Impact of homocysteine levels on mortality risk in patients with chronic limb-threatening ischemia undergoing revascularization

The current study aimed to reveal the clinical impact of plasma homocysteine levels in chronic limb-threatening ischemia (CLTI) patients undergoing revascularization. This was a sub-analysis of a prospective multicenter registry of CLTI patients, named the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia (SPINACH) study. The current analysis included 192 non-dialysis-dependent CLTI patients who underwent revascularization for CLTI, and whose plasma homocysteine levels at baseline were available. The association of clinical characteristics with homocysteine levels was evaluated with the linear regression model. The association of homocysteine levels with the mortality risk was investigated using the Cox proportional hazards regression model. Cystatin C-based estimated glomerular filtration rate (eGFR) was independently associated with log-transformed homocysteine levels; the adjusted standardized regression coefficient (95% confidence interval) was - 0.432 (- 0.657 to - 0.253; P < 0.001). Homocysteine levels were significantly associated with the mortality risk in the univariate model (P = 0.017); the unadjusted hazard ratio was 1.71 (1.13-2.50) per twofold increase. The association was significantly attenuated when adjusted for cystatin C-based eGFR (P < 0.001); the hazard ratio adjusted for cystatin C-based eGFR was 1.28 (0.80-1.90; P = 0.29). An apparent association of homocysteine levels with an increased risk of mortality could be explained by renal dysfunction. Future studies will be needed to validate the current findings.