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Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.

TitleFibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.
Publication TypeJournal Article
Year of Publication2015
AuthorsAgarwal, I, Arnold, A, Glazer, NL, Barasch, E, Djoussé, L, Fitzpatrick, AL, Gottdiener, JS, Ix, JH, Jensen, RA, Kizer, JR, Rimm, EB, Siscovick, DS, Tracy, RP, Wong, TY, Mukamal, KJ
JournalAtherosclerosis
Volume239
Issue2
Pagination539-46
Date Published2015 Apr
ISSN1879-1484
KeywordsAged, Ankle Brachial Index, Biomarkers, Brachial Artery, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cross-Sectional Studies, Female, Fibrosis, Humans, Incidence, Male, Peptide Fragments, Peripheral Arterial Disease, Predictive Value of Tests, Procollagen, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Transforming Growth Factor beta, United States, Vasodilation
Abstract<p><b>OBJECTIVE: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1016/j.atherosclerosis.2015.02.020
Alternate JournalAtherosclerosis
PubMed ID25725316
PubMed Central IDPMC4517825
Grant ListAG023629 / AG / NIA NIH HHS / United States
F30 HL118775 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
HL094555 / HL / NHLBI NIH HHS / United States
HL118775 / HL / NHLBI NIH HHS / United States
N01 HC55222 / HC / NHLBI NIH HHS / United States
N01HC35129 / HC / NHLBI NIH HHS / United States
N01HC45133 / HC / NHLBI NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
N01HC85084 / HC / NHLBI NIH HHS / United States
N01HC85085 / HC / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States