大气细颗粒物对心血管疾病的长期影响和预测研究

Ambient fine particulate matter (PM2.5) ranked the fourth leading cause of disease burden in China, after dietary factors, high blood pressure, and smoking in 2010. Studies from the United States and Europe, including the Harvard Six City Study, the American Cancer Society Study, the Multi-Ethnic Study of Atherosclerosis and Air Pollution and European Study of Cohorts for Air Pollution Effects, have investigated long-term health effect of PM2.5 exposure. However, the average concentration of PM2.5 is much higher in China, with markedly different constituents. Up to now, it is still unclear for the causal relationship of PM2.5 and its constituents with incidence and mortality of cardiovascular disease (CVD), as well as prognosis of acute myocardial infarction (AMI) patients in China. Our proposed project is aimed (1) to identify the long-term effects of PM2.5 on incidence and mortality of CVD in China based on several large-scale nation-wide cohorts, (2) to identify the long-term effects of PM2.5 on prognosis based on a large AMI patient cohort, (3) to conduct a panel study to explore relationship of personal exposure of PM2.5 with biomarkers and subclinical indicators of atherosclerosis, (4) to identify gene-environment interaction on CVD progression based a nested case-control study from the aforementioned cohorts, and (5) to predict the projected impact of PM2.5 pollution control on trends for incidence and mortality of CVD in China during 2016-2030 using CVD Policy Model-China. The proposed project will provide novel population-based evidence on the causal relationship between PM2.5 and CVD in China, and also help us to understand the potential physiological mechanisms of CVD induced by PM2.5. The expected results are pivotal to develop evidence-based policies regarding improvement of air quality and public health.

大气细颗粒物是造成我国疾病负担的第4位危险因素。欧美国家利用队列研究阐明细颗粒物的长期健康效应。但是，我国细颗粒物浓度显著高于发达国家，且组份差异较大，细颗粒物及其组份暴露对心血管健康的长期影响和预测研究在我国尚属空白。本项目拟开展以下研究：（1）利用大型前瞻性社区队列人群资料，采用先进的卫星遥感反演技术，确定细颗粒物及其组份对心血管疾病及其危险因素的长期健康效应；（2）利用急性心肌梗死患者队列，明确细颗粒物及其组份对患者预后的影响；（3）基于现有队列人群开展定群研究，进行个体细颗粒物暴露监测，明确细颗粒物及其组份对代谢组、遗传和表观遗传等指标的影响，阐明潜在致病途径；（4）基于现有队列人群开展巢式病例对照研究，探讨遗传与细颗粒物长期暴露对心血管疾病发病和死亡的交互作用；（5）在上述基础上，预测细颗粒物污染控制的健康获益。本项目能够为大气污染防治等公共卫生政策制定提供重要参考依据。

研究背景.心血管疾病（Cardiovascular Disease，CVD）是我国居民的主要死因。大气细颗粒物（fine particulate matter，PM2.5）污染是CVD重要危险因素之一。但是，我国大气污染健康风险研究起步较晚，缺少高浓度污染下研究证据。.主要研究内容.本项目依托于全国前瞻性自然人群队列和CVD患者队列，探讨PM2.5长期暴露对CVD及其危险因素的健康效应，及其对患者预后的影响；开展定群研究及病例队列研究，明确PM2.5对心血管亚临床指标的影响，探讨遗传与PM2.5暴露的交互作用；进一步基于中国心血管疾病政策模型，预测PM2.5污染控制的健康获益。.研究结果.利用我国12万例大型前瞻性自然人群队列资料研究发现，大气PM2.5每增加10 μg/m3，冠心病、高血压、糖尿病发病风险分别显著增加43%、11％和15.7％。利用北京市2013~2018年162084例急性心肌梗死患者住院资料，发现PM2.5暴露与急性心肌梗死入院显著正相关；另外，通过病例交叉设计发现PM2.5和PM10每升高10 μg/m3，房颤发作风险分别显著增加3.5%和2.7%。通过定群研究，发现大气PM2.5暴露与心率变异性和肺功能下降显著相关，但是血压控制达标者或服用ARB类降压药者，大气PM2.5暴露对心率变异性的影响减弱。利用中国心血管疾病政策模型预测发现，如果2017~2030年，PM2.5全国城市平均水平从61 μg/m3下降到55 μg/m3，我国35~84岁城市居民中能减少CVD死亡67.6万人；若年均值控制到10 μg/m3，将减少CVD死亡470万人，远超过我国25%的高血压患者控制达标或者减少30%的吸烟人群所带来的心血管健康获益。.科学意义.本项目系统阐明了大气PM2.5长期暴露对CVD及其危险因素的慢性健康效应，探讨了大气PM2.5暴露对CVD患者预后的影响，建立了相应的暴露反应关系；同时探讨了PM2.5暴露对早期亚临床指标的影响和遗传-环境交互作用；并定量预测了我国PM2.5控制的潜在获益。本项目将为我国大气污染防治政策制定和心血管病防控提供关键依据。