Helmut Schöllnberger

This article summarizes a number of presentations from a session on “Radiation and Circulatory Effects” held during the Radiation Research Society Online 67th Annual Meeting, October 3 – 6 2021.Dif...

Recent analyses of the Canadian fluoroscopy cohort study reported significantly increased radiation risks of mortality from ischemic heart diseases (IHD) with a linear dose–response adjusted for dose fractionation. This cohort includes 63,707 tuberculosis patients from Canada who were exposed to low-to-moderate dose fractionated X-rays in 1930s–1950s and were followed-up for death from non-cancer causes during 1950–1987. In the current analysis, we scrutinized the assumption of linearity by analyzing a series of radio-biologically motivated nonlinear dose–response models to get a better understanding of the impact of radiation damage on IHD. The models were weighted according to their quality of fit and were then mathematically superposed applying the multi-model inference (MMI) technique. Our results indicated an essentially linear dose–response relationship for IHD mortality at low and medium doses and a supra-linear relationship at higher doses (> 1.5 Gy). At 5 Gy, the estimated radiation risks were fivefold higher compared to the linear no-threshold (LNT) model. This is the largest study of patients exposed to fractionated low-to-moderate doses of radiation. Our analyses confirm previously reported significantly increased radiation risks of IHD from doses similar to those from diagnostic radiation procedures.

The article Dose–responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950–2003, written by Helmut Schöllnberger.

The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose–response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing different models to allow risk estimates to be based on several plausible dose–response models rather than just relying on a single model of choice. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose–response curve from MMI is located below the linear no-threshold model at low and medium doses (0–1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose–response was also found for heart diseases (0–3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose–response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general.

We propose a stochastic model for use in epidemiological analysis, describing the age-dependent development of atherosclerosis with adequate simplification. The model features the uptake of monocytes into the arterial wall, their proliferation and transition into foam cells. The number of foam cells is assumed to determine the health risk for clinically relevant events such as stroke. In a simulation study, the model was checked against the age-dependent prevalence of atherosclerotic lesions. Next, the model was applied to incidence of atherosclerotic stroke in the cohort of male workers from the Mayak nuclear facility in the Southern Urals. It describes the data as well as standard epidemiological models. Based on goodness-of-fit criteria the risk factors smoking, hypertension and radiation exposure were tested for their effect on disease development. Hypertension was identified to affect disease progression mainly in the late stage of atherosclerosis. Fitting mechanistic models to incidence data allows to integrate biological evidence on disease progression into epidemiological studies. The mechanistic approach adds to an understanding of pathogenic processes, whereas standard epidemiological methods mainly explore the statistical association between risk factors and disease outcome. Due to a more comprehensive scientific foundation, risk estimates from mechanistic models can be deemed more reliable. To the best of our knowledge, such models are applied to epidemiological data on cardiovascular diseases for the first time.

The latest A-bomb survivor data for cardiovascular diseases are analysed to investigate whether in the first years after the bombings the baseline rates of proximal survivors were markedly different compared with those of the distal survivors. This phenomenon relates to a healthy survivor selection effect. This question is important for the decision whether to include or exclude the early years of follow-up when analysing the biological effects from acute low and high dose exposures following the nuclear weapons explosions in Hiroshima and Nagasaki. The present study shows that for cerebrovascular diseases and heart diseases the baseline rates are not significantly different in the first two decades of follow-up. Thus, for these two detrimental health outcomes, there is no need to exclude distal survivors and the first decades of follow-up time when investigating the shapes of the related dose–responses.

A detailed analysis of cerebrovascular diseases (CeVD) for the cohort of workers at Mayak Production Association (PA) is presented. This cohort is especially suitable for the analysis of radiation induced circulatory diseases, due to the detailed medical surveillance and information on several risk factors. The risk after external, typically protracted, gamma exposure is analysed, accounting for potential additional internal alpha exposure. Three different endpoints have been investigated: incidence and mortality from all cerebrovascular diseases and incidence of stroke. Particular emphasis was given to the form of the dose-response relationship and the time dependence of the radiation induced risk. Young attained age was observed to be an important, aggravating modifier of radiation risk for incidence of CeVD and stroke. For incidence of CeVD, our analysis supports a dose response sub-linear for low doses. Finally, the excess relative risk per dose was confirmed to be significantly higher for incidence of CeVD compared to CeVD mortality and incidence of stroke. Arguments are presented for this difference to be based on a true biological effect.

We present an updated analysis of incidence and mortality from atherosclerotic induced ischemic heart diseases in the cohort of workers at the Mayak Production Association (PA). This cohort constitutes one of the most important sources for the assessment of radiation risk. It is exceptional because it comprises information on several other risk factors. While most of the workers have been exposed to external gamma radiation, a large proportion has additionally been exposed to internal radiation from inhaled plutonium. Compared to a previous study by Azizova et al. 2012, the updated dosimetry system MWDS-2008 has been applied and methods of analysis have been revised. We extend the analysis of the significant incidence risk and observe that main detrimental effects of external radiation exposure occur after more than about 30 years. For mortality, significant risk was found in males with an excess relative risk per dose of 0.09 (95% CI: 0.02; 0.16) while risk was insignificant for females. With respect to internal radiation exposure no association to risk could be established.