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

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.

• Authors: Isha Agarwal, Alice Arnold, Nicole L Glazer, Eddy Barasch, Luc Djousse, Annette L Fitzpatrick, John S Gottdiener, Joachim H Ix, Richard A Jensen, Jorge R Kizer, Eric B Rimm, David S Siscovick, Russell P Tracy, Tien Y Wong, Kenneth J Mukamal
• Journal: Atherosclerosis (Atherosclerosis) Vol. 239 Issue 2 Pg. 539-46 (Apr 2015) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 25725316 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Biomarkers
• Peptide Fragments
• Procollagen
• Transforming Growth Factor beta
• procollagen Type III-N-terminal peptide

Topics

• Aged
• Ankle Brachial Index
• Biomarkers (blood)
• Brachial Artery (physiopathology)
• Carotid Artery Diseases (blood, diagnosis, epidemiology, physiopathology)
• Carotid Intima-Media Thickness
• Cross-Sectional Studies
• Female
• Fibrosis
• Humans
• Incidence
• Male
• Peptide Fragments (blood)
• Peripheral Arterial Disease (blood, diagnosis, epidemiology, physiopathology)
• Predictive Value of Tests
• Procollagen (blood)
• Prognosis
• Prospective Studies
• Retinal Diseases (blood, diagnosis, epidemiology, physiopathology)
• Risk Factors
• Transforming Growth Factor beta (blood)
• United States (epidemiology)
• Vasodilation