TY - JOUR
T1 - Fibrosis and Inflammatory Markers and Long-Term Risk of Peripheral Artery Disease The ARIC Study
AU - Ding, Ning
AU - Yang, Chao
AU - Ballew, Shoshana H.
AU - Kalbaugh, Corey A.
AU - McEvoy, John W.
AU - Salameh, Maya
AU - Aguilar, David
AU - Hoogeveen, Ron C.
AU - Nambi, Vijay
AU - Selvin, Elizabeth
AU - Folsom, Aaron R.
AU - Heiss, Gerardo
AU - Coresh, Josef
AU - Ballantyne, Christie M.
AU - Matsushita, Kunihiro
N1 - Publisher Copyright:
© 2020 American Heart Association, Inc.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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 [International Classification of Diseases-Ninth Revision: 440.2–440.4] or leg revascularization [eg, International Classification of Diseases-Ninth Revision: 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.
AB - 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 [International Classification of Diseases-Ninth Revision: 440.2–440.4] or leg revascularization [eg, International Classification of Diseases-Ninth Revision: 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.
KW - epidemiology
KW - fibrosis
KW - inflammation
KW - peripheral arterial disease
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U2 - 10.1161/ATVBAHA.120.314824
DO - 10.1161/ATVBAHA.120.314824
M3 - Article
C2 - 32698688
AN - SCOPUS:85090080268
SN - 1079-5642
VL - 40
SP - 2322
EP - 2331
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 9
ER -