title: The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea.
abstract: The risk stratification in patients presenting with acute dyspnoea remains a challenge. We therefore conducted a prospective, observational cohort study enrolling 292 patients presenting to the emergency department with acute dyspnoea. A proteomic approach for antibody-free targeted protein quantification based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth factor)-binding protein 2] levels. Final diagnosis and death during follow-up were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final diagnosis in 54% of patients. In both AHF (P<0.001) and non-AHF (P=0.015) patients, LTBP2 levels at presentation were significantly higher in non-survivors compared with survivors with differences on median levels being 2.2- and 1.5-fold respectively. When assessing the cause of death, LTBP2 levels were significantly higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2 powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95% CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic) curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of 0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)]. Importantly, the predictive potential of LTBP2 persisted in patients with AHF as the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC 0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64); P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful predictor of all-cause mortality, and particularly pulmonary death. Cause-specific prediction of death would enable targeted prevention, e.g. with pre-emptive antibiotic therapy.
authors.affiliation: Department of Internal Medicine, University Hospital Basel, Switzerland. breidthardtt@uhbs.ch
authors.forename: Tobias
authors.initials: T
authors.lastname: Breidthardt
authors.forename: Griet
authors.initials: G
authors.lastname: Vanpoucke
authors.forename: Mihael
authors.initials: M
authors.lastname: Potocki
authors.forename: Tamina
authors.initials: T
authors.lastname: Mosimann
authors.forename: Ronny
authors.initials: R
authors.lastname: Ziller
authors.forename: Gregoire
authors.initials: G
authors.lastname: Thomas
authors.forename: Wouter
authors.initials: W
authors.lastname: Laroy
authors.forename: Piet
authors.initials: P
authors.lastname: Moerman
authors.forename: Thenral
authors.initials: T
authors.lastname: Socrates
authors.forename: Beatrice
authors.initials: B
authors.lastname: Drexler
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
authors.forename: Koen
authors.initials: K
authors.lastname: Kas
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000208:Acute Disease; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D002423:Cause of Death; D004417:Dyspnea / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D015415:Biomarkers; C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins