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

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Abstract
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. 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.