title: Biomarker predictors of cardiac hospitalization in chronic heart failure: a recurrent event analysis.
abstract: 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.
  
  
  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 ≥ 1 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 (HR 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.
  
  
  CONCLUSIONS
  Although BNP and TnI exhibited the strongest associations with hospitalization, etiology-dependent associations for the remaining biomarkers suggest etiology-specific mechanisms for HF exacerbation. sFlt-1 exhibited a strong association with cardiac hospitalization, highlighting its potential role as a biomarker of HF morbidity.
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Esther
authors.initials: E
authors.lastname: Vorovich
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ky
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Lee
authors.initials: L
authors.lastname: Goldberg
authors.affiliation: Cardiovascular Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: James C
authors.initials: JC
authors.lastname: Fang
authors.affiliation: Cardiovascular Medicine, University of Wisconsin, Madison, Wisconsin.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Sweitzer
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Electronic address: thomas.cappola@uphs.upenn.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
mesh_terms: D015415:Biomarkers / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011379:Prognosis; D012008:Recurrence; D014336:Troponin / Q000097:blood; D014481:United States / Q000453:epidemiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D014336:Troponin; D020097:Natriuretic Peptide, Brain; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: BNP; recurrent hospitalization; sFlt-1; troponin