今日の臨床サポート

起立性低血圧症

著者: 音羽勘一 富山県立中央病院 内科(循環器)

監修: 今井靖 自治医科大学 薬理学講座臨床薬理学部門・内科学講座循環器内科学部門

著者校正/監修レビュー済:2021/08/11
参考ガイドライン:
  1. 日本循環器学会:失神の診断・治療ガイドライン(2012年改訂版)
患者向け説明資料

概要・推奨   

  1. 起立性低血圧症の診断には、起立試験が推奨される(推奨度1)
  1. 生活指導で自覚症状が改善しない起立性低血圧症には、弾性ストッキングの装着が推奨される(推奨度2)
  1. 起立性低血圧症患者は、加齢とともに虚血性臓器障害が出現しやすくなり死亡率が増加するため、慎重な経過観察が勧められる(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
音羽勘一 : 特に申告事項無し[2021年]
監修:今井靖 : 講演料(第一三共株式会社)[2021年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 起立性低血圧症は、臥位もしくは坐位から立位への体位変換時に、急激に血圧が低下する症候群である。
  1. 無症候性のこともあるが、頭痛、後頸部痛、めまい、ふらつき、立ちくらみ、眼前暗黒感、失神などの症状を伴うことが多い。
  1. 立位後3分以内に、①収縮期血圧が20mmHg以上低下、または、②収縮期血圧の絶対値が90mmHg未満に低下、あるいは③拡張期血圧が10mmHg以上低下がみられたときに診断する。
  1. 65歳以上の高齢者の9~30%にみられ、正常血圧患者だけでなく、高血圧患者でも起こり得る[1]
  1. 起立性低血圧症を起こす病態として、高齢者、糖尿病性神経症、パーキンソン病多系統萎縮症、薬剤性、アルコール性など、さまざまな基礎疾患がみられる場合がある
 
起立性低血圧症の原因

起立性低血圧症を来す病態と疾患
参考文献:
  1. Task Force for the Diagnosis and Management of Syncope; European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Heart Failure Association (HFA); Heart Rhythm Society (HRS).Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J 2009; 30: 2631-2671.
  1. Hopson JR, Rea RF, Kienzle MG. Alterations in reflex function contributing to syncope: orthostatic hypotension, carotid sinus hypersensitivity and drug-induced dysfunction. Herz 1993; 18: 164-174.
  1. Hanlon JT, Linzer M, MacMillan JP, et al. Syncope and presyncope associated with probable adverse drug reactions. Arch Intern Med 1990; 150: 2309-2312.
  1. Cherin P, Colvez A, Deville de Periere G, et al. Risk of syncope in the elderly and consumption of drugs: a casecontrol study. J Clin Epidemiol 1997; 50: 313-320.
  1. Calkins H, Zipes DP. Hypotension and syncope. In: Zipes DP, Libby P, Bonow RO, Braunwald E, editors. Braunwald’s Heart disease. A Textbook of Cardiovascular Medicine.7th ed. Philadelphia, Elsevier Saunders 2005: 909-919.

出典

img1:  著者提供
 
 
 
  1. 一般的に予後良好だが、心疾患などの基礎疾患がある場合、その予後に依存する。高齢者では死亡率が増加するとの報告がある[2]
  1. 生活指導で症状が改善しない場合、薬物治療の適応である。
問診・診察のポイント  
  1. 緊急治療を必要とする高リスク患者を除外するため、以下の病歴を確認する。

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文献 

著者: G H Rutan, B Hermanson, D E Bild, S J Kittner, F LaBaw, G S Tell
雑誌名: Hypertension. 1992 Jun;19(6 Pt 1):508-19.
Abstract/Text The purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2%. This prevalence increased to 18.2% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology.

PMID 1592445  Hypertension. 1992 Jun;19(6 Pt 1):508-19.
著者: H Luukinen, K Koski, P Laippala, S L Kivelä
雑誌名: Arch Intern Med. 1999 Feb 8;159(3):273-80.
Abstract/Text BACKGROUND: Orthostatic hypotension (OH) predicts mortality in hypertensive persons with diabetes mellitus, but no increase in mortality has been found among random samples of home-dwelling persons with OH. We examined the risks of nonvascular and vascular deaths according to different definitions of OH among home-dwelling elderly persons.
SUBJECTS AND METHODS: The study population consisted of all persons aged 70 years or older living in 5 rural municipalities (N=969), of whom 833 (86%) participated. Orthostatic tests were successfully carried out in 792 persons by nurse examiners. Orthostatic hypotension was defined as a systolic blood pressure (BP) drop of 20 mm Hg or more or a diastolic BP drop of 10 mm Hg or more 1 minute or 3 minutes after standing up. Nonvascular and vascular deaths during the follow-up period were recorded. Data on diseases, symptoms, medications, the results of clinical examinations and tests, functional ability, and health behavior were collected at the beginning of the follow-up period.
RESULTS: Of the sample, 30% had OH: the prevalence of systolic OH 1 minute and 3 minutes after standing up was 22% and 19%, respectively; that of diastolic OH 1 minute and 3 minutes after standing up was 6% for each. No differences in the occurrence of nonvascular deaths were found according to any of these definitions. By Cox multivariate regression analysis, the hazard ratio of vascular death associated with a diastolic BP reduction of 1 mm Hg 1 minute after standing up was 1.02 (P=.03), adjusted for systolic BP postural changes at 1 and 3 minutes and a diastolic BP change at 3 minutes. Adjusted for other significant factors associated with vascular death, the hazard ratio for vascular death associated with diastolic OH 1 minute after standing up was 2.04 (95% confidence interval, 1.01-4.15). The corresponding hazard ratio for systolic OH 3 minutes after standing up was 1.69 (95% confidence interval, 1.02-2.80). Using a cutoff point of 7 mm Hg or greater for a diastolic BP change 1 minute after standing up, the hazard ratio for vascular death was highest: 2.20 (95% confidence interval, 1.23-3.93). By logistic regression analysis, the baseline associates of diastolic OH 1 minute after standing up were dizziness when turning the neck (odds ratio [OR], 2.44), the use of a calcium antagonist (OR, 2.31), the use of a diuretic medication (OR, 2.29), a high systolic BP (OR, 2.23), and a low body mass index (OR, 2.26). The baseline associates of systolic OH 3 minutes after standing up were male sex (OR, 1.52), diabetes mellitus (OR, 1.92), a high systolic BP (OR, 2.91), and a low body mass index (OR, 1.68).
CONCLUSIONS: The presence of diastolic OH 1 minute and systolic OH 3 minutes after standing up predict vascular death in older persons. They differ from each other in their prevalence and in several associates, suggesting different pathophysiologic backgrounds. Clinicians should prescribe vasodilating and volume-depleting medications with caution for elderly persons with diastolic OH 1 minute after standing up. Appropriate treatment of hypertension might be the best means to manage the different types of OH with poor vascular prognoses.

PMID 9989539  Arch Intern Med. 1999 Feb 8;159(3):273-80.
著者: Fabrizio Ricci, Raffaele De Caterina, Artur Fedorowski
雑誌名: J Am Coll Cardiol. 2015 Aug 18;66(7):848-60. doi: 10.1016/j.jacc.2015.06.1084.
Abstract/Text Orthostatic hypotension (OH) is a common cardiovascular disorder, with or without signs of underlying neurodegenerative disease. OH is diagnosed on the basis of an orthostatic challenge and implies a persistent systolic/diastolic blood pressure decrease of at least 20/10 mm Hg upon standing. Its prevalence is age dependent, ranging from 5% in patients <50 years of age to 30% in those >70 years of age. OH may complicate treatment of hypertension, heart failure, and coronary heart disease; cause disabling symptoms, faints, and traumatic injuries; and substantially reduce quality of life. Despite being largely asymptomatic or with minimal symptoms, the presence of OH independently increases mortality and the incidence of myocardial infarction, stroke, heart failure, and atrial fibrillation. In this review, we outline the etiology and prevalence of OH in the general population, summarize its relationship with morbidity and mortality, propose a diagnostic and therapeutic algorithm, and delineate current challenges and future perspectives.

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 26271068  J Am Coll Cardiol. 2015 Aug 18;66(7):848-60. doi: 10.10・・・
著者: F Charbonneau
雑誌名: Can J Cardiol. 1998 Jul;14 Suppl D:16D-17D.
Abstract/Text
PMID 9713422  Can J Cardiol. 1998 Jul;14 Suppl D:16D-17D.
著者: Jade A Gehrking, Stacy M Hines, Lisa M Benrud-Larson, Tonette L Opher-Gehrking, Phillip A Low
雑誌名: Clin Auton Res. 2005 Apr;15(2):71-5. doi: 10.1007/s10286-005-0246-y.
Abstract/Text OBJECTIVE: There is uncertainty as to the minimum duration of head-up tilt (HUT) needed to detect orthostatic hypotension (OH). The orthostatic duration has variably been recommended to be 1, 2, 3, and 5 minutes. The purpose of the current study was 1) to determine the minimum duration of HUT necessary to detect OH and 2) to identify different patterns of orthostatic blood pressure (BP) response in patients with OH.
DESIGN/METHODS: We evaluated the medical records of 66 consecutive patients (mean age 70.0+/-10.1 years; 64% male) seen at Mayo Clinic-Rochester from 2000-2001 who fulfilled the criteria for OH (systolic blood pressure [SBP] reduction > or = 20 mmHg within 3 minutes of HUT) during routine clinical autonomic studies. All patients completed an autonomic reflex screen with continuous monitoring of heart rate and BP during supine rest and 5 minutes of 70 degree HUT. Severity of autonomic deficits was quantified with the Composite Autonomic Severity Score (CASS).
RESULTS: Overall, BP was the lowest at 1 minute with gradual and partial recovery over the following 4 minutes. Eighty-eight percent of patients (N=58) developed OH by 1 minute of HUT, with an additional 11% (N=7) developing OH by 2 minutes and the remaining 1% (N=1) developing OH by 3 minutes. We identified two broad patterns of SBP response to HUT. Forty-eight percent (N=32) of patients demonstrated an initial drop in SBP (> or = 20 mm Hg),which remained stable until tilt-back. Thirty-six percent (N=24) demonstrated an initial drop (> or = 20 mmHg) followed by a progressive decline in SBP until tilt-back. Repeated measures analysis of variance confirmed that the SBP change in response to HUT differed significantly among patients with a stable vs. progressive pattern [F(3,32)=25.1, p<0.001). Patients with the progressive pattern also had more severe adrenergic impairment on the CASS (p=0.03) and were more likely to have their tilt test terminated early (prior to 5 minutes) due to presyncope (p<0.0001) than patients with the stable pattern.
CONCLUSIONS: One minute of HUT will detect OH in the great majority (88%) of patients and three minutes will detect the balance. Orthostatic stress beyond 2 minutes is necessary to detect the pattern of progressive OH. Since this group has more severe adrenergic deficits than the group with stable OH, we suggest that the progressive pattern is due to greater impairment of compensatory reflexes. Recognition of the group with progressive fall in BP is important since this group may be at greater risk of orthostatic syncope.

PMID 15834762  Clin Auton Res. 2005 Apr;15(2):71-5. doi: 10.1007/s1028・・・
著者: Satish R Raj
雑誌名: Clin Auton Res. 2005 Apr;15(2):67-8. doi: 10.1007/s10286-005-0265-8.
Abstract/Text
PMID 15834760  Clin Auton Res. 2005 Apr;15(2):67-8. doi: 10.1007/s1028・・・
著者: Christopher H Gibbons, Roy Freeman
雑誌名: Neurology. 2006 Jul 11;67(1):28-32. doi: 10.1212/01.wnl.0000223828.28215.0b.
Abstract/Text OBJECTIVE: To investigate the prevalence, symptoms, and neurophysiologic features of delayed orthostatic hypotension (OH).
METHODS: Blood pressures (BP) were measured at 1-minute intervals on 230 patients during 60 degrees head-up tilt for 45 minutes and standing for 5 minutes. OH was defined as a sustained fall in BP (>or=20 mm Hg systolic or >or=10 mm Hg diastolic) and delayed OH as a sustained BP fall occurring beyond 3 minutes of standing or upright tilt table testing. Beat-to-beat BP, tests of cardiovagal function, and sympathetic-adrenergic function were performed.
RESULTS: Of patients with OH, only 46% had OH within 3 minutes of head up tilt; 15% had OH between 3 and 10 minutes; and 39% had OH only after 10 minutes of tilt table testing. The magnitude and the temporal distribution of the BP fall did not differ between those with and without symptoms of orthostatic intolerance. Patients with OH beyond 10 minutes tended to be younger (p < 0.05), have smaller BP falls during phase II of the Valsalva maneuver (p < 0.01), and have greater phase IV overshoot (p < 0.01).
CONCLUSIONS: Delayed orthostatic hypotension occurred in 54% of our tested population and was associated with milder abnormalities of sympathetic adrenergic function, suggesting this disorder may be a mild or early form of sympathetic adrenergic failure.

PMID 16832073  Neurology. 2006 Jul 11;67(1):28-32. doi: 10.1212/01.wnl・・・
著者: H Lahrmann, P Cortelli, M Hilz, C J Mathias, W Struhal, M Tassinari
雑誌名: Eur J Neurol. 2006 Sep;13(9):930-6. doi: 10.1111/j.1468-1331.2006.01512.x.
Abstract/Text Orthostatic (postural) hypotension (OH) is a common, yet under diagnosed disorder. It may contribute to disability and even death. It can be the initial sign, and lead to incapacitating symptoms in primary and secondary autonomic disorders. These range from visual disturbances and dizziness to loss of consciousness (syncope) after postural change. Evidence based guidelines for the diagnostic workup and the therapeutic management (non-pharmacological and pharmacological) are provided based on the EFNS guidance regulations. The final literature research was performed in March 2005. For diagnosis of OH, a structured history taking and measurement of blood pressure (BP) and heart rate in supine and upright position are necessary. OH is defined as fall in systolic BP below 20 mmHg and diastolic BP below 10 mmHg of baseline within 3 min in upright position. Passive head-up tilt testing is recommended if the active standing test is negative, especially if the history is suggestive of OH, or in patients with motor impairment. The management initially consists of education, advice and training on various factors that influence blood pressure. Increased water and salt ingestion effectively improves OH. Physical measures include leg crossing, squatting, elastic abdominal binders and stockings, and careful exercise. Fludrocortisone is a valuable starter drug. Second line drugs include sympathomimetics, such as midodrine, ephedrine, or dihydroxyphenylserine. Supine hypertension has to be considered.

PMID 16930356  Eur J Neurol. 2006 Sep;13(9):930-6. doi: 10.1111/j.1468・・・
著者: J J van Lieshout, A D ten Harkel, W Wieling
雑誌名: Clin Auton Res. 2000 Feb;10(1):35-42.
Abstract/Text Treatment with head-up tilt sleeping and low-dose fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic blood pressure in patients with neurogenic orthostatic hypotension. The aim of the present study was to examine whether the improvement in orthostatic blood pressure during combined treatment with low-dose fludrocortisone and nocturnal head-up tilt in patients with neurogenic orthostatic hypotension can be attributed to expansion of plasma volume or to increased total peripheral resistance. The effects of a 3-week treatment with fludrocortisone and nocturnal head-up tilting on the postural changes in arterial pressure, heart rate, and cardiac output (pulse contour) were evaluated in eight consecutive patients with orthostatic hypotension. The period during which the patients were able to remain in the standing position without orthostatic complaints increased minimally from 3 to 10 minutes. The decrease in arterial pressure after 1 minute of standing--(means with standard deviations in parentheses) systolic, 49 (20) mm Hg; diastolic, 18 (11) mm Hg--before treatment was produced by a greater than normal decrease in cardiac output: 37% (10%) in patients with neurogenic orthostatic hypotension versus -14% (8%) in control subjects. Treatment increased upright arterial pressure from 83 (19) mm Hg systolic and 55 (13) mm Hg diastolic to 114 (22) mm Hg systolic and 60 (16) mm Hg diastolic by limiting the decrease in cardiac output. Body weight increased but hematocrit did not change. Leg pressure-volume relationship decreased in the two patients studied. The responses of plasma renin activity and aldosterone to orthostatic stress prior to treatment were subnormal and became even lower after treatment. The improvement in upright blood pressure in orthostatic hypotension during treatment with fludrocortisone and nocturnal head-up sleeping is the result of a reduction in the orthostatic decrease in cardiac output. Preliminary data suggest that the expanded body fluid volume is allocated to the perivascular space rather than to the intravascular space.

PMID 10750642  Clin Auton Res. 2000 Feb;10(1):35-42.
著者: Victoria E Claydon, Christoph Schroeder, Lucy J Norcliffe, Jens Jordan, Roger Hainsworth
雑誌名: Clin Sci (Lond). 2006 Mar;110(3):343-52. doi: 10.1042/CS20050279.
Abstract/Text Water drinking improves OT (orthostatic tolerance) in healthy volunteers; however, responses to water in patients with PRS (posturally related syncope) are unknown. Therefore the aim of the present study was to examine whether water would improve OT in patients with PRS. In a randomized controlled cross-over fashion, nine patients with PRS ingested 500 ml and 50 ml (control) of water 15 min before tilting on two separate days. OT was determined using a combined test of head-up tilting and lower body suction and expressed as the time required to induce presyncope. We measured blood pressure and heart rate (using Portapres) and middle cerebral artery velocity (using transcranial Doppler). SV (stroke volume) and TPR (total peripheral resistance) were calculated using the Modelflow method. OT was significantly (P<0.02) greater after drinking 500 ml of water than after 50 ml (25.4+/-1.5 compared with 19.8+/-2.3 min respectively). After ingestion of 500 ml of water, blood pressure during tilting was higher, the tiltinduced reduction in SV was smaller and the increase in TPR was greater (all P<0.05). The correlation coefficient of the relationship between cerebral blood flow velocity and pressure was lower after 500 ml of water (0.43+/-0.1 compared with 0.73+/-0.1; P<0.05), indicating better autoregulation. In conclusion, drinking 500 ml of water increased OT and improved cardiovascular and cerebrovascular control during orthostasis. Patients with PRS should be encouraged to drink water before situations likely to precipitate a syncopal attack.

PMID 16321141  Clin Sci (Lond). 2006 Mar;110(3):343-52. doi: 10.1042/C・・・
著者: Cristian Podoleanu, Roberto Maggi, Michele Brignole, Francesco Croci, Alexander Incze, Alberto Solano, Enrico Puggioni, Emilian Carasca
雑誌名: J Am Coll Cardiol. 2006 Oct 3;48(7):1425-32. doi: 10.1016/j.jacc.2006.06.052. Epub 2006 Sep 14.
Abstract/Text OBJECTIVES: This study sought to assess the efficacy of compression bandage of legs and abdomen in preventing hypotension and symptoms.
BACKGROUND: Progressive orthostatic hypotension can occur in elderly people during standing.
METHODS: Twenty-one patients (70 +/- 11 years) affected by symptomatic progressive orthostatic hypotension underwent 2 tilt-test procedures, with and without elastic bandage of the legs (compression pressure 40 to 60 mm Hg) and of the abdomen (compression pressure 20 to 30 mm Hg) in a randomized crossover fashion. Leg bandage was administered for 10 min and was followed by an additional abdominal bandage for a further 10 min. Symptoms were evaluated by a 7-item Specific Symptom Score (SSS) questionnaire before and after 1 month of therapy with elastic compression stockings of the legs (prescribed in all patients irrespective of the results of the tilt study).
RESULTS: In the control arm, systolic blood pressure decreased from 125 +/- 18 mm Hg immediately after tilting to 112 +/- 25 mm Hg after 10 min of sham leg bandage and to 106 +/- 25 mm Hg after 20 min despite the addition of sham abdominal bandage. The corresponding values with active therapy were 129 +/- 19 mm Hg, 127 +/- 17 mm Hg (p = 0.003 vs. control), and 127 +/- 21 mm Hg (p = 0.002 vs. control). In the active arm, 90% of patients remained asymptomatic, versus 53% in the control arm (p = 0.02). During the month before evaluation, the mean SSS score was 35.2 +/- 12.1 with dizziness, weakness, and palpitations accounting for 64% of the total score. The SSS score decreased to 22.5 +/- 11.3 after 1 month of therapy (p = 0.01).
CONCLUSIONS: Lower limb compression bandage is effective in avoiding orthostatic systolic blood pressure decrease and in reducing symptoms in elderly patients affected by progressive orthostatic hypotension.

PMID 17010806  J Am Coll Cardiol. 2006 Oct 3;48(7):1425-32. doi: 10.10・・・
著者: Robert Winker, Alfred Barth, Daniela Bidmon, Ivo Ponocny, Michael Weber, Otmar Mayr, David Robertson, André Diedrich, Richard Maier, Alex Pilger, Paul Haber, Hugo W Rüdiger
雑誌名: Hypertension. 2005 Mar;45(3):391-8. doi: 10.1161/01.HYP.0000156540.25707.af. Epub 2005 Feb 7.
Abstract/Text Orthostatic intolerance is a syndrome characterized by chronic orthostatic symptoms of light-headedness, fatigue, nausea, orthostatic tachycardia, and aggravated norepinephrine levels while standing. The aim of this study was to assess the protective effect of exercise endurance training on orthostatic symptoms and to examine its usefulness in the treatment of orthostatic intolerance. 2768 military recruits were screened for orthostatic intolerance by questionnaire. Tilt-table testing identified 36 cases of orthostatic intolerance out of the 2768 soldiers. Subsequently, 31 of these subjects with orthostatic intolerance entered a randomized, controlled trial. The patients were allocated randomly to either a "training" (3 months jogging) or a "control" group. The influence of exercise training on orthostatic intolerance was assessed by determination of questionnaire scores and tilt-table testing before and after intervention. After training, only 6 individuals of 16 still had orthostatic intolerance compared with 10 of 11 in the control group. The Fisher exact test showed a highly significant difference in diagnosis between the 2 groups (P=0.008) at the end of the study. Analysis of the questionnaire-score showed significant interaction between time and group (P=0.001). The trained subjects showed an improvement in the average symptom score from 1.79+/-0.4 to 1.04+/-0.4, whereas the control subjects showed no significant change in average symptom score (2.09+/-0.6 and 2.14+/-0.5, respectively). Our data demonstrate that endurance exercise training leads to an improvement of symptoms in the majority of patients with orthostatic intolerance. Therefore, we suggest that endurance training should be considered in the treatment of orthostatic intolerance patients.

PMID 15699447  Hypertension. 2005 Mar;45(3):391-8. doi: 10.1161/01.HYP・・・
著者: Oleg Gorelik, Dorit Almoznino-Sarafian, Vita Litvinov, Irena Alon, Miriam Shteinshnaider, Eynat Dotan, David Modai, Natan Cohen
雑誌名: Gerontology. 2009;55(2):138-44. doi: 10.1159/000141920. Epub 2008 Jun 27.
Abstract/Text BACKGROUND: Postural hypotension induced by transition from supine to sitting position and measures for its prevention in heart failure has not been investigated.
OBJECTIVE: Our purpose was to evaluate the prevalence of postural hypotension and associated clinical manifestations as well as the contribution of various risk factors for postural hypotension on transition from lying to sitting in older patients with decompensated heart failure, and to study the eventual preventive effect of leg bandaging.
METHODS: Seating-induced postural hypotension (>or=20 mm Hg systolic and/or >or=10 mm Hg diastolic blood pressure fall) was assessed on the first study day in 108 patients aged >or=60 years, hospitalized for acutely decompensated heart failure. On the next day, in patients manifesting postural hypotension, compression bandages were applied along both legs before seating. Blood pressure, heart rate, O(2) saturation, and the occurrence of dizziness or palpitations were recorded prior to and 1, 3 and 5 min following seating.
RESULTS: Postural hypotension occurred in 49.1% of patients. Dizziness and/or palpitations manifested in 25%. Diastolic (36.1%) versus systolic (23.1%) postural hypotension prevailed (p=0.05). On univariate analysis, postural hypotension was associated with female sex (p=0.03), more severe heart failure (p=0.05), longer bedrest (p=0.04), higher supine systolic (p=0.01) or diastolic (p=0.002) blood pressure, nonischemic heart failure (p=0.002), and not using nitrates (p = 0.01). On multivariate analysis, longer bedrest (OR=1.58, 95% CI=1.13-2.2, p<0.001), higher supine diastolic blood pressure (OR=1.33, 95% CI=1.1-1.61, p=0.001), and nonischemic heart failure (OR=3.48, 95% CI=1.4-8.63, p=0.009) were the most predictive of postural hypotension. Compression bandages prevented postural hypotension in 21 of 49 patients and decreased the degree of postural blood pressure fall (p<0.001).
CONCLUSION: Seating-induced postural hypotension is common among older inpatients with decompensated heart failure, especially with longer bedrest, higher supine diastolic blood pressure and non-ischemic etiology. Leg compression bandaging may be useful for the prevention of postural hypotension in these patients.

Copyright 2008 S. Karger AG, Basel.
PMID 18583904  Gerontology. 2009;55(2):138-44. doi: 10.1159/000141920.・・・
著者: J C Denq, T L Opfer-Gehrking, M Giuliani, J Felten, V A Convertino, P A Low
雑誌名: Clin Auton Res. 1997 Dec;7(6):321-6.
Abstract/Text Orthostatic hypotension (OH) is the most disabling and serious manifestation of adrenergic failure, occurring in the autonomic neuropathies, pure autonomic failure (PAF) and multiple system atrophy (MSA). No specific treatment is currently available for most etiologies of OH. A reduction in venous capacity, secondary to some physical counter maneuvers (e.g., squatting or leg crossing), or the use of compressive garments, can ameliorate OH. However, there is little information on the differential efficacy, or the mechanisms of improvement, engendered by compression of specific capacitance beds. We therefore evaluated the efficacy of compression of specific compartments (calves, thighs, low abdomen, calves and thighs, and all compartments combined), using a modified antigravity suit, on the end-points of orthostatic blood pressure, and symptoms of orthostatic intolerance. Fourteen patients (PAF, n = 9; MSA, n = 3; diabetic autonomic neuropathy, n = 2; five males and nine females) with clinical OH were studied. The mean age was 62 years (range 31-78). The mean +/- SEM orthostatic systolic blood pressure when all compartments were compressed was 115.9 +/- 7.4 mmHg, significantly improved (p < 0.001) over the head-up tilt value without compression of 89.6 +/- 7.0 mmHg. The abdomen was the only single compartment whose compression significantly reduced OH (p < 0.005). There was a significant increase of peripheral resistance index (PRI) with compression of abdomen (p < 0.001) or all compartments (p < 0.001); end-diastolic index and cardiac index did not change. We conclude that denervation increases vascular capacity, and that venous compression improves OH by reducing this capacity and increasing PRI. Compression of all compartments is the most efficacious, followed by abdominal compression, whereas leg compression alone was less effective, presumably reflecting the large capacity of the abdomen relative to the legs.

PMID 9430805  Clin Auton Res. 1997 Dec;7(6):321-6.
著者: H Tanaka, H Yamaguchi, H Tamai
雑誌名: Lancet. 1997 Jan 18;349(9046):175. doi: 10.1016/S0140-6736(97)24003-1.
Abstract/Text
PMID 9111544  Lancet. 1997 Jan 18;349(9046):175. doi: 10.1016/S0140-6・・・
著者: Vishal Gupta, Lewis A Lipsitz
雑誌名: Am J Med. 2007 Oct;120(10):841-7. doi: 10.1016/j.amjmed.2007.02.023.
Abstract/Text Orthostatic hypotension is a common problem among elderly patients, associated with significant morbidity and mortality. While acute orthostatic hypotension is usually secondary to medication, fluid or blood loss, or adrenal insufficiency, chronic orthostatic hypotension is frequently due to altered blood pressure regulatory mechanisms and autonomic dysfunction. The diagnostic evaluation requires a comprehensive history including symptoms of autonomic nervous system dysfunction, careful blood pressure measurement at various times of the day and after meals or medications, and laboratory studies. Laboratory investigation and imaging studies should be based upon the initial findings with emphasis on excluding diagnoses of neurodegenerative diseases, amyloidosis, diabetes, anemia, and vitamin deficiency as the cause. Whereas asymptomatic patients usually need no treatment, those with symptoms often benefit from a stepped approach with initial nonpharmacological interventions, including avoidance of potentially hypotensive medications and use of physical counter maneuvers. If these measures prove inadequate and the patient remains persistently symptomatic, various pharmacotherapeutic agents can be added, including fludrocortisone, midodrine, and nonsteroidal anti-inflammatory drugs. The goals of treatment are to improve symptoms and to make the patient as ambulatory as possible rather then trying to achieve arbitrary blood pressure goals. With proper evaluation and management, the occurrence of adverse events, including falls, fracture, functional decline, and myocardial ischemia, can be significantly reduced.

PMID 17904451  Am J Med. 2007 Oct;120(10):841-7. doi: 10.1016/j.amjmed・・・
著者: Fiona Kearney, Alan Moore
雑誌名: Expert Rev Cardiovasc Ther. 2009 Nov;7(11):1395-400. doi: 10.1586/erc.09.130.
Abstract/Text Orthostatic hypotension (OH) is a common disorder in older adults with potentially serious clinical consequences. Understanding the key underlying pathophysiological processes that predispose individuals to OH is essential when making treatment decisions for this group of patients. In this article, we discuss the key antihypotensive agents used in the management of OH in older adults. Commonly, midodrine is used as a first-line agent, given its supportive data in randomized, controlled trials. Fludrocortisone has been evaluated in open-label trials and has long-established usage in clinical practice. Other agents are available and in clinical use, either alone or in combination, but larger randomized trial evaluations are yet to be published. It is important to bear in mind that a patient may be taking medications that predispose to or exacerbate the symptoms of OH. Withdrawal of such medications, where possible, should be considered before commencing other pharmacological agents that attenuate the symptoms of OH.

PMID 19900022  Expert Rev Cardiovasc Ther. 2009 Nov;7(11):1395-400. do・・・
著者: M S Kochar
雑誌名: Curr Hypertens Rep. 2000 Oct;2(5):457-62.
Abstract/Text Several mechanisms counteract the gravitational forces on blood and maintain systemic arterial pressure and cerebral perfusion upon assumption of the upright posture. Failure of these mechanisms can lead to a postural decrease in blood pressure. Postural hypotension is defined as a reduction of at least 20 mm Hg in systolic blood pressure or at least a 10 mm Hg decrease in diastolic blood pressure. Acute postural hypotension is usually due to fluid or blood loss and responds well to fluid repletion. Chronic postural hypotension is due to drugs or endocrine or neurogenic disorders. A functional classification based on severity of symptoms is useful in monitoring the patient's condition and documenting improvement with treatment. Whenever possible, the reversible causes of chronic postural hypotension should be treated. For symptomatic treatment, a stepped approach starting with nonpharmacologic measures is recommended. Fludrocortisone, midodrine, indomethacin, and atrial tachypacing are recommended, in that order, for patients in whom nonpharmacologic measures prove insufficient. Other drugs can be added if necessary. The goal of treatment is to make the patient as ambulatory and symptom-free as possible without causing supine hypertension.

PMID 10995521  Curr Hypertens Rep. 2000 Oct;2(5):457-62.
著者: K Kita, K Hirayama
雑誌名: Neurology. 1988 Jul;38(7):1095-9.
Abstract/Text Amezinium metilsulfate is a new, indirectly acting sympathomimetic drug which exclusively affects postganglionic sympathetic neurons and inhibits both intraneuronal monoamine oxidase and norepinephrine reuptake. We examined the short-term effects of amezinium in five patients with severe neurogenic orthostatic hypotension. Single-dose administration of amezinium (10 mg) raised both the supine and sitting mean blood pressures by 15 to 45 mm Hg for 8 hours, with a slight increase in the plasma norepinephrine level. Repeated administration of amezinium (10 to 40 mg/d) produced an increase in sitting blood pressure in three patients and improvement of the orthostatic symptoms in all patients without remarkable recumbent hypertension. The heart rate was increased in two patients. The results indicate that amezinium is of therapeutic value for the treatment of neurogenic orthostatic hypotension. The adrenergic effect of amezinium on the blood pressure and heart rate apparently was related to a slight increase in endogenous norepinephrine in the presence of alpha- and beta-adrenoreceptor supersensitivity.

PMID 3386828  Neurology. 1988 Jul;38(7):1095-9.
著者: Nobutoshi Iida, Syozo Koshikawa, Tadao Akizawa, Yoshiharu Tsubakihara, Fumiaki Marumo, Takashi Akiba, Yoshindo Kawaguchi, Akio Imada, Chikao Yamazaki, Masashi Suzuki
雑誌名: Am J Nephrol. 2002 Jul-Aug;22(4):338-46. doi: 65224.
Abstract/Text BACKGROUND: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase.
METHODS: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study.
RESULTS: In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions.
CONCLUSIONS: These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.

Copyright 2002 S. Karger AG, Basel
PMID 12169865  Am J Nephrol. 2002 Jul-Aug;22(4):338-46. doi: 65224.
著者: Tadao Akizawa, Shozo Koshikawa, Nobutoshi Iida, Fumiaki Marumo, Takashi Akiba, Yoshindo Kawaguchi, Akio Imada, Chikao Yamazaki, Masashi Suzuki, Yoshiharu Tubakihara
雑誌名: Nephron. 2002 Apr;90(4):384-90. doi: 54725.
Abstract/Text Orthostatic hypotension is one of the major factors interfering with everyday activities in hemodialysis patients, but there has been no effective agent for treating it. In order to clarify the clinical effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on orthostatic hypotension of hemodialysis patients, we conducted a randomized, double-blind comparative trial. 149 regular hemodialysis patients with orthostatic hypotension were randomly allocated to three groups and L-DOPS at doses of 400 mg, 200 mg or placebo was orally administrated to each group 30 min before starting every hemodialysis for 4 weeks. Changes of blood pressure (BP) in orthostatic hypotension immediately after completion of hemodialysis and symptoms related to orthostatic hypotension were compared between the three groups. In the 400-mg group, systolic and diastolic BP after standing increased significantly and the drop of mean BP after standing was also reduced compared with pretreatment levels. No such changes were observed in the placebo group. Fatiguability, malaise/weakness, dizziness and light-headed feeling, the interdialytic symptoms commonly observed in hemodialysis patients who developed orthostatic hypotension, were improved to a significant extent in the L-DOPS group compared with the placebo group. In particular, the improvement was more remarkable for the L-DOPS 400-mg group than the placebo group in patients with diabetic nephropathy, lower systolic BP after standing, and the long duration type of orthostatic hypotension. The incidence of adverse events was comparable between the three groups, and all recovered after discontinuation of L-DOPS or concomitantly administered drugs, or without any treatment. These findings indicate that L-DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension.

Copyright 2002 S. Karger AG, Basel
PMID 11961396  Nephron. 2002 Apr;90(4):384-90. doi: 54725.
著者: C J Mathias, J M Senard, S Braune, L Watson, A Aragishi, J E Keeling, M D Taylor
雑誌名: Clin Auton Res. 2001 Aug;11(4):235-42.
Abstract/Text This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

PMID 11710796  Clin Auton Res. 2001 Aug;11(4):235-42.
著者: R Freeman, L Landsberg, J Young
雑誌名: Neurology. 1999 Dec 10;53(9):2151-7.
Abstract/Text OBJECTIVE: To study the therapeutic effect and mechanism of action of 3,4-DL-threodihydroxyphenylserine (DL-DOPS) in neurogenic orthostatic hypotension.
METHODS: The blood pressure (BP) response to an orthostatic challenge on DL-DOPS was compared with that of placebo in a randomized, double-blind, placebo-controlled, crossover trial in 10 patients. The mechanism of action of DOPS was studied by measuring forearm vascular resistance and changes in supine and upright plasma DL-DOPS and norepinephrine levels. The effect of DL-DOPS on the quality of life was determined by questionnaire.
RESULTS: DL-DOPS increased the supine (p<0.001) and upright (p<0.05) systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both p<0.01). The peak SBP on DL-DOPS in the supine position occurred 300 minutes after ingestion of the medication. The increase in BP was accompanied by an increase in plasma levels of norepinephrine and DL-DOPS in both the supine and upright positions after DL-DOPS ingestion (p<0.0001). There was a trend toward improvement in symptoms of orthostatic intolerance.
CONCLUSION: DL-DOPS improved features of neurogenic orthostatic hypotension in patients with central and peripheral autonomic nervous system disease. There was an increase in plasma norepinephrine. No major side effects occurred.

PMID 10599797  Neurology. 1999 Dec 10;53(9):2151-7.
著者: Gillian M Keating
雑誌名: Drugs. 2015 Feb;75(2):197-206. doi: 10.1007/s40265-014-0342-1.
Abstract/Text The norepinephrine prodrug droxidopa (NORTHERA™) is approved in the US for the treatment of orthostatic dizziness, lightheadedness, or the 'feeling that you are about to black out' in adults with symptomatic neurogenic orthostatic hypotension associated with primary autonomic failure (e.g. Parkinson's disease, multiple system atrophy or pure autonomic failure), dopamine β-hydroxylase deficiency or nondiabetic autonomic neuropathy. This article reviews the clinical efficacy and tolerability of droxidopa in symptomatic neurogenic orthostatic hypotension, as well as summarizing its pharmacological properties. Oral droxidopa was effective in the shorter-term treatment of patients with symptomatic neurogenic orthostatic hypotension, with improvements seen in symptoms, the impact of symptoms on daily activities and standing systolic blood pressure. More data are needed to confirm the longer-term efficacy of droxidopa. Droxidopa was generally well tolerated, although patients should be monitored for supine hypertension.

PMID 25559422  Drugs. 2015 Feb;75(2):197-206. doi: 10.1007/s40265-014-・・・
著者: P A Low, J L Gilden, R Freeman, K N Sheng, M A McElligott
雑誌名: JAMA. 1997 Apr 2;277(13):1046-51.
Abstract/Text OBJECTIVE: To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Midodrine hydrochloride, an alpha-agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone.
DESIGN/METHODS: A total of 171 patients with orthostatic hypotension participated in a multicenter, randomized, placebo-controlled study. They were randomized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study, comprising single-blind run-in (at week 1) and washout at weeks 5 and 6, with an intervening double-blind period (weeks 2 to 4).
SETTING: Twenty-five centers, with most patients evaluated in referral centers.
MAIN OUTCOME MEASURES: The primary end points were improvement in standing systolic BP, symptoms of lightheadedness, and a global symptom relief score (by the investigator and patient separately).
RESULTS: Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications (3 in the midodrine group, 6 in the placebo group). In the evaluable patients, midodrine resulted in improvements in standing systolic BP at all time points (P<.001 at visits 2, 3, 4, and 5), in reported symptoms by the end of the second week of treatment (P=.001), and in the global symptom relief score rated by both the patient (P=.03) and the investigator (P<.001). There was no effect by center, severity of orthostatic hypotension, use of fludrocortisone or compression garments, or diagnosis. The main adverse effects were those of pilomotor reactions, urinary retention, and supine hypertension.
CONCLUSIONS: Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.

PMID 9091692  JAMA. 1997 Apr 2;277(13):1046-51.
著者: J Jankovic, J L Gilden, B C Hiner, H Kaufmann, D C Brown, C H Coghlan, M Rubin, F M Fouad-Tarazi
雑誌名: Am J Med. 1993 Jul;95(1):38-48.
Abstract/Text PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure.
PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years).
METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level).
RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%).
CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

PMID 7687093  Am J Med. 1993 Jul;95(1):38-48.
著者: Ariel Izcovich, Carlos González Malla, Matias Manzotti, Hugo Norberto Catalano, Gordon Guyatt
雑誌名: Neurology. 2014 Sep 23;83(13):1170-7. doi: 10.1212/WNL.0000000000000815. Epub 2014 Aug 22.
Abstract/Text OBJECTIVE: Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain. We performed a systematic review to evaluate the efficacy and safety of midodrine in patients with SOH and RRS.
METHODS: We searched multiple electronic databases without language restriction from their inception to June 2013. We included randomized controlled trials of patients with SOH or RRS that compared treatment with midodrine against a control and reported data on patient important outcomes. We graded the quality of evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
RESULTS: Eleven trials involving 593 patients were included in this review. Three studies addressed health-related quality of life in patients with RRS, showing improvement with midodrine: risk difference 14% (95% confidence interval [CI] -3.5 to 31.6), very low confidence. Seven studies addressed symptom improvement and provided poolable data showing improvement with midodrine in patients with SOH: risk difference 32.8% (95% CI 13.5-48), low confidence; and RRS: risk difference 63.3% (95% CI 47.6-68.2), very low confidence. Five studies reported syncope recurrence in patients with RRS showing improvement with midodrine: risk difference 37% (95% CI 20.8%-47.4%), moderate confidence. The most frequent side effects in the midodrine arm were pilomotor reactions (33.6%, risk ratio 4.58 [95% CI 2.03-10.37]).
CONCLUSIONS: Evidence warranting low/moderate confidence suggests that midodrine improves clinical important outcomes in patients with SOH and RRS.

© 2014 American Academy of Neurology.
PMID 25150287  Neurology. 2014 Sep 23;83(13):1170-7. doi: 10.1212/WNL.・・・
著者: R D Hoeldtke, D H Streeten
雑誌名: N Engl J Med. 1993 Aug 26;329(9):611-5. doi: 10.1056/NEJM199308263290904.
Abstract/Text BACKGROUND AND METHODS: Patients with orthostatic hypotension caused by autonomic neuropathy frequently have a decreased red-cell mass. This would be expected to compromise their effective circulating blood volume and aggravate the orthostatic hypotension. We studied the effect of increasing the red-cell mass with erythropoietin, given subcutaneously in a dose of 50 U per kilogram of body weight three times a week for 6 to 10 weeks to eight patients with orthostatic hypotension--four men, one teenage boy, and three women (age range, 17 to 68 years). Four patients had type I diabetes mellitus and autonomic neuropathy, three patients had pure autonomic failure, and one patient had sympathotonic orthostatic hypotension. Seven patients received fludrocortisone (0.1 or 0.2 mg per day) before, during, and after the trial of erythropoietin. The red-cell volume, plasma volume, and hemodynamic response to orthostatic stress were measured before and after therapy.
RESULTS: Erythropoietin increased the mean (+/- SD) hematocrit from 0.34 +/- 0.04 to 0.45 +/- 0.04 (P < 0.005) and increased the red-cell volume from 16.8 +/- 3.9 to 25.3 +/- 3.1 ml per kilogram (P < 0.005), but had no effect on plasma volume. The systolic blood pressure increased from 81 +/- 11 to 100 +/- 24 mm Hg (P < 0.01) and the diastolic blood pressure increased from 46 +/- 10 to 63 +/- 18 mm Hg (P < 0.01) while the patients were standing. The average systolic and diastolic blood pressure while the patients were supine did not increase significantly, although hypertension in the supine position developed in three patients. Orthostatic dizziness improved during treatment in six of the eight patients.
CONCLUSIONS: In patients with orthostatic hypotension, increasing the red-cell volume with erythropoietin elevates blood pressure while standing. Possible long-term adverse effects are not known.

PMID 8341335  N Engl J Med. 1993 Aug 26;329(9):611-5. doi: 10.1056/NE・・・
著者: Artur Fedorowski, Bo Hedblad, Olle Melander
雑誌名: Eur J Epidemiol. 2011 Jul;26(7):537-46. doi: 10.1007/s10654-011-9578-1. Epub 2011 Apr 13.
Abstract/Text Orthostatic hypotension (OH) is associated with increased total mortality but contribution of specific death causes has not been thoroughly explored. In this prospective study, authors followed up 32,068 individuals without baseline history of cancer or cardiovascular disease (69% men; mean age, 46 years; range, 26-61 years) over a period of 24 years. Hazard ratios (HRs) for total and cause-specific mortality associated with presence of OH and by quartiles of postural systolic blood pressure response (∆SBP) were assessed using multivariate adjusted Cox regression model. A total of 7,145 deaths (22.3%, 9.4 deaths/1,000 person-years) occurred during follow-up. Those with OH (n = 1,943) had higher risk of death due to injury (HR, 1.88; 1.37-2.57) and neurological disease (HR, 2.21; 1.39-3.51). Analogically, risk of death caused by injury and neurological disease increased across the quartiles of ∆SBP from hyper- (Q1(SBP), +8.5 ± 4.7 mmHg) to hypotensive response (Q4(SBP), -13.7 ± 5.7 mmHg; HR, 1.32; 1.00-1.72, and 1.84; 1.20-2.82, respectively) as did also risk of death due to respiratory disease (Q4(SBP) vs. Q1(SBP): HR, 1.53; 1.14-2.04). In contrast, risk curve for cerebrovascular death was U-shaped with nadir in the mildly hypotensive 3rd quartile of ∆SBP (-5.0 ± 0.1 mmHg, Q3(SBP) vs. Q1(SBP): HR, 0.75; 0.54-1.03; P for linear trend = 0.021). Additionally, cardiovascular mortality was increased among 5,805 rescreened participants (mean age, 53 years; 9.8% OH positive: HR, 1.54; 1.24-1.89, and Q4(SBP) vs. Q1(SBP): 1.27; 1.02-1.57, respectively). In summary, increased mortality predicted by blood pressure fall on standing is associated with injuries, neurodegenerative, and respiratory diseases, as well as with cardiovascular disease in older adults. Moreover, both increase and pronounced decrease of SBP during early orthostasis indicate higher risk of cerebrovascular death.

PMID 21487956  Eur J Epidemiol. 2011 Jul;26(7):537-46. doi: 10.1007/s1・・・
著者: Christine D Jones, Laura Loehr, Nora Franceschini, Wayne D Rosamond, Patricia P Chang, Eyal Shahar, David J Couper, Kathryn M Rose
雑誌名: Hypertension. 2012 May;59(5):913-8. doi: 10.1161/HYPERTENSIONAHA.111.188151. Epub 2012 Mar 19.
Abstract/Text Heart failure causes significant morbidity and mortality. Distinguishing risk factors for incident heart failure can help identify at-risk individuals. Orthostatic hypotension may be a risk factor for incident heart failure; however, this association has not been fully explored, especially in nonwhite populations. The Atherosclerosis Risk in Communities Study included 12363 adults free of prevalent heart failure with baseline orthostatic measurements. Orthostatic hypotension was defined as a decrease of systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg with position change from supine to standing. Incident heart failure was identified from hospitalization or death certificate disease codes. Over 17.5 years of follow-up, orthostatic hypotension was associated with incident heart failure with multivariable adjustment (hazard ratio: 1.54 [95% CI: 1.30-1.82]). This association was similar across race and sex groups. A stronger association was identified in younger individuals ≤55 years old (hazard ratio: 1.90 [95% CI: 1.41-2.55]) than in older individuals >55 years old (hazard ratio: 1.37 [95% CI: 1.12-1.69]; interaction P=0.034). The association between orthostatic hypotension and incident heart failure persisted with exclusion of those with diabetes mellitus, coronary heart disease, and those on antihypertensives or psychiatric or Parkinson disease medications. However, exclusion of those with hypertension somewhat attenuated the association (hazard ratio: 1.34 [95% CI: 1.00-1.80]). We identified orthostatic hypotension as a predictor of incident heart failure among middle-aged individuals, particularly those 45 to 55 years of age. This association may be partially mediated through hypertension. Orthostatic measures may enhance risk stratification for future heart failure development.

PMID 22431580  Hypertension. 2012 May;59(5):913-8. doi: 10.1161/HYPERT・・・
著者: Kathryn M Rose, Marsha L Eigenbrodt, Rebecca L Biga, David J Couper, Kathleen C Light, A Richey Sharrett, Gerardo Heiss
雑誌名: Circulation. 2006 Aug 15;114(7):630-6. doi: 10.1161/CIRCULATIONAHA.105.598722. Epub 2006 Aug 7.
Abstract/Text BACKGROUND: An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations.
METHODS AND RESULTS: We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987-1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR = 1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR = 2.0; 95% CI, 1.6 to 2.7) and other deaths (HR = 2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio = 1.1; 95% CI, 0.8 to 1.6).
CONCLUSIONS: OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

PMID 16894039  Circulation. 2006 Aug 15;114(7):630-6. doi: 10.1161/CIR・・・
著者: K H Masaki, I J Schatz, C M Burchfiel, D S Sharp, D Chiu, D Foley, J D Curb
雑誌名: Circulation. 1998 Nov 24;98(21):2290-5.
Abstract/Text BACKGROUND: Population-based data are unavailable concerning the predictive value of orthostatic hypotension on mortality in ambulatory elderly patients, particularly minority groups.
METHODS AND RESULTS: With the use of data from the Honolulu Heart Program's fourth examination (1991 to 1993), orthostatic hypotension was assessed in relation to subsequent 4-year all-cause mortality among a cohort of 3522 Japanese American men 71 to 93 years old. Blood pressure was measured in the supine position and after 3 minutes of standing, with the use of standardized methods. Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) of >/=20 mm Hg or in diastolic blood pressure of >/=10 mm Hg. Overall prevalence of orthostatic hypotension was 6.9% and increased with age. There was a total of 473 deaths in the cohort over 4 years; of those who died, 52 had orthostatic hypotension. Four-year age-adjusted mortality rates in those with and without orthostatic hypotension were 56.6 and 38.6 per 1000 person-years, respectively. With the use of Cox proportional hazards models, after adjustment for age, smoking, diabetes mellitus, body mass index, physical activity, seated systolic blood pressure, antihypertensive medications, hematocrit, alcohol intake, and prevalent stroke, coronary heart disease and cancer, orthostatic hypotension was a significant independent predictor of 4-year all-cause mortality (relative risk 1.64, 95% CI 1.19 to 2.26). There was a significant linear association between change in systolic blood pressure from supine position to standing and 4-year mortality rates (test for linear trend, P<0.001), suggesting a dose-response relation.
CONCLUSIONS: Orthostatic hypotension is relatively uncommon, may be a marker for physical frailty, and is a significant independent predictor of 4-year all-cause mortality in this cohort of elderly ambulatory men.

PMID 9826316  Circulation. 1998 Nov 24;98(21):2290-5.

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