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typical 24-hour day, the incidence of hypotension was as high as 70% in those with cervical lesions.18 In addition our unpublished data suggest that the incidence of hypotension is 2.5 fold increased in veterans with SCI compared to age-matched veterans without SCI.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 (Norris) 将低血压 (BP) 患者描述为缺乏耐力、疲倦的人 容易抱怨四肢冰冷，并且无法进行长时间的脑力或体力工作；他 被引述说； “他们并没有完全生病，但也很少康复。” 1 然而，最近的一些 论文对低血压是一个健康问题的观念提出了挑战，甚至认为低血压是一种健康问题。 理想的“正常”血压。2、3 据报道，患有 T5 以上脊髓损伤 (SCI) 的个体很难 慢性低血压，4-11 阵发性直立性低血压 (OH) 12-16 和餐后低血压。17 事实上，我们最近报道称，在典型的一天 24 小时内，低血压的发生率 在患有宫颈病变的患者中，这一比例高达 70%。 18 此外，我们未发表的数据表明， 与同龄退伍军人相比，患有 SCI 的退伍军人低血压发生率增加 2.5 倍 没有SCI。然而，慢性低血压往往没有在临床上得到解决，因为绝大多数 低血压个体仍然无症状。也就是说，一般医学文献中有证据 支持无症状低血压、认知缺陷、情绪不良变化之间的关联 和生活质量（QOL）。与血压正常、年龄匹配的对照组相比，其他健康受试者 据报道，患有慢性无症状低血压的人认知速度减慢，单词回忆能力减少19个， 20 反应准确性下降，21 注意力有限，20 反应时间延长，19, 21, 22 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存在显着关联，23-30 焦虑，25, 26 不明原因的疲倦，24, 31 以及健康感不佳。32 尽管许多人患有低血压 患有慢性 SCI 的个体仍然无症状，并且不会引起临床怀疑 我们认为，干预措施并已证明无症状的慢性低血压会产生不良影响 认知后果。33-35 必须认识到，认知障碍叠加在 许多 SCI 患者已经经历过的身体、社交和情感限制可能 严重影响自主性和社会独立性，从而降低生活质量。36, 37 有令人信服的证据 一般医学文献中的证据表明，服用米多君后全身血压会升高 盐酸给药可增加静息脑血流量 (CBF) 并改善 CBF 对 认知测试可以使患有慢性低血压的健康个体获得更好的测试表现。 38, 39 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 不足，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 研究表明，患有 SCI 的低血压个体的全身血压显着升高。 43, 44 然而， 一般来说，描述米多君血压作用的数据是在低血压患者的小样本中收集的。 实验室观察期间患有 SCI 的受试者，44、45 全身血压持续升高对患者的益处 CBF、认知功能、情绪和生活质量尚未在 SCI 人群中进行严格研究。数据 该试点项目中产生的能量将用于为大规模临床试验提供动力，以确定 血压持续升高对人的 CBF、认知功能、情绪和生活质量的临床益处 与SCI。