S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension

Respirology. 2018 Aug;23(8):771-779. doi: 10.1111/resp.13302. Epub 2018 Apr 2.

Abstract

Background and objective: Molecular biomarkers are needed to refine prognostication and phenotyping of pulmonary hypertension (PH) patients. S100A12 is an emerging biomarker of various inflammatory diseases. This study aims to determine the prognostic value of S100A12 in PH.

Methods: Exploratory microarray analysis performed on peripheral blood mononuclear cells (PBMC) collected from idiopathic pulmonary fibrosis (IPF) patients suggested an association between S100A12 and both PH and mortality. So the current study was designed to evaluate for an association between S100A12 in peripheral blood collected from two well-phenotyped PH cohorts in two other centres to derive and validate an association between S100A12 protein serum concentrations and mortality.

Results: The majority of the patients in the discovery and validation cohorts were either World Health Organization (WHO) group 1 (pulmonary arterial hypertension (PAH)) or 3 (lung disease-associated) PH. In the discovery PH cohort, S100A12 was significantly increased in patients with PH (n = 51) compared to controls (n = 22) (29.8 vs 15.7 ng/mL, P < 0.001) and negatively correlated with cardiac output (r = -0.58, P < 0.001) in PH patients. When S100A12 data were pooled from both cohorts, PAH and non-PAH PH patients had higher S100A12 compared to healthy external controls (32.6, 30.9, 15.7 ng/mL; P < 0.001). S100A12 was associated with an increased risk in overall mortality in PH patients in both the discovery (n = 51; P = 0.008) and validation (n = 40; P < 0.001) cohorts.

Conclusion: S100A12 levels are increased in PH patients and are associated with increased mortality.

Keywords: biomarkers; inflammatory heart disease; prognosis; pulmonary hypertension; translational studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cardiac Output*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / mortality*
  • Hypertension, Pulmonary / physiopathology
  • Leukocytes, Mononuclear
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Prognosis
  • S100A12 Protein / blood*

Substances

  • Biomarkers
  • S100A12 Protein
  • S100A12 protein, human