CORRESPONDENCE: LETTER TO THE EDITOR
Throw the Window Out the Door
Brett D. Thombs, PhD*,
Kapil Parakh, MD, MPH and
Roy C. Ziegelstein, MD1
* Department of Psychiatry, Institute of Community and Family Psychiatry, SMBD—Jewish General Hospital, 4333 Cote Ste Catherine Road, Montreal, QC H3T 1E4, Canada (Email: brett.thombs{at}mcgill.ca).
Recently, Dickens et al. (1) reported that neither depression before myocardial infarction (MI), assessed retrospectively, nor depression 12 months post-MI is associated with cardiac mortality up to 8 years after MI. They hypothesized that the association between depression and post-MI mortality may be limited to a defined window of time post-MI and concluded that "defining the window when intervention for depression might benefit survival is crucial." However, neither current evidence nor their results support a search for a "window" of this nature.
To demonstrate the existence of a "window," it would be necessary to show that studies measuring depression during some window period find an association with mortality, whereas studies measuring depression outside of that period do not. In fact, many, but not all, studies that assess depression soon after an MI report an association with mortality (2,3). Studies that have assessed depression both pre-MI and soon after an MI disagree whether recurrent depression (4) or incident depression (5,6) predicts mortality. Similarly, it is unclear whether depression measured 6 months or longer post-MI is associated with mortality (4,7), although there is evidence that the longitudinal trajectory of post-MI depressive symptoms may be related to mortality (7) or to cardiovascular events (8).
The results reported by Dickens et al. (1) do not clarify this issue. Surprisingly, among their results, they found that patients who had depression both pre-MI and 12 months post-MI had a significantly lower mortality risk (p = 0.03; 0 deaths in 53 depressed patients vs. 32 in 387 nondepressed patients). The authors did not, however, report baseline data for patients with and without depression that might have helped explain this result. The finding was no longer significant in the multivariate model (p = 0.97), but this may be because of the modeling strategy used in their study. Dickens et al. (1) used discharge medications as one of the measures of MI severity, although the rationale for this is unclear. Since discharge medication is associated with survival after an MI and may itself be influenced by depression (9), this unjustified modeling approach is problematic. The authors preselected variables for their regression model based on associations with cardiac death and overfit the model by including far too many predictors per outcome event (78 cardiac deaths, 25 predictors, ratio = 3.1 to 1). Both practices are known to produce spurious results that are not likely to generalize to other samples (10). Indeed, such a low ratio of outcomes to predictors produces coefficient estimates that are either less than one-half or more than 2 times actual values more than 50% of the time (11).
In summary, it is not clear how existing evidence or the results of the study by Dickens et al. (1) supports searching for a "window" when intervention for depression might affect survival. Instead, more work is needed to develop a better understanding of the longitudinal trajectory and natural history of depression in patients with MI.
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Footnotes
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1 Please note: Dr. Ziegelstein is supported by NIH R21NS048593. 
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References
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1. Dickens C, McGowan L, Percival C, et al. Depression is a risk factor for mortality after myocardial infarction: fact or artifact? J Am Coll Cardiol 2007;49:1834-1840.[Abstract/Free Full Text]2. van Melle JP, de Jonge P, Spijkerman TA, et al. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis Psychosom Med 2004;66:814-822.[Abstract/Free Full Text] 3. Sorensen C, Friis-Hasche E, Haghfelt T, Bech P. Postmyocardial infarction mortality in relation to depression: a systematic critical review Psychother Psychosom 2005;74:69-80.[CrossRef][Web of Science][Medline] 4. Lesperance F, Frasure-Smith N, Talajic M. Major depression before and after myocardial infarction: its nature and consequences Psychosom Med 1996;58:99-110.[Abstract/Free Full Text] 5. de Jonge P, van den Brink RH, Spijkerman TA, Ormel J. Only incident depressive episodes after myocardial infarction are associated with new cardiovascular events J Am Coll Cardiol 2006;48:2204-2208.[Abstract/Free Full Text] 6. Grace SL, Abbey SE, Kapral MK, Fang J, Nolan RP, Stewart DE. Effect of depression on five-year mortality after an acute coronary syndrome Am J Cardiol 2005;96:1179-1185.[CrossRef][Web of Science][Medline] 7. Lesperance F, Frasure-Smith N, Talajic M, Bourassa MG. Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction Circulation 2002;105:1049-1053.[Abstract/Free Full Text] 8. Kaptein KI, de Jonge P, van den Brink RH, Korf J. Course of depressive symptoms after myocardial infarction and cardiac prognosis: a latent class analysis Psychosom Med 2006;68:662-668.[Abstract/Free Full Text] 9. Bush DE, Ziegelstein RC, Patel UV, et al. Post-myocardial infarction depression Evid Rep Technol Assess 2005;123:1-8(Summ). 10. Babyak MA. What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models Psychosom Med 2004;66:411-421.[Abstract/Free Full Text] 11. Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysisII. Accuracy and precision of regression estimates. J Clin Epidemiol 1995;48:1503-1510.[CrossRef][Web of Science][Medline]
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