- 學位論文
大氣懸浮微粒短期暴露對心血管系統健康效應之研究
The Effects of Short-term Ambient Particulate Matters Exposure on the Cardiovascular System
摘要
隨著心血管疾病的罹病率的大幅增加，心血管疾病的防治已成為全世界公共衛生政策的重要議題。除了傳統的個人風險因子外，空氣污染近年來逐漸被確認為導致心血管疾病的重要環境風險因子。歐美地區大量的流行病學研究結果已證實大氣中懸浮微粒短期暴露與心血管疾病的罹病率和死亡率的增加有顯著相關。然而亞洲地區的空氣污染嚴重程度、人口結構、生活習慣、以及疾病型態並不同於歐美國家，其研究結果並不能完全推論亞洲地區的狀況。因此，本論文研究的目的在於探討台灣地區大氣懸浮微粒及其中化學成分的短期暴露的對心血管疾病罹病率的影響，以及大氣懸浮微粒短期暴露對臨床症狀前期血壓及血流動力學變化的影響。 本論文共分為三個部分，第一部分是以時間序列研究（Time-series study）方式探討大氣細懸浮微粒（Particulate matter with an aerodiameter <2.5μm, PM2.5）及其中化學成分的短期暴露對台大醫院缺血性心臟病及急性腦中風急診住院率的影響。研究結果發現大氣細懸浮微粒及其中化學成分，硝酸鹽、硫酸鹽、有機碳、及元素碳的短期暴露，以及一氧化碳及臭氧氣狀污染物和缺血性心臟病急診住院率呈現顯著正相關，其相關性在女性及65歲以下病患族群較為顯著。硝酸鹽及元素碳的短期暴露和急性出血性中風急診就診率呈現正相關；而大氣細懸浮微粒的化學成分則在夏季以及大於65歲和女性族群中增加缺血性中風急診就診的風險。第二部分是利用橫斷式研究（Cross-sectional study）探討大氣懸浮微粒（Particulate matter with an aerodiameter <10μm, PM10）及其他氣狀污染物短期暴露對健康族群臨床前期血壓的變化。研究結果顯示包括大氣懸浮微粒、二氧化硫、二氧化氮、一氧化碳、及臭氧短期暴露導致收縮壓及脈搏壓下降。大氣懸浮微粒導致脈搏壓下降的現象在男性、大於60歲的族群、以及居住於工業區的族群更為顯著。第三部分是利用個案小組研究（Panel study）評估大氣細懸浮微粒及其學成分短期暴露對心臟及血管的血流動力學參數變化的影響。結果發現大氣細懸浮微粒其中硝酸鹽、硫酸鹽、有機碳、及元素碳化學成分短期暴露會導致脈搏壓下降、左心室收縮力、心搏出量、心輸出量、及血管順應性下降，但分組分析發現該效應在服用降血壓藥物個案變的不顯著。若進一步將個案分為有正常日夜間血壓節率變化的Dippers (日夜間平均收縮壓差 >10 mmHg)和無正常日夜間血壓節率變化Non-dippers (日夜間平均收縮壓差 <10 mmHg)進行分組分析，發現大氣細懸浮微粒的短期暴露會導致Non-dippers個案脈搏壓的下降以及心臟收縮力及血管順應性的降低。 綜合以上研究結果，本論文證實空氣污染短期暴露，尤其是大氣懸浮微粒及有關交通或工業排放的污染物會導致缺血性心臟病及急性腦中風的急診就診率增加。大氣懸浮微粒及特定之化學分短期暴露對血壓並未顯著上升，反而在臨床前期發現包括脈搏壓、心臟收縮力、以及血管順應性降低等血流動力學的變化，導致灌流不足可能是進一步誘發缺血性心臟病及急性腦中風的可能致病機轉。此外，研究結果亦顯示空氣污染和心血管疾病之間的關係在不同年齡、性別、心臟風險因子、以及不同季節間呈現不同的易感性。
並列摘要
The increasing morbidity of cardiovascular disease (CVD) over the recent decades has become a major focus of public health worldwide. In addition to traditional individual risk factors, ambient air pollution is gaining recognition as an important risk factor for CVD. Numerous epidemiological studies have consistently reported that ambient air pollution, especially particulate matter (PM), is associated with CVD in North America and Europe. However, there is an urgent need to fill the knowledge gap of our understanding of the impact of air pollution on health in Asia, the region with the worst air pollution in the world and varied emitted sources and population structure from the Western countries. Therefore, the aims of this thesis were to investigate the short-term effects of PM and its constituents exposure on the cardiovascular morbidity, subclinical blood pressure (BP), and hemodynamic changes in Taiwan. This thesis includes three parts. The first part is composed of two time-series studies. The time-series design were applied to evaluate the effects of fine particulate matter (PM2.5) and its constituents on daily emergency room (ER) visits for ischemic heart disease (IHD) and cerebrocvascular disease (CBVD) in Taipei, Taiwan. The results showed that PM2.5 mass and the four PM2.5 constituents, including nitrate, sulfate, organic carbon (OC), and elemental carbon (EC), increased ER visits for IHD. Females and patients aged less than 65 had greater risk for IHD by particulate pollutants. For hemorrhagic stroke, estimated relative risks (RRs) of ER visits were 1.13 (1.04 to 1.22) and 1.08 (1.02 to 1.15) for an interquartile range (IQR) increase in nitrate and EC on the current-day. For ischemic stroke, increased RRs of ER visits of 1.12 (1.02 to 1.23), 1.09 (1.00 to 1.19), 1.19 (1.06 to 1.32), and 1.18 (1.07 to 1.30) were observed in the warm season for an IQR increase in 2-day average of PM2.5, sulfate, OC, and EC, respectively. PM2.5 and OC were associated with increased RRs of ER visits for ischemic stroke among patients aged 65 years or older and female patients. The second part is a cross-sectional design to evaluate the associations between brachial BP and short-term exposure to five air pollutants: particulate matter with an aerodiameter <10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). The results revealed that pulse pressure was consistently decreased by all five pollutants, with changes of -1.5 (-2.0 to -1.1), -0.6 (-0.9 to -0.4), -2.4 (-3.0 to -1.8), -1.2 (-1.6 to -0.9), and -1.4 (-1.8 to -0.9) mm Hg for IQR increases in 3-day lagged PM10, SO2, NO2, CO, and O3, respectively. PM10 exposure was more strongly associated with reduction of pulse pressure among men, over 60 years of age, those with hypertension and living in the industrial township. In the third part, we applied a panel to assess 24-h time-weighted average BP and hemodynamic changes due to short-term exposure to PM2.5 and the four constituents. Hemodynamic parameters, including left ventricular contractility, stroke volume, cardiac output, and brachial artery compliance, exhibited maximal reductions of 9.3% (3.7 to 14.9), 9.8% (3.9 to 15.7), 8.3% (3.1 to 13.6), and 10.6% (4.6 to 16.5) in response to an IQR increase in PM2.5 constituents. The hemodynamic changes in response to PM2.5 constituents became insignificant among participants with anti-hypertensive medication. Stratified analyses showed that short-term PM2.5 exposure contributes to a sustained pulse pressure narrowing and cardiac and vasomotor dysfunction in non-dippers, whose nocturnal systolic BP decrease <10 mm Hg and have been recognized as an important cardiovascular risk factor.. In conclusion, the results of these studies demonstrate that shot-term air pollutants exposure, especially traffic- and/or industrial-emitted PM, are associated with the increase in ER visits for CVD and CBVD. Our findings suggest that short-term PM exposure may not increase BP, however, it can adversely affect preclinical hemodynamic changes, including pulse pressure narrowing and impaired cardiac contractility and vascular compliance. The hypoperfusion caused by cardiac and vasomotor dysfunction may further contribute to the attack of IHD and acute stroke. The study results also demonstrate that individual characteristics, including age, sex, or predisposing cardiovascular risk factors, and seasonality may modify the effects of short-term PM exposure on hemodynamics and CVD morbidity.