BNP (Brain Natriuretic Peptide) and Neuroimmune Characteristics of Chronic Heart Failure and Depression

“BNP and Neuroimmune Characteristics of Chronic Heart Failure and Depression”

Project leader: Paul J. Mills
Project duration: 2005 - 2009
Funding: National Institutes of Health USA (HL-073355 and HL-57265 to PJM), Swiss National Science Foundation (IZKOBO-122843/1 to PW)       

Congestive heart failure (CHF) is a major public health concern, affecting more than 4.5 million Americans with 550,000 cases being diagnosed each year. CHF is characterized by neuroimmune activation, including increased levels of proinflammatory cytokines and increased leukocyte activation and adhesion. Depression is the most robust behavioral predictor of premature mortality and morbidity among patients with CHF. A relatively large literature documents neuroimmune and cellular adhesion molecule alterations in patients with major depression, but translation of these observations into clinically relevant outcomes in CHF patient s remains incomplete. No studies have examined whether neuroimmune activation is the underlying pathophysiological mechanism through which depression worsens outcomes in patients with CHF. This study will examine BNP levels and neuroimmune (norepinephrine, IL-6, TNF-alpha, IL-1beta, CRP) and cellular adhesion molecule (sICAM-1 and sP -selectin levels, CD11a and CD11b expression on peripheral blood mononuclear cells (PBMC), and PBMC chemotaxis) characteristics in 200 CHF patients with and without major depression and 100 non-CHF controls with and without major depression. CHF patients with and without major depression will be followed in a naturalistic prospective design over 18 months to examine neuroimmune, adhesion molecule contributions to adverse clinical outcomes. The overarching hypothesis of this study is that neuroimmune and adhesion molecule activation constitute an important pathophysiological pathway linking depression to worse outcomes in CHF. 

Wirtz, P.H., Hong, S., Redwine , L.S., Tafur , J., Rutledge, T., Ziegler, M., Greenberg , B., Mills, P.J. (2009). Depressive symptoms are associated with soluble P-selectin ( sP -selectin) reactivity to acute exercise in heart failure. Biological Psychiatry 65(9): 801-807. [Link] 

Redwine , L.S., Wirtz , P.H., Hong, S., Pandzic , I., Cammarata , S., Tafur , J., Carter, S.M., Greenberg, B. & Mills, P.J. (2009). A potential shift from adaptive immune activity to non-specific inflammatory activation associated with higher depression symptoms in congestive heart failure patients. J Card Fail 15(7):607-15. [Link]

Wirtz , P.H., Redwine , L.S., Hong, S., Linke , S., Rutledge, T., Greenberg, B.H., Dimsdale , J.E., Mills, P. (2010). Increases in B-type natriuretic peptide (BNP) after acute mental stress in male heart failure patients are associated with alcohol consumption. J Stud Alcohol Drugs 71(5):768-94. [Link]

Wirtz , P.H., Redwine , L.S., Linke , S., Hong, S., Rutledge, T., Greenberg, B.H., Mills, P. (2010). Circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) independently predict depressive symptom severity after 12 months in heart failure patients.  Brain Behav Immun 24(3):266-369. [Link]

Wirtz, P.H. & Redwine , L.S., & Mills, P.J. (2010). Inflammation as a predictor of depression in heart failure. Brain Behav Immun 24(2):174-175. [Link]

Redwine , L.S. Wirtz, P.H., Hong, S., Bosch, J., Ziegler, M., Greenberg , B.H., Mills, P.J. (2010). Depression as a potential modulator of beta-adrenergic-associated leukocyte mobilization in heart failure patients. J Am Coll Cardiol 56(21):1720-7. [Link]