Purpose
The purpose of this study was to assess the association between antidepressant use and incident coronary heart disease (CHD) events in a sample of individuals without known baseline heart disease.

Participants and methods
We studied a group of 970 randomly selected community-dwelling adults in the 1995 Nova Scotia Health Survey, who were followed for up to 10 years. Antidepressant usage was classified according to class. Primary outcomes were acute coronary syndrome hospitalizations or cardiac death, determined by centralized, standardized ratings.

Results
During a follow-up period of 10 years, there were 147 incident CHD events (139 acute coronary syndromes and 8 cardiac deaths) during the 8129 person-years of observation (incidence rate=18.1 events/1000 person-years). In a model controlling for age, sex, Framingham risk score, time to last annual exam, aspirin exposure, and depressive symptoms, an increased risk of CHD events was associated with tricyclic antidepressant exposure (adjusted hazard ratio, 2.10; 95% confidence interval, 1.09–4.06; p =0.027).

Conclusion
In this prospective population-based study, exposure to tricyclic antidepressants was associated with higher risk of first CHD events

Davidson, Karina W.

Rosenberg, Leah B.

Shah, Ashish

Shapiro, Peter A.

Shimbo, Daichi

Whang, William

English

PubMed

Columbia University Academic Commons

Exposure to Tricyclic Antidepressants is Associated with anIncreased Risk of Incident CHD Events in a Population-basedStudyLeah B Rosenberg, BA,Medicine, Columbia University Medical Center, New York, NYWilliam Whang, MD,Cardiology, Columbia University Medical Center, New York, NYDaichi Shimbo, MD,Medicine, Columbia University Medical Center, New York, NYAshish Shah, MD,Medicine, Columbia University Medical Center, New York, NYPeter A Shapiro, MD, andPsychiatry, Columbia University Medical Center, New York, NYKarina W Davidson, PhDMedicine and Psychiatry, Columbia University Medical Center, New York, NYAbstractPURPOSE—The purpose of this study was to assess the association between antidepressant useand incident coronary heart disease (CHD) events in a sample of individuals without knownbaseline heart disease.PARTICIPANTS AND METHODS—We studied a group of 970 randomly-selected community-dwelling adults in the 1995 Nova Scotia Health Survey, who were followed for up to ten years.Antidepressant usage was classified according to class. Primary outcomes were acute coronarysyndrome hospitalizations or cardiac death, determined by centralized, standardized ratings.RESULTS—During a follow-up period of ten years, there were 147 incident CHD events (139acute coronary syndromes and 8 cardiac deaths) during the 8,129 person-years of observation(incidence rate = 18.1 events/1000 person years). In a model controlling for age, sex, Framinghamrisk score, time to last annual exam, aspirin exposure, and depressive symptoms, an increased riskof CHD events was associated with tricyclic antidepressant exposure (adjusted hazard ratio, 2.10;95% confidence interval, 1.09–4.06; p=0.027).© 2009 Elsevier Ireland Ltd. All rights reserved.Corresponding Address: Leah Rosenberg or Karina Davidson, Columbia University Medical Center, PH9-948, New York, NY10032.Academic Addresses: Authors 1, 3, 4, and 6: Same as corresponding address. Author 2: Division of Cardiology, Columbia UniversityMedical Center, Harkness Pavilion 366, 180 Fort Washington Ave. NY, NY 10032. Author 5: 622 W. 168 St. Box 427, New York NY10032This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providingthis early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before itis published in its final citable form. Please note that during the production process errors may be discovered which could affect thecontent, and all legal disclaimers that apply to the journal pertain.NIH Public AccessAuthor ManuscriptInt J Cardiol. Author manuscript; available in PMC 2011 November 5.Published in final edited form as:Int J Cardiol. 2010 November 5; 145(1): 124–125. doi:10.1016/j.ijcard.2009.06.036.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptCONCLUSION—In this prospective population-based study, exposure to tricyclicantidepressants was associated with higher risk of first CHD events.INTRODUCTIONDepression has been associated with worse prognosis in individuals with establishedcoronary heart disease and with the development of coronary heart disease.1 However, therehave been few population-based investigations testing the impact of antidepressant use onlong-term CHD incidence.2,3,4,5 In this report we present the results of a prospectiveanalysis of the relationship between antidepressant medication use and risk of incident CHDduring 10-year follow-up of a population-based cohort.METHODSSUBJECTSThe study sample included patients enrolled in the 1995 Nova Scotia Health Survey study, apopulation-based survey by Heart Health Nova Scotia in partnership with the Nova ScotiaDepartment of Health. The targeted population consisted of all non-institutionalized NovaScotians age 45 and older, known to be CHD-free, whose names were listed in the MedicalService Insurance register, the government-sponsored, universal health insurance plan. Wedefined the period of follow-up for each participant as starting at the participant’s age atbaseline and extending until either his/her age at first CHD event or age on March 31, 2005for those who did not have an event during the follow-up period.At the home visit, the nurse requested all prescription and nonprescription medications andsupplements, and recorded the generic drug name, the brand name, the number of pills in thebottle, the date of the prescription, and the dosing instructions. Drugs were coded using theWorld Health Organization Nordic Anatomical, Therapeutic, and Chemical codeclassification valid in 1995.6The main outcome variable was incidence of nonfatal or fatal CHD, as categorized by theInternational Classification of Diseases.7 All deaths are reported to provincial offices, whichin turn notify the national census bureau, Statistics Canada, which applies a nationallyconsistent process of determining the underlying cause of death. Nonfatal CHD wasassessed by primary discharge hospital code, collected in the centralized, computerized,single-payer medical system.Depressive symptoms were assessed at baseline with the Center for Epidemiological StudiesDepression Scale.Nurses visited the subjects at home for the baseline measures and recorded all prescriptionmedications. Antidepressants were categorized as TCAs, SSRIs and Others.STATISTICAL ANALYSISBaseline characteristics of the participants were compared by use of antidepressantmedications and by drug class. Data are expressed as means and standard deviations, orpercentages. Multivariable proportional hazards models were used to estimate the hazardratio associated with antidepressant use, with adjustment for possible confounders includingFramingham risk score and depressive symptoms. All statistical analyses were performedusing SPSS statistical software version for Windows 16.0 (Chicago, IL).Rosenberg et al. Page 2Int J Cardiol. Author manuscript; available in PMC 2011 November 5.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptRESULTSOf the 970 patients, 40 (4%) possessed at least one prescription for an antidepressant atbaseline (1995), and 930 did not. Baseline clinical characteristics are shown in Table 1.Length of follow-up did not vary for the antidepressant class and nonuser categories. Of the40 participants using an antidepressant, 14 were on selective serotonin reuptake inhibitors(SSRIs), 25 were on tricyclic antidepressants (TCAs), and one patient was taking both.During follow-up of ten years, there were 147 incident CHD events (139 acute coronarysyndromes and 8 cardiac deaths) during the 8,129 person-years of observation (incidencerate = 18.1 events/1000 person years). In a proportional hazards model controlling for age,sex, Framingham risk score, time to last annual exam, aspirin exposure, and baselinedepressive symptoms, TCA exposure predicted a higher risk of 10-year incident CHD events(adjusted hazard ratio, 2.10; 95% confidence interval, 1.09–4.06; p<0.05) (Table 2). Afteradjustment for the same factors, the association of SSRI exposure with CHD events was notsignificant (relative risk 1.33, 95% CI 0.49–3.64).DISCUSSIONIn this population-based survey we found a statistically significant association between TCAuse and risk of 10-year incident CHD events. The relation between tricyclic use and incidentCHD events persisted after multivariable adjustment for possible confounders, includingannual visit, use of another cardioprotective medication (aspirin), the Framingham risk scoreand depressive symptoms. As antidepressant use can be viewed as a marker for depressivesymptoms, our data support the existing evidence linking the presence of depression todevelopment of coronary heart disease. However, our data are also consistent withcardiovascular harm associated with tricyclic use, this time with long-term follow-up.Our findings substantiate the results of a previous study of 2247 union health plan members,8 which reported a relative risk for myocardial infarction of 2.2 (95% CI 1.2–3.8) amongTCA users, although this study did not adjust for depressive symptoms. Our findings supportanother observation of this study that identified no increased risk of MI with SSRI exposure.Other similar investigations have been limited by short follow-up periods, usually not morethan 8 weeks in duration.9In this observational study of 970 Nova Scotians without pre-existing CHD, we observed anassociation between exposure to TCAs and incident CHD over a ten-year follow-up period.This increased risk suggests a mechanism of cardiotoxicity independent of the well-knownarrhythmogenic effects of TCAs. Further research is indicated to determine the underlyingpathways between tricyclic exposure and increased incidence of CHD seen in long-termfollow-up in a general population.AcknowledgmentsThe authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in theInternational Journal of Cardiology.10Grant Support:This work was supported by grants HL80665, HL-76857, HL-84034, HL088117, and HL072866 from the NationalHeart, Lung, and Blood Institute, Bethesda, MD. The National Health and Welfare of Canada, Ottawa, Ontario; theNova Scotia Department of Health, Halifax; and the Heart and Stroke Foundation of New Brunswick, Saint John,supported the original data collection. The project described was also supported by grant UL1 RR024156 from theNational Center for Research Resources, Bethesda as well as the Sarnoff Foundation for Cardiovascular Research,McLean, VA.Rosenberg et al. Page 3Int J Cardiol. Author manuscript; available in PMC 2011 November 5.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptReferences1. Lichtman JH, et al. Depression and coronary heart disease: recommendations for screening, referral,and treatment: a science advisory from the American Heart Association Prevention Committee ofthe Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiologyand Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsedby the American Psychiatric Association. Circulation. 2008; 118:1768–1775. [PubMed: 18824640]2. Hippisley-Cox J, Pringle M, et al. Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care. BMJ. 2001; 323:666–669. [PubMed: 11566831]3. Penttinen J, Valonen P. Use of psychotropic drugs and risk of myocardial infarction: a case-controlstudy in Finnish farmers. Int J Epidemiol. 1996; 25:760–762. [PubMed: 8921453]4. Monster TB, Johnsen S, et al. Antidepressants and risk of first-time hospitalization for myocardialinfarction: a population-based case control study. Am J Med. 2004; 117:732–737. [PubMed:15541322]5. Lapane K, Zierler S, et al. Is the use of psychotropic drugs associated with increased risk ofischemic heart disease? Epidemiology. 1995; 4:376–381. [PubMed: 7548344]6. WHO Collaborating Centre for Drug Statistics Methodology. Oslo: WHO Collaborating Centre forDrug Statistics Methodology. Anatomical Therapeutic Chemical (ATC) classification index. 1995.7. International Classification of Diseases, Ninth Revision. International Statistical Classification ofDiseases, 10th Revision. codes 410.x–414.x and codes I21.x–I25.x8. Hillel WC, Gibson G, Alderman MH. Excess Risk of Myocardial Infarction in Patients Treated withAntidepressant Medications: Association with Use of Tricyclic Agents. The American Journal ofMedicine. 2000 January.108:2–8. [PubMed: 11059434]9. Summary, Evidence Report/Technology Assessment: Number 7. Rockville, MD: Agency for HealthCare Policy and Research; 1999. Treatment of depression: newer pharmacotherapies.http://www.ahcpr.gov/clinic/deprsumm.htm10. Coats AJ. Ethical authorship and publishing. Int J Cardiol. 2009; 131:149–150. [PubMed:19046787]Rosenberg et al. Page 4Int J Cardiol. Author manuscript; available in PMC 2011 November 5.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptRosenberg et al. Page 5Table 1Baseline Variables for the Canadian, Population-based Sample (N=970)Variable Mean(SD) NAge, y 61 (11.20)Female, % 516 (53.2)Framingham RiskScore7.96 (3.88)Time to last annualexam1 year, %709 days (73.1)2 year, % 149 days (15.4)3 year, % 112 days (11.5)SSRI exposure, % 15 patients (1.4)Tricyclic exposure,%26 patients (2.8)Aspirin exposure, % 59 (6.1)Int J Cardiol. Author manuscript; available in PMC 2011 November 5.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptRosenberg et al. Page 6Table 2Predictors of Incident Coronary Heart DiseasePredictor Category ofExposureBivariate Hazard Ratio(95%CI)Adjusted* Bivariate HazardRatio (95%CI)Sex of Participant Female (vs Male) 1.69(1.21–2.34) -Age Per SD (1 SD = 11.20yrs)1.66 (1.42–1.93) -Risk Score Per SD (1 SD = 3.88points)1.83 (1.57–2.13) -SSRI 1.35 (0.43–4.23) 1.33(0.49–3.64)TricyclicAntidepressants2.88(1.46–5.68) 2.10(1.09–4.06)Aspirin exposure 1.37(0.76–2.47) 1.13(0.65–1.96)Int J Cardiol. Author manuscript; available in PMC 2011 November 5.

Exposure to tricyclic antidepressants is associated with an increased risk of incident CHD events in a population-based study

http://dx.doi.org/10.1016/j.ijcard.2009.06.036

Exposure to tricyclic antidepressants is associated with an increased risk of incident CHD events in a population-based study

Abstract

Similar works

Full text

Available Versions

Columbia University Academic Commons