Approximately 4 in 10 patients with HF have elevated inflammatory risk

Approximately 40% of patients with HF have elevated inflammatory risk, regardless of ejection fraction, according to the global POSEIDON study. Elevated hsCRP was consistently associated with a cardio-kidney-metabolic phenotype and more advanced HF.

This summary is based on the publication of Lam CSP, Contreras J, Darwesh R, et al. - Prevalence and predictors of high inflammatory risk in heart failure subtypes: findings from the global POSEIDON study. Eur J Heart Fail. 2026 May 10:xuag155. [Online ahead of print]. doi: 10.1093/ejhf/xuag155.

Introduction and methods

Background

Inflammation is increasingly recognized as an important contributor to HF pathophysiology [1-3]. hsCRP, a downstream biomarker of interleukin-6 (IL-6) signaling, is widely used to identify patients with elevated inflammatory risk and is currently being used to select participants for ongoing anti-inflammatory HF trials. However, contemporary global data on the prevalence of elevated inflammatory risk across HF phenotypes have been lacking.

Aim of the study

The aim of the study was to determine the prevalence of high inflammatory risk (defined as hsCRP ≥2 mg/L) and identify its clinical correlates in a large, prospective, real-world cohort of patients with HF across the full LVEF spectrum.

Methods

POSEIDON was a prospective, cross-sectional, global study conducted at 317 sites in 18 countries between 2023 and 2025 enrolling 18,904 individuals. This analysis included 11,809 adults with HF and available hsCRP measurements (3714 with HFpEF, 2176 with HFmrEF, and 5919 with HFrEF). Patients with recent hospitalization, unplanned visit or infection 60 days prior were excluded.

Main results

• Elevated hsCRP (≥2 mg/L) was present in:
  • 38.8% of patients with HFpEF.
  • 38.1% of patients with HFmrEF.
  • 38.2% of patients with HFrEF.
• Median hsCRP concentrations were similar across HF subtypes.
• Patients with elevated hsCRP consistently demonstrated a more severe cardio-kidney-metabolic phenotype across all HF subtypes. Compared with patients with hsCRP <2 mg/L, patients with elevated hsCRP were more likely to be female and to have hypertension, CKD, obesity, worse NYHA functional class, and higher NT-proBNP levels.
• Multivariable analyses identified smoking, rheumatic/autoimmune/inflammatory disease, obesity, reduced eGFR, dyslipidaemia, and worse NYHA functional class as independent predictors of elevated hsCRP.
• These independent predictors were largely consistent across HFpEF, HFmrEF, and HFrEF. The only significant interaction was obesity, which showed a stronger association with elevated hsCRP in HFpEF than in the other HF phenotypes (interaction P=0.001).
• IL-6 concentrations were similar across HF subtypes and showed a moderate positive correlation with hsCRP:
  • HFpEF: r=0.573.
  • HFmrEF: r=0.553.
  • HFrEF: r=0.578.
  • (All P<0.001).

Conclusion

In this large global real-world study, approximately 40% of patients with HF had elevated inflammatory risk, irrespective of HF subtype. Elevated hsCRP was consistently associated with a cardio-kidney-metabolic phenotype and more advanced HF across the HF spectrum.

Find this article online at Eur J Heart Fail.

References

1. Pugliese NR, Pellicori P, Filidei F, De Biase N, Maffia P, Guzik TJ, et al. Inflammatory pathways in heart failure with preserved left ventricular ejection fraction: implications for future interventions. Cardiovasc Res 2023;118:3536–55. https://doi.org/10.1093/cvr/cvac133
2. Schiattarella GG, Rodolico D, Hill JA. Metabolic inflammation in heart failure with preserved ejection fraction. Cardiovasc Res 2021;117:423–34. https://doi.org/10.1093/cvr/cvaa217
3. Adamo L, Rocha-Resende C, Prabhu SD, Mann DL. Reappraising the role of inflammation in heart failure. Nat Rev Cardiol 2020;17:269–85. https://doi.org/10.1038/s41569-019-0315-x