EXPERT REACTION: Almost 1 in 3 cardiovascular deaths in the US could be because of lead

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Low-level lead exposure may be responsible for around 30 per cent of premature deaths from cardiovascular disease in the USA each year, according to international researchers.  Researchers monitored the lead levels in more than 14,000 people over 20 years and found that even low-level lead exposure (between 1-5 micrograms of lead per decilitre of blood) increases the risk of premature death. The researchers say the study calls into question the assumption that there are ‘safe levels’ of lead exposure and suggests that low-level environmental lead exposure is a leading risk factor for premature death in the USA, particularly from cardiovascular disease.

Journal/conference: The Lancet Public Health

DOI: 10.1016/S2468-2667(18)30025-2

Organisation/s: Simon Fraser University, Canada

Media Release

From: The Lancet

Historical lead exposure may be linked to 256000 premature deaths from cardiovascular disease in adults the USA each year

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. [1]

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.” [2]

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.” [2]

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.”


This study was funded by the Artemis Fund and Simon Fraser University. It was conducted by researchers from Simon Fraser University, University of California at Berkeley, University of Rochester School of Medicine and Dentistry, Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine.


[2] Quote direct from author and cannot be found in the text of the Article.

[3] The authors note that these estimates are comparable to the annual number of deaths in the US in people who currently smoke (483000 deaths a year). This is because the risk of death from lead exposure is lower (HR = 1.37, 95%CI = but more prevalent across the population (in the study, 90% of participants were exposed to lead). Comparatively, 20% of the US population smoke, but the risk of premature death is higher (HR=1.75 95%CI = 1.50-2.05) than for low-level lead exposure.


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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Adjunct Professor Peter Baghurst is Former Head of the Public Health Research Unit, Women's and Children's Hospital, University of Adelaide

As noted by the authors, the study relies entirely on just one blood lead measurement made 20 years before the outcomes were assessed.

As was also noted quite properly, by the authors, they cannot rule out the possibility that their findings were due to the statistical phenomenon of ‘residual confounding’. The baseline characteristics (Table 1) showed that those study-subjects with the lowest lead exposure were more likely to: be white, younger, more educated, and have better incomes, smoke less, drink less alcohol, be more physically active, be less likely to have diabetes, eat more healthily, and have lower body mass indices.

The statistical modelling would have had to be extremely thorough to adequately ‘control’ for all these factors which are protective against cardiovascular and ischaemic heart disease mortality. There is no mention in the paper that any interactions were tested (eg, is not smoking at age 60 more protective than not smoking at age 20?) – so there is a strong possibility that the authors’ findings may be a consequence of residual confounding.

An especially curious aspect of the paper is the finding (see the red lines in Figure 1), that the hazard ratios, (which are incorrectly referred to, synonymously, as ‘risks’!) are utterly unrelated to blood lead levels above 5µg/dl. In other words, if blood lead levels double from 5µg/dl to 10 µg/dl the risk of dying of any cause does not increase! How do they explain this?

During the years in which lead exposure has decreased in Australia (as in the US, due to the removal of lead from petrol and paint), there has been a pleasing decrease in cardiovascular disease mortality – but this has been attributed largely to much faster and better treatment following heart attacks, and (more controversially) to better dietary habits, especially lower saturated fat-intakes.

Last updated: 13 Mar 2018 3:58pm
Terrie Moffitt, Nannerl O. Keohane University Professor at Duke University and Associate Director of the Dunedin Multidisciplinary Health and Development Study at the University of Otago

"This important study alerts us to the possibility that people exposed to lead in years past can end up with heart disease years later.

"Environmental laws drastically reduced the amount of lead in New Zealand’s environment. But the older generation who are now entering the peak age of risk for heart disease are unaware their health may be still be affected today by lead they were exposed to as children, before the laws changed.

"It can be difficult for American studies like this one to isolate lead as an active ingredient in disease because Americans with the highest levels of lead in their blood tend to be poorer, less educated, heavy smokers, and eat an unhealthy diet. These factors all increase heart disease.

"In New Zealand, children of all backgrounds, rich or poor, breathed airborne lead before it was banned from petrol. If New Zealand studies also find a link between childhood lead and midlife heart disease, that would strengthen the evidence. The Dunedin Study plans to look into it." 

Last updated: 13 Mar 2018 1:11pm
Nick Wilson, Professor of Public Health at the University of Otago

"This new study is a large and well-conducted one. Furthermore, the findings are very plausible given that it is well established scientifically that lead exposure is linked to high blood pressure and heart disease. People in New Zealand also used to have relatively high lead levels – and so it is likely that many New Zealanders have also suffered from heart disease where exposure to lead (especially from lead in petrol) made some contribution.

"Indeed, this burden was prolonged due to the failure of many New Zealand Governments in the 1970s and 1980s to not act decisively despite good scientific evidence showing that lead levels were lowering the IQ of New Zealand children. But even if lead played some role in contributing heart disease it is unlikely to have been as important over the last 50 years in New Zealand as has smoking, a diet high in saturated fats from meat and dairy products, and physical inactivity.

"Fortunately, heart disease rates are currently declining as New Zealanders quit smoking, consume more healthy fats (like olive oil), and also take treatments such as blood pressure lowering drugs and statins."

Last updated: 13 Mar 2018 1:08pm
Dr Paul Harvey is a Postdoctoral Researcher from the Department of Environmental Sciences from Macquarie University

The current research detailing lead exposure as a risk factor for cardiovascular diseases brings once again into the research and public realm, the notion that there is no safe level of lead exposure.

Although the study was conducted in the USA, this work has implications in Australia where we often see lead exposures in a number of inner city areas, for example in Sydney and Melbourne, as well as in mining communities and also nationally through drinking water fixtures and fittings.

While the data and evidence is strong in the USA for a link between lead exposure and cardiovascular disease, there would need to be a similar study conducted in Australia to determine the extent of the association and correlation of lead exposure and cardiovascular disease here. This is due to the slightly different exposures pathways, population demographic, health care and lifestyle habits in Australia as compared to the USA.

Last updated: 12 Mar 2018 3:18pm
Stuart Khan is a Professor of Civil & Environmental Engineering at the University of New South Wales

In decades past, drinking water was seen to be a comparatively minor source of exposure to lead for most people in Australia. That’s because there were other much more significant sources including leaded petrol and paints. However, since lead has been largely phased out for those uses, exposure through drinking water may be much more significant than it was. With the focus now on low-level exposure, I think the onus will increasingly be on Australian drinking water quality managers to ensure that safe levels are not exceeded.

The city of Flint, Michigan in the USA has been dealing with a major water quality crisis regarding lead contamination since 2014. This crisis has reminded Australian water quality managers that lead is a contaminant, which we cannot afford to become complacent about. The Australian water industry has long recognised lead as an important water quality contaminant, but in many water supplies it requires constant vigilance to control. 

Although lead can enter drinking water from contaminated supplies, a more common problem involves lead being leached from pipes and other plumbing materials. This is particularly common where poor procedures have been used for welding and soldering. Household tap fittings, such as some water filters, can also contain lead-based components, which can leach lead into the water. Australian cities have a very wide variety of materials, which have been used for drinking water supply pipes and plumbing. As a result, we can expect that low levels of lead will continue to be detected in some Australian drinking water samples from time to time. 

Experiences with the commissioning of the water supply system for the new Perth Children’s Hospital reinforce just how difficult lead can be to manage in some systems. In that case, the construction company spent more than a year trying understand and resolve the lead contamination that was being measured in the hospital drinking water. Many techniques, including flushing the pipes, we tried to reduce the contamination, but were mostly unsuccessful. That issue is still not fully resolved.

Lead contamination in school plumbing systems is also something I believe we should be paying closer attention to. I think this is of particular concern when the students come back to school after a long summer break. Under those circumstances, there is potential for water to have sat stagnating, with warm summer temperatures, in the school plumbing system. These are ideal conditions for lead to be leached from the pipes to the drinking water. Such a scenario is all the more significant when we consider that many of the risks around which lead exposure is controlled are considered to be greatest for children, compared to adults. In my opinion, state governments should mandate that all schools develop water quality management plans and ensure that such plans are effectively implemented.

Last updated: 12 Mar 2018 3:14pm
Dr Ian Musgrave is a Senior Lecturer in the Faculty of Medicine, School of Medicine Sciences, within the Discipline of Pharmacology at the University of Adelaide.

Lead is a well known persistent environmental toxin. While most Australians would be aware of chronic exposure to lead's effects on brain development and behaviour in children, fewer will be aware that long-term exposure to relatively low levels of lead increases blood pressure and the risk of heart and blood vessel disease.

This new paper in The Lancet “Low-level lead exposure and mortality in US adults: a population-based cohort study” extends our knowledge of the kinds of lead levels that increase risk, and the degree to which the risk is increased.

The study looked at a representative sample of the adult US population. After measurement of blood lead and other baseline health measures, the subjects were followed for 17-22 years. Blood pressure and other health information, as well as causes of death, were followed over this time.

The study's strength is that it was able to follow a defined population over a sufficiently long time. However, the study only measured blood lead once, at the beginning of the study, and although they tried to correct for other causes of heart disease such as smoking and obesity, they may not have been able to correct all for possible contributory causes of death and so may overestimate the risk due to lead. In this study subjects with the highest levels of blood lead had a 37 per cent greater risk of premature death from any cause and a 70 per cent greater risk of death from heart disease.

The study suggested that almost one-third of deaths due to heart disease was attributable to lead exposure. This estimate is about ten times higher than previous estimates, but the careful measurement of blood lead and the long-term followup make this estimate plausible.

The other main finding is that lead levels generally considered to have minimal health impact were associated with higher death from heart disease. This suggests that lead has a larger public health impact than previously recognised. Even if the risks found in this study are an overestimate.

Most of the focus on lead in Australia has been in towns near lead mining and smelting facilities, where public health approaches may need to be reevaluated in the light of these findings. However, urban settings may also be impacted. While lead petrol was phased out in the 1970s, as was lead paint, recent studies show that some urban areas in Sydney and Melbourne have high soil lead levels, exceeding the Australian regulatory guideline of 300 mg/kg.

This could potentially lead to exposures that will have adverse effects on heart health. Again, public health approaches may need to be re-evaluated in urban areas in the light of these findings.

Last updated: 12 Mar 2018 3:12pm
Ivan Kempson is an Associate Professor of Biophysics and a Foundation Fellow at the Future Industries Institute, University of South Australia

The data are cause for concern. Many toxic effects of lead have been known for decades but it is only with studies, such as this, of increasing rigour, that the longer term effects and more subtle effects are being identified.

Research, especially over the past decade, have been indicating that the acceptable degree of exposure to lead is progressively less and less.

This latest study drives home the long term impact that lead exposure, even below previously accepted levels, has significant impact on public health.

Australia has had a long history of lead mining and smelting which supports many of our technological advances. Lead pollution in various centres around Australia are well known. There have been many excellent initiatives from councils, governments and industries to reduce lead pollution and conduct remediation.

The data from this study show that past initiatives to reduce lead exposure in Australia will have significant benefit for current and future generations of Australians in terms of health and well-being.

However, this new insight into the impact of low lead level exposure should direct more efforts into the remediation of polluted sites around Australia and reduce our current definition of what is considered safe. 

Last updated: 12 Mar 2018 3:09pm
Professor Mark Patrick Taylor is from the Dept of Environmental Sciences at Macquarie University

This new study confirms earlier, emerging views that lead is a significant contributor to heart disease in exposed populations. There is no reason to assume that Australia has been immune to the consequences of lead exposure as detailed in the new Lancet study.
In Australia, we released more than 240,000 tonnes of lead from petrol over its 70 years of use in motor vehicles, causing elevated blood lead levels, particularly in major cities.
Other recent research has confirmed that previously elevated lead-in-air exposures were associated detrimental outcomes and anti-social behaviours, including increased rates of aggressive crime and death by assault.
Blood lead levels in major cities declined rapidly following the removal of lead from petrol and are now low (i.e. typically < 2 µg/dL). However, the best available estimates indicate that up to 100,000 Australian children may have a blood lead level at some time in their first five years exceeding 5 µg/dL, the Australian guidelines for intervention.
Sources of lead exposure for most Australian children today are from legacy lead that have been deposited in garden soils and dusts or come from the former use of lead in paints.
However, some lead mining and smelting communities are still subject to significant environmental injustices due to the massive lead exposures they continue to be subjected to. The communities most exposed are Broken Hill, (NSW), Mount Isa (Qld), and Port Pirie (SA).
For example, recent data shows that the average lead in air in the lead smelting town of Port Pirie is the worst in Australia being some 200 times higher than that in Sydney.
Broken Hill lead in air levels are around 40 times higher than those in Sydney and Mount Isa lead in air levels remains elevated at approximately 20 times those in Sydney.

Thus, it is not surprising that the most recent data shows that approximately 50 per cent of all children under five years of age in these three communities have a blood lead level > 5 µg/dL (the upper acceptable level in Australia). Indigenous children are more greatly impacted, with approximately 70 per cent of Indigenous children in Broken Hill having a blood lead > 5 µg/dL. Similar disparities occur in Mount Isa and Port Pirie.
As one of the top 15 nations in terms of GDP, the Australian public should be incredulous that we have permitted such blatant injustices to be imposed upon sensitive populations (children), for which the effects will not fully bear fruit until their later years.
Moreover, while the lead-related decrements due to lost IQ, behavioural problems and missed life opportunities will impact those most exposed, all of society will pay via economic losses and societal costs.

Last updated: 12 Mar 2018 3:07pm

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