Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral Artery Disease

Abstract

Aim: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated.Methods: We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening.Results: CAD was found in 224 patients (1-vessel [1-VD], n = 92; 2-vessel [2-VD], n = 65; 3-vessel disease [3-VD], n = 67). No significant difference was found in the FGF-21 levels between 224 patients with CAD and 193 without CAD (median 26.0 vs. 25.9 pg/mL). FGF-21 levels in 4 groups of CAD(−), 1-VD, 2-VD, and 3-VD were 25.9, 37.2, 19.4, and 0.0 pg/mL. FGF-21 tended to be highest in 1-VD and lowest in 3-VD, but the difference did not reach statistical significance. PAD was found in 38 patients. Compared to the 379 patients without PAD, 38 with PAD had CAD more often (87% vs. 50%), especially 3-VD (P < 0.001). FGF-21 levels were lower in patients with PAD than in those without PAD (0.0 vs. 30.7 pg/mL, P < 0.02). In multivariate analysis, the FGF-21 level was an independent factor for PAD, but not for CAD. Odds ratio for PAD was 2.13 (95%CI= 1.01–4.49) for a low FGF-21 level (< 15.6 pg/mL).Conclusion: No significant difference was found in the FGF-21 levels between patients with and without CAD. However, FGF-21 levels were low in patients with PAD, and were a factor for PAD independent of atherosclerotic risk factors.

Plasma Heme Oxygenase-1 Levels in Patients with Coronary and Peripheral Artery Diseases

“…The severity of PAD was classified from stage I to IV according to Fontaine's classification. This study followed the methods of our previous study by Miyazaki et al [ 17 ]. Any patients with a history of percutaneous coronary intervention or cardiac surgery were excluded.…”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…In EAT from T2DM patients with multivessel CAD, FGF-21 gene expression is reduced [ 317 ], and in patients undergoing cardiac surgery, FGF-21 expression in EAT increases after surgery, suggesting a role protecting from surgery-related inflammatory response [ 319 ]. However, several studies have shown that increased levels of circulating FGF-21 are associated with the presence of atherosclerosis [ 337 , 338 , 339 , 340 , 341 ], although there are contradictory results [ 342 ].…”

High plasma FGF21 levels predicts major cardiovascular events in patients treated with atorvastatin (from the Treating to New Targets [TNT] Study)

“…There are also some limitations. Participants were not further stratified into subgroups based on the number of coronary arteries involved or degree of stenosis, however another cross-sectional study found no significant difference in plasma FGF21 levels among CHD patients by numbers of stenosed coronary arteries involved [26]. The present study was a post-hoc analysis of the TNT trial, though all analyses were performed after pre-stating Data are expressed as median (interquartile range).…”

“…In rodent models, cardiomyocytes can secrete FGF21 in response to global cardiac ischemia [19]. However, some human studies have shown no associations between FGF21 levels and CVD [25,26]. Nevertheless, these studies are limited by having a cross-sectional design and relatively small sample size (n b 420).…”