Elevated inflammatory risk was identified in nearly 40% of patients with heart failure (HF) across the ejection fraction spectrum in a large global cohort analysis. The POSEIDON study, published in the European Journal of Heart Failure, evaluated the prevalence and clinical correlates of elevated high-sensitivity C-reactive protein (hsCRP) across HF phenotypes in routine clinical practice.

POSEIDON prospectively enrolled 18,904 individuals across 317 sites in 18 countries between 2023 and 2025. The analysis included 11,809 patients with HF and available hsCRP measurements, including 3714 with heart failure with preserved ejection fraction (HFpEF), 2176 with heart failure with mildly reduced ejection fraction (HFmrEF), and 5919 with heart failure with reduced ejection fraction (HFrEF). Patients with recent infections were excluded.
Elevated hsCRP levels (≥2 mg/L) were observed in 38.8% of patients with HFpEF, 38.1% with HFmrEF, and 38.2% with HFrEF. Across HF subtypes, patients with elevated hsCRP were more likely to be female and to have chronic kidney disease, obesity, worse New York Heart Association (NYHA) functional class, and higher N-terminal pro-B-type natriuretic peptide levels.

Multivariable analyses identified smoking, rheumatic, autoimmune, or inflammatory disease, obesity, reduced estimated glomerular filtration rate (eGFR), dyslipidemia, and worse NYHA class as independent predictors of elevated hsCRP. Body mass index showed a stronger association with hsCRP in HFpEF than in other HF phenotypes (interaction P=0.001). Interleukin-6 showed a moderate correlation with hsCRP across all HF subtypes.

The findings showed a substantial prevalence of elevated inflammatory risk across HF phenotypes and linked elevated hsCRP with a cardio-kidney-metabolic profile and greater HF severity.