Cardiovascular disease in persons with depressive & anxiety disorders

Transcription

1 Crdiovsculr disese in persons with depressive & nxiety disorders

2 124 chpter 7 crdiovsculr disese in persons with depressive nd nxiety disorders 125 ABSTRACT Bckground Associtions between depression, nd possibly nxiety, with crdiovsculr disese hve been estblished in the generl popultion nd mong hert ptients. This study exmined whether crdiovsculr disese ws more prevlent mong lrge cohort of depressed nd/or nxious persons. In ddition, the role of specific clinicl chrcteristics of depressive nd nxiety disorders in the ssocition with crdiovsculr disese ws explored. Methods Bseline dt from the Netherlnds Study of Depression nd Anxiety were used, including persons with current (i.e. pst yer) or remitted DSM-IV depressive or nxiety disorder (N = 2315) nd helthy controls (N = 492). Additionl clinicl chrcteristics (subtype, durtion, severity, nd psychoctive mediction) were ssessed. Crdiovsculr disese (stroke nd coronry hert disese) ws ssessed using lgorithms bsed on selfreport nd mediction use. Results Persons with current nxiety disorders showed n bout three-fold incresed prevlence of coronry hert disese (OR nxiety only = 2.70, 95% CI = ; OR comorbid nxiety/depression = 3.54, 95% CI = ). No ssocitions were found for persons with depressive disorders only or remitted disorders, nor for stroke. Severity of depressive nd nxiety symptoms - but no other clinicl chrcteristics - most strongly indicted incresed prevlence of coronry hert disese. Conclusion Within this lrge psychopthology-bsed cohort study, prevlence of coronry hert disese ws especilly incresed mong persons with nxiety disorders. Incresed prevlence of coronry hert disese mong depressed persons ws lrgely owing to comorbid nxiety. Anxiety - lone s well s comorbid to depressive disorders - s risk indictor of coronry hert disese deserves more ttention in both reserch nd clinicl prctice. Nicole Vogelzngs Adrie Seldenrijk Artjn TF Beekmn Hein PJ vn Hout Peter de Jonge Brend WJH Penninx Journl of Affective Disorders 2010; 125; INTRODUCTION In 1993 Frsure-Smith et l 1. showed tht fter myocrdil infrction, depressed persons were four-to-five times s likely to die within the next six months thn their nondepressed counterprts. Although this initil observtion turned out to overestimte the true reltionship between depression nd hert disese 2, since then, mny studies hve exmined their ssocition. Both depression nd hert disese re leding disorders when considering disese burden. The World Helth Orgniztion projected depression nd hert disese to become number 1 nd 2, respectively, on the list of diseses with the gretest loss of disbility djusted life yers in 2030 in high-income countries nd number 2 nd 3 worldwide 3. This suggests n enormous possible gin in public helth nd disese burden when depression, hert disese nd especilly their comorbidity could be prevented through incresing knowledge on the link between these two disbling diseses. Reserch thus fr hs minly focused on two kinds of popultions: hert disese ptients nd the generl popultion. Met-nlyses hve shown tht mong hert ptients depression is ssocited with n 1.8 to 2.6 incresed risk of subsequent crdiovsculr event or deth 2, 4, 5, while in the generl popultion depression increses risk of crdiovsculr disese (CVD) bout 1.6 to 1.8 times 2, 6-8. Although, s suggested by Nicholson et l. 2, these estimtes my still be inflted due to incomplete nd bised reporting of djustment for conventionl risk fctors nd CVD severity. Studies on prevlence of CVD within psychopthology-bsed popultion re lrgely lcking. From psychitrist perspective, it would be of gret importnce to know whether cliniclly depressed ptients indeed hve higher prevlence of CVD nd how much incresed exctly this prevlence is. Wht s more, it hs hrdly been ddressed whether specific chrcteristics of depression, such s ge of onset, durtion, or severity of the disorder could further determine the exct CVD probbility, or whether the ssocition is restricted to specific subtypes, such s typicl or melncholic depression. This knowledge could give insight into underlying mechnisms tht relte depression nd CVD s well s into which ptients should be most closely monitored for crdiovsculr dysfunctioning. Besides depression, some studies hve suggested nxiety to be ssocited with CVD s well Anxiety disorders led to comprble levels of disbility s depression nd hert disese 12 nd hve been found to increse risk of premture ll-cuse nd crdiovsculr deth 13, 14. The ssocition between nxiety nd CVD, however, hs been fr less studied thn the link between depression nd hert disese. Even less studied hs been the ssocition between nxiety chrcteristics (subtype, durtion, nd severity) nd CVD. Furthermore, s depression nd nxiety re often found to be co-morbid, it would be of gret importnce to study the ssocition between depression nd nxiety with CVD in concert. This could shed light on the specificity of ssocitions between depressive nd nxiety disorders nd CVD. Therefore, in the present study within lrge cohort of depressed nd/or nxious persons nd helthy controls we exmined the (extent of the) ssocition between the presence of psychitric dignosis of depressive nd/or nxiety disorder with CVD. In ddition, we ssessed the specificity of these ssocitions by directly compring depressive

3 126 chpter 7 crdiovsculr disese in persons with depressive nd nxiety disorders 127 with nxiety disorders nd by exmining whether specific chrcteristics of depressive nd/or nxiety disorders (subtype, durtion, severity, nd psychoctive mediction) could be identified tht indicte incresed probbility of CVD. MethodS Smple The Netherlnds Study of Depression nd Anxiety (NESDA) is n ongoing cohort study designed to investigte the long-term course nd consequences of depressive nd nxiety disorders. Prticipnts were 18 to 65 yers old t bseline ssessment in nd were recruited from the community (19%), generl prctice (54%) nd secondry mentl helth cre (27%). A totl of 2981 persons were included, consisting of persons with current or pst depressive nd/or nxiety disorder (N = 2329) nd helthy controls (N = 652). A detiled description of the NESDA study design nd smpling procedures cn be found elsewhere 15. The reserch protocol ws pproved by the Ethicl Committee of prticipting universities nd fter complete description of the study ll respondents provided written informed consent. As subclinicl symptoms of on the one hnd depressive nd nxiety disorders nd on the other hnd CVD could to certin degree resemble ech other (e.g. feeling tired or pin on the chest) nd could therefore flsely indicte or elevte n ssocition between them, persons with subthreshold symptoms of depression or nxiety but no forml dignosis of depressive or nxiety disorder (N = 158) nd persons who self-reported CVD without reporting ccompnying pproprite mediction use (N = 16) were excluded (see below for more detils), leving 2807 persons for the present nlyses. Psychopthology nd clinicl chrcteristics Presence of depressive disorder (mjor depressive disorder nd dysthymi) nd nxiety disorder (socil phobi, generlized nxiety disorder, pnic disorder nd gorphobi) ws estblished using the Composite Interview Dignostic Instrument (CIDI) ccording to DSM- IV criteri 16. The CIDI is highly relible nd vlid instrument for ssessing depressive nd nxiety disorders 17 nd ws dministered by specilly trined reserch stff. Bsed on CIDI, prticipnts were ctegorized s hving no, current (i.e. in pst yer), or remitted (lifetime, but not current) depressive nd/or nxiety disorder. In ddition, ctegoricl vrible ws constructed clssifying persons s hving no depressive or nxiety disorder, remitted depressive or nxiety disorder, current depressive disorder only, current nxiety disorder only, or current depressive nd nxiety disorder. Clinicl chrcteristics exmined included the subtype, durtion nd severity of the depressive or nxiety disorder. Next to CIDI dignoses, subtypes of depressive disorder included first onset versus recurrent mjor depressive disorder (bsed on CIDI interview), presence of n typicl symptom profile, nd presence of melncholic symptom profile. Atypicl symptom profile (mood rectivity nd 2 of hyperphgi, hypersomni, leden prlysis, nd interpersonl rejection sensitivity) ws constructed by comprison of items of the 28-item self-report Inventory of Depressive Symptoms (IDS 18 ) with DSM-IV criteri for typicl depression following Novick s lgorithm 19. Similrly, melncholic symptom profile (lck of mood rectivity or loss of plesure nd 3 of distinct mood qulity, mood worse in morning, erly morning wkening, psychomotor retrdtion or gittion, norexi/ weight loss, nd guilt feelings) ws constructed bsed on comprison of IDS items with DSM-IV criteri using the lgorithm proposed by Khn 20. Additionlly, for both depressive nd nxiety disorders distinction ws mde between lte onset ( 30 yers old) nd erly onset (< 30 yers old) of the psychitric disorder, s derived from the CIDI interview. Using the Life Chrt method 21, detiled ccount of the presence of depressive nd nxiety symptoms during the pst four to five yers ws ssessed mong persons with depressive or nxiety disorders. From this, the percent of time ptients reported depressive or nxiety symptoms ws computed s mesure of durtion. Severity of depressive symptoms ws ssessed by mens of the IDS; severity of nxiety symptoms by mens of the 21-item Beck Anxiety Inventory (BAI 22 ). To ccount for possible psychoctive mediction effects, mediction use ws ssessed bsed on drug continer inspection of ll drugs used in the pst month nd clssified ccording to the World Helth Orgniztion Antomicl Therpeutic Chemicl (ATC) clssifiction 23. As effects of psychoctive mediction re likely negligible when used infrequently, use of psychoctive mediction ws only considered present when tken on regulr bsis (t lest 50% of the time). Antidepressnts included selective serotonin reuptke inhibitors (ATC-code N06AB), tricyclic ntidepressnts (N06AA) nd other ntidepressnts (N06AF/N06AX). Benzodizepines included ATC-codes N03AE, N05BA, N05CD nd N05CF. Crdiovsculr disese Crdiovsculr disese (CVD) included stroke, ngin pectoris, myocrdil infrction, percutneous trnsluminl coronry ngioplsty nd coronry rtery bypss grfting nd ws djudicted using stndrdized lgorithms considering self-report nd mediction use (bsed on drug continer inspection nd ATC coding). During the interview, prticipnts were sked if they ever hd stroke, hert condition or hert ttck, nd to specify the kind of condition. In ddition, it ws sked whether subjects were ever troubled by chest pin during physicl strin nd whether the pin disppered within 10 min fter stnding still or tking tblet under the tongue. If subjects responded positively on both questions this ws regrded s n indiction of ngin pectoris (symptoms). Stroke ws identified by self-report supported by use of either nticogulnt/ntipltelet gents (ntithrombotic gents [ATC-code B01], cetylslicylic cid [N02BA01; 50% use of 100 mg], or crbslte clcium [N02BA15]), ny mediction for hypertension (ntihypertensives [C02], diuretics [C03], bet blocking gents [C07], clcium chnnel blockers [C08], gents cting on reninngiotensin system [C09]), or lipid modifying gents (C10). Angin pectoris nd myocrdil infrction were only considered present when self-report (or symptoms) of the disese ws supported by use of mediction for coronry hert disese (CHD; bet blocking gents [C07], nitrte vsodiltors [C01DA], clcium chnnel blockers [C08], or nticogulnt/ ntipltelet gents [B01, N02BA01 50% use of 100 mg, N02BA15]). When self-report ws not confirmed by mediction use, CVD ws considered to be undetermined nd

4 128 chpter 7 crdiovsculr disese in persons with depressive nd nxiety disorders 129 subjects were excluded from the nlyses (N = 16). When ngin symptoms (N = 510) were not supported by mediction use, persons were considered s hving no CVD (N = 413). Percutneous trnsluminl coronry ngioplsty nd coronry rtery bypss grfting were bsed on self-report only. CVD ws subdivided into stroke nd CHD (ngin pectoris, myocrdil infrction, ngioplsty or bypss). For sensitivity nlyses, s bet blockers re sometimes prescribed for nxiety symptoms, secondry mesure of CHD excluded persons with symptoms of ngin pectoris nd use of bet blocker only (N excluded = 32). Covrites Sociodemogrphic chrcteristics included ge, sex, nd yers of eduction. As lifestyle chrcteristics cn be ssocited with both CVD nd depression/nxiety, smoking sttus (never, former, current), lcohol intke (< 1, 1-14, > 14 drinks per week), physicl ctivity (mesured with the Interntionl Physicl Activity Questionnire 24 in MET-minutes [rtio of energy expenditure during ctivity compred to rest times the number of minutes performing the ctivity] per week) nd body mss index (BMI; weight in kilogrms divided by height in meters squred) were ssessed. Sttisticl nlyses Smple chrcteristics were compred cross persons with nd without CVD using independent t-tests for continuous vribles nd χ 2 tests for dichotomous nd ctegoricl vribles. Logistic regression nlyses ssessed the ssocition with CVD for depressive nd nxiety disorders seprtely nd simultneously, before nd fter djustment for priori selected covrites (sociodemogrphic [ge, sex, yers of eduction] nd lifestyle [smoking sttus, lcohol intke, physicl ctivity, BMI]). Next, consistency of ssocitions with regrd to CVD were ssessed by conducting seprte djusted logistic regression nlyses for subtypes of CVD (stroke nd CHD) nd subtypes of CHD (ngin pectoris, myocrdil infrction, nd CHD surgery [ngioplsty or bypss]). Specificity of ssocitions with regrd to clinicl spects of the depressive or nxiety disorder ws ssessed in sub-smple of persons with current depressive nd/or nxiety disorders using sociodemogrphic-djusted logistic regression nlyses. First, the ssocition with CVD of depressive disorder versus nxiety disorder ws directly compred. Second, ssocitions between specific depressive disorder or nxiety disorder chrcteristics (subtype, durtion, severity, nd psychoctive mediction use) nd CVD were exmined. Results Men ge of the present smple ws 41.8 (SD = 13.0) yers, 66.4% were women, 19.4% hd remitted nd 63.1% hd current depressive or nxiety disorder, while 5.6% hd CVD. Tble 1 describes smple chrcteristics compring persons with nd without CVD. Persons with CVD were older, more often men, less educted, more often former smoker, less often moderte drinker, nd hd higher BMI. Also, persons with CVD more often hd current nxiety disorder, but not depressive disorder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mple chrcteristics by crdiovsculr disese sttus Bsed on independent t-test for continuous vribles nd χ 2 tests for dichotomous nd ctegoricl vribles.

5 130 chpter 7 crdiovsculr disese in persons with depressive nd nxiety disorders 131 Tble 2 describes the results of undjusted nd djusted logistic regression nlyses ssessing the ssocition of depressive nd nxiety disorders with CVD. Remitted disorders were not sttisticlly significntly ssocited with CVD, but fter djustment current depressive nd current nxiety disorders were (OR = 1.59, 95% CI = ; OR = 2.18, 95% CI = , respectively). When the presence or bsence of depressive or nxiety disorder ws combined in one ctegoricl vrible, odds of CVD were incresed for persons with current nxiety disorder lone (OR = 1.96, 95% CI = ) s well s for those with combined current nxiety nd depressive disorder (OR = 2.35, 95% CI = ) compred to helthy controls. Incresed likelihood of CVD ws not observed for persons with current depressive disorder only (OR = 0.93, 95% CI = ). Next, effects of depression/nxiety sttus were ssessed seprtely for odds of hving stroke nd odds of hving CHD (Tble 3). Depressive nd nxiety disorders were not ssocited with stroke. In contrst, persons with current nxiety disorder were 2.5 to 3.5 times more likely to hve CHD (OR nxiety only = 2.70, 95% CI = ; OR nxiety nd depression = 3.54, 95% CI = ). No significnt ssocition ws found for persons with depressive disorder only (OR = 1.41, 95% CI = ). To gin some insight into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ssocition of depressive nd nxiety disorders with crdiovsculr disese Bsed on logistic regression nlyses undjusted nd djusted for ge, sex, yers of eduction, smoking sttus, lcohol intke, physicl ctivity nd body mss index. the direction of the ssocition between psychopthology nd CHD, we repeted the current nlysis mong persons with n erly onset ( 30 yers) of depressive or nxiety disorder (N excluded = 269). Since CHD hrdly occurs before the ge of 30, n erly onset suggests tht psychopthology ws present before CHD. Within persons with n erly onset of depressive or nxiety disorder similr results were found (OR depression only = 1.37, 95% CI = ; OR nxiety only = 2.37, 95% CI = ; OR nxiety nd depression = 3.26, 95% CI = ; dt not tbulted). An dditionl nlysis excluded persons (N = 32) who erned their sttus of CHD only bsed on ngin symptoms nd use of bet blocker -sometime used to relieve nxiety symptoms -, but substntil ssocitions remined (OR nxiety only = 2.06, 95% CI = ; OR nxiety nd depression = 2.89, 95% CI = ; dt not tbulted). When exmining CHD subtypes (ngin pectoris, myocrdil infrction, nd CHD surgery) ssocitions for current nxiety disorder (with or without depressive disorder) were found for ll (see Tble 3). Depressive disorders lone lso showed incresed odds of especilly ngin pectoris nd myocrdil infrction, but these were not sttisticlly significnt. Becuse ssocitions of psychopthology were only found with CHD nd not stroke, ll following nlyses were conducted with CHD s the outcome. Figure 1 shows tht within persons with current psychopthology (N = 1770), persons with current nxiety disorder hd lmost 80% incresed odds to hve CHD compred to persons with current depressive disorder (OR = 1.77, 95% CI = ), lbeit this ws not sttisticlly significnt. Odds of CHD for persons hving n nxiety disorder in ddition to depressive disorder were more thn twofold incresed compred to hving depressive disorder lone (OR = 2.40, 95% CI = ). Tble 4 shows the results of seprte sociodemogrphic-djusted logistic regression nlyses exmining ssocitions of depressive nd nxiety disorder chrcteristics with CHD in the sub-smple of persons with current psychopthology (N = 1770). No specific subtype of depressive disorder ws ssocited with CHD. For persons with current nxiety disorder ssocitions with CHD were consistent for persons with generlized nxiety disorder, socil phobi, pnic disorder nd gorphobi. Durtion of depressive or nxious complints ws lso not ssocited with CHD. However, the severity of depressive symptoms (OR per SD increse=1.32, 95%CI= ) nd of nxiety symptoms (OR per SD increse=1.36, 95%CI= ) were significntly ssocited with CHD. In fct, it ppered tht the results from Figure 1 showing somewht higher OR in persons with comorbid depression nd nxiety in comprison to the OR in persons with nxiety disorders lone could be explined by severity of symptoms. After dditionl djustment for severity of depressive nd nxiety symptoms, odds of CHD for persons with nxiety disorders were eqully incresed, irrespective of dditionl depressive disorder (OR nxiety only=1.86, 95%CI= ; OR nxiety nd depression=1.95, 95%CI= ). Lstly, psychoctive mediction use did not sttisticlly significntly increse odds of CHD, but trend ws found for use of benzodizepines nd higher odds of CHD (OR=1.60, 95%CI= ). Benzodizepine use did not ffect the before presented results (i.e. ORs of CHD s presented in Tble 3 nd Figure 1 were very similr fter dditionl djustment for benzodizepine use).

6 132 chpter 7 crdiovsculr disese in persons with depressive nd nxiety disorders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urrent depressive disorder N = 418 Current nxiety disorder N = 504 Current depressive nd nxiety disorder N = 848 Figure 1. OR for coronry hert disese in persons with current depressive nd/or nxiety disorder 'D..-35#,-).-//01-#,0/+.,-.# +3E6# >;AB#:;C>@%;<A# #;A># >;%C# :;<:@$;?B# ;A%# A;B:# :;%:@%;A:# ;?># Bsed on logistic regression nlyses djusted for ge, sex, nd eduction. 'D..-35# #,0/+.,-.#+3E6# >;C<#A;AB@<;AA# #;:># =;?<# A;:=@AA;BB#;:%# >;B$# :;$?@<;B<# ;:B# 'D..-35#,-).-//01-#23,# #,0/+.,-.#?;$B#>;A?@AA;?$# F;::A#?;<%# A;?B@A%;?<#;:A# >;>?# :;<$@B;=<# ;A=# Discussion # # TABLE 3. Assocition of depressive nd nxiety disorders with crdiovsculr disese subtypes Bsed on logistic regression nlyses djusted for ge, sex, yers of eduction, smoking sttus, lcohol intke, physicl ctivity nd body mss index; in ll nlyses the specific crdiovsculr disese or coronry hert disese subtype ws compred to persons without ny crdiovsculr disese (N = 2651). This study exmined the ssocition between dignosed depressive nd nxiety disorders nd crdiovsculr disese within lrge cohort of depressed nd/or nxious persons nd helthy controls. The results show tht, individully, both depressive nd nxiety disorders re ssocited with CVD. However, the incresed prevlence of CHD mong depressive persons ppered to be minly owing to comorbidity of nxiety disorders. No ssocitions were found with stroke. Severity of depressive nd nxiety symptoms - but no other clinicl fctors - identified those with the highest prevlence of CHD. Reltively few studies hve exmined the link between nxiety nd CHD nd most of these studies ssessed nxiety symptoms, but not dignosis. Although the link between nxiety (symptoms) nd CHD hs been more consistently found in initilly CHD-free popultions thn mong hert ptients, 25 recent study 26 showed tht both generlized nxiety disorder, s well s severity of nxiety symptoms were ssocited with n incresed risk of mjor dverse crdic events in ptients with stble coronry rtery disese. Our results demonstrte tht within psychopthology-bsed popultion the prevlence of CHD is incresed cross wide rnge of dignosed nxiety disorders (socil phobi, generlized nxiety disorder, pnic disorder nd gorphobi). In fct, persons who suffered from ny nxiety disorder in the pst yer were bout three times s likely to

7 134 chpter 7 crdiovsculr disese in persons with depressive nd nxiety disorders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hve CHD. Given the widespred prevlence of nxiety disorders, these results suggest tht the role of nxiety disorders in CHD is importnt nd hs been lrgely overlooked thus fr. These findings lso suggests tht crdic symptoms in nxiety persons might relly indicte hert disese nd underdignosing hert disese in nxiety ptients might be problem. The possible overlp in symptoms between nxiety disorders nd hert disese could lso pose problem in exmining the ssocition between these two. We tried to hndle this issue by only including definite cses of nxiety nd by confirmtion of mediction use pproprite for CVD. Even when further excluding persons with symptoms of chest pin nd use of bet-blocker only - sometimes described to relieve nxiety symptoms - ssocitions of nxiety disorders with CHD remined. Moreover, ssocitions between nxiety disorders nd CHD were found cross different types of both CHD nd nxiety disorders nd were not confined to for instnce ngin pectoris nd pnic disorder, supporting the conclusion tht the strong ssocition observed between nxiety nd CHD is rel. TABLE 4. Assocition of depressive nd nxiety disorder chrcteristics with coronry hert disese CHD = coronry hert disese. Bsed on logistic regression nlyses djusted for ge, sex, nd eduction; ech line represents single nlysis; b within sub-smple of persons with current (pst yer) depressive disorder: N = 1266; first onset vs. recurrent: persons with dysthymi only (N = 44) were excluded; c within sub-smple of persons with current (pst yer) nxiety disorder: N = 1352; d within sub-smple of persons with current (pst yer) depressive nd/or nxiety disorder: N = 1770; e per SD increse: IDS: SD = 12.9; BAI: SD = Although depressive disorder dignosis ws ssocited with CVD, this reltionship ppered to be lrgely explined by comorbid nxiety. Previous reserch in the generl popultion nd mong hert ptients consistently showed n ssocition between depression nd CVD. Importntly, these studies often did not tke into ccount comorbid nxiety, but mny depressed persons hve co-morbid nxiety disorder (in our smple 67%). Similr to our study within psychopthology-bsed popultion, Strik et l. 27 found tht nxiety nd not depressive symptoms were n independent predictor of crdic events mong hert ptients nd ccounted for the reltionship between depressive symptoms nd crdic events. Longitudinl studies should further disentngle the ssocitions between depression, nxiety nd CHD. Considering clinicl chrcteristics, highest prevlences of CHD were found mong those with the most severe symptoms of depression nd nxiety. This might suggest tht more severe symptoms induce n extr incresed risk of CHD. Otherwise, s symptom scles of depression nd nxiety often include set of somtic items, it is possible tht severity of depression or nxiety prtly reflects severity of hert complints. 28 Otherwise, somtic helth fctors might be more importnt in depressive disorders tht re ssocited with CVD. This might lso (prtly) explin why other studies, mostly conducted within somewht older popultions, which generlly hve more somtic conditions, do find more support of reltionship between depression nd CVD. Little evidence ws found of other clinicl chrcteristics of depressive or nxiety disorders to be specificlly relted to CHD. Although we hd expected longer lsting psychitric disorders to be ssocited with higher prevlence of CVD, the results did not corroborte this. This finding somewht decreses the plusibility of depressive nd nxiety disorders directly cusing CVD. Also, ssocitions with remitted psychitric disorders were not sttisticlly significnt, perhps prtly due to decresed relibility of dignosis ssessment in the more fr wy pst. On more positive side, this might suggest tht when persons remit from depressive or nxiety disorders, the odds of CHD decreses. Further, ntidepressnt mediction use ws not ssocited with CHD. Tricyclic ntidepressnts hve been well described to hve crdiovsculr effects, 29 but this might

8 136 chpter 7 crdiovsculr disese in persons with depressive nd nxiety disorders 137 hve been counterblnced in our study by the fct tht these medictions re therefore contr-indicted in hert ptients. Benzodizepine use ws somewht more prevlent mong persons with CHD, but whether they increse risk of CVD or whether this finding is reflection of poorer helth sttus in persons with CVD, cnnot be decided from this study. Interestingly, our results only show n ssocition with CHD, but not with stroke. Although some studies do relte psychopthology to stroke, 30 this hs been much less exmined thn CHD. We exmined the ssocition between depression, nxiety nd stroke in reltively young popultion where stroke ws not very prevlent nd we were not ble to distinguish between ischemic or hemorrhgic stroke. As n ssocition of depression nd nxiety with specificlly ischemic stroke is expected, hemorrhgic strokes might hve diluted the ssocition. Our study hs some importnt strengths. We mde use of lrge smple of persons with dignosed psychopthology to investigte whether true psychitric dignoses of both depression nd nxiety re indeed ssocited with heightened prevlence of CVD. Furthermore, we were ble to exmine the effects of lrge mount of clinicl chrcteristics of depressive nd nxiety disorders. Some limittions hve to be noted s well. Our results re bsed on cross-sectionl dt. This mkes it impossible to drw ny conclusions bout the cuslity of ssocitions between depressive nd nxiety disorders nd CHD. However, strong ssocition between nxiety disorder nd CHD existed in persons with n onset of psychopthology before 30 yers. Since CHD hrdly occurs before the ge of 30, n erly onset suggests tht psychopthology ws present before CHD. Additionlly, s depression nd nxiety re highly comorbid nd hd n erly onset in most persons (only 269 of 2315 hd lte onset), it is unlikely tht the finding tht nxiety is more strongly thn depression ssocited with CHD ws bised by the cross-sectionl design. Another limittion is tht the presence of hert disese ws not verified by generl prctice or hospitliztion records. However, self-report ws confirmed by mediction use nd previous reserch hs shown good concordnce between self-report of hert disese 31, 32 nd generl prctitioners informtion, with especilly little overreporting. In conclusion, our results show tht nxiety disorders re more strongly ssocited with coronry hert disese thn depressive disorders nd might prtly ccount for the widely reported ssocition between depression nd hert disese. The highest prevlence of CHD is found mong those with the most severe psychitric symptoms, such s those persons with comorbid depression nd nxiety. Anxiety s possible risk fctor for crdiovsculr disese needs to be more elbortely investigted in future reserch, nd deserves more ttention in clinicl cre s well. Reference List 1. Frsure-Smith N, Lespernce F, Tljic M. Depression following myocrdil infrction. Impct on 6-month survivl. JAMA 1993 October 20;27015.: Nicholson A, Kuper H, Hemingwy H. Depression s n etiologic nd prognostic fctor in coronry hert disese: met-nlysis of 6362 events mong prticipnts in 54 observtionl studies. Eur Hert J 2006 December;2723.: Mthers CD, Loncr D. Projections of globl mortlity nd burden of disese from 2002 to PLoS Med 2006 November;311.:e Brth J, Schumcher M, Herrmnn-Lingen C. Depression s risk fctor for mortlity in ptients with coronry hert disese: met-nlysis. Psychosom Med 2004 November;666.: Vn Melle JP, De Jonge P, Spijkermn TA et l. Prognostic ssocition of depression following myocrdil infrction with mortlity nd crdiovsculr events: metnlysis. Psychosom Med 2004 November;666.: Rugulies R. Depression s predictor for coronry hert disese. review nd met-nlysis. Am J Prev Med 2002 July;231.: Wulsin LR, Singl BM. Do depressive symptoms increse the risk for the onset of coronry disese? A systemtic quntittive review. Psychosom Med 2003 Mrch;652.: Vn der Kooy K, Vn Hout H, Vn Mrwijk H, Mrten H, Stehouwer C, Beekmn A. Depression nd the risk for crdiovsculr diseses: systemtic review nd met nlysis. Int J Geritr Psychitry 2007 July;227.: Kwchi I, Colditz GA, Ascherio A et l. Prospective study of phobic nxiety nd risk of coronry hert disese in men. Circultion 1994 My;895.: Albert CM, Che CU, Rexrode KM, Mnson JE, Kwchi I. Phobic nxiety nd risk of coronry hert disese nd sudden crdic deth mong women. Circultion 2005 Februry 1;1114.: Fn AZ, Strine TW, Jiles R, Mokdd AH. Depression nd nxiety ssocited with crdiovsculr disese mong persons ged 45 yers nd older in 38 sttes of the United Sttes, Prev Med 2008 My;465.:

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