Relationship between fineparticulate air pollution and ischaemic heart disease morbidity and mortality

Wuxiang Xie, Gang Li, Dong Zhao, Xueqin Xie, ZaihuaWei, Wei Wang, Miao Wang, Guoxing Li, Wanru Liu, Jiayi Sun, Zhangrong Jia, QianZhang, Jing Liu

题目：PM2.5空气污染与缺血性心脏病发病率与死亡率的关系

汇报人：蒲利红

时间：2015.10.22 16:00-17:00

地点：病房楼三层超声心动一部示教室

ABSTRACT

Objective To assess therelationship between fine particulate matter concentration and ischaemic heartdisease morbidity and mortality.

Methods A time-series study conducted in Beijing from 1January 2010 to 31 December 2012. Data on 369 469 IHD cases and 53 247 IHDdeaths were collected by the Beijing Monitoring System for Cardiovascular Diseases,which covers all hospital admissions and deaths from IHD from Beijing’s populationof 19.61 million.

Results Thedose–response relationships between PM2.5 and IHD morbidity and mortality werenon-linear, with a steeper dose–response function at lower concentrations and ashallower response at higher concentrations.

Conclusions PM2.5concentration was significantly associated with IHD morbidity and mortality inBeijing. Our findings provide a rationale for the urgent need for stringentcontrol of air pollution to reduce PM2.5 concentration.

研究目的：评估PM2.5与缺血性心脏病发病率和死亡率之间的关系。

研究方法：一项于2010年1月1日至2012年12月31之间实施时间序列研究，并通过北京心血管疾病监测系统采集了369469例IHD和52247例IHD死亡病例。该监测系统覆盖北京近2000万人群的所有IHD住院及死亡信息。

研究结果：主要发现PM2.5与缺血性心脏病发病率和死亡率存在显著关系但非线性，在较低浓度ＰＭ2.5时剂量－反应曲线较陡， 而在较高浓度时较平缓。

讨论：结果表明PM2.5与缺血性心脏病发病率和死亡率具有显著相关性。研究者们进一步指出，目前迫切需要对减少PM2.5浓度进行紧急措施。

Introduction

A meta-analysis that combined theresults from 13 studies solely using either mortality or admission datareported that PM 2.5 pollution was significantly associated with the risk ofmyocardial infarction. However, to fully reflect the association between PM2.5and ischaemic heart disease bothnon-fatal and fatal cases and both in-hospital and out-of-hospital deaths,should be considered. Moreover, this meta-analysis did not include studies fromdeveloping countries where PM2.5 pollution is more severe, so the associationbetween PM2.5 and IHD at very high levels of pollution is still unclear.

A cohort study explored theexposure–response relationship for cardiovascular mortality in relation toPM2.5 from active smoking, second-hand smoke and ambient air pollution, andfound that the exposure–response function is extremely steep at very low PM2.5levels and flattens out at high levels . However, the shape of the dose–responserelationship between PM2.5 and cardiovascular risk in a real and severe airpollution environment is still unclear.

之前有一篇Mata分析的文章总结了13项研究，单独用了死亡率或住院率，得到了PM2.5与心梗显著相关的结论。但是想要全面分析PM2.5与缺血性心脏病的关系，需要包括所有非致命的和致命的病例，所有院内和院外死亡的病例，而且这项研究没有包括发展中国家PM2.5污染更严重的地区，所以高浓度PM2.5和缺血性心脏病的关系仍然是不清楚的。

还有一个国外关于PM2.5与心血管疾病死亡率关系的队列研究，研究的是来自吸烟、二手烟和当地严重空气污染的PM2.5，发现在较低浓度 ＰＭ２.5时暴露－反应作用较明显， 而在较高浓度PM2.5反应作用低平。但是在一个真实且严重的空气污染环境中的剂量-反应关系仍然不清楚。

METHODS
PM2.5 and weather data
The US embassy Beijing Air Quality Monitor is atop the embassy building locatedin Chaoyang district, reporting hourly PM2.5 concentrations .A previous study has demonstrated that the datafrom the monitor exhibited approximately the same trend as citywide PM2.5 concentrations. Coverage includes 79.2% of Beijing’stotal population and all areas of high population density (>5000people/km2). The area also covers 97.8% of the tertiary hospitals and 79.3% ofthe secondary hospitals in Beijing that admit IHD cases. If the cumulative timeof missing hourly PM2.5 data was <12 h during a day, that day was consideredas qualified and the daily averaged PM2.5 concentration was calculated directly(1060 days). Otherwise, daily averages were calculated using linearinterpolation (36 days). Meteorological data on daily mean temperature,relative humidity and dew-point temperature were obtained from the ChinaMeteorological Data Sharing Service System.

Health data
IHD cases were identified by the Beijing Monitoring System for CardiovascularDiseases which links the routinely collected records in the Beijing HospitalDischarge Information System and the Beijing Vital Registration MonitoringSystem. The
Hospital Discharge Information System is operated by the Beijing Public HealthInformation Center and covers discharges from all government and privatehospitals at secondary or tertiary level in Beijing. The Vital RegistrationMonitoring System is managed by Beijing Center for Disease Control and Preventionand covers all deaths in Beijing. Any hospital admissions or death records forthe same patient that occurred within 28 days were assumed to relate to onecase and were excluded. Finally, 369 469 cases of IHD morbidity were analysed.These included 199 209 cases of acute IHD, 111 851cases of chronic IHD and 58409 cases of other types of IHD. Mortality outcomes included 53 247 IHD deaths,among which 13 867 and 39 380 deaths occurred in and out of hospital,respectively.

PM2.5和气象数据

每小时PM2.5浓度的数据是通过朝阳区美国大使馆楼顶的空气监测器收集的，之前有研究证明检测器收集到的方圆40km的PM2.5浓度可以近似反应这个城市PM2.5的趋势。研究覆盖了79.2%的北京人口和所有人口密集的地区，覆盖了期间北京97.8%的三级医院和79.3%的二级医院的所有缺血性心脏病的病例。用线性内插法对缺失数据进行填充后得到完整的日均浓度。气象数据包括平均气温、相对湿度和露点，是通过中国气象数据共享服务系统获得的。

健康数据资料

IHD病例是北京心血管疾病监测系统通过北京公共卫生信息中心管理的北京出院信息系统和北京疾病控制预防中心管理的北京生命登记监测系统采集的，覆盖了北京所有地区的二三级公有和私有医院，发病率数据中排除了28天内住院并死亡的同一病例（认为是一个病例，纳入死亡组），最后收集了369469例IHD 住院和53247例死亡病例。该监测系统覆盖北京近2000万人群的所有IHD住院及死亡信息。包括199209急性、11851慢性及58409其他病例，13867例院内死亡，39380例院外死亡。

RESULTS
IHD morbidity and mortality
Of the all IHD cases thatoccurred during the study period, 59.9% of the data were male cases and 44.6%were under 65 years of age. Among all death cases, 74.0% occurred out ofhospital. On average, 337 IHD cases and 49 deaths occurred per day.

PM2.5 concentration and weatherconditions

Duringthe 1096 days, the mean daily PM2.5 concentration was 96.2 μg/m3, with a range from3.9 to 493.9 μg/m3. Only 47.4% of thedaily PM2.5 concentrations achieved the target of Chinese Ministry of EnvironmentalProtection 2010, 22.2% achieved the target of the US National Ambient AirQuality Standards and 15.3% achieved thetarget of WHO Air Quality Guidelines.

Associations between PM2.5concentration and IHD risk
There were clear dose–responserelationships of PM2.5 concentration with IHD morbidity and mortality. Theserelationships are non-linear with a steeper dose–response function at lowerconcentrations and a shallower response at higher concentrations. Afteradjusting for day of the week, seasonality and other time-varying influencesand weather conditions, a 10 μg/m3 increase in PM2.5 was associated with a0.27% increase in IHD morbidity and a 0.25% increase in IHD mortality on thesame day.

Significantlag associations of PM2.5 with IHD morbidity were observed at lag 1, 2 and 3 days,no significant lag association with IHD mortality was noted.

Thecurrent day and lag 0–2 days associations of PM2.5 with different types of IHDwere all significant.

Asignificantly stronger lag association was found for chronic IHD cases versusacute cases and for non-fatal cases versus fatal cases，while no significant difference was observed for the associationsof PM2.5 with in-hospital deaths versus out-of-hospital deaths.

The associations of PM2.5with IHD by age and gender

Theassociations of 3-day or 5-day average concentration with both IHD morbidityand mortality were significantly stronger among the older people.

Among people aged ≥65 years, current-day, 3-day and 5-day average of PM2.5 were

significantly associated withboth IHD morbidity and mortality. However, for those aged<65 years, significant associations wereonly found with IHD morbidity.

Theassociations of current-day, 3-day and 5-day average of PM2.5 with IHD morbidityand mortality were all significant among men and women. The current-day association with IHDmorbidity was stronger in women . However, no gender difference for IHDmortality.

IHD cases and deaths advanced by PM2.5pollution

therewere 4099 cases and 855 deaths advanced by PM2.5 pollution over expected ratesif daily levels had not exceeded the Chinese target (75 μg/m3) during the studyperiod. The corresponding numbers were 6860 cases and 1312 deaths for the UStarget (35 μg/m3) and 7703 cases and 1475 deaths for WHO target (25 μg/m3).

IHD发病率与死亡率

在所有IHD住院病例中，男性和65岁以上人群占多数。在所有IHD死亡病例中，74%发生在院外。因PM2.5污染平均每天有337人因IHD住院、49人因IHD死亡。

PM2.5与气候条件

北京平均ＰＭ2.5浓度为９６.2μg/m3，波动范围3.9 -493.9 μg/m3， 在研究期间， 47.4%日平均

ＰＭ2.5浓度达到2010中国环境保护管理局目标，只有22.2%达到美国空气质量标准，仅15.3％达到世界卫生组织空 气 质 量指 南 标 准。

PM2.5与IHD风险的关系

ＰＭ２.5浓 度 和Ｉ ＨＤ 发病率和死 亡 率 之 间 的 剂 量－反 应 关 系 呈 非 线性， 在较低浓度 ＰＭ２.5时剂量－反应曲线较陡， 而在较高浓 度 时 较 平 缓。ＰＭ２.5 浓 度 每 增 加１０μg/m3， 同 日ＩＨＤ 发病率增加0.27％， 死亡率增加0.25％。

GAM模型拟合结果：滞后1、2、3天PM2.5与 IHD发病率显著相关，而与死亡率没有显著的滞后效应。

当天和滞后0-2天PM2.5与所有类型的IHD都显著相关。

慢性IHD及非致命性IHD的滞后效应更明显，而对于死亡病例来说，PM2.5对院内和院外死亡的滞后效应无明显差异。

年龄和性别差异
PM2.5与IHD的发病率和死亡率在老年人群中更显著，特别是第3、5天。65岁以上人群在当天、第3、5天的发病率、死亡率显著相关，而65岁以下人群相关性仅表现在发病率上。

男女人群的发病率、死亡率与PM2.5均相关，特别在当天、滞后3、5天，对于发病率来说，女性人群更显著相关，而对于死亡率来说，男女无明显差异。

PM2.5引发的额外IHD发病与死亡

在3年研究期间，北京PM2.5浓度超出中国目标引发了4099例额外IHD病例和855例额外死亡病例，超出美国目标引发了6860例额外IHD病例和1312例额外死亡病例，超出WHO目标引发了7703例额外IHD病例和1475例额外死亡病例。

DISCUSSION

Thisstudy provides strong evidence of the associations of PM2.5 with IHD morbidityand mortality in Beijing. The exploration of the dose–response relationshipbetween
PM2.5 concentration and IHD risk is crucial to determine the pattern and scopeof the adverse response.

The findingthat an increase in PM2.5 at very low levels was sufficient to induce a significantadverse response on IHD morbidity and mortality implies that there is nothreshold for safety of PM2.5 pollution.

Althoughat higher PM2.5 concentrations the slope of the curve became shallower, therisk continued to rise as PM2.5 concentration was higher, implying that thereis no saturation effect for the risk of IHD at a high level of PM2.5concentration.

Thisstudy provide clear evidence to support that people older than 65 years aremore sensitive to PM2.5 pollution. These findings indicate that older personsare more sensitive to the elevated PM2.5 and should stay at home when PM2.5 concentrationis extremely high.

Possiblybecause of the higher level of PM2.5 pollution in Beijing, a longer lagassociation was noted. Interestingly, we found a significantly stronger lagassociation for chronic IHD cases versus acute cases and for non-fatal cases versusfatal cases, a difference which has not been reported previously as far as weknow.

研究为北京PM2.5浓度与IHD的相关性提供了强有力的证据，而得出的剂量反应关系对指导应对措施是非常关键的。

在较低浓度 ＰＭ２.5时剂量－反应曲线较陡，表明对PM2.5的防护要从低浓度开始，没有阈值。

虽然在较高浓度时曲线较平缓，但若PM2.5升高IHD的风险也在进一步增高，表明PM2.5的影响没有饱和状态，高浓度PM2.5时更应该做好防护。

研究表明65岁以上人群对PM2.5更敏感，在PM2.5浓度很高时，老年人应该待在家里，尽量避免接触。

可能由于北京PM2.5浓度水平较高，研究得出了更长时的滞后效应，以往研究往往只得出0-2天的滞后效应。研究还得出慢性IHD及非致命性的IHD比急性和致命性的IHD有明显更长的滞后效应，这也是以往研究中没有报告过的。