Joint Associations of High-Sensitivity C-Reactive Protein and Albumin with Incident Heart Failure: A Prospective Cohort Study.

Background: Although elevated high-sensitivity C-reactive protein (hs-CRP) and lower albumin (ALB) are each associated with increased heart failure (HF) risk, and inflammation and hypoalbuminemia are correlated in HF patients, evidence on their joint associations with incident HF is lacking. While C-reactive protein to albumin ratio (CAR) has been associated with HF, it shows no advantage over CRP alone. We therefore aimed to examine the independent and joint associations of hs-CRP and ALB with incident HF and to compare their predictive value with CAR. Methods: In this prospective observational cohort study, we included 61,488 participants from the Kailuan Study without HF at baseline. hs-CRP and ALB were measured in 2010, and participants were stratified into four groups according to hs-CRP (<2 or ≥2 mg/L) and ALB (<46.1 or ≥46.1 g/L), with 46.1 g/L representing the cohort median. Incident HF was identified through hospital records and insurance data. Cox models estimated hazard ratios (HRs), and predictive performance was assessed using the C-index, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). Results: Over 11.3 years of follow-up, 1444 participants (2.35%) developed HF. Significant additive interactions were observed between hs-CRP, ALB, and HF risk. Compared with normal hs-CRP and above-median ALB, elevated hs-CRP and below-median ALB were associated with a 2.01-fold higher HF risk (HR 2.01, 95% CI 1.73-2.34). Among the evaluated models, the model incorporating the joint hs-CRP-ALB classification had the highest numerical C-index (0.7803). Compared with the fully adjusted model, the NRI and IDI were 0.2496 and 0.0012, respectively. Conclusion: Hs-CRP and ALB are independently and jointly associated with HF risk.