Revisiting an Inverse Dose-Fractionation Effect of Ionizing Radiation Exposure for Ischemic Heart Disease: Insights from Recent Studies

Overview

Journal Radiat Res

Specialties Genetics
Radiology

Date 2024 May 21

PMID 38772552

Authors

Lydia B Zablotska

Mark P Little

Nobuyuki Hamada

Affiliations

Soon will be listed here.

Abstract

Over the last two decades, there has been emerging evidence suggesting that ionizing radiation exposures could be associated with elevated risks of cardiovascular disease (CVD), particularly ischemic heart disease (IHD). Excess CVD risks have been observed in a number of exposed groups, with generally similar risk estimates both at low and high radiation doses and dose rates. In 2014, we reported for the first time significantly higher risks of IHD mortality when radiation doses were delivered over a protracted period of time (an inverse dose-fractionation effect) in the Canadian Fluoroscopy Cohort Study. Here we review the current evidence on the dose-fractionation effect of radiation exposure, discuss potential implication for radiation protection policies and suggest further directions for research in this area.

Citing Articles

Bismuth Oxide Nanoparticle-Enhanced Poly(methyl methacrylate) Composites for I-131 Radiation Shielding: A Combined Simulation and Experimental Investigation.

Marshall S, Boonpeng K, Buapud N, Chimhashat S, Chuaymuang J, Kwandee P Polymers (Basel). 2025; 17(5).

PMID: 40076082 PMC: 11902673. DOI: 10.3390/polym17050590.

Responses of the carotid artery to acute, fractionated or chronic ionizing irradiation, and differences from the aorta.

Hamada N, Kawano K, Hirota S, Yusoff F, Nomura T, Saito Y Sci Rep. 2025; 15(1):7712.

PMID: 40044924 PMC: 11883035. DOI: 10.1038/s41598-025-92710-5.

References

Jacob P, Ruhm W, Walsh L, Blettner M, Hammer G, Zeeb H . Is cancer risk of radiation workers larger than expected?. Occup Environ Med. 2009; 66(12):789-96. PMC: 2776242. DOI: 10.1136/oem.2008.043265. View

Ozasa K, Shimizu Y, Suyama A, Kasagi F, Soda M, Grant E . Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases. Radiat Res. 2011; 177(3):229-43. DOI: 10.1667/rr2629.1. View

Hamada N, Kawano K, Nomura T, Furukawa K, Yusoff F, Maruhashi T . Temporal Changes in Sparing and Enhancing Dose Protraction Effects of Ionizing Irradiation for Aortic Damage in Wild-Type Mice. Cancers (Basel). 2022; 14(14). PMC: 9321929. DOI: 10.3390/cancers14143319. View

Zablotska L, Little M, Jack Cornett R . Potential increased risk of ischemic heart disease mortality with significant dose fractionation in the Canadian Fluoroscopy Cohort Study. Am J Epidemiol. 2013; 179(1):120-31. PMC: 3864716. DOI: 10.1093/aje/kwt244. View

Linet M, Slovis T, Miller D, Kleinerman R, Lee C, Rajaraman P . Cancer risks associated with external radiation from diagnostic imaging procedures. CA Cancer J Clin. 2012; 62(2):75-100. PMC: 3548988. DOI: 10.3322/caac.21132. View

Zhang W, Haylock R, Gillies M, Hunter N . Mortality from heart diseases following occupational radiation exposure: analysis of the National Registry for Radiation Workers (NRRW) in the United Kingdom. J Radiol Prot. 2019; 39(2):327-353. DOI: 10.1088/1361-6498/ab02b2. View

Azizova T, Bannikova M, Grigoryeva E, Briks K, Hamada N . Mortality from various diseases of the circulatory system in the Russian Mayak nuclear worker cohort: 1948-2018. J Radiol Prot. 2022; 42(2). DOI: 10.1088/1361-6498/ac4ae3. View

Little M, Gola A, Tzoulaki I . A model of cardiovascular disease giving a plausible mechanism for the effect of fractionated low-dose ionizing radiation exposure. PLoS Comput Biol. 2009; 5(10):e1000539. PMC: 2759077. DOI: 10.1371/journal.pcbi.1000539. View

Simonetto C, Schollnberger H, Azizova T, Grigoryeva E, Pikulina M, Eidemuller M . Cerebrovascular Diseases in Workers at Mayak PA: The Difference in Radiation Risk between Incidence and Mortality. PLoS One. 2015; 10(5):e0125904. PMC: 4416824. DOI: 10.1371/journal.pone.0125904. View

10.

Rombouts C, Aerts A, Quintens R, Baselet B, El-Saghire H, Harms-Ringdahl M . Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose rate irradiation. Int J Radiat Biol. 2014; 90(7):560-74. DOI: 10.3109/09553002.2014.905724. View

11.

Boice Jr J, Cohen S, Mumma M, Ellis E, Cragle D, Eckerman K . Mortality among mound workers exposed to polonium-210 and other sources of radiation, 1944-1979. Radiat Res. 2014; 181(2):208-28. DOI: 10.1667/RR13395.1. View

12.

. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007; 37(2-4):1-332. DOI: 10.1016/j.icrp.2007.10.003. View

13.

Little M, Tawn E, Tzoulaki I, Wakeford R, Hildebrandt G, Paris F . A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms. Radiat Res. 2007; 169(1):99-109. DOI: 10.1667/RR1070.1. View

14.

Wakeford R, Tawn E . The meaning of low dose and low dose-rate. J Radiol Prot. 2010; 30(1):1-3. DOI: 10.1088/0952-4746/30/1/E02. View

15.

Kendall G, Little M, Wakeford R, Bunch K, Miles J, Vincent T . A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006. Leukemia. 2012; 27(1):3-9. PMC: 3998763. DOI: 10.1038/leu.2012.151. View

16.

Little M, Wakeford R, Bouffler S, Abalo K, Hauptmann M, Hamada N . Review of the risk of cancer following low and moderate doses of sparsely ionising radiation received in early life in groups with individually estimated doses. Environ Int. 2021; 159:106983. PMC: 9118883. DOI: 10.1016/j.envint.2021.106983. View

17.

Stewart F, Akleyev A, Hauer-Jensen M, Hendry J, Kleiman N, MacVittie T . ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context. Ann ICRP. 2012; 41(1-2):1-322. DOI: 10.1016/j.icrp.2012.02.001. View

18.

Takahashi I, Shimizu Y, Grant E, Cologne J, Ozasa K, Kodama K . Heart Disease Mortality in the Life Span Study, 1950-2008. Radiat Res. 2017; 187(3):319-332. DOI: 10.1667/RR14347.1. View

19.

Little M, Wakeford R, Borrego D, French B, Zablotska L, Adams M . Leukaemia and myeloid malignancy among people exposed to low doses (<100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies. Lancet Haematol. 2018; 5(8):e346-e358. PMC: 6130888. DOI: 10.1016/S2352-3026(18)30092-9. View

20.

Lubin J, Adams M, Shore R, Holmberg E, Schneider A, Hawkins M . Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts. J Clin Endocrinol Metab. 2017; 102(7):2575-2583. PMC: 5505197. DOI: 10.1210/jc.2016-3529. View