Environmental exposure to lead: old myths never die
Authors: Wen-Yi Yang, Zhen-Yu Zhang, Blerim Mujaj, Lutgarde Thijs, Jan A Staessen
Journal: The Lancet Public Health (2018)

Based on an analysis of NHANES III, published in The Lancet Public Health (April, 2018), Bruce Lanphear and colleagues1Lanphear BP Rauch S Auinger P Allen RW Hornung RW Low-level lead exposure and mortality in US adults: a population-based cohort study.Lancet Public Health. 2018; 3: e177-e184Summary Full Text Full Text PDF PubMed Scopus (188) Google Scholar propose that environmental exposure to lead, even at blood concentrations lower than 5 μg/dL, entails a population-attributable risk of cardiovascular mortality of 37·4%, thereby equalling the risk of smoking. This conclusion contrasts with expert opinion. Based on a comprehensive review of the literature, Navas-Acien and coworkers2Navas-Acien A Guallar E Silbergeld EK Rothenberg SJ Lead exposure and cardiovascular disease—a systematic review.Environ Health Perspect. 2007; 115: 472-482Crossref PubMed Scopus (582) Google Scholar concluded that there is sufficient evidence to infer a causal association of hypertension with lead exposure, but that the evidence is inconclusive to deduce a causal relation of cardiovascular outcomes with lead exposure. In our meta-analysis,3Nawrot TS Thijs L Den Hond EM Roels HA Staessen JA An epidemiological re-appraisal of the association between blood pressure and lead: a meta-analysis.J Hum Hypertens. 2002; 16: 123-131Crossref PubMed Scopus (166) Google Scholar a doubling of blood lead was associated with minimally higher blood pressure, only averaging 1·0 mm Hg (95% CI 0·5–1·4) for systolic blood pressure and 0·6 mm Hg (0·4–0·8) for diastolic blood pressure. A common point of view is that hypertension explains the association of cardiovascular endpoints with lead exposure. However, our analysis of NHANES 2003–2010 showed weak and inconsistent associations of blood pressure with blood lead.4Hara A Thijs L Asayama K et al.Blood pressure in relation to environmental lead exposure in the National Health and Nutrition Examination Survey 2003 to 2010.Hypertension. 2015; 65: 62-69Crossref PubMed Scopus (41) Google Scholar This finding excludes current environmental lead exposure as major causal contributor to hypertension in the USA.4Hara A Thijs L Asayama K et al.Blood pressure in relation to environmental lead exposure in the National Health and Nutrition Examination Survey 2003 to 2010.Hypertension. 2015; 65: 62-69Crossref PubMed Scopus (41) Google Scholar Notably, in the report by Lanphear and colleagues, associations of cardiovascular and coronary mortality with blood lead remained significant after adjustment for hypertension.1Lanphear BP Rauch S Auinger P Allen RW Hornung RW Low-level lead exposure and mortality in US adults: a population-based cohort study.Lancet Public Health. 2018; 3: e177-e184Summary Full Text Full Text PDF PubMed Scopus (188) Google Scholar A major limitation of Lanphear and colleagues' study is its exclusive focus on mortality. The introduction of stroke units and the wide availability of invasive coronary care and thrombolysis reduced the case-fatality rate of most cardiovascular complications of hypertension. Not accounting for non-fatal events therefore limits the generalisability of their report. Moreover, the authors did not report on the association of non-cardiovascular mortality with blood lead, an issue of relevance because cardiovascular illness and renal impairment go hand in hand, and environmental exposure to lead might increase the vulnerability of people at risk of chronic kidney disease.5Muntner P He J Vupputuri S Coresh J Batuman V Blood lead and chronic kidney disease in the general United States population: results from NHANES III.Kidney Int. 2003; 63: 1044-1050Summary Full Text Full Text PDF PubMed Scopus (154) Google Scholar The effect sizes reported in Lanphear and colleagues' report inflate the estimates of the population-attributable risk, because they were computed for the 90th to the 10th percentile intervals of the blood lead distribution.1Lanphear BP Rauch S Auinger P Allen RW Hornung RW Low-level lead exposure and mortality in US adults: a population-based cohort study.Lancet Public Health. 2018; 3: e177-e184Summary Full Text Full Text PDF PubMed Scopus (188) Google Scholar Computing this metric assumes causality, which cannot be deduced from an observational longitudinal study. Not surprisingly, all cardiovascular risk factors clustered within the highest third of the blood lead distribution.1Lanphear BP Rauch S Auinger P Allen RW Hornung RW Low-level lead exposure and mortality in US adults: a population-based cohort study.Lancet Public Health. 2018; 3: e177-e184Summary Full Text Full Text PDF PubMed Scopus (188) Google Scholar Blood lead probably serves as a surrogate for socioeconomic disadvantage and unequal access to health care. The authors adjusted for household income,1Lanphear BP Rauch S Auinger P Allen RW Hornung RW Low-level lead exposure and mortality in US adults: a population-based cohort study.Lancet Public Health. 2018; 3: e177-e184Summary Full Text Full Text PDF PubMed Scopus (188) Google Scholar but this adjustment is insufficient to correct for the differential impact of powerful social and ethnic confounders on morbidity and mortality. The authors might address this issue by reporting the interaction terms between ethnicity and blood lead and showing that the estimates of the risk function slopes are similar across income groups. In conclusion, in Lanphear and colleagues' report,1Lanphear BP Rauch S Auinger P Allen RW Hornung RW Low-level lead exposure and mortality in US adults: a population-based cohort study.Lancet Public Health. 2018; 3: e177-e184Summary Full Text Full Text PDF PubMed Scopus (188) Google Scholar hypertension is unlikely to explain the association between mortality and blood lead, and the underlying mechanisms remain unknown, precluding informed preventive strategies and targeted allocation of resources to reduce cardiovascular disease risk. The Research Unit Hypertension and Cardiovascular Epidemiology received an unrestricted grant from the International Lead Association for a study in workers employed at a lead recycling plant (ClinicalTrials.gov, number NCT02243904). Environmental exposure to lead: old myths never die – Authors' replyWen-Yi Yang and colleagues were troubled that our results1 contrast with expert opinion and concluded that hypertension is unlikely to explain the current association between concentrations of lead in blood and mortality. They also argued that, because the underlying mechanism of lead is unknown, it precludes preventive strategies and targeted allocation of resources to reduce cardiovascular disease risk. Full-Text PDF Open AccessLow-level lead exposure and mortality in US adults: a population-based cohort studyLow-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. Full-Text PDF Open Access