Arsenic-contaminated well water has been shown to increase the risk of
atherosclerosis. Because of involving
S-adenosylmethionine,
homocysteine may modify the risk by interfering with the biomethylation of ingested
arsenic. In this study, we assessed the effect of plasma
homocysteine level and urinary
monomethylarsonic acid (MMA(V)) on the risk of
atherosclerosis associated with
arsenic. In total, 163 patients with
carotid atherosclerosis and 163 controls were studied. Lifetime cumulative
arsenic exposure from well water for study subjects was measured as index of
arsenic exposure.
Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA(V) (MMA%) was calculated by dividing with total
arsenic species in urine, including
arsenite,
arsenate, MMA(V), and
dimethylarsinic acid (DMA(V)). Results of multiple linear regression analysis show a positive correlation of plasma
homocysteine levels to the cumulative
arsenic exposure after controlling for
atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of
arsenic exposure on the risk of
atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma
homocysteine levels did not confer an independent risk for developing
atherosclerosis in the study population. However, the risk of having
atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% (> or =16.5%) and high
homocysteine levels (> or =12.7 micromol/l) as compared to those with low MMA% (<9.9%) and low
homocysteine levels (<12.7 micromol/l). Elevated
homocysteinemia may exacerbate the formation of
atherosclerosis related to
arsenic exposure in individuals with high levels of MMA% in urine.