Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome

Circulation. 2007 Feb 27;115(8):962-71. doi: 10.1161/CIRCULATIONAHA.106.650846. Epub 2007 Feb 5.

Abstract

Background: Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non-ST-elevation acute coronary syndrome.

Methods and results: Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non-ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P<0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro-B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and creatinine clearance.

Conclusions: GDF-15 is a new biomarker of the risk for death in patients with non-ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Biomarkers
  • C-Reactive Protein / analysis
  • Chest Pain / blood
  • Chest Pain / diagnosis*
  • Chest Pain / mortality
  • Coronary Disease / blood
  • Coronary Disease / diagnosis*
  • Coronary Disease / mortality
  • Cytokines / blood*
  • Female
  • Growth Differentiation Factor 15
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Prognosis
  • Recurrence

Substances

  • Biomarkers
  • Cytokines
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • C-Reactive Protein