Modernized Collaborative Care to Reduce the Excess CVD Risk of Depressed Patients

 简介(申请人提供)：心血管疾病(CVD)是美国男性和女性的头号杀手，其经济负担很大，而且还在上升。患有抑郁症的成年人发生心血管事件的风险较高，心血管疾病预后较差。不幸的是，过去的抑郁症治疗试验并没有观察到预期的心血管益处。对这些无效结果的一种新的解释是，这些试验中的干预措施都涉及先前存在的CVD患者，在CVD的自然历史中实施得太晚了。为了开始评估我们的假设，即在临床CVD发作之前治疗抑郁症可以降低CVD风险，我们进行了一项为期8年的积极抑郁症试验的跟踪研究，即IMPACT试验。与常规护理患者相比，没有基线心血管疾病的干预患者发生致命性/非致命性心肌梗死或中风的风险降低48%。尽管这些 结果支持我们的假设，他们是后随机的和观察性的，CVD结果不是预先指定的终点，并且收集了最少的机械性数据。为了满足目前对强大的前瞻性试验的需求，我们提出了一项第二阶段随机对照试验，对象为216名患有抑郁障碍和心血管风险升高但没有临床心血管疾病的初级保健患者(=50岁，60%女性，40%非裔美国人，5%拉丁裔)。患者将随机接受为期一年的eIMPACT，即我们的现代版本的Impact干预，或常规护理。EIMPACT是一种协作性的分步护理干预措施，涉及一个多学科团队，提供与患者偏好一致的循证抑郁症治疗。我们将通过整合计算机化的认知行为治疗和通过电话提供其他治疗组件来实现干预措施的现代化。我们的中心假设是，eIMPACT将通过减少自主神经功能障碍、全身炎症和血小板激活来改善被认为是心血管风险的晴雨表的抑郁症成年人的内皮功能障碍。我们将通过实现这些特定的目标来检验我们的中心假说：(1)确定eIMPACT是否可以降低抑郁症患者的过度心血管风险(主要结果：内皮功能障碍；探索性结果：心血管事件)；(2)检查eIMPACT对心血管风险影响的候选机制(次要结果：自主神经功能障碍、全身炎症和血小板激活的标志)。一项积极的试验将产生证明和设计一项多点、事件驱动的第三阶段试验以证实eIMPACT在降低心血管疾病风险方面的有效性所需的机械原理、疗效证据和效应大小估计。这一系列研究的主要预期结果表明，抑郁症治疗降低了心血管疾病风险，这将产生实质性的积极影响。它将为心血管疾病预防工作确定一个新的治疗目标(抑郁症)，并将为提供者配备一个新的可传播和可扩展的工具(EIMPACT)，以同时治疗抑郁症和管理大量高危患者的心血管风险。总而言之，临床实践的这些变化应该转化为降低心血管疾病的发病率、死亡率和成本。

 DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the number one killer of American men and women, and its economic burden is substantial and on the rise. Adults with depression are at elevated risk of CVD events and poor CVD prognosis. Unfortunately, past trials of depression treatments have not observed the anticipated cardiovascular benefits. A novel explanation for these null results is that the interventions in these trials, which all involved patients with preexisting CVD, were delivered too late in the natural history of CVD. To begin to evaluate our hypothesis that treating depression before clinical CVD onset could reduce CVD risk, we conducted an 8-year follow-up study of a positive depression trial, the IMPACT trial. Intervention patients without baseline CVD had a 48% lower risk of fatal/nonfatal myocardial infarction or stroke than did usual care patients. Although these results support our hypothesis, they are post hoc and observational, CVD outcomes were not pre-specified endpoints, and minimal mechanistic data was collected. To address the current need for a well-powered, prospective trial, we propose a Phase 2 randomized controlled trial of 216 primary care patients (=50 years, 60% female, 40% African American, 5% Latino) with a depressive disorder and elevated CVD risk but no clinical CVD. Patients will be randomized to one year of eIMPACT, our modernized version of the IMPACT intervention, or usual care. eIMPACT is a collaborative stepped care intervention involving a multidisciplinary team delivering evidenced-based depression treatments consistent with patient preference. We will modernize our intervention by incorporating computerized cognitive-behavioral therapy and delivering other treatment components via telephone. Our central hypothesis is that eIMPACT will improve endothelial dysfunction, which is considered a barometer of CVD risk, in depressed adults by decreasing autonomic dysfunction, systemic inflammation, and platelet activation. We will test our central hypothesis by carrying out these specific aims: (1) to determine whether eIMPACT reduces the excess CVD risk of depressed patients (primary outcome: endothelial dysfunction; exploratory outcome: incident CVD events) and (2) to examine candidate mechanisms underlying the effect of eIMPACT on CVD risk (secondary outcomes: markers of autonomic dysfunction, systemic inflammation, and platelet activation). A positive trial would generate the mechanistic rationale, efficacy evidence, and effect size estimates that are needed to justify and design a multisite, event-driven Phase 3 trial to confirm eIMPACT's efficacy in reducing CVD risk. Demonstrating that depression treatment reduces CVD risk, the primary expected outcome of this line of research, would have a substantial positive impact. It would identify a novel treatment target (depression) for CVD prevention efforts, and it would equip providers with a new disseminable and scalable tool (eIMPACT) to simultaneously treat depression and manage CVD risk of a large cohort of high-risk patients. Collectively, these changes to clinical practice should translate into reduced CVD morbidity, mortality, and costs.