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September 24, 2026European Journal of Preventive CardiologyOpen Access

Higher chronic systemic inflammation linked to ~43% greater MACE risk.

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Why the study?

Mechanisms linking systemic inflammation to cardiac remodelling and cardiovascular risk remain incompletely understood, including the role of cytokine-mediated signalling and gene-environment interactions.

Does chronic systemic inflammation (measured by GlycA) associate with adverse cardiac remodelling and increased risk of major adverse cardiovascular events?

Population

488,079 UK Biobank participants with metabolomic, proteomic profiling, CMR imaging, and longitudinal outcomes

Comparison

Higher GlycA levels vs lower GlycA levels (lowest quintile)

Design

Population-based cohort study with machine learning and multivariable analyses

Follow-up

Longitudinal outcomes (duration not specified)

Key result

Higher chronic systemic inflammation (highest vs lowest GlycA quintile) was associated with a 43% increased risk of major adverse cardiovascular events (HR 1.43; 95% CI 1.38-1.49).

Authors

MCMattia CorianòSTShamin TahasildarLHLing Huang

Discussion

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Key expert perspectives

Captured external expert commentary on this paper, strongest first. Original sources are linked where available.

DODeclan O'ReganBHF Chair of Cardiovascular AI, Imperial College London

“The surprising aspect was the significant link between social factors and mental health with inflammation and heart damage – alongside more established risk factors like smoking and inactivity. There was also a strong genetic component, with some individuals being naturally more resistant or susceptible to the inflammatory damage resulting from different lifestyles.”

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DODeclan O'ReganBHF Chair of Cardiovascular AI, Imperial College London

“Chronic stress, from many different causes, may trigger long-term inflammation with no initial symptoms. But we can now see how this leads to adverse changes in the heart that precede any symptoms of cardiovascular disease. Social disadvantage is emerging as a key risk factor for heart disease and potentially an important public health intervention.”

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DBDr. Bryan WilliamsChief Scientific and Medical Officer

“Inflammation is part of the body's healing process, but there is also a darker side to it. This large-scale study found people with higher levels of inflammation experienced silent changes to the structure of their hearts and had a higher risk of major cardiac events including heart attacks and strokes.”

British Heart FoundationNews-Medical.Net

Overview

Should not yet change risk stratification or therapy; extends observational links between GlycA, IL-1–mediated remodeling, and MACE.

Key Points

  • To investigate how cytokine-mediated signaling, genetic background, and environmental exposures drive systemic inflammation, cardiac remodeling, and major adverse cardiovascular events.
  • Analyzed subsets of 488,079 UK Biobank participants with nuclear magnetic resonance-quantified glycoprotein acetyls (GlycA), proteomic profiling, machine learning-derived cardiac magnetic resonance imaging, and longitudinal outcomes.
  • Employed multivariable linear regression, mediation analysis of 80 inflammatory proteins, exposome-wide association modeling, and multi-ancestry polygenic risk scores to evaluate gene-environment interactions and risk of major adverse cardiovascular events (MACE).
  • Higher GlycA levels were associated with lower left ventricular indexed end-diastolic volume (β = -2.09) and stroke volume (β = -1.12), alongside compensatory increased heart rate (β = 1.38; all P < 10^-228).
  • Interleukin-1 receptor antagonist mediated 27% of the GlycA effect on end-diastolic volume (average causal mediated effect -0.53 [95% CI, -0.64 to -0.41]; P < 10^-16).
  • Participants in the highest GlycA quintile had higher MACE risk compared to the lowest (adjusted HR 1.43 [95% CI, 1.38-1.49]), with trunk fat and smoking as leading environmental drivers modified by polygenic risk.

Study Design

Type

Cohort (n=488,079)

Structured PICO

Does chronic systemic inflammation (measured by GlycA) associate with adverse cardiac remodelling and increased risk of major adverse cardiovascular events?

P
Population
488,079 UK Biobank participants with metabolomic, proteomic, and cardiac magnetic resonance imaging data evaluated for inflammation and cardiovascular risk.
E
Exposure
Higher levels of chronic inflammation quantified using glycoprotein acetyls (GlycA)
C
Comparator
Lower levels of chronic inflammation (lowest GlycA quintile)
O
Outcome
Cardiac phenotypes (left ventricular indexed end-diastolic volume, stroke volume, heart rate) and major adverse cardiovascular events (MACEs)hard clinical

Main Result

Hazard Ratio: 1.43 (95% CI 1.38–1.49)

Chronic systemic inflammation, driven by environmental and genetic factors, is associated with adverse cardiac remodelling and increased cardiovascular risk, with cytokines like IL-1 acting as potential mediators.

Trending Research#1 this week

A large UK Biobank study linking chronic inflammation from environmental and genetic factors to adverse cardiac remodeling and increased MACE risk is driving discussion on the social and biological determinants of heart disease.

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Cite This Study

Corianò et al. (2026) conducted a cohort in Cardiovascular risk and cardiac remodelling (n=488,079). Chronic systemic inflammation (GlycA levels) vs. Lowest GlycA quintile was evaluated on Major adverse cardiovascular events (MACEs) (HR 1.43, 95% CI 1.38-1.49). Higher chronic systemic inflammation (highest vs lowest GlycA quintile) was associated with a 43% increased risk of major adverse cardiovascular events (HR 1.43; 95% CI 1.38-1.49).

synapsesocial.com/papers/6ab4e005463eab04a4ba767fhttps://doi.org/10.1093/eurjpc/zwag435
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