High-Sensitivity CRP Identified as a Powerful Prognostic Marker in Heart Failure with Reduced Ejection Fraction: AHJ, December 2025

According to a recent study, in heart failure with reduced ejection fraction (HFrEF) patients, elevated high-sensitivity C-reactive protein (hs-CRP) levels independently predict higher all-cause mortality and increased risk of cardiovascular, pulmonary, and renal complications. The authors suggest that hs-CRP may serve as a valuable prognostic marker to identify high-risk patients who might benefit from more intensive monitoring and targeted anti-inflammatory interventions.

These findings are published in December 2025 in American Heart Journal.

Inflammation’s Growing Importance in Heart Failure

Heart failure with reduced ejection fraction (HFrEF) is a complex clinical syndrome driven by neuro-hormonal, metabolic, and inflammatory disturbances. Although biomarkers such as NT-proBNP are routinely used to assess severity and prognosis, inflammation has emerged as a key contributor to adverse outcomes. High-sensitivity CRP, widely used in cardiovascular prevention, has not been fully characterized in its prognostic value for patients with established HFrEF. Understanding its significance could provide clinicians with an accessible, low-cost tool to identify patients at high risk of deterioration.

This new analysis using the TriNetX Global Collaborative Network addresses this knowledge gap by evaluating long-term outcomes in patients with varying levels of hs-CRP.

Study Overview

Researchers conducted a retrospective cohort study using electronic medical records from 130 healthcare organizations worldwide. Adults aged 18 to 90 years who had a documented diagnosis of HFrEF—defined as left ventricular ejection fraction ≤40%, were eligible for inclusion.

Patients were stratified into two groups based on hs-CRP levels: high (≥3.1 mg/L) and low (≤3.0 mg/L). After propensity score matching to balance demographic and clinical variables, the final analysis included two equal cohorts of 2,374 patients each. Outcomes were assessed over a five-year follow-up period, focusing on mortality as the primary endpoint and major cardiorenal and respiratory complications as secondary outcomes.

Key Findings from the Study

• Over five years, elevated hs-CRP was associated with significantly higher all-cause mortality (39% vs 28.7%).
• Elevated hs-CRP also correlated with significantly higher rates of acute kidney injury (27% vs 21.2%) and chronic kidney disease (21.7% vs 17.3%).
• Cardiovascular complications were also more common, including increased risk of coronary artery disease (24.4% vs 19%) and pulmonary edema (12.3 vs 9.5%)—conditions that worsen hospitalizations and quality of life.
• Notably, pulmonary embolism occurred nearly twice (2.4% vs 1.4%) as often in patients with high hs-CRP, highlighting a potential link between inflammation and thrombosis risk.

These findings position hs-CRP not merely as a general inflammatory marker but as a clinically meaningful prognostic indicator in the HFrEF population.

Clinical Importance: Using hs-CRP to Guide Risk Stratification and Therapeutic Decisions

These results underscore the potential value of incorporating hs-CRP into routine evaluation of patients with HFrEF. Elevated hs-CRP identifies individuals at higher risk of mortality and multisystem complications, enabling clinicians to prioritize them for closer monitoring, early intervention, and potentially more aggressive treatment strategies.

The findings also support the growing interest in targeting inflammation as a therapeutic approach in heart failure. Although specific anti-inflammatory treatments for HFrEF remain under investigation, identifying patients with an inflammatory phenotype could help tailor therapies, improve prognostication, and refine clinical decision-making. Routine hs-CRP measurement offers a simple, inexpensive, and widely accessible tool that could be easily integrated into existing heart failure management pathways.

Reference: Essien E, Carboo A, Nwaezeapu K, Agyekum A, Berchie P, Owusu-Achiaw J, Mensa-Yawson K, Bediako EM. High-Sensitivity C-Reactive Protein as a Prognostic Indicator in Heart Failure with Reduced Ejection Fraction: Evidence from the TriNetX Database. American Heart Journal. 2025 Dec 1;290:26.