Lead Exposure and Plasma Homocysteine in Older Men: A Mechanism of Neurotoxicity and Vascular Toxicity?

Accumulating evidence suggests that nonoccupational exposures to lead may increase the risk for cardiovascular and neurologic outcomes such as hypertension and accelerated decline in cognition. Chronic low-level exposures, as measured by bone lead levels, are likely at least as important as acute exposures, as measured in blood lead. Elevated levels of plasma homocysteine (Hcy) are associated with cognitive decline and dementia, as well as cardiovascular disease.

Materials and Methods:
To examine lead's potential contribution to Hcy-mediated pathways in the development of these conditions, we evaluated bone and lead levels in association with plasma Hcy levels assessed up to 3 times over 6 years in a sample of 900 older men (mean age: 69 years) living in the Boston area. Analyses were adjusted for age, education, smoking, alcohol consumption, intake of vitamins B6 and B12, folate intake, and waist circumference.

Higher levels of lead independently predicted significantly higher levels of plasma Hcy. These findings held whether lead was measured in blood, cortical bone (tibia), or trabecular bone (patella). An interquartile range increment in blood lead (3 μg/dL) was associated with plasma Hcy levels that were 0.74 nmol/L higher (95% CI: 0.48-1.00; P<0.001). This increase in Hcy was similar to the increase in serum Hcy we observed for study participants who were about 9 years apart in age. Results pertaining to bone lead were similar; for example, an interquartile range in tibia lead (14 μg/dL) was associated with plasma Hcy levels that were 0.35 nmol/L higher (95% CI: 0.11-0.60; P = 0.005).

The single previously published study of lead exposure and Hcy found a significant association with blood lead, but not bone lead. Using repeated measurements of Hcy, our results complement and expand these prior findings, suggesting that lead may exert its neuro- and vascular toxicity, both acutely and chronically, by elevating Hcy.