Lead-Related Mortality, CVD Death Higher Than Previous Estimates

Nancy A. Melville

March 16, 2018

With evidence that even low levels of lead exposure can increase the risk for premature death, a new study estimates that as many as 256,000 premature deaths from cardiovascular disease and 185,000 deaths from ischemic heart disease in the United States each year are linked to lead exposure in people over age 44  years.

"Our findings suggest that, of 2.3 million deaths every year in the USA, about 400 000 are attributable to lead exposure, an estimate that is about ten times larger than the current one," the authors report.

Previous estimates of lead-related mortality rates looked primarily at deaths among those with levels above 5 μg/dL (<0.24 μmol/L); however, increased mortality rates are also seen below 5 μg/dL but have not been adequately assessed, the authors said.

"Concentrations of lead in blood lower than 5 μg/dL (<0.24 μmol/L) are an important, but largely ignored, risk factor for death in the USA, particularly from cardiovascular disease," they write.

The findings by lead author, Bruce Lanphear, MD, from Simon Fraser University, Vancouver, British Columbia, Canada, and colleagues were published online March 12 in Lancet Public Health.

The observational study evaluated data from the Third National Health and Nutrition Examination Survey (NHANES-III) on 14,289 people in the United States older than 20 years between 1988 and 1994 and at the end of 2011.

They found that low-level lead exposure, defined as 1.0 μg/dL to 5.0 μg/dL — which is the current action level for adults in the United States and is linked to cardiovascular mortality —  was significantly associated with an increased risk for all cause-mortality (hazard ratio [HR], 1.38; 95% CI, 1.15 - 1.66), cardiovascular disease mortality (HR, 1.95; 95% CI, 1.46 - 2.60), and ischemic heart disease mortality (HR, 2.57; 95% CI, 1.56 - 4.52).

The results were not significantly changed after adjustment for such factors as hypertension, diabetes, high-density lipoprotein cholesterol, household income, or alcohol intake.

"In other studies, amounts of lead in blood lower than 10 μg/dL (<0.483 μmol/L) were associated with cardiovascular disease mortality, but our study is the first to test whether the relation with cardiovascular disease mortality was evident in a population with concentrations of lead in blood below 5 μg/dL," the authors write.

Sources of lead exposure are expansive, ranging from lead in the environment from historical use in paint, fuel, and lead pipes in older housing to lead batteries, industrial sources, and exposures from food.

Whereas increased awareness of the harms of lead exposure have resulted in substantial reductions in concentrations of lead in the blood over the past 50 years, the amounts currently found in adults are nevertheless 10 times to as much as 100 times higher than were observed in people living in the preindustrial era (700 to 1000 years ago), the authors note.

In the study, participants overall had baseline levels of lead ranging from less than 1 to 56 µg/dL, for an average of 2.7 µg/dL.

As many as 20% of participants (3632) had blood level concentrations that were at least 5 μg/dL.

Those with the highest levels of blood concentrations were older; were less educated; were more likely to be male, to smoke tobacco, to consume larger amounts of alcohol, and to have less healthy diets; and had elevated cholesterol and higher rates of hypertension or diabetes.

Of the participants, 8% (1150) had undetectable levels of lead in their blood and were used as reference, with a reference level of 0.7 µg/dL.

During the study (a median of 19.3 years), 4422 participants died, including 1801 (38%) deaths from cardiovascular disease and 988 (22%) from ischemic heart disease.

Compared with participants who had lead blood concentrations of 1.0 μg/dL, those with concentrations of 6.7 μg/dL had a 37% greater risk for premature death from any cause (HR, 1.37; 95% CI, 1.17 - 1.60); a 70% greater risk for cardiovascular disease mortality (HR, 1.70; 95% CI, 1.30 - 2.22), and about twice the risk for ischemic heart disease mortality (HR, 2.08; 95% CI, 1.52 - 2.85).

Using those figures, the authors estimated the proportion of deaths in adults aged 44 years or older that could have been prevented if there had not been historical exposure to lead.

They estimated that overall, 18% of all deaths in the United States each year would be among people with lead levels above 1 µg/dL.

In addition, they estimated that 28.7% of premature cardiovascular deaths (256,000/ 892,000) and 37.4% of all ischemic heart disease deaths (185,000/495,000) could be attributed to lead exposure.

"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," lead author Lanphear said in a press statement.

"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."

Public health measures that are vital in preventing lead exposure include abating older housing, phasing out lead-containing jet fuels, replacing lead plumbing lines, and reducing emissions from smelters and lead battery facilities, Lanphear said.

Limitations of the study include the reliance on baseline measures of exposure to predict death over the study's two-decade period; in addition, the use of death certificates for the underlying cause of death did not allow for adjustments for confounders, such as exposure to air pollutants or arsenic.

The estimated number of deaths associated with lead exposure were nevertheless a surprise — and even were similar to the number of deaths from current tobacco smoke exposure when accounting for the fact that far more people in the United States are exposed to lead than to smoke tobacco, the authors note.

"The HR for all-cause mortality from tobacco exposure was larger than that for concentration of lead in blood, but only 20% of the US population smoked tobacco," they explain.

"By contrast, 90% of participants were exposed to lead; a smaller relative risk for a prevalent exposure can result in a larger population attributable fraction."

Studies have shown that mechanisms linking lead with cardiovascular toxicity include an increased risk for hypertension, peripheral arterial disease, electrocardiographic abnormalities, and left ventricular hypertrophy.

Efforts to reduce lead exposure, though making some progress, still need to be persistent, the authors say.

"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," the authors say.

"Still, lead represents a leading cause of disease and death, and it is important to continue our efforts to reduce environmental lead exposure."

In terms of treatment, while chelation therapy is known to be effective for acute lead toxicity, few studies have shown any significant treatment for chronic, lower-level lead exposure. However, senior author Lanphear asserted that clinicians can nevertheless help in terms of prevention.

"I think clinicians should certainly be thinking about those risks when it comes to patients who are involved in occupations and hobbies involving lead exposures," he told theheart.org | Medscape Cardiology.

"And in general, we need to do a better job advocating for ways to prevent disease in our patients," he said.

"Clinicians are barely keeping their heads above water with responsibilities in the clinic, but ultimately, the public does look to clinicians for answers to our health problems, and it seems to me that at least part of our time as physicians needs to be devoted to how do we think about prevention, even if that's not our primary role."

Epidemiologist and pediatrician Philip Landrigan, MD, who published a commentary concurrently with the study, said the findings importantly look well beyond previous studies in exposure levels.

"We've known for quite a while that lead is toxic to the cardiovascular system, but what's new here is that none of the previous analyses have looked at levels below about 20 or 10 micrograms," Landrigan, who is dean for global health, Ethel H. Wise Professor, and chairman of the Department of Preventive Medicine at the Icahn School of Medicine at Mount Sinai in New York City, told theheart.org | Medscape Cardiology.

"This study looked about as low as you can go using the data from the NHANES study and found the correlation between blood lead levels and cardiovascular mortality even at these low levels."

Low levels of lead in the blood are well known to be linked to brain health in children, including lower IQ and behavioral issues, and prevention of exposure is a high priority for pediatricians.

But Landrigan agreed that the new findings suggest that awareness should also extend to treatment of adults, and he even plans to take action to raise the issue with the US Preventive Services Task Force.

"I'm planning to put a proposal to the US Preventive Services Task Force suggesting that blood lead screening become part of the standard workup when an internist or family physician evaluates a person's risk of heart disease," he said.

"They routinely address smoking, alcohol, exercise, and diet, and I'm going to propose that they also consider adding lead to the roster."

Landrigan added that the study is also particularly important on a global level in light of the known toll that pollution takes in low- and middle-income countries, where its effect on noncommunicable disease mortality exceeds that of any recognized behavioral and metabolic risk factors.

"The time has come to end inattention to the contribution of pollution to mortality from non-communicable diseases and to thoroughly re-examine lead's role in changing global patterns of cardiovascular disease," Landrigan said.

"The information that emerges from this reassessment will increase understanding of lead's contribution to mortality from non-communicable diseases, could foster collaboration between the environmental and chronic disease research communities, guide realignment of cardiovascular disease prevention strategies, and ultimately save lives."

The study was funded by the Artemis Fund and Simon Fraser University. The authors and Landrigan have disclosed no relevant financial relationships.

Lancet Public Health. Published online March 12, 2018. Abstract, Editorial  

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