Homocysteine, the cholesterol of the 21^st century. Impact of hyperhomocysteinemia on patency and amputation-free survival after intervention for critical limb ischemia

Purpose: 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). Methods: 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. Results: 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 μmol/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 μmol/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). Conclusion: 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.