Prevention & lipidsCohort study
Gene–environment interactions shape cytokine-mediated inflammation and cardiovascular risk
- Prospective cohort study
- population-based
- mediation analysis
- exposome-wide association study
Authors' conclusion
Chronic systemic inflammation is associated with reduced left ventricular volumes and increased cardiovascular risk in the community, with circulating cytokines and growth factors including IL-1 and TNF identified as potential mediators of these associations.
Study context
- Population
- UK Biobank participants with metabolomic and proteomic profiling, cardiac magnetic resonance (CMR) imaging and longitudinal outcomessubsets analysed
- Participants
- 488,079 participants
- Exposure
- Higher vs lower glycoprotein acetyls (GlycA)
Main finding
GlycA associations with CMR phenotypes and MACE
Adjusted hazard ratio
1.43
95% CI 1.38–1.49
Highest GlycA quintile vs Lowest GlycA quintile
adjusted HR 1.43 (95% CI 1.38–1.49)
As reported in the abstract
- Higher GlycA: LV indexed end-diastolic volume, β
- −2.09
- Higher GlycA: stroke volume, β
- −1.12
- Higher GlycA: heart rate, β
- 1.38
- P for LV volume, stroke volume and heart rate associations
- all P<10-228
Observational data: associations, not effects.
Further findings
Mediation of GlycA effect on end-diastolic volume by IL-1 receptor antagonist
- Proportion mediated
- 27%
- Average causal mediated effect
- −0.53 (95% CI −0.64 to −0.41; P<10-16)
Determinants of GlycA
- Trunk fat mass, β
- 0.35
- Current smoking, β
- 0.39
- Trunk fat mass, current smoking, psychological distress and low socioeconomic status strongest determinants
- all P<10-50
Gene–environment interaction
- CV polygenic risk scores modified associations between environmental exposures, inflammation and MACE
Original publication
Gene–environment interactions shape cytokine-mediated inflammation and cardiovascular risk. Eur J Prev Cardiol. Published 18 September 2026. doi:10.1093/eurjpc/zwag435
Summarised from the published abstract; every number is checked against it