遗传易感性在多大程度上改变了空气污染物与卒中风险之间的关联,目前尚不清楚。这项研究旨在调查长期暴露于空气污染物和遗传易感性对中风风险的单独和联合关联。
■这项研究的参与者是在2006年至2010年之间由英国生物银行招募的。对这些参与者进行随访,直到卒中事件发生或数据审查。与长期暴露于空气污染物相关的卒中事件的危险比(HR)和95%CI是通过拟合粗和校正Cox比例风险模型来估计的。此外,计算多基因风险评分是为了评估多基因风险评分是否改变了暴露于空气污染物与卒中的相关性.
■本研究包括总共502480名受试者。排除后,452196名参与者被纳入最终分析。在11.7年的中位随访时间内,观察到11334例中风事件,平均年龄为61.60岁,男性占总病例的56.2%。长期暴露于空气动力学直径小于2.5µm的颗粒物(调整后的HR,1.70[95%CI,1.43-2.03])或空气动力学直径小于10µm的颗粒物(调整后的HR,1.50[95%CI,1.36-1.66]),二氧化氮(调整后的HR,1.10[95%CI,1.07-1.12]),和氮氧化物(调整后的HR,1.04[95%CI,1.02-1.05])与卒中风险增加明显相关。同时,具有高遗传风险和暴露于高空气污染物的参与者约45%(31%,61%;空气动力学直径小于2.5µm的颗粒物),48%(33%,65%;空气动力学直径小于10µm的颗粒物),51%(35%,69%;二氧化氮),和39%(25%,55%;氮氧化物)与遗传风险低和暴露于低空气污染物的人群相比,中风的风险更高,分别。值得注意的是,我们观察到遗传易感性与空气污染物在卒中事件中的相加和乘法相互作用.
■长期暴露于空气污染物与卒中风险增加相关,尤其是在遗传风险高的人群中。
The extent to which genetic susceptibility modifies the associations between air pollutants and the risk of incident stroke is still unclear. This
study was designed to investigate the separate and joint associations of long-term exposure to air pollutants and genetic susceptibility on stroke risk.
The participants of this
study were recruited by the UK Biobank between 2006 and 2010. These participants were followed up from the enrollment until the occurrence of stroke events or censoring of data. Hazard ratios (HRs) and 95% CIs for stroke events associated with long-term exposure to air pollutants were estimated by fitting both crude and adjusted Cox proportional hazards models. Additionally, the polygenic risk score was calculated to estimate whether the polygenic risk score modifies the associations between exposure to air pollutants and incident stroke.
A total of 502 480 subjects were included in this
study. After exclusion, 452 196 participants were taken into the final analysis. During a median follow-up time of 11.7 years, 11 334 stroke events were observed, with a mean age of 61.60 years, and men accounted for 56.2% of the total cases. Long-term exposures to particulate matter with an aerodynamic diameter smaller than 2.5 µm (adjusted HR, 1.70 [95% CI, 1.43-2.03]) or particulate matter with an aerodynamic diameter smaller than 10 µm (adjusted HR, 1.50 [95% CI, 1.36-1.66]), nitrogen dioxide (adjusted HR, 1.10 [95% CI, 1.07-1.12]), and nitrogen oxide (adjusted HR, 1.04 [95% CI, 1.02-1.05]) were pronouncedly associated with increased risk of stroke. Meanwhile, participants with high genetic risk and exposure to high air pollutants had ≈45% (31%, 61%; particulate matter with an aerodynamic diameter smaller than 2.5 µm), 48% (33%, 65%; particulate matter with an aerodynamic diameter smaller than 10 µm), 51% (35%, 69%; nitrogen dioxide), and 39% (25%, 55%; nitrogen oxide) higher risk of stroke compared with those with low genetic risk and exposure to low air pollutants, respectively. Of note, we observed additive and multiplicative interactions between genetic susceptibility and air pollutants on stroke events.
Chronic exposure to air pollutants was associated with an increased risk of stroke, especially in populations at high genetic risk.