Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study

TY - JOUR

T1 - Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study

AU - Kempf, Tibor

AU - Sinning, Jan-Malte

AU - Quint, Anja

AU - Bickel, Christoph

AU - Sinning, Christoph

AU - Wild, Philipp S

AU - Schnabel, Renate

AU - Lubos, Edith

AU - Rupprecht, Hans J

AU - Münzel, Thomas

AU - Drexler, Helmut

AU - Blankenberg, Stefan

AU - Wollert, Kai C

PY - 2009/6

Y1 - 2009/6

N2 - 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.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.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.

AB - 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.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.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.

KW - Acute Coronary Syndrome/diagnosis

KW - Aged

KW - Angina Pectoris/diagnosis

KW - Female

KW - Growth Differentiation Factor 15/blood

KW - Humans

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Radiography

KW - Regression Analysis

KW - Risk Factors

KW - Survival Analysis

U2 - 10.1161/CIRCGENETICS.108.824870

DO - 10.1161/CIRCGENETICS.108.824870

M3 - SCORING: Journal article

C2 - 20031597

VL - 2

SP - 286

EP - 292

JO - CIRC-CARDIOVASC GENE

JF - CIRC-CARDIOVASC GENE

SN - 1942-325X

IS - 3

ER -