Rev. Bras. Reumatol. vol.56 número1

w w w . r e u m a t o l o g i a . c o m . b r

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

Original

article

The

impact

of

comorbidities

on

the

physical

function

in

patients

with

rheumatoid

arthritis

Wanessa

Vieira

Marques

,

Vitor

Alves

Cruz

,

Jozelia

Rego

,

Nilzio

Antonio

da

Silva

b_{DepartmentofRheumatology,HospitaldasClínicas,MedicalSchool,UniversidadeFederaldeGoiás,Goiânia,GO,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received22August2014 Accepted28January2015 Availableonline10August2015

Keywords:

Rheumatoidarthritis Comorbidities Physicalfunction Mobility

a

b

s

t

r

a

c

t

Objectives:Toinvestigatetheassociationofcomorbiditieswithmobilitylimitationand func-tionaldisabilityinpatientswithrheumatoidarthritisandtoidentifywhichcomorbidity indicatoristhemostappropriatetodeterminethisassociation.

Methods:Sixtyrheumatoidarthritispatientswereenrolledinacross-sectionalstudyfor aperiodof11months.Comorbiditieswereassessed usingthreeindicators:(i)thetotal numberofcomorbidities;(ii)theCharlsoncomorbidityindex;and(iii)thefunctional comor-bidityindex.DiseaseactivitywasassessedusingtheDiseaseActivityScore28.Functional capacitywasmeasuredusingtheHealthAssessmentQuestionnaire,andmobilitywas mea-suredusingTimedUpandGoTestandFive-Times-Sit-to-StandTest.Statisticalanalysiswas performedusingastepwiselog-linearmultipleregressionwithasignificancelevelof5%.

Results:Inthefinalmodel,onlycomorbiditywasassociatedwithmobilitylimitation.The functionalcomorbidityindexscoreexplained19.1%ofthevariabilityofthe Five-Times-Sit-to-StandTest(coefficientofdetermination[R2_{]=0.191)and19.5%oftheTimedUpandGo}

Testvariability(R2_{=0.195).Withregardtofunctionaldisability,theassociatedfactorswere}

comorbidityanddiseaseactivity,whichtogetherexplained32.9%ofthevariabilityofthe HealthAssessmentQuestionnairescore(adjustedR2_=0.329).

Conclusion:Comorbiditieswereassociatedwithmobilitylimitationandfunctionaldisability inrheumatoidarthritispatients.Thefunctionalcomorbidityindexprovedtobean appro-priatecomorbidityindicatortodeterminethisassociation.

©2015ElsevierEditoraLtda.Allrightsreserved.

∗ _{Correspondingauthor.}

E-mail:wanessavmarques@yahoo.com.br(W.V.Marques).

http://dx.doi.org/10.1016/j.rbre.2015.07.009

Influência

das

comorbidades

na

capacidade

funcional

de

pacientes

com

artrite

reumatoide

Palavras-chave:

Artritereumatoide Comorbidades Capacidadefuncional Mobilidade

r

e

s

u

m

o

Objetivos: Investigaraassociac¸ãodascomorbidadescomalimitac¸ãodamobilidadeecom aincapacidadefuncionalempacientescomartrite reumatoide,bemcomoidentificaro indicadordecomorbidademaisapropriadoparadeterminaressaassociac¸ão.

Métodos: Emumestudotransversalforamincluídos60pacientescomartritereumatoide porumperíodode11meses.Comorbidadesforamavaliadaspormeiodetrêsindicadores: (i)númerototaldecomorbidades;(ii)índicedecomorbidadedeCharlson;e(iii)índicede comorbidadefuncional. Aatividadedadoenc¸afoiavaliadapelo Índicede Atividadeda Doenc¸a28.AcapacidadefuncionalfoimensuradapeloQuestionáriodeAvaliac¸ãodaSaúde, eamobilidadefoimensuradapelostestessenta-levantadacadeiracincovezesetimedgetup andgo.Aanáliseestatísticafoirealizadaatravésderegressãomúltiplalog-linearStepwise comníveldesignificânciade5%.

Resultados: Nomodelofinal,apenasofatorcomorbidadesesteveassociadoàmobilidade. Oescore noíndicede comorbidadefuncional explicou19,1%da variabilidade doteste senta-levantadacadeiracincovezes(coeficientededeterminac¸ão[R2_{]=0,191)e19,5%da}

variabilidadedotimedgetupandgo(R2_{=0,195).Emrelac¸ãoàincapacidadefuncional,os}

fatoresassociadosforamofatorcomorbidadeseaatividadedadoenc¸aqueemconjunto explicaram32,9%da variabilidadedoescoredoQuestionáriodeAvaliac¸ãodaSaúde(R2

ajustado=0,329).

Conclusão: Ascomorbidadesestãoassociadascomalimitac¸ãodamobilidadeea incapaci-dadefuncionalempacientescomartritereumatoide.Oíndicedecomorbidadefuncional demonstrouserumindicadordecomorbidadeapropriadoparadeterminaressaassociac¸ão. ©2015ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Rheumatoidarthritis(RA)isachronic,progressive,systemic inflammatorydiseasewhichmainlyaffectsthesynovial mem-brane of joints, which may cause general impairment in functionalstatusofpatients.1

Thestudyoffunctionaldisabilityandassociatedfactorsin RAisrelevant,sincethefunctionalstatusisrelatedtoother clinicaloutcomesinthispopulation,suchasmortality,2,3_loss

ofworkcapacity,4,5_{anduseofhealthresources.}6,7

Thereisincreasingevidencepointingtotheeffectofthe comorbidityfactorinfunctionaldisabilityinpatientswithRA. Radneretal.8,9_{demonstratedthenegativeimpactof}

comor-biditiesinallareasoffunctionalcapacity,regardlessofthe levelof disease activity.Michaudet al.,10 _{ina longitudinal}

study,showedthatageover65yearsandpresenceof comor-biditieswerethemainpredictorsoffunctionalcapacitylossin RAandthatthesefactorsnotassociatedwiththetreatmentof RAhadthegreatesteffectinscoreprogression,asmeasuredby theHealthAssessmentQuestionnaire(HAQ),incomparison withtheeffectofthetreatmentwithbiologicalagents.

ThestudyofNortonetal.11_{showedaconsiderable}

preva-lenceofcomorbiditiesatthetimeofdiagnosisofRAandthat it increasesover the courseofthe disease.After a15-year follow-up,81%ofRApatientspresentedcomorbiditiesand,in addition,presenceofcomorbiditieswasassociatedwith mor-talityandlossoffunctionalcapacityinthesepatients.11_Inan

11-yearlongitudinalstudy,VandenHoeketal.12_observedthat

somaticcomorbiditiesanddepressionwereassociatedwith decreasedfunctionalcapacity.

The published literature reveals that comorbidities are commonconditionsinthispopulation,andonaverageeach patient with RA has 1.6 comorbidities; and this number increaseswithage.13,14_{Inthissense,therehasbeenagrowing}

interestfromresearchersinstudyingcomorbiditiesandtheir impactondifferentclinicaloutcomesinRA,suchas hospital-ization,mortality,functionalcapacityandmedicalcosts.13–15

Comorbidity is defined as a disease or medical condi-tion that coexists with the disease of interest, identified, in this case as RA.13 _{There are several ways to assess}

comorbidities.13,15 _{Theassessmentofthe impactof}

comor-biditiesindifferentclinicaloutcomesinpatientswithRAis usually performedthrough asimple countingof the num-berofexistingcomorbiditiesfromaspecificlistestablished byresearchers.15 _{Usingsuchanapproach,eachconditionis}

equallyscored,irrespectiveofitsweight.15

Anotherwayofmeasuringcomorbiditiesinvolvestheuse ofvalidatedcomorbidityindexesforpredictingacertain clin-icaloutcome.13_{Mostofcomorbidityindexesaredesignedto}

determinemortality,whichisthecaseofCharlson comorbid-ityindex(CCI)16_{andKaplan–Feinsteinindex.}17_CCIhasbeen

developedbyCharlsonetal.,16_{andcontainsalistof19}

condi-tions,eachofthemhavingaweightaccordingtoitsone-year riskofdeath.Thereisalsoacomorbidityindexspecifically developedtopredictfunctionality,thefunctionalcomorbidity index(FCI).18_{FCIwasdevelopedbyGrolletal.}18_usinga

North-Americanpopulationaffectedmainlybyorthopedicproblems and that used the Quality of Life Questionnaire (SF-36) to quantifythesubjects’functionalcapacity.

throughtheHealthAssessmentQuestionnaire(HAQ)and/or bythephysicaldomaincomponentoftheQualityofLife Ques-tionnaire(SF-36);these toolswere developed toassess the functional capacity of patients in activities of daily living. Noneofthesestudieshasaddedmobilitytestsinthe assess-mentoffunctionality.Thus,thementionedstudies8–12_didnot

analyzetheassociationofcomorbiditieswithmobility limita-tioninpatientswithRA.

Thepurposeofthisstudywastoinvestigatetheassociation ofcomorbidities,measuredbythreeindicatorsofcomorbidity (totalnumberofcomorbidities,CCIandFCI)withmobility lim-itationandfunctionaldisabilityinpatientswithRA,aswellas toidentifywhichindicatorofcomorbidityismostappropriate todeterminethisassociation.

Methods

Studydesignandparticipants

Across-sectionalstudyincludingpatientswithRAwascarried outtoevaluatetheassociationofcomorbiditieswithmobility limitationandfunctionaldisabilityintheseindividuals.

Sixtypatientsparticipatedinthestudyandwererecruited from the Rheumatology Outpatient Clinic of Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Goiás(UFG)inthecityofGoiânia,from September13,2012 toAugust22,2013.

At inclusion, all patients met the American College of Rheumatology (ACR 1987) criteria for RA.19 _{Thosesubjects}

withhospitalizationduetoacuteinfectionintheperiodof sixmonthspriortotheinterviewandwithpresenceofsome temporarydisabilitymakingitimpossibletocarryout mobil-ity tests (e.g.,foot fracture) were excluded. Thestudy was approvedbytheResearchEthicsCommitteeoftheHospital das Clínicas (UFG)and all participantssigned aninformed consentform.

Assessmenttools

At the time study enrollment, patients completed a stan-dardizedquestionnaire,includingdetailsof:(i)demographic factorssuchasage,genderand self-reportedrace;(ii) pres-enceofapositiverheumatoidfactor(RF);(iii)diseaseduration; (iv)existing comorbidities;(v)historyoffallsina12-month periodprecedingtheinterview;(vi)useofwalkingaids;(vii) medications inuse; (viii)lifestyle habits (i.e., smoking sta-tus–currentorformersmoker,neversmoked)andphysical activitypractice.Thisquestionnairewassupplementedwith informationfromparticipants’medicalrecords.

In this standardized questionnaire, comorbidities were evaluatedthroughalistofchronicdiseases,accordingtothose coveredbyCCI16_andFCI.18_{Thepresenceofotherchronic}

dis-easesnotincludedintheseindexesbutreportedbypatients andconfirmedintheirmedicalrecordswasalsoregistered. Fromthesecollecteddata,comorbiditiesweremeasuredby threeindicators:(i)totalnumberofcomorbidities(NCom);(ii) CCIscore;and(iii)FCIscore.

CCIiscomposedofalistof19comorbidities,andeach dis-easehasaweightrangingfrom1to6,establishedaccording

toitsone-yearriskofdeath.16_{ThescoreobtainedinCCIis}

assigned by summing all comorbiditiespresent with their respective weights, resulting in a number which can vary from0to33.16

FCIisalistof18comorbidities,withnodifferenceinweight amongthem.18_{FCIscoreisobtainedbysummingall}

comor-bidities,rangingfrom0to18.18

Inthe“connectivetissuediseases”itemcontemplatedin CCI, thetool consideredas “comorbidcondition” the pres-ence ofsystemiclupuserythematosus,polymyositis,mixed connective tissue disease and polymyalgia rheumatica, as suggestedbyCharlsonetal.16_{Ontheotherhand,inFCI,in}

its“arthritis” item,onlypresenceofosteoarthritiswas con-sidered.

DiseaseactivitywasassessedbytheDiseaseActivityScore basedon28jointsandonESRvalue(DAS-28/ESR).20

To assess mobility limitation, the following tests were applied:(i)Five-Times-Sit-to-StandTest(STS)21_and(ii)Timed

UpandGoTest(TUG).22

STStestisusedtoevaluatemusclestrengthoflowerlimbs, mobilityandriskoffalls.21,23,24_{Thistest,measuresthefastest}

timetostandandsitfiveconsecutivetimeswitharmsfolded. Thelongerthetimespenttocompletethetest,theworsethe individualmobility.21

TUGtestisusedtoidentifypatientsatriskoffallsandwith mobility restriction.22,25 _{Toperformthis test,the patientis}

timedwhiletheyrisefromanarmchair,walkatacomfortable andsafepacetoalineonthefloor3maway,turnandwalk backtothechairandsitdownagain.Thegreaterthetime,the worsetheindividualmobility.22

FunctionaldisabilitywasmeasuredbytheHealth Assess-mentQuestionnaire(HAQ).26,27

Statisticalanalysis

Continuousdataareshownasmean(standarddeviation[SD]) ormedian(interquartilerange[IQR]),whereappropriate,and categoricaldatawereshownasfrequency(percentages).

Aregressionanalysisusingquasi-likelihoodmodel,28_with

variancefunctionproportionaltothemeanandlogarithmic link function, was carried out, in order to investigate the associationofindicatorsofcomorbidity(NCom,CCIandFCI) withmobilitylimitation(STSandTUG)andfunctional disabil-ity(HAQ).Tomonitortheeffectofconfounding variables,a linearregression modelusingstepwise regressionwas con-structed.Thepotentialconfounding variableschosenwere: age, gender, disease duration,physicalactivity, positive RF test,DAS-28/ESRscore.

The final model ofmultiple regression analysis for the dependentvariablesSTS,TUGandHAQwascalledstepwise log-linearregression.

Thecomparisonbetweencomorbidityindicators,withthe aimtoestablishthemostappropriatetooltodeterminethe association of comorbidities with mobility limitation and functional disabilityinpatientswithRA,wasperformedby comparingthecoefficientsofdetermination(R2)ofadjusted modelsagainsteachindicator.29

Table1–Characteristicsofparticipants.

Characteristics Values

Demographics

Age,mean(SD)(min–max),years 59(9.1)(43–80)

Women,n(%) 53(88.3%)

Self-reportedrace,n(%)

Caucasian 26(43.3%)

African 11(18.3%)

Brown 23(38.3%)

PositiveRF,n(%) 43(71.7%)

Diseaseduration,mean(SD)(min–max),years 11.5(8.9)(0.4–30) Historyoffalls,n(%) 16(26.7%) Useofwalkingaids,n(%) 8(13.3%) Smokersorformersmokers,n(%) 37(61.7%) Practitionersofphysicalactivity,n(%) 10(16.7%)

Evaluationofcomorbidities

NComscore,mean(SD)(min–max) 3.6(2.1)(0–8) CCIscore,mean(SD)(min–max) 0.25(0.51)(0–2) FCIscore,mean(SD)(min–max) 2.0(1.5)(0–5)

Diseaseactivityassessment

ESR,median(IQR),mm/hour 22.5(10.5–34.5) DAS-28/ESR,mean(SD)(min–max) 3.7(1.4)(0.5–6.8)

Mobilityassessment

STS,median(IQR),seconds 12.5(10.5–20.4) TUG,median(IQR),seconds 12.8(10.9–16.3)

Assessmentoffunctionalcapacity

HAQscore,mean(SD)(min–max) 1.07(0.76)(0–3)

SD,standarddeviation;IQR,interquartilerange;RF,rheumatoid factor;NCom,totalnumberofcomorbidities;CCI,Charlson comor-bidityindex;FCI,functionalcomorbidityindex;ESR,erythrocyte sedimentationrate;DAS-28/ESR,DiseaseActivityScorebasedon 28jointsandonESRvalue;STS,Five-Times-Sit-to-StandTest;TUG, TimedUpandGoTest;HAQ,HealthAssessmentQuestionnaire.

Results

Clinicalfeaturesofparticipants

Sixtypatientsparticipatedinthestudy.Patientcharacteristics aresummarizedinTable1.

Table2depictsthecomorbiditiesthatmakeupCCIandFCI, aswellasthenumberofpatientsaffectedbyeach comorbid-itypresentintheseindexes.Theprevalenceofcomorbidities given byCCI was 21.7%, i.e., 13 patients had at least one comorbidity,accordingtothisindicator.Intheotherhand,the evaluationbyFCIshowedthat49(81.7%)patientshadatleast onecomorbidity.

Patients had other comorbidities, besides those shown inTable2,suchasfibromyalgia,anemia,epilepsy, hypothy-roidism, secondarySjögren syndrome and cardiac arrhyth-mias.Thus,theprevalenceofcomorbiditiesgivenbyNCom was90%,i.e.,54patientshadatleastonecomorbidity.

Analysisoftheassociationofcomorbiditieswithmobility limitationandfunctionaldisability

Table3summarizeslog-linearregressionunivariateanalyses offactorsassociatedwithmobilitylimitation(STSandTUG) andfunctionaldisability(HAQ)inpatientswithRA.

The independent factors that significantly explain part ofthe variability ofSTSin the univariatemodelwere: age (coefficientofdetermination[R2]=0.074;p=0.023),male gen-der(R2_{=0.058;p=0.049),diseaseduration(R}2_{=0.056;p=0.042),}

NCom score (R2_{=0.121; p=0.005) and FCI score (R}2_=0.191, p<0.001).Theindependentfactorsassociatedwith variabil-ity of TUG in the univariate model were: age (R2_=0.063; p=0.052), NCom score (R2=0.144, p=0.005) and FCI score (R2_{=0.195; p=0.001). On the other hand, the independent}

factors associated with variability of HAQ in the univari-atemodelwere:diseaseduration(R2_{=0.047;p=0.040),NCom}

score(R2_{=0.077;p=0.012),FCIscore(R}2_{=0.178,p<0.001)and}

DAS-28/ESR(R2_{=0.244,p<0.001)(Table3).}

Thelog-linearregressioncurvesofthemainindependent factorsassociatedwithvariabilityofmobility(STSandTUG) andfunctionalcapacity(HAQ)areshowninFig.1.

Inthefinalmodeloflog-linearregressionusingstepwise regression with respecttofactors associated withmobility limitation(STSandTUG),onlythe“comorbidities”factor, eval-uatedbyFCI,wassignificant(Table4).Theexponentvalues ofbetacoefficient(expˇ)fortheassociationbetweenFCIand STSwas1.128(95%confidenceinterval[95%CI]1.062–1.201;

p<0.001);andforTUGwas1172(95%CI1.073–1.285;p=0.001) (Table4).

Astofactorsassociatedwithfunctionaldisability(HAQ)in thefinalmodel,thefollowingvariablesweresignificant: dis-easeactivity,measuredbyDAS-28/ESR(expˇ=1.279, 95%CI 1.132–1.451; p<0.001)and comorbiditiesasassessedbyFCI (expˇ=1.167,95%CI1.054–1.290;p=0.005)(Table4).FCIand DAS-28/ESRfactorsweresignificanttoexplain,together,32.9% ofthevariabilityofHAQscore(adjustedR2_{=0.329)(Table4).}

Comparisonamongcomorbidityindicators

FCIprovedtobethemostappropriatecomorbidityindicator todeterminetheassociationofcomorbiditieswithmobility limitation(STSand TUG)and functionaldisability(HAQ)in patients withRA,accordingtovalues ofthe coefficientsof determination(R2_{)ofcomorbidityindicators(NCom,CCIand}

FCI)(Table3).

TheR2_{valueforanassociationbetweenFCIandSTSwas}

0.191;forTUGwas0.195;andforHAQwas0.178.Ontheother hand,R2_{betweenNComandSTSwas0.121;forTUG,R}2_=0.144;

andforHAQ,R2_{=0.077.AndtheR}2_{valuebetweenCCIandSTS}

was0.021;forTUG,R2=0.000;andforHAQ,R2=0.000(Table3).

Discussion

This study demonstrated the association of comorbidities withmobilitylimitationandfunctionaldisabilityinpatients withRAandindicatedFCIasanappropriatecomorbidityindex indeterminingthisassociation.

Table2–ComorbiditiesthatcomposetheCharlson

comorbidityindexandthefunctionalcomorbidityindex

andnumberofaffectedpatients.

Comorbidities n

Osteoporosis 28

Arthritis(osteoarthritis)b ₂₇ Visualdeficits(cataract,glaucoma,macular

degeneration)b

17

Obesityand/orBMI>30kg/m2b ₁₂

Uppergastrointestinaltractdisease(ulcer,hernia, reflux)a,b

11

Diabetesmellitustype2a,b ₉

Depressionb ₅

Anxietyorpanicsyndromeb ₃

Auditorydeficits(difficultyhearing,even withhearingaids)b

3

Congestiveheartfailurea,b ₁

Peripheralvasculardiseasea,b ₁

Cerebrovasculardiseasea,b ₁

Chronicobstructivepulmonarydiseasea,b ₁

Asthmab ₁

Neurologicaldisease(Parkinson’sdisease)b ₁

Connectivetissuediseasea ₀

Liverdisease(mild,moderateorsevere)a ₀

Anginab_{/myocardialinfarction}a,b ₀

Degenerativediskdisease(spinalstenosis,orsevere chroniclowbackpain)b

0

Dementiaa ₀

Hemiplegiaa ₀

Moderateorseverekidneydiseasea ₀

Non-metastaticsolidtumora ₀

Leukemiaa ₀

Lymphomaa ₀

Solidmetastatictumora ₀

AIDSa ₀

CCI, Charlson comorbidity index; FCI, functional comorbidity index;BMI,bodymassindex;AIDS,acquiredimmunodeficiency syndrome.

a _{ComorbiditypresentinCCI.}

b _{ComorbiditypresentinFCI.}

was32.9%;and“diseaseactivity”,measuredbyDAS-28/ESR, wasthemainvariableresponsibleforexplainingpartofthis variability, followed bythe factor “comorbidities”,assessed byFCI. In the finalmodel – afterFCI and DAS-28/ESRhad explainedpartofthevariabilityofHAQscore,andafterFCI hadexplainedpart ofthevariabilityofSTSand TUG–the remaininganalyzedvariablesdidnotcontributesignificantly toexplain the mobilitylimitation and functional disability observed,showingtheimportanceofthefactor “comorbidi-ties”inthefaceofothervariables,suchasage,gender,disease duration,physicalactivityandapositiveRF.

FunctionaldisabilityinRAischaracterizedbyits multi-dimensionality,beingassociatedwithmultiplefactors,aside thefactor“comorbidities”,8–12_suchaspain,30,31_reducedjoint

mobility,30_{articularcartilagedestruction,}32_{decreasedmuscle}

strength,31_{diseaseduration}33_{anddiseaseactivity.}31

Theassociationofcomorbiditieswithfunctionaldisability inpatientswithRAhasbeenshowninsomestudies,8–12 _in

whichtheauthorsassessedthefunctionalcapacityofpatients throughactivitiesofdailylivingquestionnaires(HAQand/or SF-36).

Toour knowledge,thisis thefirst study onRApatients todeterminetheassociationofcomorbiditieswithmobility limitationmeasuredbytimedtests(STSandTUG).

ThefactthatRAisresponsibleforageneralimpairment intermsoffunctionalstatusofpatients,causingimpairment inactivitiesofdailyliving,musclestrengthandmobilityand increasing the risk offalls, emphasizes the importanceof mobilitystudiesinthispopulation.31,34,35

Theriskoffallscanbeevaluatedthroughthetimespent toperformSTSandTUGtests24,25,36_{and,inparallel,studies}

haveshownaworseperformanceonthesetestsinpatients withRA,whencomparedtothepopulationwithoutRA.37,38

Böhleretal.36_{showedthatdiseaseactivityandfunctional}

disability (HAQ) in patientswith RAcorrelated with worse performanceinSTSandTUGtests;but theauthorsdidnot evaluatethe association ofcomorbidities withriskoffalls. Jamisonetal.39_{demonstratedthatpatientswithRAwitha}

his-toryoffallsexhibitedahighernumberofcomorbiditiesthan thosewithoutsuchhistory,drawingattentiontothe associa-tionbetweencomorbiditiesandtheoccurrenceoffallsinthis population.AsoccurredinthestudybyBöhleretal.,36_Jamison

etal.39_{havenotstudiedtheassociationofcomorbiditieswith}

performancetestsforfallriskassessment(STSandTUG). Thestudyoffactorsassociatedwithriskoffallsinpatients with RA isa relevant task, sincethe risk of fallsin these patientsisincreased.34–37,39,40_{Falls,inturn,arerelatedtothe}

occurrenceoffractures;andthiscontingencyhastheeffect ofcompromisingthefunctionality,worseningtheprognosis ofrheumatologicdiseases.35_{Alsonoteworthyisanincreased}

prevalenceofosteoporosisinpatientswithRA.11,13,15_Inour

study,28patients(47%)hadosteoporosis,andthisisa comor-biditywhichincreasesfracturerisk.37,41

In the present study, we evaluated the association of comorbiditieswithmobilitylimitationandfunctional disabil-ity inpatients with RAby computingthe total number of comorbidities(NCom)and throughthe scoreobtainedwith theuseofCCIandFCI.

FCIprovedtobethemostappropriatecomorbidity indica-torindeterminingthisassociation,whencomparedtoNCom andCCIinoursample.Theassociationofcomorbidities evalu-atedbyFCIwasstrongerversusthatmeasuredbyNCom.This resultwasexpected,sinceFCIhasbeenspeciallydeveloped asatooltopredictfunctionality.18_{Thisfindingishighlighted}

by the fact that RA patients studied often presentedwith comorbiditiespresentinFCI,thesebeingconditionsclearly associatedwithfunctionalimpairment.18

Ontheotherhand,thelackofassociationofthose comor-biditiesassessedbyCCIinoursample,notwithstandingthe demonstrationofthisrelationshipwiththeuseofCCIinother studies,8,9,11_{canbeexplainedintwoways.First,wemust}

con-siderthatCCIwasprimarilydevelopedasaninstrumentto predictmortality.16_{Andsecondly,wedidnotfindinour}

sam-pleareasonableamountofcomorbiditiespertainingtothe calculationofICC,andthisfactmayhavehamperedthe abil-ity ofthis indexinpredictingfunctionalityinourpatients. Perhapsthisscenariowouldrequirealargersample,asthe comorbidities that make up CCI are not those most often foundinoutpatientswithRA.8,9,11

Table3–Analysisofindependentfactorsassociatedwithmobilitylimitation(Five-Times-Sit-to-StandTestandTimed

UpandGoTest)andfunctionaldisability(HealthAssessmentQuestionnaire).

Independentvariables Dependentvariables

STS TUG HAQ

Age,years R2 _0.074a _0.063a _0.002

Malegender R2 _0.058a _{0.010 0.000}

PositiveRF R2 _{0.000 0.000 0.000}

Diseaseduration,years R2 _0.056a _{0.020 0.047}a

Physicalactivity R2 _{0.000 0.003 0.013}

NComscore R2 _0.121b _0.144b _0.077b

CCIscore R2 _{0.021 0.000 0.000}

FCIscore R2 _0.191b _0.195b _0.178b

DAS-28/ESR R2 _{0.033 0.056 0.244}b

STS,Five-Times-Sit-to-StandTest;TUG,TimedUpandGoTest;HAQ,HealthAssessmentQuestionnaire;R2_{,coefficientofdetermination;RF,} rheumatoidfactor;NCom,totalnumberofcomorbidities;CCI,Charlsoncomorbidityindex;FCI,functionalcomorbidityindex;DAS-28/ESR, DiseaseActivityScorebasedon28jointsandonESRvalue.

Univariatelog-linearregressions. a _{Significantp≤ 0.05.}

b _{Significantp≤ 0.01.}

reportsandonmedicalrecords;thus,thisidentificationwas subjecttounderdiagnosis, whencompared toasystematic searchofassociateddiseases.Inaddition, inNCom indica-torallcomorbiditiesreportedbypatientsandpresentintheir medicalrecordswereconsidered,withoutestablishing spe-cificcriteriaonwhichdiseaseswouldbe,ornot,takeninto

account.ThismethodmayhavehamperedtheabilityofNCom indicatorindeterminingtheassociationwithfunctional dis-abilityinoursample,whereasotherstudieshavestressedthis association.10–12

Thus, it becomes apparent the importance of knowing whatarethemaincomorbiditiesthatultimatelyinfluencethe

DAS-28/ESR

FCI FCI

STS TU

G

HA

Q

HA

Q

30

10

3

2

1

0

3

2

1

0

2 4 6

0 1 2 3 4 5 0 1 2 3 4 5

15 20

20 40 60

25

E(TUG) = exp{2.43 + 0.159(ICF)} E(TSL) = exp{2.46 + 0.116(ICF)}

E(HAQ) = exp{–1.05 + 0.282(DAS–28)} E(HAQ) = exp{–0.42 + 0.217(ICF)}

FCI

0 1 2 3 4 5

Fig.1–Log-linearregressioncurvesofthemainpredictorsofmobilityvariability(Five-Times-Sit-to-StandTestandTimed UpandGoTest)andfunctionalcapacity(HealthAssessmentQuestionnaire).Scatterplotswithlog–linearregressioncurves.

STS,Five-Times-Sit-to-StandTest;TUG,TimedUpandGoTest;HAQ,HealthAssessmentQuestionnaire;FCI,functional

Table4–Impactofcomorbidity(functionalcomorbidityindex)anddiseaseactivity(DiseaseActivityScorebased

on28jointsandonESRvalue)inmobility(Five-Times-Sit-to-StandTestandTimedUpandGoTest)andfunctional

capacity(HealthAssessmentQuestionnaire).

Dependentvariables Independentvariables exp(ˇ) 95%CI p AdjustedR2

STS FCI 1.128 1.062–1.201 <0.001 0.191

TUG FCI 1.172 1.073–1.285 0.001 0.195

HAQ FCI 1.167 1.054–1.290 0.005 0.329

DAS-28/ESR 1.279 1.132–1.451 <0.001

STS,Five-Times-Sit-to-StandTest;TUG,TimedUpandGoTest;HAQ,HealthAssessmentQuestionnaire;exp(ˇ),exponentialofbetacoefficient; 95%CI,confidenceintervalof95%;R2_{,coefficientofdetermination;FCI,functionalcomorbidityindex;DAS-28/ESR,DiseaseActivityScorebased} on28jointsandonESRvalue.

Multivariatelog-linearregressionmodelusingstepwiseregression.

functionalityinpatients withRA;withthis,we canobtain moresuitable criteria,when establishingthe comorbidities associatedwithfunctionalstatusofthispopulation.

This study has relevance for pointing out the effect of

comorbiditiesonlimitingthemobilityand,hence,on increas-ingtheriskoffallsinpatientswithRA;itmustbetakeninto

accountthatthetestsused(STSandTUG)arerecommended

inthefallriskassessment.Inaddition,thestudyalsodraws attentiontotheuseofFCIasanalternativetooltoevaluate theimpactofcomorbiditiesonfunctionalityofpatientswith RA.

Inconclusion,thecomorbiditiesinpatientswithRAare associatedwithmobilitylimitationandfunctionaldisability; andtheindicatorFCIisanappropriatecomorbidityindexin thedeterminationofthisassociation.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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