Affiliation:
1. From the Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA (I.A., E.B.R.); Department of Medicine, Boston University, MA (N.L.G.); Department of Research and Education, St. Francis Hospital/SUNY at Stony Brook, NY (E.B.); Department of Biostatistics (M.L.B.), Department of Epidemiology (A.L.F.), and Cardiovascular Health Research Unit, Department of Medicine (D.S.S.), University of Washington, Seattle; Department of Medicine (L.D.) and Channing Division of...
Abstract
Background—
Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown.
Methods and Results—
We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- β (TGF-β), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-β (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β’s pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95% confidence interval [CI], 1.01–1.14) and heart failure (HR per SD=1.08; CI, 1.01–1.16) but not myocardial infarction or stroke. TGF-β was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02–1.31), heart failure (HR per SD=1.16; CI, 1.01–1.34), and stroke (HR per SD=1.20; CI, 1.01–1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (
P
interaction <0.05).
Conclusions—
Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-β has a stronger fibrogenic effect in the setting of inflammation is warranted.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
30 articles.
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