TY - JOUR
T1 - Fibrosis-related biomarkers and incident cardiovascular disease in older adults the cardiovascular health study
AU - Agarwal, Isha
AU - Glazer, Nicole L.
AU - Barasch, Eddy
AU - Biggs, Mary L.
AU - Djousse, Luc
AU - Fitzpatrick, Annette L.
AU - Gottdiener, John S.
AU - Ix, Joachim H.
AU - Kizer, Jorge R.
AU - Rimm, Eric B.
AU - Sicovick, David S.
AU - Tracy, Russell P.
AU - Mukamal, Kenneth J.
N1 - Publisher Copyright:
© 2014 American Heart Association, Inc.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - 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- ß (TGF-ß), 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-ß (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-ß'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-ß 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-ß has a stronger fibrogenic effect in the setting of inflammation is warranted.
AB - 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- ß (TGF-ß), 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-ß (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-ß'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-ß 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-ß has a stronger fibrogenic effect in the setting of inflammation is warranted.
KW - Cardiovascular diseases
KW - Collagen
KW - Epidemiology
KW - Heart failure
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U2 - 10.1161/CIRCEP.114.001610
DO - 10.1161/CIRCEP.114.001610
M3 - Article
C2 - 24963008
AN - SCOPUS:84907901497
SN - 1941-3149
VL - 7
SP - 583
EP - 589
JO - Circulation: Arrhythmia and Electrophysiology
JF - Circulation: Arrhythmia and Electrophysiology
IS - 4
ER -
