Lp(a) and interleukin-6 are independent, additive predictors of coronary events: MESA and UK Biobank (Bhatia et al., JACC 2025)

Original title: Association of Lipoprotein(a) and Interleukin-6 With Cardiovascular Risk: MESA and UK Biobank

J Am Coll Cardiol · 25 November 2025 · 6

Bhatia HS, McParland J, Rikhi R, Tsai M, Szklo M, Tsimikas S, Yeang C, Shapiro MD

In 6,514 MESA and 26,574 UK Biobank participants, Lp(a) (hazard ratios 1.13 and 1.11 per unit) and IL-6 (1.22 and 1.19) each predicted CHD, ASCVD and peripheral vascular disease independently without interaction, and the combination of high Lp(a) and high IL-6 identified the highest-risk group (hazard ratios 1.72 and 1.39). Sets up the question of whether IL-6 inhibition and Lp(a) lowering are complementary.

Original abstract

Background: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease (ASCVD) risk, and vascular inflammation is one mechanism through which Lp(a) causes ASCVD.

Objectives: The authors aimed to evaluate whether interleukin-6 (IL-6), a biomarker associated with inflammation and cardiovascular disease, helps risk-stratify individuals with elevated Lp(a).

Methods: Data from participants in the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 6,514) and the UK Biobank (UKB) (n = 26,574) were used for this analysis. The associations between Lp(a) and IL-6 with coronary heart disease (CHD) (defined as myocardial infarction or resuscitated cardiac arrest), ASCVD (CHD and ischemic stroke), and peripheral vascular disease (PVD) were evaluated separately and with mutual adjustment in Cox proportional hazard models adjusted for traditional cardiovascular risk factors and high-sensitivity C-reactive protein (hsCRP). HRs were presented per standard deviation. Participants were also grouped by Lp(a) level (≤50 or >50 mg/dL [125 nmol/L]) and IL-6 level (≤ median or > median) in similar models.

Results: Participants with higher IL-6 levels were more likely to have higher body mass index, systolic blood pressure, triglycerides, and hsCRP with lower high-density lipoprotein cholesterol. Lp(a) (HR: 1.13; 95% CI: 1.04-1.23 in MESA; HR: 1.11; 95% CI: 1.09-1.13 in UKB) and IL-6 (HR: 1.22; 95% CI: 1.10-1.35 in MESA; HR: 1.19; 95% CI: 1.15-1.24 in UKB) were both independently associated with CHD events when evaluated separately. When evaluated together, no significant change was noted, and interaction testing was not significant. Similar results were seen for ASCVD and PVD. When participants were categorized by both Lp(a) and IL-6 levels, the strongest association for each outcome was noted when both levels were high (for CHD: HR: 1.72; 95% CI: 1.25-2.36 in MESA; HR: 1.39; 95% CI: 1.12-1.72 in UKB).

Conclusions: In 2 independent primary prevention cohorts, Lp(a) and IL-6 were independent predictors of ASCVD risk, and their combination identified individuals at highest risk.

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