Chronic Lower Leg Heating for the Treatment of Hypertension in Older Women

项目摘要 老年妇女（≥65岁）的高血压患病率高于老年男子，而血液中的高血压水平则低于老年男子。 在美国，老年妇女的血压控制率较低。不受控制的高血压是一种主要的 心血管疾病发病率和死亡率的危险因素。尽管标准治疗和坚持最佳药物 治疗方案中，超过50%的老年高血压女性血压控制不足（例如>140/90 mmHg）， 控制率进一步降低，新的2017年最近建议了更积极的BP目标， ACC/AHA高血压指南。因此，药物治疗单独控制的有效性 老年妇女中的高血压是有限的;因此，也需要非药物方法来帮助 降低老年高血压妇女的血压和心血管发病率及死亡率。一种佐剂，非- 在降低BP方面提供希望的药理学方法是“热疗法”。反复（慢性） 已发现全身热暴露可降低健康人的血压。这是否也是真的， 高血压患者的局部肢体发热尚不清楚。本研究项目的全球目标 旨在研究家庭下肢热疗对老年女性的降压效果， 高血压，并检查这种治疗方式对神经血管健康的影响， 这些病人。具体目标1将检验慢性小腿热疗结合 在降低老年高血压女性患者血压方面，降压药物优于单用药物治疗上级。我们将 将老年高血压妇女随机分配到干预组或对照组。患者 干预组将通过水浸进行8周的家庭小腿热疗， 膝关节循环浴（水温42°C，每周4次，每次45分钟），而 对照组将以相同的频率将腿浸入热中性水浴（33°C）中， 持续时间所有患者还将接受固定剂量的氯噻酮（一种利尿剂，25 mg口服，每日一次）。我们 将比较动态血压、血压控制率以及患者对治疗的依从性和可接受性 在群体之间。具体目标2将检验慢性下肢热疗将改善 一氧化氮的生物利用度，可以减少交感神经血管收缩，改善血管功能， 老年高血压女性我们将使用最先进的显微神经造影术多普勒超声， 压平眼压计和皮肤微透析以评估交感神经控制，导管指数 和阻力血管舒张功能，以及指示基础代谢的间质代谢物（即硝酸盐和亚硝酸盐）。 在目标1中登记的所有患者在热疗8周之前和之后的一氧化氮生物利用度。信息 从本研究项目中获得的信息将指导循证临床实践。预计我们的研究 可能导致修订高血压指南，将家庭热疗作为辅助治疗， 用于老年女性以及其他患者人群的抗高血压药物。

PROJECT SUMMARY The prevalence of hypertension is greater in older (≥65 years) women than in older men, while the blood pressure (BP) control rate is lower in older women in the United States. Uncontrolled hypertension is a major risk factor for cardiovascular morbidity and mortality. Despite standard therapy and adherence to optimal drug regimens, over 50% of older hypertensive women still have inadequate BP control (e.g. >140/90 mmHg), and the control rate is further reduced with more aggressive BP targets recommended recently by the new 2017 ACC/AHA Hypertension Guidelines. Thus, the effectiveness of drug treatment alone in the control of hypertension among older women is limited; hence, non-pharmacological approaches are also needed to help reduce BP and cardiovascular morbidity and mortality in older hypertensive women. One adjuvant, non- pharmacological approach that offers promise in lowering BP is “heat therapy”. Indeed, repeated (chronic) whole-body heat exposure has been found to decrease BP in healthy humans. Whether this is also true after regional limb heating in hypertensive patients is unknown. The global objectives of this research project are to investigate the BP lowering effect of home-based lower leg heat therapy in older women with hypertension, and to examine the impact of this therapeutic modality on neural-vascular health in these patients. Specific Aim 1 will test the hypothesis that chronic lower leg heat therapy combined with an antihypertensive drug is superior to drug treatment alone in lowering BP in older hypertensive women. We will randomly assign older hypertensive women to either an intervention group or a control group. Patients in the intervention group will perform 8 weeks of home-based lower leg heat therapy via water immersion up to the knee in a circulated bath (water temperature 42°C, 4 times per week, 45 min per session), whereas patients in the control group will immerse their legs in a thermoneutral water bath (33°C) at the same frequency and duration. All patients will also receive a fixed dose of chlorthalidone (a diuretic, 25 mg orally once daily). We will compare ambulatory BP, the BP control rate, and patient adherence and acceptability to treatment between the groups. Specific Aim 2 will test the hypothesis that chronic lower leg heat therapy will improve nitric oxide bioavailability which can decrease sympathetic vasoconstriction and improve vascular function in older hypertensive women. We will use state-of-the-art techniques of microneurography, Doppler ultrasound, applanation tonometry, and cutaneous microdialysis to assess sympathetic neural control, indices of conduit and resistance vessel vasodilator function, and interstitial metabolites (i.e. nitrate and nitrite) indicative of basal nitric oxide bioavailability in all patients enrolled in Aim 1 before and after 8 weeks of heat therapy. Information obtained from this research project will guide evidence-based clinical practice. It is anticipated that our study may lead to revision of hypertension guidelines to incorporate home-based heat therapy as adjuvant to antihypertensive drug(s) for older women, as well as other patient populations.