BNP and Neuroimmune Characteristics of CHF & Depression

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，每年诊断出超过550，000例新病例，占所有住院人数的10%。抑郁症是症状性HF患者发病率和过早死亡率最可靠的行为预测因子，发病率范围为20%-45%，取决于HF的严重程度。我们正在进行的项目HL-073355正在研究HF患者与抑郁症相关的病理生理学。很少有研究系统地研究抑郁症的发展和进展与症状性HF的发展和进展及其相关的神经免疫和行为机制。通过招募有发生症状性HF风险但目前无症状的个体，即美国心脏病学会/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（MDD）的发生率和时间进程、症状性HF的发生、HF和MDD之间的潜在神经免疫和行为机制，以及与心血管临床结局的相关性。我们将入组522例高危（定义为BNP > 100 pg/ml）ACC/AHA B期患者，在入组时进行研究，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（UCSD）Hillcrest和拉霍亚医疗中心的HF团队以及位于拉霍亚的退伍军人事务部圣地亚哥医疗保健系统（VASDHS）的密切合作，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量表（BDI）和DSM疾病结构化临床访谈（SCID）对抑郁症状的表征。神经免疫评估将包括BNP、CRP、TNF-1、IL-12、IL-6、sICAM-1、sP-选择素、儿茶酚胺的循环水平和白细胞功能评估。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（合并心血管事件住院和/或死亡）以及MDD的发生或复发。这项前瞻性研究的结果有可能为MDD如何在疾病的早期阶段促进HF进展提供新的见解。更好地了解MDD在此阶段可能影响HF的作用和机制，可以支持临床相关的早期MDD干预工作，此时有效的抑郁治疗可能对HF的病程产生更大的影响。 公共卫生相关性：抑郁症是心力衰竭患者发病率和过早死亡率最可靠的行为预测因子，尽管这种关系的机制尚不清楚。在美国心脏病学会/美国心脏协会（ACC/AHA）分类的无症状B期患者队列中，我们将前瞻性跟踪抑郁症状、症状性C/D期心力衰竭的发展和进展以及与不良临床心血管结局的相关性，并在自然主义框架内确定潜在的神经免疫、行为和心理社会机制。

DESCRIPTION (provided by applicant): 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-1, IL-12, 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. PUBLIC HEALTH RELEVANCE: Depression is the most robust behavioral predictor of morbidity and premature mortality among patients with heart failure, although the mechanisms of this relationship are poorly understood. In a cohort of American College of Cardiology/American Heart Association (ACC/AHA) classification asymptomatic Stage B patients, we will prospectively track depressive symptoms, the development and progression to symptomatic Stages C/D heart failure, and associations with adverse clinical cardiovascular outcomes, as well as determine potential neuroimmune and behavioral and psychosocial mechanisms within a naturalistic framework.