Depression: A Risk Factor and Two Riddles about Poor Prognosis in ACS

Updated:May 19,2014

Disclosure:  Dr. Spring has nothing to disclose.
Pub Date:  Monday, Feb. 24, 2014
Author:  Bonnie Spring, PhD
Affiliation:  Director, Center for Behavior and Health, Professor of Preventive Medicine, Northwestern University School of Medicine, Chicago, Ill.

Citation

Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N, Freedland KE, Jaffe AS, Leifheit-Limson EC, Sheps DS, Vaccarino V, Wulsin L; on behalf of the American Heart Association Statistics Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation. doi: 10.1161/CIR.0000000000000019.
http://circ.ahajournals.org/lookup/doi/10.1161/CIR.0000000000000019

Article Text

Depression is prevalent in acute coronary syndrome (ACS) and has been associated with increased morbidity and mortality.1-3  Yet, despite the many prospective studies that link depression to poor outcome after ACS, depression has not been formally recognized in national health guidelines as a poor prognostic indicator. The Writing Group for this Scientific Statement undertook a systematic review to evaluate whether change is warranted.4

A search protocol was implemented to identify all English language publications in MEDLINE, Current Contents, and PsycINFO through July 24, 2011 that examined the association between depression and all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events after ACS (myocardial infarction or unstable angina).  A total of 53 individual studies and 4 meta-analyses met inclusion criteria and showed heterogeneity in terms of the sample demographics, the definition and measurement of depression, and length of follow-up.   Positive studies identified associations of varying magnitudes, and a minority of the studies showed negative findings.  The Writing Group’s appraisal, reflected in the Scientific Statement, is that the preponderance of evidence supports the recommendation that the AHA should elevate depression to the status of a risk factor for adverse medical outcomes in patients with ACS.

The Writing Group applied rigorous definitional criteria when interpreting depression as risk factor.  Specifically, they analyzed only prospective studies and required that depression be linked to cardiac events and mortality, rather than only to intermediate outcomes.  Two important riddles remain, however.  The first riddle concerns whether there is a plausible biological mechanism to account for the observed association between depression and post-ACS mortality.  The second riddle concerns whether there are practical clinical implications of the association between depression and adverse outcomes following ACS.

Confidence that depression is causally important for coronary disease outcome would be enhanced by evidence that the risk factor meets the Bradford Hill criterion of having a biologically plausible mechanism to explain its association to disease outcome.5  As Hill noted, the ability to comprehend or shed light on causal mechanisms inevitably is limited by the current state of biomedical knowledge.  In the case of potential causal mechanisms to link depression and coronary heart disease, the list of contenders is very long indeed.  As the Statement suggests, potential biological mediators of depression’s effects on adverse outcomes include neuroendocrine dysfunction, disturbances in autonomic cardiac control, enhanced platelet activity in depression, endothelial dysfunction, and inflammation.  Another suggestion is that depression may contribute to poor cardiac outcomes by potentiating the adverse metabolic effects of diabetes and obesity on the heart.  Equally likely is the prospect that depression fosters untoward effects by increasing the odds that health risk behaviors such as smoking, physical inactivity, and treatment non-adherence will indirectly mar the process of recovery from ACS.

Even more challenging than the riddle of what mechanism links depression to poor ACS outcome is the riddle regarding any practical implications of the association.  To date, there is no compelling evidence that treating depression improves survival after ACS.6 The premise of the Statement is that such evidence is not yet available, but will be forthcoming.  Let us hope this proves to be the case and that we will eventually learn how to treat post-ACS depression sufficiently well to improve survival.  If so, depression may emerge as a genuinely “causal risk factor” for ACS outcome.7  Until then, we might wish to consider whether intervening positively to foster wellness, well-being, or resilience, rather than solely to alleviate depression could hold added potential to improve disease outcomes.8,9

References

  1. Hemingway H, Marmot M. Evidence based cardiology: psychosocial factors in the aetiology and prognosis of coronary heart disease. Systematic review of prospective cohort studies. BMJ. 1999;318:1460,1467.
  2. Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KRR, Nemeroff CB, Bremner JD, Carney RM, Coyne JC, Delong MR, Frasure-Smith N, Glassman AH, Gold PW, Grant I, Gwyther L, Ironson G, Johnson RL, Kanner AM, Katon WJ, Kaufmann PG, Keefe FJ, Ketter T, Laughren TP, Leserman J, Lyketsos CG, McDonald WM, McEwen BS, Miller AH, Musselman D, O’Connor C, Petitto JM, Pollock BG, Robinson RG, Roose SP, Rowland J, Sheline Y, Sheps DS, Simon G, Spiegel D, Stunkard A, Sunderland T, Tibbits Jr P, Valvo WJ. Mood Disorders in the Medically Ill: Scientific Review and Recommendations. Biological Psychiatry. 2005;58:175-189.
  3. Frasure-Smith N, Lespérance F. Depression and cardiac risk: Present status and future directions. Heart. 2010;96:173-176.
  4. Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N, Freedland KE, Jaffe AS, Leifheit-Limson EC, Sheps DS, Vaccarino V, Wulsin L; on behalf of the American Heart Association Statistics Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation. doi: 10.1161/CIR.0000000000000019.
  5. Hill AB. The Environment and Disease: Association or Causation? Proceedings of the Royal Society of Medicine 1965;58(5):295–300.
  6. Writing Committee for the ENRICHD Investigators. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: The Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) randomized trial. JAMA. 2003;289:3106-3116.
  7. Kraemer HC, Kazdin AE, Offord DR, Kessler RC, Jensen PS, Kupfer DJ. Coming to terms with the terms of risk. Archives of General Psychiatry. 1997;54:337-343.
  8. Cook JW, Spring B, McChargue D, Hedeker D. Hedonic capacity, cigarette craving and diminished positive mood.  Nicotine and Tobacco Research 2004;6(1):37-45
  9. Boehm JK, Kubzansky LD. The heart's content: The association between positive psychological well-being and cardiovascular health. Psychological Bulletin, 2012;138(4):655-691.

-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --
 

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