Abstract

Hyperhomocysteinemia has been associated with vascular disease in many epidemiologic studies, but only a few have reported on the relation between hyperhomocysteinemia and aneurysms of the abdominal aorta (AAAs). Although these studies showed higher homocysteine concentrations in patients with AAA than in controls, little attention had been given to possible confounding factors. Most patients with AAA are of older age, have an impaired renal function, and have other risk factors for cardiovascular disease. This matched case-control study investigated the relation between homocysteine concentration (before and after methionine loading) and AAA, taking into account possible confounders such as age, sex, and concentrations of creatinine and B vitamins. Patients with a history of AAA were recruited from the outpatient clinic; 60% had already undergone surgery for their AAA. They were asked to invite a friend or neighbor to participate as a control subject (age-matched and sex-matched). Concentrations of homocysteine, vitamin B6, vitamin B12, folate, and creatinine were determined in the fasting state, and blood was taken for methylenetetrahydrofolate reductase (MTHFR) mutation analysis. Six hours after oral methionine loading, the postmethionine load homocysteine concentration was determined. Univariate analysis showed an odds ratio (OR) of 2.2 (95% confidence interval (CI), 0.9 to 5.5) for the risk of AAA for the highest quartile of homocysteine concentration. After adjustment for creatinine, the OR was markedly reduced to 1.24 (95% CI, 0.42 to 3.66), and this risk further attenuated in the multivariate analysis. Univariate analysis of the B vitamins showed an increased risk of AAA for the bottom quartile of vitamin B6 (OR, 3.75; 95% CI, 1.22 to 11.54), which even increased after adjustments. The relative risk associated with the MTHFR 677TT polymorphism was 2.1 (95% CI, 0.9 to 5.3). Vitamin B6, but not homocysteine, is an independent risk factor for AAA. The role of vitamin B6 in the pathogenesis of AAA needs to be further elucidated.

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