Do We Underestimate Risk of Mortality due to Lead Exposure?

Abstract

Background/Aim: Studies using data from the National Health and Nutrition Examination Survey-III (NHANES-III) have demonstrated significant associations between blood lead levels and increased mortality. However, blood lead reflects primarily recent exposure and lead mobilized from internal organs. Bone lead represents cumulative lead burden and thus is a better biomarker for assessing chronic impacts, but its in vivo assessment requires special K-x-ray fluorescence (KXRF) instrumentation. Our team used KXRF measurements of lead in bone and blood lead levels in participants of the Normative Aging Study to develop an algorithm predicting bone lead levels from a combination of blood lead levels and standard biochemical, hematologic, and questionnaire data. We examined the associations of our algorithm-estimated bone lead levels and mortality in NHANES-III.Methods: We included 11,065 adults followed up to December 31, 2015. Estimated tibia and patella bone lead levels were calculated using our prediction algorithm. We used survey-weighted Cox proportional hazards models to compute hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During the median follow-up of 22.4 years (216,565 person-years), 4,103 participants died (mortality rate=1,895 per 100,000 adults/year). Means (95% CIs) of blood lead, tibia lead, and patella lead were 3.47 μg/dL (3.27-2.67), 2.98 μg/g (2.23-3.75), and 3.04 μg/g (1.94-4.14), respectively. After adjustment for potential confounders, the HRs comparing participants at the 90th vs. 10th percentiles of exposure with regards to all-cause mortality were 1.25 (95% CI: 1.05-1.50) for blood lead, 1.91 (1.36-2.68) for tibia lead, 2.00 (1.45-2.77) for patella lead; for CVD mortality, 1.67 (1.20-2.34) for blood lead, 1.89 (0.98-3.67) for tibia lead, 2.24 (1.26-4.00) for patella lead; and for cancer mortality, 1.35 (0.98-1.84) for blood lead, 2.52 (1.30-4.90) for tibia lead, 2.45 (1.29-4.66) for patella lead.Conclusions: These findings suggest that risk assessment based on blood lead levels may underestimate the true mortality risk of lead exposure.