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Circ Arrhythm Electrophysiol. 2014 Aug;7(4):583-9. doi: 10.1161/CIRCEP.114.001610. Epub 2014 Jun 24.

Fibrosis-related biomarkers and incident cardiovascular disease in older adults: the cardiovascular health study.

Author information

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 Network Medicine (E.B.R.), Brigham and Women's Hospital, Boston, MA; Department of Medicine, University of Maryland Medical School, Baltimore (J.S.G.); Department of Medicine, University of California San Diego and Veterans Affairs San Diego Healthcare System (J.H.I.); Departments of Medicine, Epidemiology, and Population Health, Albert Einstein College of Medicine, Bronx, NY (J.R.K.); Department of Biochemistry, University of Vermont, Burlington (R.P.T.); and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.). Isha_Agarwal@hms.harvard.edu.
2
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 Network Medicine (E.B.R.), Brigham and Women's Hospital, Boston, MA; Department of Medicine, University of Maryland Medical School, Baltimore (J.S.G.); Department of Medicine, University of California San Diego and Veterans Affairs San Diego Healthcare System (J.H.I.); Departments of Medicine, Epidemiology, and Population Health, Albert Einstein College of Medicine, Bronx, NY (J.R.K.); Department of Biochemistry, University of Vermont, Burlington (R.P.T.); and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).

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.

KEYWORDS:

cardiovascular diseases; collagen; epidemiology; heart failure

PMID:
24963008
PMCID:
PMC4140969
DOI:
10.1161/CIRCEP.114.001610
[Indexed for MEDLINE]
Free PMC Article

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