Title: Occupational Exposure to Ionising Radiation and Mortality from Ischaemic Heart Disease
Funder: Department of Health and Social Care

Abstract: Background: Epidemiological studies have suggested an association between protracted exposure to low-level radiation and cardiovascular disease risk, which is important for radiological protection because at present the possibility of such an association is not considered. However, an important limitation for valid inferences regarding this association is the limited number of confounding factors, including importantly tobacco smoking, which generally could not be included in the occupational cohort studies. Most data from the UK comes from cohorts of workers in the nuclear industry, but collecting information on smoking history and other confounders for all workers in the cohort would be prohibitively expensive (as well as impossible for part of the cohort given the retrospective nature). This important question can nonetheless be addressed through a case-control study nested within a cohort for which such information is available. We have access to such a case-control study nested in the BNFL Sellafield workers cohort, which was previously set up by one of the co-applicants to investigate effects of shift-work and noise exposure, but not radiation, on circulatory diseases, and also includes information on important confounders including tobacco smoking. Aim: The proposed project aims to use the available case-control study to re-examine the association between external gamma radiation dose, and ideally also internal doses from intakes of radionuclides, and ischaemic heart disease (IHD) mortality adjusted for important lifestyle and occupational confounding factors. Research Plan: The 1:1 matched case-control study of Sellafield industrial workers including 635 IHD cases and 635 controls will be linked to estimates of external radiation dose from monitoring data and ideally also internal dose, primarily liver doses from plutonium available from the recently completed EU SOLO project (which also involved all parties in this proposal). Data are further available on tobacco smoking history, blood pressure, height, weight, occupational exposure to noise, and shift-work. Standard conditional logistic regression statistical methods for matched case-control studies will be employed to analyse the data; additionally employing statistical mediation analyses to investigate whether blood pressure and body-mass-index confound associations between IHD mortality and radiation exposure or are on the causal pathway. Potential effects of other, unmeasured confounders, will be assessed through additional sensitivity analyses using Monte Carlo or Bayesian simulations. Research Team: The project will be conducted by researchers from the Universities of Bristol and Manchester, and involve occupational epidemiology and exposure assessment science (Dr de Vocht; PI), radiation epidemiology (Prof Wakeford), occupational medicine (Prof Agius), medical statistics and epidemiology (Prof McNamee) and medicine and clinical epidemiology (Prof Martin). These partners currently also collaborate on a project funded in the previous round of this radiation research programme, with Dr de Vocht similarly as Principal Investigator. Public Health England have agreed that, subject to approvals, they will facilitate linkage of the case-control study to the database of radiation doses. Potential Impact/influence on policy field: If successful, the results of this project will directly inform radiological protection policy as to the existence of, and magnitude of, increased circulatory disease risk from low-level ionising radiation exposure.

Lay abstract: Studies of groups of people, including nuclear industry workers, have suggested that long-term exposure to low levels of radiation may cause heart and circulatory disease (such as stroke). Current regulations assume that this risk does not exist, so it is important to find out whether this is correct, so that regulations can be changed if it does exist. Previous studies looked at this, but generally were not able to look at other factors which might explain the results. For example, shift-work and noise may also cause heart disease, and also occur in the nuclear industry. Then there are things that people do, like smoking cigarettes, which are also important. In an ideal world, a new study of all British nuclear industry workers could be carried out to study this. This study could then also take into account all these other important factors. However, this would be expensive and would take a long time. We will conduct a study of nuclear industry workers who died of heart attacks, and compare their radiation exposure to other workers from the same industry who did not die of heart attacks at the time of the original study (control workers). This type of study (a &ldquo;nested case-control study&rdquo;) is quicker than looking at all workers, and can deal with other factors that are not to do with radiation. One of us did such a study with these workers, but for other reasons. We will build on this study to look at the effect of radiation. The study includes 635 workers who died of a heart attack, and we will compare their radiation exposure to that of 635 workers who were alive at that time. Important other factors (smoking, other workplace exposures) and other contributors of heart disease (such as high blood pressure) will also be included. We also plan to look at whether there is a risk from exposure to radioactive materials (like plutonium). This study is important for people who work in the British nuclear industry, but will also help other people, such as nurses and patients, who might be exposed to radiation.

Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CARDIOVASCULAR