Association of Circulating Hepatocyte Growth Factor and Risk of Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis

Abstract

Higher levels of hepatocyte growth factor (HGF) have been associated with the presence of peripheral arterial disease (PAD), but prospective associations are unknown. We examined the association of circulating HGF levels with incident PAD. Between 2000 and 2002, HGF was measured in 6742 Multi-Ethnic Study of Atherosclerosis participants without PAD. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015. Incident low ankle-brachial index (ABI), defined as an ABI < 0.9 and a decline of ≥ 0.15, was assessed among 5736 individuals who had an ABI > 0.9 at baseline and ≥1 follow-up ABI measurement 3 to 10 years later. There were 116 clinical PAD and 197 low ABI events that occurred over a median follow-up of 14 and 9 years, respectively. After adjustment for demographic and clinical variables, a standard deviation increment of HGF (303 ng/L) was associated with an increased risk of clinical PAD (hazard ratio: 1.21; 95% confidence interval [CI]: 1.05-1.39) but not a low ABI (rate ratio: 1.03; 95% CI: 0.85-1.25). In conclusion, higher HGF levels were modestly associated with an increased risk of developing clinical PAD.

Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk

“…In this scenario, plasma biomarkers, only requiring one blood sample collection, yielded promising results in the prediction of both atherosclerosis extension and/or incident CVD events (12)(13)(14)(15)(16) . Plausible biomarkers include several circulating proteins that are involved in different pathogenic steps of the atherosclerotic plaque development, such as matrix metalloproteinases (MMPs) (17)(18)(19) , smooth muscle cells (SMC) (20)(21)(22)(23) and endothelial cells (EC) (20,(24)(25)(26)(27) growth factors (GFs), as well as mediators of apoptosis (20,(28)(29)(30)(31) and inflammation (20,32,33) . However, available studies focused on small subsets of these biomarkers and/or did not consider the complex interrelationship among them.…”

Obesity‐related inflammatory protein signature in cardiovascular clinical outcomes: results from the Gutenberg Health Study

“…Lowering IL-6 concentrations by targeting the upstream pathway with canakinumab was associated with a lower rate of cardiovascular events, independent of lipid-lowering, highlighting the substantial pathophysiological consequences of IL-6 for CVD [23]. Increased serum HGF has also been linked with cardiovascular complications, including myocardial infarction, congestive HF, ischemic retinopathy, and peripheral arterial disease [24][25][26][27]. In addition to IL-6 and HGF, CSF-1, ADA, IL-12B, TRANCE, and AXIN1 were also positively associated with obesity.…”

Angiogenesis-related proteins as biomarkers for peripheral artery disease

“…There is some conflicting literature regarding the direction of the association between HGF levels and PAD. Garg and colleagues (2020) found that elevated HGF levels were correlated with a higher risk of PAD development [ 38 ]. In contrast, multiple investigations have shown the effectiveness of transfecting pro-angiogenic HGF plasmid DNA into patients with PAD to improve clinical outcomes [ [39] , [40] , [41] ].…”