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Depression as Risk Factor for Mortality after Coronary Artery Bypass Surgery

CITATION:  Lucas, S., Shuhaiber, J. H., Macleod, J., Smith, G. D., et al. (2003). Depression as risk factor for mortality after coronary artery bypass surgery. The Lancet, 362(9394), 1499-1511.

ABSTRACT:  A. John Macleod and George Davey Smith correctly note that improving quality of life is justification enough to encourage greater recognition and treatment of depression. However, we find little basis for their concerns that such efforts may create unrealistic expectations about the benefits of treatment and that evidence for the "direct effects of depression" would somehow distract attention from established primary and secondary prevention efforts for coronary heart disease. As we indicated, there are various potential social and behavioural mechanisms by which depression may confer increased risk of mortality, including non-adherence to prescribed medical therapies, physical inactivity, and smoking. Moreover, there are also plausible biological mechanisms that could contribute to this increased risk-for example, increased platelet activation1 metabolic abnormalities,2 autonomic disregulation including reduced heart rate variability,3 and altered immune function and inflammation,4 all of which have been found to characterise depressed patients and may be associated with adverse prognosis. We do not know if these factors are responsible for the increased mortality observed among depressed patients after CABG, or if altering these factors affects survival. Although MacLeod and Davey Smith may be sceptical of this possibility, it is an empirical question that can only be answered through further research. We also take issue with the statement that results of the ENRICHD trial "provide little evidence that depression causes heart disease". This statement is not only untrue but represents a serious misunderstanding of the ENRICHD trial. First, these patients already had heart disease, and data from the ENRICHD trial showed that depression was associated with increased mortality, independently of disease severity.5 Second, there are many possible explanations for why changes in depression did not translate into improved survival. For example, changes in depression were modest and did not necessarily alter underlying pathophysiological processes. Third, the ENRICHD trial was the first (and is the only) randomised behavioural intervention trial to attempt to reduce morbidity and mortality in depressed and socially isolated patients with existing coronary disease. Although the primary results of the trial showed no survival benefit for the group who received cognitive therapy, certain patients did benefit, including patients taking antidepressant medication. These data raise the possibility that altering biological pathways associated with depression may reduce adverse clinical events. Although we should not abandon current primary and secondary prevention efforts, given the mounting evidence that depression is prevalent among patients after CABG and is associated with increased mortality and morbidity, we believe that the time is right to initiate clinical trials to find out if treating depression improves not only quality of life but also clinical outcomes. To be complacent about our existing therapies and ignore these results would do a disservice to the millions of patients with cardiac disease.


1 Blumenthal JA, Lett HS, Babyak MA, et al. Depression as a risk factor for mortality after coronary artery bypass surgery. Lancet 2003; 362: 604-09.

2 Zindrou D, Taylor KM, Bagger JP. Preoperative haemoglobin concentration and mortality rate after coronary artery bypass surgery. Lancet 2002; 359: 1747-48.

3 Guck TP, Elsasser GN, Kavan MG, Baronc EJ. Depression and congestive heart failure. Congest Heart Fail 2003; 9: 163-69.

4 Boylan MJ, Lytle BW, Loop FD, et al. Surgical treatment of isolated left anterior descending coronary stenosis. Comparison of left internal mammary artery and venous autograft at 18 to 20 years of follow-up. J Thorac Cardiovasc Surg 1994; 107: 657-62.

5 Woods SE, Noble G, Smith JM, Hasselfeld K. The influence of gender in patients undergoing coronary artery bypass graft surgery: an eight-year prospective hospitalized cohort study. J Am Coll Surg 2003; 196: 428-34.