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Objective: We developed prediction models for bone lead using blood lead levels and other standard covariates in a community-based cohort of older men., Methods: Participants having bone lead levels measured by K X-ray fluorescence were included in the model selection process (n = 825). Predictors of each tibia and patella lead were identified in three quarters of the population and then predicted the bone lead levels in the remaining one quarter and in the Community Lead Study., Results: Eighteen predictors were selected for tibia (blood lead, age, education, occupation, smoking status, pack-years of cigarette, serum levels of phosphorus, uric acid, calcium, creatinine and total and high-density lipoprotein cholesterols, hematocrit, body mass index, systolic and diastolic blood pressure, and diagnoses of cancer and diabetes; R2 = 0.32) and 16 for patella lead (among the predictors included in the tibia model diagnosis of cancer, serum levels of calcium, and total cholesterol were not included in patella lead model, but diagnosis of hypertension was included; R2 = 0.34), respectively. The correlation coefficients between the observed and predicted values were 0.43 to 0.50 for tibia and 0.52 to 0.58 for patella lead in internal and external validation. We applied these predicted bone lead models to the Third National Health and Nutrition Examination Survey (NHANES-III) to examine associations with hypertension and found relatively more significant associations compared with blood lead., Conclusions: This study suggests that the prediction equations may be used to predict bone lead levels in other community-based cohorts with reasonable accuracy.

Objective: The objective of this study is to investigate the mobilization of lead from bone to blood (endogenous exposure) in a large epidemiologic population., Methods: Study subjects were 776 participants in the Normative Aging Study. The subjects had their tibia lead, patella lead, blood lead, and urinary N-telopeptide (NTx) levels measured 1 to 4 times from 1991 to 2002. Regression models were estimated to quantify the association between tibia and patella lead and blood lead. We studied nonlinearity of the association, and explored possible factors that may modify it, including age and NTx levels., Results and Conclusions: There is significant association between bone lead and blood lead, and the association is nonlinear. The nonlinear associations between blood lead and bone lead are not significantly modified by age and NTx.

Background: Outdoor air pollution and lead exposure can disturb cardiac autonomic function, but the effects of both these exposures together have not been studied., Methods: We examined whether higher cumulative lead exposures, as measured by bone lead, modified cross-sectional associations between air pollution and heart rate variability among 384 elderly men from the Normative Aging Study. We used linear regression, controlling for clinical, demographic, and environmental covariates., Results: We found graded, significant reductions in both high-frequency and low-frequency powers of heart rate variability in relation to ozone and sulfate across the quartiles of tibia lead. Interquartile range increases in ozone and sulfate were associated respectively, with 38% decrease (95% confidence interval = -54.6% to -14.9%) and 22% decrease (-40.4% to 1.6%) in high frequency, and 38% decrease (-51.9% to -20.4%) and 12% decrease (-28.6% to 9.3%) in low frequency, in the highest quartile of tibia lead after controlling for potential confounders. We observed similar but weaker effect modification by tibia lead adjusted for education and cumulative traffic (residuals of the regression of tibia lead on education and cumulative traffic). Patella lead modified only the ozone effect on heart rate variability., Conclusions: People with long-term exposure to higher levels of lead may be more sensitive to cardiac autonomic dysfunction on high air pollution days. Efforts to understand how environmental exposures affect the health of an aging population should consider both current levels of pollution and history of lead exposure as susceptibility factors.

Background: Lead exposure and psychological stress have been independently associated with hypertension in various populations, and animal studies suggest that when they co-occur, their effects may be exacerbated., Objectives: We examined whether psychological stress modifies the impact of cumulative lead exposure (measured as bone lead levels) on hypertension and blood pressure in Boston-area community-exposed men participating in the Normative Aging Study., Methods: We evaluated the modifying effect of stress on lead exposure on baseline hypertension status (513 participants) and on blood pressure in those without hypertension (237 participants), cross-sectionally. In baseline nonhypertensives, we examined the same risk factors in relation to prospective risk of developing hypertension., Results: Cross-sectional analysis revealed a positive interaction between stress and tibia lead on systolic blood pressure, after adjusting for age, body mass index, family history of high blood pressure, education, smoking, alcohol consumption, physical activity, and nutritional factors. In prospective multivariate analyses, high stress also modified the effect of tibia lead and patella lead on the risk of developing hypertension. Those reporting high stress had 2.66 [95% confidence interval (CI), 1.43-4.95] times the risk of developing hypertension per standard deviation increase in tibia lead and had 2.64 (95% CI, 1.42-4.92) times the risk per standard deviation increase in patella lead., Conclusion: To our knowledge, these are the first analyses to look at interactive effects of stress and lead on hypertension in humans. These results suggest that the effect of lead on hypertension is most pronounced among highly stressed individuals, independent of demographic and behavioral risk factors.

Background: Recent evidence suggests that cumulative lead exposure among adults in nonoccupational settings can adversely affect cognitive function. Which cognitive domains are affected has not been explored in detail., Methods: We used nonlinear spline regressions and linear repeated-measures analysis to assess the association between scores on a battery of cognitive tests over time and both blood and bone lead concentrations in the Normative Aging Study, a cohort of community-dwelling elderly men. Bone lead was measured from 1991 through 1999 with K-shell x-ray fluorescence. A total of 1089 men with a mean (+/-standard deviation) age of 68.7 (+/-7.4) years with blood lead measurements, 761 of whom also had valid bone lead measurements, completed at least one of a battery of cognitive tests. Approximately 3.5 years later, 69% of the men had at least one repeat test. Cognitive testing was performed from 1993 through 2001., Results: On a cross-sectional basis, there was little association between blood or bone lead and cognitive test scores. Change in performance over time on virtually all tests worsened as bone lead increased, with the most robust effects on performance and reaction time scores on visuospatial/visuomotor tests., Conclusions: Low-level cumulative exposure to lead in nonoccupational settings may adversely affect cognitive function, particularly in the visuospatial/visuomotor domain.