Homocysteine, the Cholesterol of the 21stCentury. Impact of Hyperhomocysteinemia on Patency and Amputation-Free Survival After Intervention for Critical Limb Ischemia

Abstract

To assess the prevalence of hyperhomocysteinemia and determine any correlation to the clinical and technical outcome of peripheral arterial revascularization for critical limb ischemia (CLI). Between October 1, 2002, and December 31, 2006, 953 revascularization procedures were performed for CLI in a high-volume tertiary referral vascular/endovascular unit. Fasting plasma homocysteine was accurately measured preoperatively in 225 patients (124 men; mean age 75.8 years, range 45-98), who formed the basis for the study. All patients had multilevel disease (TASC II C and D lesions), and 73% had single vessel runoff. Composite primary endpoints included primary, assisted primary, and secondary patency; amputation-free survival; and all-cause mortality. The prevalence of hyperhomocysteinemia was 30% [69 patients (36 men; mean age 78.2 years, range 53-93)]; most (88%) of the patients showed a mild elevation in homocysteine (13-20 micromol/L). Patients with hyperhomocysteinemia had significantly lower primary, assisted primary, and secondary patency rates at all intervals to 36 months (3.3%, 10.8%, and 11.2%, respectively; p<0.001) after the intervention compared to patients with normal homocysteine levels (50.8%, 54.6%, and 57.1%, respectively). The mean amputation-free survival was significantly lower for patients with hyperhomocysteinemia (54.8% versus 81.0%, p=0.008). Overall, 27% of the normal homocysteine group progressed to vessel occlusion compared to 65% of the hyperhomocysteinemia group (p<0.0001). There was no significant difference between groups with respect to 4-year cumulative all-cause mortality (p=0.331). In a multivariate logistic regression analysis, only a homocysteine level >13.0 micromol/L was found to be significantly associated with adverse outcomes, such as amputation (OR=3.4, 95% CI 1.27 to 9.01; p=0.015) and graft occlusion (OR=7.97, 95% CI 3.63 to 17.5; p<0.0001). Hyperhomocysteinemia appears to be an independent risk factor for the progression of vascular disease and is an adverse prognostic factor for CLI patients undergoing peripheral arterial revascularization.