Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population: Observations from the dallas heart study

Anand K Rohatgi, Parag Patel, Sandeep R Das, Colby R. Ayers, Amit Khera, Abelardo Martinez-Rumayor, Jarett D Berry, Darren K McGuire, James A de Lemos

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)172-182
Number of pages11
JournalClinical Chemistry
Volume58
Issue number1
DOIs
StatePublished - Jan 2012

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Growth Differentiation Factor 15
Coronary Artery Disease
Mortality
Population
Electron beam computed tomography
Hazards
Odds Ratio
Troponin T
X Ray Computed Tomography
Brain Natriuretic Peptide
Body Surface Area
Medical problems
Cardiac Myocytes
C-Reactive Protein
Atherosclerosis
Smoking
Statistics
Hypertension
Kidney
Plasmas

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

@article{618376af2576428eb182bff3172398f6,
title = "Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population: Observations from the dallas heart study",
abstract = "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.",
author = "Rohatgi, {Anand K} and Parag Patel and Das, {Sandeep R} and Ayers, {Colby R.} and Amit Khera and Abelardo Martinez-Rumayor and Berry, {Jarett D} and McGuire, {Darren K} and {de Lemos}, {James A}",
year = "2012",
month = "1",
doi = "10.1373/clinchem.2011.171926",
language = "English (US)",
volume = "58",
pages = "172--182",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry Inc.",
number = "1",

}

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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