糖尿病与发炎指标CRP..ppt

糖尿病與發炎指標CRP 吳達仁醫師成大醫學院附設醫院內科部內分泌新陳代謝科 CRP FromAcutePhaseProteintoCardiovasculardisease CRPisasymmetricalringmoleculethatconsistsof5noncovalentbutassociateprotomers Eachprotomerhas2calciumionsresponsibleforthespecificbindingofphosphochlorine Phosphochlorineisacommonconstituentofmanybacterialandfungalpolysaccharidesandmostbiologiccellmembranes suchasthephosphochlorineresiduesofC orcapsular polysaccharideofStreptococcuspneumoniae Theproteinwasnamed C reactive becauseofthisreaction Astablepentamericprotein compoundwithahalf lifeof19hours withoutdiurnalvariation CRPisapathogenicmarkerandanonspecificmarkerofinflammation CRPissynthesizedinresponsetotheacutephaseofabacterialorfungalinfection MolecularStructureandMorphologyofHumanCRP Negativelystainedelectronmicrographshowingthetypicalpentamericdisc likestructureface onandside on arrows Ribbondiagramofthecrystalstructure showingthelectinfoldandthetwocalciumatoms spheres intheligand bindingsiteofeachprotomer Space fillingmodeloftheCRPmolecule showingasinglephosphocholinemoleculelocatedintheligand bindingsiteofeachprotomer PepysMB etal ClinInvest2003 111 1805 1812 AssaysofCRPandReferenceRanges Duringtheacutephaseofinfection serumCRPlevelsweremeasuredbyratenephelometry serumCRPassay Theseassayshavealowerlimitofdetectionofonly6to10mg l Amoresensitivelatexparticle enhancedimmunoturbidimetricassay highsensitivity hs CRPassay hasbeendevelopedthathasalowerlimitofdetection orsensitivity ofabout0 15mg l Itisusedtoassessforcardiovascularrisk Theriskfactorsbyhs CRPlevels CDC AHA CRP 1mg lislowCVDriskCRP1to3mg lismoderateCVDriskCRP3to10mg lishighCVDriskCRPlevels 10mg lgenerallyindicatesbacterialinfection DemographicandDescriptiveCharacteristicsoftheUSPopulationWithoutaPreviousDiagnosisofHypertensionFromNHANESIII MatthiasB etal DiabetesCare2004 27 1680 1687 WOSCOPS OverlapAnalysis Frequencyper100 OntreatmentLDL WOSCOPSGroup Circulation 1998 97 1440 45 TheEffectsofAtorvastatinversusSimvastatinonAtherosclerosisProgressionStudy ASAP AtorvastatinreducedCRPlevelstoagreaterextentthansimvastatin vanWissenS etal Atherosclerosis 2002 165 361 366 P 0 001fordifferencebetweengroups P 0 02fordifferencebetweengroups 50 45 40 35 30 25 20 15 10 5 0 1Year 2Years Atorvastatin Simvastatin Percentchangeinhs CRP 44 9 14 0 40 1 19 7 InfluenceofBaselineBMIonAbilityofAtorvastatintoModifyCVRiskFactors REVERSALStudy P 0 01 P 0 01 P 0 05 NichollsSJ etal AmJCardiol2006 97 1553 7 TotalChLDL CCRP EffectsofSwitchingPravastatintoCerivastatinonC ReactiveProtein Butyrylcholinesterase andLipids Patientswereeligibleforinclusioniftheyhadanactiveprescriptionforpravastatinforatleast3months Subjectswereconvertedfrompravastatin10mg 40mgdailytocerivastatin0 2mg 0 8mgdailyatequipotentdoses MedianCRPlevelsatthepravastatinphase 6weeksofcerivastatin and12weeksofcerivastatin were0 380mg dL 0 403mg dL and0 364mg dLp 0 772 respectively Conclusion MedianCRPremainedstablewithpravastatinandcerivastatinuse althoughTCandLDLdecreased ThefurtherdeclineobservedwithLDL butnotCRPsuggestsdifferingeffectsofstatinsonLDLandCRP ShinnAH etalCurrMedResOpin 2005 2 207 213 RiskFactorsforCHD ModifiableHypertensionHighLDLcholesterolLowHDLcholesterolCigarettesmokingPhysicalinactivityDiabetesObesity BMI 30 Thrombogenic hemostaticstateAtherogenicdiet Non modifiableAgeMalesexFamilyhistoryofprematureCHD NationalCholesterolEducationProgramAdultTreatmentPanelIII 2002 NIHPublicationNo 02 5215 FactorsAssociatedwithIncreasedorDecreasedCRP HigherCRPHypertensionHyperglycemiaLowHDL highTGSmokingObesityMetabolicsyndromeEstrogen progesteroneuseChronicinfection LowerCRPIncreaseexerciseAlcoholconsumptionWeightlossMedication StatinFibrate HypertensionandDyslipidaemiaAreMajorRiskFactorsforCHD KannelW In Hypertension PathophysiologyandTreatment NewYork McGraw Hill Inc 1977 888 909 CastelliWP AmJMed 1984 76 4 12 CHDincidence 1000 ProbabilityofCVD 1000 Age 40 50 60 70 Framinghamstudy SBP mmHg inmen TC mg dL inmen ConcomitantHypertensionandDyslipidemiaIncreasetheRiskofDevelopingFatalCVD AdaptedfromDeBackerGetal EurJCardiovascPrevRehabil 2003 10 suppl1 S1 S78 Dyslipidemia Hypertension Dyslipidemia Hypertension TC271mg dL 7mmol L SBP180mmHg TC271mg dL 7mmol L SBP180mmHg HypertensionandHighCholesterolareTwiceasPrevalentinAdultswithDMComparedtothosewithoutDM ArchivesofInternalMedicine2002 162 427 433 P 0 001 HypertensionandDyslipidemiaCommonlyOccursinDiabetesinTaiwan TADE2002 Prevalence Highuricacid Dyslipidemia Obesity Hypertension C反應蛋白 CRP 可加強TC HDL比值預估首度心肌梗塞發生之風險 RidkorPM Circulation1996 97 2007 11 冠心病風險 TC HDL比值 CRP C RP mg L 01234 N 1 008 代謝異常數目 代謝異常包括 肥胖高血壓高三酸甘油脂症低HDL C高胰島素血症 Festaetal Circulation2000 102 42 7 C反應蛋白 CRP 與代謝異常數目InsulinResistanceAtherosclerosisStudy 54321 P 0 001 AlbertMA etal Circulation 2003 107 443 AlcoholConsumptionandPlasmaC RP ManyAssaysDevelopedBeforehs CRPAreMoreSensitiveThan hs CRPAssay Asearlyas1981 asolid phasesingle antibodycompetitiveradioimmunoassaywithasinglerabbitanti CRPantibodydirectlyimmobilizedontoamagneticparticlehadasensitivityof0 05mg l Withuseofadouble antibodycompetitiveradioimmunoassay thesensitivitywasincreasedfurtherto0 003mg l Anin houseELISACRPassaydevelopedin1997hasasensitivityof0 007mg landwasusedin1999toevaluatethehs CRPtestforclinicaluse In2000 animmunoradiometricassay IRMA wasdevelopedwithpolyclonalantibodiesofCRPimmobilizedonmicrotiterplatesandmonoclonalantibodiesofCRPlabeledwith125I IRMAhadasensitivityof0 05mg l 36 4 Atorvastatin 5 2 Pravastatin ChangeinCRPlevelsfrombaseline Change P 0 001vspravastatin 40 30 20 10 0 1 8 2 9 18Months 2 8 3 0 Baseline Atorvastatin Pravastatin CRP mg L RelationshipBetweenAdiponectinandGlycemicControl BloodLipids andInflammatoryMarkersinMenWithType2Diabetes MatthiasB etal DiabetesCare2004 27 1680 1687 Thecorrelationmatrixamongchangesoflipidprofileandstudiedcardiovascularriskfactorsattheendof12 weekfenofibratetreatment n 39 ChangesoftheStudiedRiskFactorsattheEndof12 weekFenofibrateTreatment n 39 BindingandInternalizationofC reactiveProteinbyFcgammaReceptorsonHumanAorticEndothelialCells HAEC MediatesBiologicalEffects SeveralreportsshowedthatCRPbindstoFcgammareceptorsonleukocytes CRP 100microg mL significantlyupregulatedsurfaceexpressionofFcgammareceptors CD32 aswellasCD64onHAECs P 0 01 Preincuba