The scientific question of whether protracted low-dose or low-dose-rate exposure to external radiation is causally related to the risk of circulatory disease continues to be an important issue for radiation protection. Previous analyses of a matched case-control dataset nested in a large cohort of UK nuclear fuel cycle workers indicated that there was little evidence that observed associations between external radiation dose and ischemic heart disease (IHD) mortality risk [OR = 1.35 (95% CI: 0.99–1.84) for 15-year-lagged exposure] could alternatively be explained by confounding from pre-employment tobacco smoking, BMI or blood pressure, or from socioeconomic status or occupational exposure to excessive noise or shiftwork. To improve causal inference about the observed external radiation dose and IHD mortality association, we estimated the potential magnitude and direction of non-random errors, incorporated sensitivity analyses and simulated bias effects under plausible scenarios. We conducted quantitative bias analyses of plausible scenarios based on 1,000 Monte Carlo samples to explore the impact of exposure measurement error, missing information on tobacco smoking, and unmeasured confounding, and assessed whether observed associations were reliant on the inclusion of specific matched pairs using bootstrapping with 10% of matched pairs randomly excluded in 1,000 samples. We further explored the plausibility that having been monitored for internal exposure, which was an important confounding factor in the case-control analysis for which models were adjusted, was indeed a confounding factor or whether it might have been the result of some form of selection bias. Consistent with the broader epidemiological evidence-base, these analyses provide further evidence that the dose-response association between cumulative external radiation exposure and IHD mortality is non-linear in that it has a linear shape plateauing at an excess risk of 43% (95% CI: 7–92%) on reaching 390 mSv. Analyses of plausible scenarios of patterns of missing data for tobacco smoking at start of employment indicated that this resulted in relatively little bias towards the null in the original analysis. An unmeasured confounder would have had to have been highly correlated (r_p > 0.60) with cumulative external radiation dose to importantly bias observed associations. The confounding effect of “having been monitored for internal dose” was unlikely to have been a true confounder in a biological sense, but instead may have been some unknown factor related to differences over time and between sites in selection criteria for internal monitoring, possibly resulting in collider bias. Plausible patterns of exposure measurement error negatively biased associations regardless of the modeled scenario, but did not importantly change the shape of the observed dose-response associations. These analyses provide additional support for the hypothesis that the observed association between external radiation exposure and IHD mortality may be causal.

长期低剂量或低剂量率暴露于外部辐射是否与循环系统疾病风险有因果关系的科学问题仍然是辐射防护的一个重要问题。先前对嵌套在英国核燃料循环工作人员的大型队列中的匹配病例对照数据集的分析表明，几乎没有证据表明外部辐射剂量与缺血性心脏病 (IHD) 死亡风险之间存在关联 [OR = 1.35 (95% CI) : 0.99–1.84) 15 年滞后暴露] 也可以通过就业前吸烟、BMI 或血压、社会经济地位或职业暴露于过度噪音或轮班工作的混杂因素来解释。为了改进关于观察到的外部辐射剂量和 IHD 死亡率关联的因果推断，我们估计了非随机误差的潜在幅度和方向，在可能的情况下结合了敏感性分析和模拟偏差效应。我们对基于 1,000 个 Monte Carlo 样本的合理情景进行了定量偏倚分析，以探索暴露测量误差、吸烟信息缺失和未测量混杂的影响，并评估观察到的关联是否依赖于使用 bootstrapping with在 1,000 个样本中随机排除 10% 的匹配对。我们进一步探讨了内部暴露监测的合理性，这是调整模型的病例对照分析中的一个重要混杂因素，确实是一个混杂因素，或者它是否可能是某种形式的选择偏倚的结果. 与更广泛的流行病学证据基础一致，这些分析提供了进一步的证据，表明累积外部辐射暴露与 IHD 死亡率之间的剂量反应关联是非线性的，因为它具有线性形状，在 43% (95% CI：7–92%）达到 390 mSv。对就业开始时吸烟缺失数据模式的可能情景的分析表明，这导致原始分析中对零值的偏倚相对较小。未测量的混杂因素必须高度相关（r 这些分析提供了进一步的证据，表明累积外部辐射暴露与 IHD 死亡率之间的剂量反应关联是非线性的，因为它具有线性形状，达到 43%（95% CI：7-92%）的额外风险390 毫希沃特。对就业开始时吸烟缺失数据模式的可能情景的分析表明，这导致原始分析中对零值的偏倚相对较小。未测量的混杂因素必须高度相关（r 这些分析提供了进一步的证据，表明累积外部辐射暴露与 IHD 死亡率之间的剂量反应关联是非线性的，因为它具有线性形状，达到 43%（95% CI：7-92%）的额外风险390 毫希沃特。对就业开始时吸烟缺失数据模式的可能情景的分析表明，这导致原始分析中对零值的偏倚相对较小。未测量的混杂因素必须高度相关（r_p > 0.60) 累积外部辐射剂量对观察到的关联产生重要偏差。“已监测内部剂量”的混杂效应不太可能是生物学意义上的真正混杂因素，而可能是一些未知因素，与内部监测选择标准中随时间和地点之间的差异有关，可能导致在对撞机偏差中。无论建模场景如何，暴露测量误差的合理模式都会使关联产生负偏倚，但并没有重要地改变观察到的剂量反应关联的形状。这些分析为观察到的外部辐射暴露与 IHD 死亡率之间的关联可能是因果关系的假设提供了额外的支持。