Affiliation:
1. Division of Cardiology, Department of Internal Medicine
2. The Donald W. Reynolds Cardiovascular Clinical Research Center, Dallas, TX
3. Department of Internal Medicine, and
4. Department of Clinical Sciences, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
Abstract
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.
Funder
University of Texas Southwestern Medical Center
U.S. Public Health Service
NIH
National Center for Research Resources
Clinical Research
Alere San Diego, Inc.
North and Central Texas Clinical and Translational Science Initiative
National Heart, Lung, and Blood Institute
American Heart Association
Alere, Inc.
Roche Diagnostics
Publisher
Oxford University Press (OUP)
Subject
Biochemistry, medical,Clinical Biochemistry
Cited by
148 articles.
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