Prevention & lipids

The Prognostic Value of Serum Interleukin-6 Concentrations for 9 Cardiovascular and Mortality Outcomes: The Cross Cohort Collaboration (CCC)

J Am Coll CardiolPublished Pooled individual-participant data analysis of prospective cohort studies

Main findingResult — go to the resultAdjusted hazard ratio 2.12 95% CI 1.88–2.39

Authors' conclusion

In this large, harmonized, individual-level participant data analysis of prospective cohorts, higher IL-6 concentrations were strongly associated with 9 cardiovascular and mortality outcomes after controlling for clinical covariates.

Study context

Population
Community-based, diverse prospective cohorts with blood IL-6 measurements
Participants
59,396 participants14 cohorts
Exposure
Highest vs lowest IL-6 quartile
Outcome
Incident CV events and mortality (MI, stroke, AF, HF, total CHD, total CVD, all-cause mortality, CVD-specific mortality, CHD-specific mortality)
Methodological detailsmultiethnic, 14 cohorts, multivariable-adjusted
  • Multiethnic
  • 14 cohorts
  • Multivariable-adjusted

Main finding

As reported in the abstract

Adjusted hazard ratio

2.12

95% CI 1.88–2.39

Highest IL-6 quartilevs Lowest IL-6 quartile
adjusted HR 2.12 (95% CI 1.88–2.39)
Weakest association: MI, HR
1.45 (1.28-1.64) (95% CI)

Observational data: associations, not effects.

Further findings

Subgroups (CKD, DM, high-sensitivity C-reactive protein (hsCRP), BMI) and secondary prevention

Findings robust and consistent in all key subgroups and in secondary prevention

Discrimination (AUC)

IL-6 alone showed modest additive discrimination beyond hsCRP for stroke, HF, cardiovascular disease (CVD), coronary heart disease (CHD) and mortality

Original publication

The Prognostic Value of Serum Interleukin-6 Concentrations for 9 Cardiovascular and Mortality Outcomes: The Cross Cohort Collaboration (CCC). J Am Coll Cardiol. Published 27 May 2026. doi:10.1016/j.jacc.2026.04.015

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