Circulatory Effects Seen with A-Bomb Radiation (CME/CE)

Survivors of the atomic bomb blasts at Hiroshima and Nagasaki have an increased risk of dying from heart disease and stroke, researchers found.

The estimated excess relative risk per Gy was 9% for stroke and 14% for heart disease (P?0.02 for both), Yukiko Shimizu, DMSc, of the Radiation Effects Research Foundation in Hiroshima, and colleagues reported online in BMJ.

Significant estimated increases in risk started at doses of 0.5 Gy and higher.

“The effect of radiation on risk of circulatory disease is potentially a very important public health concern,” the researchers wrote.

“Given the widespread use of multiple computed tomography scans, and other relatively high-dose diagnostic medical procedures, as well as radiotherapy that exposes the heart, the implications are substantial insofar as effects occur at doses under 1 Gy.”

But they cautioned that “robust confirmatory evidence from other studies is needed.”

To explore the relationship between radiation exposure and circulatory disease, Shimizu and colleagues looked at more than 50 years of data from the Life Span Study, which has prospectively followed survivors of the atomic bomb blasts in Japan since 1950.

The analysis included 86,611 individuals who were exposed to radiation at doses ranging from 0 to more than 3 Gy, although 86% received less than 0.2 Gy.

Through 2003, 9,622 of the participants died from stroke and 8,463 died from heart disease.

For stroke, a quadratic formula fit the data better than a linear dose-response model, indicating relatively low risk of stroke at lower radiation doses. The linear dose-response model provided the best fit to the data for heart disease, suggesting an excess risk even at lower doses. However, there was not a significant increase in estimated risk for exposures less than 0.5 Gy.

Adjusting for smoking, alcohol intake, education, occupation, obesity, and diabetes had very little effect on the risk estimates, the researchers wrote.

To control for the possible misclassification of cancers as circulatory diseases, the researchers re-ran their analysis after excluding those individuals with a history of cancer.

In this analysis, the excess relative risk for stroke became nonsignificant (P=0.11), but that for heart disease remained significant (P=0.03).

In an accompanying editorial, Mark Little, PhD, of Imperial College London, said the study “adds to a growing body of evidence suggesting an association between cardiovascular disease and exposure to low-moderate levels of radiation, as well as the well-known (and mechanistically well-understood) association at high doses.”

“However,” he continued, “statistical associations do not prove a causal association, and it is unclear whether the biological mechanisms operating at high doses of radiation apply to low doses.”

Previous studies, including some randomized controlled trials, have linked high doses of radiation from treatment for Hodgkin’s disease and breast cancer to excess deaths from cardiovascular disease.

Studies looking at lower doses, however, have yielded mixed results.

James Thrall, MD, radiologist-in-chief at Massachusetts General Hospital and chair of the American College of Radiology’s board of chancellors, said the results of the current study were not surprising.

“We have known for a long time that sufficient radiation can have adverse effects on the circulation,” Thrall said in an interview.

However, he noted that significant associations among the atomic bomb survivors were identified only for doses higher than 0.5 Gy, which is roughly equal to 500 mSv.

Radiation exposure from typical CT scans ranged from 2 to 31 mSv in a recent study. (See CT Scans May Deliver Higher-than-Expected Radiation Doses)

Thrall said that risk of circulatory disease is not a consideration when clinicians are weighing the risks and benefits of a CT scan.

“And I would say that this article does not suggest that that’s a serious concern.”

The potential mechanisms underlying the association between radiation exposure and circulatory disease remains unclear, but the researchers said “evidence suggests that pro-inflammatory responses to radiation, cellular loss or functional changes in the endothelium, or microvascular damage” may be involved.

The editorialist Little noted, however, “although we have evidence for [inflammation's] involvement in the development of cardiovascular disease at high doses of radiation, the mechanism is unclear at low and moderate doses, particularly for occupational exposure, where people receive on average much less than one electron track per cell per day.”

The study authors noted some limitations of the study:

The ascertainment of circulatory disease from death certificates has limited diagnostic accuracy. Analyses for potential confounders were incomplete. There were uncertain associations for exposures below 0.5 Gy. There is inadequate information about biological mechanisms. Generalizability to Western populations is uncertain.

Little also pointed to the selection of patients, particularly in the early years of follow-up, as a weakness because these individuals would have been exposed to war and stressful conditions, which increase the risk of cardiovascular disease.

The Radiation Effects Research Foundation in Hiroshima and Nagasaki is a private nonprofit foundation funded by the Japanese Ministry of Health, Labor, and Welfare and the U.S. Department of Energy, the latter in part through the National Academy of Sciences.

Neither the study authors nor the editorialist reported any conflicts of interest.

source : www.medpagetoday.com

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