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Cumulative Lead Exposure Linked to Death from CVD

By Negin Martin
November 2009

Marc G. Weisskopf, Ph.D., Sc.D.
"The findings with bone lead are dramatic," said Weisskopf. "It is the first time we have had a biomarker of cumulative exposure to lead and the strong findings suggest that it is a more critical biomarker than blood lead." (Photo courtesy of Marc Weisskopf)

Howard Hu, M.D., Sc.D.
Senior author Howard Hu holds the National Science Foundation International Department Chair in Environmental Health Sciences at the University of Michigan - one of the many honors he has received for his research into the health effects of lead and other environmental toxicants. (Photo courtesy of the University of Michigan School of Public Health)

A collaborative study that included three NIEHS grantees - Marc G. Weisskopf, Ph.D., Sc.D., Joel Schwartz, Ph.D., and Howard Hu, M.D., Sc.D. - underscores the cumulative effects of exposure to lead and is the first study to investigate the association between mortality and lead levels in bone. According to the findings, which were published in the journal Circulation, lead levels in bone are significantly associated with increased risk of mortality from cardiovascular disease (CVD) and lower life expectancy.

Measuring lead levels in bone allowed this group of scientists to take into account the cumulative lead exposure of each subject from predominantly non-occupational sources years earlier. Circulating lead has a half-life of 30 days in blood, but once deposited in bone tissue, it can persist for decades. "The findings with bone lead are dramatic," observed Weisskopf, first author of the study. ( NIEHS "This is the first time we have had a biomarker of cumulative exposure to lead and the strong findings suggest that it is a more critical biomarker than blood lead."

Weisskopf ( NIEHS is an assistant professor of Environmental Health and Epidemiology at the Harvard School of Public Health. Both Weisskopf and his co-author Schwartz ( NIEHS are core members of the Harvard NIEHS Center for Environmental Health. The senior author of the study, Hu,( NIEHS is a clinical investigator and a professor of Environmental Health Sciences, Epidemiology and Internal Medicine at the University of Michigan (UM).

The 868 men enrolled in the study were selected from the Normative Aging Study, a longitudinal cohort of men initiated in 1963 in the Greater Boston area by the Department of Veterans Affairs. At enrollment, the men were between 21 and 80 years old with no prior history of heart condition, diabetes or cancer. Volunteers reported every 3 to 5 years for an extensive health evaluation. In the 1990s, 1235 subjects provided blood samples, and 868 men submitted to K-shell x-ray fluorescence of the patella, or kneecap, and the tibia, a large bone in the shin, for lead measurements. By March 2007, 241 of the volunteers had passed away. A board-certified cardiologist reviewed the death certificates and categorized all cardiac-related deaths and cancers.

Higher levels of lead in patella were associated with increased rate of mortality for all causes and particularly ischemic heart disease. Patella lead levels were sorted into high, middle and low tertiles of exposure. After comparing the mortality in the high and low lead level groups, the researchers discovered that the high group had a 2.5-fold greater risk of death due to all causes, a 6-fold greater risk of death due to cardiovascular disease and an 8-fold increase in risk of death from ischemic heart disease. The researchers found no association between levels of lead in bone and cancer mortality.

Blood lead levels of volunteers were only slightly higher than the U.S. average and were not associated with risk of death in any category. These findings highlight the importance of using bone lead levels, and not just blood lead levels, as a biomarker for lead exposure in future studies.

Researchers acknowledged that since most volunteers in the study were white men, more research is needed before generalizing the results for women and minorities.

Based on these findings, the effects of exposure to lead are cumulative and increase the risk of death even years after exposure. Almost no organ is immune to lead toxicity. The authors believe that adverse effects of lead on cardiac rhythm, vascular structure and neuronal signaling, as well as enhanced oxidative stress, may contribute to the increased mortality due to cardiac disorders.

Heart disease is still the number one cause of death and disability in the U.S. despite a steady decline in cardiovascular mortality over the last few decades. Traditional risk factors do not entirely explain this decline; however, it does coincide with tougher measures on environmental exposures and the mid-1990s ban on lead in gasoline.

Citation: Weisskopf MG, Jain N, Nie H, Sparrow D, Vokonas P, Schwartz J, and Hu H. ( NIEHS 2009. Circulation 120(12):1056-1064. Epub ahead of print.

(Negin Martin, Ph.D., is a biologist in the NIEHS Laboratory of Neurobiology Viral Vector Core Facility and a 2009 Science Communication Fellow with Environmental Health Sciences. She recently completed a postdoctoral fellowship with the NIEHS Membrane Signaling Group.)

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