Universität zu Köln

Schurgers, L. J., Burgmaier, M., Ueland, T., Schutters, K., Aakhus, S., Hofstra, L., Gullestad, L., Aukrust, P., Hellmich, M., Narula, J. and Reutelingsperger, C. P. (2016). Circulating annexin A5 predicts mortality in patients with heart failure. J. Intern. Med., 279 (1). S. 89 - 98. HOBOKEN: WILEY. ISSN 1365-2796

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Abstract

BackgroundNatriuretic peptides are currently used to predict mortality in patients with heart failure (HF). However, novel independent biomarkers are needed to improve risk stratification in these patients. We hypothesized that annexin A5 (anxA5) would be highly expressed by organs which are generally affected by HF and that circulating anxA5 levels would predict mortality in HF patients. MethodsWe prospectively determined the diagnostic value of anxA5, N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and estimated glomerular filtration rate (eGFR) to predict mortality in 180 HF patients during a median follow-up of 3.6years. Studies were conducted with anxA5(-/-) mice to investigate the underlying mechanisms. ResultsAnxA5 levels were significantly elevated in HF patients compared to healthy control subjects. Cox regression analysis demonstrated that anxA5, NT-proBNP and eGFR all predict mortality independently. AnxA5 significantly improved the diagnostic efficiency of NT-proBNP alone (improvement of c-statistic from 0.662 to 0.705, P<0.001) and also combined with eGFR and CRP (improvement of c-statistic from 0.675 to 0.738, P<0.001) to predict mortality in the Cox regression model. Receiver operating characteristic curve analysis showed that anxA5 predicted 3-year survival (area under curve 0.708) with an optimal cut-off value of 2.24ngmL(-1). Using anxA5(-/-) mice, we demonstrated that anxA5 is highly expressed in organs that are often affected by HF including lung, kidney, liver and spleen. Lysis of these organs invitro resulted in a marked and significant increase in anxA5 concentrations. ConclusionAnxA5 improves the diagnostic efficiency of conventional biomarkers to predict mortality inHF patients. Whereas natriuretic peptides originate from the myocardium, high circulating anxA5 levels in patients with HF are likely toreflect peripheral organ damage secondary to HF.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schurgers, L. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Burgmaier, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ueland, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schutters, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aakhus, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofstra, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gullestad, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aukrust, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellmich, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Narula, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reutelingsperger, C. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-292891
DOI:	10.1111/joim.12396
Journal or Publication Title:	J. Intern. Med.
Volume:	279
Number:	1
Page Range:	S. 89 - 98
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2796
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC KIDNEY-DISEASE; NATRIURETIC PEPTIDE; INFLAMMATORY MARKERS; CARDIAC-HYPERTROPHY; AMBULATORY PATIENTS; RISK-FACTORS; HEALTH ABC; APOPTOSIS; CELLS; CARDIOMYOPATHY Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29289