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

现代化协作护理可降低抑郁症患者的过度 CVD 风险

• 批准号: 9250190
• 负责人: Jesse C Stewart
• 金额: $ 60.2万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-21 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9250190
• 关键词: Address; Adult; African American; Aftercare; American; Antidepressive Agents; Autonomic Dysfunction; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Caring; Clinical; Clinical Trials; Cognitive Therapy; Data; Depressed mood; Depressive disorder; Disease Outcome; Early treatment; Economic Burden; Event; Exhibits; Female; Follow-Up Studies; Goals; Health Care Costs; Incidence; Indiana; Inflammation; Intervention; Latino; Mediating; Mediator of activation protein; Mental Depression; Modernization; Moods; Morbidity - disease rate; Myocardial Infarction; Natural History; Onset of illness; Outcome; Pathogenesis; Patient Care; Patient Preferences; Patient risk; Patients; Phase; Phase III Clinical Trials; Platelet Activation; Primary Health Care; Prognostic Factor; Provider; Public Health; Randomized; Randomized Controlled Trials; Research; Risk; Risk Factors; Site; Specific qualifier value; Stroke; Telephone; Testing; Translating; Visit; Woman; cardiovascular disorder prevention; cardiovascular disorder risk; clinical practice; clinically relevant; cohort; collaborative care; computerized; cost; depressed patient; depressive symptoms; design; disorder risk; endothelial dysfunction; evidence base; follow-up; high risk; hypercholesterolemia; improved; men; mortality; multidisciplinary; novel; outcome forecast; prevent; primary outcome; programs; prospective; public health relevance; secondary outcome; tool; treatment as usual; treatment effect; treatment trial; virtual

 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.

 描述（申请人提供）： 心血管疾病（CVD）是美国男性和女性的头号杀手，其经济负担巨大且呈上升趋势。患有抑郁症的成年人发生 CVD 事件的风险较高，且 CVD 预后较差。不幸的是，过去的抑郁症治疗试验并未观察到预期的心血管益处。对这些无效结果的一个新解释是，这些试验中的干预措施都涉及既往患有 CVD 的患者，但在 CVD 自然史中实施得太晚。为了开始评估我们的假设，即在临床 CVD 发病前治疗抑郁症可以降低 CVD 风险，我们对一项积极的抑郁症试验（IMPACT 试验）进行了为期 8 年的随访研究。与常规护理患者相比，没有基线 CVD 的干预患者发生致命/非致命心肌梗塞或中风的风险降低 48%。虽然这些 结果支持我们的假设，它们是事后和观察性的，CVD 结果不是预先指定的终点，并且收集了最少的机械数据。为了满足当前对强有力的前瞻性试验的需求，我们提议对 216 名患有抑郁症和 CVD 风险升高但没有临床 CVD 的初级保健患者（= 50 岁，60% 女性，40% 非裔美国人，5% 拉丁裔）进行 2 期随机对照试验。患者将被随机分配接受为期一年的 eIMPACT（我们的 IMPACT 干预的现代化版本）或常规护理。 eIMPACT 是一种协作性阶梯式护理干预措施，涉及多学科团队，提供符合患者偏好的循证抑郁症治疗方法。我们将通过纳入计算机化认知行为疗法并通过电话提供其他治疗成分来现代化我们的干预措施。我们的中心假设是，eIMPACT 将通过减少自主神经功能障碍、全身炎症和血小板活化来改善抑郁成人的内皮功能障碍，内皮功能障碍被认为是 CVD 风险的晴雨表。我们将通过实现以下具体目标来检验我们的中心假设：(1) 确定 eIMPACT 是否会降低抑郁症患者的过度 CVD 风险（主要结果：内皮功能障碍；探索性结果：CVD 事件事件）和 (2) 检查 eIMPACT 对 CVD 风险影响的潜在机制（次要结果：自主神经功能障碍、全身性炎症和心血管疾病的标志物） 血小板活化）。一项积极的试验将产生机制原理、疗效证据和效应大小估计，这些都是证明和设计多中心、事件驱动的 3 期试验所需的，以确认 eIMPACT 在降低 CVD 风险方面的功效。证明抑郁症治疗可降低心血管疾病风险（这一研究的主要预期结果）将产生重大的积极影响。它将为 CVD 预防工作确定一个新的治疗目标（抑郁症），并将为提供者提供一种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 CVD 风险。总的来说，临床实践的这些变化应该转化为心血管疾病发病率、死亡率和费用的降低。