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: 9057137
• 负责人: Jesse C Stewart
• 金额: $ 69.6万
• 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/9057137
• 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; Goals; Health; Health Care Costs; Incidence; Indiana; Inflammation; Intervention; Latino; Mediating; Mediator of activation protein; Mental Depression; Moods; Morbidity - disease rate; Myocardial Infarction; Natural History; Onset of illness; Outcome; Pathogenesis; Patient Preferences; 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; Staging; Stroke; Telephone; Testing; Translating; Visit; Woman; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; clinical practice; clinically relevant; cohort; collaborative care; computerized; cost; depressed patient; depressive symptoms; design; endothelial dysfunction; evidence base; follow-up; high risk; hypercholesterolemia; improved; men; mortality; multidisciplinary; novel; outcome forecast; prevent; primary outcome; programs; prospective; secondary outcome; tool; treatment as usual; treatment effect; treatment trial

 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（由申请人提供）：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。成年抑郁症患者发生CVD事件的风险升高，CVD预后不良。不幸的是，过去的抑郁症治疗试验没有观察到预期的心血管益处。对这些无效结果的一种新解释是，这些试验中的干预措施都涉及既存心血管疾病的患者，但在心血管疾病的自然史中实施得太晚了。为了开始评估我们的假设，即在临床CVD发作前治疗抑郁症可以降低CVD风险，我们对一项阳性抑郁症试验IMPACT试验进行了8年的随访研究。基线时无心血管疾病的干预患者发生致命性/非致命性心肌梗死或卒中的风险比常规治疗患者低48%。虽然这些 结果支持我们的假设，它们是事后的和观察性的，CVD结果不是预先指定的终点，并且收集了最少的机制数据。为了解决目前对一项具有良好把握度的前瞻性试验的需求，我们提出了一项2期随机对照试验，纳入216名患有抑郁症和CVD风险升高但无临床CVD的初级保健患者（≥ 50岁，60%女性，40%非洲裔美国人，5%拉丁裔）。患者将被随机分配到一年的eIMPACT，我们的IMPACT干预的现代化版本，或常规护理。eIMPACT是一种协作式阶梯式护理干预，涉及多学科团队，提供符合患者偏好的循证抑郁症治疗。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成分来实现干预的现代化。我们的中心假设是，eIMPACT将改善内皮功能障碍，这被认为是心血管疾病风险的晴雨表，在抑郁症的成年人减少自主神经功能障碍，全身炎症，血小板活化。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是否降低抑郁症患者的过度CVD风险（主要结局：内皮功能障碍;探索性结局：偶发CVD事件）和（2）检查eIMPACT对CVD风险影响的潜在机制（次要结局：自主神经功能障碍，全身炎症和血小板活化的标志物）。一项积极的试验将产生机制原理、疗效证据和效应量估计，这些都是证明和设计多中心、事件驱动的3期试验以证实eIMPACT在降低CVD风险方面的疗效所需的。证明抑郁症治疗可以降低心血管疾病的风险，这是这一系列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风险患者的CVD风险。总的来说，这些临床实践的变化应转化为降低CVD发病率，死亡率和成本。