10 December 2013

MEDSCAPE Comments on Recent Institute of Medicine Agent Orange Report

Agent Orange Exposure Linked to Stroke

Pauline Anderson
December 10, 2013
Stroke has been added to the growing list of possible health effects Vietnam veterans may face long term after exposure to Agent Orange.
In response to new evidence showing a statistically significant overall increase in stroke associated with exposure to chemical in Agent Orange, a committee examining these health effects has moved stroke to the "limited and suggestive" evidence category.
However, the published data do not permit distinguishing hemorrhagic from ischemic stroke, said the authors of the updated report, Veterans and Agent Orange: Update 2012 : Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Ninth Biennial Update).
The evidence already suggested an association between exposure to the chemicals and hypertension, ischemic heart disease, and type 2 diabetes, as well as Parkinson's disease and some cancers.
Elsewhere in the 900-page report, the committee concluded that on the basis of newly reviewed evidence and in previous reports, there is also "limited or suggestive" evidence of an association between exposure to the chemicals of interest and Parkinson's disease.
The committee concluded that on the basis of new evidence and previous reports, evidence is inadequate or insufficient to determine whether there is an association between exposure to chemicals of interest and Alzheimer's disease.
Herbicide Mixtures
The current document was produced by a committee chaired by Mary K. Walker, professor, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque. It presents the committee's review of peer-reviewed scientific reports concerning associations between health outcomes and exposure to chemicals in herbicides used in Vietnam that were published from October 2010 to September 2012 and the integration of this new information into the existing database.
From 1962 to 1971, the US military sprayed herbicides over Vietnam to strip the thick jungle canopy that could conceal opposition forces, to destroy crops that those forces might depend on, and to clear tall grasses and bushes from the perimeters of US base camps and outlying fire-support bases.
The herbicide mixtures used were named according to the colors of identification bands painted on the storage drugs. The main chemical sprayed was Agent Orange, a 50-50 mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T).
Because of continuing complaints and uncertainty about long-term health effects of sprayed herbicides in Vietnam vets, Congress passed the Agent Orange Act of 1991, which directed the Secretary of Veterans Affairs to ask the National Academy of Sciences (NAS) to comprehensively evaluate scientific and medical information on the health effects of exposure to Agent Orange and other herbicides used in Vietnam. The legislation also instructed the Secretary to ask the NAS to conduct updates every 2 years for 10 years to draw conclusions from newly available literature.
In response to the first request, the Institute of Medicine convened a committee whose conclusions were published in 1994. The work of later committees resulted in the publication of biennial updates and of focused reports on the scientific evidence regarding type 2 diabetes, acute myeloid leukemia in children, and the latent period for respiratory cancer.
The Veterans Education and Benefits Expansion Act of 2001 mandated that the biennial updates continue through 2014.
In this most recent update, one of the studies the committee looked at was the Prospective Investigation of Vasculature in Uppsala Seniors, a small study (n = 35) that examined the relationship among several chemicals that have dioxin-like activity and stroke incidence.
Contrasting high and low quartiles, the study found a strong (relative risk, 3.8) and statistically significant albeit imprecise (95% confidence interval, 1.2 - 12.2) relationship between exposure and stroke after adjustment for relevant potentially confounding factors. A statistically significant dose-response relationship was also seen across exposure quartiles.
Prior literature shows an overall increase in stroke and cerebrovascular disease associated with exposure to chemicals of interest in environmental, occupational, and Vietnam veteran populations. Human and animal studies have demonstrated biological plausibility of the connection between exposure to chemicals of interest and stroke, which is strongly linked to hypertension, cardiovascular disease, and diabetes, conditions already in the limited and suggestive evidence category.
After weighing all these factors, the committee voted to move stroke to the limited and suggestive category.
The published data did not permit the committee to distinguish hemorrhagic from ischemic stroke, but given that only a small percentage of strokes are the hemorrhagic type in the Western population, this was not seen as an impediment, according to the report.

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