Associations between blood lead and urinary cadmium concentrations and all-cause and specific causes of mortality: estimating intervention effects using the parametric g-formula

Abstract Objective Previous studies in the US reported a high mortality risk associated with higher blood lead levels (BLLs) and urinary cadmium (UCd) levels. The aim of this study was to extend the follow-up of the previous analyses and use the parametric g-formula to estimate the 27-year risk of all-cause and specific causes of mortality. Methods We used data on 14,311 adults aged ≥ 20 years enrolled in the NHANES-III between 1988 and 1994 and followed up through Dec 31, 2015. Time and cause of death were determined from the National Death Index records. We used the parametric g-formula with pooled logistic regression models to estimate the relative and absolute risk of all-cause, cardiovascular, and cancer mortality under different potential threshold interventions on BPb and UCd concentrations. Results Median follow-up was 22.5 years, 5,167 (36%) participants died by the end of the study; 1,550 from cardiovascular disease and 1,135 from cancer. An increase of BLLs and creatinine corrected UCd from the 5th (0.70 µg/dL and 0.04 µg/g for BLLs and UCd ) to the 95th percentile (9.70 µg/dL and 1.63 µg/g for BLLs and UCd) was associated with an increased risk of all-cause by 138% (95% CI, 14 to 196) and a 126% (95% CI, 77 to 383). BLLs and UCd were associated with an increase of 109% (95% CI, 4 to 268) and 37% (95% CI, -0.20 to 239) in the risk of cardiovascular mortality when comparing the 5th to the 95th percentiles of exposure. The corresponding increase in risk for cancer mortality was 287% (95% CI, 12 to 691) and 144% (95% CI, -0.34 to 281) for BLLs and UCd, respectively. We found higher risk differences among men and older participants as compared to their counterparts. Conclusion Interventions to reduce historical exposures to lead and cadmium could have prevented several deaths, especially among individuals ≥ 50 years of age as well as in men.