Association of Klotho and FGF23 with cardiovascular outcomes in diabetic older adults with chronic limb-threatening ischemia: a prospective study

Abstract

Peripheral arterial disease (PAD) is more prevalent in individuals with type 2 diabetes mellitus (T2DM). The most severe complication of PAD is chronic limb-threatening ischemia (CLTI), which is associated with major adverse cardiovascular events (MACE) and major adverse limb events (MALE) following lower limb revascularization (LER). This study investigates the relationship between baseline levels of Klotho and FGF23 and the risk of cardiovascular and limb-related outcomes after LER in a selected cohort of older adults. The study enrolled 109 older patients with PAD and CLTI requiring LER. Baseline levels of Klotho and FGF23 were measured, and their associations with subsequent MACE and MALE were analyzed over a 12-month follow-up period. Using stepwise multivariable logistic regression and Cox proportional hazards models, we found that among 109 older patients with PAD and CLTI undergoing LER, independent predictors of MACE included age (p = 0.016), male sex (p = 0.006), BMI (p = 0.004), diabetes duration (p = 0.031), hypertension (p = 0.013), and smoking status (p < 0.001), with higher FGF23 (p < 0.001) and lower Klotho levels (p = 0.002) significantly associated with increased risk; in the Cox model, increased Klotho was linked to a reduced risk of MACE (95% CI: 0.994–1.000, p = 0.022), while multivariate analysis for MALE confirmed Klotho as an independent predictor (p < 0.01). These findings reinforce the hypothesis that altered baseline levels of Klotho, and FGF23 are associated with adverse cardiovascular and limb outcomes in diabetic individuals over 75 years old with PAD and CLTI, highlighting their potential role as biomarkers for post-revascularization risk stratification.