| Background:Ambient particulate matter(PM)pollution has been known as a major issue for environmental and public health globally,and China's situation is more severe.The role of fine particulate matter(PM2.5)exposure as a risk factor has been consistently linked to increased cardiovascular morbidity and mortality in populations,especially for susceptible subgroups of the elderly.Numerous studies focused on PM2.5 and ultrafine particles,for they could be inhaled and deposited in lung and translocate into the blood.In addition,with the size of particles decreased,the health hazards increased.A few epidemiological and clinical studies have reported the progress of particulate health hazards and physiological and pathological mechanisms.In recent years,more and more studies have begun to pay attention to the effects of PM2.5 and their chemical components on cardiovascular health.Clinical and toxicological researches found that the transition metals and other chemical components in PM2.s,can result in cardiovascular health hazards through affecting the autonomic nerve function of the heart and internal ionic balance.Domestic research on the cardiovascular health of the elderly population exposure to chemical components in PM2.5 is still rarely reported.The traditional clinical and epidemiological research on cardiovascular health effects indicators focus on blood lipids,blood glucose,inflammatory factors and other biochemical indicators,as well as blood pressure and other physiological indicators,but the heart rate variability still arouses insufficient attentionHeart rate variability(HRV),the variation in the time intervals between adjacent heartbeats,namely R-R intervals,is directly related to the body's interdependent regulatory systems,reflects the autonomic nervous system activity and quantitative assessment the tension and balance of cardiac sympathetic nerve and vagus nerve,to determine the cardiovascular disease and prognosis.HRV is used to determine the degree and the regular of heart rate changes,and thus to determine the impact on cardiovascular activity by measuring the variability of continuous normal R-R interval.In general,HRV is regulated by the autonomic nervous system and sympathetic activity increases heart rate and decreases HRV,whereas parasympathetic activity decreases heart rate and increases HRV.HRV is high with a well-conditioned heart and could be affected by age,cardiac status,reflexes,physical or mental stress,drug administration,rennin-angiotensin system and others.Decreased HRV,which can cause the sympathetic tone increased,and reduce the ventricular fibrillation threshold,is an unfavorable factor;Increased HRV,which can lead the parasympathetic tension increasing,and increase the ventricular fibrillation threshold,is a protective factor.HRV is a valuable indicator of predicting sudden cardiac death and arrhythmia events and is expected to be used to assess the cardiovascular health effects of exposure to PM2.5 and its chemical components.In the elderly population,cardiovascular damage is associated with major risk factors and the complex interactions of environment and heredity.Meteorological factors,especially extreme temperatures(heat waves or cold waves),are closely related to cardiovascular disease events under relatively fixed ethnic and demographic factors The extreme temperatures will cause an increase in the number of hospital admissions and deaths.Epidemiological and statistical studies have confirmed that heat waves or cold waves are independent risk factors for cardiovascular disease.In addition,the impact of individual medication on cardiovascular health is very significant.The elderly population physical function degenerative changes,heart,the health status of blood vessels and other organs decreased,taking anti-hypertensive,lipid-lowering drugs can regulate and the stability of cardiovascular health,it plays an important role Therefore,evaluating the impact of cardiovascular health of particulate matter pollution and other environmental factors need to consider the modification effects of temperatures and the medicationObjective:This study was designed as a panel that aims to elucidate the associations between PM2.5 and their chemical component exposure and adverse cardiovascular outcomes among the middle elderly and elderly patients with coronary heart disease in Beijing.Exposures to PM2.5 and their chemical components and cardiovascular health related physiological and biochemical indices of subjects were measured repeatedly to identify the effect indicators sensitive to exposures to the exposures,and explore methods assessing health effects of individual exposures to PM2.5 and their chemical components in middle elderly and elderly populationMethods:Based on temporal and spatial distributions of ambient air pollutants in urban Beijing,The study areas were Dingfuzhuang-Gaojing Community located at Chaoyang District adjacent to the East 5th Ring Road,and outdoor PM2.5 monitoring were performed in 2016,and samples were analyzed for maid chemical components The investigation was designed as a panel among the middle elderly and elderly patients with coronary heart disease,while indoor PM2.5 and its chemical components were calculated using indoor and outdoor relationship coefficient(I/O ratio).The personal time-activity patterns information was collected by questionnaire and then the individual exposures to PM2.5 and its related chemical components were estimated through micro-environmental model.Individual health indicators like levels of hs-CRP and serum lipid were tested by collecting the fasting blood and heart rate variability were tested by using dynamic electrocardiograph(ECG).Mixed model was applied to evaluating the health effects of PM2.5 and its chemical components exposures on participants' physiological and biochemical indices,identifying the cardiovascular health effect indicators sensitive to exposures to the exposures,and providing policy support and theorical basis for early prevention and control of cardiovascular diseases and formulating measures to prevent and control air pollution.1.Temporal and spatial distributions of ambient air status in urban Beijing.Daily environmental monitoring information of the city and each site data of Beijing from 2014 to 2016 were collected,and PM2.5 and other ambient air pollutants were characterized by comparing their seasonal and regional diversity to elucidate the time change trends and spatial distributions of PM2.5 pollution,which provide basis for the selection of research areas.Meteorological data of Beijing were also collected simultaneously,and in consideration of association between sensible temperature with both air temperature and humidity,apparent temperature was calculated through daily air temperature and dew point temperature to elucidate its seasonal variation trends.2.Characterization of size fractions and main chemical components of ambient PM2.5in Beijing.Dingfuzhuang-Gaojing Community,Chaoyang District adjacent to the East 5th Ring Road were selected as study areas based on city PM2.5 pollution status and spatio-temporal distributions,where ambient air PM2.5 monitoring were carried out consecutively from 1st Dec 2015 to 31th Jan 2017,and the 24-h PM2.5 samples were collected by using middle volume(80?120 L/min)ambient fine particulate matter sampler and analyzed for metal and metalloid elemental composition,water-soluble ions and polycyclic aromatic hydrocarbons using Inductively Coupled Plasma Mass Spectrometry(ICP-MS),Ion Chromatography(IC)and High Performance Liquid Chromatography Respectively(HPLC),identifying distribution characteristics of PM2.5 main chemical species.Size fractions were characterized by using Single Particle Aerosol Time of Flight Mass Spectrometry(SPAMS)from 1st Dec 2015 to 31th Jan 2016.3.Follow-up investigations based on a panel among middle elderly and elderly community residents.The sample size was determined according to the estimating table for single group repeated measurement,and 22 subjects with coronary heart disease,aged 50?75,from the communities in east urban Beijing were recruited In accordance with the inclusion and exclusion criteria,following 4 follow-up investigations were performed during a period from January to April,2016.During each follow-up interval,personal exposures and health measurement were performed for each subject at the same time.(1)Questionnaire survey.During the first follow-up,the baseline characteristics regarding the individual basic information,lifestyle,eating habit,medications,dwelling environment and activity-travel patterns were collected by using a structured questionnaire.And then the data of medication and activity-travel patterns one week ago were collected during the following 3 follow-ups.(2)Exposure estimation.Outdoor PM2.5 and related chemical components measured by analyzing ambient PM2.5 samples collected consecutively for the concentrations of metal and metalloid elemental composition,water-soluble ions and polycyclic aromatic hydrocarbons,and then indoor concentrations were calculated using I/O ratio of Beijing from cited references.(3)Health measurement.Individual cardiovascular inflammatory indicators including Blood sugar,low density lipoprotein,high density lipoprotein,total triglycerides,total cholesterol,fibrinogen and other biochemical indices were test by collecting the fasting blood and time domain indices of HRV including SDNN,SDANN,rMSSD,pNN50 and frequency domain indices of HRV including HF,LF,VLF,LF/HF were test by using 24h ECG.The study protocol was submitted and approved by the ethical review board at National Institute of Environmental Health,Chinese Center for Disease Prevention and Control and all participants were informed the purposes of the investigation,benefits and possible losses thoroughly and provided their written informed consent4.Study on acute cardiovascular effects of exposures to PM2.5 and their chemical components in middle elderly and elderly population.(1)Firstly,all observation data gained from repeated measurement including personal exposures to PM2.5 and their chemical components based on micro-environmental model and individual time-activity patterns,HRV indices,inflammatory markers and coagulation indicator were analyzed using basic statistical methods.According to normality test appropriate descriptive statements(arithmetic average or inter-quartile range)were used to describe subjects'exposure indices and health indices,and logarithmic transformation was applied to the observations in line with skewed distribution.Secondly,random analysis of variance was performed with for transformed data from 4 groups observation from follow-ups.Thirdly,lagged,cumulative mean and running mean of personal exposure and meteorological factors were calculated and mixed model were applied to analyzing the effects of those variates on HRV and risk factors of CVD to filter sensitive cardiovascular indices.Fourthly,Collinearity diagnostics were applied to determining the correlation between PM2.5 exposures and chemical components exposures,and single-pollutant model,double-pollutant model and multi-pollutant were built successively with random effect and fixed effect in all models to analyze effects of PM2.5 and their related chemical components exposures on cardiovascular health indices.Effect modification by medication use and meteorological factor were considered by performing sensitivity analysis.Statistical analysis was performed using SAS 9.3 statistical package and mixed model(PROC MIXED).p<0.05 was considered statistically significant without otherwise specifiedResults:Nowadays,PM2.5 remains to be primary ambient pollutant in Beijing with considerably high pollution levels and varied in a wide range with seasonal and regional variations.Medians of PM2.5 mass concentrations in Beijing were 66.5 ?g/m3(5.2 ?g/m3?392.6 ?g/m3),56.6 ?g/m3(7.1 ?g/m3?477.5 ?g/m3)and 55.5 ?g/m3(7.4 ?g/m3?394.5 ?g/m3)from 2014 to 2016,respectively,showing a decrease trend year by year.Though the degree of reduction appeared to be limited with a year-on-year decline of 14.9%and 1.9%.Severe polluted weather mainly occurred in winter,that was from November to January in next year.While there were grades for the spatial distributions of PM2.5 mass concentrations decreasing from south to north,and the annual means of PM2.5 mass concentrations remained to be regional characteristics of high in south-east and low in north-west apparently.2.Ambient PM2.5 samples were collected consecutively at self-monitoring site based on Dingfuzhuang community and Gaojing Community in east urban Beijing,and chemical species including metal and metalloid elemental compositions,water-soluble ions and polycyclic aromatic hydrocarbons were determined using high-sensitivity analytic instruments.The analyzing results indicated that Zn,Se,Cu,Ti,Fe,B,Al,Pb,Mn,As,Sb,Na,K,Ca,Si,Mg,Ba,Rees,SO42-and NO3" were main chemical components of PM2.5.Monitoring data during December 2015 and January 2016 showed that median of PM2.5-As concentration were more than 1.3 times the national standard reference limit,and maximum concentrations of 24h PM2.5-Pb and PM2.5-Cd were 0.6 and 2.2 times the national standard reference limit.Monitoring data during January and April 2016 showed that medians of PM2.5 and related chemical components of hazy weather were apparently higher than those of non-hazy weather with a range of 1.4 to 7.3 times.There were significantly different between hazy weather and non-hazy weather for PM2.5 and all related chemical components observations.Principle factor analysis were applied to extraction 3 factors from the main chemical components mass by using orthogonal matrix transformations,variance contribution ratio of the first factor was 57.2%with loads of transition metal elements represented by Zn,Cd and Cu,secondary particles represented by Sulfates,nitrates and Selenium were more than 0.8.And the ratio of the second factor was 20.8%,with loads of Rees,alkaline earth metals and transition metals represented by Ti and Fe were 0.98,0.97 and 0.95,respectively.The load of platinum family elements was 0.84 and the third factor' ratio was 5.7%.In addition,size fractions of were characterized by using high throughput mass spectrometry PM2.5 and related chemical components.The results showed that,mass of particles under 2.5 micrometers mainly appeared in sections ranged from 0.3 to 1.0 micrometers,with a peak in section from 0.4 to 0.5 micrometers.while concentrations of those under 0.2 micrometers and greater than 1.9 micrometers were low.Number concentrations mainly appeared in sections from 0.3 to 1.3 micrometers,most concentrated in section from 0.4 to 0.5 micrometers.Through mass concentrations under 0.3 micrometers were very low,number concentration of Sb,Si,As,Cu,Hg,Pb,Mg,Zn,Ti and chlorine accounted for a considerable proportion.The study results indicated that,these typical chemical species in PM2.5 deserved more attentions for their potential cardiovascular effects.3.During the follow-up survey,all 22 subjects accomplished 4 follow-up investigations for exposure estimates and health measurement.The average of age was 60.1,and 50%were women,12 individuals' fasting blood-glucose were greater than 6.1 mmol/L(54.5%)and a participant's TC was greater than 6.22 mmol/L as well as TG greater than 2.26 mmol/L(4.5%).Random analysis of variance for 4 groups of repeated observations showed that there were significant between the main body effect for rMSSD and TC.By applying mixed model to analyzing repeated observations,pNN50 and rMSSD as sensitivity indicators were filtered and lagging effects of exposure to PM2.5 and PM2.5-Pb were obvious.By comparing diverse models,it confirmed that the estimates for health effects of lag6 to lag3 exposure to PM2.5 and related chemical components were significantly different.Temperature was regarded as an independent risk factor for CVD and either heat wave or cold wave could result in CVD deaths.In this study,single temperature variate model and double variates of temperature and exposure to PM2.5 model were compared,and results showed for sensitive HRV indices,exposure to PM2.5 could cooperate with the effect of temperature on cardiovascular health.Beta-blocker use could increase HRV in CHD patients.In this study,effect modification of Beta-blocker use was obvious.When controlling exposures to PM2.5 and PM2.5-Pb,protective effects of Beta-blocker use on cardiovascular health were observed.Results from multi-variate model showed that exposure to PM2.5 related chemical components could cooperate with the adverse effect of PM2.5 alone on cardiovascular health,additionally this synergistic effect could be more significant for exposure to chemical components in advance.Conclusions:During January to April 2016;PM2.5 and related chemical components mass concentrations in hazy days were significantly higher than those in the non-hazy days.Mass concentrations of particles under 2.5 micrometers in accord with number concentrations appeared to be unimodal distribution.And poisonous and hazardous components main occurred in sections under 1.0 micrometers,whose effects on cardiovascular health deserved more attentions.The methods developed,improved and applied in this study and data gained aggrandized monitoring PM2.5 and related chemical components considerably,and enlarged the data accumulation of characteristics of size fractions and chemical components of particles in areas with middle pollution levels.Applying to micro-environmental model combined with time-activity patterns to assessment individual's exposures to PM2.5 and related chemical components are more precise than using data from environmental air quality monitoring site alone.This study provided evidences that short-term exposures to PM2.5 and PM2.5 related chemical components were associated with HRV indices of pNN50 and rMSSD as well as hs-CRP in a panel of middle aged and elderly subjects,through the associations were varied depend on diversity of PM2.5 related chemical components and distinguished across various days' lag.The results showed pNN50 and rMSSD decreased in association with exposures to PM2.5 and PM2.5 related chemical components at lags 3 to 5,which indicated damage effects on heart functions and autonomic nervous functions of acute exposures to PM2.5 related chemical components.pNN50 and rMSSD were filtered as sensitive indices of HRV,which provided new thought for applying HRV to evaluation cardiovascular influences of exposures to PM2.5.In the study,potential effect modification and confounding from medication use and meteorological factors were controlled.Among study subjects on daily beta-blocker medication,protective effect was obvious compared with those without medication under the same exposure situations.The results in this study provide guidance of health on the appropriate protection and medication for high-risk groups with CVD,but also theoretical basis and data support to help strengthening the prevention and control of CVD. |
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