Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study.
BACKGROUND
Growth-differentiation factor-15 (GDF-15) is a stress-responsive transforming growth factor-beta-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.


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.


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.
Kempf
Tibor
T
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Sinning
Jan-Malte
JM
Quint
Anja
A
Bickel
Christoph
C
Sinning
Christoph
C
Wild
Philipp S
PS
Schnabel
Renate
R
Lubos
Edith
E
Rupprecht
Hans J
HJ
Münzel
Thomas
T
Drexler
Helmut
H
Blankenberg
Stefan
S
Wollert
Kai C
KC
D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000401:mortality; D000368:Aged; D000787:Angina Pectoris / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000401:mortality; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011859:Radiography; D012044:Regression Analysis; D012307:Risk Factors; D016019:Survival Analysis
D055436:Growth Differentiation Factor 15