Twenty-six-year NHANES III follow-up finds regular aspirin cuts ASCVD mortality by 52% specifically in adults with elevated Lp(a) (Am J Prev Cardiol 2024)

Original title: Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a)

Am J Prev Cardiol · 27 April 2024 · 8

Razavi AC, Richardson LC, Coronado F, Dzaye O, Bhatia HS, Mehta A, Quyyumi AA, Vaccarino V, Budoff MJ, Nasir K, Tsimikas S, Whelton SP et al.

Using NHANES III (1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a), the authors studied 2,990 adults aged 40-70 without clinical ASCVD (representing roughly 73 million US adults; mean age 50, 86% non-Hispanic White, 53% female, 7% regular aspirin users), linked to mortality records over a median 26-year follow-up. Among those with elevated Lp(a) (50 mg/dL or above), ASCVD mortality incidence was markedly lower in regular aspirin users than non-users (1.2 vs. 3.9 per 1,000 person-years). In multivariable modelling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality in those with elevated Lp(a) (hazard ratio 0.48, 95% CI 0.28-0.83), but showed no benefit in those without elevated Lp(a) (hazard ratio 1.01, 95% CI 0.81-1.25; P for interaction = 0.001). Regular aspirin use for primary prevention is associated with substantially lower ASCVD mortality specifically in adults with elevated Lp(a), a finding the authors suggest has direct implications for how aspirin is used in primary prevention.

Original abstract

Objective: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort.

Methods: Eligible participants were aged 40-70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up.

Results: Among 2,990 persons meeting inclusion criteria (∼73 million US adults), the mean age was 50 years, 86% were non-Hispanic White, 9% were non-Hispanic Black, 53% were female, and 7% reported regular aspirin use. The median Lp(a) was 14 mg/dL and the proportion with elevated Lp(a) was similar among those with versus without regular aspirin use (15.1% versus 21.9%, p = 0.16). Among individuals with elevated Lp(a), the incidence of ASCVD mortality per 1,000 person-years was lower for those with versus without regular aspirin use (1.2, 95% CI: 0.1-2.3 versus 3.9, 95% CI: 2.8-4.9). In multivariable modeling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28-0.83), but not for those without elevated Lp(a) (HR=1.01, 95% CI: 0.81-1.25; p-interaction=0.001).

Conclusion: Regular aspirin use was associated with significantly lower ASCVD mortality in adults without clinical ASCVD who had elevated Lp(a). These findings may have clinical and public health implications for aspirin utilization in primary prevention.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.