N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease

PLoS One. 2015 Jun 5;10(6):e0126741. doi: 10.1371/journal.pone.0126741. eCollection 2015.

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 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<0.001). NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001) along with age, and use of insulin and acenocumarol.

Conclusions: NT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / mortality
  • Female
  • Follow-Up Studies
  • Galectin 3 / blood
  • Heart Failure / diagnosis
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Neoplasms / complications
  • Neoplasms / diagnosis*
  • Peptide Fragments / blood*
  • Proportional Hazards Models
  • Risk Factors
  • Triglycerides / blood
  • Troponin I / blood

Substances

  • Biomarkers
  • Galectin 3
  • Peptide Fragments
  • Triglycerides
  • Troponin I
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein

Grants and 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 collection and analysis, decision to publish, or preparation of the manuscript.