IL-6 May Modify Coronary Artery Disease Risk Associated with Elevated Lp(a): JAMA
Researchers have found in a primary prevention cohort study that the risk of incident coronary artery disease (CAD) associated with elevated lipoprotein(a) [Lp(a)] is influenced by levels of interleukin-6 (IL-6), a key inflammatory biomarker. Individuals with lower IL-6 levels exhibited a lower Lp(a)-related CAD risk, suggesting that inflammation plays an important role in mediating cardiovascular risk. These findings support the use of IL-6 as a biomarker of inflammatory risk and indicate that it may help identify patients who could benefit from targeted preventive strategies, particularly among those with elevated Lp(a). The study was published in JAMA Cardiology by Niekbachsh M. and colleagues.
For thorough assessment of the interplay between lipid profile and inflammation, recruitment took place from March 2006 until October 2010 within a population-based sample of United Kingdom adults. The researchers specifically enrolled the members of the UK Biobank who had no previous history of either coronary artery disease or aortic valve stenosis and had gone through the procedure of comprehensive plasma proteomics. Their subsequent analysis for the duration of June 2025 until April 2026 involved classification of exposures as a function of the lipoprotein(a) level, which divided the subjects into those with levels less than 125 nmol/L and those with the levels of 125 nmol/L or above, in addition to measurement of the inflammatory biomarkers of interleukin-1β, interleukin-18, interleukin-6, and neutrophil to lymphocyte ratio.
Key findings:
- Statistical analysis conducted on the study produced convincing quantitative data based on the huge number of 43,512 participants from the UK Biobank dataset.
- Among this strong baseline sample, 6,975 people or exactly 16.0% of the population had significantly high lipoprotein(a) levels of 125 nmol/L or greater.
- Demographically, 24,079 participants, which constitutes 55.3%, were females, and the mean age in years with its standard deviation was 56.5 (8.2).
- Researchers followed up the participants for a very long period of time and reported the median follow-up with quartiles 1-3 at 13.5 (12.7-14.3) years for incident coronary artery disease and 13.6 (12.9-14.4) years for incident aortic valve stenosis.
- Using multivariable-adjusted Cox proportional hazard model, the highest association with the two diseases was found in interleukin-6 among the various inflammatory markers used.
- In particular, interleukin-6 concentrations actually affected the lipoprotein(a)-mediated risk for developing coronary artery disease with a hazard ratio of 1.43 (95% confidence interval, 1.25-1.63) among patients with lipoprotein(a) concentrations of 125 nmol/L or greater in quartile 4 of interleukin-6.
- On the other hand, patients allocated to quartile 1 of interleukin-6 actually showed an even safer hazard ratio of 1.09 (95% confidence interval, 0.85-1.38) that produced a significant correlation (P = 0.008).
- Also, despite the significance of the P value for interaction of .02 obtained with the interaction between lipoprotein(a) and neutrophil to lymphocyte ratio, it was only considered suggestive and did not stay significant when corrected for multiple testing, with no inflammatory biomarkers being able to modify the risk for aortic valve stenosis mediated by lipoprotein(a).
Conclusively, in this study of primary prevention, the risk for incident coronary artery disease conferred by lipoprotein(a) is affected by interleukin-6, such that there is lower associated risk under conditions of lower levels of inflammatory markers. This suggests that interleukin-6 is a highly actionable marker of inflammatory risk that may modify the risk for coronary artery disease posed by lipoprotein(a). These conclusive multivariate results constitute the bedrock of modern cardiovascular medicine since it confirms that lipid levels need to be assessed together with inflammatory markers.
Reference:
Mohammadnia N, Li L, Ezzat D, et al. Lipoprotein(a), Inflammation, and Risk of Coronary Artery Disease and Aortic Valve Stenosis. JAMA Cardiol. Published online June 24, 2026. doi:10.1001/jamacardio.2026.1852
