VascularConnectiveTissueDisease
Thesedisordersaffectthemainproteinsthatareresponsibleforthestrengthandintegrity
ofallofourorgans,vessels,skinandbones.Theycauseweaknessinthebloodvessels,
particularlythearteries,thatcanleadtovascularproblemssuchasaneurysms,aortic,
carotidcoronary,visceraldissections,andspontanousruptures.
Background
Connectivetissuesaretissuesthroughoutthebodythatsupportandbindcellstogether.
Containingproteinssuchascollagenandelastin,connectivetissuescanbeinjuredor
inflamedasaresultofinheriteddiseases,autoimmunediseases,andenvironmental
exposure.Becauseconnectivetissueislocatedthroughtheentirebody,vascularconnective
tissuedisorderscanaffectmanypartsofthebodyincludingthebones,eyes,skin,nervous
system,andlungs.VascularCTDiseasessuchasthefourdescribedbelow,affectthewallof
themajorarteriesandaorta,anditsweakeningincreasestheriskofaorticaneurysmand
dissection.
Connectivetissuessignificantlyaffecttheaortabecausetheaortaisexposedtohighshear
stress,orpressurefromtheconstantflowofblood.Theaortaisaverywelldesignedpipe
thatmustconvertchaoticflowintoanorganizedstream.Imaginepeopleleavingasporting
eventoraconcert:thereisinitialchaos,buteventuallylinesformattheexitandweproceed
outthedoor.Inmuchthesamemanner,twositesofchaosexistintheaorta.Thefirstisat
theaorticroot,wherebloodshootsoutoftheheartandmustbe"corralled"intoan
organizedmanner.Thisactivechangingofthechaoticenergytoorganizedflowrequires
strength.Ifthestrengthlayeroftheaortaisdysfunctional,thestressmyinternallybreakthe
aorta(atypeADissection).Thesecondsiteofchaosisattheendoftheaorticarch,where
bloodmustlooparoundandheaddownwardstosupplytotheabdomenandlegs.Theturn
thatthebloodmakesintheaorticarchisalsoaverychaoticandenergeticphenomena.
Consequently,theaortamaytearatthisjunctureaswell(aso-calledtypeBDissection).
Manypatientsdonotknowthattheymayhaveaninheritedcondition.Patientswhoreceive
treatmentattheAorticSurgeryCenterandareknownorfoundtohaveaconnectivetissue
disordersuchasMarfansyndrome,Ehlers-Danlos,oramyloidosis,mustbereferredtothe
DivisionofClinicalvascularGenetics.Moreover,allpatientswhoundergoaorticsurgery
musthavesamplessenttoourpathologydepartment.Anypatientwhoexhibitsevidenceof
connectivetissuedisruptionorabnormaltissueconsistencymayalsobereferredforgenetic
testinguponfurthercounsel.
Western Vascular Institute, Department of Vascular and Endovascular Surgery, University College Hospital, Galway
Tel:+353 91 542535
Fax:+353 91 785871
E.Mail: [email protected]
Web: www.vascular.ie
MarfanSyndrome
Many have speculated that Abraham Lincoln had Marfan syndrome because of his height, his stooped posture, his long limbs, and certain other aspects of
his appearance.
Marfansyndromeisageneticdisorderthatcausesabnormaldevelopmentof
fibrillin,whichisacomponentoftheconnectivetissue.Althoughthediseasemay
rangefrommildtosevere,manypatientswithMarfansyndromeareverytall,thin,
long-limbed,andloose-jointed.Themostseriousrisksassociatedwiththedisease
occurintheheartandaorta:weaknessoftheconnectivetissuesputspatientswith
Marfansyndromeatriskforaorticaneurysm,heartvalvedisease,andaortic
dissection.Thereasonisthatthereisastructuralweaknessinthewalloftheaorta.
Thefibrillinhelpsmaintaintheintegrityoftheaorta,whenitisexposedtohigh
pressure.Itsabsenceallowsforaneurysmstodevelopanddissectionstooccurat
earlyages.Itisimportanttorealizethatanychangeinsizeofanaorticroot
aneurysminapatientwithMarfansyndromeisanindicationtomeetwithanaortic
specialist.Whensurgeryisindicated,oftentheoperationcanbeperformedasa
valve-sparingprocedure,withexcellentlong-termresults.
Loeys-DietzSyndrome
Loeys-Dietzsyndrome(LDS)isanothergeneticdisorderthatsharessimilaritieswith
Marfansyndrome.Itaffectsproteinscalledtransforminggrowthfactorbeta
receptor1and2,whicharealsopartoftheconnectivetissuefoundthroughoutthe
body.SomefeaturesofLDSoverlapwithMarfansyndrome,includingaortic
aneurysmordissection,leakageofthemitralvalve,looseflexiblejoints,andothers.
OtherfeaturesofLDSareunique,suchasarteriesthattwistandwind,aneurysmsin
arteriesotherthantheaorta,widelyspacedeyes,cleftpalate,wideorsplituvula,
heartdefectsincludingatrialseptaldefect,bicuspidaorticvalve,andmanyother
features.Thesepatientshaveveryunstableaortictissueandshouldhaveasurgical
evaluationassoonasthediagnosisofLoeys-Dietzismade.
Western Vascular Institute, Department of Vascular and Endovascular Surgery, University College Hospital, Galway
Tel:+353 91 542535
Fax:+353 91 785871
E.Mail: [email protected]
Web: www.vascular.ie
BicuspidAorticValve
Bicuspidaorticvalveisanabnormalformationoftheaorticvalve.Approximatelytwo
percentofthepopulationhasabicuspidvalve.Oftenpatientswillhavean
awarenessofitspresence,astheywerefoundtohaveamurmurduringaroutine
physicalexamination.Bicuspidvalvestendtowearoutsoonerthantrilealfetvalves,
asbloodpassesthroughtheleafletswithmoreturbulence.Thesevalvesalsohavea
tendencytoleakearlierthantrileafletvalves.Inabouthalfofpatientswithbicuspid
valvedisease,anaorticrootaneurysmbeginstodevelopbyage30.Therateof
growthisvariable,butbyage30-50,manypatientshavedevelopedananeurysmof
significantsize.Inthesepatients,theaneurysmdevelopsnotbecauseofthevalve,
butbecauseofageneticdefectintheascendingaorta.Anyproceduretoaddressthe
valvemustalsoaddresstheaorticaneurysm.
Ehlers-DanlosSyndromes
Ehlers-DanlosSyndromesareagroupofgeneticdisordersthatsharefeaturessuch
aseasybruising,looseandflexiblejoints,fragileskin,andweakenedconnective
tissues.Amongthesubgoupsofthesyndromeisthevasculartype,whichis
characterizedbyruptureofthearteriesandbowel,clubfoot,andother
manifestations.OthertypesofEhlers-Danlossyndromesincludethosemarkedby
hypermobilityofthejoints,skinlaxity,fragileglobeoftheeyes,spinecurvature,and
otherfeatures.PeoplewithEhlers-Danlossyndromeareatriskforaorticaneurysm
becauseofweakeninginthewalloftheaorta.
FamilialThoracicAorticAneurysmAndDissection
Familialthoracicaorticaneurysmanddissection(familialTAADaffectstheupper
partoftheaorta,neartheheart.Thispartoftheaortaiscalledthethoracicaorta
becauseitislocatedinthechest.Othervesselsthatcarrybloodfromtheheartto
therestofthebodycanalsobeaffected.
InfamilialTAAD,theaortacanbecomeweakenedandstretchedleadingtoanAortic
dilatation,thatmayleadtoasuddentearingofthelayersintheaortawalland
aorticdissection,allowingbloodtoflowabnormallybetweenthelayers.Theseaortic
abnormalitiesarepotentiallylife-threateningbecausetheycandecreasebloodflow
tootherpartsofthebodysuchasthebrainorothervitalorgans,orcausetheaorta
tobreakopenandrupture.
Western Vascular Institute, Department of Vascular and Endovascular Surgery, University College Hospital, Galway
Tel:+353 91 542535
Fax:+353 91 785871
E.Mail: [email protected]
Web: www.vascular.ie
FamilialTAADmaynotbeassociatedwithothersignsandsymptoms.However,
someindividualsinaffectedfamiliesshowmildfeaturesofrelatedconditions
asMarfansyndromeorLoeys-Dietzsyndrome.Occasionally,peoplewithfamilial
TAADdevelopaneurysmsinthebrainorinthesectionoftheaortalocatedinthe
abdominalaorta.DependingonthegeneticcauseoffamilialTAADinparticular
families,theymayhaveanincreasedriskofdevelopingblockagesinsmallerarteries,
whichcanleadtoheartattackandstroke.
RiskforVascularProblemsVaries
Theriskofsignificantvascularproblemsvariesbyeachdisorder,byvascularhealthfactors
suchassmoking,hyper-homocysteniamiaandyourgenetics.
On-GoingMonitoringcanHelp
IfyouarediagnosedwithaVCTD,youmayneedongoingmonitoringtoheadoffortreatany
possiblevascularproblems.ManypatientswithaVCTDhavenosymptomsuntiltheir20sor
30s.
CharacteristicSignsofVCTDS
Theyareassociatedwithcharacteristicfacial,skeletal,eyeandskinfeatures.
ChestPain
ChestpainisoftenthefirstsignofanunderlyingvascularCTD.
EasyBrusingwithanOrthopaedicissuesataVeryYoungage
Easybruising,hyper-flexibility,andorthopaedicissuesinaveryyoungchildmaysignalan
elevatedriskforvascularCTD.
Causes
AllvascularCTDsarecausedbyspecificgeneticmutationsthatadverselyaffectthemain
buildingblocksofthehumanbody:fibrillin,collagen,andelastinproteinmolecules.
Diagnosis
Ifyouexperienceanyofthesymptomsabove,seeavascularsurgeonwhohastrainingin
geneticmedicineforanevaluation.
TheRoleofClinicalgenetictestinginestabilshimgadiagnosisremainslimitedbecausemore
than500mutationshavebeenfoundand90%ofthemutationsareuniquewithina
pedigree.
Western Vascular Institute, Department of Vascular and Endovascular Surgery, University College Hospital, Galway
Tel:+353 91 542535
Fax:+353 91 785871
E.Mail: [email protected]
Web: www.vascular.ie
Treatments
TreatmentoptionsdependonthespecifictypeofCTDandassociatedvascular
problems.Targetofrestingpulseratemustbebelow60andbloodpressureof120/80must
beachieved.WerecommedCeliprolol200mgtwicedaily.
StayingHealthy
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Seeyourvascularsurgeonregularlytocheckyourvascularandoverallhealth,
includingyourHeamocystinelevel,Ddimer,osteopoitin,osteoprogen,Directrenin
,Aldosteronelevel,FBN1,COL3A1,Proa1(III).
Ifyouneedongoingtestingtolookforaneurysms,askaboutwaystoavoidmedical
radiationexposureassociatedwithsometests,suchasechocardiogramsor
magneticresonanceangiogram(MRA)tests.
Ifyousmoke,askyourvascularsurgeontohelpyoufindasmokingcessation
programthatwillworkforyou.
Exercisesafelyandregularly,avoidoverstrecthingorliftingweights.Askyour
doctorforguidance.
Contact Information:
Professor Sherif Sultan
WesternVascularInstitute
Vascular&EndovascularSurgery
UniversityCollegeHospitalGalway
Galway
Ireland
WebSite:-www.sherifsultan.ie
NationalUniversityofIreland,
Galway
Vascular&EndovascularSurgery
E-mail:[email protected]
Tel:+35391542376/091542535
Vascular&EndovascularSurgery
Suite24
GalwayClinic
E-mail:[email protected]
Tel:+35391720122/091785861
Fax:+35391720121/091785871
Western Vascular Institute, Department of Vascular and Endovascular Surgery, University College Hospital, Galway
Tel:+353 91 542535
Fax:+353 91 785871
E.Mail: [email protected]
Web: www.vascular.ie