Orthostatic hypotension: An overlooked but clinically decisive entity

Gunja Jain; Sunny Singhal; Laxmi Kant Goyal; Ajay Mathur

doi:10.4103/jiag.jiag_24_22

REVIEW ARTICLE

Year : 2022 | Volume : 18 | Issue : 2 | Page : 86-90

Orthostatic hypotension: An overlooked but clinically decisive entity

Gunja Jain¹, Sunny Singhal², Laxmi Kant Goyal², Ajay Mathur¹
¹ Department of General Medicine, Sawai Man Singh Medical College, Jaipur, Rajasthan, India
² Department of Geriatric Medicine, Sawai Man Singh Medical College, Jaipur, Rajasthan, India

Date of Submission	12-Jun-2022
Date of Decision	19-Jun-2022
Date of Acceptance	21-Jun-2022
Date of Web Publication	15-Jul-2022

Correspondence Address:
Sunny Singhal
Department of Geriatric Medicine, Sawai Man Singh Medical College, Jaipur, Rajasthan
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiag.jiag_24_22

Abstract

Orthostatic hypotension (OH) is defined as a drop of >20 mm Hg of systolic or >10 mm Hg of diastolic blood pressure (BP) within 3 min of standing from lying position. It is a common geriatric syndrome caused by impaired orthostatic response of BP. Its clinical manifestation can range from dizziness to syncope. It is a common cause of recurrent falls and fracture in older adults. Its etiology ranges from neurological causes such as Parkinson and diabetes to hypovolemia. Drugs, especially cardiovascular drugs are also frequently identified as the cause of OH. The management of OH is primarily nonpharmacological including medication review, dietary, and lifestyle modifications. However, in partially responsive or resistant cases, medications such as fludrocortisone, midodrine, droxidopa, etc., are also used.

Keywords: Geriatric, medicines causing orthostatic hypotension, neurogenic orthostatic hypotension, treatment of orthostatic hypotension

How to cite this article:
Jain G, Singhal S, Goyal LK, Mathur A. Orthostatic hypotension: An overlooked but clinically decisive entity. J Indian Acad Geriatr 2022;18:86-90

How to cite this URL:
Jain G, Singhal S, Goyal LK, Mathur A. Orthostatic hypotension: An overlooked but clinically decisive entity. J Indian Acad Geriatr [serial online] 2022 [cited 2023 Jun 6];18:86-90. Available from: http://www.jiag.com/text.asp?2022/18/2/86/351070

Introduction

Orthostatic hypotension (OH) in older adults is a common and frequently underdiagnosed entity. It is commonly seen in geriatric outpatient department and ward, but also in emergency, trauma, neurology, cardiology, and medicine departments. It has a myriad presentation. Literature documents it being associated with high risk of fractures, falls, cerebral vascular disease coronary artery disease and other acute cardiac events with associated morbidity and mortality.^{[1],[2],[3],[4]} Thus, OH is a harbinger of significant consequences and needs thorough investigation.

OH is defined as a fall of >20 mmHg in systolic blood pressure (SBP) or >10 mmHg in diastolic blood pressure (DBP) within the first 3 min of assuming more upright postures. It is present in almost 25% of the patient presenting with syncope, 19% of older patients with trauma, and 68% of geriatric patients in medicine indoor units.^[5],[6],[7] Over the past decade, there has been a definite rise in indoor admissions related to OH.^[8]

This review article focuses on the pathophysiology, etiology, assessment, and management of OH among older adults.

Pathophysiology

Normally, a standing position is associated with a fall in SBP (5–10 mm Hg), an increase in DBP (5–10 mm Hg), and an increase in heart rate (10–25 beats/min). This is due to pooling of 500–1000 ml of blood from the thoracic cavity to lower half of the body. Furthermore, an additional 10%–15% effective reduction in plasma volume occurs secondary to osmotic shift in interstitial spaces of legs occurs leading to reduced venous return and consequent decrease in cardiac output.

Reduced cardiac output is sensed by baroreceptors in the aortic arch, carotid sinus, and venoatrial stretch receptors in the heart and lungs leading to increased sympathetic flow from the hypothalamus. Peripheral and splanchnic vasoconstriction due to norepinephrine release occurs. Renin–angiotensin system activation with vasopressin release causes vasoconstriction and an increase in effective plasma volume. Thus, an optimum hemodynamic response to standing from supine position requires a well-functioning cardiovascular and autonomic nervous system. Voluntary lower limb muscle contraction, involuntary postural changes, and movements also help in propelling a significant volume of blood toward the heart.^{[9],[10],[11]}

Any pathology that alters normal orthostatic response can lead to altered hemodynamics and resultant variations in BP response to orthostasis. Based on pathophysiology, OH can be divided into neurogenic and nonneurogenic types. In neurogenic OH, the baroreflex is impaired with a lack of increase in heart rate. In nonneurogenic OH, this reflex is preserved with reactionary increase in heart rate and compensation.

Causes

Neurogenic OH is caused by baroreceptor dysfunction and may be due to primary or secondary autonomic failure [Table 1], usually associated with low norepinephrine levels. Synucleinopathies of old age such as multiple system atrophy, Parkinsonism ^{More Details}, Lewy body dementia ^{More Details}, and pure autonomic failure have a universal component of neurogenic OH in the elderly. Besides primary failure, a number of other diseases are also associated with autonomic peripheral neuropathies (such as diabetes and amyloidosis).^[12]

Table 1: Causes of orthostatic hypotension

Click here to view

OH is often a side effect of medication that causes volume depletion, peripheral vasodilation, and autonomic dysfunction. Diuretics and beta-blockers are frequent culprits.^[13] Polytherapy is common among older patients for concomitant illnesses which also trigger OH.^{[14],[15],[16]} Volume-depleting states (hemorrhage, burns, dehydration, diarrhea, vomiting, fever, salt-losing nephropathy, etc.) can also cause OH. Other causes of OH include reduced cardiac output states (heart failure, valvular heart disease, arrhythmia, constrictive pericarditis, and myocarditis), adrenal insufficiency, thyroid disorders, pheochromocytoma, etc.^[17]

Apart from reduced sensitivity and impaired readjustment of baroreceptor in older patients due to atherosclerosis,^[18],[19] immobility, reduced blood volume, reduced cardiac output, and sympathetic nervous system response occurs.^[20],[21] The Irish longitudinal Study on Ageing showed that there is a failed recovery of heart rate on standing in aged people.^[22],[23]

Clinical Features

Symptoms of OH depend on the magnitude of orthostatic fall in blood pressure (BP) and cerebral hypoperfusion. Patients present with light-headedness, dizziness, and presyncope to syncope on assuming a sudden upright posture from sitting or lying position. Symptoms are more frequent and profound after meals, warm temperature, exertion, or prolonged standing.^[12]

Atypical symptoms such as generalized weakness, lethargy, leg buckling, neck pain, shoulder pain, or headache (coat-hanger headache)^[24] may occur. Infrequently, OH may lead to angina or stroke.^[25] Prolonged OH can lead to depression, anxiety, cognitive impairment, or dementia^[26] producing a poor quality of life.^[27]

The major concern of OH is a fall, leading to injuries, fractures, and beyond.^[28]

Evaluation

Active stand test for the diagnosis of OH requires BP measurement in supine and then standing position. With the patient resting in a supine position for 5 min, initial BP and pulse rate are measured. The patient is then asked to stand and BP and pulse rate are measured at 1 min and 3 min of standing. A reduction in 20 mm Hg or more in systolic pressure or reduction of 10 mm Hg or more in diastolic pressure is considered abnormal. However, OH that occurs after 3 min,^[29] common in older adults (delayed OH) is missed by the conventional test.

Head-up tilt test is a safer option in older adults who experience syncope with positional changes. It involves measurement of heart rate continuously and automated BP recording and is useful for the diagnosis of delayed OH.^[30] Active stand test with continuous electrocardiography and beat-to-beat BP using noninvasive photoplethysmography equipment on a finger or wrist is a more evolved technique allowing continuous BP changes and can be used to diagnose short-term fluctuations such as initial transient OH.^[31]

The absence of an appropriate compensatory increase in heart rate with the fall of BP points toward baroreceptor dysfunction (neurogenic OH).^[32] Valsalva maneuver can also help in differentiating neurogenic OH from nonneurogenic OH. The 24-h ambulatory BP recordings will help detecting supine hypertension and postprandial hypotension. Supine hypertension is a frequent association in older adults and this fluctuation in BP predisposes to cerebrovascular events.^[33]

After diagnosing the patient, further evaluation using history, physical examination, and investigations should be done to identify various causative or contributory factors.

Detailed medication list, especially cardiovascular and neuropsychiatric medications
Causes of hypovolemia (diarrhea, vomiting, fever, hemorrhage, and dehydration)
Cardiovascular diseases such as congestive heart failure, arrhythmia, or valvular heart disease
Endocrinological diseases such as thyroid conditions, Addison disease, and pheochromocytoma
Neurologic history and examination of Parkinson's and Parkinson-plus diseases
Evaluate for peripheral neuropathy. Common causes include diabetes, B12 deficiency, amyloidosis, paraneoplastic, autoimmune, HIV, etc.

Management

As OH is associated with a myriad complication causing significant morbidity and mortality in older adults, it should be treated appropriately using a combination of nonpharmacological and pharmacological approaches.

The management of OH is primarily nonpharmacological and includes medication review, behavioral modification, dietary interventions, isometric counter-pressure maneuvers, and use of abdominal binders and compression stockings.^[34],[35] Identification and withdrawal of medications which may cause or exacerbate OH is the first and most important step. However, it is often overlooked among older adults and withdrawal of culprit drug alone may help in reducing both the prevalence and severity of OH.

Patients and caregivers should be educated regarding its pathophysiology and advised to avoid prolonged standing and gradual rise from supine and sitting position (e.g., after sleep, in mornings, postmeals, etc.). As warm temperature causes skin vasodilation resulting in reduced venous return, the patient should be advised to avoid prolonged exposure to hot climate or hot showers. Further, violent coughing or excessive straining during bowel movements should be avoided and cough suppressants and laxatives should be used when appropriate. The elevation of the head end of bed by 30° will reduce nocturia, volume depletion, and supine hypertension. Lower body strengthening exercises and nonstrenuous activities should be incorporated into physical conditioning of the elderly.

Dietary changes such as small frequent and low-carbohydrate meals will help by reducing massive pooling of blood in splanchnic beds. Increasing salt and water intake to a normal diet leads to volume expansion and hence treats symptoms of OH.^[36] Acute and rapid drinking of approximately 500 ml of cold water (bolus water drinking) before orthostatic stress has been shown to significantly reduce symptoms of OH.^[35] However, caution should be taken in the elderly with concomitant kidney and cardiac decompensation. Caffeine intake in form of coffee or tea has also shown to have good response in the treatment of OH.

Various isometric counter-pressure maneuvers such as handgrip (tightly squeezing a ball in dominant hand), arm-tensing (pulling hands apart while gripped with each other), and leg crossing can be used to reduce the symptoms.^[36] The use of elastic compression garments up to the waist and abdominal binders before standing and walking can reduce peripheral pooling of blood thus improving venous return and a valuable effect on BP.^[34]

OH requires pharmacological treatment when behavioral adjustments and dietary modifications fail to improve symptoms and is debilitating. Fludrocortisone (0.05–0.2 mg/day), a synthetic mineralocorticoid, is a volume expander which increases sodium and water retention in the body.^[37] Tolerance of this drug among older adults is very poor leading to frequent discontinuation. Supine hypertension is an early and common side effect in older adults, and it can even cause heart failure. Hypokalemia and ankle edema are other common side effects. It should be used only as a short-term agent who has shown partial response to nonpharmacological measures of volume expansion.

For patients who have neurogenic OH and do not show a significant response to volume expansion (salt and water augmentation), sympathomimetic agents can be used. Midodrine and droxidopa are two Food and Drug Administration-approved sympathomimetic vasoconstrictors for the treatment of neurogenic OH. Midodrine (2.5–10 mg 2–3 times a day), an alpha-1 adrenoceptor agonist causes vasoconstriction and improves BP.^[38] It is better tolerated than fludrocortisone by the elderly. Supine hypertension, urinary retention, and scalp itch are a few side effects. This can be managed by avoidance of nighttime dosing and supine position. Midodrine can be used alone or can be combined with an abdominal binder for optimum benefits. Droxidopa (100 mg–600 mg 3 times a day), a noradrenaline prodrug, improves OH and is better tolerated than midodrine.^[39] Its adverse effects include supine hypertension, headache, and nausea and should be avoided at night. However, it is less effective in Parkinson patients receiving high doses of carbidopa.

Other drugs which can be used but not form part of standard guidelines are pyridostigmine, octreotide, desmopressin, and atomoxetine. Pyridostigmine, a cholinesterase inhibitor increases cholinergic transmission in sympathetic ganglia and increases response on standing upright.^[40] It can be used if autonomic function is preserved to some extent. Octreotide is a Somatostatin analog that acts by splanchnic vasoconstriction and thus reduces postprandial hypotension.^[41] Desmopressin can be a drug of choice in predominant nocturnal polyuria.^[42] A newer drug atomoxetine (10 mg–18 mg 2 times a day), a selective presynaptic norepinephrine reuptake inhibitor known as norepinephrine transporter inhibitor is used off-label for neurogenic OH with normal or elevated norepinephrine levels.^[43]

Conclusion

OH is an important geriatric syndrome associated with significant adverse outcomes. Understanding basic postural physiology and triggers of hypotension is the crux. Drugs and other systemic illnesses are the missed culprits. The management of OH requires significant decision-making with counseling and environmental modification of the patient. The effect of OH in cardiovascular and cerebrovascular health needs more studies to elucidate the mechanisms underlying.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Ricci F, Fedorowski A, Radico F, Romanello M, Tatasciore A, Di Nicola M, et al. Cardiovascular morbidity and mortality related to orthostatic hypotension: A meta-analysis of prospective observational studies. Eur Heart J 2015;36:1609-17.
2.	Fleg JL, Evans GW, Margolis KL, Barzilay J, Basile JN, Bigger JT, et al. Orthostatic hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial: Prevalence, incidence, and prognostic significance. Hypertension 2016;68:888-95.
3.	Min M, Shi T, Sun C, Liang M, Zhang Y, Bo G, et al. Orthostatic hypotension and the risk of atrial fibrillation and other cardiovascular diseases: An updated meta-analysis of prospective cohort studies. J Clin Hypertens (Greenwich) 2019;21:1221-7.
4.	Juraschek SP, Daya N, Appel LJ, Miller ER 3^rd, Windham BG, Pompeii L, et al. Orthostatic hypotension in middle-age and risk of falls. Am J Hypertens 2017;30:188-95.
5.	Lahrmann H, Cortelli P, Hilz M, Mathias CJ, Struhal W, Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol 2006;13:930-6.
6.	Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Junod AF, Unger PF. Prevalence of orthostatic hypotension among patients presenting with syncope in the ED. Am J Emerg Med 2002;20:497-501.
7.	Aung AK, Corcoran SJ, Nagalingam V, Paul E, Newnham HH. Prevalence, associations, and risk factors for orthostatic hypotension in medical, surgical, and trauma inpatients: An observational cohort study. Ochsner J 2012;12:35-41.
8.	Duggan E, Romero-Ortuno R, Kenny RA. Admissions for orthostatic hypotension: An analysis of NHS England Hospital Episode Statistics data. BMJ Open 2019;9:e034087.
9.	Freeman R, Abuzinadah AR, Gibbons C, Jones P, Miglis MG, Sinn DI. Orthostatic hypotension: JACC state-of-the-art review. J Am Coll Cardiol 2018;72:1294-309.
10.	Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med 2008;358:615-24.
11.	Smit AA, Halliwill JR, Low PA, Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol 1999;519:1-10.
12.	Metzler M, Duerr S, Granata R, Krismer F, Robertson D, Wenning GK. Neurogenic orthostatic hypotension: Pathophysiology, evaluation, and management. J Neurol 2013;260:2212-9.
13.	Bhanu C, Nimmons D, Petersen I, Orlu M, Davis D, Hussain H, et al. Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials. PLoS Med 2021;18:e1003821.
14.	Press Y, Punchik B, Freud T. Orthostatic hypotension and drug therapy in patients at an outpatient comprehensive geriatric assessment unit. J Hypertens 2016;34:351-8.
15.	Gaxatte C, Faraj E, Lathuillerie O, Salleron J, Deramecourt V, Pardessus V, et al. Alcohol and psychotropic drugs: Risk factors for orthostatic hypotension in elderly fallers. J Hum Hypertens 2017;31:299-304.
16.	Rivasi G, Kenny RA, Ungar A, Romero-Ortuno R. Effects of benzodiazepines on orthostatic blood pressure in older people. Eur J Intern Med 2020;72:73-8.
17.	Robertson D, Robertson RM. Causes of chronic orthostatic hypotension. Arch Intern Med 1994;154:1620-4.
18.	Callegaro CC, Taylor JA. Age-related effects of vagotonic atropine on cardiovagal baroreflex gain. Neurobiol Aging 2012;33:368-74.
19.	Vlachakis ND, Mendlowitz M, DGuia D, DGusman D. Diminished baroreceptor sensitivity in elderly hypertensives. Possible role of atherosclerosis. Atherosclerosis 1976;24:243-9.
20.	McGarry K, Laher M, Fitzgerald D, Horgan J, O'Brien E, O'Malley K. Baroreflex function in elderly hypertensives. Hypertension 1983;5:763-6.
21.	Matsukawa T, Sugiyama Y, Watanabe T, Kobayashi F, Mano T. Baroreflex control of muscle sympathetic nerve activity is attenuated in the elderly. J Auton Nerv Syst 1998;73:182-5.
22.	McCrory C, Berkman LF, Nolan H, O'Leary N, Foley M, Kenny RA. Speed of heart rate recovery in response to orthostatic challenge. Circ Res 2016;119:666-75.
23.	Moloney D, O'Connor J, Newman L, Scarlett S, Hernandez B, Kenny RA, et al. Clinical clustering of eight orthostatic haemodynamic patterns in The Irish Longitudinal Study on Ageing (TILDA). Age Ageing 2021;50:854-60.
24.	Bleasdale-Barr KM, Mathias CJ. Neck and other muscle pains in autonomic failure: Their association with orthostatic hypotension. J R Soc Med 1998;91:355-9.
25.	Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS. Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension 1992;19:508-19.
26.	Xia X, Wang R, Vetrano DL, Grande G, Laukka EJ, Ding M, et al. From normal cognition to cognitive impairment and dementia: Impact of orthostatic hypotension. Hypertension 2021;78:769-78.
27.	Pezzoli M, Garzaro M, Pecorari G, Canale A, Meistro D, Mangiardi ML, et al. Orthostatic hypotension and psychiatric comorbidities in patients with dizziness. Am J Otolaryngol 2012;33:432-6.
28.	Ooi WL, Hossain M, Lipsitz LA. The association between orthostatic hypotension and recurrent falls in nursing home residents. Am J Med 2000;108:106-11.
29.	Aydin AE, Soysal P, Isik AT. Which is preferable for orthostatic hypotension diagnosis in older adults: Active standing test or head-up tilt table test? Clin Interv Aging 2017;12:207-12.
30.	Gibbons CH, Freeman R. Delayed orthostatic hypotension: A frequent cause of orthostatic intolerance. Neurology 2006;67:28-32.
31.	Brignole M, Moya A, de Lange FJ, Deharo JC, Elliott PM, Fanciulli A, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018;39:1883-948.
32.	Norcliffe-Kaufmann L, Kaufmann H, Palma JA, Shibao CA, Biaggioni I, Peltier AC, et al. Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Ann Neurol 2018;83:522-31.
33.	Palma JA, Redel-Traub G, Porciuncula A, Samaniego-Toro D, Millar Vernetti P, Lui YW, et al. The impact of supine hypertension on target organ damage and survival in patients with synucleinopathies and neurogenic orthostatic hypotension. Parkinsonism Relat Disord 2020;75:97-104.
34.	Mills PB, Fung CK, Travlos A, Krassioukov A. Nonpharmacologic management of orthostatic hypotension: A systematic review. Arch Phys Med Rehabil 2015;96:366-75.e6.
35.	Newton JL, Frith J. The efficacy of nonpharmacologic intervention for orthostatic hypotension associated with aging. Neurology 2018;91:e652-6.
36.	Raj SR, Coffin ST. Medical therapy and physical maneuvers in the treatment of the vasovagal syncope and orthostatic hypotension. Prog Cardiovasc Dis 2013;55:425-33.
37.	Chobanian AV, Volicer L, Tifft CP, Gavras H, Liang CS, Faxon D. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension. N Engl J Med 1979;301:68-73.
38.	Izcovich A, González Malla C, Manzotti M, Catalano HN, Guyatt G. Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review. Neurology 2014;83:1170-7.
39.	Elgebaly A, Abdelazeim B, Mattar O, Gadelkarim M, Salah R, Negida A. Meta-analysis of the safety and efficacy of droxidopa for neurogenic orthostatic hypotension. Clin Auton Res 2016;26:171-80.
40.	Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM, Hines S, et al. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol 2006;63:513-8.
41.	Hoeldtke RD, Israel BC. Treatment of orthostatic hypotension with octreotide. J Clin Endocrinol Metab 1989;68:1051-9.
42.	Mathias CJ, Fosbraey P, da Costa DF, Thornley A, Bannister R. The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure. Br Med J (Clin Res Ed) 1986;293:353-4.
43.	Ramirez CE, Okamoto LE, Arnold AC, Gamboa A, Diedrich A, Choi L, et al. Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension 2014;64:1235-40.