Systematic Review and Meta-Analysis of Circula­tory Disease from Exposure to Low-Level Ionizing Radia­tion and Estimates of Potential Popula­tion Mortality Risks

Mark P. Little,¹ Tamara V. Azizova,² Dimitry Bazyka,³ Simon D. Bouffler,⁴ Elisabeth Cardis,⁵ Sergey Chekin,⁶ Vadim V. Chumak,³ Francis A. Cucinotta,⁷ Florent de Vathaire,⁸ Per Hall,⁹ John D. Harrison,⁴ Guido Hildebrandt,^10,11 Victor Ivanov,⁶ Valeriy V. Kashcheev,⁶ Sergiy V. Klymenko,³ Michaela Kreuzer,¹² Olivier Laurent,¹³ Kotaro Ozasa,¹⁴ Thierry Schneider,¹⁵ Soile Tapio,¹⁶ Andrew M. Taylor,¹⁷ Ioanna Tzoulaki,¹⁸ Wendy L. Vandoolaeghe,¹⁸ Richard Wakeford,¹⁹ Lydia B. Zablotska,²⁰ Wei Zhang,⁴ and Steven E. Lipshultz²¹

¹Radia­tion Epidemiology Branch, Na­tional Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA; ²Southern Urals Biophysics Institute, Ozyorsk, Russia; ³Research Center for Radia­tion Medicine, Kyiv, Ukraine; ⁴Health Protection Agency, Centre for Radia­tion, Chemi­cal and Environ­mental Hazards, Chilton, United Kingdom; ⁵Center for Research in Environ­mental Epidemiology (CREAL), Barcelona, Spain; ⁶Medi­cal Radiologi­cal Research Center of Russian Academy of Medi­cal Sciences, Obninsk, Russia; ⁷NASA Johnson Space Center, Space Radia­tion Program, Houston, Texas, USA; ⁸Radia­tion Epidemiology Group, INSERM (Institut Na­tional de la Santé et de la Recherche Médi­cale) Unité U1018, Institut Gustave Roussy, Villejuif, France; ⁹Department of Medi­cal Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; ¹⁰Department of Radiotherapy and Radia­tion Oncology, University of Leipzig, Leipzig, Germany; ¹¹Department of Radiotherapy and Radia­tion Oncology, University of Rostock, Rostock, Germany; ¹²Federal Office for Radia­tion Protection, Department of Radia­tion Protection and Health, Oberschleissheim, Germany; ¹³Laboratoire d’Epidémiologie, Institut de Radioprotection et de Sûreté Nucleaire, Fontenay-aux-Roses, France; ¹⁴Department of Epidemiology, Radia­tion Effects Research Founda­tion, Hiroshima City, Japan; ¹⁵CEPN (Nuclear Evalua­tion Protection Center), Fontenay-aux-Roses, France; ¹⁶Helmholtz Zentrum München, German Research Centre for Environ­mental Health, Institute of Radia­tion Biology (ISB), Radia­tion Proteomics, Oberschleissheim, Germany; ¹⁷University College London Institute of Cardiovascular Sciences & Great Ormond Street Hospital for Children, London, United Kingdom; ¹⁸Department of Epidemiology and Biostatistics, Imperial College Faculty of Medicine, London, United Kingdom; ¹⁹Dalton Nuclear Institute, University of Manchester, Manchester, United Kingdom; ²⁰Department of Epidemiology and Biostatistics, University of California San Francisco School of Medicine, San Francisco, California, USA; ²¹Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, USA


Abstract

Background: Although high doses of ionizing radia­tion have long been linked to circula­tory ­disease, evidence for an associa­tion at lower exposures remains controversial. However, recent analy­ses suggest excess relative risks at occupa­tional exposure levels.


Objectives: We performed a systematic review and meta-analy­sis to summarize informa­tion on circula­tory disease risks associated with moderate- and low-level whole-body ionizing radia­tion exposures.


Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms “radia­tion” AND “heart” AND “disease,” OR “radia­tion” AND “stroke,” OR “radia­tion” AND “circula­tory” AND “disease.” Radia­tion exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated popula­tion risks of circula­tory disease from low-level radia­tion exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.


Results: Estimated excess popula­tion risks for all circula­tory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.


Conclusions: Our review supports an associa­tion between circula­tory disease mortality and low and moderate doses of ionizing radia­tion. Our analy­sis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupa­tional groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radia­tion-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these popula­tions).


Key words: cancer, circula­tory disease, heart disease, radia­tion, stroke. 


Environ Health Perspect 120:1503–1511 (2012). http://dx.doi.org/10.1289/ehp.1204982 [Online 22 June 2012]


Address correspondence to M.P. Little, Radia­tion Epidemiology Branch, Na­tional Cancer Institute, Executive Plaza South, 6120 Executive Blvd. MSC 7238, Rockville, MD 20852-7238 USA. Telephone: (301) 402-9138 (office); (301) 875-3413 (mobile). Fax: (301) 402-0207. E-mail: mark.little@nih.gov


Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1204982).


We are grateful for the detailed and helpful comments of K. Mabuchi, A. Berrington de González, M. Cook, B. Graubard, B. Bridges, D. Stram, J. Hendry, S. Schultz-Hector, F. Stewart, B. Jones, the two referees, and an editor. 


This work was funded partially by the European Commission (EC) under contract FP6-036465 [NOn-Targeted Effects of ionising radia­tion (NOTE) integrated project]. This research was also supported by the Intramural Research Program of the Na­tional Institutes of Health (NIH) and the Na­tional Cancer Institute. This report makes use of data obtained from the Radia­tion Effects Research Founda­tion (RERF), Hiroshima and Nagasaki, Japan. RERF is a private, nonprofit founda­tion funded by the Japanese Ministry of Health, Labour and Welfare and the U.S. Department of Energy, the latter through the Na­tional Academy of Sciences. 


Neither the EC nor the NIH had any role in study design and the collection, analy­sis, and interpreta­tion of data or the writing of the article and the decision to submit it for publica­tion; all researchers are independent of all funders and sponsors. The conclusions of the report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies.


The authors declare they have no actual or potential competing financial interests.


Received 16 January 2012; Accepted 22 June 2012; Online 22 June 2012.