RESEARCH ARTICLE
N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease José Tuñón1,2,3☯*, Javier Higueras4☯, Nieves Tarín5, Carmen Cristóbal6,7, Óscar Lorenzo2,3, Luis Blanco-Colio3, José Luis Martín-Ventura2,3, Ana Huelmos8, Joaquín Alonso6,7, Álvaro Aceña1, Ana Pello1, Rocío Carda1, Dolores Asensio9, Ignacio Mahíllo-Fernández10, Lorenzo López Bescós7, Jesús Egido2,3,11, Jerónimo Farré1,2 1 Department of Cardiology, IIS-Fundación Jiménez Díaz, Madrid, Spain, 2 Autónoma University, Madrid, Spain, 3 Laboratory of Vascular Pathology, IIS-Fundación Jiménez Díaz, Madrid, Spain, 4 Department of Cardiology, Hospital Clínico Universitario San Carlos, Madrid, Spain, 5 Department of Cardiology, Hospital Universitario de Móstoles, Madrid, Spain, 6 Department of Cardiology, Hospital de Fuenlabrada, Madrid, Spain, 7 Rey Juan Carlos University, Alcorcón, Madrid, Spain, 8 Department of Cardiology, Hospital Universitario Fundación Alcorcón, Madrid, Spain, 9 Department of Biochemistry, IIS-Fundación Jiménez Díaz, Madrid, Spain, 10 Department of Preventive Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain, 11 CIBERDEM, Madrid, Spain OPEN ACCESS Citation: Tuñón J, Higueras J, Tarín N, Cristóbal C, Lorenzo Ó, Blanco-Colio L, et al. (2015) N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease. PLoS ONE 10(6): e0126741. doi:10.1371/journal.pone.0126741 Academic Editor: Ho-Chang Kuo, Kaohsiung Chang Gung Memorial Hospital, TAIWAN Received: August 2, 2014 Accepted: April 7, 2015 Published: June 5, 2015 Copyright: © 2015 Tuñón et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by grants from Fondo de Investigaciones Sanitarias (PI05/0451, PI05/1497,PI05/2475, PI05/1043, PS09/01405, PI10/ 00072, and PI10/0234, PI14/1567, Programa de Estabilización to LBC); Spanish Society of Cardiology and Spanish Heart Foundation; Spanish Society of Arteriosclerosis; RECAVA (RD06/0014/0035, www. recava.com); Fundación Lilly; and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in study design, data
☯ These authors contributed equally to this work. *
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Abstract Objective Several papers have reported elevated plasma levels of natriuretic peptides in patients with a previous diagnosis of cancer. We have explored whether N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels predict a future diagnosis of cancer in patients with coronary artery disease (CAD).
Methods We studied 699 patients with CAD free of cancer. At baseline, NT-proBNP, galectin-3, monocyte chemoattractant protein-1, soluble tumor necrosis factor-like weak inducer of apoptosis, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin I plasma levels were assessed. The primary outcome was new cancer diagnosis. The secondary outcome was cancer diagnosis, heart failure requiring hospitalization, or death.
Results After 2.15±0.98 years of follow-up, 24 patients developed cancer. They were older (68.5 [61.5, 75.8] vs 60.0 [52.0, 72.0] years; p=0.011), had higher NT-proBNP (302.0 [134.8, 919.8] vs 165.5 [87.4, 407.5] pg/ml; p=0.040) and high-sensitivity C-reactive protein (3.27 [1.33, 5.94] vs 1.92 [0.83, 4.00] mg/L; p=0.030), and lower triglyceride (92.5 [70.5, 132.8] vs 112.0 [82.0, 157.0] mg/dl; p=0.044) plasma levels than those without cancer. NT-proBNP (Hazard Ratio [HR]=1.030; 95% Confidence Interval [CI]=1.008-1.053; p=0.007) and
PLOS ONE | DOI:10.1371/journal.pone.0126741 June 5, 2015
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N-Terminal Pro-Brain Natriuretic Peptide Is Associated with Cancer
collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: L. Blanco-Colio and J. Egido have a patent on TWEAK as a biomarker. (Name: ³Soluble TWEAK as a biomarker of early atherosclerosis"; Number: ES2321466; Autónoma University of Madrid). The remaining authors have no conflicts of interest. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
triglyceride levels (HR=0.987; 95%CI=0.975-0.998; p=0.024) were independent predictors of a new cancer diagnosis (multivariate Cox regression analysis). When patients in whom the suspicion of cancer appeared in the first one-hundred days after blood extraction were excluded, NT-proBNP was the only predictor of cancer (HR=1.061; 95% CI=1.034-1.088; p
