Autonomic and Immuno-vascular Mechanisms of Antihypertensive Effects of Taichi

 说明(申请人提供)：这是1R01HL126056-01的修订版。作为对评审者的回应，我们更好地描绘了太极(TC)降低血压(BP)的潜在途径，改善了我们的控制条件以增加积极参与，缩小了我们的BP登记标准(1期和轻度2期高血压)，并将我们的随访延长到9个月。高血压(HTN)在美国和全世界都是一个普遍存在的问题。超过30%的美国成年人患有HTN，发病率随着年龄的增长而显著增加；在65岁以上的男性和女性中有78%的人患有HTN。HTN是世界范围内导致过早死亡的最重要原因之一，也是最重要的可预防死亡原因之一。许多临床试验表明，降低血压对减少心血管疾病、心血管疾病相关死亡和中风有好处。尽管HTN的治疗通常强调药物治疗，但非药物治疗的重要性被认为是疾病阻断的重要手段，并具有广泛的公共卫生意义。越来越多的证据表明，TC在降低HTN患者的血压方面是有效的，文献中的SBP范围为7-32 mm Hg，但由于现有研究的方法学质量降低，TC被认为是不确定的。非常需要严格设计的随机和对照试验。此外，TC训练降低血压的机制尚不清楚。HTN的神经源性假说描述了HTN由于交感神经系统(SNS)激活升高和副交感神经系统(PNS)损害而导致的失衡。TC练习被证明可以减少焦虑和抑郁症状等心理困扰，并减少生理唤醒，这可能会改善自主神经平衡，从而降低血压。然而，先前没有研究描述TC在HTN中降低血压的途径。因此，我们计划调查自主神经、血管动力学、免疫血管和心理变化之间的潜在途径，并与健康老龄化实践中心教育(HAP-E)控制条件进行比较，这些变化与12周TC前后血压变化有关。250名老年(60-80岁)的1期和轻度2期HTN将入选，并将测量压力反射敏感度、心率和血压变异性以及运动后心率恢复以检查自主神经调节。TC后自主神经的“再调节”被认为是通过脉搏波速度(Aim 1)和交感-肾上腺素能系统(Aim 2)调节炎症来调节TC对血压和血管健康的影响。最后，TC对自主神经调节的影响被认为是由心理因素介导的(目标3)。我们随机对照干预研究的结果将阐明TC降压疗效的心理-神经-血管-免疫学基础。此外，我们将阐明TC(“冥想运动”)在老年、“难以治疗”的高血压人群中的独特效果，这些人群将特别受益于这种行为疗法。

 DESCRIPTION (provided by applicant): This is a revised version of 1R01HL126056-01. In response to reviewers we have better delineated potential pathways of blood pressure (BP) reduction by Tai Chi (TC), enhanced our control condition to increase active participation, narrowed our BP enrollment criteria (stage 1 and mild stage 2 hypertension) and extended our follow-up to 9 months. Hypertension (HTN) is a pervasive problem in the US and worldwide. Over 30% of American adults have HTN, with the incidence increasing substantially with age; 64% of men and 78% of women over 65 having HTN. HTN is one of the most important causes of premature death worldwide and one of the most significant preventable causes of death. Numerous clinical trials have revealed benefits of lowering BP for reductions in cardiovascular (CV) disease, CV-related death and stroke. Although pharmacologic therapy is often emphasized for HTN management, the importance of non-pharmacologic approaches is recognized for disease interruption and bears vast public health significance. There is growing evidence that TC is effective in lowering BP for patients with HTN, ranging 7 - 32 mm Hg SBP in the literature but is considered inconclusive due to reduced methodological quality of existing studies. Rigorously designed randomized and controlled trials are in great need. Furthermore, the mechanisms by which TC training reduces BP are unknown. The `neurogenic hypothesis' of HTN describes the imbalance owing to elevated sympathetic nervous system (SNS) activation and parasympathetic nervous system (PNS) impairment in HTN. TC practice is shown to reduce psychological distress such as anxiety and depression symptoms and reduce physiological arousal which can potentially improve autonomic balance, resulting in reduced BP. However, no prior studies have delineated the pathways through which TC reduces BP in HTN. Thus, we plan to investigate the underlying pathways among autonomic, vascular-dynamic, immuno-vascular and psychological alterations in relation to BP changes pre to post 12-week TC compared to a Healthy Aging Practice-centered Education (HAP-E) control condition. 250 older adults (60-80 years old) with stage 1 and mild stage 2 HTN will be enrolled, and baroreflex sensitivity, heart rate and BP variability and post-exercise HR recovery will be measured to examine autonomic regulation. Post TC autonomic "re-regulation" is hypothesized to mediate TC effects on BP and vascular health measured by pulse wave velocity (Aim 1) and inflammation regulation by sympatho-adrenergic system (Aim 2). Lastly, TC effects on autonomic regulation is hypothesized to be mediated by psychological factors (Aim 3). Findings from our randomized and controlled intervention study will shed light on the psycho-neuro-vasculo-immunological underpinnings of antihypertensive efficacy of TC. Also, we would clarify the unique effects of TC ("meditative movement") in an older, "hard-to-treat" hypertensive population that would particularly benefit from this behavioral therapeutic.