Associations of Psoriatic Arthritis and Cardiovascular Conditions in a Large Population

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1 ville online: Originl rticle Associtions of Psoritic Arthritis nd Crdiovsculr Conditions in Lrge Popultion Svetln Kondrtiouk, DO Ntli Udltsov, PhD Arthur L Kltsky, MD Astrct Purpose: We studied the hypothesis tht possily vi shred inflmmtory mechnisms, psoritic rthritis (PsA) is ssocited with incresed prevlence of crdiovsculr (CV) conditions. Methods: Among multiethnic popultion of 76,465 men nd women with known demogrphics, we studied ll persons (n = 99) with confirmed outptient dignoses of PsA. Associtions of PsA with CV dignoses were studied in the entire popultion y logistic regression with six covrites. With two mtched control study sujects for ech study suject with PsA, selected risk trits for CV conditions t time of PsA dignosis were compred with findings on t-tests. Results: Study sujects with PsA did not exhiit more therothromotic disese (coronry nd cererovsculr) or dietes mellitus ut hd incresed prevlence of systemic hypertension nd hert filure compred with study control sujects. In the cse-control nlysis, study sujects with PsA hd lower men lood cholesterol, higher men ody mss index, nd higher men lood pressure compred with study control sujects; men lood glucose ws similr in oth groups. Conclusions: In this nlysis the ssocitions of PsA with CV risk fctors nd CV conditions re mixed. Except for incresed systemic hypertension, it is uncler whether PsA is relted to higher prevlence of CV disese. Introduction Psorisis is common inflmmtory skin condition with n extensive medicl literture. 1,2 Although less common, psoritic rthritis (PsA) hs lso een studied sustntilly, 1,3 6 ut there re only limited dt out PsA from popultionsed studies. Aville reports suggest reltions of oth psorisis 7,8 nd PsA 9,10 to therothromotic crdiovsculr diseses (CV), ut some studies re limited y smll numers of prticipnts, self-report of dignoses, nd homogeneity of study popultions. We present here the results of study of PsA in lrge, multiethnic, free-living popultion. We hypothesized tht PsA nd therothromotic vsculr conditions might e ssocited ecuse of shred underlying inflmmtory mechnisms. Thus, we exmined ssocited dignoses mde y physicins. A mtched cse-control nlysis yielded dt out selected trits usully considered risk fctors for CV disese. Becuse study sujects with PsA were determined from mong persons with known computer-stored previous dt, in the cse-control nlyses it ws possile to lso study chnges in the CV risk trits. Mterils nd Methods Study Popultion The study protocols were pproved y the institutionl review ord of the Kiser Permnente Medicl Cre Progrm. The study popultion consisted of 76,425 persons who, on Jnury 1, 1995, were memers of comprehensive prepid Northern Cliforni Helth Pln nd whose demogrphic trits were known from previous helth exmintions 11 for the period These persons re thought to represent cross-section of Helth Pln memers nd were clssified s follows: 43% men, 52% white, 30% Africn Americn, 11% Asin Americn, nd 5% Hispnic. The Helth Pln memers reflect the full socioeconomic spectrum of the generl popultion except for the extremes of income. Study Sujects with Psoritic Arthritis The dte for study popultion selection ws sed on the fct Svetln Kondrtiouk, DO, (left) is Hospitl-sed Specilist/Internist t the Wlnut Creek Medicl Center in CA. E-mil: svetln.kondrtiouk@kp.org. Ntli Udltsov, PhD, (center) is Dt Consultnt t the Division of Reserch in Oklnd, CA. E-mil: ntli.udltsov@kp.org. Arthur L Kltsky, MD, (right) is Senior Consultnt in Crdiology nd n Adjunct Investigtor t the Division of Reserch for the Kiser Permnente Medicl Cre Progrm in Oklnd, CA. E-mil: rthur.kltsky@kp.org. 4 The Permnente Journl/ Fll 2008/ Volume 12 No. 4

2 Associtions of Psoritic Arthritis nd Crdiovsculr Conditions in Lrge Popultion ORIGINAL Article tht outptient dignoses t visits to Helth Pln fcilities ws first stored in computers in Jnury We serched these computer files for dignoses of PsA (Interntionl Clssifiction of Diseses, 9th revision [ICD-9] code 696.0) through 2004, identifying 120 individuls (0.16%) with dignosis of PsA. A physicin investigtor performed detiled record review of the 120 possile study sujects with PsA for confirmtion of dignosis. Strong considertion ws given to cceptnce of the PsA dignosis if it ws mde y rheumtologist, ut inclusion ultimtely depended on compelling clinicl picture, including rdiologic evidence of erosive disese nd negtive findings on tests for rheumtoid fctor. Uncertin dignoses were resolved y consensus. We excluded 21 study sujects from nlysis either ecuse they did not fulfill PsA criteri estlished for this study or ecuse other (thn PsA) rheumtologic dignoses were judged more likely. Thus, there were 99 confirmed study sujects with PsA in the nlyses (0.13% of study sujects); of these, 50% were men, 70% were white, 8% were Africn Americn, 16% were Asin Americn, nd 2% were Hispnic. Anlysis of Coexistent Outptient Conditions These ssocitions were studied y logistic regression in ll 76,425 persons. Included were the following CV conditions (ICD-9 codes): systemic hypertension ( ), coronry hert disese ( ), hert filure (428), cererovsculr disese ( ), nd dietes mellitus (250). Dietes ws included ecuse from the risk viewpoint, it is widely considered coronry disese equivlent. Age-djusted nd multivrite logistic models used covrite dt otined from the helth exmintions, including self-clssified ethnicity, eduction, mritl sttus, ody mss index (BMI), cigrette smoking sttus, nd lcohol intke. These models yielded odds rtios (ORs) for reltions of PsA to ech coexistent condition, 95% confidence intervls (CIs), nd P vlues. For this study, we defined sttisticl significnce s p < Record Review nd Cse- Control Study Sujects In ddition to confirmtion of PsA dignosis, chrt review included strction of dt out weight, lood pressure, totl cholesterol, nd lood sugr t the time of dignosis. For ech confirmed study suject with PsA, two study control sujects were selected who were Helth Pln ptients t the time of first outptient PsA dignosis ut who were free of dignosed PsA, psorisis, nd other rheumtic inflmmtory conditions (rheumtoid rthritis, lupus erythemtosus, scleroderm, dermtomyositis, nd polyrteritis nodos). Ech study control suject ws mtched to the corresponding study suject with PsA for ge, sex, nd ethnicity. Dt similr to those for study sujects with PsA were strcted for these study control sujects, using dte for study control sujects closest to corresponding study sujects with PsA. Cse-Control Comprisons The mtched groups (study sujects with PsA vs study control sujects) were compred with student s t-test, with results expressed s χ-squre nd p vlues. In this mnner, we exmined trits t time of PsA dignosis, dt from the erlier exmintions, nd chnges in the mesurements etween the erlier exmintions nd dte of dignosis. Results Outptient Dignoses Associted with Psoritic Arthritis These ssocitions re presented in Tle 1. There ws incresed prevlence of systemic hypertension nd of hert filure mong the study sujects with PsA. In contrst, lthough the p vlues were >0.05 for ech, the ORs for ssocited coronry disese, cererovsculr Tle 1. Associtions of outptient dignoses with psoritic rthritis ICD-9 code (numer of study sujects with psoritic rthritis) Odds rtio 95% confidence intervl p vlue Systemic hypertension (38,461) Codes (48) Coronry hert disese 10,123) Codes (13) Hert filure (5809) Code 428 (11) Cererovsculr disese (7969) Codes (5) Dietes mellitus (12,206) Code 250 (10) Versus study control sujects without psoritic rthritis, y logistic regression, mong 76,425 persons. Covrites in models were ge, sex, rce/ethnicity, eduction level, ody mss index, smoking sttus, nd lcohol intke, determined t exmintions. Outptient dignoses Similr meditors re involved in the genesis of therosclerosis, therothromotic diseses, the group of trits known s metolic syndrome, nd systemic hypertension. 13,14 The Permnente Journl/ Fll 2008/ Volume 12 No. 4 5

3 Originl rticle Associtions of Psoritic Arthritis nd Crdiovsculr Conditions in Lrge Popultion Tle 2. Reltions of covrites nd other trits to psoritic rthritis Odds rtio Trit (referent) (95% confidence intervl) Age ( 10 yers) 0.9 ( ) Sex (femle/mle) 0.7 ( Ethnicity lck (white) 0.2 ( ) c Ethnicity Asin (white) 1.1 ( ) College grdute (no college) 1.3 ( ) Alcohol 1 2 drinks per dy (never) 0.8 ( ) Smoke >1 pck per dy (never smoker) 1.3 ( ) BMI kg/m 2 (<25 kg/m 2 ) 0.9 ( ) BMI >30 kg/m 2 (<25 kg/m 2 ) 1.7 ( ) BP >140/90 mm Hg (<120/80 mm Hg) 1.1 ( ) Totl lood cholesterol ( 10 mg/dl) 0.92 ( ) d Blood glucose ( 10 mg/dl) 0.9 ( ) Leukocyte count ( 1000/mm 3 ) 0.9 ( ) Odds rtios for exmintion trits in reltion to dignoses, y logistic regression; models include ge, sex, rce/ethnicity, mritl sttus, smoking sttus, lcohol intke. Continuous vrile. c p < d p < BMI = ody mss index; BP = lood pressure. disese, nd dietes mellitus were <1.0. Severl of the reltions of the covrites re presented in Tle 2. Age nd sex were unrelted to likelihood of the dignosis of PsA. Africn Americns hd lower PsA prevlence, ut there ws no difference etween Asin Americns, lrgely of Chinese or Filipino ethnicity, nd whites. Totl lood cholesterol level ws inversely relted to PsA. Unrelted trits included eduction level, oesity, hevy smoking, dily moderte lcohol drinking, BMI, lood pressure, lood glucose level, nd leukocyte count. Comprisons of Study Sujects with Psoritic Arthritis nd Mtched Study Control Sujects Cse-control comprisons for selected CV risk trits re shown in Tle 3. Men cholesterol levels were lower in study sujects with PsA thn in study control sujects oth t the erlier exmintions in nd t dte of dignosis. There were decreses in men cholesterol levels from the erlier to the lter mesures, slightly greter in the study sujects with PsA. The study sujects with PsA hd higher men BMI oth in nd t dignosis, ut the increse in BMI over time ws similr in oth groups. Men systolic nd distolic lood pressure ws similr in for study sujects with PsA nd study control sujects ut incresed more in the study sujects with PsA, resulting in significnt cse-control differences t time of dignosis. Blood glucose levels were similr in cses nd study control sujects t oth mesurements, nd they incresed to similr extent over time. Discussion Although the etiology of most rheumtic conditions is not well estlished, it is ccepted tht utoimmune phenomen nd chronic tissue inflmmtion re involved nd possily cusl. 9,12 The sme is true for psorisis, T-helper-cell type 1 immunologic inflmmtory skin disese 7 nd, presumly, for PsA, now clssified s one of the spondylorthritides. 6 In generl, T-cell ctivtion induces proinflmmtory cytokines nd chemokines tht re noxious to vriety of tissues. Similr meditors re involved in the genesis of therosclerosis, therothromotic diseses, the group of trits known s metolic syndrome, nd systemic hypertension. 13,14 Epidemiologic studies show tht therosclerosis hs numer of cusl risk fctors, severl of which (cigrette smoking, therogenic lipids, hypertension, nd hyperglycemi) involve cytokines, other ioctive sustnces, nd cells chrcteristic of the inflmmtory process. In fct, endovsculr inflmmtion is now considered involved in ll stges of therosclerosis development nd my well e cusl. 13,14 Despite the pprent similrities in hypotheticl noxious iologic pthwys relted to inflmmtion, the link etween rheumtic conditions nd therosclerosis remins sttisticl ssocition without estlished cusl mechnisms. We found inconsistent positive ssocitions of CV conditions with PsA. Although hypertension nd hert filure were ssocited, therothromotic disese ws not. Even though this could e interpreted s indicting lesser role for common systemic inflmmtory mechnisms thn we expected, inflmmtion is not the only possile mechnism for link mong therosclerosis, PsA, nd rheumtic conditions. 8 Shred CV risk fctors would e nother possile sis for link. Our dt show inconsistent evidence out shred risk trits lso, ut we did not hve dt out severl importnt potentil CV risk trits. Severl of these, such s mount physicl ctivity nd diet, 6 The Permnente Journl/ Fll 2008/ Volume 12 No. 4

4 Associtions of Psoritic Arthritis nd Crdiovsculr Conditions in Lrge Popultion ORIGINAL Article might e modulted y the presence of PsA. Incresed CV disese s consequence of tretment is nother interesting possiility. For exmple, use of nonsteroidl ntiinflmmtory medictions might increse risk of hypertension or of hert filure, the specific conditions we found relted to PsA. Finlly, shred genetic predilections re hypotheticlly possile, ut our dt cnnot evlute this spect. In the cse-control comprison, weight gin ws similr for study sujects with PsA nd study control sujects. The greter increse in lood pressure in study sujects with PsA could e sustntilly responsile for the hert filure disprity, especilly ecuse coronry disese, nother mjor risk fctor for hert filure, ws not more prevlent in the study sujects with PsA. Although this ws not strictly prospective nlysis, it is noteworthy tht there were no convincing reltions to the exmintion dt out lood pressure, lood glucose levels, or leukocyte count. The unexplined inverse reltion of totl lood cholesterol in to PsA might prtilly ccount for the sence of reltion of PsA to therothromotic disese. Leukocyte count, mrker of inflmmtion, ws unrelted to PsA ut hs previously een reported to e relted to cute myocrdil infrction in this popultion. 15 Not surprisingly, our dt do show tht the known reltively low prevlence of psorisis in Africn Americns 2 extends to PsA. Also, the dt show tht Asin Americns hve rtes of PsA similr to those of whites. Limittions of our study strt with the fct tht the smll numer of study sujects with PsA precluded the sttisticl power to demonstrte modest reltions to the condition. Another limittion ws our inility to study temporl reltions nd thus incident disese. We emphsize tht this ws not prospective nlysis. This should not ffect the dt out reltions of lifelong demogrphic trits (ge, sex, nd ethnicity) to PsA. However, the link the dt out eduction, BMI, smoking nd etween rheumtic lcohol-drinking hits, conditions nd nd lood tests in Tle therosclerosis 2 should not e overinterpreted s necessr- remins sttisticl ily indicting predictive ssocition trits. Strengths of the without study include the lrge, estlished multiethnic, reltively cusl stle cohort nd the fct mechnisms. tht ll dignoses were mde y physicins. We conclude tht PsA is ssocited with incresed prevlence of hypertension nd hert filure. However, evidence out other independent ssocitions etween PsA nd vsculr conditions is uncler. v Disclosure Sttement The uthor(s) hve no conflicts of interest to disclose. Tle 3. Cse-control comprisons for study sujects with psoritic rthritis Cses Study control sujects Difference p vlue Totl lood cholesterol (mg/dl) Men in Men t dignosis Men chnge Body mss index (kg/m 2 ) Men in Men t dignosis Men chnge Systolic lood pressure (mm Hg) Men in Men t dignosis Men chnge Distolic lood pressure (mm Hg) Men in Men t dignosis <0.001 Men chnge Blood glucose (mg/dl) Men in Men t dignosis Men chnge Mtched ge, sex, nd ethnicity. P vlues refer to cse-control comprisons. Dtes for study control suject dt were closest to those of dignosis of the mtched cse. The Permnente Journl/ Fll 2008/ Volume 12 No. 4 7

5 Originl rticle Associtions of Psoritic Arthritis nd Crdiovsculr Conditions in Lrge Popultion This study ws supported y grnt from the Kiser Foundtion Reserch Institute, Oklnd, CA. Dt collection from 1978 to 1985 ws supported y grnt from the Alcoholic Beverge Medicl Reserch Foundtion, Bltimore, MD. Acknowledgment Kthrine O Moore-Klopf of KOK Edit provided editoril ssistnce. References 1. Myers WA, Gottlie AB, Mese P. Psorisis nd psoritic rthritis: clinicl fetures nd disese mechnisms. Clin Dermtol 2006 Sep Oct;24(5): Schön MP, Boehncke WH. Psorisis. N Engl J Med 2005 My 5;352(18): Shee M, Urmoto KM, Gison LE, O Fllon WM, Griel SE. The epidemiology of psoritic rthritis in Olmsted County, Minnesot, USA, J Rheumtol 2000 My;27(5): Gelfnd JM, Gldmn DD, Mese PJ, et l. Epidemiology of psoritic rthritis in the popultion of the United Sttes. J Am Acd Dermtol 2005 Oct;53(4): Fitzgerld O, Dougdos M. Psoritic rthritis: one or more diseses? Best Prct Res Clin Rheumtol 2006 Jun;20(3): Mese P. Psoritic rthritis updte. Bull NYU Hosp Jt Dis 2006;64(1 2): Gelfnd JM, Neimnn AL, Shin DB, Wng X, Mrgolis DJ, Troxel AB. Risk of myocrdil infrction in ptients with psorisis. JAMA 2006 Oct 11;296(14): Kremers HM, McEvoy MT, Dnn FJ, Griel SEJ. Hert disese in psorisis. Am Acd Dermtol 2007 Aug;57(2): Hn C, Roinson DW Jr, Hckett MV, Prmore LC, Fremn KH, Bl MV. Crdiovsculr disese nd risk fctors in ptients with rheumtoid rthritis, psoritic rthritis, nd nkylosing spondylitis. J Rheumtol 2006 Nov;33(11): Christophers E. Comoridities in psorisis. Clin Dermtol 2007 Nov Dec;25(6): Collen MF, Dvis LF. The multitest lortory in helth cre. J Occup Med 1969 Jul;11(7): Frzneh-Fr A, Romn MJ. Accelerted therosclerosis in rheumtoid rthritis nd systemic lupus erythemtosus. Int J Clin Prct 2005 Jul;59(7): Person TA, Mensh GA, Alexnder RW, et l; Centers for Disese Control nd Prevention; Americn Hert Assocition. Mrkers of inflmmtion nd crdiovsculr disese: ppliction to clinicl nd pulic helth prctice: sttement for helthcre professionls from the Centers for Disese Control nd Prevention nd the Americn Hert Assocition. Circultion 2003 Jn 28;107(3): Hnsson GK. Inflmmtion, therosclerosis, nd coronry rtery disese. N Engl J Med 2005 Apr 21;352(16): Friedmn GD, Kltsky AL, Siegelu AB. The leukocyte count s predictor of myocrdil infrction. N Engl J Med 1974 Jun 6;290(23): Psorisis And Wrts I hve long hd the ide tht God creted psorisis nd wrts to tech dermtologists the merits of humility. Rtionl Drug Therpy, Vincent Joseph Deres, , Americn physicin 8 The Permnente Journl/ Fll 2008/ Volume 12 No. 4

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