Importance Anxiety is common among patients with coronary heart disease (CHD) and is associated with worse health outcomes; however, effective treatment for anxiety in patients with CHD is uncertain. Objective To determine whether exercise and escitalopram are better than placebo in reducing symptoms of anxiety as measured by the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) and in improving CHD risk biomarkers. Design, Setting, and Participants This randomized clinical trial was conducted between January 2016 and May 2020 in a tertiary care teaching hospital in the US and included 128 outpatients with stable CHD and a diagnosed anxiety disorder or a HADS-A score of 8 or higher who were older than 40 years, sedentary, and not currently receiving mental health treatment. Interventions Twelve weeks of aerobic exercise 3 times per week at an intensity of 70% to 85% heart rate reserve, escitalopram (up to 20 mg per day), or placebo pill equivalent. Main Outcomes and Measures The primary outcome was HADS-A score. CHD biomarkers included heart rate variability, baroreflex sensitivity, and flow-mediated dilation, along with 24-hour urinary catecholamines. Results The study included 128 participants. The mean (SD) age was 64.6 (9.6) years, and 37 participants (29%) were women. Participants randomized to the exercise group and escitalopram group reported greater reductions in HADS-A (exercise, -4.0; 95% CI, -4.7 to -3.2; escitalopram, -5.7; 95% CI, -6.4 to -5.0) compared with those randomized to placebo (-3.5; 95% CI, -4.5 to -2.4; P = .03); participants randomized to escitalopram reported less anxiety compared with those randomized to exercise (-1.67; 95% CI, -2.68 to -0.66; P = .002). Significant postintervention group differences in 24-hour urinary catecholamines were found (exercise z score = 0.05; 95% CI, -0.2 to 0.3; escitalopram z score = -0.24; 95% CI, -0.4 to 0; placebo z score = 0.36; 95% CI, 0 to 0.7), with greater reductions in the exercise group and escitalopram group compared with the placebo group (F1,127 = 4.93; P = .01) and greater reductions in the escitalopram group compared with the exercise group (F1,127 = 4.37; P = .04). All groups achieved comparable but small changes in CHD biomarkers, with no differences between treatment groups. Conclusions and Relevance Treatment of anxiety with escitalopram was safe and effective for reducing anxiety in patients with CHD. However, the beneficial effects of exercise on anxiety symptoms were less consistent. Exercise and escitalopram did not improve CHD biomarkers of risk, which should prompt further investigation of these interventions on clinical outcomes in patients with anxiety and CHD. Trial Registration ClinicalTrials.gov Identifier: NCT02516332.

中文翻译：

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运动、依他普仑或安慰剂对冠心病患者焦虑的影响：了解运动和艾司西酞普兰对冠心病焦虑患者的益处 (UNWIND) 随机临床试验。

重要性 焦虑在冠心病 (CHD) 患者中很常见，并且与较差的健康结果相关；然而，对 CHD 患者焦虑的有效治疗尚不确定。目的 确定运动和依他普仑在减轻医院焦虑和抑郁-焦虑量表 (HADS-A) 测量的焦虑症状和改善 CHD 风险生物标志物方面是否优于安慰剂。设40 岁以上，久坐不动，目前未接受心理健康治疗。干预 12 周的有氧运动，每周 3 次，强度为 70% 至 85% 的心率储备，依他普仑（每天最多 20 毫克）或安慰剂药片等效物。主要结果和措施 主要结果是 HADS-A 评分。CHD 生物标志物包括心率变异性、压力反射敏感性和流量介导的扩张，以及 24 小时尿儿茶酚胺。结果 该研究包括 128 名参与者。平均 (SD) 年龄为 64.6 (9.6) 岁，37 名参与者 (29%) 为女性。随机分配到运动组和依他普仑组的参与者报告说，与那些相比，HADS-A 的降低更大（运动，-4.0；95% CI，-4.7 至 -3.2；依他普仑，-5.7；95% CI，-6.4 至 -5.0）随机分配至安慰剂组（-3.5；95% CI，-4.5 至 -2.4；P = .03）；与随机参加运动的参与者相比，随机接受依他普仑的参与者报告的焦虑更少（-1.67；95% CI，-2.68 至 -0.66；P = .002）。发现 24 小时尿儿茶酚胺在干预后组间存在显着差异（运动 z 评分 = 0.05；95% CI，-0.2 至 0.3；依他普仑 z 评分 = -0.24；95% CI，-0.4 至 0；安慰剂 z 评分 = 0.36； 95% CI，0 至 0.7），与安慰剂组相比，运动组和依他普仑组的减少幅度更大（F1,127 = 4.93；P = .01），与运动组相比，依他普仑组的减少幅度更大（F1 ,127 = 4.37；P = .04)。所有组都在 CHD 生物标志物方面实现了可比但微小的变化，治疗组之间没有差异。结论及相关性 依他普仑治疗焦虑对于减轻冠心病患者的焦虑是安全有效的。然而，运动对焦虑症状的有益影响不太一致。运动和依他普仑并没有改善冠心病风险的生物标志物，这应该促使进一步研究这些干预措施对焦虑和冠心病患者临床结果的影响。试验注册 ClinicalTrials.gov 标识符：NCT02516332。