Lanphear · The Lancet. Public health 2018 · prospective cohort study · n=14289

Low-level lead exposure and mortality in US adults: a population-based cohort study.

Cited 620 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective cohort study of a nationally representative survey linked to mortality records.

PubMed 29544878 · doi:10.1016/S2468-2667(18)30025-2 · record verified 2026-08-28

What was done

Researchers analyzed 14,289 adults aged 20 years or older enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III, 1988–1994) with baseline blood lead and urine cadmium measurements. Participants were linked to the National Death Index and followed through December 31, 2011 (median follow-up 19.3 years). The authors evaluated associations and population attributable fractions between blood lead levels and all-cause, cardiovascular disease (CVD), and ischaemic heart disease (IHD) mortality.

What was found

Geometric mean blood lead was 2.71 μg/dL, and 20% (3,632 participants) had levels ≥5 μg/dL. Over follow-up, 4,422 deaths occurred (1,801 CVD, 988 IHD). An increase in blood lead from 1.0 to 6.7 μg/dL (10th to 90th percentile) was associated with all-cause mortality (hazard ratio [HR] 1.37, 95% CI 1.17–1.60), CVD mortality (HR 1.70, 95% CI 1.30–2.22), and IHD mortality (HR 2.08, 95% CI 1.52–2.85). The estimated population attributable fractions were 18.0% (95% CI 10.9–26.1) for all-cause mortality (412,000 annual US deaths), 28.7% (15.5–39.5) for CVD mortality (256,000 annual deaths), and 37.4% (23.4–48.6) for IHD mortality (185,000 annual deaths).

Why it matters

This study indicates that low-level environmental lead exposure is a major, underappreciated contributor to cardiovascular and all-cause mortality in US adults, highlighting lead reduction as a cardiovascular prevention priority.

Limits

Blood lead concentration was measured at a single baseline timepoint, failing to reflect changes in exposure over the ~19-year follow-up or cumulative lifetime skeletal burden. As an observational study, residual confounding cannot be ruled out, and population attributable fractions assume a causal relationship that observational data alone cannot confirm.

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