Orthostatic Hypotension: Mechanisms, Causes, Management

Abstract

Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP control fails. Such regulation depends on the baroreflexes, normal blood volume, and defenses against excessive venous pooling. OH is common in the elderly and is associated with an increase in mortality rate. There are many causes of OH. Aging coupled with diseases such as diabetes and Parkinson's disease results in a prevalence of 10-30% in the elderly. These conditions cause baroreflex failure with resulting combination of OH, supine hypertension, and loss of diurnal variation of BP. The treatment of OH is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension. The practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension. It is possible to achieve these goals with a combination of fludrocortisone, a pressor agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers. We provide a pragmatic guide on patient education and the patient-orientated approach to the moment to moment management of OH.

Full text

220 Copyright
©
2015 Korean Neurological Association
Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP
control fails. Such regulation depends on the baroreexes, normal blood volume, and defens-
es against excessive venous pooling. OH is common in the elderly and is associated with an
increase in mortality rate. ere are many causes of OH. Aging coupled with diseases such as
diabetes and Parkinson’s disease results in a prevalence of 10
–
30% in the elderly. ese con-
ditions cause baroreex failure with resulting combination of OH, supine hypertension, and
loss of diurnal variation of BP. e treatment of OH is imperfect since it is impossible to nor-
malize standing BP without generating excessive supine hypertension. e practical goal is to
improve standing BP so as to minimize symptoms and to improve standing time in order to
be able to undertake orthostatic activities of daily living, without excessive supine hyperten-
sion. It is possible to achieve these goals with a combination of udrocortisone, a pressor
agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic de-
fenses during periods of increased orthostatic stress. Such procedures include water bolus
treatment and physical countermaneuvers. We provide a pragmatic guide on patient educa-
tion and the patient-orientated approach to the moment to moment management of OH.
Key Words
zz
orthostatic hypotension, baroreex, supine hypertension, water bolus
.
Orthostatic Hypotension:
Mechanisms, Causes, Management
BACKGROUND
Orthostatic intolerance refers to the development of symptoms such as lightheadedness and
blurred vision when a subject stands up that clears on sitting back down. Other symptoms
include cognitive blunting, tiredness, and head and neck ache. ese symptoms are due to
cerebral hypoperfusion.
1
e posterior head and neck ache (with a coathanger distribution)
is thought to be due to ischemia of large neck muscles.
1
Other symptoms such as palpita-
tions, tremulousness, nausea, and vasomotor changes are due to sympathetic hyperactivity
and occur in patients with only partial autonomic failure.
Not every patient with orthostatic intolerance has orthostatic hypotension (OH). Com-
mon causes of orthostatic intolerance are shown in Table 1. A common cause of transient
orthostatic intolerance is reex syncope (vasovagal, vasodepressor). An otherwise normal
person suddenly faints. Vasovagal and vasodepressor syncope are both characterized by the
sudden abrupt fall in blood pressure (BP). They differ in that in vasovagal syncope, the
abrupt fall in BP, is accompanied by a similarly abrupt fall in heart rate whereas the latter is
absent in vasodepressor syncope. ey are oen triggered by pain (such as receiving an in-
jection or blood-draw) or emotional stimulus. ese occur in persons with normal barore-
exes and occur suddenly. Another cause, occurring about 5–10 times as commonly as OH,
is postural tachycardia syndrome, characterized by orthostatic intolerance coupled with or-
thostatic tachycardia.
2
OH is dened as a reduction of systolic BP of at least 20 mm Hg or
Phillip A. Low
Victoria A. Tomalia
Department of Neurology, Mayo Clinic,
Rochester, MN, USA
pISSN 1738-6586 / eISSN 2005-5013 / J Clin Neurol 2015
;
11
(
3
):
220-226 / http://dx.doi.org/10.3988/jcn.2015.11.3.220
Received January 19, 2015
Revised
January 20, 2015
Accepted
January 20, 2015
Correspondence
Phillip A. Low, MD
Department of Neurology,
Mayo Clinic, 200 First Street SW,
Rochester, MN 55905, USA
Tel +1-507-284-3375
Fax +1-507-284-3133
E-mail low@mayo.edu
cc
is is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Com-
mercial License
(
http
:
//creativecommons.org/licenses/by-nc/3.0
)
which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
JCN Open Access
REVIEW

www.thejcn.com 221
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diastolic blood pressure of at least 10 mm Hg within 3 min-
utes of standing up.
3
e “prevalence” of OH increases with age and occurs in
10–30% of elderly persons.
4
There is a moderate spread in
reported frequency of OH (Table 2). Although the values are
not population based, and therefore not true prevalences, the
numbers are pragmatically important. ey make the point
that OH in the elderly is common. BP control becomes pro-
gressively more impaired with aging, due to a multitude of
reasons including impaired baroreflex sensitivity, volume
status, and venomotor tone.
4
Part of the explanation resides
in the increased occurrence of associated conditions like dia-
betes and Parkinson’s disease as well as the eects of drugs
like anti-hypertensive agents, diuretics, and anti-Parkinsonian
drugs like levodopa. The presence of OH is associated with
increased mortality and morbidity.
4
The reason for the in-
crease in morbidity and mortality is multifold but includes
the consequences of repeated falls, resulting in fractures, head
injury, and their complications.
MAINTENANCE OF POSTURAL
NORMOTENSION
The normal human subject maintains the same BP supine
and standing. This maintenance of postural normotension
depends on a normal plasma volume, intact baroreexes, and
reasonable venomotor tone.
5
A subject with reduced plasma
volume (hypovolemia) can develop OH. Similarly, OH can
occur in some subjects (predisposed to OH) because of ex-
cessive venous pooling. e splanchnic mesenteric bed is es-
pecially important because of its large volume and baroreex
responsiveness.
6,7
Splanchnic-mesenteric volume increases
200–300% aer a meal
7
and this increased venous capacitance
causes venous pooling with resultant post-prandial OH in
predisposed subjects. Standing in normal subjects results in a
fall in blood and pulse pressure and this fall is sensed by baro-
receptors in carotid sinus and aortic arch.
5
Baroreceptor af-
ferents synapse at the nucleus of the tractus solitaries (Fig. 1).
e vagal baroreex pathway runs from the nucleus of the
tractus solitarius to the nucleus ambiguus and sends eerents
to the sinoatrial node to increase heart rate. e adrenergic
baroreex pathway runs from the nucleus of the tractus soli-
tarius to the caudal ventrolateral medulla and from there to
the rostral ventrolateral medulla. The adrenergic pathway
continues with sympathetic eerents from the rostral ventro-
lateral medulla to the interomediolateral column of the tho-
racic spinal cord, and from there to autonomic ganglia and
to the heart, arterioles, and venules. Hence, the initial fall in
BP is corrected by an increase in HR and total systemic resis-
tance. If the baroreexes fail, as in adrenergic autonomic fail-
ure, there are several consequences. ere is:
a. OH.
b. Supine hypertension (since baroreexes also prevent ex-
cessive BP increase).
c. Loss of diurnal BP variation. The normal subject has
lower nocturnal BP. Patients with baroreex failure have un-
changed or higher nocturnal BP.
Causes of orthostatic hypotension
ere are many causes of OH (Table 3). Most cases seen in
clinical practice are best divided into those with and without
CNS involvement. Patients with CNS involvement can be
Table 1. Causes of orthostatic intolerance and their differentiation
BP Reflex syncope POTS Neurogenic OH
Baseline HR Normal Normal Normal
Orthostatic HR Normal; sudden
↓
at syncope
↑
>30 bpm Reduced
Supine BP Normal Normal Normal or
↑
Orthostatic BP Normal; sudden
↓
at syncope Normal Fall
≥
20 mm Hg
BP: blood pressure, HR: heart rate, OH: orthostatic hypotension, POTS: postural tachycardia syndrome.
Table 2. Prevalence of orthostatic hypotension in certain settings
Setting Number Age (years) Prevalence (%) Reference
Nursing home 250 61–91 11 Rodstein and Zeman
29
(1957)
Outpatients 494
≥
65 24 Caird et al.
30
(1973)
VA geriatric unit 319 50–99 10.7 Myers et al.
31
(1978)
Outpatients 186
≥
65 22 MacLennan et al.
32
(1980)
Geriatric unit 272 Mean age 83 10 Lennox and Williams
33
(1980)
Geriatric unit 247
≥
60 33 Palmer
34
(1983)
Outpatients 300 Mean age 70 6.4 Mader et al.
35
(1987)
Modified from Low.
4
Clin Auton Res 2008;18 Suppl 1:8-13.
VA: veterans affairs.

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separated into those with brain or spinal cord disease. Pa-
tients with chronic OH without CNS involvement will most
commonly have OH due to diabetes. Less likely causes are
amyloid, either sporadic or inherited (tranthyretin muta-
tion), autoimmune, or paraneoplastic etiology. Some have no
cause found and are typically designated as idiopathic OH or
pure autonomic failure. If they have dream enactment behav-
ior, they are best designated pure autonomic failure, since
they likely have a synucleinopathy.
In a setting of acute onset of OH, the main considerations are
Guillain-Barre syndrome, where the diagnosis is usually obvi-
ous because of severe motor weakness, respiratory compro-
mise, and acute autoimmune autonomic neuropathy (“acute
pandysautonomia”). The latter is characterized by severe and
generalized autonomic failure without prominent motor or
sensory involvement. Other causes such as botulism, porphyr-
ia, or those due to toxic causes are uncommon. eir consider-
ation comes up if there is an acute autonomic neuropathy that
is undiagnosed and especially if there are red ags for these dis-
eases. In such circumstances, tests such as urine drug and heavy
metal screen, tests for porphyria, botulism, and paraneoplastic
panel are done.
Chronic causes of OH are much more common than acute
causes. e most common cause is mild OH due to old age
(discussed earlier). For patients with brain involvement, OH
is common in Parkinson’s disease, occurring in 20–40 per-
cent of patients, but is usually mild.
8
More severe OH occurs
in patients with multiple system atrophy or Lewy body demen-
tia.
9
Patients with alcoholic neuropathy usually do not have
OH and those who have florid OH often have Wernicke-
Korsako syndrome, with involvement of brain stem auto-
nomic structures.
10
Patients with baroreex failure, as occurs
in neck radiation or familial dysautonomia, can have OH,
but this symptom is mild compared with autonomic storms,
due to de-aerentation.
11
Most forms of olivopontocerebellar
atrophies do not have OH and patients with chronic cerebel-
lar involvement and OH should raise suspicion of the cere-
bellar subtype of MSA (MSA-C).
Management of orthostatic hypotension
It is desirable to determine if OH is neurogenic, i.e., due to a
neurologic basis and not due to hypovolemia or venous
pooling. Tests that are helpful in the evaluation of patients
are an autonomic reex screen, thermoregulatory sweat test,
24-hour urinary sodium, and supine and standing plasma
norepinephrine. e paraneoplastic panel provides a full bat-
tery of antibodies and should be considered if an autoimmune
etiology is suspected. Testing to rule out diabetes, amyloidosis
(fat aspirate, protein, and immunoelectrophoretogram), por-
phyria, B12 deciency, and inherited neuropathy are under-
Fig. 1. Baroreflex pathways for postural normotension. Baroreceptor afferents (dark blue) synapse at the nucleus of the tractus solitarius (NTS).
The vagal component of the baroreflex (green) runs from the NTS to the nucleus ambiguus (NA) and sends efferents to the sinoatrial node (SA) to
regulate heart rate. The adrenergic baroreflex pathway (red) runs from the NTS to the caudal ventrolateral medulla (CVLM), and from there to the
rostral ventrolateral medulla (RVLM). The adrenergic pathway continues with sympathetic efferents from the RVLM to the interomediolateral tho-
racic spinal cord, and from there to autonomic ganglia and to the heart, arterioles, and venules (Reprinted from Low and Singer.
5
Lancet Neurol
2008;7:451-458, with permission from Elsevier).
RVLM
CVLM
Thoracic
spinal cord
Sympathetic
output
NA
NTS
Arterial
baroreceptors
Venous
baroreceptors
Arterial
pressure
Cardiac
ouput
Total
peripheral
resistance
Skeletal muscle
and splanchnic
vessels

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taken as needed.
e autonomic reex screen is made up of the quantitative
sudomotor axon reflex test (QSART), tests of cardiovagal
function, and tests of adrenergic function.
12
QSART evalu-
ates postganglionic volumes in the forearm and 3 leg sites.
We measure heart rate variation and the Valsalva ratio in tests
of cardiovagal function.
13,14
For evaluation of adrenergic re-
exes, we evaluate beat-to-beat BP and heart rate responses
to the Valsalva maneuver and to head up tilt.
15
e autonom-
ic reex screen will help determine the severity and distribu-
tion of sudomotor, cardiovagal, and adrenergic failure. e
thermoregulatory sweat test evaluates the distribution of an-
hidrosis.
16
e pattern of anhidrosis can be very helpful. For
instance, a length-dependent neuropathy is characterized by
distal sweat loss and autoimmune autonomic ganglionopathy
by regional loss of sweating whereas pure autonomic failure or
MSA might have global anhidrosis. We digitally determine
%-anhidrosis, comprising % of anterior body surface that is
anhidrotic. Combining thermoregulatory sweet test with
QSART can also determine site of the lesion. For instance, if a
limb has normal QSART but is completely anhidrotic on TST,
the lesion is preganglionic in site.
e 24-hour urinary sodium provides 2 items of useful in-
formation. First, it helps determine if the patient is taking the
right amount of uids. e goal is an excretion of 1,500 to
2,500 mL of urine in 24 hours. Second, since sodium is cen-
tral of maintenance of plasma volume, urine excretion pro-
vides verification that the patient is taking enough salt. A
urine excretion of >170 mmol/24 hours correlates well with a
normal plasma volume.
17
Patient education
Patient education is crucial. e patient is informed on the
cause of their OH and management of the cause. For instance,
the diabetic needs to optimize blood glucose control. The
discussion then moves to the practical management of OH
(Table 4). e rst 4 items of Table 4 summarize key educa-
tional themes that the patient needs to come to terms with.
ey need to recognize that they have impaired baroreexes.
The consequences of baroreflex failure include OH, supine
hypertension, and loss of diurnal variation, since baroreexes
are no longer available to ensure a normal pattern of supine
and standing BP.
5
Pressor agents such as midodrine are avail-
able to raise BP and maintain normal standing BP but at a
price of unacceptable supine hypertension.
18
e goal is there-
fore a practical one of providing a moderate pressor eect,
sucient to raise standing BP enough such that the patient
has only modest or infrequent symptoms, and has adequate
standing time so as to be able to undertake activities of daily
living without excessive supine hypertension. Practical val-
ues are typically a standing SBP
≥
90 mm Hg and supine SBP
≤
180 mm Hg. The patient needs to be aware that OH will
vary depending on a number of variables, such as volume sta-
tus; subjects with even transiently low plasma volume, such as
on arising, will have lower BP. A meal increases splanchnic
mesenteric volume 300%
7
and this venous pooling can cause
post-prandial OH. Raised ambient heat or a warm bath are
potent vasodilators and regularly will aggravate OH. It is im-
portant to balance education of the patient on orthostatic
stressors with empowering the patient on what they can do to
raise BP. ey are told that there are 3 variables they can con-
trol: plasma volume, venous pooling, and vasomotor tone.
ey can control these variables with a simple to remember
mnemonic.
19
Abdominal binder
Compression of venous capacitance bed reduces venous
pooling and orthostatic fall in BP. e largest venous capaci-
tance bed is the splanchnic-mesenteric bed. Hence, compres-
sion of this bed by abdominal compression,
20,21
is much more
effective than compressing the leg veins, because of its low
Table 3. Causes of orthostatic hypotension
Autonomic disorders with brain involvement
Synculeinopathies (multiple system atrophy, Lewy body
dementia, and Parkinson’s disease)
Wernicke korsakoff syndrome
Baroreflex failure
Olivopontocerebellar atrophy
Autonomic disorders with spinal cord involvement
Traumatic tetraplegia
Syringomyelia
Spinal cord tumors
Multiple sclerosis
Autonomic neuropathies
The acute autonomic neuropathies
Guillain-Barre syndrome
Autoimmune autonomic ganglionopathy
Acute paraneoplastic autonomic neuropathy
Botulism
Porphyria
Toxic autonomic neuropathies, due to heavy metals and drugs
The chronic autonomic neuropathies
Diabetic autonomic neuropathy
Amyloid autonomic neuropathy
Autoimmune autonomic ganglionopathy
Familial dysautonomia and other inherited autonomic
neuropathies
Pure autonomic failure
Idiopathic autonomic neuropathy

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volume.
21
Jobst stockings are available that compress legs and
abdomen, but many patients nd the stockings very dicult
to apply. A practical alternative is to wear an abdominal bind-
er as a routine. If additional compression is needed, leg stock-
ings are additionally worn.
Bolus of water and elevating head of bed
Water-bolus treatment consists of the patient drinking two 8
ounce glasses of cold water in rapid succession. is results
in the abrupt increase in standing systolic blood pressure by
about 20 mm Hg for 1–2 hours.
22,23
e mechanism involves
activation of sympathetic adrenergic neurons; plasma con-
centrations of norepinephrine increase, and the eect can be
abolished with trimetaphan, an autonomic ganglionic block-
ing agent.
23
Patients are encouraged to time their water bolus
treatment to periods of increased orthostatic stress. For in-
stance, a subject might do one treatment on arising, another
before a shopping trip, and a third before exercising. For pa-
tients who bolus 3–4 times a day, we advise them to avoid
frequent sipping of water, so that they do not get overloaded
with water.
Patients with signicant supine hypertension are taught to
avoid lying at. ey sleep with the head of the bed elevated
4 inches and during the day rest at about a 30 degree angle.
ey are taught that their normal lying position is 30 degrees
from supine. is approach avoids the eects of supine hy-
pertension on brain vessels.
Countermaneuvers
Muscle contraction will raise BP by a muscle pressor response
and is the basis of the handgrip test.
5,24
The practical ap-
proach is for the patient to contract a group of muscles bilat-
erally for about 30 seconds, relax, and then repeat the ma-
neuver. Simple maneuvers include standing up on their toes,
or crossing their legs and squeezing.
19
Some patients manage
to unobtrusively contract their buttocks, thighs, and calves
while they stand. These maneuvers result in a transient in-
crease in total peripheral resistance.
Drugs
Midodrine is a directly acting α1-adrenoceptor agonist. It and
its active metabolite, desglymidodrine, have a duration of ac-
tion of 2–4 hours.
18
e main side-eects are supine hyper-
tension, paresthesias (including troublesome scalp-tingling),
and goose-bumps. Rarely patients develop bladder pain or an
inability to void, problems that preclude use of midodrine in
those patients.
Fludrocortisone expands plasma volume and increases
sensitivity of α-adrenoceptors.
25
It is usually used at a dose of
0.1–0.2 mg/day. Main complications are hypokalemia and
supine hypertension.
25
Droxidopa, an oral norepinephrine precursor, was shown
in a phase III treatment trial to improve symptoms and im-
prove standing systolic BP.
26
e drug was recently approved
by the FDA for rare diseases with OH. Droxidopa is general-
Table 4. Ten guiding facts in the management of OH
It is feasible to improve BP but not possible to normalize BP control because baroreflexes are impaired. The consequences of impaired baroreflexes
include OH, supine HT, and loss of diurnal variation
The goal is to improve standing BP sufficiently to minimize symptoms and undertake activities of daily living without excessive supine HT
OH will vary depending on a number of variables, including volume status, time of day, meals, ambient temperature, and physical activity
The 3 variables that the patient can control are volume, veins, and vasomotor tone. You can control these using the following tools
Abdominal binder to compress splanchnic-mesenteric veins
Bolus treatment and head-of-bed up. Water bolus will raise standing BP. Raise head of bed 4 inches to minimize effects of supine hypertension
Countermaneuvers to raise orthostatic BP
Drugs (midodrine, fludrocortisone, droxidopa, pyridostigmine)
Education
Fluids and salt
BP: blood pressure, OH: orthostatic hypotension.
Table 5. Some drugs used to treat supine hypertension
Drug Recommended dose Comments
Nitroglycerine patch 0.1 mg/hr Remember to remove in AM; headaches a problem
Losartan 50 mg in evening Take about 3–4 hours before retiring; good for PAF
Nifedipine 30 mg at night
Clonidine 0.1–0.2 mg at night Take in evening; slow onset
Hydralazine 25 mg
PAF: pure autonomic failure.

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Low PA and Tomalia VA
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ly well tolerated. It seems to have a duration of action of about
6–8 hours. Currently, midodrine remains the preferred drug.
It could potentially be preferable for patients who do not tol-
erate midodrine or who nd its duration of action unaccept-
ably short. Patients with dopamine beta-hydroxylase defi-
ciency seem to have better BP control with droxidopa than
midodrine.
Pyridostigmine, a cholinesterase inhibitor, will improve
standing BP in patients with OH without aggravating supine
hypertension.
27
is action occurs since baroreex unload-
ing occurs on standing and is minimal at rest. Cholinesterase
inhibition increases the safety factor of ganglionic transmis-
sion by delaying breakdown of acetylcholine. e main limi-
tation of pyridostigmine is its modest eect.
Education
e patient needs to recognize that because they have failure
of their baroreflexes, they will no longer have normal BP
control. ey need to understand what aggravates standing
BP and what improves it. For instance OH might be worse
rst thing in the morning, aer a meal, or on a hot day. ey
need to learn about recognizing subtle symptoms (such as
thinking less clearly or feeling tired when they stand). ey
need to know about techniques to improve OH, such as a bo-
lus or water, countermaneuvers, or venous compression.
Fluids and salt
Fluid intake of 1.25–2.50 L/day is crucial but is oen neglect-
ed in elderly people. Salt supplementation is also essential.
Most patients manage with salt added to meals but some
prefer to use salt tablets (e.g., 0.5 g or 1.0 g tablets). Many pa-
tients who have inadequate control of OH have an inade-
quate salt intake. This can be verified by checking the 24-
hour urinary sodium concentration: patients who have a
value below 170 mmol can be treated with 1–2 g supplemen-
tal sodium three times a day. Urine volume should be be-
tween 1,500 and 2,500 mL.
Management of supine hypertension
Supine hypertension is common in patients with OH. The
best management of supine hypertension is its prevention, by
choosing a drug combination coupled with patient education
that is sucient to raise standing BP suciently most of the
time. e patient can be taught to boost BP transiently dur-
ing periods of lower BP by approaches such as water bolus
and avoidance of autonomic stressors.
Patients are also taught to avoid the supine position. eir
new resting position is either the sitting position or lying
down at a 30 degree angle during the day and sleep with the
head of bed elevated 4 inches at night.
Some patients some of the time will nevertheless still de-
velop orid supine hypertension with sitting BP >180 mm Hg
SBP. Management depends on how persistent such a BP is
and how responsive it is to simple measures. For instance in
some patients, the elevations are transient lasting only half
an hour or so and may not require drug treatment. Some pa-
tients will enjoy a glass of wine and observe rapid subsidence
of hypertension. Some drugs used to treat supine hypertension
are shown in Table 5. ey are based on the notion that these
patients have residual sympathetic tone, which can be blocked
with sympathetic antagonists.
28
e particular agent selected
may depend in part on what action is optimally blocked. For
instance in PAF, renin is very low but angiotensin II is para-
doxically high and Losartan (an angiotensin II antagonist) will
reduce supine hypertension without aggravating early morn-
ing OH and decrease nocturnal sodium loss. Losartan 50 mg
is given orally about 6 pm. Clonidine is a centrally acting α2
agonist which reduces sympathetic tone. It is usually given at
a dose of 0.2 mg and works more gradually, with a delayed
onset and longer half-life so that it is oen given about meal
time. Nitroglycerine patch is simple to use, but some patients
are troubled with vascular headaches with the drug. Hydrala-
zine 25 mg or nifedipine 30 mg at night are alternatives. If
nocturnal hypotension is an issue, clonidine may be a better
option than drugs like nifedipine and hydralazine. Some pa-
tients may need a bedside commode to avoid risk of syncope
and fall when they walk to the bathroom.
In summary, OH is common, especially in the elderly. Its
eects include the risk of falls in the elderly and are associat-
ed with an increased mortality rate. Treatment of OH is im-
proving but will not be perfect since baroreexes are no lon-
ger functioning normally. e goal of treatment is to avoid
the severe eects of OH and empower the patient to boost de-
fenses against OH during periods of increased orthostatic
stress.
Conflicts of Interest
e authors have no nancial conicts of interest.
Acknowledgements
This work was supported in part by National Institutes of Health (NS
44233 Pathogenesis and Diagnosis of Multiple System Atrophy, U54
NS065736 Autonomic Rare Disease Clinical Consortium), Mayo CTSA
(UL1 TR000135), e Kathy Shih Memorial Foundation, and Mayo Funds.
e Autonomic Diseases Consortium is a part of the NIH Rare Dis-
eases Clinical Research Network (RDCRN). Funding and/or program-
matic support for this project has been provided by U54 NS065736 from
the National Institute of Neurological Diseases and Stroke (NINDS) and
the NIH Oce of Rare Diseases Research (ORDR).
The content is solely the responsibility of the authors and does not
necessarily represent the ocial views of the National Institute of Neuro-
logical Disorders and Stroke or the National Institutes of Health
.

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