Published Online
on March 31, 2009

A more recent version of this article appeared on June 1, 2009

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Original Article

Growth-Differentiation Factor-15 for Risk Stratification in Patients with Stable and Unstable Coronary Heart Disease: Results from the AtheroGene Study

Tibor Kempf¹; Jan-Malte Sinning²; Anja Quint¹; Christoph Bickel²; Christoph Sinning³; Philipp S. Wild³; Renate Schnabel³; Edith Lubos³; Hans J. Rupprecht³; Thomas Münzel³; Helmut Drexler¹; Stefan Blankenberg³ and Kai C. Wollert^1,4

¹ Hannover Medical School, Hannover, Germany;
² Federal Armed Forces Hospital, Koblenz, Germany;
³ Johannes-Gutenberg University, Mainz, Germany

⁴ E-mail: wollert.kai{at}mh-hannover.de

Background—Growth-differentiation factor-15 (GDF-15) is a stress-responsive TGF-β-related cytokine that has emerged as a prognostic biomarker in acute coronary syndrome (ACS) trial populations. Its predictive role in stable coronary heart disease (CHD) has never been assessed.

Methods and Results—The circulating levels of GDF-15 were measured by immunoradiometric assay in patients with stable angina pectoris (SAP, n=1352) or ACS (n=877) who were followed for a median of 3.6 years. SAP patients presenting with normal (<1200 ng/L), moderately elevated (1200-1800 ng/L), or markedly elevated (>1800 ng/L) GDF 15 levels had 3.6-year CHD mortality rates of 1.4, 2.7, and 15.0%, respectively (P<0.001). By backward stepwise Cox-regression analysis, that adjusted for age and gender, clinical variables, the number of diseased vessels, renal function, the levels of C-reactive protein, cardiac troponin I, and N-terminal pro-B-type natriuretic peptide, GDF 15 remained an independent predictor of CHD mortality (P<0.001). Addition of GDF-15 improved the prognostic accuracy of a clinical risk prediction model concerning CHD mortality (c-statistic, 0.84 vs. 0.74; P=0.005). Analysis of the ACS part of the study population confirmed GDF-15 as an independent predictor of CHD mortality (P<0.001). The circulating levels of GDF-15 did not predict the future risk of non-fatal myocardial infarction in patients with SAP or ACS.

Conclusions—This study identifies GDF-15 as a strong and independent predictor of CHD mortality across the broad spectrum of patients with stable and unstable CHD.

Key Words: coronary disease • biomarker • growth-differentiation factor-15 • outcome

Related Article

The Report Card on Growth Differentiation Factor 15: Consistent Marks But Not Yet Ready for Promotion

Anand Rohatgi and James A. de Lemos
Circ Cardiovasc Genet 2009 2: 209-211. [Extract] [Full Text] [PDF]

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				L. Lind, L. Wallentin, T. Kempf, H. Tapken, A. Quint, B. Lindahl, S. Olofsson, P. Venge, A. Larsson, J. Hulthe, et al. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study Eur. Heart J., October 1, 2009; 30(19): 2346 - 2353. [Abstract] [Full Text] [PDF]

				A. Rohatgi and J. A. de Lemos The Report Card on Growth Differentiation Factor 15: Consistent Marks But Not Yet Ready for Promotion Circ Cardiovasc Genet, June 1, 2009; 2(3): 209 - 211. [Full Text] [PDF]