Published online before print March 31, 2009, doi: 10.1161/CIRCGENETICS.108.824870
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Original Articles |
Growth-Differentiation Factor-15 for Risk Stratification in Patients With Stable and Unstable Coronary Heart Disease
Results From the AtheroGene Study
From the Department of Cardiology and Angiology (T.K., A.Q., H.D., K.C.W.), Hannover Medical School, Hannover, Germany; Federal Armed Forces Hospital (J.M.S., C.B.), Koblenz, Germany; and Department of Medicine II (C.S., P.S.W., R.S., E.L., H.J.R., T.M., S.B.), Johannes-Gutenberg University, Mainz, Germany.
Correspondence to Kai C. Wollert, MD, Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. E-mail wollert.kai{at}mh-hannover.de
Received September 28, 2008; accepted March 9, 2009.
Background— Growth-differentiation factor-15 (GDF-15) is a stress-responsive transforming growth factor-β-related cytokine that has emerged as a prognostic biomarker in acute coronary syndrome 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 (n=1352) or acute coronary syndrome (n=877) who were followed up for a median of 3.6 years. Stable angina pectoris patients presenting with normal (<1200 ng/L), moderately elevated (1200 to 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, which 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 versus 0.74; P=0.005). Analysis of the acute coronary syndrome 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 nonfatal myocardial infarction in patients with stable angina pectoris or acute coronary syndrome.
Conclusion— 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: growth-differentiation factor-15 • coronary heart disease • biomarker • outcome
CLINICAL PERSPECTIVE
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