male aged <55, female aged <65 years) compared to later onset ASCVD, and differences by family history, sex, and race/ethnicity in a large, multi-ethnic U.S. cohort.
Methods: We analyzed data from 27,756 individuals without prior ASCVD at baseline from a pooled cohort consisting of five U.S. prospective studies. Lp(a) levels were stratified by cohort-specific percentiles. Multivariable Cox regression assessed the association of Lp(a) with composite incident premature and non-premature ASCVD events by sex, race, and family history.
Results: Among 5276 ASCVD events over a mean follow-up of 21.1 years, 773 (14.7 %) were premature ASCVD events. A higher proportion of women (65.2% vs. 38.3%) and Black individuals (45.8% vs. 27.7%) were observed in individuals with premature ASCVD compared to those with non-premature ASCVD events. For each 50 mg/dL increase in Lp(a), the risk of premature ASCVD increased by 30 % (HR: 1.30, 95% CI: 1.28-1.51), compared to a 24 % increase for non-premature ASCVD (HR: 1.24 [1.14-1.33]). Compared with Lp(a) levels <50th percentile, Lp(a) levels ≥ 90th percentile had adjusted HRs of 1.39 (1.10-1.75) and 1.39 (1.26-1.54) for premature and non-premature ASCVD events, respectively. We observed a trend for elevated Lp(a) levels predicting premature ASCVD events more strongly in those with a family history of ASCVD and in White individuals.
Conclusion: Elevated Lp(a) is an important predictor of both premature and later onset ASCVD events.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.