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Updated: Jun 26, 2025
Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a)
Alexander C Razavi1, LaTonia C Richardson2, Fátima Coronado2
1Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, United States.
Insights
Regular aspirin use significantly reduced atherosclerotic cardiovascular disease (ASCVD) mortality in individuals with elevated Lipoprotein(a) [Lp(a)]. This finding has implications for primary ASCVD prevention strategies.
Area of Science:
- Cardiovascular Medicine
- Epidemiology
- Pharmacology
Background:
- Lipoprotein(a) [Lp(a)] is a key risk factor for atherosclerotic cardiovascular disease (ASCVD), contributing to both atherosclerosis and thrombosis.
- Understanding the interplay between Lp(a) levels and the benefits of aspirin therapy is crucial for personalized cardiovascular risk management.
Purpose of the Study:
- To investigate the association between regular aspirin use and ASCVD mortality in a US population stratified by Lipoprotein(a) [Lp(a)] levels.
- To determine if elevated Lp(a) modifies the effect of aspirin on ASCVD mortality.
Main Methods:
- Analysis of a nationally representative US cohort (NHANES III, 1988-1994) with linked mortality data.
- Participants (aged 40-70, no clinical ASCVD) were categorized based on Lp(a) levels (≥50 mg/dL vs. <50 mg/dL) and regular aspirin use (≥30 times/month).
- Weighted Cox proportional hazards regression models were used to assess ASCVD mortality over a median 26-year follow-up.
Main Results:
- Among approximately 73 million US adults, regular aspirin use was associated with a 52% lower risk of ASCVD mortality in individuals with elevated Lp(a) (Hazard Ratio=0.48).
- No significant association between regular aspirin use and ASCVD mortality was observed in individuals without elevated Lp(a) (Hazard Ratio=1.01).
- A significant interaction (p=0.001) indicated that the benefit of aspirin on ASCVD mortality was confined to those with elevated Lp(a).
Conclusions:
- Regular aspirin use demonstrates a significant protective effect against ASCVD mortality in individuals with elevated Lipoprotein(a) [Lp(a)] and no prior clinical ASCVD.
- These findings suggest that Lp(a) status may be an important consideration for primary prevention strategies involving aspirin.
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.
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