Higher levels of lipoprotein(a) (Lp(a)) are an established causal risk factor for incident atherosclerotic cardiovascular disease (ASCVD), but its role in recurrent events has been less clear.² A new large-scale study has found that in patients with existing ASCVD, higher Lp(a) levels are associated with a continuously increasing risk of recurrent events, irrespective of sex or race/ethnicity.¹

This observational cohort study analysed US medical claims data from the Family Heart Database between 2012 and 2022. The cohort included 273,770 adults (43% women, 57% men) with a diagnosis of established ASCVD and at least one Lp(a) measurement. The population was diverse, including Black (8%), Hispanic (9%), and White (59%) individuals.

The primary endpoint was the time to the first recurrent ASCVD event, defined as hospitalisation for myocardial infarction, other acute coronary syndromes, ischaemic stroke, or procedures such as percutaneous coronary intervention or coronary artery bypass grafting. The median follow-up period was 5.4 years.

During follow-up, 41,687 individuals (15%) experienced a recurrent ASCVD event. The analysis revealed a continuous relationship between higher Lp(a) levels and increased risk. After adjusting for age, sex, and race/ethnicity, the hazard ratios (HR) for recurrent ASCVD events increased with each Lp(a) category compared to those with levels <15 nmol/L.

The adjusted HRs were:

• 1.04 (95% CI 1.01–1.07) for Lp(a) levels of 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
• 1.45 (95% CI 1.39–1.51) for ≥300 nmol/L

These findings were consistent across subgroups based on sex, race/ethnicity, type of baseline ASCVD, and diabetes status. The study also suggested that high-impact LDL cholesterol-lowering therapy, particularly with PCSK9 inhibitors, may partially mitigate the risk associated with very high Lp(a) levels (≥180 nmol/L).

These findings underscore the importance of Lp(a) as a risk factor for secondary prevention in a diverse patient population. The researchers concluded that, "In 273,770 individuals with ASCVD, higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD events regardless of sex and race/ethnicity that may have been partially mitigated by high impact LDL cholesterol-lowering therapy."¹ The data highlight the need to measure Lp(a) when assessing residual risk in all individuals with ASCVD.

This study was funded by The Family Heart Foundation.

References

1. MacDougall DE, Tybjærg-Hansen A, Knowles JW, et al. Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US Family Heart Database. Eur Heart J. 2025;46(44):4762–4775. https://doi.org/10.1093/eurheartj/ehaf297

2. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43:3925–46. https://doi.org/10.1093/eurheartj/ehac361

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