The Klotho-FGF23 axis and cardiovascular outcomes in diabetic patients with chronic limb threatening ischemia: a prospective study

Abstract

Abstract Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-FGF23 axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho-FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho, and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs 446.4 ± 171.7 pg/mL, p < 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs 53.2 ± 15.4 pg/mL, p < 0.01) were significantly associated with the development of MACE. ROC analysis confirmed the predictive power of the Klotho-FGF23 axis. Furthermore, decreased Klotho serum levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p < 0.01). We found that Klotho-FGF23 axis imbalance is a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.