BNP and Neuroimmune Characteristics of CHF & Depression

7.项目总结/摘要 心力衰竭（HF）是一个主要的公共卫生问题，影响超过550万美国人， 每年诊断出55万例新病例，占所有住院病例的10%。抑郁 是有症状的糖尿病患者发病率和过早死亡率的最可靠的行为预测因子。 HF，发生率范围为20%-45%，取决于HF的严重程度。我们正在进行的项目HL-073355是 检查HF患者中与抑郁症相关的病理生理学。很少有研究系统地 检查抑郁症的发展和进展， 症状性HF及其相关的神经免疫和行为机制。通过招募个人， 发生症状性HF的风险，但目前无症状，即美国大学 心脏病学/美国心脏协会（ACC/AHA）B期患者，HL-073355的竞争性更新 将前瞻性跟踪抑郁症状和重度抑郁症的发生率和时间进程 (MDD)症状性HF的发展，与HF相关的潜在神经免疫和行为机制 和MDD，以及与心血管临床结局的相关性。我们将入组522例高风险（定义为BNP > 100 pg/ml）ACC/AHA B期患者，在摄入时对其进行研究，并每6个月进行一次，平均30 个月通过我们与加州大学圣地亚哥分校HF团队的紧密合作， （UCSD）Hillcrest和拉霍亚医疗中心，以及退伍军人事务部圣地亚哥医疗保健系统 （VASDHS）在拉霍亚，我们可以接触到大量无症状的B期患者。临床 评估将包括超声心动图和贝克抑郁症状的特征 抑郁量表（BDI）和DSM疾病结构化临床访谈（SCID）。神经免疫 评估将包括BNP、CRP、TNF-α、IL-1、IL-6、sICAM-1、sP-选择素的循环水平， 儿茶酚胺和白细胞的功能评估。除了抑郁症，其他行为和 心理社会评估将包括睡眠，健康行为（例如，吸烟、体力活动）， 心理社会压力源、应对、焦虑、社会网络和生活质量。临床结局将包括 从无症状性心功能不全转变为症状性C期和/或D期HF，临床心血管 结局（因心血管事件住院和/或死亡），以及发展或 MDD复发。这项前瞻性研究的结果有可能增加对MDD如何 可能在疾病的早期阶段促进HF进展。更好地理解角色， MDD在此阶段可能影响HF的机制可以支持临床相关的早期MDD 在有效的抑郁症治疗可能对抑郁症产生更大影响的时候， HF的过程。

7. PROJECT SUMMARY/ABSTRACT Heart failure (HF) is a major public health concern, affecting more than 5.5 million Americans, with over 550,000 new cases diagnosed each year, and accounting for up to 10% of all hospital admissions. Depression is the most robust behavioral predictor of morbidity and premature mortality among patients with symptomatic HF, with an incidence ranging from 20% to 45%, depending on HF severity. Our ongoing project HL-073355 is examining the pathophysiology associated with depression in HF patients. Few studies have systematically examined the development and progression of depression concurrent with the development of and progression to symptomatic HF and its associated neuroimmune and behavioral mechanisms. By enrolling individuals at risk for developing symptomatic HF but who are currently asymptomatic, namely American College of Cardiology/American Heart Association (ACC/AHA) Stage B patients, this competing renewal of HL-073355 will prospectively track the incidence and time course of depressive symptoms and Major Depressive Disorder (MDD), the development of symptomatic HF, potential neuroimmune and behavioral mechanisms linking HF and MDD, and associations with cardiovascular clinical outcomes. We will enroll 522 high-risk (defined as BNP >100pg/ml) ACC/AHA Stage B patients, study them at intake, and every 6 months for an average of 30 months. Through our strong collaborations with the HF teams at the University of California, San Diego (UCSD) Hillcrest and La Jolla Medical Centers, and the Veterans Affairs San Diego Healthcare System (VASDHS) in La Jolla, we have access to a large number of asymptomatic Stage B patients. Clinical assessments will include echocardiography and characterization of depressive symptoms by the Beck Depression Inventory (BDI) and the Structured Clinical Interview for DSM Disorders (SCID). Neuroimmune assessments will include circulating levels of BNP, CRP, TNF-¿, IL-1¿, IL-6, sICAM-1, sP-selectin, catecholamines, and functional assessments of leukocytes. In addition to depression, other behavioral and psychosocial assessments will include sleep, health behaviors (e.g., smoking, physical activity), psychosocial stressors, coping, anxiety, social network, and quality of life. Clinical outcomes will include transition from asymptomatic cardiac dysfunction to symptomatic Stages C and/or D HF, clinical cardiovascular outcomes (combined hospitalizations for cardiovascular events and/or death), and the development or recurrence of MDD. Findings from this prospective study have the potential to add new insights into how MDD might contribute to HF progression at early stages of the disease. A greater understanding of the role and mechanisms by which MDD may impact HF at this stage could support clinically relevant early MDD intervention efforts at a point when effective depression treatment could have a potentially greater impact on the course of HF.