Depression and Subclinical Vascular Diseases in Psoriasis · • Self reported depression in...
Transcript of Depression and Subclinical Vascular Diseases in Psoriasis · • Self reported depression in...
DepressionandSubclinicalVascularDiseasesinPsoriasis
NehalN.Mehta,MDMSCEFAHASectionChief,InflammationandCardiometabolicDiseases
NationalHeart,Lung,andBloodInstitute,USA
LaskerClinicalScholarInvestigatorNationalInstitutesofHealth,USA
ClinicalProfessorofMedicine
CaseReview:History
• 44previouslyhealthyfemalewithpsoriasisfor5years
• “cardiovascularevaluation”– Self-referred
• Beenfeeling“down”and“slow”recently
CaseReview:History• PMH:untreatedpsoriasis
• Medications:none
• Fhx:none
• SHx:+tobaccoofabout½PPD
• ROS:nocomplaints
VS:144/89;84bpm(reg);96%;height:61inches;weight:214lbsàBMI32waist:36inches;hip:35inchesàWHR~1.0
Neck:JVPat6cmH20,nocarotidbruitsLungs:clearbilaterallyCV:RRR,normalS1/S2,nomurmurs,rubsorgallopsAbd:NoHSMorpulsatileliverExt:NoedemabilaterallowerextremitiesVascular: Pulses2+inbothUEandLESkin:plaquepsoriasisontrunk,elbows,kneesandscalp;estimated~9%
BSA
CaseReview:Examination
CaseReview:LaboratoryDataLipids:• TC:186(4.8mmol/L)• LDL:129(3.6mmol/L)• TG’s:144(4.4mmol/L)• HDL:45(1.14mmol/L)Chemistry:• FastingGlc 106(2.8mmol/L)
CaseSummary• 44femalewithuntreatedmoderatepsoriasis
• +tobaccouse
• +highbloodpressure
• BMIof32(obese)
• ‘feelingdown’consistentwithpossibledepression
Whataboutinflammationassociatedwithherpsoriasis?
InflammationmattersinCVDisease
Libby, P and Ridker P. Am J of Medicine. 2002.116(6) 9-16.
Inflammation:criticalinatherosclerosis
1° & MessengerInflamm. Chemokines
• IL-1• TNF-a
• IL-6• IL-18
• MCP-1
Cellular AdhesionMolecules
• sICAM• sVCAM
• sSelectins• sESAMAcute (& chronic) Phase Reactants
hs-CRP, SAA, Lp-PLA2, WBC
Plaque Destabilization
• MMPs• IL-18• MPO
Plaque Rupture•CD40L
•EPCs
EndothelialFxn
Stary, et al. Circulation. 1995;92:1355-1374.
SeverePsoriasis• 50%increasedriskof
mortality• 5yearsoflifelost
CVDiseaseinPsoriasis
Outcome Hazard Ratio(adjusted for CV risk
factors)MI1 1.58Stroke2 1.43CV Death3 1.57MACE4 1.53
Figure. Abuabara K, et al. Br J Dermatol. 2010 Sep;163(3):586-92. 1. Gelfand, JM et al. JAMA. 2006;296:1735-1741.
2. Gelfand, JM et al. J Invest Dermatol .2009; 129:2411-2418. 3. Mehta, NN et al. Eur Heart J. 2010;31:1000-6
4. Mehta, NN et al. Am Journal Of Medicine . 2011; 776: 1-7.
Perpetuation
KeyImmuneFactorsinPsoriasis
Modifiedfrom:NestleFO,etal.NEnglJMed2009;361:496–509.
Initiation
KeratinocyteIL-1βIL-6
TNF-αTNF-αIFN-γ
TNF-α
IFN-αActivation
Natural killer T cell
Plasmacytoid dendritic cell
Myeloid dendritic cell
Macrophage
Th1 cell TNF-α IFN-γ
Antimicrobial peptides
IL-1βIL-6
TNF-αS100
CXCL8CXCL9CXCL10CXCL11CCL20
IL-17AIL-17FIL-22
Keratinocyte
Th17 cell
IL-23
IL-12
Hypothetical model based in part on non-clinical data
Libby. Circulation. 1995;91:2844–2850.
– Tlymphocyte
– Macrophagefoamcell(tissuefactor+)
– “Activated”intimalSMC(HLA-DR+)
– NormalmedialSMC
FibrouscapMedia
LumenAreaofdetail
LumenLipidcore
Lipidcore
VulnerablePlaque
StablePlaque
CellmediatedinflammationdrivesCVDSlide courtesy of Jam
es DeLem
os, MD
Whataboutinflammationassociatedwithherpsoriasis?
Whatabouther‘mood’and‘feelingslow’?
DepressionandAnxietyinPsoriasis
KurdSK,Troxel AB,Crits-Christoph P,Gelfand JM,ArchivesofDermatology,2010
DepressionandAnxietyinPsoriasis
KurdSK,Troxel AB,Crits-Christoph P,Gelfand JM,ArchivesofDermatology,2010
MI,StrokeandCVDeathareincreasedinacutedepressioninpsoriasis
Egeberg,A.ActaDermVenereol.2016Feb;96(2):218-21
LinkingPsoriasisandMoodDisorders
ConnorCJ,LiuV,Fiedorowicz JG.DermatologyResearchandPractice,2015
ConceptualFramework
Depression/Anxiety
Psoriasis
CardiovascularDiseaseInflammation
IL-6,TNF-α,GM-CSF,IL-17
IL-1β,IL-2,IL-6,TNF-α,PGE2,CRP
Canweutilizesubclinicalvasculardiseasestounderstandthis
relationship?
CT Coronary Angiography
(CCTA)
FDG PET-CT&
FDG PET-MR
Estimates direct coronary artery “plaque burden”
Estimates “inflammatory burden” and “functional
consequences”
Vascularimaginginpsoriasis:Howdoweapproachit?
FDGPET/CT– ANovelBiomarker• 18-Fluorodeoxyglucose(FDG)istakenupbycellsinproportion
totheirmetabolicactivity• Biomarkerformacrophagesinearlyatheroscleroticplaques
• recentdataàsmooth muscleorendothelialcells• Visualizesandquantifiesvascularinflammationinvivo
asStandardizedUptakeValue(SUV)
• Demonstratesfunctionalandanatomicaldata
1
5
2
4
3
FDGPETCTImageQuantification:
Figueroa et al JACC Imaging 2013
VascularInflammationAssociateswithFutureCVDEventsinNon-Psoriasis
CoronaryComputedTomographyAngiography(CCTA)– Axialimagesand3Drendering
diagonalbranches
Video provided by: Karen Rodriguez, Dr. David Bluemke
CCTAAnalyticalApproach
Lumen Volume
TotalVolume Plaque Volume
- =Plaque volume = (Artery volume) – (Lumen volume)
Plaque Index = Sum of all plaque volumes of segmentLength of segment
StudyDesign
• Cross-sectional,observational;nestedcohortstudy
• Hypothesis:Subclinicalatherosclerosis,asmeasuredbyFDGPET/CTandCCTA,willbeincreasedinpatientswithpsoriasisandcomorbiddepressionand/oranxietyascomparedtopatientswithpsoriasisalone.
Methods
159patientsprospectivelyenrolledincohortstudy
41patientsreportedhistoryofdepressionoranxietyonbaselinesurvey
40PSOpatientswithreportedcomorbiddepressionand/oranxiety
40PSOpatientsreportingnohistoryofcomorbidpsychiatricillnessmatchedbyageandsex
1patientrandomlydropped
StudySample
Self-reporteddepressionincreasesvascularinflammationinpsoriasis
Aberra,TfromMehtaLabNHLBI.Atherosclerosis.2016Aug;251:219-25.
Self-reporteddepressionisassociatedwithhighercoronaryplaqueburden
Aberra,TfromMehtaLabNHLBI.Atherosclerosis.2016Aug;251:219-25.
Non-calcifiedplaqueàacutemyocardialinfarction
Limitations/FutureDirections
• Samplesize• Cross-sectional• Limitedcharacterizationofpsychiatricdiagnoses
• Mechanism??
Conclusions
• Selfreporteddepressioninpsoriasiswasassociatedwithincreasedvasculardiseases.
• BetterriskstratificationofpsoriasispatientsbyunderstandingtheimpactofpsychiatricillnessonearlyCVdiseasemaybewarranted.
• Earlyidentificationandinterventionmaycontributetoreducingtheburdenofcardiovasculardiseases.