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Updated: Jun 25, 2026

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Published on: October 12, 2017

Lipoprotein(a), Inflammation, and Risk of Coronary Artery Disease and Aortic Valve Stenosis

Niekbachsh Mohammadnia1,2, Linke Li2,3,4, Daniel Ezzat2,4,5

  • 1Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

JAMA Cardiology
|June 24, 2026
PubMed

Insights

Elevated lipoprotein(a) [Lp(a)] risk for coronary artery disease (CAD) is modified by interleukin-6 (IL-6) levels. Lower IL-6 levels reduce Lp(a)-associated CAD risk in primary prevention.

Area of Science:

  • Cardiovascular Medicine
  • Inflammation Research
  • Proteomics

Background:

  • Elevated lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular diseases, but its clinical impact varies.
  • Low-grade inflammation's role in modifying Lp(a)-associated cardiovascular risk is debated.

Purpose of the Study:

  • To investigate if inflammatory biomarkers modify the risk of coronary artery disease (CAD) and aortic valve stenosis (AS) associated with elevated Lp(a).
  • To identify specific inflammatory markers that interact with Lp(a) to influence cardiovascular risk in a primary prevention setting.

Main Methods:

  • Analysis of plasma proteomic profiles from UK Biobank participants (n=43,512) without prevalent CAD or AS.
  • Utilized multivariable-adjusted Cox proportional hazards models to assess interactions between Lp(a) levels and inflammatory biomarkers (IL-1β, IL-18, IL-6, NLR).
  • Primary outcome: incident CAD; Secondary outcome: incident AS, with median follow-up of 13.5 years.

Main Results:

  • Interleukin-6 (IL-6) significantly modified Lp(a)-associated risk for incident CAD (P for interaction = .008).
  • Higher IL-6 levels amplified Lp(a)-associated CAD risk, while lower IL-6 levels attenuated it.
  • No significant modification of Lp(a)-associated risk for incident AS by any tested inflammatory biomarker was observed.

Conclusions:

  • Interleukin-6 is identified as a key inflammatory biomarker that modifies the risk of coronary artery disease associated with elevated lipoprotein(a).
  • Lower IL-6 levels may mitigate the cardiovascular risk conferred by high Lp(a) in primary prevention.
  • Findings highlight the potential of targeting inflammation to manage Lp(a)-related cardiovascular risk.
Abstract

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