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Review and meta-analysis of epidemiological associations between low/moderate doses of ionizing radiation and circulatory disease risks, and their possible mechanisms

机译:审查和荟萃分析低/中剂量电离辐射与循环系统疾病风险之间的流行病学关联及其可能的机制

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Although the link between high doses of ionizing radiation and damage to the heart and coronary arteries has been well established for some time, the association between lower-dose exposures and late occurring cardiovascular disease has only recently begun to emerge, and is still controversial. In this paper, we extend an earlier systematic review by Little et al. on the epidemiological evidence for associations between low and moderate doses of ionizing radiation exposure and late occurring blood circulatory system disease. Excess relative risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well-known (but unobserved) risk factors, and there is statistically significant (p < 0.00001) heterogeneity between the risks. This heterogeneity is reduced, but remains significant, if adjustments are made for the effects of fractionated delivery or if there is stratification by endpoint (cardiovascular disease vs. stroke, morbidity vs. mortality). One possible biological mechanism is damage to endothelial cells and subsequent induction of an inflammatory response, although it seems unlikely that this would extend to low-dose and low-dose-rate exposure. A recent paper of Little et al. proposed an arguably more plausible mechanism for fractionated low-dose effects, based on monocyte cell killing in the intima. Although the predictions of the model are consistent with the epidemiological data, the experimental predictions made have yet to be tested. Further epidemiological and biological evidence will allow a firmer conclusion to be drawn.
机译:尽管高剂量电离辐射与心脏和冠状动脉损害之间的联系已经建立了一段时间,但低剂量暴露与晚期心血管疾病之间的关联只是最近才开始出现,并且仍存在争议。在本文中,我们扩展了Little等人的早期系统综述。关于中低剂量电离辐射暴露与晚期血液循环系统疾病之间的关联的流行病学证据。流行病学研究中每单位剂量过量的相对风险至少在两个数量级上变化,这可能是由于众所周知(但未观察到)的风险因素造成的混淆和效果改变的结果,并且在统计学上差异很大(p <0.00001)风险。如果针对分次递送的效果进行了调整,或者如果按终点进行了分层(心血管疾病与卒中,发病率与死亡率),则这种异质性会降低,但仍然很重要。一种可能的生物学机制是对内皮细胞的损害和随后的炎症反应的诱导,尽管这似乎不太可能扩展到低剂量和低剂量率暴露。 Little等人的最新论文。基于内膜中单核细胞的杀伤,有人提出了一种可能的更合理的分次低剂量效应机制。尽管该模型的预测与流行病学数据一致,但是所做的实验预测尚未得到检验。进一步的流行病学和生物学证据将可以得出更坚定的结论。

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