Elevated lipoprotein(a) [Lp(a)] is a known causal risk factor for atherosclerotic cardiovascular disease (ASCVD), with vascular inflammation considered a key mechanism.² A new analysis has investigated whether interleukin-6 (IL-6), a biomarker of inflammation, can help to further stratify cardiovascular risk in individuals with elevated Lp(a). The study analysed data from two large, independent primary prevention cohorts: the Multi-Ethnic Study of Atherosclerosis (MESA) and the UK Biobank (UKB).¹

This analysis utilised data from 6,514 participants in the MESA cohort and 26,574 participants from the UKB. Researchers used Cox proportional hazard models to evaluate the associations between Lp(a) and IL-6 levels with several cardiovascular outcomes. The models were adjusted for traditional cardiovascular risk factors and high-sensitivity C-reactive protein (hsCRP).

The primary outcomes assessed were:

• Coronary heart disease (CHD), defined as myocardial infarction or resuscitated cardiac arrest.
• ASCVD, defined as CHD and ischaemic stroke.
• Peripheral vascular disease (PVD).

Participants were also categorised into groups based on their Lp(a) level (≤50 or >50 mg/dL) and IL-6 level (≤ median or > median) to assess combined risk.

The analysis found that both Lp(a) and IL-6 were independently associated with CHD events. In the MESA cohort, the hazard ratio (HR) per standard deviation was 1.13 (95% CI: 1.04–1.23) for Lp(a) and 1.22 (95% CI: 1.10–1.35) for IL-6. Similarly, in the UKB cohort, the HR was 1.11 (95% CI: 1.09–1.13) for Lp(a) and 1.19 (95% CI: 1.15–1.24) for IL-6. These associations did not significantly change when both biomarkers were evaluated in the same model, and no significant interaction was observed. Similar results were noted for ASCVD and PVD outcomes.

When participants were grouped by both biomarker levels, the analysis revealed that the highest risk for CHD was among individuals with both high Lp(a) (>50 mg/dL) and high IL-6 (> median) levels. This group had an HR for CHD of 1.72 (95% CI: 1.25–2.36) in MESA and 1.39 (95% CI: 1.12–1.72) in UKB, compared to the group with low levels of both markers.

This study demonstrates that Lp(a) and IL-6 are independent predictors of ASCVD risk in primary prevention populations. The authors concluded that in two independent cohorts, "Lp(a) and IL-6 were independent predictors of ASCVD risk, and their combination identified individuals at highest risk."¹ These findings suggest that assessing both Lp(a) and IL-6 may improve cardiovascular risk stratification, helping to identify a high-risk patient subgroup that could be targeted for more intensive preventive measures.

References

1. Bhatia HS, McParland J, Rikhi R, et al. Association of Lipoprotein(a) and Interleukin-6 With Cardiovascular Risk: MESA and UK Biobank. J Am Coll Cardiol. 2025;86(21):2000-2013. https://doi.org/10.1016/j.jacc.2025.08.101

2. Bhatia HS, Wilkinson MJ. Lipoprotein(a): evidence for role as a causal risk factor in cardiovascular disease and emerging therapies. J Clin Med. 2022;11(20):6040. https://doi.org/10.3390/jcm11206040

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