TY - JOUR
T1 - Fibrosis-related biomarkers and large and small vessel disease
T2 - The Cardiovascular Health Study
AU - Agarwal, Isha
AU - Arnold, Alice
AU - Glazer, Nicole L.
AU - Barasch, Eddy
AU - Djousse, Luc
AU - Fitzpatrick, Annette L.
AU - Gottdiener, John S.
AU - Ix, Joachim H.
AU - Jensen, Richard A.
AU - Kizer, Jorge R.
AU - Rimm, Eric B.
AU - Siscovick, David S.
AU - Tracy, Russell P.
AU - Wong, Tien Y.
AU - Mukamal, Kenneth J.
N1 - Funding Information:
This research was supported by contracts HL118775 , HL094555 , N01HC85084 , N01HC35129 , N01HC85085 , N01HC45133 , HHSN268201200036C , HHSN268200800007C , N01 HC55222 , N01HC85079 , N01HC85080 , N01HC85081 , N01HC85082 , N01HC85083 , N01HC85086 , and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org .
Publisher Copyright:
© 2015.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Objective: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels. Methods: We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998. Results: After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR]=1.36 per doubling of TGF-β, 95% confidence interval [CI]=1.04, 1.78) and retinal venular diameter (1.63μm per doubling of TGF-β, CI=0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102mm per doubling of PIIINP, CI=0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI=-0.39,-0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy. Conclusions: Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.
AB - Objective: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels. Methods: We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998. Results: After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR]=1.36 per doubling of TGF-β, 95% confidence interval [CI]=1.04, 1.78) and retinal venular diameter (1.63μm per doubling of TGF-β, CI=0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102mm per doubling of PIIINP, CI=0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI=-0.39,-0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy. Conclusions: Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.
KW - Atherosclerosis
KW - Fibrosis
KW - Peripheral artery disease
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U2 - 10.1016/j.atherosclerosis.2015.02.020
DO - 10.1016/j.atherosclerosis.2015.02.020
M3 - Article
C2 - 25725316
AN - SCOPUS:84923353953
SN - 0021-9150
VL - 239
SP - 539
EP - 546
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -