BNP and Neuroimmune Characteristics of CHF & Depression

描述（由申请人提供）：充血性心力衰竭（CHF）是一个主要的公共卫生问题，影响超过450万美国人，每年诊断出55万例。CHF的特征是神经免疫激活，包括促炎细胞因子水平升高，白细胞激活和粘附增加。抑郁是慢性心力衰竭患者过早死亡和发病的最可靠的行为预测因子。大量文献记录了重度抑郁症患者的神经免疫和细胞粘附分子改变，但将这些观察结果转化为CHF患者的临床相关结果仍不完整。没有研究证实神经免疫激活是否是抑郁症恶化CHF患者预后的潜在病理生理机制。本研究将检测200例伴有和不伴有重度抑郁的CHF患者和100例伴有和不伴有重度抑郁的非CHF对照组的BNP水平、神经免疫（去甲肾上腺素、IL-6、tnf - α、il -1 β、CRP）和细胞粘附分子（sICAM-1和sp -选择素水平、外周血单个核细胞（PBMC） CD11a和CD11b表达以及PBMC趋化性）特征。采用自然的前瞻性设计，对伴有或不伴有重度抑郁症的CHF患者进行为期18个月的随访，以检查神经免疫、粘附分子对不良临床结果的影响。本研究的首要假设是，神经免疫和粘附分子激活构成了一个重要的病理生理途径，将抑郁与CHF的不良预后联系起来。

DESCRIPTION (provided by applicant): 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 patients 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.