Blood Lead Is a Predictor of Homocysteine Levels
Lead and homocysteine are both associated with cardiovascular disease and cognitive dysfunction. We evaluated the relations among blood lead, tibia lead, and homocysteine levels by cross-sectional analysis of data among subjects in the Baltimore Memory Study, a longitudinal study of 1,140 randomly selected residents in Baltimore, Maryland, who were 50-70 years of age. Tibia lead was measured by Cd K-shell X-ray fluorescence. The subject population had a mean ± SD age of 59.3 ± 5.9 years and was 66.0% female, 53.9% white, and 41.4% black or African American. Mean ± SD blood lead, tibia lead, and homocysteine levels were 3.5 ± 2.4 µg/dL, 18.9 ± 12.5 µg/g, and 10.0 ± 4.1 µmol/L, respectively. In unadjusted analysis, blood lead and homocysteine were moderately correlated (Pearson's r = 0.27, p < 0.01). After adjustment for age, sex, race/ethnicity, educational level, tobacco and alcohol consumption, and body mass index using multiple linear regression, results revealed that homocysteine levels increased 0.35 µmol/L per 1.0 µg/dL increase in blood lead (p < 0.01). The relations of blood lead with homocysteine levels did not differ in subgroups distinguished by age, sex, or race/ethnicity. Tibia lead was modestly correlated with blood lead (Pearson's r = 0.12, p < 0.01) but was not associated with homocysteine levels. To our knowledge, these are the first data to reveal an association between blood lead and homocysteine. These results suggest that homocysteine could be a mechanism that underlies the effects of lead on the cardiovascular and central nervous systems, possibly offering new targets for intervention to prevent the long-term consequences of lead exposure.
As a result of centuries of human use, lead is omnipresent in the environment. Commercial use of this substance continues even though its toxic effects have been recognized since ancient times (Nriagu 1983), and more recent studies report health effects associated with lower and lower lead doses (Canfield et al. 2003; Glenn et al. 2003; Nash et al. 2003; Schwartz et al. 2000). Lead is not rapidly cleared from the body; the biologic residence time of lead in blood is measured in days, whereas the biologic residence time of lead in bone is on the order of years to decades (Hu et al. 1998). In occupational and general population samples, low blood lead levels have been associated with increased blood pressure and elevated risk of hypertension, effects that may be progressive (Cheng et al. 2001; Glenn et al. 2003; Nash et al. 2003); increased circulatory and cardiovascular mortality (Lustberg and Silbergeld 2002); and progressive declines in cognitive function over time, even years after cessation of occupational exposure (Schwartz et al. 2000, 2002, in press). One of the key remaining problems in the research of lead toxicity is that the mechanisms for these effects are not well understood.
Interestingly, homocysteine is also associated with cardiovascular disease and cognitive dysfunction (Dufouil et al. 2003; Homocysteine Collaboration 2002). Homocysteine is an independent risk factor for vaso-occlusive disease; elevated levels of homocysteine increase the risk of heart disease, stroke, and peripheral vascular disease and, perhaps through vascular mechanisms, cognitive dysfunction (Bautista et al. 2002; Dufouil et al. 2003; Homocysteine Collaboration 2002; Prins et al. 2002; Ravaglia et al. 2003; Wald et al. 2002). Vascular damage by homocysteine may occur through impaired vascular endothelial and smooth muscle cell function (Rodrigo et al. 2003). The mechanisms of this impairment may involve inhibition of nitric oxide synthesis, increased oxidative stress, proliferation of vascular smooth muscle cells, and altered elasticity of the vascular wall (Rodrigo et al. 2003).
Despite the similarities in these health effects, the relation of homocysteine and lead dose has not been previously examined. Herein, we report associations of blood lead, tibia lead, and homocysteine in a population-based study of persons 50-70 years of age in Baltimore, Maryland. Participants were selected from the general population, and most are without occupational lead exposure.
Lead and homocysteine are both associated with cardiovascular disease and cognitive dysfunction. We evaluated the relations among blood lead, tibia lead, and homocysteine levels by cross-sectional analysis of data among subjects in the Baltimore Memory Study, a longitudinal study of 1,140 randomly selected residents in Baltimore, Maryland, who were 50-70 years of age. Tibia lead was measured by Cd K-shell X-ray fluorescence. The subject population had a mean ± SD age of 59.3 ± 5.9 years and was 66.0% female, 53.9% white, and 41.4% black or African American. Mean ± SD blood lead, tibia lead, and homocysteine levels were 3.5 ± 2.4 µg/dL, 18.9 ± 12.5 µg/g, and 10.0 ± 4.1 µmol/L, respectively. In unadjusted analysis, blood lead and homocysteine were moderately correlated (Pearson's r = 0.27, p < 0.01). After adjustment for age, sex, race/ethnicity, educational level, tobacco and alcohol consumption, and body mass index using multiple linear regression, results revealed that homocysteine levels increased 0.35 µmol/L per 1.0 µg/dL increase in blood lead (p < 0.01). The relations of blood lead with homocysteine levels did not differ in subgroups distinguished by age, sex, or race/ethnicity. Tibia lead was modestly correlated with blood lead (Pearson's r = 0.12, p < 0.01) but was not associated with homocysteine levels. To our knowledge, these are the first data to reveal an association between blood lead and homocysteine. These results suggest that homocysteine could be a mechanism that underlies the effects of lead on the cardiovascular and central nervous systems, possibly offering new targets for intervention to prevent the long-term consequences of lead exposure.
As a result of centuries of human use, lead is omnipresent in the environment. Commercial use of this substance continues even though its toxic effects have been recognized since ancient times (Nriagu 1983), and more recent studies report health effects associated with lower and lower lead doses (Canfield et al. 2003; Glenn et al. 2003; Nash et al. 2003; Schwartz et al. 2000). Lead is not rapidly cleared from the body; the biologic residence time of lead in blood is measured in days, whereas the biologic residence time of lead in bone is on the order of years to decades (Hu et al. 1998). In occupational and general population samples, low blood lead levels have been associated with increased blood pressure and elevated risk of hypertension, effects that may be progressive (Cheng et al. 2001; Glenn et al. 2003; Nash et al. 2003); increased circulatory and cardiovascular mortality (Lustberg and Silbergeld 2002); and progressive declines in cognitive function over time, even years after cessation of occupational exposure (Schwartz et al. 2000, 2002, in press). One of the key remaining problems in the research of lead toxicity is that the mechanisms for these effects are not well understood.
Interestingly, homocysteine is also associated with cardiovascular disease and cognitive dysfunction (Dufouil et al. 2003; Homocysteine Collaboration 2002). Homocysteine is an independent risk factor for vaso-occlusive disease; elevated levels of homocysteine increase the risk of heart disease, stroke, and peripheral vascular disease and, perhaps through vascular mechanisms, cognitive dysfunction (Bautista et al. 2002; Dufouil et al. 2003; Homocysteine Collaboration 2002; Prins et al. 2002; Ravaglia et al. 2003; Wald et al. 2002). Vascular damage by homocysteine may occur through impaired vascular endothelial and smooth muscle cell function (Rodrigo et al. 2003). The mechanisms of this impairment may involve inhibition of nitric oxide synthesis, increased oxidative stress, proliferation of vascular smooth muscle cells, and altered elasticity of the vascular wall (Rodrigo et al. 2003).
Despite the similarities in these health effects, the relation of homocysteine and lead dose has not been previously examined. Herein, we report associations of blood lead, tibia lead, and homocysteine in a population-based study of persons 50-70 years of age in Baltimore, Maryland. Participants were selected from the general population, and most are without occupational lead exposure.