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Review and meta-analysis of epidemiological associations between low/moderate doses of ionizing radiation and circulatory disease risks, and their possible mechanisms

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Abstract

Although the link between high doses of ionizing radiation and damage to the heart and coronary arteries has been well established for some time, the association between lower-dose exposures and late occurring cardiovascular disease has only recently begun to emerge, and is still controversial. In this paper, we extend an earlier systematic review by Little et al. on the epidemiological evidence for associations between low and moderate doses of ionizing radiation exposure and late occurring blood circulatory system disease. Excess relative risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well-known (but unobserved) risk factors, and there is statistically significant (p < 0.00001) heterogeneity between the risks. This heterogeneity is reduced, but remains significant, if adjustments are made for the effects of fractionated delivery or if there is stratification by endpoint (cardiovascular disease vs. stroke, morbidity vs. mortality). One possible biological mechanism is damage to endothelial cells and subsequent induction of an inflammatory response, although it seems unlikely that this would extend to low-dose and low-dose-rate exposure. A recent paper of Little et al. proposed an arguably more plausible mechanism for fractionated low-dose effects, based on monocyte cell killing in the intima. Although the predictions of the model are consistent with the epidemiological data, the experimental predictions made have yet to be tested. Further epidemiological and biological evidence will allow a firmer conclusion to be drawn.

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Acknowledgments

The authors are grateful for the detailed and helpful comments of the editor and two referees. This work was funded partially by the European Commission under contracts FI6R-CT-2003-508842 (RISC-RAD) and FP6-036465 (NOTE). The Mayak worker analysis by Drs. Azizova and Muirhead was conducted with support from the European Commission’s Euratom Nuclear Fission and Radiation Protection Programme as part of the SOUL project; more details of this analysis can be found in separate papers by the study investigators.

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Correspondence to M. P. Little.

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This paper is based on a presentation given at the International Conference on Late Health Effects of Ionizing Radiation, 4–6 May 2009, Georgetown University, Washington DC, USA.

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Little, M.P., Tawn, E.J., Tzoulaki, I. et al. Review and meta-analysis of epidemiological associations between low/moderate doses of ionizing radiation and circulatory disease risks, and their possible mechanisms. Radiat Environ Biophys 49, 139–153 (2010). https://doi.org/10.1007/s00411-009-0250-z

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