New estimates suggest that 256000 premature deaths from cardiovascular disease - including 185000 deaths from ischemic heart disease - in the USA may be linked to historical lead exposure in middle-aged and older adults (people currently aged 44 years or over), according to an observational study following 14300 people for almost 20 years, published in The Lancet Public Health journal.
Previous estimates, which assumed that low-level lead exposure did not increase the risk of premature death, produced substantially fewer deaths. However, this new study finds that low-level lead exposure (between 1-5 micrograms of lead per decilitre of blood) increases the risk of premature death, especially from cardiovascular disease. Lead exposure is linked to high blood pressure, hardening of the arteries and ischemic (coronary) heart disease.
Exposure occurs from lead that remains in the environment from historic use in fuel, paint and plumbing, as well as ongoing exposures from foods, emissions from industrial sources, and contamination from lead smelting sites and lead batteries. 
This study is the first to estimate the number of deaths in the United States from low-level lead exposure using a nationally-representative sample.
"Our study estimates the impact of historical lead exposure on adults currently aged 44 years old or over in the USA, whose exposure to lead occurred in the years before the study began," says lead author Professor Bruce Lanphear, Simon Fraser University, Canada. "Today, lead exposure is much lower because of regulations banning the use of lead in petrol, paints and other consumer products, so the number of deaths from lead exposure will be lower in younger generations. Still, lead represents a leading cause of disease and death, and it is important to continue our efforts to reduce environmental lead exposure." 
The study used data from the Third National Health and Nutrition Examination Survey (NHANES-III) for 14289 people in the USA aged 20 years or older between 1988 and 1994, and the end of 2011. All participants had a medical examination, including a blood test for lead - a measure of past and ongoing exposures to lead - and a urine test for cadmium at the start of the study.
After an average of 19.3 years, 4422 people died including 1801 from cardiovascular disease and 988 from heart disease.
At the outset, the average level of lead found in the participants' blood was 2.7 μg/dL, but ranged from less than 1 to 56 μg/dL. One in five participants (3632 people) had levels of 5 μg/dL or more, and those with the highest levels of lead in their blood were older, less educated, more likely to be male, smoke, consume larger amounts of alcohol, have less healthy diets, have higher cholesterol, and more likely to have hypertension or diabetes.
Almost one in 10 participants had lead levels that were undetectable to the blood test, so were given a reference level of 0.7 μg/dL (8%, 1150/14289 participants).
Overall, people who had high lead levels (6.7 μg/dL) were at 37% greater risk of premature death from any cause, 70% times greater risk of cardiovascular death, and double the risk of death from ischemic heart disease, compared with people with lower levels (1 μg/dL).
Using these risk levels, the authors also estimated the current proportion of deaths in adults aged 44 years or older in the USA that could have been prevented if historical exposure to lead had not occurred.
Overall, they found that up to 18% of all deaths every year in the USA (412000/2.3 million) would be among people who had levels of lead above 1 μg/dL. They estimated that 28.7% of premature cardiovascular disease deaths (256000/ 892000) could be attributable to lead exposure, including a high proportion of ischemic heart disease deaths (lead was linked to 37.4% of all IHD deaths [185000/495000]).
These results were adjusted for age, sex, household income, ethnic origin, diabetes, BMI, smoking status, alcohol consumption, diet, physical activity, and amount of cadmium in urine.
"Our study calls into question the assumption that specific toxicants, like lead, have 'safe levels', and suggests that low-level environmental lead exposure is a leading risk factor for premature death in the USA, particularly from cardiovascular disease," says Professor Lanphear. "Estimating the contribution of low-level lead exposure is essential to understanding trends in cardiovascular disease mortality and developing comprehensive strategies to prevent cardiovascular disease. Currently, low levels of lead exposure are an important, but largely ignored risk factor for deaths from cardiovascular disease. Public health measures, such as abating older housing, phasing out lead-containing jet fuels, replacing lead-plumbing lines, and reducing emissions from smelters and lead battery facilities, will be vital to prevent lead exposure." 
The authors note some limitations, including that their results rely on one blood lead test taken at the start of the study and therefore cannot determine any effect of further lead exposure after the study outset. The authors were also unable to control for all potential confounding factors, such as exposure to arsenic or air pollution, which are also risk factors for cardiovascular disease.
Writing in a linked Comment, Professor Philip Landrigan, Icahn School of Medicine at Mount Sinai, USA, says: "A recurrent theme in lead poisoning research has been the realization that lead has toxic effects on multiple organ systems at relatively low levels of exposure previously thought to be safe... A key conclusion to be drawn from this analysis is that lead has a much greater impact on cardiovascular mortality than previously recognized... [The authors] suggest that the time has come to end neglect of pollution's contribution to non-communicable diseases' mortality and to thoroughly re-examine lead's role in changing global patterns of cardiovascular disease."
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