Mechanisms of the Relaxation Response in Elderly Hypertensives

描述（由申请人提供）：收缩期高血压是一种疾病，其特征是收缩压与正常舒张压相关的显著升高。通常，这种情况发生在50岁以下的人群中，并与中风和心肌梗死的风险增加有关。虽然有许多有效的治疗原发性/舒张性高血压的方法，但收缩期高血压的治疗由于传统治疗方法的副作用而变得复杂。这限制了治疗选择，并导致许多高危个体得不到治疗。我们最近完成了一项初步研究，表明8周的放松反应（RR）训练可显著降低SH患者的收缩压。收缩压显著降低9.4 mmHg，脉压显著降低7.9 mmHg。这一发现表明RR可能是一种有效的干预措施，在该患者群体中几乎没有不良后果。在其他实验中，我们发现RR增加了年轻成年志愿者呼出的一氧化氮和女性志愿者的血浆一氧化氮。由于一些原发性高血压患者的一氧化氮水平较低，因此一氧化氮可用性异常可能导致SH，并可能被RR改变。然而，RR影响SH的实际机制仍未确定。由于已知RR会改变交感神经反应，这可能是解释RR对SH影响的一种机制。导致这种影响的其他机制可能包括通过一氧化氮产生的改变或交感神经唤起（即应激反应）中的激素改变来改变血管功能。我们假设RR降低收缩压和脉压而没有明显的副作用，这是通过增加一氧化氮的产生和/或降低应激激素水平（肾上腺素和皮质醇）来实现的。为了验证这一假设，我们建议进行一项随机对照试验（n=90），其中老年SH患者将接受8周的RR干预或健康教育（HE）。主要结果是收缩压和脉压的变化。次要结果是一氧化氮、应激激素和心理健康的变化。进一步的分析将评估其他对BP和PP的混杂影响。目的1：评估与HE（对照组）相比，8周的RR干预是否会降低收缩压和脉压，且无明显副作用。目的2：评估与HE相比，8周的RR训练是否能提高一氧化氮水平。目的3：评估与HE相比，8周的RR训练是否能降低应激激素（肾上腺素和皮质醇）并改善心理健康（整体严重程度指数和焦虑）。虽然收缩压和脉压升高是心血管事件的重要危险因素，但由于担心副作用，许多医生不愿治疗这种疾病。考虑到药物控制收缩压的挑战和许多降压药产生的副作用的普遍存在，确定非药物方法来降低老年收缩期高血压(定义为收缩压140毫米汞柱，舒张压正常（舒张压<90毫米汞柱）患者的收缩压，可能对这种疾病的治疗有重要意义。这些积极的影响可能具有重要的经济意义，为当前的药物治疗方法提供了一种低成本的辅助治疗，并有可能降低心血管事件的发生率。

DESCRIPTION (provided by applicant): Systolic Hypertension is a disorder which is characterized by significant elevations in systolic blood pressure in association with normal diastolic blood pressure. Typically, this develops in individuals >50 years of age and is associated with an increased risk of stroke and myocardial infarction. While there are many effective therapies for essential/diastolic hypertension, the treatment of systolic hypertension is complicated by side effects from traditional therapies. This limits therapeutic options and has resulted in a number of at-risk individuals being left untreated. We have recently completed a preliminary study showing that 8-weeks of relaxation response (RR) training significantly reduced systolic blood pressure in individuals with SH. Systolic blood pressure was significantly decreased by 9.4 mmHg and pulse pressure by 7.9 mmHg. This finding would suggest that the RR may be an effective intervention with few to no adverse consequences in this patient population. In other experiments, we found that the RR increased exhaled nitric oxide in young adult volunteers and plasma nitric oxide in female volunteers. Since nitric oxide levels are low in some patients with essential hypertension, abnormalities in nitric oxide availability could be contributing to SH and might be altered by the RR. However, the actual mechanism by which the RR affects SH remains undetermined. Since the RR is known to alter sympathetic responses, this may be one mechanism which explains the effect of the RR on SH. Other mechanisms contributing to this effect could include alteration of vascular function via changes in nitric oxide production or hormonal alterations in sympathetic arousal (i.e., stress response). We hypothesize that the RR reduces systolic blood pressure and pulse pressure without significant side effects and that this occurs by increasing nitric oxide production and/or by reducing stress hormone levels (epinephrine and cortisol). To examine this hypothesis, we propose conducting a randomized, controlled trial (n=90) in which older adults with SH will receive either 8-weeks of RR intervention or Health Education (HE). The primary outcome is change in systolic blood pressure and pulse pressure. Secondary outcomes are changes in nitric oxide, stress hormones and psychological well-being. Additional analyses will be conducted to assess for other confounding effects on BP and PP. Aim 1: Assess if an 8-week RR intervention will decrease systolic blood pressure and pulse pressure compared with HE (control) without significant side effects. Aim 2: Evaluate whether 8-weeks of RR training increases levels of nitric oxide compared with HE. Aim 3: Assess whether 8-weeks of RR training decreases stress hormones (epinephrine and cortisol) and improves psychological well-being (global severity index and anxiety) compared with HE. While elevated systolic blood pressure and pulse pressure are important risk factors for cardiovascular events, concerns about side effects leave many physicians reluctant to treat this condition. Given the challenges of controlling systolic blood pressure pharmacologically and the prevalence of side effects produced by many antihypertensive agents, identification of non-pharmacologic approaches to decrease systolic blood pressure in older Systolic Hypertension (defined as SBP >140 mm Hg with normal diastolic blood pressure (DBP <90 mm Hg) patients could contribute significantly to the treatment of this condition. These positive effects could have significant economic implications by providing a low-cost adjunctive therapy to current pharmacologic approaches and potentially reduce the incidence of cardiovascular events.