慢性病的环境因素分析

EnvironmentalDriversofChronicDisease

Basedonthereport

EnvironmentalThreatstoHealthyAging

byJillSteinMD,TedSchettlerMD,MPH,MariaValentiandBenRohrer

2010GreaterBostonPhysiciansforSocialResponsibility(/Boston)andTheScienceandEnvironmentalHealthNetwork()第1页，共56页。WhatWeWillCoverEnvironmentalfactorsarekeydriversofmanycommonchronicdiseasesEnvironmentalfactorsalterkeybiologicalpathwaysleadingtochronicdiseaseImportantenvironmentaldeterminantsofhealthinclude:Foodsystem/nutritionanddietToxicchemicalsBuiltenvironment/physicalactivityPsychological&socioeconomicstressExamplesofcrosscuttingsolutionsforhealthypeople&ahealthyenvironment第2页，共56页。Scope&ContextoftheProblemAcenturyofchangeinnatural,builtandsocialenvironmentshascaused

majorchangesinthepatternsanddistributionofdiseases.Weareseeingdramaticincreasesinchronicdiseases,andatyoungerages,manyofwhich,suchasdiabetes,arethemselvesriskfactorsfordementia.Theover-65populationwillnearlydoubleby2030tomorethan71million,sharplyincreasingthenumberofpeopleatriskofchronicdiseasesofaginglikeAlzheimer’sandParkinson’sdiseases,amongothers.Environmentalfactorsplayakeyroleinhealthacrossthelifespan.Thustheyofferamajorpreventionopportunity.第3页，共56页。TheChangingEnvironmentand

DiseasePatternsDuringthepastcentury,humanactivityhasalteredvirtuallyallaspectsoftheworld’secosystems:Pervasivespreadofsyntheticchemicals;airandwaterpollution.Industrializedfoodsupply.Destructionofcriticalnaturalhabitats,stressingecosystems.Climatechange.Howwelive,eat,work,playandsocializehavesubstantiallychanged:Builtenvironmentshaveincreasedsocialisolationformanypeople;reducedphysicalactivity.Growingincomegapincreasesdiseaserisk.Diseasesofcivilization-obesity,diabetes,cardiovasculardisease,hypertension.第4页，共56页。EnvironmentDrivesChronicDiseaseWesternDiseaseClusterDiabetesObesityAbnormalLipidsMetabolicSyndromeCardiovascularDiseaseFoodsystem/DietFossilFuelsSocioeconomicStressChemicalsBuiltEnvironment/TransportationInflammationDisruptedInsulinSignalingOxidativeStress

Alzheimer’sParkinson’sAlteredPathwaysEnvironmentalFactorsChronicDisease第5页，共56页。ProfoundPublicHealthImpact

OfEnvironmentally-DrivenWesternDiseaseClusterObesity/overweight–2/3USadults,prevalencex2in~25yrsPre/Diabetes–40%USadults,prevalenceDM~x2over20yrs

Cardiovasculardisease–stillleadingcauseofdeath.Hypertensionincreasing./nchs/FASTATS/lcod.htm,Hajjar03Metabolicsyndrome=earlysignsofotherclusterdiseases;35%adults,~55%>60yrsFordES05Alzheimer’sdisease–½>84yrsold,5.3MAlzheimer’sAssoc.第6页，共56页。Alzheimer’sDisease/dementiaNotaninevitablefeatureofnormalaging.Progressiveimpairmentofmemoryandmultipleothercognitivefunctions,severeenoughtointerferewithdailyfunctioning.Expectedtotriplebymid-centurytoover13million.Likelycausedbyvarying combinationsofgeneticand environmentalfactors.

AnnualcostsinUSover$150billion.第7页，共56页。Parkinson’sDiseaseProgressivemovementdisorderthatincludestremors,stiffness,andslowmovement.Mayleadtoseveredisability.Likelycausedbyvariablecombinationsofgeneticandenvironmentalfactors.About50,000newcasesannuallyinUS.*PrevalenceinUSexpectedtodoubleby2030.**

DuetothelackofregistriesandbaselinedataonParkinson’sDisease,thefiguresusedhereareestimates.

第8页，共56页。Alzheimer’sandParkinson’sDiseasesCharacterizedby:

abnormalproteindepositschronicinflammationabnormaloxidativestressManyneuroscientistsarebeginningtothinkofsomeneurodegenerativediseasesalongacontinuum,withoutclearlydistinctboundariesinclinicalorpathologicalmanifestations

第9页，共56页。ContinuumofAge-AssociatedCognitiveImpairment第10页，共56页。EnvironmentDrivesChronicDiseaseEarlylifeexperiencescaninfluencelater-lifehealthanddisease.Multiplefactorsinteracttoinfluencehealth&disease.

Environmentalfactorscanalternaturalpathwayswhich

inturncanleadtochronicdisease.

Anecologicalhealthframeworkconsiderstheindividualinthecontextoffamily,community,societyandecosystem.

BasicPrinciples第11页，共56页。ToxicexposuresoxidativestressObesity,hypertension,Cardiovasculardisease,diabetesAlzheimer’s,dementia,Parkinson’sLowbirthweightEarlylifeexperiencescaninfluencelater-lifehealth,diseaseAgingbeginsatconception第12页，共56页。MultipleFactorsInteracttoInfluenceHealth&Diseasebuilt

environmentdiseasestressenergychemicalsnutrients第13页，共56页。Anecologicalhealthframeworkconsiderstheindividualinthecontextoffamily,community,society,andecosystem.第14页，共56页。AlteredPathwaysEnvironmentDrivesChronicDiseaseEnvironmentalFactorsInflammationDisruptedInsulinSignalingOxidativeStressChronicDiseaseMechanismsofAction第15页，共56页。Definedbymicroscopic

characteristics&laboratorytest:inflammatorycells&mediatorsCLASSICALCONCEPT

OFINFLAMMATIONDefinedbyappearance.“Calor,dolor,rubor,tumor.”Heat,pain,redness,swelling.TheNewConceptofInflammation“Atherosclerosisisaninflammatorydisease.”(2)Ross,Russell.Atherosclerosis–AnInflammatoryDisease.NEJM1999,340(2);115-126.第16页，共56页。第17页，共56页。InsulinSignaling=

NormalMetabolismInsulinsignaling↓

bloodsugar↓

arterydisease↓

triglycerides第18页，共56页。Insulinsignaling↑bloodsugar

↑

arterydisease

↑

triglyceridesInflammationOxidativestressDisruptedInsulinSignaling=

InflammatoryMetabolism第19页，共56页。AlteredPathwaysEnvironmentDrivesChronicDiseaseEnvironmentalFactorsChronicDiseaseFoodSystem/Diet第20页，共56页。

NovelNutrientsArePervasive,PromoteInflammatoryMetabolism第21页，共56页。What’s“Novel”intheWesternDiet?“Hypotheticalschemeoffat,fattyacid(ω6,ω3,transandtotal)intake(aspercentageofcaloriesfromfat)andintakeofvitaminsEandC(mg/d).Datawereextrapolatedfromcross-sectionalanalysesofcontemporaryhunter-gathererpopulationsandfromlongitudinalobservationsandtheirputativechangesduringthepreceding100years[75].”FromAPSimopoulos,Theimportanceoftheratioofomega-6/omega-3essentialfattyacids.Biomedicine&Pharmacotherapy56(2002)365-379.Years%ofcaloriesfromfatmg/day第22页，共56页。HighGlycemicCarbohydratesIncreasetheRiskofChronicDiseaseHighglycemiccarbohydratesbreakdownquicklyduringdigestion,rapidlyreleasingglucose(sugar)intothebloodstream.ΔPlasmaInsulin,mg/dlTime,minsINSULINEMICRESPONSELowglycemicfoodHighglycemicfood第23页，共56页。第24页，共56页。PropertiesofFattyAcids

Omega-3

Omega-6

SaturatedFood

Perishable Durable IncreasedinSystem

Shortshelflife Processedfoodsfactoryfarmed

Increasedin Longshelflifeanimals pasture-fed animals

Immune

Anti-inflammatory

Inflammatory&

InflammatoryProperties

Anti-inflammatory

Evolutionary

Recentmarked

Recentmarked

RecentmarkedContext

decline

increase

increase第25页，共56页。↓Omega-3,(↑Omega-6)

Insulinsignaling↑bloodsugar

↑

arterydisease

↑

triglyceridesInflammationOxidativestressNovelNutrientsDisruptInsulinSignaling,

DriveInflammatoryMetabolismSaturatedfat↓Antioxidants

HighGlycemicCarbohydratesFructose

第26页，共56页。Increaserisks

saturatedandtransfatshighglycemiccarbohydrateslackoffruits/vegetables/omega3sexcessomega6s?Reducerisks

fruits,vegetablesomega3slowglycemiccarbohydratesMediterraneandietInfluenceofNutrition

onChronicDisease

第27页，共56页。BenefitsofMediterranean-TypeDiet

onChronicDiseaseRiskClinicalinterventionstudies70%↓heartattacks,cardiacdeath&totalmortalityDeLogeril9460%

↓cardiaceventsinCVDpatients*Ornish98~50%↓metabolicsyndromeEsposito0439%↓inCRPEsposito04↓insulinresistanceEsposito04↓weightEsposito04Prospectiveobservationstudies80%↓diabetesMartinez-Gonzalez08~31%↓all-cause&cardiovascularmortality,22%↓cancermortality**calculatedfromSofi08

73%Alzheimer’smortality

Scarmeas0725-30%↓Parkinson’sdiseaseGao0778%↓childhoodasthmamaternaldietChatzi08*10%lowfat,vegetariandiet+exercise,stressreduction**Forevery2pointincreaseinadherence(ona9pointscale),riskreductionswereobservedof0.91forallcausemortality,0.91forCVmortality,0.94foroccurrenceandmortalityfromneoplasm.Toconveytheimplicationsofthesefindings,wehaveappliedtheriskreductionsacrossa9pointadherencescaletoyieldacalculated~31%↓all-cause&CVmortalityanda22%↓incancermortality.第28页，共56页。Benefitsof

Sustainably-ProducedFoodNutritionalbenefits:Generallyhigherlevelsofvitamins,mineralsandphytochemicals(oftendependentonsoilquality)

HigherOmega-3contentOrganicsamplescontainedhigherconcentrationsofpolyphenolsandantioxidantsin75%ofthematchedpairsrepresentingthosenutrients

Benefitsforfarmworkersandcommunities:Reducedexposuretopesticides

第29页，共56页。AlteredPathwaysEnvironmentDrivesChronicDiseaseEnvironmentalFactorsChronicDiseaseToxicChemicalsAirpollution,Leadandotherheavymetals,somePesticides,BisphenolAandotherEndocrineDisruptors第30页，共56页。第31页，共56页。LeadCumulativeoccupationalexposure↑cognitiveimpairmentShih20072xriskParkinson’sCoon2006Cumulativecommunityexposure

↑cognitiveimpairmentShih2006Upto15yearscognitiveagingWeisskopf2004AnimalstudiesofearlylifeexposureLate-lifeAlzheimer’smarkersBasha2005,Lahiri2007

第32页，共56页。PesticidesParkinson’sDiseaseHumanstudies-24/31studiesshow↑risksforPD.(OR1.6-7)Brown2006Animals-Rotenone¶quatdamagedopaminergicneuronsinstriatalregionofbrainUverskyVN2004-Combinationsofmanebandparaquat;prenatalexposure“primes”thebrain,increasingadultsusceptibilityCory-Slechta2005Cognitivedecline/dementiaLowlevelfungicidesinvineyards3.5xpoorattention,memoryBaldi2001

Occupationalexposureinmenassociatedwith2xriskofdevelopingADBaldi2003InsulinResistance,metabolicsyndrome

Lee2006,2007,2007Somepersistentpesticidesshowstrongdose-responserelationtoinsulinresistance andmetabolicsyndrome.

第33页，共56页。Foundinpolycarbonateplastic,resins,sealants.Exposuresarenearlyubiquitous.Endocrinedisruptor,oxidativestress.Causesfataccumulation&insulin

resistanceatlowlevels(animals).Alanso-Magdelena2006,Wada20073-fold↑Cardiovasculardisease.Lang20082-fold↑InsulinResistance.Lang2008

BisphenolA

polycarbonate第34页，共56页。Insulinsignaling↑bloodsugar

↑

arterydisease

↑

triglyceridesInflammationOxidativestressEnvironmentalFactorsDisruptInsulinSignaling,

DriveInflammatoryMetabolismEndocrine

Disruptors-BPA,dioxins,PCBs,somepesticides

SaturatedfatHighGlycemicCarbohydratesAirPollution↓Antioxidants

↓Omega-3

Fructose

SomePesticidesLead,otherheavymetals第35页，共56页。AlteredPathwaysEnvironmentDrivesChronicDiseaseEnvironmentalFactorsChronicDiseaseBuiltEnvironmentPhysicalActivity第36页，共56页。HealthBenefitsofPhysicalActivityReducedongoinglevelsofoxidativestressandinflammatoryburden.

Brooks2008,Attipoe2008InverselyassociatedwiththerisksofAlzheimer’s/dementiaandcognitivedecline.Rovio2005SubjectsatriskforADwhowalked150min.perweekshowedimprovementsincognitionwhilethecontrolgroupshowednonetchangefrombaselineat1.5yrs.Lautenschlager2008Increasingphysicalactivityatanyageimprovesphysicalandemotionalwellbeing.第37页，共56页。WalkableCitiesProjectsCommunityGardensFarmer’sMarketsRailstoTrailsLivableCommunitiesEnhanceHealthyAging第38页，共56页。Cuba-lostfossilfuels↑biking,walking,localplant-basedfood↑physicalactivity

50%↓obesity50%↓mortality:DM51%,CVD35%,stroke20%,allcause18%FrancoMetal.ImpactofEnergyIntake,PhysicalActivity,andPopulation-wideWeightLossonCardiovascularDiseaseandDiabetesMortalityinCuba,1980-2005.AJE166,12;Sept.19,2007SustainableFood&TransportationSolutions:

TheCubaExample第39页，共56页。GreenSpace

ReducesStress,Mortality,ImprovesCognitiveFunctionShortenspostsurgicalrecoverytime,reducesneedforpainmedications.

Ulrich‘84Attentiondeficitsimproveafterawalkinthepark.Effect=methylphenidate.

Taylor’08Accesstogreenspacereducestheeffectofpovertyonmortalityby~50%.Mitchell‘08第40页，共56页。Insulinsignaling↑bloodsugar

↑

arterydisease

↑

triglyceridesInflammationOxidativestressEnvironmentalFactorsDisruptInsulinSignaling,

DriveInflammatoryMetabolismObesityEndocrine

Disruptors-BPA,dioxins,PCBs,somepesticides

InactivitySaturatedfatHighGlycemicCarbohydratesAirPollution↓Antioxidants

↓Omega-3

Fructose

Lead,otherheavymetalsSomePesticides第41页，共56页。AlteredPathwaysEnvironmentDrivesChronicDiseaseEnvironmentalFactorsChronicDiseaseSocio-Economic

StressDepression,poverty,violence,inadequatehealthcare第42页，共56页。Socioeconomic,PsychosocialStressorsStress,depressionriskfor CVD,AD

Sesso,Kario,OwnbyPeoplewithlowerSEstatusareatriskforexposuretomultipleenvironmentalhazards↑damage.Lead+stress

↑cognitiveimpairment

Glass2009Lead+airpollution↑CVautonomicdysfunctionPark2008第43页，共56页。

Peoplewholiveinneighborhoodsthatlacksocialcohesion,sidewalks,orsafetylimittheirexerciseandhaveanincreasedriskofdepressionandpossiblyobesity.

BerkeEM07,MolnarBE04EffectsoftheBuiltEnvironmentonHealth第44页，共56页。Insulinsignaling↑bloodsugar

↑

arterydisease

↑

triglyceridesInflammationOxidativestressEnvironmentalFactorsDisruptInsulinSignaling,

DriveInflammatoryMetabolismObesityEndocrine

Disruptors-BPA,dioxins,PCBs,somepesticides

InactivitySaturatedfatHighGlycemicCarbohydratesAirPollution↓Antioxidants

↓Omega-3

Fructose

Lead,otherheavymetalsSomePesticidesStress第45页，共56页。MultipleFactorsInteracttoInfluence

Health

&

Disease第46页，共56页。EnvironmentalFactorsChronicDisease

AlteredBiologicalPathways↑GreenhouseGasesClimateCrisis

Heat,drought,storms,fires,icesheetinstability,sealevelrise,lossofglacialirrigation,refugees,foodinsecurity/starvation,tropicaldiseases

EnvironmentalFactorsDriveChronicDiseaseandtheClimateCrisis

第47页，共56页。Solutions

for

HealthyPeople&AHealthyPlanet第48页，共56页。MajorIllnessesArePreventable

PersonalActionstoProfoundlyReduceRisks

PersonalLevel–“ApproachestoHealthyLiving”Eathealthy–whole,fresh,unprocessed,plantbasedfoodsAvoidtoxicantswheneverpossibleExerciseBesociallyengaged

第49页，共56页。Localized,diversifiedandsustainablefoodproduction

Clean,renewableenergy

↓

airpollution,chemicalexposuresMasstransitthatconnectswithbikepathsandsidewalks

canreduce

airpollution&obesityChemicalregulatoryreform“Safersubstitute”programsandgreenproductdesign↓toxicexposures,ecosystem,wildlifecontamination;jobcreationUniversalhealthcarediseaseprevention&equitablehealthcare.MajorIllnessesArePreventablePolicyInitiativestoProfoundlyReduceRisks第50页，共56页。MajorIllnessesArePreventablePolicyInitiativestoProfoundlyReduceRisksExamplesofSpecificInitiatives:Nutrition–Reform