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Cardiac-related Hospitalization and/or Death Associated With Immune Dysregulation and Symptoms of Depression in Heart Failure Patients

From the Department of Medicine (L.S.R., A.M.) and Department of Psychiatry (P.J.M., S.H., T.R., V.R.), University of California, San Diego; and Department of Psychiatry and Biobehavioral Sciences and Neuropsychiatric Institute and Cousins Center for Psychoneuroimmunonology (M.R.I.), University of California, Los Angeles.

Address correspondence and reprint requests to Laura Redwine, PhD, VA San Diego Healthcare System 151, 3350 La Jolla Village Drive, San Diego, CA 92161. E-mail: lredwine{at}vapop.ucsd.edu

Objective: Congestive heart failure (CHF) patients with depressive symptoms have a greater risk of morbidity and mortality. Immune activity such as inflammation is increasingly implicated as underlying this relationship. However, it is unknown whether there is a broader spectrum of immune dysregulation beyond inflammatory activity. This study examined in CHF patients the relationship of depressive symptoms with cellular immune activity measured by Th1/Th2 ratios and cardiac rehospitalization and/or death.

Method: Eighteen patients with CHF (mean age = 62, NYHA classes II–IV) were enrolled and depressive symptoms were measured with interviewer ratings using the Hamilton Rating Scale-Depression. For the determination of Th1/Th2 ratios, intracellular cytokine expression of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) CD4+ T cells were measured by flow cytometry. Plasma interleukin-6 levels were measured to ascertain circulating inflammatory cytokine activity. Patient records were examined for cardiac related rehospitalization or cardiac related death over a two-year period after baseline depression and immune measures were taken.

Results: Higher depression scores were associated with a prospective increase in incidence of cardiac related hospitalizations and/or death (p = .037). Lesser IFN-gamma/IL-10 expressing CD4+ T cell ratios were related to higher depressive symptom scores at baseline (p = .005) and a prospective increased incidence of cardiac related hospitalization or death over a two-year period (p = .05).

Conclusions: A shift in the Th1/Th2 ratio may play a role in the association between depressive symptoms and morbidity and mortality in CHF patients, suggesting broader immune dysregulation than previously considered.

Key Words: heart failure • B-type natriuretic peptide • ejection fraction • depressed mood • immune dysregulation • cardiac rehospitalization

Abbreviations: CHF = congestive heart failure; IFN = interferon; IL = interleukin; NYHA = New York Heart Association; BNP = B-type natriuretic peptide; HAM-D = Hamilton Depression Scale; EF = ejection fraction; BMI = body mass index.

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