ReviewNoncodingRNAsversusProteinBiomarkersinCardiovascularDiseaseChristianSchulte,1,2,3,@TemoBarwari,1AbhishekJoshi,1,4,@TanjaZeller,2,3andManuelMayr,1,*,@Thedevelopmentofmoresensitiveproteinbiomarkerassaysresultsincontinuousimprovementsindetectability,extendingtherangeofclinicalapplicationstothedetectionofsubclinicalcardiovasculardisease(CVD).However,theseeffortshavenotyetledtoimprovementsinriskassessmentcomparedwithexistingriskscores.NoncodingRNAs(ncRNAs)havebeenassessedasbiomarkers,andmiRNAshaveattractedmostattention.Morerecently,otherncRNAclasseshavebeenidentified,includinglongnoncodingRNAs(lncRNAs)andcircularRNAs(circRNAs).Here,wecompareemergingncRNAbiomarkersinthecardiovascularfieldwithproteinbiomarkersfortheirpotentialinclinicalapplication,focusingonmyocardialinjury.NecessityforNovelBiomarkersinCVDBiomarkershaveguidedtreatmentdecisionsforCVDoverthepast50years(Box1).Forcardiactroponins(cTns)(seeGlossary),thisisapparentinthelatestandfourthuniversaldefinitionofmyocardialinfarction(MI):forthefirsttimemyocardialinjuryisdefinedalongsidemyocardialin-farctionasadifferentdiseaseentity,asaresultoftheongoingimprovementsofassaysensitivitiesallowingfordetectionofminutechangesincirculatingcTnlevels.Consequently,evensettledelevationsofcTnlevelscanbedetected[1].Aflipsideofthisincreaseinsensitivityisanincreasedlikelihoodoffalsepositives,requiringnewdefinitionsofpathologicalvaluesinacuteandchronicsettings,orthedefinitionofnewdiseasestateswhereverylowlevelsofthedetectedbiomarkercaptureaseparatephaseofthediseaseprocess(seeClinician’sCorner).Thus,thereisstillaneedtoimproveuponandcomplementexistingbiomarkersforCVD.Inthisrespect,anapproachofcomplementarybiomarkercombinationseemsattractive.CirculatingnoncodingRNAs(ncRNAs)arecurrentlybeingassessedasalternativeandcomplementarybiomarkercandidates,andinitialresults,especiallyformiRNAs,showpotentialforimplementationinclinicalresearch.FurtherncRNAspecies,suchaslongnoncodingRNAs(lncRNAs)andcircularRNAs(circRNAs)havepropertiesofcirculat...
