Although depression symptoms are associated with an increased risk of recurrent cardiovascular disease in patients who have experienced an acute coronary syndrome (ACS) event, the exact mechanisms remain poorly understood. Inflammation has been suggested to be a mechanism in the depression–ACS prognosis link, as raised concentrations of inflammatory biomarkers, especially C reactive protein (CRP), are associated with recurrent cardiovascular events.1 In the few studies that have examined the relation between depression status and CRP concentrations after an ACS event, depression and CRP concentrations were assessed 2–6 months after the index ACS event, when the rate of depression remission would already be relatively high.2–4 The objective of this study was to examine the relation between the course of depression and CRP concentrations after an ACS event

Davidson, Karina W.

Paulino, R.

Rieckmann, N.

Shimbo, Daichi

English

Columbia University Academic Commons

SCIENTIFIC LETTERRelation between C reactive protein and depressionremission status in patients presenting with acute coronarysyndromeD Shimbo, N Rieckmann, R Paulino, K W Davidson. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Heart 2006;92:1316–1318. doi: 10.1136/hrt.2005.075861Although depression symptoms are associated with anincreased risk of recurrent cardiovascular disease inpatients who have experienced an acute coronarysyndrome (ACS) event, the exact mechanisms remain poorlyunderstood. Inflammation has been suggested to be amechanism in the depression–ACS prognosis link, as raisedconcentrations of inflammatory biomarkers, especiallyC reactive protein (CRP), are associated with recurrentcardiovascular events.1 In the few studies that have examinedthe relation between depression status and CRP concentra-tions after an ACS event, depression and CRP concentrationswere assessed 2–6 months after the index ACS event, whenthe rate of depression remission would already be relativelyhigh.2–4 The objective of this study was to examine therelation between the course of depression and CRP concen-trations after an ACS event.METHODSPatients were enrolled from an ancillary study of COPES(Coronary Psychosocial Patient Evaluation Study), a multi-site, observational cohort study designed to investigate theaetiology and naturalistic course of depressive symptoms inthe three-month period after an ACS event. Patients wereeligible for inclusion in COPES if they had been hospitalisedfor an ACS event (either acute myocardial infarction with orwithout ST segment elevation or unstable angina) and scoredbetween 0 and 4 (indicative of no depressive symptoms) or> 10 (at least mild depressive symptoms) on the BeckDepression Inventory (BDI) within one week after the indexACS event. The BDI is a self-report measure of depressivesymptom severity, and a score of > 10 is associated withincreased mortality risk after an ACS event.5 The BDI wasreadministered three months after enrolment.Of the 275 patients enrolled in the COPES parent studybetween May 2003 and May 2005, 162 (58.9%) consented toa substudy in which blood was drawn to assess CRPconcentrations at baseline and at the three-month followup. Substudy participants did not differ from non-partici-pants on age, sex, baseline depression score and severalclinical variables (p . 0.20) (table 1 lists the variables). Ofthe 162 participants, 59 (36.4%) did not get their blooddrawn at three months: 50 patients (30.9%) were lost tofollow up, 5 (3.0%) declined follow up and 4 (2.5%) died.As the primary objective of this study was to determine therelation between CRP concentration and depression remis-sion status over time, patients were classified into threecomparison groups: persistently depressed (BDI score> 10 atbaseline and after three months), remittently depressed (BDIscore > 10 at baseline and , 10 after three months) andpersistently non-depressed (BDI score 0–4 at baseline and, 10 after three months).After centrifugation, serum samples were stored in aliquotportions at270 C˚ until they were shipped to a core laboratory(Specialty Laboratories, Valencia, California, USA) for analy-sis of high sensitivity CRP concentrations. Concentrations ofCRP were determined by turbidimetry (Bayer Diagnostics,Leverkusen, Germany). We divided CRP concentrations intotwo categories: ( 3 mg/l and . 3 mg/l as previouslydescribed.1 A cut off of 3 mg/l identifies a group at increasedrisk for recurrent events and death after an ACS event.1Written informed consent was obtained from all participants,and the study was approved by the research ethicscommittees of the three university-affiliated hospitals fromwhich the participants were recruited (Mount Sinai Hospital,New York, New York; University of Medicine & Dentistry ofNew Jersey, New Jersey; and Yale–New Haven Hospital, NewHaven, Connecticut, USA).Differences in baseline characteristics between groups anddifferences in CRP concentrations in depression groups wereanalysed by univariate analyses of variance or x2 analyses. Totest for the impact of potential confounders that werespecified a priori, a hierarchical logistic regression analysiswas conducted. We used two-tailed tests of significance andSPSS statistical software (V.12.0; SPSS Inc, Chicago, Illinois,USA).RESULTSOf 103 patients, 58 (56.3%) were depressed (BDI score > 10)and 45 (43.7%) were non-depressed (BDI score ( 4) atbaseline. After three months, 21 patients (20.4%) wereclassified as persistently depressed, 24 (23.3%) as remittentlydepressed and 55 (53.4%) as persistently non-depressed.Three patients (2.9%) became newly depressed at follow up(non-depressed at baseline and depressed at three months).As we were primarily interested in studying the relationbetween depression remission status and CRP concentra-tions, these three patients were omitted from the analysis.Thus, the final study sample comprised 100 patients.Among the three groups (persistently depressed, remit-tently depressed and persistently non-depressed), the per-centages of women and patients with a history ofhypercholesterolaemia were significantly higher in theremittently depressed group than in the persistently non-depressed group (table 1). The groups did not otherwisediffer significantly in clinical characteristics.At baseline, no significant differences were found in CRPconcentrations among the three groups (95.2%, 79.2%, and72.7% respectively, p = 0.10). At three months (fig 1),persistently depressed patients were more likely to haveraised CRP concentrations than were the persistently non-depressed group (p = 0.002). Compared with the remit-tently depressed patients, the persistently non-depressedAbbreviations: ACS, acute coronary syndrome; BDI, Beck DepressionInventory; COPES, Coronary Psychosocial Patient Evaluation Study; CRP,C reactive protein1316www.heartjnl.comgroup also were less likely to have raised CRP concentrations,although this difference was not significant (p = 0.08). CRPconcentrations did not differ significantly between theremittently and persistently depressed patients (p = 0.36).The differences in raised CRP concentrations among the threegroups remained unchanged after controlling for age, sex,body mass index, diabetes mellitus, hypertension, hyperch-olesterolaemia, history of congestive heart failure, Killip classand statin use at any time during the three months after theindex ACS event.DISCUSSIONOur study is the first to assess depression and CRPconcentrations within one week after an ACS event andagain after three months. We found that depression remis-sion status three months after an ACS event was significantlyassociated with raised CRP concentrations, independent ofseveral possible confounders.To our knowledge, three other studies have examined therelation between depression and inflammatory biomarkerconcentrations after an ACS event.2–4 Only one study hasshown that depressive symptoms are significantly associatedwith increased concentrations of CRP, independent of severalconfounders.4 As these cross-sectional studies assesseddepression and CRP concentrations about 2–6 months afterthe index ACS event, discrepant results may be explained bythe inclusion of patients with new-onset depression in thedepressed group and those with remittent depression in thenon-depressed group.Spontaneous improvement in BDI scores after an ACShospitalisation is associated with a significantly greatersurvival of patients with at least mild baseline depressivesymptoms than of patients whose BDI scores remain raised.5Our data suggest a dose–response-like relation betweendepression remission status after an ACS event and raisedCRP concentrations. Thus, the lower survival rate observedamong persistently depressed patients may be associatedwith raised CRP concentrations and, conversely, the highersurvival rate observed among patients with remittentdepression may be associated with lower CRP concentrations.Our study has potential limitations. Although theseassociations are plausible, our study cannot discriminatebetween the several possible causal directions betweendepression and inflammation. The study is also limited bythe size of the cohort and the lack of information aboutantidepressant use. Further research should be conducted toconfirm our findings and to examine whether raised CRPconcentrations mediate the relation between depressioncourse and the recurrence of cardiovascular events.Authors’ affiliations. . . . . . . . . . . . . . . . . . . . .D Shimbo, K W Davidson*, Behavioral Cardiovascular Health &Hypertension Program, Department of Medicine, Columbia UniversityMedical Center, New York, USAN Rieckmann, Department of Psychiatry, Mount Sinai School ofMedicine, New York, USAR Paulino, Zena and Michael A Wiener Cardiovascular Institute,Department of Medicine, Mount Sinai School of Medicine, New York,USA*Also the Zena and Michael A Wiener Cardiovascular Institute,Department of Medicine, Mount Sinai School of Medicine, New York,USAThis work was supported by grants HC25197, HL072866, HL04458and HL76857 from the National Heart, Lung, and Blood Institute,National Institutes of Health, Bethesda, Maryland. The funding sourcesupported the collection and analyses of data, but had no direct role inthe interpretation of data, the writing of the report and the decision tosubmit the paper for publication.Competing interests: None declared.Correspondence to: Dr Daichi Shimbo, Behavioral CardiovascularHealth & Hypertension Program, Department of Medicine, ColumbiaUniversity Medical Center, 622 W 168th St, PH 9-952, New York, NY10032, USA; ds2231@columbia.eduAccepted 10 February 2006Table 1 Group characteristicsDepression categoryp ValuePersistent (n = 21) Remittent (n = 24)Persistent non-depression (n = 55)Mean age (years) 59.1 (SD 16.4) 60.3 (SD 11.5) 60.5 (SD 10.6) 0.91Women 52.4% 75.0%* 36.4% 0.01Current smoker 23.8% 29.2% 12.7% 0.19Diabetes mellitus 14.3% 33.3% 21.8% 0.30History of hypertension 71.4% 65.2% 67.9% 0.91History of hypercholesterolaemia 65.0% 87.0%* 67.9% 0.01Overweight (BMI 25–29.9 kg/m2) 30.0% 50.0% 41.8% 0.53Obese (BMI >30 kg/m2) 50.0% 37.5% 38.2% 0.81History of CHF 9.5% 0 5.6% 0.34Killip class >II 9.5% 4.2% 3.2% 0.57Statin use at baseline 40.0% 62.5% 41.5% 0.19Statin use at any time during the 3months of follow up81.0% 87.5% 90.9% 0.49*Significantly different from the persistently non-depressed group (p,0.05); assessed by self-report at baseline.BMI, body mass index; CHF, congestive heart failure.30.954.271.41009070806040503020010Persistentlynon-depressedPatients (%)RemittentdepressedPersistentlydepressed69.145.828.6Figure 1 Relation of depression remission status and raised C reactiveprotein (CRP) concentrations three months after an acute coronarysyndrome event. The grey area indicates raised CRP concentrations(. 3 mg/l) and the white area, not raised CRP concentrations( 3 mg/l). p = 0.002 for comparison between persistently depressedand persistently non-depressed patients; p = 0.08 for comparisonbetween persistently non-depressed and remittently depressed patients.Scientific letter 1317www.heartjnl.comREFERENCES1 Biasucci LM. CDC/AHA workshop on markers of inflammation andcardiovascular disease: application to clinical and public health practice.Clinical use of inflammatory markers in patients with cardiovascular diseases:a background paper, Circulation 2004;110:e560–7.2 Schins A, Tulner D, Lousberg R, et al. Inflammatory markers in depressed post-myocardial infarction patients. J Psychiatr Res 2005;39:137–44.3 Lesperance F, Frasure-Smith N, Theroux P, et al. The association betweenmajor depression and levels of soluble intercellular adhesion molecule 1,interleukin-6, and C-reactive protein in patients with recent acute coronarysyndromes. Am J Psychiatry 2004;161:271–7.4 Miller GE, Freedland KE, Duntley S, et al. Relation of depressive symptoms toC-reactive protein and pathogen burden (cytomegalovirus, herpes simplexvirus, Epstein-Barr virus) in patients with earlier acute coronary syndromes.Am J Cardiol 2005;95:317–21.5 Lesperance F, Frasure-Smith N, Talajic M, et al. Five-year risk ofcardiac mortality in relation to initial severity and one-year changes indepression symptoms after myocardial infarction. Circulation2002;105:1049–53.IMAGES IN CARDIOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .doi: 10.1136/hrt.2005.082784Resolution of dynamic left ventricular outflow tract obstruction caused by retained native leafletsfollowing mitral valve replacement using medical treatmentA72-year-old woman with atrial fibrilla-tion underwent surgical treatment forsevere mitral regurgitation and wor-sening breathlessness. Previous echocardio-graphy showed preserved systolic functionwith prominent septal knuckle. Coronaryangiography identified two vessel coronarydisease.Operative findings revealed an essentiallyunremarkable mitral valve with dilatedannulus and dilated poorly contractile leftventricle. A Carpentier Edwards prosthesiswas inserted leaving the entire mitral appa-ratus intact to preserve ventricular function.Severe tricuspid regurgitation requiredannuloplasty and two bypass grafts wereplaced. Haemodynamic instability postopera-tively was unresponsive to inotropic therapyand subsequent echocardiography showedsevere left ventricular outflow tract (LVOT)obstruction caused by prominent septalknuckle and systolic anterior motion of theretained anterior mitral valve leaflet (panelsA and B). Peak LVOT gradient was120 mm Hg and the patient remainedbreathless on minimal exertion. Becausethe patient was frail she was managedmedically by cessation of digoxin and gra-dual introduction of bisoprolol. Within twomonths the LVOT gradient reduced to8 mm Hg with only mild symptomatic lim-itation (panels C and D). She remains welland recently attended an outpatient reviewat six months post-surgery.LVOT obstruction is recognised after mitralvalve replacement with chordal preservationand a very high mortality has previouslybeen reported. Inotropes may exacerbateobstruction by reducing left ventricularcavity size. Intraoperative transoesophagealechocardiography is advisable followingvalve replacement, particularly in cases ofseptal hypertrophy where the anteriormitral valve leaflet should be excised.This case demonstrates successful medicalmanagement of LVOT obstruction using b blockade which should be considered in patientsunsuitable for reoperation.J WattK J HoggM Dantonjonnywatt@hotmail.comPanels A and B: Apical long axis view showing Carpentier Edwards mitral prosthesis with retainednative valve and septal knuckle during diastole (A) and during systole (B) where there is dynamic leftventricular outflow tract obstruction caused by systolic anterior motion of the native anterior mitralvalve leaflet. Panels C and D: Apical five chamber view showing continuous wave Doppler trace ofpeak LVOT gradient mean 120 mm Hg (patient in atrial fibrillation) post-surgery (C) andapproximately 8 mm Hg at two months after introduction of a b blocker (D).1318 Scientific letterwww.heartjnl.com

Relation between C reactive protein and depression remission status in patients presenting with acute coronary syndrome

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Relation between C reactive protein and depression remission status in patients presenting with acute coronary syndrome

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