Circulating Biomarkers for Predicting Cardiovascular Disease Risk; a Systematic Review and Comprehensive Overview of Meta-Analyses.docVIP

CirculatingBiomarkersforPredictingCardiovascular DiseaseRisk;aSystematicReviewandComprehensive OverviewofMeta-Analyses ThijsC.vanHolten1*,LeonieF.Waanders2,PhilipG.deGroot1,JoostVissers3,ImoE.Hoefer4, GerardPasterkamp4,MennoW.J.Prins2,MarkRoest1 1Laboratory for Clinical Chemistry and Hematology, UMC Utrecht, Utrecht, The Netherlands, 2Philips Research Laboratories, Philips, Eindhoven, The Netherlands, 3ResearchandDevelopment,FutureDiagnostics,Wijchen,TheNetherlands,4ExperimentalCardiologyDepartment,UMCUtrecht,Utrecht,TheNetherlands Abstract Background:Cardiovasculardiseaseisoneofthemajorcausesofdeathworldwide. Assessingtheriskforcardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovasculardisease,therearenocomprehensivestudiescomparingtherelevanceofeachbiomarker.Weperformeda systematicreviewofmeta-analysesonlevelsofserologicalbiomarkersforatherothrombosistocomparetherelevanceof themostcommonlystudiedbiomarkers. MethodsandFindings:MedlineandEmbasewerescreenedonsearchtermsthatwererelatedto‘‘arterialischemicevents’’ and‘‘meta-analyses’’. Themeta-analysesweresortedby patientgroups withoutpre-existing cardiovascular disease,with cardiovasculardiseaseandheterogeneousgroupsconcerninggeneralpopulations,groupswithandwithoutcardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular eventsinclude,fromhightolowresult:cardiactroponinsIandT,C-reactiveprotein