| Backgrounds and ObjectivesCardiovascular disease (CVD) refers to the class of heart and vascular diseases including myocardial infarction, stroke, hypertension, disease of pulmonary circulation, peripheral vascular disease and cerebrovascular disease. With the developing of economy and the improving of the living standard, CVD is common now and constitutes a major threat to public health. In China, the first disease with the highest proportion to be suffered is CVD, and it was also the top death cause in developed countries. The etiology of CVD is complicated. Besides the biological factors, the psychological and environmental factors also play an important role.Along with the industrialization speeding up, the environmental pollution is day by day serious. The WHO estimates that air pollution is responsible for 3 million premature deaths each year. Numerous epidemiologic studies also demonstrated associations between increased concentrations of air pollutants and CVD. Thus many epidemiologists focused on the study of the relationship of air pollution and human health, with the purpose of providing evidence for the main mechanisms that link air pollution with CVD. Numerous studies showed an increased risk of mortality, hospital admissions and emergency room (ER) visits for myocardial infarction, ischemic stroke, ischemic heart disease and cardio-cerebrovascular disease in relation to increased air pollution levels, but some studies didn't find the associations. Along with the research went through, the research of subgroup that is sensitive to the effects of air pollution is also carried out, but the results were different.Because several factors differ among countries or districts such as the level of environmental pollution, the composition of the population and socioeconomics, and with the development of epidemiological study design, confounding factors and bias can be controlled better, the acute effect of air pollution can be evaluated more accurate.Time-stratified case-crossover study was used to analyze the effect of air pollutants (PM10, SO2, NO2) on the acute onset of cardio-cerebrovascular disease (ACD) in our study. Additionally, similar analyses were undertaken to examine whether associations between air pollution and ACD were similar between men and women, people above 65 years old and below, and by seasons (spring, summer, autumn, winter). To examine potential effect modification of the influence of air pollutants on the risk of ACD, analyses stratified by the presence or absence of a secondary diagnosis (chronic ischemic heart disease, hypertension, diabetes, hyperlipemia) were conducted, for exploring the subgroups that are at higher risk for ACD due to increased air pollutant exposure. The subgroups with or without drinking and smoking are also considered.Material and methodsThe residents in Hangzhou are taken as study's population. The information of ACD cases were extracted from the center of disease prevention and control in Hangzhou city (HZ CDC) from 2002～2004. And the monitoring data was collected from four monitoring points that set in Shangcheng district, Xiacheng district, Fuyang city and Jiande city, every monitoring point monitors 100 thousand people. One case is only denoted by one time within-28days, classified into the time of the first acute onset of disease in the cycle.The data about the mean daily concentration of air pollutions (PM10, SO2, NO2) during the study's period were provided bythe center for environmental surveillance in Hangzhou city. The meteorological factors including mean daily temperature and daily relative humidity in the same period were collected from the center for meteorological agency in Hangzhou city.The time-stratified case-crossover design was used. In this design, a specified referent window is identified for each subject that includes the case event matched to a set of control, or nonevent, periods for the same individual. The analytic approach compares exposures occurring during case events, defined as the "hazard" or "at-risk" period, with exposures for control periods, in which the outcome of interest did not occur. The case-crossover design and the time-series model are all the method to evaluate the acute effect of air pollutants on human health, generally speaking, they have the similar results. To avoid bias, we used the time-stratified approach, which divides time into strata and uses the remainder of the days in each stratum as the referents for a case in that stratum, so there was several control times before or after the case time in a matched set. Concentrations on the concurrent day and previous 1 to 3 days (lag0～lag3) and 2- (lag01) to 4-day (lag03) lagged moving average concentrations were evaluated. The concentrations of lag01 were the average of lag0 and lag1, and so forth. But the control period didn't consider the effect. Single-pollutant model was fitted, and the lag time was selected according the maximum OR.The statistical analysis was composed of two parts, descriptive analysis and model fitting of case-crossover design. The descriptive analysis included the description of ACD, air pollutants and meteorological factors, difference analysis and correlation analysis were also carried out. The associations between ACD cases and levels of air pollutants concentrations were estimated using the odds ratios (OR) and their 95% confidence intervals (CI), which were produced using conditional logistic regression with weights equal to the number of ACD cases on that day. We also conducted separate analyses for season and subgroups with different characters, for the purpose of studying the relationship between air pollutants and ACD, and exploring the potentially sensitive groups to air pollutants.All the data management and descriptive analysis were performed by SPSS 13.0 for windows software package, and all reported p values were based on two-sided tests, a p value of <0.05 was considered statistically significant. Time-stratified referent selection was realized with procedure written by Visual Basic 6.0 software, and the acute effect of air pollutants on ACD were performed by survival package of R 2.9.2 software. Results1. January 1, 2002 to December 29, 2004, a total of 1618 cases were collected from the four monitoring points, as 5 cases with the date of ACD were missing, 1613 cases were brought into our study at last. During the study period, the total cases of every year showed an increasing tendency. The proportion of male was somewhat more than that of female, and the value of the people above 65 years old was 74.89%. The number of the patients with the second diagnosis of hypertension was more than that without, and the numbers of the patients with chronic ischemic heart disease, diabetes, hyperlipemia, the habit of drinking or smoking were less than the opposite subgroup.2. The data of air pollutants could relatively substituted population exposure level for individual. Each variable were presented as abnormal distribution. The median daily concentration of PM10, SO2 and NO2 were 113.00μg/m3 (14.00μg/m3 to 476.00μg/m3), 46.00μg/m3 (14.00μg/m3 to 132.00μg/m3) and 53.00μg/m3 (18.00μg/m3 to 135.00μg/m3), respectively. The days that PM10 levels exceeded current limits (150μg/m3) accounted for 20.38% during study period, and the days (=80μg/m3) of NO2 was 10.69%, but SO2 level was under the criteria. The median daily concentrations of air pollutants separated by season were found statistically significance, lower in summer and higher in winter according to the median values. The values of PM10 were decreased with year, however, SO2 and NO2 weren't observed significant difference separated by year.3. After adjusted for meteorological factors, the OR of ACD by a 10μg/m3 increase in PM10 at same day was 0.998 (0.986～1.009). For a 10μg/m3 increase in SO2, the OR was 1.017 (0.981～1.054) in the whole year (lag0), and NO2 exposure (lag0) was associated with ACD with OR was 1.006 (0.969～1.045).4. Separated by season, no association was founded between air pollutants and ACD in spring, summer and autumn. In winter, the ORs of ACD by a 10μg/m3 increase in PM10, SO2 and NO2 were 1.018(0.999～1.036), 1.078(1.022～1.138), 1.028(0.970～1.090), respectively. Besides, no associations were observed between air pollutants and ACD of men, subgroup with above 65 years old or below, but a significant result was found between SO2 and ACD of female. The results showed that residents may at higher risk for ACD due to increased air pollutant exposure in winter, and female may more sensitive to air pollutants than male.5. No associations were observed between air pollutants and ACD of subgroup with or without chronic ischemic heart disease, hypertension, diabetes, hyperlipemia, habit of drinking or habit of smoking, as same as the results of the subgroup without these diseases or habits. Compared the OR values of these subgroups, no statistical heterogeneity were observed except between the patients with and without smoking habits at lag2.ConclusionBased on the time-stratified case-crossover design, short-term effect of daily mean concentration of air pollutants adjusted for meteorological factors on the acute onset of cardio-cerebrovascular disease was evaluated. There were adverse effects of air pollution on ACD, and the effect values varied with season, most serious in winter. Female might especially sensitive to the adverse effects of air pollution, and the results of single-factor subgroup analyses showed that people without smoking habit was at greater risk of ACD associated with air pollution. In a word, female, the people without smoking habit might the sensitive group to the effects of air pollution on ACD.
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