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www.revportcardiol.org

Revista Portuguesa de

Cardiologia

Portuguese Journal of Cardiology

ORIGINAL ARTICLE

Investigating the association between ambient

particulate matter (PM 10 ) exposure and blood pressure values: Results from the link between the Portuguese Health Examination Survey and air quality data

Vânia Gaio

a,b,∗

, Rita Roquette

a,c

, Alexandra Monteiro

d

, Joana Ferreira

d

, Carlos Matias Dias

a,b

, Baltazar Nunes

a,b

aDepartmentofEpidemiology,InstitutoNacionaldeSaúdeDoutorRicardoJorgeIP(INSA,IP),Lisboa,Portugal

bNOVANationalSchoolofPublicHealth,PublicHealthResearchCenter,UniversidadeNOVAdeLisboa,Lisboa,Portugal

cNovaIMSInformationManagementSchool,UniversidadeNOVAdeLisboa,Lisboa,Portugal

dCESAM&DepartmentofEnvironmentandPlanning,UniversidadedeAveiro,Aveiro,Portugal

Received18August2021;accepted3February2022 Availableonline9January2023

KEYWORDS Particulatematter;

Bloodpressure;

INSEF2015;

Airqualitydata

Abstract

Introductionandobjectives:Highbloodpressure(BP)remainsamajormodifiablecardiovascu- lar(CV)riskfactor.Severalepidemiologicstudieshavebeenperformedtoassesstheassociation betweenairpollutionexposureandthisCVriskfactorbutresultsremaininconsistent.Thisstudy aimstoestimatetheeffectofshort-termPM10exposure(averagepreviousthree-dayconcen- tration)ondiastolic(DBP)andsystolic(SBP)bloodpressurevaluesoftheresidentmainland Portuguesepopulation.

Methods:Our study wasbased onavailable DBP andSBP data from 2272participants from thefirst PortugueseHealthExaminationSurvey (INSEF,2015)livingwithina30 kmradiusof atleastoneairqualitymonitoringstation,withavailablemeasurementsofparticulatematter withanaerodynamicequivalentdiameter≤10␮m(PM10).Weuseddatafromtheairquality monitoringnetworkofthePortugueseEnvironmentAgencytoobtaintheindividualallocated PM10concentrations.GeneralizedlinearmodelswereusedtoassesstheeffectofPM10exposure onDBPandSBPvalues.

Results:NostatisticallysignificantassociationwasfoundbetweenPM10exposureandbothDBP andSBPvalues(0.42%DBPchangeper10␮g/m3ofPM10 increment(95%confidenceinterval (CI):−0.85;1.70)and0.47%SBPchangeper10␮g/m3ofPM10increment(95%CI:−0.86;1.79)).

Resultsremainunchangedafterrestrictingtheanalysistohypertensiveorobeseparticipants orchangingthePM10assessmentmethodology.

Correspondingauthor.

E-mailaddress:vania.gaio@insa.min-saude.pt(V.Gaio).

https://doi.org/10.1016/j.repc.2022.02.011

0870-2551/©2023SociedadePortuguesadeCardiologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Conclusions: InviewofthePM10levelsobservedin2015,ourresultssuggeststhatexposureto PM10concentrationshaveasmallornoeffectonthebloodpressurevalues.Otherairpollutants and mixturesofpollutants thatwere notincludedinourstudy shouldconsideredinfuture studies.

©2023SociedadePortuguesadeCardiologia.Publishedby ElsevierEspa˜na, S.L.U.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by- nc-nd/4.0/).

PALAVRAS-CHAVE Partículas;

Pressãoarterial;

INSEF2015;

Qualidadedoar

Investigandoaassociac¸ãoentreaexposic¸ãoapartículasambientais(PM10)eos valoresdapressãoarterial:resultadosdaligac¸ãodedadosdoInquéritoNacional deSaúdecomExameFísicoedaqualidadedoar

Resumo

Introduc¸ãoeobjetivo: Apressãoarterialelevada(PA)continuaaserumimportantefatorde riscocardiovascular(CV)modificável.Váriosestudosepidemiológicostêmsidorealizadospara avaliaraassociac¸ãoentreaexposic¸ãoàpoluic¸ãodoareestefatorderiscoCV,masosresultados permaneceminconsistentes.Esteestudotemcomoobjetivoestimaroefeitodaexposic¸ãode curtadurac¸ãoàsPM10(concentrac¸ãomédiadosúltimostrêsdias)nosvaloresdapressãoarterial diastólica(PAD)esistólica(PAS)dapopulac¸ãoresidenteemPortugalContinental.

Métodos: Onossoestudobaseou-senosdadosdisponíveisdePADePASde2272participantes doprimeiroInquéritoNacionaldeSaúdecomExameFísico(INSEF,2015)queviviamnumraiode 30kmdepelomenosumaestac¸ãodemonitorac¸ãodaqualidadedoarcommedic¸õesdisponíveis dematerialparticuladocomdiâmetroaerodinâmico≤10␮m(PM10).Foramutilizadososdados darededemonitorac¸ãodaqualidadedoardaAgênciaPortuguesadoAmbienteparaatribuiras exposic¸õesindividuaisdePM10.Osmodeloslinearesgeneralizadosforamutilizadosparaestimar oefeitodaexposic¸ãoàsPM10nosvaloresdePADePAS.

Resultados: Nenhuma associac¸ão estatisticamente significativa foi encontrada entre a exposic¸ãoaPM10 eosvalores dePADePAS(0,42%deincrementodePADporcadaaumento de 10 ␮g/m3 dePM10 [ICde95%:−0,85; 1,70] ede 0,47%de incrementode PASpor cada aumentode10␮g/m3[IC95%:−0,86;1,79]).Osresultadospermaneceraminalteradosapós restringiraanáliseaosparticipanteshipertensosouaosparticipantesobesosouapósalterac¸ão dametodologiaparaatribuirasexposic¸õesindividuaisdePM10.

Conclusões: Tendoemconsiderac¸ãoosníveisdePM10observadosem2015,osnossosresultados sugeremqueaexposic¸ãoàsconcentrac¸õesdePM10teráumefeitopequenoounenhumefeito sobreosvaloresdapressãoarterial.Outrospoluentesatmosféricosemisturasdepoluentesque nãoforamincluídosnonossoestudodevemseranalisadosemestudosfuturos.

©2023SociedadePortuguesadeCardiologia.PublicadoporElsevierEspa˜na,S.L.U.Este ´eum artigo OpenAccess sobumalicenc¸aCCBY-NC-ND(http://creativecommons.org/licenses/by- nc-nd/4.0/).

Introduction

Highblood pressure(BP)or hypertensionremains amajor modifiable cardiovascular (CV) risk factor, beingresponsi- bleforatleast45%of alldeathsduetoheartdiseaseand 51%of deathsduetostroke.1,2 Worldwide, itisestimated thataround31%ofadultsaged25yearsandoverhadhyper- tension, defined as systolic BP (SBP) ≥140 mmHg and/or diastolicBP(DBP)≥90mmHg.3InPortugal,accordingtothe PortugueseHealthExaminationSurvey(INSEF),theoverall prevalence ofhypertension,in thepopulation aged25---74 yearsof age,was36.0%,in2015, definedashavingaSBP

≥140mmHgand,or,aDBP≥90mmHgand,or,takinganti- hypertensivemedication.4

The causes of high blood pressure are complex and are related to genetic, behavioral and environmental

factors, including air pollution exposure.5 Over the last decades, several epidemiological studies assessed the associationbetween airpollutionexposure, includingpar- ticulatematter(PM),andBPvalues.Evidencefromarecent meta-analysiswhich pooled studies published before May 2017, supports the association between PM10 and a DBP elevation.Theauthorsofthismeta-analysisfoundaDBPele- vationof0.86mmHg,95%CI(0.37;1.35)and0.15mmHg, 95% CI (0.01---0.29) per each 10 ␮g/m3 increase of PM10

in long (≥30 days) and short-term (<30 days) periods of exposure,respectively.6Theevidencecompiledinthissys- tematicreview failed tosupportthe association between PM10andSBPvalues.

DirectPMtranslocationintotheblood,oxidativestress, inflammatorymediatorproductionandneuroendocrineacti- vationarethepotentialbiologicalmechanismsresponsible 252

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for the pathophysiological mechanisms through which PM exposure canraiseblood pressure,includingvasculardys- function and aortic stiffness,7 sodium retention at the kidneylevel8andchronickidneydiseas.9AccordingtoNew- manand hiscolleagues,the firstthreepathophysiological responsesassociatedwithBPelevationwilloccurinafew hourtodaysafterexposureandarereversiblewhereasthe lastphysiologicalresponsewilloccurmainlyinalong-term exposurecontextandwillbeirreversible.10

To the bestof ourknowledge, in Portugal,the associ- ationbetweenPMexposure andbloodpressurevalueshas neverbeenpublishedbefore.Consequently,ourstudyaims toassess/investigate theassociation between individually allocatedenvironmentalPM10concentrationsandindividual levelSBPandDBP,consideringashortperiodoftime(previ- ousthreedaysbeforebloodpressuremeasurements)asthe window of exposure,in the mainland resident Portuguese populationagedbetween25and74yearsold,in2015.

Methods

Studypopulation

This study used data from the first Portuguese National Health Examination Survey (INSEF), collected between February and December 2015. This survey was described in moredetail byNunes etal.11 The present analysiswas restrictedtothesubsampleofINSEFparticipantsfrommain- land Portugal (n=3467) who consented to have their data linked,providedaresidencezipcodenumber,wereliving withina 30-kmradius of an airqualitymonitoring station with available PM10 concentration values and had blood pressurevaluesmeasuredinINSEF(n=2272).TheINSEFsur- vey received approval from the Ethics Committee of the PortugueseNationalHealthInstituteDoutorRicardoJorge, the National DataProtection Authority (Authorization no.

9348/2010)andfromtheregionalEthicsCommittees.

Healthrelateddata

Healthdata collectionin INSEFwasperformed by trained health professionals, according to the European Health ExaminationSurvey(EHES)procedures.12Bloodpressureval- ues were measured according to the previous published studyofRodriguesandcolleagues.4

Sociodemographic (age, sex, educational level and occupation), lifestyle (smoking, excessive alcohol con- sumption,sedentaryandunhealthydiet)andhealthstatus variables (diagnosed-dyslipidemia, diagnosed diabetes, lipid-lowering medication usage and diabetes medication usage)wereobtainedbyself-reportthroughtheinterview.

Smoker’s definition includes current daily and occasional smokers and excessive alcohol consumption was defined as reporting three or more days/week of consumption of at least one of the following alcoholic beverages:

wine, beer, brandy/spirits, Port wine/martini/liqueur, whiskey/gin/vodka. Unhealthy diet was defined as no consumption of fruit and vegetables at least once a day andsedentary wasdefinedasreportingreading,watching

televisionorothersedentaryactivitiesasthebestdescrip- tionofleisuretimeactivitiesduringthelast12months.

Environmentalexposureassessment

HourlyvalidatedPM10valueswereobtainedfromtheQualAr database,available online at the PortugueseEnvironment Agency(APA)website(https://qualar.apambiente.pt/)and theindividualallocatedPM10concentrationswereobtained aspreviouslyreportedbyGaioetal.13Briefly,foreachindi- vidualtheallocatedthree-dayaveragePM10 concentration wastheweightedaverageofthree-dayaveragedPM10con- centrationsofallstationswithina30kmradiusfromeach participant’sresidence.Thisaverage wasweightedbythe inverseofthesquareddistancebetweentheresidenceand theairqualitymonitoringstations.

The individually allocated three-day average tem- peratures were also obtained using data from the NationalOceanicandAtmosphericAdministrationdatabase (www.ncdc.noaa.gov)andweassumedthethree-dayaver- agevalueoftheclosesttemperaturemonitoringstationas beingrepresentativeoftheindividualexposure.

Statisticalanalysis

Thestatisticalanalysiswasperformed usingtheRstatisti- cal package version 3.6.3.14 All estimates were weighted to account for different selection probabilities resulting from the complex sample design of INSEF 2015 and to match the geographic region, age group and sex popu- lation distribution of 2015. T-test and the Wilcoxon test were usedto accessdifferences of quantitative variables according to their adherence to the normal distribution or not. Proportions were compared using Pearson’s chi- squaredtest.Thesignificancelevelforallanalysiswasset at5%.

Regression coefficients of effect (ˇ) of PM10 on DBP and SBP with the corresponding 95% confidence intervals (CIs)wereobtainedbygeneralizedlinearregressionmodels analyses for each 1 ␮g/m3 increment of PM10. We used thesvyglm function fromthe ‘‘survey’’ Rpackage torun eachGaussianfamilymodelwithalinklogfunction(fam- ily=gaussian (link=‘‘log’’)). Then, percent change per 10

␮g/m3incrementofPM10 withcorresponding95%CIswere calculatedbyusingtheformula100×[exp(ˇ)−1]*10.Addi- tionally, to obtain estimates comparable with previous studies,wealsorunthemodelsusingthe(family=gaussian (link=‘‘identity’’))toobtainresults inmmHg increaseper each10␮g/m3incrementofPM10andtheseresultsarepre- sentedassupplementarydata.

First,anunadjustedexposure-outcomemodelwasfitted for each outcome. Then, a second model confounder- adjusted for sex(Male/Female), age group (25---49 years;

50---74 years), educational level (Low education/Medium education/High education), occupation (White-collar occupation/Blue-collar occupation), smoking (smoker/no smoker), excessive alcohol consumption (Yes/No), seden- tary (Yes/No), unhealthy diet (Yes/No) and individual allocatedthree-dayaveragetemperature(continuous)was performedforeachoutcome.Additionally,astheobjective wastoassessonlytheshort-termeffectsofPM10exposure,

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Table1 Descriptionofthegeneralcharacteristicsofthestudyparticipants.

Characteristics Total(n=2272) Males(n=1037) Females(n=1235)

Age(n=2272)--- %

25---49yearsold 53.0 53.6 52.4

50---74yearsold 47.0 46.4 47.6

Levelofeducation(n=2271)---%a

Loweducation 57.8 62.1 54.0

Mediumeducation 21.9 21.9 21.9

Higheducation 20.3 16.0 24.1

Occupation(n=2102)---%b

White-collaroccupation 63.6 56.1 70.7

Blue-collaroccupation 36.4 43.9 29.3

Lifestylesvariables---%

Smokers(n=2272)c 21.5 27.0 16.6

Excessivealcoholconsumers(n=2271)d 35.8 53.5 20.0

Unhealthydiet(n=2271)e 36.4 46.0 27.8

Sedentary(n=2258)f 45.0 42.0 48.0

Hypertension(n=2272)---%g 36.4 40.8 32.4

Hypertensivemedication(n=2272)h 25.1 24.4 25.7

Diastolicbloodpressure(n=2272)---mmHg(mean,SD) 74.0(10.2) 76.1(9.9) 72.0(9.9) Systolicbloodpressure(n=2272)mmHg(mean,SD) 125.1(16.0) 130.0(14.3) 120.8(16.3) Individualallocated

3-Dayaveragetemperature(n=1887)---C(mean,SD) 16.1(4.0) 16.1(4.0) 16.1(4.0) 3-DayaveragePM10(n=2272)---C(mean,SD) 18.7(8.3) 18.6(8.2) 18.7(8.4)

a Loweducation:levels0---2oftheISCED2011;mediumeducation:levels3---4oftheISCED2011;higheducation:levels5---8ofthe ISCED2011.

b White-collaroccupation:Managers,Professionals,TechniciansandAssociateProfessional,ClericalSupportWorkersandServicesand SalesWorkers;Blue-collaroccupation:SkilledAgriculturalWorkers,CraftandRelatedTradesWorkers,PlantandMachineOperatorsand ElementaryOccupations.

c Smokersincludecurrentdailyandoccasionalsmokers.

d 3 or more days/week of consumption of at least one of the following alcoholic beverages (wine, beer, brandy/spirits, port wine/martini/liqueur,whisky/gin/vodka).

e Noconsumptionoffruitandvegetablesatleastonceaday.

f Reading,watchingTVorothersedentaryactivitiesdeclaredasthebestdescriptionoftheleisuretimeactivitiesduringthelast12 months.

g DefinedasmeasuredSBP140mmHgormeasuredDBP90mmHgorself-reportoftakingantihypertensivemedication.

h Self-reportoftakingantihypertensivemedication.Resultsinboldarethosewithstatisticallysignificantdifferencebetweenfemales versusmales,accordingtothePearson’schi-squaretest(p<0.05).

an adjustment for the long-term effect of PM10 was also includedbyaddingthevariableone-previousyearaverage ofPM10 concentrations.

Toassessthesensitivityofouranalysistothe30kmradius criteria,wealsofitthemodelsconsideringonlyparticipants living within a 20 km radius of an air quality monitoring stationwithavailablePM10 measurements.Toevaluatethe sensitivityofouranalysisregardingtheexposureassessment method,wealsofitthemodelsconsideringthemodeledPM10

concentrations obtainedbytheapplicationof anumerical airqualitymodel---theWRF-CAMxmodelingsystemthathas beenextensivelyappliedoverPortugalregionwithsatisfac- toryskills,aspreviouslydescribed.13

Finally, wealsorepeat theanalysisafterexcluding the participants taking anti-hypertensive medication and also when considering only more vulnerable groups, namely restricting the analysis to the hypertensive participants (definedasmeasuredSBP≥140mmHgormeasuredDBP≥90 mmHgorself-reportoftakingantihypertensivemedication)

or participants withabdominal obesity (assessed by using theformula:waisttoheightratio>0.5).

Results

Participants’characteristicsandPM10 values description

Thegeneralcharacteristics((TableS1)analyzedweresim- ilaramongincludedandexcludedparticipants.Amongthe 2272participantsin ourstudy,52.8% werefemales,53.0%

agedbetween25and49yearsold,57.8%hadloweducation leveland63.6% hadawhite-collaroccupation.Mostparti- cipantsreportedtobenon-smokers(78.5%),non-excessive alcoholconsumers (64.2%),tohavea healthydiet(73.6%) andtobenotsedentary(55.0%).Theprevalenceofhyper- tensionwas36.4%and25.1%oftheparticipantsreportedto takeantihypertensivemedication.ThemeanvaluesofDBP

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Figure1 Boxplot ofthePM10 distributionaccordingtosex.Thedashedlines representthedailylimitvalue givenbytheEU AmbientAirQualityDirectives(nottobeexceedonmorethan35days/year)andalsobytheWorldHealthOrganizationairquality guidelines(notexceededmorethan3days/year).

andSBPwere74.4mmHgand125.1mmHg,respectivelyand theIndividualallocatedthree-dayaveragetemperaturewas 16.1C.Differencesbetweenmalesandfemaleswerefound regardinglevelofeducation,occupation,smoking,alcohol consumption,unhealthydiet,hypertensionprevalenceand bloodpressurevalues(Table1).

Theindividualallocatedthree-dayaveragePM10concen- trationvaluesrangedbetween3.31␮g/m3and64.35␮g/m3 (median=17.19␮g/m3,IQR=12.40---24.27␮g/m3)anddiffer- encesbetweenmalesandfemaleswerenotfound(Figure1).

The distributionofthethree-dayaveragePM10 concentra- tionvalues isabove thedaily limitvalue given bythe EU Ambient AirQuality Directives(nottobeexceedonmore than 35/year) and alsoby the WorldHealth Organization air quality guidelines (not tobe exceed more than three days/year).

AssociationbetweenPM10 anddiastolicblood pressureandsystolicbloodpressurevalues

There was no association between individual allocated three-dayaveragePM10 concentrationandDBPor SBPval- ues(0.42%DBPincreasepereach10␮g/m3PM10increment, 95% CI: −0.85%; 1.70% and 0.47% SBP increase per each 10␮g/m3 PM10 increment, 95%CI:−0.86%; 1.79%).Corre- spondent estimatesin mmHg increaseper each 10␮g/m3 increment of PM10 are presented assupplementary data, in Table S9(0.33 mmHgDBP increase pereach 10␮g/m3 PM10increment,95%CI:−0.62%;1.27%and0.57mmHgSBP increasepereach10␮g/m3PM10increment,95%CI:−1.10%;

2.54%).Similarresultswereobtainedinthestratifiedanal- ysis,whenconsideringonlymalesorfemales(Table2).

Sensitivityanalysis

Regarding thesensitivity analysis,whenwe restricted our sample totheparticipants livingwithin a20km radius of

an air quality monitoring stationwith available PM10 val- ues,similarresultswerefoundwhenconsidering thetotal sample andalsowhenconsidering both malesor females.

Pereach10␮g/m3PM10increment,therewasa0.51%(95%

CI: −1.35; 2.37) increase in the DBP values and a 0.75%

(95% CI: −1.02; 2.53) increase in the SBP values, being theseresults not statistically significant (Table S2). When we considered different exposure periods of time(2 pre- vious days or 5 previous days instead of three previous days)similarresultswere found (Tables S3and S4). Addi- tionally,whenweconsideredtheindividualallocatedPM10

concentrationsobtainedbytheairqualitymodelingsystem (WRF-CAMx),noassociationswereneitherfound(TableS5).

Finally,whenwerestrictedouranalysistoparticipantsnot takinghypertensivemedication,orwhenweconsideredonly moresusceptibleindividualslikethoseobeseordiagnosed withhypertension,resultsremainsimilar(TablesS6---S8).

Discussion

Mainfindingofthisstudy

In this study, no statistically significant association was foundbetweenPM10exposureandbothDBPandSBPvalues.

However,thepointestimatesobtainedweresimilaroreven higher than those from the last published meta-analysis abouttheglobalassociationbetweenambientairpollution andbloodpressure6(DBP:0.33versus0.15mmHgincrease pereach10 ␮g/m3PM10 increment;SBP:0.57versus0.21 mmHgincreasepereach10␮g/m3PM10increment).These results were consistently maintained by the sensitivity analysis performed, especially when considering a more restrictivecriteriatotheexposureassessment(participants living within a 20 km radius of an air quality monitoring stationwithavailable PM10 values),when considering the twoorfiveprevious daysinsteadofthreeprevious daysas theexposureperiodoftime,whenconsideringanindividual

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Table2 PercentchangesinDBPandSBPper10␮g/m3incrementofPM10accordingtosex.

%Changeper10␮g/m3ofPM10increment

DBP SBP

Total(n=2272)

Unadjustedmodel −0.73 (−1.92;0.47) −0.60(−1.88;0.69)

Adjustedmodel* 0.42(−0.85;1.70) 0.47(−0.86;1.79)

Males(n=1037)

Unadjustedmodel −0.61 (−1.95;0.73) −0.50 (−1.87;0.88)

Adjustedmodel* −0.04(−1.09;1.02) 0.68(−0.81;2.18)

Females(n=1235)

Unadjustedmodel −0.80(−2.84;1.25) −0.64(−2.75;1.46)

Adjustedmodel* 0.76(−1.42;2.94) 0.16(−1.98;2.31)

DBP:diastolicbloodpressure;SBP:systolicbloodpressure.

* Adjustedforage, sex,educationallevel,occupation,smoking status,excessivealcoholconsumption,unhealthydiet,sedentary, individualallocatedambienttemperature,individualallocated1-yearaverageofPM10concentrations.

allocatedPM10 concentrationsobtainedfromanairquality model instead of the direct measurements from the air monitoringstationsorwhenconsideringonlyhypertensive, participants with abdominal obesity or participants not takinganti-hypertensivemedication.

Whatisalreadyknownonthistopic

Accordingtoarecentsystematicreviewandmeta-analysis performedontheassociationbetweenambientairpollution andbloodpressure,thatpoolsstudiespublishedbeforeMay 2017,6evidencealreadysupportedtheassociationbetween short-termPM10exposureandDBPvalues(0.15mmHg,95%

CI:0.01;0.29,pereach10␮g/m3increaseofPM10),which ourstudy wasunabletoconfirm.However,thepoint esti- mateobtainedinourstudywashigherthantheonereported bythecitedmeta-analysis(0.33versus0.15mmHgincrease pereach10␮g/m3PM10increment).Additionally,thesame meta-analysisdidnotsupporttheassociationbetweenPM10

exposureandSBPvalues(0.21mmHg,95%CI:−0.01;0.43, per each 10 ␮g/m3 increaseof PM10), which is inconcor- dancewithourresults.

Itisimportanttomentionthatthepolledestimatesofthe meta-analysis previously mentioned6 were obtained using data from studies mostly from America and Asia regions where the levelsof PM10 arehigher in comparisonto the majorityoftheEuropeancountries.Whenweconsideronly thepoolingoftheestimatesfromstudiesperformedinEuro- peancountries,15---18wefounda−0.01mmHgDBPdecrease (95%CI:−0.14;0.13)pereach10␮g/m3increaseofPM10. Accordingly,whenconsideringonlyEuropeancountries,the publishedmeta-analysisalsodidnotsupporttheassociation betweenshort-termexposuretoPM10anddiastolic(DBP)or systolic(SBP)bloodpressurevalues,whichiscorroborated byourstudy.

After the publication of the previously cited meta- analysis,6additionalstudieswerepublishedonthisissuebut theassociationbetweenshort-termPM10exposureandblood pressurevaluesremainscontroversial.19,20 Themajority of the studies, mostlyperformed in China,provide evidence ofapositive associationbetweenPM10 andblood pressure

values19,21 but there are some other studies that did not support this association.20 For instance, in a panel study performed inItaly andSweden,witha rangeof PM10 val- uescomparabletothosefromPortugal,noassociationswere foundbetweenPM10levelsandeithersystolic(SBP)ordias- tolic(DBP)bloodpressurebutshort-termexposuretoPM10

resultsinreductionsincarotidelasticityamongelderlypop- ulationwhichmeansthatPMexposurecouldbeassociated withotherimportantCVoutcomes.20

Whatthisstudyadds

This study suggests that exposure to PM10 concentrations in the levels observed in Portugal,similar to other Euro- peancountries,haslittleornoeffectonthebloodpressure values, however it could have impactin other important cardiovascular outcomes. In fact, in a recent published studyperformed inthe Portuguese population,13 asignifi- cantassociationbetweenshort-termPM10 exposure(3-day average PM10 concentration) and white blood cells (WBC) amongfemales wasfound (a2.76%WBC increase,95% CI:

0.65---4.87,pereach 10␮g/m3PM10 increment) suggesting that PM10 exposure couldimpact onother outcomes with potentialtomediatea cardiovascularevent. Additionally, itis also importanttomentionthat studies reportingsig- nificant results are more likely to be published and the possibility of a publication bias on this issue cannot be rejected.22,23

The point estimates obtained in this study were not statistically significant, which will be probably due to the lack of statistical power to estimate effects of this magnitude with a sample size of just over two thousand participants. However, even if the point estimates had statistical significance, we considered that obtained esti- mates would represent a small effectof the exposure to PM10concentrationsonbloodpressure,takingintoaccount thedaily meanvalues of PM10 concentrations observed in thePortuguese context,in 2015 (three-dayaverage PM10: 18.7␮g/m3).

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Limitationsofthisstudy

Ourstudyhassomelimitations.Afirstoneisrelatedtothe exposureassessmentmethod,duetothehighdistancecon- sideredbetweenparticipants’residenceandtheairquality monitoring stations (30 km)in the inclusion criteria. The number and the spatial distribution of air quality moni- toringstations inthe Portuguese mainlanddoes not allow us toapplya more restrictive distance due to asubstan- tialsamplereductionthatcouldcompromisethepowerof the estimates and result in selection bias. However, our resultsremainsimilarwhenweapplymorerestrictivecrite- ria(includingonlyparticipantslivingwithina20kmradius of an air quality monitoring station with available PM10

measurements) or when we used data from a numerical model.

Asecondlimitationofourstudyisrelatedtothepossibil- ityofanerroneousassumptiononthetemporalrelationship betweenexposuretoPM10andtheBPchanges.Infact,the considered timewindow of exposure, that wasthe three previousdaysinourstudy,variedalotinthepreviouslypub- lishedstudies,rangingfromdaystomonthsandevenyears.

Despite the time window of PM exposure that is causally linkedtoBPlevelsisnotwellestablished,accordingtothe perspectiveofNewmanandhiscollaborators,10itwillbeon theorderofafew daysgiventherapidoccurrence ofthe physiologicalresponseswherebyPMinfluencesonBP.Conse- quently,weassumedthattheaveragethreepreviousdays’

PM10 concentrationswere adequate torepresent theindi- vidual exposure of each participant.Additionally, we also testedtheassociationswhenconsideringtwoandfivepre- vious daysinstead of the three previous days and results remainthesame.

Finally, even considering the adjustment for several potential confounders, thereis stilla possibility that the observed estimates could have been affected by resid- ual confounding due to other unmeasured confounders.

In addition, effect estimates presented in this study were based on a single-pollutant model and consid- ering only PM10, due the scarce available air quality monitoring data for the remaining air pollutants, but thereareimportantinteractionsbetweentheatmospheric pollutants, namely the potential additive effects of mul- tiple pollutants, that should be considered in future studies.24,25

Conclusions

Tothebestofourknowledge,thisisthefirststudyassess- ingtheassociation betweenanair pollutantexposureand the blood pressure values in Portugal. Our results sug- gest that exposure to the PM10 levels observed in 2015, have a small or no effect on the blood pressure val- ues. However, we only analyzed one of a large amount of air pollutants, and future studies should investigate whether the exposure to other air pollutants, including particulatematter ofa smaller size, canexplain some of the causal link between short-term exposure to ambient air pollution and diastolic or systolic blood pressure val- ues.

Funding

INSEF was developed as part of the pre-defined project financed under the Public Health Initiatives Program.

‘‘Improvement of epidemiological health information to supportpublichealthdecisionandmanagementinPortugal.

Toward reduced inequalities, improved health and bilat- eralcooperation’’witha1.500.000D Grant fromIceland, Liechtenstein and Norway from EEA Grants and the Por- tuguese Government. The present study was also funded bythe Portuguese Foundation for Scienceand Technology (FCT)(PhDScholarshipReference:SFRH/BD/129426/2017).

J. Ferreira was funded by national funds (OE), through FCT --- Fundac¸ão para a Ciência e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. CESAM received financial supportby FCT/MCTES(UIDP/50017/2020+UIDB/50017/2020),through nationalfunds.

Conflicts of interest

Theauthorsdeclarethattheyhavenoconflictsofinterest.

Acknowledgments

Theauthorsaregratefultoalltheprofessionalsandpartici- pantsinvolvedintheINSEF.Theauthorsarealsogratefulto thePortugueseEnvironmentalAgency(APA)formakingthe airqualitydataavailable.

Appendix A. Supplementary data

Supplementary material associated with this article can be found in the online version at doi:10.1016/

j.repc.2022.02.011.

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