Fibrosis-related biomarkers and large and small vessel disease: The Cardiovascular Health Study. Issue 2 (April 2015)

• Record Type: Journal Article
• Authors: Agarwal, Isha; Arnold, Alice; Glazer, Nicole L.; Barasch, Eddy; Djousse, Luc; Fitzpatrick, Annette L.; Gottdiener, John S.; Ix, Joachim H.; Jensen, Richard A.; Kizer, Jorge R.; Rimm, Eric B.; Siscovick, David S.; Tracy, Russell P.; Wong, Tien Y.; Mukamal, Kenneth J.
• Is Part Of: Atherosclerosis. Volume 239:Issue 2(2015)
• Page Start: 539
• Page End: 546
• Publication Date: 2015-04
• Subjects: Fibrosis -- Peripheral artery disease -- Atherosclerosis; ABI ankle-brachial index -- CHS Cardiovascular Health Study -- FMD flow-mediated vasodilation -- IMT intima-media thickness -- PAD peripheral artery disease -- PIIINP procollagen type III N-terminal propeptide -- TGF-β transforming growth factor-β; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.02.020
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: 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 (1.63 μm 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 (0.102 mm 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. Highlights: We measured serum concentrations of two complementary fibrosis-related biomarkers. Fibrosis markers were associated with measures of large vessel disease and incident peripheral artery disease. Our results suggest that fibrosis may be related to the development of large vessel atherosclerosis in older adults.