title: Prediction of long-term survival in chronic heart failure by multiple biomarker assessment: a 15-year prospective follow-up study.
abstract: BACKGROUND
  In chronic heart failure (CHF), several plasma biomarkers identify subjects at risk of death over the midterm. However, their long-term predictive value in the context of other candidate predictors has never been assessed. This information may prove valuable in the management of a chronic disease with a long natural history, as CHF is today.
  
  
  OBJECTIVE
  We aimed to assess the very-long-term prognostic power of a set of biomarkers to identify CHF patients at highest risk for all-cause mortality.
  
  
  METHODS
  A group of 106 consecutive outpatients with CHF (85 male and 21 female, median age 56 y) was followed for 15 years. Echocardiographic tracings and blood samples were collected at study entry to evaluate cardiac function, plasma atrial natriuretic peptide (ANP), aldosterone, and erythropoietin, and plasma renin activity. The relationships between biomarkers, clinical and echocardiographic variables, and mortality were assessed.
  
  
  RESULTS
  After 15 years, 86 of the 106 patients (81%) had died. Multivariate analysis showed that ANP was the best independent predictor of survival over several clinical, echocardiographic, and humoral variables (hazard ratio: 5.62, 95% confidence interval: 3.37-9.39, P < 0.001 for plasma levels < median value of 71 pg/mL). Plasma renin activity and erythropoietin provided prognostic information in univariate analysis, but lost their predictive power when adjusted for covariates.
  
  
  CONCLUSIONS
  The present study represents the longest available follow-up of patients with CHF evaluating the prognostic power of multiple biomarkers. It shows that a simple assessment of plasma ANP levels is the strongest long-term predictor of death in all stages of heart failure.
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, 2nd Faculty of Medicine, Sapienza University, Rome, Italy. massimo.volpe@uniroma1.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Pietro
authors.initials: P
authors.lastname: Francia
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tocci
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.forename: Sara
authors.initials: S
authors.lastname: Cangianiello
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Elena Rao
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.forename: Mario
authors.initials: M
authors.lastname: Condorelli
mesh_terms: D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality*; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D004921:Erythropoietin; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin