In survivors of acute coronary syndromes (ACS; unstable angina or myocardial infarction), depression is highly prevalent [1] and increases the risk of adverse medical outcomes, independent of other prognostic risk markers [2, 3] . After ACS, adherence to recommended medications (e.g. aspirin, statins and -blockers) is crucial to prevent recurrent events or mortality [4–6], yet rates of adherence to these medications are poor [7–9] . Depressed patients are especially likely to be poorly adherent [8–11] . Thus, poor medication adherence may explain some of the increased risk of depression and adverse clinical outcomes after ACS

Burg, Matthew M.

Chaplin, William F.

Davidson, Karina W.

Kronish, Ian M.

Rieckmann, Nina

Schwartz, Joseph E.

Psychotherapy and Psychosomatics

PubMed

Columbia University Academic Commons

Fax +41 61 306 12 34E-Mail karger@karger.chwww.karger.com Letter to the Editor after discharge, the first month and the first 3 months. The per-centage was subtracted from 100 to obtain the percentage of non-adherent days, so that the hazard ratios (HR) in the Cox propor-tional hazards models reflected risk associated with poorer ad-herence. For patients who had an MACE or who died in the first 3 months, adherence was computed up until the week of the event. Medical covariates included the Charlson comorbidity index  [15] and left ventricular ejection fraction (normal/mild dysfunction:  6 40%; moderate/severe dysfunction:  ! 40%)  [16] . Partial correla-tions and Cox proportional hazards models were used, adjusting for age and sex, treating study site as stratum. All continuous pre-dictors were standardized. The degree of mediation was assessed by the percent reduction in the Cox regression coefficient for de-pressive symptoms when aspirin adherence was included in the model.  The COPES parent study included 457 ACS patients, of which 172 took part in the aspirin monitoring study. Refusers of the monitoring study had higher levels of in-hospital depressive symptoms  [12] . Four patients had an MACE within the first 7 days after discharge and were excluded from the present analyses. The mean age was 59.4 years (SD = 12.2 years), 45% of the patients were female and 86% white. Controlling for age, sex and site, baseline depressive symp-toms were significantly correlated with poorer 7-day, 1-month and 3-month aspirin adherence (partial r: 0.22, 0.26 and 0.19, re-spectively; all p  ! 0.02). After 1 year, there had been 14 MACE/ACM events (8%). Adjusting for age, sex and site, poorer 7-day (adjusted standardized HR, sHR: 1.76; CI: 1.14–2.73) and 1-month aspirin adherence (adjusted sHR: 1.75; CI: 1.18–2.60) as well as baseline depressive symptoms (adjusted sHR: 1.53; CI: 1.02–2.29) were each individually associated with 1-year MACE/ACM. A similar, yet nonsignificant association was found for poorer 3-month aspirin adherence (adjusted sHR: 1.45; CI: 0.97–2.17; p = 0.054). When both baseline depressive symptoms and 7-day aspi-rin adherence were entered into the age- and sex-adjusted model, the HR for depressive symptoms decreased substantially (adjust-ed sHR: 1.34; CI: 0.89–2.01), whereas poorer 7-day aspirin adher-ence remained a significant predictor (adjusted sHR: 1.64; CI: 1.06–2.54). The effect size for depressive symptoms decreased by 31% ( fig.  1 ) when 7-day aspirin adherence was included in the analysis. Controlling for left ventricular ejection fraction and Charlson comorbidity index did not alter these results (data not shown). Similarly, poorer 1-month aspirin adherence decreased the effect size for baseline depressive symptoms by 29% (adjusted sHR for depressive symptoms: 1.37; CI: 0.88–2.13; adjusted sHR for poorer 1-month adherence: 1.65; CI: 1.11–2.45).  Depression in cardiac patients has been linked to several bio-logical and behavioral dysregulations  [16, 17] . The present study shows that a modifiable patient behavior – medication adher-ence – may account for some of the clinical outcome risk associ-ated with increased depressive symptoms after ACS. The Heart and Soul Study, which tested biological and behavioral depression  In survivors of acute coronary syndromes (ACS; unstable an-gina or myocardial infarction), depression is highly prevalent  [1] and increases the risk of adverse medical outcomes, independent of other prognostic risk markers  [2, 3] . After ACS, adherence to recommended medications (e.g. aspirin, statins and   -blockers) is crucial to prevent recurrent events or mortality  [4–6] , yet rates of adherence to these medications are poor  [7–9] . Depressed pa-tients are especially likely to be poorly adherent  [8–11] . Thus, poor medication adherence may explain some of the increased risk of depression and adverse clinical outcomes after ACS. We used data from 168 participants in the medication moni-toring substudy  [12] of the observational Coronary Psychosocial Evaluation Studies (COPES)  [13] to test this hypothesis. This sub-study included hospitalized ACS patients who were prescribed a daily dose of aspirin, neither used a weekly pillbox nor lived in a nursing home, and had a score of  6 10 or  ! 5 on the Beck Depres-sion Inventory  [14] (see Rieckmann et al.  [12] for study sample characteristics and eligibility criteria, and Davidson et al.  [13] for details on outcome event ascertainment). Aspirin adherence over 90 days after hospital discharge was measured using the Medica-tion Event Monitoring System (MEMS; APREX Corp., Fremont, Calif., USA) device. Each time the MEMS bottle is opened, the date and time is permanently recorded on a computer chip in the cap. Patients received a 90-day supply of their prescribed aspirin dose in an MEMS bottle. They were informed that their adherence was being monitored, but they did not receive adherence counsel-ing. The outcome was the 1-year first occurrence of a major ad-verse cardiac event (MACE; nonfatal myocardial infarction, ur-gent cardiac revascularization or unstable angina hospitalization) or all-cause mortality (ACM). The study complies with the Dec-laration of Helsinki. The institutional review boards of each study site approved the study  [12] . Adherence, defined as the percentage of days the correct num-ber of pills (1) was taken, was computed across the first 7 days  Received: September 9, 2010  Accepted after revision: November 28, 2010  Published online: June 30, 2011  © 2011 S. Karger AG, Basel  Accessible online at:www.karger.com/pps  Psychother Psychosom 2011;80:316–318  DOI: 10.1159/000323168  Aspirin Adherence, Depression and One-Year Prognosis after Acute Coronary Syndrome  Nina Rieckmann  a , Matthew M. Burg  b, f , Ian M. Kronish  c , William F. Chaplin  e , Joseph E. Schwartz  b , Karina W. Davidson  b, d  a   Berlin School of Public Health, Charité University Medical Center,  Berlin , Germany;  b   Department of Medicine, Columbia University College of Physicians and Surgeons,  c   Division of General Internal Medicine and  d   Mount Sinai Heart, MountSinai School of Medicine, and  e   Department of Psychology,St. Johns University,  New York, N.Y. , and  f   Section of Cardiovascular Medicine, Yale University School of Medicine,  New Haven, Conn. , USA Letter to the Editor 317mediators in a sample of 1,017 patients with stable coronary heart disease  [18] , found that self-reported medication adherence ex-plained only a small portion (5%) of the association between de-pressive symptoms and future clinical events, as opposed to 31% in our study. However, different mechanisms may account for the increased risk in depressed stable heart disease patients (the pop-ulation of the Heart and Soul Study) as compared to depressed ACS patients. Also, electronic monitoring in our study provided a more objective measure of adherence and yielded higher nonad-herence rates in comparison to the Heart and Soul Study  [12] . In addition, our follow-up was shorter than that in the Heart and Soul Study, and the impact of adherence on event-free survival may decrease over time.  Generalizability of the current study is limited by the relatively small sample size. Also, the study participants had lower levels of depressive symptoms than the study refusers  [12] , and the restric-tion of range may have attenuated both the associations between adherence and depression, and between depressive symptoms and MACE/ACM. It also remains to be shown whether poor aspirin adherence is a marker of overall poor medication adherence across all cardioprotective medications  [6] . Lastly, it is possible that aspi-rin, due to anti-inflammatory effects, may reduce depressive symptoms. A recent case-control study of a sample of 345 commu-nity-dwelling women showed that the use of aspirin was associated with a significantly decreased incidence of major depressive disor-der after the age of 50 years  [19] . In the current COPES substudy, however, we had previously found that higher aspirin adherence was not associated with subsequent improvements in depressive symptoms over time; in fact, changes in depressive symptoms pre-ceded changes in aspirin adherence, but not vice versa  [12] . Still, it is possible that better aspirin adherence may lead to later changes in depressive symptoms in the long run. This will need to be ex-plored in future studies with repeated assessments of depressive symptoms further away from the index ACS event. In conclusion, this study provides evidence that poorer aspirin adherence may account for a substantial part of the excess prog-nostic risk associated with depressive symptoms after ACS. Pro-moting medication adherence in combination with depression treatment may more effectively improve the medical prognosis for depressed patients than simply treating depression.  Acknowledgments  This study was supported by grants HC-25197, HL-088117, HL-76857 and HL-84034 from the National Institutes of Health (NIH), Bethesda, Md., USA, and by grant UL1 RR024156 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Disclosure Statement  The authors have no conflict of interest to declare.  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Aspirin Adherence, Depression and One-Year Prognosis after Acute Coronary Syndrome

Aspirin Adherence, Depression and One-Year Prognosis after Acute Coronary Syndrome

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