title: Metabonomics analysis of plasma reveals the lactate to cholesterol ratio as an independent prognostic factor of short-term mortality in acute heart failure.
abstract: OBJECTIVE
  Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value.
  
  
  METHODS
  We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for (1)H NMR--based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings.
  
  
  RESULTS
  Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P = 0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort.
  
  
  CONCLUSIONS
  This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care.
authors.affiliation: INSERM I2MC, UMR 1048, Université UPS, Equipe, Obésité et Insuffisance Cardiaque: Approches Moléculaires et Cliniques, Toulouse, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Desmoulin
authors.forename: Michel
authors.initials: M
authors.lastname: Galinier
authors.forename: Charlotte
authors.initials: C
authors.lastname: Trouillet
authors.forename: Matthieu
authors.initials: M
authors.lastname: Berry
authors.forename: Clément
authors.initials: C
authors.lastname: Delmas
authors.forename: Annie
authors.initials: A
authors.lastname: Turkieh
authors.forename: Pierre
authors.initials: P
authors.lastname: Massabuau
authors.forename: Heinrich
authors.initials: H
authors.lastname: Taegtmeyer
authors.forename: Fatima
authors.initials: F
authors.lastname: Smih
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouet
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019344:Lactic Acid / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve
chemical_list: D019344:Lactic Acid; D002784:Cholesterol