Biomarker Predictors of Cardiac Hospitalization in Chronic Heart Failure: A Recurrent Event Analysis

Background: Identification of heart failure (HF) patients at risk for hospitalization may improve care and reduce costs. We evaluated 9 biomarkers as predictors of cardiac hospitalization in chronic HF. Methods and Results: In a multicenter cohort of 1,512 chronic HF outpatients, we assessed the association between 9 biomarkers and cardiac hospitalization with the use of a recurrent events approach. Over a median follow-up of 4 years, 843 participants experienced hospitalizations (total 2,178 hospitalizations). B-type natriuretic peptide (BNP) and troponin I (TnI) exhibited the strongest associations with risk of hospitalization (hazard ratio [HR] 3.8 [95% confidence interval (CI) 2.9-4.9] and HR 3.3 [95% CI 2.8-3.9]; 3rd vs 1st tertiles). Soluble Fms-like tyrosine kinase receptor 1 (sFlt-1) exhibited the next strongest association (HR 2.8 [95% CI 2.4-3.4]), followed by soluble Toll-like receptor 2 (BR 2.3 [95% CI 2.0-2.8]) and creatinine (HR 1.9 [95% CI 1.6-2.4]). Within ischemic/nonischemic subgroups, BNP and TnI remained most strongly associated. Except for creatinine, HRs for all biomarkers studied were smaller within the ischemic subgroup, suggesting greater importance of cardiorenal interactions in decompensation of ischemic HF. Conclusion: Although BNP and TnI exhibited the strongest associations with hospitalization, etiology-dependent associations for the remaining biomarkers suggest etiology-specific mechanisms for BF exacerbation. sFlt-1 exhibited a strong association with cardiac hospitalization, highlighting its potential role as a biomarker of HF morbidity.