High prevalence of mild hyperhomocysteinemia in patients with abdominal aortic aneurysm

Purpose:In vitro studies have recently demonstrated that homocysteine interacts with the aortic wall by inducing both elastolysis and endothelial perturbation. The aim of this study was to evaluate homocysteine plasma levels and their relationships with aortic diameter and endothelial damage in patients with abdominal aortic aneurysm. Subjects and Methods: Fifty-eight consecutive male patients (mean age, 69.5 +/- 6.6 years; age range, 49-78 years) who underwent abdominal aortic aneurysm surgery were enrolled in the study. Twenty-two of 58 patients had no clinical or instrumental evidence of atherosclerosis. Sixty control subjects were age matched and sex matched with the patients. In all of the subjects, we evaluated total homocysteine and thrombomodulin plasma levels and the distribution of the C677T methylenetetrahydrofolate reductase gene mutation. Results: Hyperhomocysteinemia was found in 26 (48%) of the 58 patients with abdominal aortic aneurysm, and homocysteine plasma levels were significantly higher in patients than in control subjects (15.7 +/- 6.5 mu mol/L vs 9.6 +/- 3.9 mu mol/L; P < .0001). In addition, the subgroup of patients with abdominal aortic aneurysm who did not show evidence of atherosclerosis showed homocysteine plasma levels significantly higher than those in the controls (14.8 +/- 6.1 mu mol/L vs 9.6 +/- 3.9 mu mol/L; P < .001). A larger aneurysmal size was detected in hyperhomocysteinemic patients than in those with normal homocysteine plasma levels (5.09 +/- 0.84 an vs 5.79 +/- 1.5 an; P < .05). The genotype distribution of the C677T methylenetetrahydrofolate reductase mutation was as follows: TC 21%, TC 55%, and CC 24% in the patients; TT 10%, TC 58%, and CC 32% in the controls. Moreover, in patients a significant correlation (P < .005) between homocysteine plasma level and 677TT methylenetetrahydrofolate reductase genotype was found. Thrombomodulin plasma levels were significantly higher (P < .00005) in patients (median, 30 ng/mL; range, 10-164 ng/mL) than in controls (median, 19 ng/mL; range, 13-44 ng/mL), and thrombomodulin levels were significantly higher (P < .005) in hyperhomocysteinemic patients (median, 39.5 ng/mL; range, 15-164 ng/mL) than in normohomocysteinemic patients (median, 27.5 ng/mL; range, 10-85 ng/mL). In addition, in patients with abdominal aortic aneurysm, a direct significant correlation (P < .005) was found between homocysteine and thrombomodulin. Conclusions: These data indicate an association between the presence of AAA in patients selected for surgical treatment of AAA and elevated homocysteine plasma levels and suggest that homocysteine may induce endothelial perturbation and stimulation in these patients.