Increase in Blood Pressure: Effects on Cognition, Mood and Life Quality in SCI

血压升高：对 SCI 患者认知、情绪和生活质量的影响

• 批准号: 9110753
• 负责人: Jill M. Wecht
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9110753
• 关键词: Acute; Address; Adrenergic Agents; Adrenergic alpha-Agonists; Adverse event; Age; Antihypertensive Agents; Anxiety; Attention; Autonomic Dysreflexia; Belief; Benign; Blood Flow Velocity; Blood Pressure; Cardiovascular system; Cerebrovascular Circulation; Cervical; Chronic; Clinical; Clinical Management; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Data; Digit structure; Disease; Double-Blind Method; Emotional; Etiology; Face; Fatigue; Head; Health; Hour; Hypertension; Hypotension; Impaired cognition; Incidence; Individual; Intervention; Laboratories; Lesion; Limb structure; Literature; Longitudinal Studies; Medical; Memory; Mental Depression; Midodrine; Moods; Nature; Orthostasis; Orthostatic Hypotension; Outpatients; Paper; Perception; Persons; Pilot Projects; Placebo Control; Placebos; Population; Prevalence; Process; Psyche structure; Quality of life; Randomized; Reaction Time; Reporting; Rest; Risk; Sampling; Secondary to; Severities; Speed; Spinal cord injury; Systemic blood pressure; Test Result; Veterans; Work; base; blood pressure reduction; cerebrovascular; cognitive function; cognitive performance; cognitive testing; cohort; experience; falls; hypertension treatment; improved; middle cerebral artery; mortality; normotensive; performance tests; processing speed; public health relevance; response; social

In 1927, Norris described individuals with low blood pressure (BP) as persons who lacked stamina, tired easily, complained of cold extremities and showed an inability to do prolonged mental or physical work; he was quoted as saying; "they are not exactly ill; yet they are rarely well." 1 However, several more recent papers have challenged the notion that low BP is a health concern, and even suggest that hypotension is the ideal "normal" BP.2, 3 Individuals with spinal cord injury (SCI) above T5 are reported to struggle with chronic hypotension,4-11 episodic orthostatic hypotension (OH) 12-16 and post-prandial hypotension.17 In fact, we recently reported that, over the course of a typical 24-hour day, the incidence of hypotension was as high as 70% in those with cervical lesions.18 In addition our unpublished data suggest that the incidence of hypotension is 2.5 fold increased in veterans with SCI compared to age-matched veterans without SCI. However, chronic hypotension is often not clinically addressed because the vast majority of hypotensive individuals remain asymptomatic. That said there evidence in the general medical literature supporting associations between asymptomatic hypotension, cognitive deficits, adverse changes in mood and quality of life (QOL). Compared to normotensive age-matched controls, otherwise healthy subjects with chronic asymptomatic hypotension are reported to have slowed cognitive speed, 19 fewer word recall, 20 decreased accuracy of response,21 limited attention,20 prolonged reaction times,19, 21, 22 and reduced memory and concentration capacity. 21, 22 In addition, several papers have reported findings suggesting significant associations between chronic hypotension and increased incidence of depression,23-30 anxiety,25, 26 unexplained tiredness,24, 31 and poor perception of well being.32 Although many hypotensive individuals with chronic SCI remain asymptomatic and do not raise clinical suspicion warranting intervention, we believe, and have demonstrated that asymptomatic chronic hypotension has adverse cognitive consequences.33-35 It must be appreciated that the superimposition of cognitive impairment on the physical, social and emotional limitations already experienced by many individuals with SCI may severely impact autonomy and social independence thereby diminishing QOL.36, 37 There is compelling evidence in the general medical literature suggesting that elevation in systemic BP, following midodrine hydrochloride administration, increases resting cerebral blood flow (CBF) and improves CBF responses to cognitive testing resulting in better test performance in healthy individuals with chronic hypotension. 38, 39 Because it is believed that the etiology of hypotension in the SCI population is the result of adrenergic insufficiency, midodrine, an alpha-adrenergic agonist, is considered a first line treatment, 40-42 and we have demonstrated significant increases in systemic BP in hypotensive individuals with SCI.43, 44 However, in general, data describing the BP effect of midodrine have been collected in small samples of hypotensive subjects with SCI during laboratory observations,44, 45 the benefit of sustained elevation in systemic BP on CBF, cognitive function, mood and QOL has not been rigorously studied in the SCI population. Data generated in this pilot project will be used to power a large-scale clinical trial to determine the clinical benefit of sustained increases in BP on CBF, cognitive function, mood and QOL in persons with SCI.

1927年，诺里斯将低血压（BP）患者描述为缺乏耐力，疲劳， 容易，抱怨四肢冰冷，表现出无法做长时间的脑力或体力工作;他 他说：“他们没有病，但他们很少好。“1然而，最近几次 一些论文对低血压是一个健康问题的观点提出了质疑，甚至认为低血压是一个健康问题。 理想的“正常”BP。2，3据报道，T5以上脊髓损伤（SCI）的个体难以与 慢性低血压、4-11例阵发性体位性低血压（OH）12-16例和餐后痉挛17例。 事实上，我们最近报道，在典型的24小时内，低血压的发生率是 在宫颈病变患者中高达70%。18此外，我们未发表的数据表明， 与年龄匹配的退伍军人相比，SCI退伍军人的低血压发生率增加了2.5倍 没有SCI。然而，慢性低血压通常在临床上得不到解决，因为绝大多数的低血压患者都是低血压患者。 感染者仍无症状。在一般的医学文献中有证据表明 支持无症状性低血压、认知缺陷、情绪不良变化之间的相关性 生活质量（QOL）。与血压正常的年龄匹配的对照组相比， 据报道，慢性无症状低血压患者的认知速度减慢，单词回忆减少19个， 20例反应准确性下降，21例注意力有限，20例反应时间延长，19、21、22例反应时间减少， 记忆力和集中力。21，22此外，几篇论文报告的研究结果表明， 慢性低血压与抑郁症发病率增加之间的显著相关性，23-30 焦虑，25，26不明原因的疲劳，24，31和对幸福的感知差。 慢性SCI患者仍无症状，不会引起临床怀疑 我们认为，并已证实，无症状慢性低血压对 认知后果。33 -35必须认识到，认知障碍的叠加 许多SCI患者已经经历过的身体、社会和情感上的限制， 严重影响自主性和社会独立性，从而降低QOL。36，37 一般医学文献中的证据表明，米多君后全身血压升高 盐酸盐给药，增加静息脑血流量（CBF），并改善CBF对 认知测试导致慢性低血压健康个体的测试性能更好。三十八、三十九 因为人们认为SCI人群中低血压的病因是肾上腺素能的结果， 因此，米多君，一种α-肾上腺素能激动剂，被认为是一线治疗，40-42，我们有 在患有SCI的肥胖个体中，显示出全身血压显著升高。43，44然而， 一般来说，描述米多君BP效应的数据是在小样本的降压药中收集的。 在实验室观察期间，SCI受试者，44，45全身血压持续升高的益处 脑血流、认知功能、情绪和生活质量尚未在SCI人群中进行严格的研究。数据 在这个试点项目中产生的将被用来驱动一个大规模的临床试验，以确定 血压持续升高对CBF、认知功能、情绪和QOL的临床获益 关于SCI