Ionising radiation and cardiovascular disease: systematic review and meta-analysis
Authors: Little Mark P , Azizova Tamara V , Richardson David B , Tapio Soile , Bernier Marie-Odile , Kreuzer Michaela , Cucinotta Francis A , Bazyka Dimitry , Chumak Vadim , Ivanov Victor K , Veiga Lene H S , Livinski Alicia , Abalo Kossi , Zablotska Lydia B , Einstein Andrew J , Hamada Nobuyuki 
Published: March 2023

Abstract

Objective
To systematically review and perform a meta-analysis of radiation associated risks of cardiovascular disease in all groups exposed to radiation with individual radiation dose estimates.

Design
Systematic review and meta-analysis.

Main outcome measures
Excess relative risk per unit dose (Gy), estimated by restricted maximum likelihood methods.

Data sources
PubMed and Medline, Embase, Scopus, Web of Science Core collection databases.

Eligibility criteria for selecting studies
Databases were searched on 6 October 2022, with no limits on date of publication or language. Animal studies and studies without an abstract were excluded.

Results
The meta-analysis yielded 93 relevant studies. Relative risk per Gy increased for all cardiovascular disease (excess relative risk per Gy of 0.11 (95% confidence interval 0.08 to 0.14)) and for the four major subtypes of cardiovascular disease (ischaemic heart disease, other heart disease, cerebrovascular disease, all other cardiovascular disease). However, interstudy heterogeneity was noted (P<0.05 for all endpoints except for other heart disease), possibly resulting from interstudy variation in unmeasured confounders or effect modifiers, which is markedly reduced if attention is restricted to higher quality studies or those at moderate doses (<0.5 Gy) or low dose rates (<5 mGy/h). For ischaemic heart disease and all cardiovascular disease, risks were larger per unit dose for lower dose (inverse dose effect) and for fractionated exposures (inverse dose fractionation effect). Population based excess absolute risks are estimated for a number of national populations (Canada, England and Wales, France, Germany, Japan, USA) and range from 2.33% per Gy (95% confidence interval 1.69% to 2.98%) for England and Wales to 3.66% per Gy (2.65% to 4.68%) for Germany, largely reflecting the underlying rates of cardiovascular disease mortality in these populations. Estimated risk of mortality from cardiovascular disease are generally dominated by cerebrovascular disease (around 0.94-1.26% per Gy), with the next largest contribution from ischaemic heart disease (around 0.30-1.20% per Gy).

Conclusions
Results provide evidence supporting a causal association between radiation exposure and cardiovascular disease at high dose, and to a lesser extent at low dose, with some indications of differences in risk between acute and chronic exposures, which require further investigation. The observed heterogeneity complicates a causal interpretation of these findings, although this heterogeneity is much reduced if only higher quality studies or those at moderate doses or low dose rates are considered. Studies are needed to assess in more detail modifications of radiation effect by lifestyle and medical risk factors.

Systematic review registration
PROSPERO CRD42020202036