Introduction
Definition of orthostatic hypotension
Epidemiology
Clinical features
Treatment
Conclusion
References

 

 

 

Introduction

Orthostatic hypotension or postural hypotension is a relatively common condition in the elderly population. It is an important cause of preventable falls in the elderly and this article summarises the most recent advances in this field from epidemiology, clinical presentation and management.

 

Definition of orthostatic hypotension

Orthostatic hypotension (OH) is defined as a drop in systolic blood pressure (SBP) of more than 20mmHg and/or more than 10mmHg in diastolic blood pressure (DBP) in the first three minutes after standing.

Orthostatic intolerance (OI), in comparison, is when patients develop symptoms of OH, but the fall in blood pressure does not fulfil the current criteria for OH.

Impairment of stabilisation is the increased time for the blood pressure to return to the baseline readings after standing and delayed OH is when there is a significant drop in the SBP and/or DBP, after the first three minutes of standing.

 

Epidemiology

A number of studies have reviewed the prevalence of OH in recent years. The Irish TILDA study analysed data from 4,475 persons after an active standing test. There were three responses, namely the impairment of early stabilisation, early OH and delayed OH. It found that—in persons aged between 50 and 59 years—the blood pressure stabilisation took less than 30 seconds, whilst in older age groups, it took more than 30 seconds. The prevalence of impaired blood pressure stabilisation was 15%, increasing to 41% in persons over 80 years. The total prevalence of OH was 6.9%, increasing to 18% for persons over the age of 80 years.1

In the Swedish Good Aging in Skane study (GAS-SNAC), 1,400 individuals were randomly selected from a database on ageing. The study concluded that OH was a risk factor for mild cognitive dysfunction.2

Freud et al conducted a retrospective analysis of 571 patients over 90 years to examine the prevalence of systolic and diastolic OH. They found that the prevalence of systolic OH is more common than diastolic OH. Systolic OH was seen in 25% and diastolic OH was seen in 15% of their patients. The mortality rate was higher in patients with OH at 30% than in those that did not have OH at 22%. However, the authors made an important observation. OH was not an independent risk factor for mortality in various other comorbidities.3

Delayed OH is supposed to happen after three minutes of testing. The exact significance of delayed OH was studied by Gibbons et al, and they found that the delayed hypotension is not a benign entity. In their 10-year follow up study, they showed that 54% of individuals with delayed OH developed OH, and 31% of them developed alpha-synucleinopathy. The mortality was 29% with delayed OH, 64% with OH, and 9% with controls.4

Gurevich et al found that the delayed OH is associated with female gender and younger age (less than 65 years) in their observation of 270 patients with OH who underwent tilt table testing.5

In a prospective study of 290 nursing home residents, Hartog et al found that the OH was prevalent in 36% of individuals. Surprisingly, they did not find an association between a previous fall and OH. They also observed that the patients with OH are associated with successful rehabilitation.6 OH is associated with falls in many previous studies so this study comes as statistical surprise that needs to be explained.

It is clear that falls are related to activity. If the residents in nursing home are bed bound then it is expected that they will fall less frequently. As the authors also found that patients who had OH were likely to have successful rehabilitation, it again, proves the point that OH is a treatable entity.

As opposed to the findings above, Joditis et al found that 60% of patients with OH had a history of falls in the previous six months versus 42% without OH.7

Vasovagal syncope is seen commonly in children, and particularly in hot and humid weather. Similar observations were made by Huang et al. In their retrospective study they found that 40% of the syncope occurred in the summer months, compared to 29% in winter months, in patients taking antihypertensive medications.8

The exact prevalence of OH is difficult to estimate due to many technical issues. These include patients who cannot stand to measure the standing blood pressure. These conditions include patients with fracture of hips, femurs, ankles, spine, pubic rami, etc.

Muangpaisan et al tried to get the exact magnitude of OH in patients with hip fractures. They found that 21% of their male patients with hip fracture and 8% of female patients had OH.9

The prevalence of orthostatic intolerance and its significance was found by O’Connell et al, who studied 5,692 community dwelling adults aged over 50 years in the Irish Longitudinal Study on Ageing. The authors found OI in 6.7% of participants. Moreover they found that the OI is related to frailty than OH.10

 

Clinical features

A diagnosis of OH is made after a stand up test or head tilt up test. The tilt table test is often carried out to investigate syncope, OH or a postural orthostatic tachycardia syndrome (POTS).

POTS can be diagnosed when the heart rate increases by 30bpm on a tilt table test or on active stand up test, in the first 10 minutes. However, the diagnosis of POTS, on the tilt table test or after stand up test, does not necessarily mean that patients are symptomatic or will become symptomatic in future.11

OH can remain asymptomatic, particularly in patients with dementia. One study included 154 patients with dementia out of which 50 had Lewy Body Dementia, 50 had Alzheimer’s dementia and 54 had mixed AD/vascular dementia. The patients underwent measurement for postural blood pressure. 43% of them had a diagnostic blood pressure for OH, but only 27% were symptomatic for OH during the test. 63% of patients did not have symptoms.12

Patients with OH often present with symptoms of dizziness or vertigo. So far common experience dictated that dizziness is a symptom of OH while vertigo is sign of vestibular dysfunction. An interesting observation came from Choi et al. In their small study of 33 patients they were able to demonstrate a rotatory vertigo, downbeat nystagmus and horizontal nystagmus in 10% of patients after a Shillong squat-stand test.13

Feeney et al recruited 3,765 persons from the Irish Longitudinal study of Ageing (TILDA) and beat to beat blood pressure was measured. This data was correlated to the Stressful Life Events (SLE) self reported questionnaire. The analysis showed that SLEs are associated with slow recovery from orthostatic heart rate and blood pressure.14

A correlation was also found to exist in the degree of SBP and DBP, in various positions. Sung et al found that SBP and DBP are higher in supine position in patients with OH compared with patients without OH. They also found that the carotid-femoral pulse wave velocity was higher in patients with OH.15

Syncope is a transient loss of consciousness by decreased cerebral blood flow. It can be a result of reflex sensitivity, OH, cardiac diseases, hypoperfusion, autonomic failure, etc. A relationship was studied between syncope and the level of Troponin T and the outcomes were reported by Chris et al. The study showed that patients presenting with syncope to the emergency departments had a 52% chance of having adverse events in 30 days if they have a higher value of high sensitivity cardiac Troponin T.16

Parkinson’s disease is also a condition that is often associated with OH. Jost et al, however, found that there is no correlation between the severity of OH and the duration of PD.17

OH can cause dizziness and its association is less established with loss of balance. An objective relationship between OH and balance was studied by Shen et al. They studied 36 patients with OH and hypertension, and 140 patients with hypertension but without OH. They found that there was no difference after prolonged standing.18

Unexplained OH remains unexplained if not investigated further. Krishnan et al found that the amino-terminal of BNP, the NT-proBNP, is elevated in 15% of unexplained OH.19 This means that at least some patients with unexplained OH have some explanation.

Lee et al found that recurrence of syncope was more common in unexplained syncope.20 This finding is possibly explained by the fact the patients who have known cause for syncope often receive treatment.

Another question is whether OH is in anyway related to the stiffness of the arterial wall? Lu et al tried to find an answer to the question. They proved that in OH the arterial wall stiffness is increased, and there is modulation of heart rate variability.21

OH can also be caused by a variety of conditions such as dehydration, obstruction to blood flow, vasodilatation or autonomic neuropathy.

Patients with neurogenic OH have a generally decreased tone of sympathetic nervous system. Mar et al in their retrospective analysis of 83 patients with neurogenic OH, found that patients can be categorised into two types; those with raised standing norepinephrine levels and those with normal levels. Those who have higher levels had lesser falls in systolic and diastolic BP compared to those with normal levels.22

As the association between OH and autonomic failure is well established now, orthostatic intolerance without OH is increasingly recognised in patients with autonomic failure.23

Initial OH is OH in the first 30 seconds. It may get missed in the time taken to tie, inflate cuff and measure the BP. McJunkin et al discovered a new method in which, the cuff is inflated before the patient stands up. This way there are more chances of detecting OH in first 30 seconds. They found that OH can be detected in 3.4% of their patients. This is an important study because some patients with OH may be missed during routine clinical examination.24

In addition, OH can be associated with congestive heart failure, hypertension, or cerebrovascular diseases. The association of these disorders with OH was statistically correlated by a study by Clark et al. They developed a score called the DROP score in a hope that the OH can be diagnosed from the score.

 

Treatment

It seems that most of the research is carried out in patients with neurogenic OH. The research can be broadly divided into pharmaceutical and non-pharmaceutical.

Norepinephrine is a neurotransmitter at sympathetic nerve terminals. The norepinephrine is therefore responsible for vasoconstriction, which then maintains blood pressure. Droxidopa is a prodrug of norepinephrine. Patients with Parkinson’s disease and neurogenic orthostatic hypotension treated with droxidopa were investigated in a randomised placebo controlled multicenter clinical phase III trial by Hauser et al.25 The Orthostatic Hypotension Assessment Scale, item 1, was reported to be improved by 2.3 in the active group, compared to the placebo group at 1.3. The mean increase in systolic BP at week one was 6.4 for droxidopa versus 0.7mmHg for placebo. The study did not show any statistical significance in improvement in subsequent weeks up to four. The headaches and dizziness were slightly more in the droxidopa group compared to the control group.25

Droxidopa has also also been studied in a randomised control manner in symptomatic neurogenic OH. It was given initially for a few weeks. Responders were randomised to receive droxidopa for 14 days or placebo. Withdrawal of droxidopa did not influence symptoms statistically. The authors have concluded that further studies are needed.26

Atomoxetine is norepinephrine transport blocker. Ramirez et al in a randomised control study found that paediatric doses of atomoxetine are superior to midodrine in certain aspects. In 65 patients with OH due to autonomic failure, they hypothesised and proved that atomoxetine improves standing blood pressure. The mean difference in standing BP was 7.5mmHg. There was no significant difference in sitting BP compared to the 0.3mmHg of standing BP with midodrine.27

In a small study of 13 patients with neurogenic OH, Figueroa et al showed that mild abdominal compression of around 10mmHg before standing can abolish OH to some extent.28 This comes as a surprise since it is commonly believed that abdominal pressure decreases the venous return.

An interesting therapy was tried in a Malaysian centre on only two patients of spinal cord injury with OH, diagnosed on head up tilt table test. The two patients received electrical stimulation therapy weekly for one hour for four weeks on their lower abdominal and major leg muscles. In one patient the OH was abolished, while in the other patient symptoms of OH had disappeared.29

Elastic compression stockings are prescribed to the patients of OH. Quinn et al found in 90 patients that 43% of patients never used possibly because of difficulty in using.30

 

Conclusion

Impairment of stabilisation of blood pressure and OH increases with age. Delayed OH and OI are not benign entities and OI is associated with frailty. OH is a risk factor for mortality and for the development of cognitive dysfunction. Syncope due to OH is commoner in summer months than in winter months.

Patients with diagnosis of POTS can remain asymptomatic as can patients with dementia. Persons with slow recovery of heart rate and blood pressure, can have more stressful life events.

Other findings are that patients with OH have higher SBP and lower DBP in a supine position, patients with OH can have decreased balance and other clinical features such vertigo and nystagmus and patients with syncope with higher Troponin T levels have more adverse outcomes in the long run. In addition, we detect more patients with OH if we inflate the cuff before standing.

Droxidopa, which is a prodrug for norepinephrine, has limited use in the treatment of OH. Atomoxetine in paediatric dosages are slightly better than midodrine, in responses to standing SBP. Abdominal compression bands are not very popular with patients, though useful. Manual compression of abdomen and electrical stimulation of upper thigh muscles are shown to be useful in small studies, and need further evaluation.

   

KEY POINTS:

1

The impairment of stabilisation of blood pressure increases with age like OH.

2

Delayed OH can be associated with the development of synucleinopathies.

3

OH is a risk for mortality and for a cognitive dysfunction.

4

OH can remain asymptomatic in demented persons.

5

Atomoxetine in paediatric doses have better systolic blood pressure response than midodrine.

 

Anil Mane Consultant in elderly care, Bangor University Hospital

Tapajauti Chaudhury

Prem Ohri

Conflict of interest: none declared

 


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