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.
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July 13 2012
The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea
Tobias Breidthardt;
*Departments of Internal Medicine, Nephrology and Cardiology, University Hospital Basel, Switzerland
Correspondence: Dr Tobias Breidthardt (email [email protected]).
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Griet Vanpoucke;
Griet Vanpoucke
†Pronota NV, Zwijnaarde (Ghent), Belgium
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Mihael Potocki;
Mihael Potocki
*Departments of Internal Medicine, Nephrology and Cardiology, University Hospital Basel, Switzerland
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Tamina Mosimann;
Tamina Mosimann
*Departments of Internal Medicine, Nephrology and Cardiology, University Hospital Basel, Switzerland
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Ronny Ziller;
Ronny Ziller
*Departments of Internal Medicine, Nephrology and Cardiology, University Hospital Basel, Switzerland
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Gregoire Thomas;
Gregoire Thomas
†Pronota NV, Zwijnaarde (Ghent), Belgium
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Wouter Laroy;
Wouter Laroy
†Pronota NV, Zwijnaarde (Ghent), Belgium
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Piet Moerman;
Piet Moerman
†Pronota NV, Zwijnaarde (Ghent), Belgium
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Thenral Socrates;
Thenral Socrates
*Departments of Internal Medicine, Nephrology and Cardiology, University Hospital Basel, Switzerland
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Beatrice Drexler;
Beatrice Drexler
*Departments of Internal Medicine, Nephrology and Cardiology, University Hospital Basel, Switzerland
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Alexandre Mebazaa;
Alexandre Mebazaa
‡U942 Inserm, Univ Paris 7 Diderot, APHP Department of Anesthesiology and Critical Care Medicine, Hôpital Lariboisière, France
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Koen Kas;
Koen Kas
†Pronota NV, Zwijnaarde (Ghent), Belgium
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Christian Mueller
Christian Mueller
*Departments of Internal Medicine, Nephrology and Cardiology, University Hospital Basel, Switzerland
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Publisher: Portland Press Ltd
Received:
February 03 2012
Revision Received:
May 14 2012
Accepted:
May 16 2012
Accepted Manuscript online:
May 16 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 123 (9): 557–566.
Article history
Received:
February 03 2012
Revision Received:
May 14 2012
Accepted:
May 16 2012
Accepted Manuscript online:
May 16 2012
Citation
Tobias Breidthardt, Griet Vanpoucke, Mihael Potocki, Tamina Mosimann, Ronny Ziller, Gregoire Thomas, Wouter Laroy, Piet Moerman, Thenral Socrates, Beatrice Drexler, Alexandre Mebazaa, Koen Kas, Christian Mueller; The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea. Clin Sci (Lond) 1 November 2012; 123 (9): 557–566. doi: https://doi.org/10.1042/CS20120058
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