UNCORRECTED PROOF 1 The relationship and prognostic impact of low-T3 syndrome and NT-pro-BNP in 2 cardiovascular patients 3 Roman Pfister a, ⁎, Nicole Strack a , Klaus Wielckens b , Gebhart Malchau b , 4 Erland Erdmann a , Christian A. Schneider a 5 a Department III of Internal Medicine, Herzzentrum, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany 6 b Department of Clinical Chemistry, University of Cologne, Germany 7 8 abstract article info 9 Article history: 10 Received 4 August 2008 11 Received in revised form 13 January 2009 12 Accepted 31 March 2009 13 Available online xxxx 14 15 16 17 Keywords: 18 NT-pro-BNP 19 Low-T3 syndrome 20 Prognosis 21 Cardiac dysfunction 22 Objectives: Low-T3 syndrome is highly prevalent and independently prognostic in cardiovascular patients. 23 The relationship and prognostic impact with the cardiac marker NT-pro-BNP have not been thoroughly 24 investigated. 25 Methods: Thyroid hormone levels and NT-pro-BNP were assessed in 615 consecutive patients hospitalized for 26 cardiovascular disease. Patients with primary overt or latent thyroid disorder, hormone replacement, 27 thyreostatic and amiodarone therapy were excluded. The association with and predictive impact on mortality 28 were examined. 29 Results: 36 (7.1%) patients had low-T3 syndrome. After adjustment for known confounders, NT-pro-BNP was 30 significantly associated with fT3 and low-T3 syndrome. fT3 (HR 0.58, 95%CI 0.34–0.98) and low-T3 syndrome 31 (HR 3.0, 95%CI 1.4–6.3) were predictive for mortality after adjustment for NT-pro-BNP levels and other 32 cardiovascular prognostic variables. In patients with fT3 levels within the normal range, fT3 and NT-pro-BNP 33 stratified by median values showed complementary prognostic information with the highest risk for 34 mortality in patients with low normal fT3 and high NT-pro-BNP (HR 10.5, 95%CI 3.2–34.6). 35 Conclusions: fT3 and low-T3 syndrome are significantly related to NT-pro-BNP in patients with cardiovascular 36 disease, but are predictors of mortality independently of NT-pro-BNP and other known cardiovascular risk 37 parameters. 38 © 2009 Published by Elsevier Ireland Ltd. 39 40 41 42 43 44 1. Introduction 45 Thyroid hormones and especially the biologically active hormone tri- 46 iodothyronine (T3) are essential for cardiovascular homeostasis [1]. In 47 patients with systemic illness from different causes the low-T3 48 syndrome was described which is characterized by decreased fT3 levels 49 accompanied by normal thyroxine (T4) and thyrotropin (TSH) values 50 resulting from a decrease in peripheral conversion of T4 into T3 [2]. 51 Although the pathophysiologic impact of the low-T3 syndrome is not yet 52 clear, it is highly prevalent in patients with cardiovascular disease and 53 indicates increased mortality [3–8]. In patients with heart failure, the 54 low-T3 syndrome especially correlates with disease severity and is 55 independently associated with unfavourable prognosis [5]. 56 B-type natriuretic peptides are the most accurate serum markers of 57 cardiac dysfunction [9]. They are increasingly applied in clinical routine 58 for diagnosis and prognostic evaluation of patients with cardiovascular 59 disease [10,11]. Thyroid hormones directly activate B-type natriuretic 60 peptides and significantly elevated peptide values are described in 61 patients with overt and latent hyperthyreoidism [12–14]. In patients 62 with left-ventricular dysfunction or heart failure an inverse correlation 63 between fT3 and natriuretic peptides was found [15]. To our knowledge, 64 the association of low-T3 syndrome with B-type natriuretic peptides and 65 the prognostic impact have not been analysed. Studying this association 66 is of great interest for the closer understanding of the low-T3 syndrome 67 in cardiovascular patients and its application as a prognostic marker, as 68 low-T3 syndrome might just be a sign of advanced cardiac dysfunction 69 without independent prognostic information. 70 The aim of this study was to evaluate the relationship and prognostic 71 impact of thyroid hormone levels and the N-terminal-part of pro-BNP 72 (NT-pro-BNP) in patients without manifest or latent thyroid dysfunction 73 and with cardiovascular disease. Based on previous reports on fT3 and 74 natriuretic peptides, we hypothesized that the low-T3 syndrome is 75 associated with NT-pro-BNP levels. 76 2. Subjects and methods 77 2.1. Patients 78 The demographic and clinical characteristics of the patients have 79 recently been published in a study about the prognostic value of NT- 80 pro-BNP in cardiac patients [10]. Briefly, all patients admitted to a International Journal of Cardiology xxx (2009) xxx–xxx ⁎ Corresponding author. Tel.: +49 221 478 32493; fax: +49 221478 32355. E-mail address: romane.pfister@uk-koeln.de (R. Pfister). IJCA-11992; No of Pages 5 0167-5273/$ – see front matter © 2009 Published by Elsevier Ireland Ltd. doi:10.1016/j.ijcard.2009.03.137 Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard ARTICLE IN PRESS Please cite this article as: Pfister R, et al, The relationship and prognostic impact of low-T3 syndrome and NT-pro-BNP in cardiovascular patients, Int J Cardiol (2009), doi:10.1016/j.ijcard.2009.03.137