Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study

Cardiovasc Diabetol. 2016 Apr 8:15:60. doi: 10.1186/s12933-016-0375-8.

Abstract

Background: Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor ß family and has been associated with inflammation, cancer, aging, diabetes mellitus (DM) and atherosclerosis. Determinants of GDF-15 have been investigated in several conditions. We aimed to investigate determinants of GDF-15 plasma levels in patients with angiographically proven coronary artery disease (CAD).

Methods: Four hundred and seventy three consecutive patients with CAD were investigated between May 2009 and February 2011. Patients were separated into those with stable CAD (SCAD) and with ST-elevation and non-ST-elevation myocardial infarction (STEMI and NSTEMI). Blood samples for determination of GDF-15 were obtained before coronary angiography. Determinant of GDF-15 levels were analyzed by logistic regression analysis in unadjusted and adjusted models. Study endpoints were cardiovascular death (CV-death), myocardial infarction, unstable angina, unplanned revascularization, stent thrombosis and stroke assessed at a mean follow-up of 188 (177.2-243) days.

Results: Overall median and (25-27th percentile) GDF-15 level was 1212.8 pg/ml (833.2-1957 pg/ml). GDF-15 was significantly higher in STEMI compared to SCAD and NSTEMI groups (P < 0.0001). In a multivariate regression analysis advanced age, DM, acute hyperglycemia (AHG), CRP and chronic kidney disease (CKD) were independent predictors of elevated GDF-15 levels (P < 0.05). Receiver operating curve analysis of GDF-15 for prediction of CV-death showed an area under the curve of 0.852 with a confidence interval of 0.745-0.960, P < 0.0001. The estimated cut-off was 2094.6 pg/ml with a sensitivity of 76 % and specificity of 80 %.

Conclusion: In patients with CAD undergoing PCI with stent implantation, GDF-15 is determined by advanced age, acute and chronic hyperglycemia, inflammation and CKD. GDF-15 is a valuable predictor of CV-death in a population of CAD patients after PCI.

Keywords: Acute coronary syndrome; Acute hyperglycemia; Coronary artery disease; Diabetes mellitus; Growth differentiation factor 15.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Coronary Angiography / methods
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / metabolism*
  • Female
  • Growth Differentiation Factor 15 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / therapy
  • Myocardial Ischemia / complications
  • Myocardial Ischemia / metabolism
  • Prognosis
  • Prospective Studies

Substances

  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15