Low-level Lead Exposure and Mortality in US Adults: A Population-based Cohort Study

Background: Lead exposure is a risk factor for cardiovascular disease mortality, but the number of deaths in the USA attributable to lead exposure is poorly defined. We aimed to quantify the relative contribution of environmental lead exposure to all-cause mortality, cardiovascular disease mortality, and ischaemic heart disease mortality. Methods: Our study population comprised a nationally representative sample of adults aged 20 years or older who were enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III) between 1988 and 1994 and followed up to Dec 31, 2011. Participants had completed a medical examination and home interview and had results for concentrations of lead in blood, cadmium in urine, and other relevant covariates. Individuals were linked with the National Death Index. This study presents extended follow-up of an earlier analysis. Findings: We included 14289 adults in our study. The geometric mean concentration of lead in blood was 2·71 µg/dL (geometric SE 1·31). 3632 (20%) participants had a concentration of lead in blood of at least 5 µg/dL (≥0·24 μmol/L). During median follow-up of 19·3 years (IQR 17·6–21·0), 4422 people died, 1801 (38%) from cardiovascular disease and 988 (22%) from ischaemic heart disease. An increase in the concentration of lead in blood from 1·0 µg/dL to 6·7 µg/dL (0·048 μmol/L to 0·324 μmol/L), which represents the tenth to 90th percentiles, was associated with all-cause mortality (hazard ratio 1·37, 95% CI 1·17–1·60), cardiovascular disease mortality (1·70, 1·30–2·22), and ischaemic heart disease mortality (2·08, 1·52–2·85). The population attributable fraction of the concentration of lead in blood for all-cause mortality was 18·0% (95% CI 10·9–26·1), which is equivalent to 412000 deaths annually. Respective fractions were 28·7% (15·5–39·5) for cardiovascular disease mortality and 37·4% (23·4–48·6) for ischaemic heart disease mortality, which correspond to 256000 deaths a year from cardiovascular disease and 185000 deaths a year from ischaemic heart disease. Interpretation: Low-level environmental lead exposure is an important, but largely overlooked, risk factor for cardiovascular disease mortality in the USA. A comprehensive strategy to prevent deaths from cardiovascular disease should include efforts to reduce lead exposure