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以收缩压显著升高伴正常舒张压为特征的疾病。通常情况下，这发生在>50岁的个体中，并且与中风和心肌梗死的风险增加有关。虽然原发性/舒张期高血压有许多有效的治疗方法，但收缩期高血压的治疗因传统治疗的副作用而复杂化。这限制了治疗选择，并导致许多有风险的人得不到治疗。我们最近完成的一项初步研究表明，8周的放松反应（RR）训练显著降低了SH患者的收缩压。收缩压显著下降9.4 mmHg，脉压显著下降7.9 mmHg。这一发现表明，RR可能是一种有效的干预措施，在该患者人群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，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的实际机制仍不确定。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。促成这种效应的其他机制可能包括通过一氧化氮产生的变化或交感神经唤醒中的激素改变来改变血管功能（即，应激反应）。我们假设RR降低收缩压和脉压而没有显著的副作用，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。将进行额外分析，以评估对BP和PP的其他混杂效应。目标1：评估与HE（对照）相比，8周RR干预是否会降低收缩压和脉压，且无显著副作用。目的2：评估与HE相比，8周的RR训练是否增加了一氧化氮水平。目标3：评估与HE相比，8周的RR训练是否降低了应激激素（肾上腺素和皮质醇）并改善了心理健康（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，但对副作用的担忧使许多医生不愿意治疗这种疾病。考虑到控制收缩压的挑战和许多抗高血压药物产生的副作用的普遍性，确定非药物方法来降低老年收缩期高血压（定义为SBP >140 mm Hg，舒张压正常（DBP <90 mm Hg））患者的收缩压，可能会显著有助于治疗这种疾病。这些积极的影响可能具有显着的经济意义，提供了一个低成本的替代治疗，目前的药理学方法，并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.