细颗粒物暴露、遗传易感性与卒中发病风险：一项前瞻性队列研究。
Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study.
机构信息
Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (K.H., J.J., J.L., X.N., S.C., J.C., L.Z., Y. Li, J.H., D.G., F. Liu, X. Lu).
Key Laboratory of Cardiovascular Epidemiology (K.H., J.J., J.L., S.C., J.C., L.Z., Y. Li, J.H., D.G., F. Liu, X. Lu), Chinese Academy of Medical Sciences, Beijing, China.
出版信息
Stroke. 2024 Jan;55(1):92-100. doi: 10.1161/STROKEAHA.123.043812. Epub 2023 Nov 29.
BACKGROUND
Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors.
METHODS
This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM and polygenic risk score with incident stroke and the potential effect modifications.
RESULTS
Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride.
CONCLUSIONS
Long-term exposure to PM was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.
背景
遗传因素和环境空气污染都会增加中风的风险。然而，目前尚不清楚空气污染与中风风险之间的关联是否受到中风及其危险因素的遗传易感性的影响。
方法
本前瞻性队列研究纳入了 40827 名无中风病史的中国成年人。使用基于卫星的每月 1 公里分辨率的细颗粒物（PM）估算值进行暴露评估。基于东亚人群全基因组关联研究中确定的 534 个遗传变异，我们构建了 6 个中风及其危险因素（包括心房颤动、血压、2 型糖尿病、体重指数和甘油三酯）的多基因风险评分。应用 Cox 比例风险模型评估 PM 和多基因风险评分与中风事件的风险比和 95%置信区间，以及潜在的效应修饰作用。
结果
在中位随访 12.06 年期间，共记录了 3147 例中风事件。与 PM 暴露最低四分位数相比，最高四分位数组中风的风险比（95%CI）为 2.72（2.42-3.06）。在遗传风险较高的个体中，中风的相对风险比遗传风险较低的个体高 57%（1.57；1.40-1.76）。尽管未发现统计学上的显著交互作用，但同时处于 PM 最高和遗传风险最高的参与者发生中风的风险最高，约为 PM 最低和遗传风险最低组的 4 倍（风险比，3.55 [95%CI，2.84-4.44]）。当评估 PM 和血压、2 型糖尿病、体重指数、心房颤动和甘油三酯的遗传风险联合作用对中风风险的影响时，也观察到类似的递增梯度。
结论
长期暴露于 PM 与不同遗传易感性的中风风险增加有关。我们的研究结果强调了在中风预防中全面评估空气污染和遗传风险的重要性。
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