Lp(a)'s coronary risk is amplified in patients with high cholesterol or triglycerides, but not for aortic stenosis or stroke, UK Biobank study of 127,958 finds (Am J Prev Cardiol 2025)

Original title: The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank

Am J Prev Cardiol · 22 May 2025 · 7

Ao L, Noordam R, Jukema JW, van Heemst D, Willems van Dijk K

This UK Biobank study included 127,958 unrelated European-ancestry participants (54.7% women) without baseline coronary artery disease (CAD), calcific aortic valve stenosis (CAVS) or ischaemic stroke, to test whether Lp(a)'s associated risk varies by co-occurring cardiovascular risk factors. Each 10 mg/dL increase in Lp(a) was associated with higher risk of CAD (HR 1.05, 95% CI 1.04-1.06), CAVS (HR 1.06, 95% CI 1.04-1.09) and, more weakly, ischaemic stroke (HR 1.01, 95% CI 0.99-1.03). For CAD specifically, significant interactions were found between Lp(a) and total cholesterol (P = 0.001), LDL-C (P = 4e-4) and triglycerides (P = 0.026): participants with Lp(a) of 50 mg/dL or above who were also in the highest quartile of total cholesterol, LDL-C or triglycerides showed additive interaction, with relative excess risk due to interaction (RERI) of 0.42, 0.44, and 0.39 respectively. No such interactions were found for CAVS or ischaemic stroke. The authors conclude Lp(a)-associated CAD risk is particularly pronounced in those whose cholesterol and triglyceride levels already exceed guideline thresholds.

Original abstract

Background: : Although Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease, it is unclear whether the associated risk is similar in the presence of other concomitant risk factors. Here, we aimed to investigate the interactions between Lp(a) and common cardiovascular risk factors on coronary artery disease (CAD), calcific aortic valve stenosis (CAVS) and ischemic stroke (IS).

Methods: : We included 127,958 unrelated European-ancestry participants from UK Biobank (54.7 % women) with data available on Lp(a) and without a baseline history of CAD, CAVS and IS. Multivariable-adjusted Cox proportional hazards interaction models were used to study whether the associations of Lp(a) with outcomes varied based on the level of total cholesterol (Total-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG) and other cardiovascular risk factors.

Results: : Higher Lp(a) levels were associated with higher risks of CAD, CAVS and IS. Per 10 mg/dL increase in Lp(a), hazard ratios [95 % confidence interval] were 1.05 [1.04, 1.06], 1.06 [1.04, 1.09], and 1.01 [0.99, 1.03] for CAD, CAVS and IS, respectively. For CAD, interactions were observed between Lp(a) and Total-C (Pinteraction =0.001), LDL-C (Pinteraction =4e-4) and TG (Pinteraction =0.026). In more detail, participants with Lp(a) ≥ 50 mg/dL in the highest quartile of Total-C, LDL-C and TG showed evidence of additive interaction in CAD, with relative excess risk due to interaction (RERI) of 0.42 (0.17, 0.67), 0.44 (0.18, 0.71), and 0.39 (0.12, 0.67), respectively. No such interactions were observed in CAVS and IS.

Conclusions: Lp(a)-associated CAD risk seems to particularly affect those having levels of Total-C, LDL-C and TG above the thresholds from clinical guidelines.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.