Article Impact Level: HIGH Data Quality: STRONG Summary of European Heart Journal, ehaf297. https://doi.org/10.1093/eurheartj/ehaf297 Dr. Diane E. MacDougall et al.
Points
- Elevated lipoprotein(a) levels were continuously associated with increased risk of recurrent atherosclerotic cardiovascular events in a large, diverse cohort of over 273,000 individuals with existing ASCVD.
- Risk for recurrent events rose progressively with Lp(a) levels, reaching a hazard ratio of 1.45 for those with levels ≥300 nmol/L compared to individuals with levels below 15 nmol/L.
- Women and Black individuals were more likely to have elevated Lp(a), highlighting significant demographic disparities in cardiovascular risk profiles.
- High-impact LDL cholesterol-lowering therapies such as PCSK9 inhibitors and high-dose statins significantly reduced recurrent event risk in patients with Lp(a) levels ≥180 nmol/L.
- The study underscores the need for targeted treatment strategies, including aggressive LDL lowering, to manage elevated Lp(a) and reduce cardiovascular recurrence in high-risk patients.
Summary
This study aimed to evaluate the association between lipoprotein(a) [Lp(a)] levels and the risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events, and the potential mitigating effects of LDL cholesterol-lowering therapies. Data were obtained from a cohort of 273,770 individuals with ASCVD, including a broad demographic representation of sex, race/ethnicity, and comorbidities. The cohort was followed for a median of 5.4 years, during which the incidence of recurrent ASCVD events such as myocardial infarction and stroke was assessed. Results showed that higher Lp(a) levels were continuously associated with increased risk for recurrent ASCVD events. Hazard ratios for recurrent ASCVD events were calculated for various Lp(a) levels, with an adjusted hazard ratio of 1.04 (95% CI: 1.01–1.07) for Lp(a) levels between 15–79 nmol/L, 1.15 (95% CI: 1.12–1.19) for 80–179 nmol/L, 1.29 (95% CI: 1.25–1.33) for 180–299 nmol/L, and 1.45 (95% CI: 1.39–1.51) for Lp(a) ≥300 nmol/L, compared to Lp(a) levels <15 nmol/L.
The study also highlighted significant demographic differences in Lp(a) levels, with women and Black individuals likelier to have elevated Lp(a) levels. The study further examined the impact of LDL cholesterol-lowering therapies, particularly high-impact drugs like PCSK9 inhibitors and high-dose statins, on patients with elevated Lp(a). Among those with Lp(a) levels ≥180 nmol/L, the use of high-impact LDL-lowering therapies significantly reduced the risk of recurrent cardiovascular events, suggesting a potential therapeutic avenue for managing high Lp(a) levels in ASCVD patients.
In conclusion, this study provides robust evidence that elevated Lp(a) levels are a continuous risk factor for recurrent cardiovascular events in patients with ASCVD. Furthermore, the findings underscore the importance of LDL cholesterol-lowering therapy, particularly high-impact options, in mitigating the cardiovascular risks associated with elevated Lp(a), emphasizing the need for personalized treatment strategies for patients with high Lp(a) levels.
Link to the article: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf297/8124887
References MacDougall, D. E., Tybjærg-Hansen, A., Knowles, J. W., Stern, T. P., Hartsuff, B. K., McGowan, M. P., Baum, S. J., Wilemon, K. A., & Nordestgaard, B. G. (2025). Lipoprotein(A) and recurrent atherosclerotic cardiovascular events: The US Family Heart Database. European Heart Journal, ehaf297. https://doi.org/10.1093/eurheartj/ehaf297
