Orthostatic hypotension

Orthostatic hypotension (OH) is an independent predictor of mortality and the cause of significant morbidity associated with falls.

A common problem in frail older people. OH-related hospitalizations increase markedly with age.

Common causes include drugs (e.g., alpha-blockers, central sympatholytics, tricyclic antidepressants, phosphodiesterase-5 inhibitors, and antihypertensives, including beta-blockers), diseases causing peripheral neuropathy (e.g., diabetes mellitus and amyloidosis), and synucleinopathies (i.e., Parkinson disease, dementia with Lewy bodies, pure autonomic failure, and multiple system atrophy or Shy-Drager syndrome).

Acute or subacute onset suggests an autoimmune or paraneoplastic disorder.

OH is increasingly recognized as a common comorbidity of hypertension, both because of the pathophysiology of hypertension itself, and also because the measurement of OH is derived from the difference between two blood pressures (lying or sitting, and standing), the absolute value of which will be greater with a higher starting blood pressure.

Treatment consists of addressing any underlying pathology, when possible, followed by discontinuing or reducing the dose of aggravating drugs, and introducing nonpharmacologic countermeasures (e.g., liberalization of salt intake, use of abdominal binders or compression stockings). Short-acting vasopressors, such as midodrine, or droxidopa (a norepinephrine prodrug) are adjunctive therapies when nonpharmacologic measures are insufficient. Volume expansion (using mineralocorticoid therapy) may be used after these therapies due to limited evidence for its use, and a number of undesirable adverse effects.

OH is defined as a fall in systolic blood pressure of at least 20 mmHg (at least 30 mmHg in patients with hypertension) and/or a fall in diastolic blood pressure of at least 10 mmHg within 3 minutes of standing.[1]Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72. http://www.ncbi.nlm.nih.gov/pubmed/21431947?tool=bestpractice.com When OH has an underlying neurogenic cause (e.g., peripheral neuropathy or synucleinopathies) it is associated with a blunted increase in heart rate, typically less than 15 bpm.[2]Norcliffe-Kaufmann L, Kaufmann H, Palma JA, et al. Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Ann Neurol. 2018 Mar;83(3):522-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867255 http://www.ncbi.nlm.nih.gov/pubmed/29405350?tool=bestpractice.com

OH becomes clinically significant if it is accompanied by symptoms of cerebral hypoperfusion, which can lead to syncope and falls.[3]Mol A, Bui Hoang PTS, Sharmin S, et al. Orthostatic hypotension and falls in older adults: a systematic review and meta-analysis. J Am Med Dir Assoc. 2019 May;20(5):589-97.e5. http://www.ncbi.nlm.nih.gov/pubmed/30583909?tool=bestpractice.com OH is associated with increased risk of dementia and cardiovascular disease, and is an independent risk factor for all-cause mortality.[4]Rawlings AM, Juraschek SP, Heiss G, et al. Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline. Neurology. 2018 Aug 21;91(8):e759-68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107267 http://www.ncbi.nlm.nih.gov/pubmed/30045960?tool=bestpractice.com [5]Fagard RH, De Cort P. Orthostatic hypotension is a more robust predictor of cardiovascular events than nighttime reverse dipping in elderly. Hypertension. 2010 Jul;56(1):56-61. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.110.151654?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed http://www.ncbi.nlm.nih.gov/pubmed/20458003?tool=bestpractice.com [6]Fedorowski A, Stavenow L, Hedblad B, et al. Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmo Preventive Project). Eur Heart J. 2010 Jan;31(1):85-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800919 http://www.ncbi.nlm.nih.gov/pubmed/19696189?tool=bestpractice.com ​ This topic concentrates on OH caused by autonomic problems.