Growing evidence shows that exposure to lead in the environment is associated with cardiovascular disease, including increased risk of hypertension. However, those studies have looked at lead concentrations in blood, not bone lead, a better indicator of cumulative lead exposure over time. In a new study, researchers at the Harvard School of Public Health (HSPH) and the University of Michigan School of Public Health found that bone lead was associated with a higher risk of death from all causes, particularly from cardiovascular disease. It is the first study to analyze the association between bone lead and mortality.

The study appears online on September 8, 2009, on the website of the journal Circulation and will appear in a later print edition. 

“The findings with bone lead are dramatic. It is the first time we have had a biomarker of cumulative exposure to lead and the strong findings suggest that, even in an era when current exposures are low, past exposures to lead represent an important predictor of cardiovascular death, with important public health implications worldwide,” said Marc Weisskopf, assistant professor of environmental and occupational epidemiology at HSPH and lead author of the study.

Air pollution was the main source of lead in the environment in recent years, though it has been decreasing since leaded gasoline was banned in the U.S. in the mid-1990s. Most of the lead circulating in the body is deposited in bone and remains there for years, unlike blood lead, which has a half life of about 30 days. Since adverse effects from lead on the cardiovascular system would be expected to show up over time, the researchers expected that bone lead would be a better marker of chronic toxicity.

The researchers, led by Weisskopf and senior author Howard Hu, professor of environmental health, epidemiology and internal medicine at the University of Michigan School of Public Health, analyzed data from 868 participants in the Department of Veterans Affairs Normative Aging Study, a study of aging in men that began in 1963. Blood lead and bone lead—analyzed using X-ray fluorescence—were measured for each of the participants. The results showed that the risk of death from cardiovascular disease was almost six times higher in men with the highest levels of bone lead compared to men with the lowest levels. The risk of death from all causes was 2.5 times higher in men with the highest levels of lead compared to those with the lowest levels. The results appeared independent of age, smoking, education, race, alcohol, physical activity, BMI, high density lipoprotein or total cholesterol levels, hypertension or diabetes.

There are a number of mechanisms, such as increased oxidative stress, by which lead exposure may result in cardiovascular mortality, say the authors. They also note that, in addition to high blood pressure, exposure to lead has been associated with widened pulse-pressure (an indicator of arterial stiffening) and heart disease.

Given that bone lead may be a better biomarker of cumulative lead exposure than blood lead, it may be the best predictor of chronic disease from exposure to lead in the environment. “In addition to spurring further public health measures to reduce exposure to lead and to begin monitoring for cumulative exposure, mechanistic and clinical research is needed to determine if opportunities exist to conduct targeted screening and treatment that can further reduce the burden of cardiovascular disease for the millions of adults who have had years of elevated lead exposure in the past,” said Hu.

Reference:    Harvard School of Public Health, Lead in bone associated with increased risk of death from cardiovascular disease in men, Boston, MA, September 9, 2009

Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies.  

The mechanism of lead induced toxity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress.  

Oxidative stress plays important role in pathogenesis of lead-induced toxity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase.  

Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling.  

This review summarizes recent findings of the mechanism of the lead-induced toxity and possibilities of its prevention. 

Reference:  Nemsadze K, Sanikidze T, Ratiani L, Gabunia L, Sharashenidze T., Mechanisms of lead-induced poisoning, Tbilisi State Medical University; National Center of child development, Georgian Med News. 2009 Jul-Aug;(172-173):92-6.

CO Exposure could make them more vulnerable to disease

A UCLA study has discovered that chronic exposure during pregnancy to miniscule levels of carbon monoxide damages the cells of the fetal brain, resulting in permanent impairment. The journal BMC (BioMed Central ) Neuroscience published the findings June 22 in its online edition.

“We expected the placenta to protect fetuses from the mother’s exposure to tiny amounts of carbon monoxide,” said John Edmond, professor emeritus of biological chemistry at the David Geffen School of Medicine at UCLA. “But we found that not to be the case.”

The researchers exposed pregnant rats to 25 parts per million carbon monoxide in the air, an exposure level established as safe by Cal/OSHA, California’s division of occupational health and safety.

Dr. Ivan Lopez, UCLA associate professor of head and neck surgery, tested the rats litters 20 days after birth. Rats born to animals who had inhaled the gas suffered chronic oxidative stress, a harmful condition caused by an excess of harmful free radicals or insufficient antioxidants.

“Oxidative stress damaged the baby rats brain cells, leading to a drop in proteins essential for proper function,” said Lopez. “Oxidative stress is a risk factor linked to many disorders, including autism, cancer, Alzheimer’s, Parkinson’s, Lou Gehrig’s disease, multiple sclerosis and cardiovascular disease. We know that it exacerbates disease.”

“We believe that the minute levels of carbon monoxide in the mother rats environment made their offspring more vulnerable to illness,” added Edmond. “Our findings highlight the need for policy makers to tighten their regulation of carbon monoxide.”

Tobacco smoke, gas heaters, stoves and ovens all emit carbon monoxide, which can rise to high concentrations in well-insulated homes. Infants and children are particularly vulnerable to carbon monoxide exposure because they spend a great deal of time in the home.

No policies exist to regulate the gas in the home. Most commercial home monitors sound an alarm only hours after concentrations reaches 70 parts per million – nearly three times the 25 parts per million limit set by Cal/OSHA.

A grant from the University of California’s Tobacco-related Disease Research Program supported the research.

Reference: Elaine Schmidt, UCLA study reveals how tiny levels of carbon monoxide damage fetal brains, UCLA, 6/25/2009