Evidence on lead and the burden of cardiovascular disease (CVD) derived from National Health and Nutrition Examination Survey (NHANES) data, a general sample of the U.S. population, lacks sufficient representation of American Indians. Moreover, there is limited prospective evidence on lead and incident CVD outcomes.

We evaluated if blood lead levels were associated with CVD mortality and incidence in American Indian adults from the Strong Heart Study (SHS).

Whole blood samples collected in 1998–1999 among 1,818 participants was analyzed for lead using inductively coupled plasma mass spectrometry. CVD incidence and mortality were available through 2019. We used progressively adjusted multivariable Cox proportional hazards models to estimate the risk of composite CVD and coronary heart disease (CHD) mortality and incidence by baseline blood lead levels.

The median (p20, p80) blood lead was 22.5 (14.2, 37.3) µg/L, similar to that of a representative sample of US adults in NHANES 1999-2000. During follow-up, 578 (31.8%) participants had a composite CVD event and 454 (25.0%) participants had a CHD event. After adjustment for demographic, lifestyle, and cardiovascular risk factors, the hazard ratio (95% CI) per change across the 80^th to 20^th quantiles in blood lead was 1.15 (1.02-1.30) and 1.22 (1.08- 1.37) for CVD and CHD mortality, respectively, and 1.13 (1.02-1.24) and 1.12 (0.99-1.25) for CVD and CHD incidence, respectively. In flexible dose-response models, the associations appeared to be non-linear, with a clear increased risk of CVD and CHD mortality at blood lead concentrations above 35 µg/L.

Blood lead levels in American Indian adults, which are comparable to populations in the U.S. and globally, were associated with increased risk of CVD and CHD incidence and mortality. These findings highlight the importance of further reducing lead exposure, including American Indian communities. https://doi.org/10.1289/EHP16309