Orthostatic hypotension: definition, classification and evaluation.

PURPOSE: Orthostatic hypotension (OH) is a common and clinically important disorder. Published papers vary regarding the definitions of OH and methodologies of evaluation. Moreover, substantial gaps in the skills and knowledge required for assessment of OH have been reported by clinicians. We aimed to provide current information regarding the definition, classification and evaluation of OH. METHODS: We performed a comprehensive search of medical databases, using the following keywords: "postural hypotension" or "orthostatic hypotension", combined with: "definition", "classification", "diagnosis", "evaluation" or "meaning". We selected for this review the most relevant recent publications and key papers in the field, published in the English language. RESULTS: Current data regarding definitions, classification and the evaluation of OH are reviewed. The various aspects of OH assessment are extensively discussed. Considerable discrepancies exist between the published guidelines regarding the methodology of OH diagnosing. We propose an algorithm for OH evaluation and a standardized protocol for bedside determination of OH by healthcare providers. CONCLUSIONS: Correct assessment of OH is essential for its accurate diagnosis. The methodology of OH evaluation has not been sufficiently standardized. We emphasize the clinical importance of the uniform investigation of OH, according to the current guidelines for OH definition and meaning.

Neurogenic hyperadrenergic orthostatic hypotension: a newly recognized variant of orthostatic hypotension in older adults with elevated norepinephrine (noradrenaline).

Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine (NE) (noradrenaline). We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma NE. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based on standing NE, patients were dichotomized into a hyperadrenergic OH group [hyperOH: upright NE ≥ 3.55 nmol/l (600 pg/ml), n=19] or a non-hyperadrenergic OH group [nOH: upright NE < 3.55 nmol/l (600 pg/ml), n=64]. Medical history and data from autonomic testing, including the Valsalva manoeuvre (VM), were analysed. HyperOH patients had profound orthostatic falls in blood pressure (BP), but less severe than in nOH [change in SBP (systolic blood pressure): -53 ± 31 mmHg compared with -68 ± 33 mmHg, P=0.050; change in DBP (diastolic blood pressure): -18 ± 23 mmHg compared with -30 ± 17 mmHg, P=0.01]. The expected compensatory increase in standing heart rate (HR) was similarly blunted in both hyperOH and nOH groups [84 ± 15 beats per minute (bpm) compared with 82 ± 14 bpm; P=0.6]. HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM and a shorter VM phase 4 BP recovery time (16.5 ± 8.9 s compared with 31.6 ± 16.6 s; P<0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic OH, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand whether hyperOH patients will progress to nOH or whether this represents a different disorder.

The prevalence and pathological correlates of orthostatic hypotension and its subtypes when measured using beat-to-beat technology in a sample of older adults living in the community.

BACKGROUND: beat-to-beat technology is increasingly used for investigating orthostatic intolerance (OI) but the prevalence of orthostatic hypotension (OH) diagnosed with this technology is unclear. OBJECTIVES: (i) to use beat-to-beat technology to define the prevalence of OH, (ii) to investigate the pathological correlates of OH, (iii) to report the diversity of postural BP responses. METHODS: cross-sectional study of adults ≥ 65 years. BP responses to a 3-min head-up tilt were analysed. RESULTS: of 326 participants, 203(62.3%) were females. The median (IQR) age was 73 (70-78). One hundred and ninety-one (58.6%) met standard (20 mmHg systolic/10 mmHg diastolic) criteria for OH. The prevalence was higher in females (60.1% F versus 56.1% M); 47% were arteriolar subtype, 33% were venular, 9% were mixed and 11.0% could not be classified. Morphological analysis identified 102 subjects with 'small drop, overshoot', 131 with 'medium drop, slow recovery' and 31 with 'large drop, nonrecovery'. Those with OH had a lower BMI (P = 0.02), a higher resting heart rate (P = 0.005), were more likely to take a psychotropic (P = 0.02), have vertigo (P = 0.004) and report OI (P = 0.02). The 95th centile for the duration of systolic BP (SYSBP) decay >20 mmHg was 175 s and the slope of systolic BP decay was 4.75 mmHg/s. The 5th centile for percentage recovery of SYSBP was 81.4%. CONCLUSION: (i) beat-to-beat methods identify a higher prevalence of OH than sphygmomanometry, (ii) the pathological correlates of OH diagnosed in this manner are similar to those described for sphygmomanometry, (iii) there is a diverse pattern of orthostatic BP decay that could be used in future research to predict adverse outcomes in OH.

[Variants of orthostatic hypotension. New classification and diagnostic methods].

The article presents a new classification of postural hypotension (pH) and PH detailed characteristics by parameters of arterial pressure, central and peripheral hemodynamics including cerebral circulation; describes methods of detection of different PH variants; gives original data on modified diagnostic criteria and diagnosis of one of the least studied variants of PH - initial PH.

[Different types of initial orthostatic depression reactions in hypertensive patients undergoing active tilt table testing].

AIM: To study hemodynamic responses early in the course of active tilt table testing, their correlation with changes in cerebral blood flow in hypertensive patients. MATERIAL AND METHODS: A total of 41 patients with essential hypertension (EH) stage I-II at moderate and high risk (10 males, 31 females aged 48-75 years) were examined using standard clinical and device tests. Ultrasonic investigation of the extracranial arteries was made in duplex scanning regime (Acuson XP 128, USA). To determine initial orthostatic depression reactions we conducted active tilt table testing according to the protocol developed in the department of innovative diagnostic techniques. RESULTS: In conduction of the modified active tilt table testing 2 types of initial depression orthostatic reaction (OR) were identified: with short and long fall of blood pressure. In the latter type BP regressed more (18+/-8 vs 22+/-10), they had more frequent atherosclerosis of extracranial arteries. CONCLUSION: Hypertensive patients with prolonged initial orthostatic reactions had frequent cerebral hypertensive crises and syncope, initial higher BP, multivessel atherosclerotic lesions of the carotid arteries aggravating cerebral circulation.

Predicting outcomes on head-up tilt based on orthostatic hypotension patterns.

OBJECTIVE: To assess the frequency of different orthostatic hypotension (OH) patterns in patients having supine hypertension with OH ('SHOH') versus patients with OH and normal supine blood pressure ('OH alone'); and to relate OH patterns with outcomes on head-up tilt. METHODS: Consecutive patients with nonspecific dizziness were studied with a 10-min supine, 30-min head-up tilt test. Supine hypertension was diagnosed when supine systolic blood pressure (SBP) was at least 140 mmHg and/or supine diastolic blood pressure was at least 90 mmHg. OH was defined as SBP reduction of at least 20 mmHg within 3 min of tilt. OH patterns were identified corresponding to SBP time-curves during the initial 5 min of tilt: progressive, sustained and transient patterns. RESULTS: Among 400 patients tested, 31 had 'SHOH' and 39 had 'OH alone'. Frequencies of OH patterns were similar in both groups. The progressive OH pattern predicted symptomatic hypotension, leading to early tilt termination in all 'SHOH' and 88% of 'OH alone' patients. In comparison, tilt was early terminated in 33-48% of patients with sustained OH, transient OH and without OH. Early tilt termination was unrelated to age, gender, magnitude of supine SBP, pulse pressure and nadir SBP within 5 min tilt. CONCLUSIONS: Five minutes of postural challenge permitted assessing OH patterns. Outcome on protracted tilt was related to OH patterns, the worse outcome being likened to progressive OH, both in patients with 'SHOH' and in patients with 'OH alone'. Future studies will show whether OH patterns may serve as guidance for blood pressure therapy in selected patients.

Treatment of orthostatic hypotension with octreotide.

The purpose of this study was to evaluate the therapeutic potential of the somatostatin analog octreotide in patients with orthostatic hypotension. Octreotide was administered sc, and its pressor effect was assessed while the patients were semirecumbent and on the tilt table. We also studied the effect of octreotide on blood pressure while patients walked. The efficacy of therapy was assessed by measuring the duration of walking (walking time) before the onset of hypotension. Low doses of octreotide (0.2-0.4 micrograms/kg) had a pressor effect in all patients with progressive autonomic failure (n = 7), multiple system atrophy (n = 7), and diabetic autonomic neuropathy (n = 8), but not in patients with sympathotonic orthostatic hypotension (n = 6). Larger doses (0.4-1.6 micrograms/kg) resulted in a sustained (greater than or equal to 50 min) increase in blood pressure during walking in four of six patients with progressive autonomic failure and in one of six patients with multiple system atrophy. Some patients in whom octreotide failed to stabilize upright blood pressure had a satisfactory response to the drug after pretreatment with dihydroergotamine (10 micrograms/kg, sc). Patients with diabetic autonomic neuropathy, although sensitive to the pressor effect of octreotide, often developed nausea or abdominal cramps after moderate doses (greater than 1.0 micrograms/kg). These results indicate that the pressor effect of octreotide is sufficiently potent to prevent orthostatic hypotension in some patients with autonomic neuropathy. Others require treatment with both dihydroergotamine and octreotide to achieve a stable upright blood pressure.

Orthostatic hypotension: causes, mechanisms, and influencing factors.

Blood pressure homeostasis is particularly challenged by moving to an upright position. The autonomic nervous system, structural factors, infravascular volume, and circulating and local hormones influence the body's response to a change in posture. Disorders of the autonomic nervous system can result in orthostatic hypotension. Both neurogenic and nonneurogenic disorders can contribute, and distinguishing between the two causes is important for both diagnosis and management. It is also important to recognize various factors in daily life that influence orthostatic hypotension.

Classification of autonomic disorders.

Recent advances in our understanding of the pathophysiology of cardiovascular regulation and the metabolism of catecholamines have enabled us to develop an improved system of classification of autonomic disorders. Patients with autonomic impairment, clinically unassociated with other neurological abnormalities, are considered to have the Bradbury-Eggleston syndrome (idiopathic orthostatic hypotension, pure autonomic failure). Individuals whose autonomic failure is accompanied by degeneration in other neurological systems are classified as having the Shy-Drager syndrome (multiple system atrophy with autonomic failure). Patients in whom a deficiency of the enzyme dopamine-beta-hydroxylase is present from birth have many features suggestive of the Bradbury-Eggleston syndrome but manifest normal sweating and biochemically have an elevated plasma and urinary dopamine level. Recognition of these individuals is of particular importance because they are uniquely responsive to treatment with oral dihydroxyphenylserine (L-DOPS). A fourth disorder is baroreflex failure; this disorder is usually due to surgery, trauma, radiation or other injury to the ninth or tenth cranial nerves or the medullary nuclei which their fibers innervate. Patients with baroreflex failure have oscillations between hypertension and hypotension, but these alterations are poorly correlated with posture. Very high levels of plasma norepinephrine are found during the hypertensive phase of baroreflex failure. Baroreflex failure is generally responsive to treatment with clonidine. In conclusion, the diagnosis and therapy of autonomic disorders has improved due to the more precise taxonomy now current.

[Etiological aspects of orthostatic hypotension]. / Aspects étiologiques des hypotensions orthostatiques.

Orthostatic hypotension (OH) must be distinguished from supine hypotension made worse by standing up and, in particular, from vasovagal syncope. At first approximation, asympathicotonic invariable pulse OH virtually always related to an organic lesion of the baroreflex arch must be distinguished from variable pulse OH which is usually functional and may also be due to organic lesions with exclusive or predominant sympathetic system disorders. In case of doubt, it may be useful to measure palmar and plantar sympathetic potentials. The principal causes of variable pulse OH are therapeutic drugs, absolute or relative hypovolaemia, endocrine diseases (adrenal insufficiency, phaeochromocytoma), spinal quadriplegia and two congenital diseases including dopamine beta-hydroxylase deficiency. In Guillain-Barré syndrome, diabetes and alcoholism, the OH pulse may be variable or invariable. The main causes of asympathicotonic OH are ageing, post-prandial period, certain infections (e.g. tabetic neurosyphilis, botulism, EBV and HIV infections), a few systemic diseases and isolated neurological diseases. Among the systemic diseases responsible for OH are diabetes, alcoholism and chronic liver diseases of other causes, porphyria, lead poisoning, Biermer's disease, amyloidosis, several connective tissue diseases, including systemic lupus erythematosus, and some cancers associated or not with Lambert-Eaton syndrome. Among isolated neurological diseases are the familial diseases described by Riley and Day, multisystem atrophies (first described by Shy and Dager) and pure peripheral dysautonomia. To differentiate the latter from an incipient Shy-Dager syndrome, it may be helpful to use pharmacological tests: plasma catecholamine levels measurements in supine position, and clonidine test with repeated growth hormone assays in upright position.

[Methods of investigating orthostatic hypotension]. / Méthodes d'exploration des hypotensions orthostatiques.

Orthostatic hypotension, which is common mainly in the elderly, is in many cases related to hypovolemia and/or vasodilators intake. However, when an impairment of the autonomic nervous system is suspected, orthostatic hypotension severity and mechanism may be investigated. The most common tests are the head upright tilt-test and the Valsalva manoeuvre. Both of them examine the baroreflex system as a whole, and become non invasive tests with the development of finger arterial blood pressure continuous measurement. Each part of the baroreflex system may be investigated separately. So, cardiac vagal responses to ocular compression, to carotid sinus massage, to respiratory change or to atropine infusion, may be tested. On the other hand, sympathetic efferent pathways may be stimulated in a variety of ways, such as isometric exercise, cutaneous cold, mental arithmetic, norepinephrine infusion, or tiltest. None of these tests should be applied systematically, but according to the clinical features.

Orthostatic intolerance in 6 degrees head-down tilt and lower body negative pressure loading.

6 degrees head-down tilt bed rest experiment for 6 days was conducted at Nihon University Itabashi Hospital for 10 male athletes. In order to observe the orthostatic intolerance due to six days head-down tilt bed rest, 70 degrees head up tilt tests were performed before and after the head-down tilt. Two types of orthostatic intolerance were distinguished by the time course of their cardiovascular responses. One was vagotonia type and the other was brain anemia type. The latter type was commonly seen among astronauts after space flight due to the lack of plasma volume. As this volume change is considered to be initiated by some fluid loss from the lower extremities, analysis was made to clarify the relation between the leg volume change and the types of orthostatic intolerance. Nakayama proposed a Heart Rate Controllability Index, which is calculated from the initiate leg volume change and heart rate increase in head up tilt, for an indicator of the orthostatic intolerability. The index was applied to the subjects of six days head-down tilt above mentioned. For the subjects who showed a sign of presyncopy, the index values were higher or lower than that of the rest subjects who showed no sign of presyncopy. In order to evaluate the validity of the index, another experiment was conducted to induce an orthostatic intolerance by a different way of loading. The same types of orthostatic intolerance were observed and the index value hit high in the brain anemia type of orthostatic intolerance, while the vagotonia type showed relatively lower values than the normal group.

[Idiopathic orthostatic hypotension (IOH) and sympathotonic orthostatic hypotension (SOH)].

IOH occurs as progressive autonomic failure (PAF) without any neurologic symptoms indicating multiple system atrophy or Parkinson's disease. The responsible lesion for IOH is yet obscure but has been suggested to be in the peripheral sympathetic nerves, since postganglionic sympathetic neurons in IOH fail to release norepinephrine and there present extensive supersensitivities to exogenous pressors. SOH is characterized as marked tachycardia induced by hypotensive stress like standing, and is less sensitive to the administered catecholamines. Careful examinations by some pharmacological studies are essential to diagnose IOH and SOH in patients with orthostatic hypotension.

Clinical classification of syncope.

Syncope is a presenting symptom, and in itself is not a diagnosis. An etiology or a mechanism must be sought in all cases. Currently, most clinicians classify syncope on clinical grounds by attempting to ascertain its etiology. They then use this classification to guide further management. Using this approach, reflex syncope is the most common form of syncope, occurring in approximately 60% of syncope presentations. Orthostatic hypotension presents in around 15% with arrhythmic syncope in 10% and structural heart disease as the cause of syncope in 5%; in 10% of patients no diagnosis is made. An alternative classification system uses the mechanism of syncope derived from an implanted ECG loop recorder (ILR). While this approach may be of value for optimizing therapy, it cannot be considered as the primary classification since ILRs are not typically implanted early in the evaluation process of most patients. ILRs are usually placed after "risk stratification" in those deemed not to be at high risk but remain in the uncertain etiology category. Furthermore, there exists, in current ILR technology, lack of ambulatory blood pressure monitoring capability. Thus, vasodilation leading to hypotension, the main trigger of cerebral hypoperfusion other than bradycardia, cannot be detected and is currently unavailable for use in a mechanistic-based classification. Thus, the etiological classification remains the basis for both risk stratification and subsequent clinical management.

Orthostatic hypotension: a new classification system.

AIMS: Orthostatic hypotension (OH) is a common condition, which is defined as a reduction in systolic blood pressure of >or=20 mmHg or diastolic blood pressure of >or=10 mmHg within 3 min of orthostatic stress. Utilizing total peripheral resistance (TPR) and cardiac output (CO) measurements during tilt-table testing (Modelflow method), we classified OH into three categories, namely arteriolar, venular, and mixed. The principle defect in arteriolar OH is impaired vasoconstriction after orthostatic stress, reflected by absence of the compensatory increase in TPR. In venular OH, the predominant defect is excessive reduction in venous return, reflected by a large drop in CO after orthostatic stress with marked tachycardia. Mixed OH is due to a combination of both these mechanisms. METHODS AND RESULTS: We analysed haemodynamic parameters of 110 patients with OH and categorized them as arteriolar, venular, or mixed. Significant differences between the groups were found for the magnitude and time to reach nadir of the systolic blood pressure drop post-head-up tilt. The mixed OH category had the largest systolic blood pressure reduction (42.5, 31.9, 53.3 mmHg, P < 0.001) and the longest nadir time (18.6, 20, 30.7 s, P = 0.002). CONCLUSION: This is a practical classification tool and when validated physiologically, this system could be useful in directing treatment of OH.