A peer-reviewed study of children living in or near Syracuse, New York found that above-normal levels of arsenic in urine were associated with signs of early-stage asymptomatic heart disease.
After correcting for diet, second-hand smoke and other factors, investigators concluded that proximity to industrial sites was the main source of exposure.
A similar relationship between arsenic and changes to the heart and circulatory system previously was noted in adults, many of whom progress to full-blown heart disease. The long-term implications for children, however, are unclear.
Early-stage, symptomless heart disease in children is normally associated with chronic, well-understood, and often unavoidable risk factors such as genetics. kidney disease, and diabetes.
Reducing exposure to arsenic, leading to presumably lower risk of heart problems, is possible through appropriate water treatments or avoidance of certain foods.
Exposure through the environment, however, is a thornier issue as many industrial sites contaminated with arsenic — some located near peoples’ homes — are sources of less obvious exposure, such as through inhalation.
The paper, published June 30 on the JAMA Network, is the first to establish an association between arsenic levels and subclinical cardiovascular disease (CVD) in children.
The cross-sectional study analyzed “spot” (random, or one-off) urine samples from 245 children, ages 9 to 11. (This diverges from many studies that collect all of a patient’s urine over a prescribed period, usually 24 hours).
The subjects were a subset of the much broader Environmental influences on Child Health Outcomes (ECHO) Program under the auspices of the National Institutes of Health (NIH).
Because concentration in urine reflects an individual’s water intake, hydration state and physical activity, arsenic levels were expressed as a ratio to concentration levels of creatinine, a muscle breakdown product and biomarker for kidney function.
Creatinine is present in all urine samples from healthy individuals.
Normalizing arsenic to creatinine levels is typically undertaken when concentrations of arsenic exceed 10 micrograms per liter in urine. In this instance, the decision was based simply on sample availability.
After adjusting for other independent variables, investigators calculated an average arsenic concentration of 7.76 micrograms per gram of creatinine. This value was somewhat higher than the average of 7.08 micrograms per gram across the U.S. for children aged 6 to 11 years.
About subclinical cardiovascular disease
Subclinical CVD is defined as early-stage physical changes to the heart or circulatory system that do not yet cause symptoms, but which could be dangerous if they progress.
In the study, investigators focused on three biomarkers: carotid intima media thickness (CIMT), pulse wave velocity (PWV), and echocardiography-determined cardiac remodeling (CR).
Carotid-femoral PWV assesses aortic stiffness, while cardiac remodeling involves cell- and/or tissue-level changes that suggest previous or ongoing cardiac injury.
A measure of carotid atherosclerotic vascular disease, CIMT quantifies the thickness of the intima and media, the inner two layers of the carotid artery.
Early detection, before symptoms emerge, may suggest the need for aggressive treatment to mitigate associated heart disease risk before patients develop symptoms or suffer cardiac events.
After adjusting for confounding variables — such as sex, race and socioeconomic status — researchers found an association between elevated arsenic levels (normalized against creatinine) and increases in carotid intima media thickness. This relationship was statistically significant for total (non-adjusted) arsenic concentrations as well.
Arsenic concentrations also were higher in children with concentric hypertrophy, a form of cardiac remodeling in which the walls of the left ventricle thicken but the tissue itself does not increase in overall size. Here the adjusted arsenic levels were 16.77 micrograms per gram of creatinine, which is more than twice the baseline for individuals in this age group.
Elevated arsenic was not associated with PWV or arterial stiffness.
Common arsenic exposures
Since antiquity, arsenic has enjoyed a complicated reputation as both a cure and a poison.
It has also been used as a pesticide, but unlike organic bug and weedkillers, which eventually break down in the environment, arsenic persists because it is a metal. Although some forms such as organo-arsenic compounds (mainly found in aquatic organisms) are less toxic than others, ingestion of arsenic in any form is risky.
Children ingest arsenic mostly through foods and water. Almost all water contains some arsenic, with drinking water concentrations in the U.S. ranging from about one microgram per liter, on average, to about 9 micrograms in samples taken in Nevada and as high as 166 micrograms per liter in some regions of Utah.
Although arsenic was added to processed foods as recently as the early 1900s, that practice has stopped. Nevertheless, arsenic is everywhere and cannot be totally eliminated from foods.
According to one European study, the average adult consumes close to 40 micrograms per day (0.56 micrograms per kg of body weight) of inorganic arsenic, which is easily eliminated due to its water solubility.
Many foods are high in arsenic including some whose moderate intake is normally associated with good health — rice and rice products, mushrooms, poultry and some fruit juices.
The man-made environment is another potential source of arsenic, for example industrial sites such as glass works and smelters and certain products such as pressure-treated lumber.
Given its ubiquity in nature, it could just be that arsenic’s toxicity, like that of many other substances, is a matter of dosage. During the 1970s and 1980s, several research groups were investigating the possibility that the element, like selenium and boron, was required in minute quantities for good health.
Arsenic plays a role in the metabolism of methionine, an essential amino acid, and in gene silencing, a natural, ongoing process by which the body turns genes off (and on). Additional studies suggest it may interact beneficially with selenium, another natural “poison” whose benefits in very small doses are well documented.
Based on this work, the U.S. Environmental Protection Agency (EPA) concluded that “information from experimental studies with rats, chicks, minipigs, and goats demonstrates the plausibility that arsenic, at least in inorganic form, is an essential nutrient.”
A later assessment, however, suggested the topic was in “need of further research.”
Can it all come down to geography?
Investigators found no significant connection between arsenic levels in their study cohort and either second-hand smoke, water consumption, or food categories under the U.S. Dept. of Agriculture’s (USDA) Healthy Eating Index.
But they did note higher arsenic concentrations in several healthy foods the children ate, including beans, greens, seafood, and plant proteins. Those four foods, in fact, contributed to more than half of subjects’ daily intake of arsenic.
The authors did find clusters of high and low urine arsenic levels throughout the geographic region under study, and the high-level regions tended to be close to industrial or former industrial sites.
They found one “significant cluster” of elevated total arsenic southeast of Onondaga Lake near Syracuse, in an area “aligned with prevailing winds and watershed runoff.” Southeast Onondaga is a current superfund site as a result of industrial and municipal sewage discharges over the last 100 years.
This area, the authors conclude, is “the likely route of exposure to inorganic arsenic species in our cohort,” and “might represent a hot spot for arsenic exposure.”
Early detection is key
Since this study only examines one point in the lives of these subjects, it is impossible to predict long-term outcomes for any specific individual. However, subclinical CVD, including those adversely associated with high arsenic levels, are considered “asymptomatic stepping stones to clinical CVDs and stroke, and predict a variety of poor health outcomes, including accelerated aging, frailty, cognitive decline, and all-cause mortality.
Long-term studies on individuals with these risk factors have shown that men who reach age 50 without any major risk factor have 90% lower lifetime risk of experiencing a major cardiac event. For women the risk reduction is 79%.
The good news is there is plenty of time for diagnosis, monitoring, mitigation and treatment for affected children and even adults. Advanced imaging technology, which has enabled the in-depth study of CIMT and cardiac remodeling, also provides a means of monitoring the impact of diet and lifestyle changes, particularly at the earliest signs of trouble.
