摘要目的:分析空气污染、遗传易感性与房颤患者全因死亡和心血管结局风险的关联。方法:基于英国生物银行前瞻性队列数据，纳入2006-2010年注册、年龄在40~69岁的房颤患者，剔除随访期间失访或资料不全者，共5 814名研究对象。根据每名研究对象的地理编码居住地址估算长期空气污染暴露的年均值。以每名研究对象的全因死亡、心血管疾病、心力衰竭（心衰）、心肌梗死（心梗）和脑卒中的遗传风险评分来评估相应的遗传易感性。采用Cox比例风险回归模型分析空气污染、遗传易感性与房颤患者发生全因死亡和心血管结局风险的关联。结果:在12.4年的中位数随访期间，新发了929名（15.98%）全因死亡与1 772名（30.48%）非致命性心血管事件。多因素调整结果显示，暴露于更高的PM 2.5、PM 10、NO x、NO 2与心血管死亡、心衰、心梗和脑卒中的发生风险增加相关，风险比（ HR）值范围为1.26~1.48。其中PM 2.5暴露每增加1个四分位间距（ IQR），心血管死亡、心衰、心梗和脑卒中的 HR值分别为1.33（95% CI：1.14~1.54）、1.42（95% CI：1.31~1.54）、1.46（95% CI：1.30~1.64）、1.43（95% CI：1.27~1.61）。而NO x、NO 2暴露每增加1个 IQR，全因死亡风险均增加9%，对应的 HR值分别为1.09（95% CI：1.02~1.17）与1.09（95% CI：1.01~1.17）。相较于低遗传易感性，高遗传易感性的房颤患者心梗与脑卒中的发生风险更高，对应的 HR值分别为1.39（95% CI：1.04~1.87）与1.46（95% CI：1.09~1.95）。与低空气污染暴露的房颤患者相比，高空气污染暴露的心血管死亡的调整后人群归因分值为33.57%（95% CI：17.87%~46.26%），心衰为28.61%（95% CI：20.67%~35.75%），心梗为33.35%（95% CI：20.97%~43.79%），脑卒中为42.29%（95% CI：30.05%~52.71%）。此外，PM 2.5、NO x、NO 2暴露与高遗传易感性在心梗发生风险上有相加交互作用。NO x、NO 2暴露与高遗传易感性在心衰发生风险上也有相加交互作用（均 P<0.05）。 结论:空气污染、遗传易感性均会增加房颤患者全因死亡和心血管结局风险。

abstractsObjective:To analyze the association between air pollution, genetic susceptibility, and the risk of all-cause mortality and cardiovascular outcomes in patients with atrial fibrillation (AF).Methods:AF patients aged between 40-69 years old registered in the United Kingdom Biobank from 2006 to 2010 were included. After excluding those lost to follow-up or with incomplete data during follow-up, 5 814 subjects were analyzed. Long-term exposure to air pollution was estimated at the geocoded residential address of each participant. Genetic risk scores for all-cause mortality, cardiovascular disease, heart failure, myocardial infarction, and stroke were constructed separately for each object to assess the corresponding genetic susceptibility. The Cox proportional hazards model was used to analyze the association between air pollution, genetic susceptibility, and the risk of all-cause mortality and cardiovascular outcomes in AF patients.Results:During a median follow-up of 12.4 years, there were 929 of all-cause mortality (15.98%) and 1 772 of cardiovascular events (30.48%). Multivariable-adjusted analyses revealed that higher exposure to PM 2.5, PM 10, NO x, and NO 2 was associated with an increased risk of cardiovascular disease mortality, heart failure, myocardial infarction, and stroke, with hazard ratios ( HRs) ranging from 1.26 to 1.48. Specifically, for each interquartile range ( IQR) increase in PM 2.5 exposure, the HRs for the outcomes mentioned above were 1.33 (95% CI: 1.14-1.54), 1.42 (95% CI: 1.31-1.54), 1.46 (95% CI: 1.30-1.64), and 1.43 (95% CI: 1.27-1.61), respectively. Both NO x and NO 2 exposures were associated with a 9% increased risk of all-cause mortality per IQR increment, with corresponding HRs of 1.09 (95% CI: 1.02-1.17) and 1.09 (95% CI: 1.01-1.17), respectively. Individuals with high genetic susceptibility to AF had a higher risk of myocardial infarction and stroke compared to those with low genetic susceptibility, with corresponding HRs of 1.39 (95% CI: 1.04-1.87) and 1.46 (95% CI: 1.09-1.95), respectively. Compared to AF patients with low air pollution exposure, those with high air pollution exposure have adjusted population attributable fractions of up to 33.57% (95% CI: 17.87%-46.26%) for cardiovascular mortality, 28.61% (95% CI: 20.67%-35.75%) for heart failure, 33.35% (95% CI: 20.97%-43.79%) for myocardial infarction, and 42.29% (95% CI: 30.05%-52.71%) for stroke. Furthermore, there was an additive interaction between PM 2.5, NO x, and NO 2 exposure and high genetic susceptibility on the incidence of myocardial infarction. An additive interaction was also observed between NO x, NO 2 exposure, and high genetic susceptibility on the incidence of heart failure (all P<0.05). Conclusions:Both air pollution and genetic susceptibility increase the risk of all-cause mortality and cardiovascular outcomes in AF patients.