Fibrosis and Inflammatory Markers and Long-Term Risk of Peripheral Artery Disease: The ARIC Study.

TitleFibrosis and Inflammatory Markers and Long-Term Risk of Peripheral Artery Disease: The ARIC Study.
Publication TypeJournal Article
Year of Publication2020
AuthorsDing N, Yang C, Ballew SH, Kalbaugh CA, McEvoy JW, Salameh M, Aguilar D, Hoogeveen RC, Nambi V, Selvin E, Folsom AR, Heiss G, Coresh JJ, Ballantyne CM
Secondary AuthorsMatsushita K
JournalArterioscler Thromb Vasc Biol
Volume40
Issue9
Pagination2322-2331
Date Published2020 09
ISSN1524-4636
KeywordsAged, Biomarkers, C-Reactive Protein, Critical Illness, Female, Fibrosis, Galectin 3, Humans, Incidence, Inflammation Mediators, Intermittent Claudication, Ischemia, Male, Middle Aged, Peripheral Arterial Disease, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States
Abstract

OBJECTIVE: Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD. Approach and Results: In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996-1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis [-: 440.2-440.4] or leg revascularization [eg, -: 38.18]) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 [1.05-1.31] per 1 SD increment) and critical limb ischemia (1.25 [1.05-1.49] per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 [1.02-1.27] and 1.22 [1.02-1.45], respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 [1.18-1.52] and 1.34 [1.09-1.65], respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 [0.815-0.871]) improved the risk prediction of PAD (ΔC statistics, 0.011 [0.002-0.020]).

CONCLUSIONS: Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.

DOI10.1161/ATVBAHA.120.314824
Alternate JournalArterioscler Thromb Vasc Biol
PubMed ID32698688
PubMed Central IDPMC7678951
Grant ListK24 HL152440 / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201000021C / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
R01 HL134320 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
R21 HL133694 / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States