High-sensitivity C-reactive protein and all-cause mortality in patients with ischemic heart failure with reduced ejection fraction

Background Systemic inflammation contributes to the development and progression of ischemic heart failure with reduced ejection fraction (HFrEF). High-sensitivity C-reactive protein (hs-CRP) may help identify high-risk patients, but determinants of elevated hs-CRP and its prognostic value in ischemic HFrEF require further clarification. Purpose To investigate clinical determinants of elevated hs-CRP and assess its association with all-cause mortality in patients with ischemic HFrEF. Methods In this prospective cohort study, 1,666 patients with ischemic HFrEF were stratified by baseline hs-CRP (<2 mg/L vs ≥2 mg/L). Baseline clinical, laboratory, and echocardiographic characteristics were compared between groups. Multivariable logistic regression was used to identify factors independently associated with elevated hs-CRP. Associations between hs-CRP and all-cause mortality were evaluated using multivariable Cox proportional hazards models adjusting for baseline covariates. Subgroup analyses were performed to assess effect modification by comorbidities and statin use. Results Compared with patients with hs-CRP <2 mg/L, those with hs-CRP ≥2 mg/L were older, had more advanced New York Heart Association (NYHA) functional class, greater comorbidity burden, and worse cardiac structure and function on echocardiography. In multivariable logistic regression, higher NYHA class, smoking, dyslipidemia, chronic heart failure, anemia, and chronic kidney disease were independently associated with elevated hs-CRP. Patients with elevated hs-CRP had a higher cumulative incidence of all-cause mortality (Figure 1). During a median follow-up of 3.4 years, hs-CRP ≥2 mg/L was independently associated with increased all-cause mortality (adjusted hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.06–1.91; p=0.018). Each 1-SD increase in log-transformed hs-CRP was associated with an 8% higher mortality risk. A linear association between hs-CRP and all-cause mortality was observed (Figure 2). Associations were generally consistent across subgroups, with a significant interaction by statin use (p for interaction=0.042). Conclusions Elevated hs-CRP identifies a high-risk phenotype in ischemic HFrEF, characterized by adverse clinical and echocardiographic features and independently higher all-cause mortality. These findings support hs-CRP as a pragmatic biomarker for risk stratification and a potential inflammation-related therapeutic target in ischemic HFrEF.