Effects of confounding and effect-modifying lifestyle, environmental and medical factors on risk of radiation-associated cardiovascular disease

Abstract Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD. A recent systematic review of radiation and CVD highlighted substantial inter-study heterogeneity in effect, possibly a result of confounding or modifications of radiation effect by non-radiation factors, in particular by the major lifestyle/environmental/medical risk factors. Methods: We assessed effects of confounding by lifestyle/environmental/medical risk factors on radiation-associated CVD and investigated evidence for modifying effects of these variables on CVD radiation dose-response, using data assembled for a recent systematic review. Results: There are 42 epidemiologic studies which are informative on effects of adjustment for confounding or risk modifying factors on radiation-associated CVD. Of these 22 were studies of groups exposed to substantial doses of radiation for therapy or diagnosis. The remaining 20 studies were of groups exposed at much lower levels of dose and/or dose rate. Only four studies suggest substantial effects of adjustment for lifestyle/environmental/medical risk factors on radiation risk of CVD; however, there were also substantial uncertainties in the estimates in all of these studies. There are fewer suggestions of effects that modify the radiation dose response; only two studies, both at lower levels of dose, report the most serious level of modifying effect. Conclusions: There are still large uncertainties about confounding factors or lifestyle/environmental/medical variables that may influence radiation-associated CVD, although indications are that there are not many studies in which there are substantial confounding effects of these risk factors.