TY - JOUR
T1 - Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population
T2 - Observations from the dallas heart study
AU - Rohatgi, Anand K
AU - Patel, Parag
AU - Das, Sandeep R
AU - Ayers, Colby R.
AU - Khera, Amit
AU - Martinez-Rumayor, Abelardo
AU - Berry, Jarett D
AU - McGuire, Darren K
AU - de Lemos, James A
PY - 2012/1
Y1 - 2012/1
N2 - BACKGROUND: Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined. METHODS: We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30-65 years (55% women, 49% black). GDF-15 was analyzed in prespecified categories (<1200; 1200-1799; and ≥1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC >10 Agatston units), increased CAC (CAC ≥100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths). RESULTS: Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P < 0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15≥1800 ng/L was associated with CAC>10 (odds ratio 2.1; 95% CI 1.2-3.7; P =0.01), CAC ≥100 (odds ratio 2.6; 95% CI 1.4-4.9; P =0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1-5.9, P < 0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1-5.8, P = 0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P = 0.025), the integrated discrimination index (0.028; P < 0.0001) and the category-less net reclassification index (0.42;P = 0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro - B-type natriuretic peptide, and cardiac troponin T. CONCLUSIONS: GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for risk stratification in the general population merits further evaluation.
AB - BACKGROUND: Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined. METHODS: We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30-65 years (55% women, 49% black). GDF-15 was analyzed in prespecified categories (<1200; 1200-1799; and ≥1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC >10 Agatston units), increased CAC (CAC ≥100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths). RESULTS: Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P < 0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15≥1800 ng/L was associated with CAC>10 (odds ratio 2.1; 95% CI 1.2-3.7; P =0.01), CAC ≥100 (odds ratio 2.6; 95% CI 1.4-4.9; P =0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1-5.9, P < 0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1-5.8, P = 0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P = 0.025), the integrated discrimination index (0.028; P < 0.0001) and the category-less net reclassification index (0.42;P = 0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro - B-type natriuretic peptide, and cardiac troponin T. CONCLUSIONS: GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for risk stratification in the general population merits further evaluation.
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U2 - 10.1373/clinchem.2011.171926
DO - 10.1373/clinchem.2011.171926
M3 - Article
C2 - 22065155
AN - SCOPUS:84863393862
SN - 0009-9147
VL - 58
SP - 172
EP - 182
JO - Clinical chemistry
JF - Clinical chemistry
IS - 1
ER -