Immunobiology 217 (2012) 652–656 Contents lists available at SciVerse ScienceDirect Immunobiology jo u rn al homepage: www.elsevier.de/imbio The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure Marina Harutyunyan a , Michael Christiansen b , Julia S. Johansen c , Lars Køber a , Christian Torp-Petersen d , Jens Kastrup a,∗ a Department of Medicine B, The Heart Centre, Rigshospitalet, Copenhagen University Hospital and Faculty of Health Sciences, Denmark b Department of Clinical Biochemistry and Immunology, State Serum Institute, Denmark c Department of Medicine and Oncology, Herlev University Hospital, Denmark d Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark a r t i c l e i n f o Article history: Received 21 September 2011 Accepted 12 November 2011 Keywords: Biomarker Heart failure hs-CRP NT-proBNP Prognostic factor YKL-40 a b s t r a c t Background: Despite progress in management of patients with heart failure (HF) these patients still have a poor prognosis. We tested the hypothesis whether the inflammatory biomarker YKL-40 alone or in com- bination with high-sensitivity C-reactive protein (hs-CRP) and/or N-terminal-pro-B natriuretic peptide (NT-proBNP) could be a new prognostic biomarker for all-cause mortality in patients with HF. Methods and results: A total of 717 of the 1000 patients with severe left ventricular systolic dysfunction included in the EchoCardiography and Heart Outcome Study were included in Denmark and had blood sample available for serum YKL-40 determination. Mean age of patients was 70 years, and 73% were male. During the 7 years follow-up period 458 patients died. Patients were categorised according to serum YKL- 40 at entry into four quartiles: quartile I with median serum YKL-40 = 60 g/L (5–95% Confidence interval (CI): 30–82), quartile II: YKL-40 = 107 g/L (CI: 86–132), quartile III: YKL-40 = 169 g/L (CI: 142–221), and quartile IV: YKL-40 = 286 g/L (CI: 230–770). Hazard ratios for all-cause mortality were with quartile I as reference 1.33 (CI: 0.99–1.80), 1.35 (CI: 0.99–1.82), and 1.54 (CI: 1.14–2.08) for serum YKL-40 II to IV quartiles, respectively following multivariable adjustment for cardiovascular risk factors (age, left ventricular ejection fraction, gender, history of heart failure, ischemic heart disease, chronic pulmonary disease, diabetes mellitus, stroke, hypertension, NT-proBNP, hs-CRP, and renal function). Conclusion: Serum YKL-40 is significantly associated with all-cause mortality in patients with HF and could potentially be a new prognostic biomarker in these patients. © 2011 Elsevier GmbH. All rights reserved. Introduction Heart failure (HF) is a consequence of cardiac overload and injury, and characterized by clinical symptoms due to cardiac impairment. Despite progress in management, patientswith HF Abbreviations: HF, heart failure; hs-CRP, high-sensitivity C-reactive protein; NT-proBNP, N-terminal-pro-B natriuretic peptide; CI, confidence interval; ECM, extracellular matrix; IHD, ischemic heart disease; STEMI, ST-elevation myocardial infarction; LVEF, left ventricular ejection fraction; ECHOS, EchoCardigraphy and Heart Outcome Study; NYHA, New York Heart Association; CV, coefficient of vari- ations; eGFR, estimated glomerular filtration rate; WMI, wall motion index; MI, myocardial infarction; HT, hypertension; COPD, chronic obstructive pulmonary dis- ease; DM, diabetes mellitus; TIA, transient ischemic attack; BetaBL, beta-blocker; ACE-I, angiotensin converting enzyme inhibitors; AT-II-BL, AT-II antagonists; CaBL, calcium blockers. ∗ Corresponding author at: Department of Medicine B, The Hearth Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copen- hagen, Denmark. Tel.: +45 3545 2819/2817; fax: +45 35452705. E-mail address: jens.kastrup@rh.regionh.dk (J. Kastrup). have a poor prognosis, and the morbidity and mortality in these patients remain high. The biomarkers N-terminal-pro-B natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs- CRP) have been the focus for monitoring and risk assessment in patients with HF (Hammerer-Lercher et al. 2006; Scirica et al. 2009; Tang et al. 2008). Since inflammatory pathways may promote extracellular matrix (ECM) remodelling and HF progression (Radauceanu et al. 2008), recent research has focused on new inflammatory biomark- ers as YKL-40. YKL-40 is a highly conserved heparin-, chitin-, and collagen- binding glycoprotein and mainly produced by macrophages, neutrophils and cancer cells (Johansen et al. 2009; Lee et al. 2011). YKL-40 regulates vascular endothelial growth factor (Francescone et al. 2011) and has a role in inflammation, angiogenesis, cell proliferation and differentiation, and remodelling of the ECM (Francescone et al. 2011; Gratchev et al. 2008; Johansen et al. 2009; Kzhyshkowska et al. 2006, 2007; Lee et al. 2011; Rathcke et al. 2009). Hypoxia and interleukin 6 stimulates YKL-40 production (Junker et al. 2005). 0171-2985/$ – see front matter © 2011 Elsevier GmbH. All rights reserved. doi:10.1016/j.imbio.2011.11.003