| Title: | Joint associations of Interleukin-6 and apolipoprotein B with major adverse cardiovascular events in the UK biobank |
| Journal: | Progress in Cardiovascular Diseases |
| Published: | 21 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42628893/ |
| DOI: | https://doi.org/10.1016/j.pcad.2026.08.008 |
Publication 20938
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Abstract
AIMS: The relative contributions of inflammatory and atherogenic lipoprotein pathways to residual cardiovascular risk remain unclear. We examined the joint and independent associations of interleukin-6 (IL-6) and apolipoprotein B (ApoB) with major adverse cardiovascular events (MACE) and mortality.</p>
METHODS: Among 34,064 UK Biobank participants free of prevalent atherosclerotic cardiovascular disease with Olink proteomics, multivariable Cox models estimated hazard ratios (HRs) for MACE (myocardial infarction (MI), stroke, or cardiovascular death), MACE components, and all-cause mortality. Models adjusted for demographics, HDL cholesterol, triglycerides, lipid-lowering therapy, hypertension, diabetes, smoking, eGFR, BMI, and high sensitivity C-reactive protein. Participants were additionally classified into four groups by median IL-6 and an ApoB threshold of 90 mg/dL.</p>
RESULTS: Over a median 13.6 years, 2551 (7.5%) MACE events occurred. In continuous models, IL-6 and ApoB were each independently associated with MACE (IL-6 HR 1.11 per SD, 95% CI 1.07-1.16; ApoB HR 1.12 per SD, 95% CI 1.07-1.17), and a simultaneous 1-SD increase in both biomarkers conferred 22% higher MACE risk. Associations were endpoint-specific: ApoB was strongest for MI (HR 1.20, 1.14-1.27), IL-6 for cardiovascular death (HR 1.20, 1.12-1.29) and all-cause mortality (HR 1.17, 1.14-1.20). In categorical analyses, MACE risk rose stepwise relative to the Low IL-6, Low ApoB reference: HR 1.22 (95% CI 1.05-1.41) for high ApoB alone, 1.33 (95% CI 1.15-1.55) for high IL-6 alone, and 1.55 (95% CI 1.34-1.78) for both.</p>
CONCLUSION: IL-6 and ApoB were independently associated with cardiovascular events, with atherogenic lipoprotein burden predominating for MI and inflammatory signaling for cardiovascular and all-cause death.</p>
11 Authors
- Patrick Cheon
- James T McParland
- Sean Doherty
- Rishi R Rikhi
- Bradley J Petek
- Shahzeb Khan
- Nicholas Chew
- Garima Sharma
- Jared Spitz
- Dinesh Kalra
- Michael D Shapiro
1 Application
| Application ID | Title |
|---|---|
| 97439 | Association of emerging cardiovascular disease biomarkers and markers of metabolic health with subclinical atherosclerosis, clinical atherosclerotic cardiovascular disease, and mortality |
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