Clin Auton Res (2014) 24:3–13 DOI 10.1007/s10286-013-0219-5

REVIEW ARTICLE

The relationship between orthostatic hypotension and falling in older adults Brett H. Shaw • Victoria E. Claydon

Received: 19 June 2013 / Accepted: 1 November 2013 / Published online: 20 November 2013  Springer-Verlag Berlin Heidelberg 2013

Abstract Falls are devastating events and are the largest contributor towards injury-related hospitalization of older adults. Orthostatic hypotension (OH) represents an intrinsic risk factor for falls in older adults. OH refers to a significant decrease in blood pressure upon assuming an upright posture. Declines in blood pressure can reduce cerebral perfusion; this can impair consciousness, lead to dizziness, and increase the likelihood of a fall. Although theoretical mechanisms linking OH and falls exist, the magnitude of the association remains poorly characterized, possibly because of methodological differences between previous studies. The use of non-invasive beat-to-beat blood pressure monitoring has altered the way in which OH is now defined, and represents a substantial improvement for detecting OH that was previously unavailable in many studies. Additionally, there is a lack of consistency and standardization of orthostatic assessments and analysis techniques for interpreting blood pressure data. This review explores the previous literature examining the relationship between OH and falls. We highlight the impact of broadening the timing, degree, and overall duration of blood pressure measurements on the detection of OH. We discuss the types of orthostatic stress assessments currently used to evaluate OH and the various techniques capable of measuring these often transient blood pressure changes. Overall, we identify future solutions that may better clarify the relationship between OH and falling risk in order to gain a more precise understanding of potential mechanisms for falls in older adults.

B. H. Shaw
V. E. Claydon (&) Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada e-mail: [email protected]

Keywords Orthostatic hypotension
Falls
Older adults
Blood pressure monitoring
Orthostatic stress testing

Introduction Fall-related injuries comprise a major component of the high health care costs incurred by older adults, and are a significant cause of morbidity and mortality for those affected. Annually, 1 in 3 individuals over the age of 65 are expected to experience a fall [32, 55, 98]. In the United States, approximately 1.67 million older adults are treated in the emergency department annually for a fall-related injury [82], and over 3 million older adults report a fallrelated medical condition in a given year [5]. The etiology of falls is complex and multifactorial. Generally, increasing age and the presence of co-morbidities predispose individuals to falling [1]. Cardiovascular impairments represent one intrinsic risk factor that can impact falling risk in various ways [3]. These include side effects from medication, polypharmacy, or the presence of cardiovascular disorders such as hypertension, cardiac arrhythmias or orthostatic hypotension (OH) (Fig. 1) [11, 18, 23, 91]. OH refers to a significant fall in blood pressure that occurs upon assuming an upright posture (Table 1). When upright 500–1000 ml of blood pools in the legs and splanchnic vasculature, resulting in decreased venous return to the heart, and subsequently a transient reduction in blood pressure [52]. This is normally compensated for by activation of arterial baroreceptors, resulting in a withdrawal of parasympathetic activity and increase in sympathetic activity, which increases heart rate and vascular resistance [22, 52]. However, if cardiovascular

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Standing

Venous pooling and capillary filtration

Effective blood volume and venous return

Medications/polypharmacy Cardiac arrhythmias

Upright blood pressure/OH

Impaired baroreflex control Impaired cerebral autoregulation

Hypertension

Cerebral blood flow Presyncope Loss of conciousness/syncope

Impaired balance and mobility

Impaired cognitive function

Falling

Fig. 1 Theoretical mechanisms by which impaired blood pressure control impacts falling risk in older adults. Dotted box indicates a proposed direct pathway linking orthostatic hypotension (OH) and falling. Standing can elicit a large and/or sudden decline in blood pressure. This may be compounded by a poor blood pressure recovery, particularly if baroreflex function is impaired. Ultimately, hypotension can cause cerebral hypoperfusion, leading to loss of consciousness, or syncope. Normally cerebral blood flow is maintained at a constant level over a range of arterial pressures through autoregulatory mechanisms in the cerebral vasculature [75]. However, if the pressure falls below the lower limit for autoregulatory control for a period of time, or if autoregulation is impaired, cerebral perfusion can be compromised. This may or may not be associated with prodromal symptoms (presyncope) prior to loss of consciousness {Note that while much of the symptomatology associated with presyncope is related to cerebral hypoperfusion (dizziness, visual disturbance etc.) some presyncopal symptoms/signs are due to associated autonomic activation (e.g. sweating or pallor) [96]}. The associated loss of postural tone during a syncopal event leads to a fall. Indirect mechanisms linking OH and falling include the negative impact of OH on cognitive functioning, which could serve as an intermediary mechanism between OH and falling risk in older adults [39, 50]. Certain medications (particularly diuretics, vasodilators, and cardioinhibitory drugs) can adversely impact the magnitude and duration of the blood pressure decline when upright [27]. Drug effects are compounded by polypharmacy, common in the elderly [40]. Presyncope may proceed into frank syncope, or loss of consciousness may be avoided, but fall susceptibility remains through associated impairments in balance and mobility [8, 31, 48]. Cardiac arrhythmias and certain structural cardiac disorders can reduce cardiac output with associated hypotension [87]. Hypertension is associated with impaired baroreflex function, and predisposes to impairments in cognitive function and cerebral autoregulatory control [16, 39]. Gray font indicates pathways impacted by advancing age

control mechanisms are impaired, adequate compensation can fail, and OH can result. The prevalence of OH has been shown to rise with age [30, 47, 77], with a prevalence of 10–30 % in ambulatory older adults [44]. It is estimated

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that 2–10 % of falls occur secondary to abnormal blood pressure responses such as OH [29, 69]. This equates to approximately $2.3 billion of the reported total health care costs in the United States incurred as a result of fall-related injuries in older adults in a given year [12]. Despite the numerous studies that have examined the association between OH and falling risk, the relationship remains poorly characterized. Here we will explore the theoretical mechanisms that link OH and falls, and review the previous literature testing this association. We will highlight the recent expansion of definitions for OH and the importance that broadening the timing, degree, and overall duration of blood pressure measurements could have on the results of previous studies. We will also examine methodological considerations for consistently provoking and evaluating these blood pressure changes. Overall, we aim to identify future solutions that may clarify the potential cardiovascular mechanisms for devastating falling events in older adults.

Proposed mechanisms linking OH and falls There are a number of possible mechanisms by which OH can influence falling in older adults (Fig. 1). The relationship between OH and fainting, or syncope, could serve as a direct mechanism through which postural blood pressure decreases could cause a falling event. Falls and fainting episodes have conventionally been considered as two separate entities, but they can be challenging to differentiate, as both share the same end result of an individual coming to rest unintentionally on the ground. It has been suggested that 2–10 % of falls in older adults may occur secondary to impaired hemodynamic responses [29, 69] and loss of consciousness is estimated to result in as many as 10 % of falls [64, 69]. OH could also be linked to falls through indirect mechanisms. In many cases loss of consciousness is avoided, but increased fall susceptibility remains through presyncope (symptoms or signs of impending loss of consciousness) and associated physiological impairments [75, 96]. For instance, in older adults with Parkinson’s disease or diabetes mellitus, those with OH have poorer balance scores in comparison to those without OH [8, 31, 48]. Poor balance is a known risk factor for falls [19, 69], and has been suggested to increase this risk threefold [70]. Cognitive impairment is also a risk factor for falls [1]. Blood pressure impairments including OH, hypertension, as well as acute and chronic cerebral hypoperfusion are associated with impaired cognitive performance in older adults [10, 39, 50, 60, 71, 96]. Multivariable analyses suggest cognitive deficits increase falling risk threefold

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Table 1 Current definitions of orthostatic hypotension OH definition

Hemodynamic criteria

Upright timing

Symptom criterion

Test(s) applied

1996 consensus [38]

•C20 mmHg ;SAP and/or C10 mmHg ;DAP

B3 min

No

Head-up tilt, active stand

•C 20 mmHg ;SAP and/or C10 mmHg ;DAP

B3 min

No

•Response must be sustained •Supine SAP C160 mmHg: C30 mmHg ;SAP

Head-up tilt, active stand

B3 min

No

Head-up tilt, active stand

2011 consensus [17] Fedorowski [15]

•Supine SAP 90–160 mmHg: C20 mmHg ;SAP

Initial [17]

•C 40 mmHg ;SAP and/or C 20 mmHg ;DAP

B15 s

Yes

Active stand

Delayed [17]

•C 20 mmHg ;SAP and/or C10 mmHg ;DAP

C3 min

Yes

Head-up tilt, active stand

Recovery [20]

1996 consensus criteria with any of:

•Supine SAP B90 mmHg: C15 mmHg ;SAP

No

•No recovery: sustained or progressively worsening OH •Partial recovery: SAP recovery of C10 mmHg within 2 min •Late recovery: partial recovery and a late recovery of an additional C10 mmHg at 5 min SAP systolic arterial pressure, DAP diastolic arterial pressure

[70]. Therefore, cognitive functioning could serve as an intermediary mechanism between blood pressure impairments and falling risk in older adults. Finally, certain medications are known to increase falling risk and the prevalence of OH, but it is not known whether this is an independent effect, or an interaction [17, 19, 61]. Polypharmacy compounds this effect [40]. Before the mechanisms linking OH and falls can be understood, it is important that standardized techniques are used for proper assessment and identification of insufficient blood pressure responses to orthostasis.

Techniques for assessing orthostatic blood pressure control There are two key factors that influence recordings of blood pressure responses to an orthostatic challenge: the measuring device used, and the type of orthostatic assessment. Different combinations of these factors influence the accuracy with which OH can be observed. Blood pressure monitoring techniques The ‘gold-standard’ of blood pressure measurement is the use of an intra-arterial cannula, usually inserted in the radial artery [36]. This allows continuous beat-to-beat monitoring of blood pressure, but has several limitations including being invasive, time-consuming, inappropriate for routine clinical measurements, and somewhat expensive [25]. It has also been found to reduce orthostatic tolerance during head-up tilt testing (HUTT) [83]. As such,

invasive blood pressure monitoring is not indicated for the measurement of cardiovascular responses to orthostasis. Auscultatory blood pressure assessments have been validated against intra-arterial measurements [13, 56], but only provide intermittent measurements of blood pressure. This is particularly problematic when evaluating initial OH, where transient blood pressure falls meeting OH criteria may be missed with infrequent measurements. Arterial tonometry is a non-invasive method of measurement of beat-to-beat blood pressure that compares reasonably well to intra-arterial recordings [54, 74, 99]. However, difficulties in accurately measuring rapid changes in arterial pressure have been reported with this method [74, 81]. In general, non-invasive beat-to-beat techniques are somewhat limited by equipment cost and intricacies, including the need to calibrate with every subject, and to accurately compensate for the hydrostatic and morphological differences between brachial and digital/radial pressure recordings [24]. Finger-cuff plethysmography also offers a non-invasive method to measure beat-to-beat blood pressure [58]. This method is well supported, has been validated against intraarterial recordings [33, 34, 42, 51, 68], and meets acceptable criteria for bias and precision [35, 76]. Although somewhat expensive, most modern finger plethysmography devices incorporate automated algorithms for calibration, as well as hydrostatic and morpohological wave-form correction. Therefore, this approach is preferred for evaluating OH, given that some forms of OH present in a rapid and transient fashion that could only be captured by beatto-beat monitoring [17, 94]. However, this also presents an additional challenge in determining the duration of OH

123

6

123

Passive tilt

120 100 80 60

130 110 90 70 50

Heart rate (bpm)

140

130 110 90 70 50

Heart rate (bpm)

Orthostatic stress testing involves recording blood pressure from two different body positions. There is no standard clinical test that is used for the diagnosis of OH [4]. Different tests can evoke different physiological responses. Some tests are passive, and the participant does not contract their musculature to bring about the change in posture (Fig. 2a). In contrast, active tests in which the person contracts large muscles to transfer between positions will cause compression of vessels near these muscle groups, and this can impact the blood pressure change (Fig. 2b). Although these differences are recognized, few studies have systematically compared various tests [63, 97]. This has important implications for the diagnostic criteria used to classify OH, as well as the association OH has with other physiological variables. HUTT with beat-to-beat plethysmography is recognized as the reference standard for orthostatic stress testing [7, 59, 97]. This is a passive procedure that can be continued until presyncope is reached, particularly if additional provocation (pharmacological or physiological) is used [14, 28], and this may be useful clinically to evaluate cardiovascular reflex control and permit symptom-recognition in those with symptomatic OH. It may also be of benefit in populations who have difficulty standing without assistance, or for clinical studies where a controlled stimulus is desired independent of patient effort or ability to stand. However, although frequently used for the diagnosis of OH, it is not widely regarded as the ‘gold-standard’ for this practice [7, 53]. In some populations with limited mobility for whom standing is inappropriate, a passive supine-to-seated procedure has been utilized [6, 73]. It is not known how cardiovascular or hemodynamic responses to this test compare to other orthostatic stresses, although they are likely to be attenuated due to the more modest orthostatic stress. The lying-to-standing procedure requires the subject to lie in a supine position for 5–10 min, followed by an active movement to a standing position, where the subject will remain motionless for an additional 5 min [53]. This procedure is easier to administer than HUTT, as it only requires blood pressure monitoring equipment to perform, enabling its use in a research setting, hospital, family physician clinic, or even at home, and better resembles the ambulatory situation of the patient. However, it may be

Supine

Blood pressure (mmHg)

Orthostatic assessments

a

40 0

1

2

3

4

Time (minutes)

b Blood pressure (mmHg)

needed to cause functional impairment. One study of older adults demonstrated that when the single lowest beat is used to detect OH, the prevalence was 86 % [92]. In contrast, a 15-s average of the same beat-to-beat data found a prevalence of 49 %, raising the question as to what is a clinically meaningful approach.

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Supine

Active stand

140 120 100 80 60 40 0

1

2

3

4

Time (minutes)

Fig. 2 Beat-to-beat blood pressure responses from a healthy subject during: a head-up tilt test (passive); and b lying-to-standing test (active). Note the larger initial orthostatic changes in blood pressure with active compared to passive standing. This is likely due to larger decreases in total peripheral resistance occurring early after active standing [80] secondary to rises in intra-abdominal pressure during active standing that expel blood from the splanchnic bed to the heart and stimulate the arterial baroreceptors to reduce blood pressure [86]. The solid black line indicates the heart rate response to the procedure

challenging for those with limited mobility to perform the posture transition in a timely manner and maintain the standing position for the duration of the test, even if no symptoms of dizziness are felt. The sit-to-stand technique follows a similar protocol to the lying-to-standing procedure, but evokes a smaller perturbation in blood pressure due to the smaller degree of posture change [4]. This test is advantageous in that the participant can remain relatively immobile through the entire procedure; this is useful in research studies examining cerebral hemodynamics during orthostatic stress, where movement can impact the quality of recordings [43, 79]. The effectiveness of this active test in detecting OH has been questioned when compared to HUTT [7]. However, similar to the lying-to-standing test, it is easy to administer in a range of settings, closely resembles the ambulatory situation of the patient, and does not require much equipment. While this range of tests provides flexibility for assessment in different populations and settings, the lack of consistency in the tests used to evaluate orthostatic blood pressure responses has likely contributed to controversy in

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the literature [4]. It is important to understand how the physiological responses differ between tests to accurately evaluate the incidence and prevalence of OH, as well as its relationship with other physiological variables.

Defining responses to orthostatic stress Physiological responses to orthostatic stress can be defined according to hemodynamic and symptomatic responses. These responses vary depending on the type of orthostatic stress, the measurement tool used, as well as the time at which blood pressure measurements are made (Fig. 3) [4]. They can be impacted by various confounding factors including time of day, presence of hypertension, and medication use [17]. The lack of measurement standardization makes it challenging to create an accurate unified definition for OH and impacts the clarity of research studies that wish to discriminate OH solely by its presence. Several different definitions of OH have been proposed (Table 1). These definitions are primarily based on hemodynamic criteria, but some also include an assessment of symptoms. Lack of consistency concerning the presence of symptoms has important implications, given that some individuals can tolerate extremely low blood pressures without reporting symptoms [62]. Consensus definition

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definition of OH compared to normotensive or mildly hypertensive individuals. This suggests that the consensus criteria may cause overestimation or underestimation of orthostatic intolerance in individuals with high or low supine blood pressure, respectively [15]. Accordingly, a revised definition was proposed accounting for the subjects’ resting blood pressure (Table 1). Other reports have supported this recommendation [2, 95]. Both the consensus definition and Fedorowski criteria are applied to orthostatic responses during passive HUTT to at least 60, or during active standing [17]. However, these tests can produce different blood pressure responses [7, 63] (Fig. 2), and the nature of the orthostatic stress impacts the proportion of subjects found with OH [21]. Initial orthostatic hypotension Initial OH refers to the immediate drop in blood pressure (within 15 s of posture change) that occurs when upright, usually after active standing [17] (Table 1). Passive tilting also evokes an initial blood pressure drop, but it is generally insufficient to meet the outlined criteria, which are based on an active stand protocol [84, 94]. The concern with this condition is that the severe initial decline in blood pressure can occur so suddenly that baroreflex responses cannot compensate in a timely manner to recover and maintain adequate blood pressure and cerebral perfusion [88]. This form of OH may have implications in older adults, particularly those on medications impacting cardiovascular control [93]. A recent study found that 15 % of long-term care residents fell after rising to standing [64]. This represents a high-risk activity for older adults, and initial OH could potentially exacerbate this falling risk.

OH is most commonly defined by the 1996 consensus definition [38] (Table 1); however, it is unclear whether this is the best way to identify clinically relevant OH [38]. This definition was created primarily on the basis of clinical experience, as sophisticated studies of blood pressure responses were unavailable at the time [95]. It fails to account for blood pressure declines occurring after 3 min and originally did not incorporate any criteria relating to the duration of the blood pressure decline [38]. Accordingly, single measurements of blood pressure that met OH criteria would be considered to represent OH. A recent addition to this definition [17] included an additional criterion for a sustained decline in blood pressure. However, specific recommendations for qualifying a sustained blood pressure decline were not given. Many research studies and clinical evaluations fail to account for a sustained component and employ the 1996 consensus definition.

Delayed OH was first described by Streeten and Anderson [85] in a case-series of seven patients presenting with frequently occurring symptoms of syncope and OH, but who upon assessment only showed hemodynamic responses that met OH criteria with a prolonged time delay (Table 1). One previous study found that of 108 participants with OH in response to tilting, the OH occurred after 3 min in 54 % of individuals studied [21]. Interestingly, both passive tilt and active standing can evoke delayed OH despite the different responses induced by the two tests.

Fedorowski criteria

Steady-state recovery from orthostasis

Fedorowski et al. [15] demonstrated in a large cohort (n = 924) of middle-aged adults that a higher proportion of those individuals with severe systolic hypertension (C160 mmHg) are likely to meet criteria for the consensus

Steady-state recovery refers to a transient recovery of blood pressure after exposure to orthostasis but while still upright. Gehrking et al. [20] essentially defined three forms of recovery from 1996 consensus OH criteria (Table 1).

Delayed orthostatic hypotension

123

8

Supine

Upright

160 140

120 100 80 60 40

87/37

120 100 80 60 40 1

0

2

Heart rate (bpm)

Blood pressure mmHg)

a

4

3

Time (minutes) Supine

Upright

160 140

120 100 80 60 40

69/38

120 100 80 60 40 1

0

2

Heart rate (bpm)

Blood pressure mmHg)

b

4

3

Time (minutes) Upright 122/71

120 100 80 60 40 1

0

2

120 100 80 60 40

Heart rate (bpm)

Supine

160 140

120 100 80 60 40

Heart rate (bpm)

Blood pressure mmHg)

c

4

3

Time (minutes)

d Blood pressure mmHg)

Fig. 3 Beat-to-beat tracings illustrating blood pressure changes consistent with definitions of orthostatic hypotension (OH). a initial OH; b 1996 consensus OH; c 2011 consensus OH; d, delayed OH. Boxes identify the period of OH, including the nadir 5-s beat-tobeat blood pressure average that was attained during that time. The solid black line indicates the heart rate response to the procedure. In panels c and d the blood pressure continued to decline without recovery until the test was stopped and the individual was returned to the supine position. The tracings in panels b and c could both be considered to meet consensus criteria for OH, depending on the timing and duration of the blood pressure assessments, despite markedly different response patterns (b labile blood pressure and a robust heart rate response; c progressive decline in blood pressure with little heart rate increase, compatible with an autonomic failure-like response). These different blood pressure responses may or may not be associated with differing susceptibility to falling. The implications of the timing, magnitude and duration of blood pressure declines in terms of clinical relevance and falling risk are unclear

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Supine

Upright

160 140 120 100 80 60 40

70/39

0

1

2

3

8

9

10

Time (minutes)

Percentage recovery criteria have also been utilized [66]. In older adults, a slower recovery of blood pressure may be a more valuable indicator of orthostatic intolerance compared to the maximal drop or average change [65]. Similarly, individuals with OH with impaired blood pressure recovery are reported to be at increased risk of falling [29], frailty [67], and all-cause mortality [41]. These data suggest that the precise timing of the maximal blood pressure fall may not be as important as how well it is recovered after the initial drop.

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In order to properly evaluate both initial and delayed forms of OH, as well as the recovery responses, it is pertinent to use beat-to-beat measurements to faithfully capture these sudden and transient changes in blood pressure. It is also important to consider data analysis techniques in terms of defining the nadir and recovery pressures, as different timeaveraged segments will alter the magnitude of these blood pressure changes [92]. A final consideration is the evaluation of heart rate responses to these procedures, which can

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provide valuable information about cardiovascular reflex function. For example, the orthostatic heart rate response may provide a useful marker of frailty [67] and the integrity of cardiac baroreflex function [46].

Association between OH and falling in older adults There is a theoretical relationship between orthostatic blood pressure declines and falling in older adults as outlined above (Fig. 1). Indeed, in patients with OH, falls are the most frequent presenting feature, occurring in 64 % of patients [9]. This theoretical association has been examined mainly by a number of large observational studies; some of which evaluated a number of fall risk factors, while others focused specifically on blood pressure as the explanatory variable of interest (Table 2). Some studies suggest that OH is a risk factor for falls [18, 23, 29, 57, 66, 72, 89, 92]. In these studies, the average effect for the association between OH and falling was reported as an odds ratio of 2.2 or relative risk of 2.3. In these studies, three found a direct association between OH and future falls [23, 29, 72], and two others with retrospective fall history [66, 92]. Interestingly, the others only found an increased risk of subsequent falls in individuals with uncontrolled hypertension and OH [18] or in previous fallers with OH [57]. Additional studies have found no association between the two variables [37, 45, 49, 90]. These inconsistencies may be the result of the measurement device used, type of orthostatic stress test, definition of orthostatic blood pressure changes, or method of ascertaining fall history. Heitterachi et al. [29] and van der Velde et al. [92] found some of the strongest effects for an association between OH and falls, while also following the most rigorous methodological approach for detecting OH in using HUTT with beat-to-beat blood pressure monitoring. Overall, the manual sphygmomanometer was the most frequently used blood pressure measuring device (eight studies). Unless repeated measurements are made, this device provides only a single blood pressure value upon analysis; this is important given that repeated measurements can be needed to detect OH [26], particularly if criteria for sustained OH/impaired recovery are to be employed. In total, five of the studies in Table 2 used beat-to-beat methods for evaluating blood pressure; however, these studies did not all find significant results. In all studies that have used beat-to-beat technology, there is generally a lack of clarity and consistency into how the nadir blood pressure is defined. Should a lowest single beat be the most physiologically important value in calculating the gross change? Or, is an average of beats over a period of time a better marker of a substantial decline in blood pressure causing functional impairments? This

9

greatly impacts the incidence of OH [92]. van der Velde et al. [92] showed that 5 s averages of beat-to-beat data using the 1996 consensus definition of OH were most strongly associated with falling risk in older adults. This methodological choice is an important finding that should be incorporated and reported by future studies in this area. The 1996 consensus definition of OH was used in all reported studies to categorize subjects based on blood pressure declines; this fails to account for the expanded definitions of OH currently being used [17]. The timing of blood pressure measurement after assuming an upright posture also varies. Some studies define the changes based on measurements made at 1 min, while others make an evaluation at 3 min. This seems to impact the relationship; Romeo-Ortuno et al. [66] found an association between initial, but not consensus, OH and falling. Only one study considered whether the blood pressure decline was sustained [66], as recommended in the revised consensus statement [17]. Using beat-to-beat technology, Maurer et al. [49] made measurements at multiple specific time points within the first 3 min, but did not find any relationship with falling history. They based their analysis upon blood pressure responses at specific time points, rather than measuring gross changes, and did not examine any blood pressure declines that occurred after the 3-min time point, and so did not evaluate more delayed or sustained forms of OH [85]. Additionally, they used the sit-to-stand test, which they felt was not ideal for their subject group of elderly long-term care residents [49] and has been suggested to have a lower diagnostic accuracy for detecting OH in comparison to HUTT [7]. All studies in Table 2 that used the sit-to-stand procedure did not find a significant relationship between OH and falls. The lying-to-standing test is the most often used orthostatic stress test in the studies examined in Table 2 (eight studies). Only three of these studies found a direct association between OH and falls. In contrast, both studies using HUTT found a significant effect. It is known that different orthostatic assessments yield varying physiological responses, which may impact the reliability of detecting OH [7, 63]. Furthermore, most of the described studies relied on selfreported measurements of falling history, with the possibility of reporting bias. None of these studies evaluated the potential downstream mechanism of cerebral hemodynamics and its implications for falling risk. Recently, one study found that individuals with impaired cerebral vasoreactivity to carbon dioxide had an increased risk of falling in a cohort of community dwelling older adults [78]. However, cerebral autoregulation, measured using cerebral blood flow changes in response to a sit-to-stand test, was not associated with falling rate. They did not report any relationship between blood pressure

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Table 2 Review of previous literature investigating the association between orthostatic hypotension and falls References

N

Definition of OH

Blood pressure measurement

Orthostatic stress test

CBF

Falls assessment

Key findings

Rutan et al. [72]

4,931

Consensus

Manual sphyg

Lying-tostanding

No

Prospective self-report

Odds-ratio of 1.5 (CI 1.0–2.2) for frequent falling amongst participants with OH

Tinetti et al. [89]

300

Consensus

Manual sphyg

Lying-tostanding

No

Prospective self-report

24 % reduced risk of falls in multifaceted risk intervention group (including OH treatment)

Graafmans et al. [23]

354

Consensus

Manual sphyg

Lying-tostanding

No

Prospective self-report

Odds-ratio of 2.0 (CI 1.0–4.2) for OH in recurrent fallers

Luukinen et al. [45]

788

Consensus

Manual sphyg

Sit-to-stand

No

Prospective self-report

Relative-risk of 1.3 (CI 0.8–1.9) for OH in recurrent fallers Risk ratio of 2.2 (CI 1.5-3.4) for dizziness in recurrent fallers

Ooi et al. [57]

844

Consensus

Manual sphyg

Lying-tostanding

No

Prospective incident reports

Relative-risk of 2.6 (CI 1.7–4.0) for recurrent falls in previous fallers with OH compared to previous fallers without OH

Tromp et al. [90]

1,285

Consensus

Manual sphyg

Lying-tostanding

No

Prospective self-report

OH was not associated with falling risk

Kario et al. [37]

266

Consensus

Manual sphyg

Lying-tostanding

No

Prospective self-report

Heitterachi et al. [29]

70

Consensus

Beat-to-beat measurement

Head-up tilt test

No

Prospective self-report

Lower standing systolic blood pressure associated with falling risk, but not asymptomatic OH. Individuals with symptomatic OH were excluded prior to entering the study Relative-risk of 1.7 (CI 1.1–2.6) for OH in fallers compared to non-fallers

Maurer et al. [49]

111

Initial, consensus

Beat-to-beat measurement

Sit-to-stand

No

Prospective incident reports

Neither definition of OH was associated with falls

van der Velde et al. [92]

192

Consensus

Beat-to-beat measurement

Head-up tilt test

No

Retrospective

Odds ratio of 2.5 (CI 1.4–4.7) for being a previous faller in those with OH compared to those without OH

Sorond et al. [78]

419

None reported

Beat-to-beat measurement

Sit-to-stand

Yes

Prospective self-report

Marginal association between decreased cerebral vasoreactivity to carbon dioxide and falling rate

RomeroOrtuno et al. [66]

442

Initial, consensus

Beat-to-beat measurement

Lying-tostanding

No

Retrospective

Those with initial OH were more likely to report previous falling history than those without (25 % compared to 10 %). No relationship between consensus OH and falling was found

Gangavati et al. [18]

722

Consensus

Manual sphyg

Lying-tostanding

No

Prospective self-report

Hazard ratio of 2.5 (CI 1.3–5.1) for falling in participants with uncontrolled hypertension and OH

OH orthostatic hypotension, CBF cerebral blood flow, CI confidence interval, sphyg sphygmomanometer

changes and falling outcome in this study. Further evaluation of cerebral hemodynamics and its relationship to falling risk is needed to clarify the results of this study.

Conclusions A clear theoretical relationship exists between OH and falling in older adults, through both direct and indirect physiological mechanisms. However, the magnitude of these effects remains poorly characterized. The increasing availability and use of beat-to-beat blood pressure monitoring equipment has altered the way in which OH is now defined. More consistent methodological approaches need to be undertaken in analyzing beat-to-beat data, as there is little consistency between studies. The latest recommendations

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[17] suggest that a blood pressure decline must be sustained in order to qualify as OH; however, the timing of a sustained response remains poorly characterized and was only incorporated in one of the studies we reviewed. Finally, a gap exists in the literature in assessing the potential relationship between cerebral hemodynamics and falling risk. Future studies should include measurements of cerebral blood flow to better characterise this relationship. Identification of the blood pressure markers that best characterize cardiovascular risk for falls will aid the selection of interventions to most appropriately manage this risk. Additionally, if consistent methodological approaches can be devised using standardized assessments, equipment, and analysis techniques, the subset of older adults at risk of falls due to impaired hemodynamic control can be more effectively identified. Overall, this will lead to better identification

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and management of cardiovascular risk factors for falls in older adults. Acknowledgments Supported by team grants from the Canadian Institutes for Health Research (funding reference numbers AMG100487 and TIR-103945). This work was also supported in part by a Heart and Stroke Foundation of Canada New Investigator Award (VEC).

References 1. American Geriatrics Society (2001) Guideline for the prevention of falls in older persons. American Geriatrics Society, British Geriatrics Society, and American Academy of Orthopaedic Surgeons Panel on Falls Prevention. J Am Geriatr Soc 664–672 2. Braam EA, Verbakel D, Adiyaman A, Thien T (2009) Orthostatic hypotension: revision of the definition is needed. J Hypertens 27:2119–2120 (author reply 2120) 3. Carey BJ, Potter JF (2001) Cardiovascular causes of falls. Age Ageing 30(Suppl 4):19–24 4. Carlson JE (1999) Assessment of orthostatic blood pressure: measurement technique and clinical applications. South Med J 92:167–173 5. Carroll NV, Slattum PW, Cox FM (2005) The cost of falls among the community-dwelling elderly. J Manag Care Pharm 11:307–316 6. Claydon VE, Krassioukov AV (2006) Orthostatic hypotension and autonomic pathways after spinal cord injury. J Neurotrauma 23:1713–1725 7. Cooke J, Carew S, O’Connor M, Costelloe A, Sheehy T, Lyons D (2009) Sitting and standing blood pressure measurements are not accurate for the diagnosis of orthostatic hypotension. QJM 102:335–339 8. Cordeiro RC, Jardim JR, Perracini MR, Ramos LR (2009) Factors associated with functional balance and mobility among elderly diabetic outpatients. Arq Bras Endocrinol Metabol 53:834–843 9. Craig GM (1994) Clinical presentation of orthostatic hypotension in the elderly. Postgrad Med J 70:638–642 10. Czajkowska J, Ozhog S, Smith E, Perlmuter LC (2010) Cognition and hopelessness in association with subsyndromal orthostatic hypotension. J Gerontol A Biol Sci Med Sci 65:873–879 11. Darowski A, Chambers SA, Chambers DJ (2009) Antidepressants and falls in the elderly. Drugs Aging 26:381–394 12. Davis JC, Robertson MC, Ashe MC, Liu-Ambrose T, Khan KM, Marra CA (2010) International comparison of cost of falls in older adults living in the community: a systematic review. Osteoporos Int 21:1295–1306 13. Dieterle T (2012) Blood pressure measurement–an overview. Swiss Med Wkly 142:w13517 14. El-Bedawi KM, Hainsworth R (1994) Combined head-up tilt and lower body suction: a test of orthostatic tolerance. Clin Auton Res 4:41–47 15. Fedorowski A, Burri P, Melander O (2009) Orthostatic hypotension in genetically related hypertensive and normotensive individuals. J Hypertens 27:976–982 16. Folino AF (2007) Cerebral autoregulation and syncope. Prog Cardiovasc Dis 50:32 17. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 21:69–72

11 18. Gangavati A, Hajjar I, Quach L, Jones RN, Kiely DK, Gagnon P, Lipsitz LA (2011) Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance, independent living, intellect, and zest in the elderly of Boston study. J Am Geriatr Soc 59:383–389 19. Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ (2007) Will my patient fall? JAMA 297:77–86 20. Gehrking JA, Hines SM, Benrud-Larson LM, Opher-Gehrking TL, Low PA (2005) What is the minimum duration of head-up tilt necessary to detect orthostatic hypotension? Clin Auton Res 15:71–75 21. Gibbons CH, Freeman R (2006) Delayed orthostatic hypotension: a frequent cause of orthostatic intolerance. Neurology 67:28–32 22. Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G (2002) Dysautonomias: clinical disorders of the autonomic nervous system. Ann Intern Med 137:753–763 23. Graafmans WC, Ooms ME, Hofstee HM, Bezemer PD, Bouter LM, Lips P (1996) Falls in the elderly: a prospective study of risk factors and risk profiles. Am J Epidemiol 143:1129–1136 24. Guelen I, Westerhof BE, Van Der Sar GL, Van Montfrans GA, Kiemeneij F, Wesseling KH, Bos WJ (2003) Finometer, finger pressure measurements with the possibility to reconstruct brachial pressure. Blood Press Monit 8:27–30 25. Gupta B (2007) Invasive blood pressure monitoring. Update Anesth 23:7 26. Gupta V, Lipsitz LA (2007) Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 120:841–847 27. Hainsworth R, Claydon VE (2013) Syncope and fainting: classification and pathophysiological basis. In: Autonomic failure: a texbook of clinical disorders of the autonomic nervous system, Oxford University Press, Oxford, United Kingdom 28. Hainsworth R, El-Bedawi KM (1994) Orthostatic tolerance in patients with unexplained syncope. Clin Auton Res 4:239–244 29. Heitterachi E, Lord SR, Meyerkort P, McCloskey I, Fitzpatrick R (2002) Blood pressure changes on upright tilting predict falls in older people. Age Ageing 31:181–186 30. Hiitola P, Enlund H, Kettunen R, Sulkava R, Hartikainen S (2009) Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older. J Hum Hypertens 23:33–39 31. Hohler AD, Zuzuarregui JR, Katz DI, Depiero TJ, Hehl CL, Leonard A, Allen V, Dentino J, Gardner M, Phenix H, SaintHilaire M, Ellis T (2012) Differences in motor and cognitive function in patients with Parkinson’s disease with and without orthostatic hypotension. Int J Neurosci 122:233–236 32. Hosseini H, Hosseini N (2008) Epidemiology and prevention of fall injuries among the elderly. Hosp Top 86:15–20 33. Imholz BP, Wieling W, Langewouters GJ, van Montfrans GA (1991) Continuous finger arterial pressure: utility in the cardiovascular laboratory. Clin Auton Res 1:43–53 34. Imholz BP, Wieling W, van Montfrans GA, Wesseling KH (1998) Fifteen years experience with finger arterial pressure monitoring: assessment of the technology. Cardiovasc Res 38:605–616 35. Jansen JR, Schreuder JJ, Mulier JP, Smith NT, Settels JJ, Wesseling KH (2001) A comparison of cardiac output derived from the arterial pressure wave against thermodilution in cardiac surgery patients. Br J Anaesth 87:212–222 36. Jones A, Pratt O (2009) Physical principles of intra-arterial blood pressure measurement. World Anaesth Tutor Week 137:8 37. Kario K, Tobin JN, Wolfson LI, Whipple R, Derby CA, Singh D, Marantz PR, Wassertheil-Smoller S (2001) Lower standing systolic blood pressure as a predictor of falls in the elderly: a community-based prospective study. J Am Coll Cardiol 38:246–252 38. Kaufmann H (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res 6:125–126

123

12 39. Kennelly SP, Lawlor BA, Kenny RA (2009) Blood pressure and the risk for dementia: a double edged sword. Ageing Res Rev 8:61–70 40. Kenny RA (2003) Syncope in the elderly: diagnosis, evaluation, and treatment. J Cardiovasc Electrophysiol 14:S74–S77 41. Lagro J, Schoon Y, Heerts I, Meel-van den Abeelen AS, Schalk B, Wieling W, Olde Rikkert MG, Claassen JA (2013) Impaired systolic blood pressure recovery directly after standing predicts mortality in older falls clinic patients. J Gerontol A Biol Sci Med Sci 42. Langewouters GJ, Settels JJ, Roelandt R, Wesseling KH (1998) Why use Finapres or Portapres rather than intra-arterial or intermittent non-invasive techniques of blood pressure measurement? J Med Eng Technol 22:37–43 43. Lipsitz LA, Mukai S, Hamner J, Gagnon M, Babikian V (2000) Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke 31:1897–1903 44. Low PA (2008) Prevalence of orthostatic hypotension. Clin Auton Res 18(Suppl 1):8–13 45. Luukinen H, Koski K, Kivela SL, Laippala P (1996) Social status, life changes, housing conditions, health, functional abilities and life-style as risk factors for recurrent falls among the homedwelling elderly. Public Health 110:115–118 46. Madden KM, Lockhart C (2009) Arterial baroreflex function in older adults with neurocardiogenic syncope. Clin Invest Med 32:E191–E198 47. Masaki KH, Schatz IJ, Burchfiel CM, Sharp DS, Chiu D, Foley D, Curb JD (1998) Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program. Circulation 98:2290–2295 48. Matinolli M, Korpelainen JT, Korpelainen R, Sotaniemi KA, Myllyla VV (2009) Orthostatic hypotension, balance and falls in Parkinson’s disease. Mov Disord 24:745–751 49. Maurer MS, Cohen S, Cheng H (2004) The degree and timing of orthostatic blood pressure changes in relation to falls in nursing home residents. J Am Med Dir Assoc 5:233–238 50. Mehrabian S, Duron E, Labouree F, Rollot F, Bune A, Traykov L, Hanon O (2010) Relationship between orthostatic hypotension and cognitive impairment in the elderly. J Neurol Sci 299:45–48 51. Molhoek GP, Wesseling KH, Settels JJ, van Vollenhoven E, Weeda HW, de Wit B, Arntzenius AC (1984) Evaluation of the Penaz servo-plethysmo-manometer for the continuous, noninvasive measurement of finger blood pressure. Basic Res Cardiol 79:598–609 52. Mukai S, Lipsitz LA (2002) Orthostatic hypotension. Clin Geriatr Med 18:253–268 53. Naschitz JE, Rosner I (2007) Orthostatic hypotension: framework of the syndrome. Postgrad Med J 83:568–574 54. Nelesen RA, Dimsdale JE (2002) Use of radial arterial tonometric continuous blood pressure measurement in cardiovascular reactivity studies. Blood Press Monit 7:259–263 55. O’Loughlin JL, Robitaille Y, Boivin JF, Suissa S (1993) Incidence of and risk factors for falls and injurious falls among the community-dwelling elderly. Am J Epidemiol 137:342–354 56. Ogedegbe G, Pickering T (2010) Principles and techniques of blood pressure measurement. Cardiol Clin 28:571–586 57. Ooi WL, Hossain M, Lipsitz LA (2000) The association between orthostatic hypotension and recurrent falls in nursing home residents. Am J Med 108:106–111 58. Penaz J (1973) Photoelectric measurement of blood pressure, volume and flow in the finger. In: Digest 10th international conference on medical and biological engineering, Dresden, p 104 59. Petersen ME, Williams TR, Sutton R (1995) A comparison of non-invasive continuous finger blood pressure measurement (Finapres) with intra-arterial pressure during prolonged head-up tilt. Eur Heart J 16:1641–1654

123

Clin Auton Res (2014) 24:3–13 60. Poda R, Guaraldi P, Solieri L, Calandra-Buonaura G, Marano G, Gallassi R, Cortelli P (2012) Standing worsens cognitive functions in patients with neurogenic orthostatic hypotension. Neurol Sci 33:469–473 61. Poon IO, Braun U (2005) High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans. J Clin Pharm Ther 30:173–178 62. Protheroe CL, Ravensbergen HR, Inskip JA, Claydon VE (2013) Tilt testing with combined lower body negative pressure: a ‘‘gold standard’’ for measuring orthostatic tolerance. J Vis Exp 73 63. Rickards CA, Newman DG (2003) A comparative assessment of two techniques for investigating initial cardiovascular reflexes under acute orthostatic stress. Eur J Appl Physiol 90:449–457 64. Robinovitch SN, Feldman F, Yang Y, Schonnop R, Leung PM, Sarraf T, Sims-Gould J, Loughin M (2013) Video capture of the circumstances of falls in elderly people residing in long-term care: an observational study. Lancet 381:47–54 65. Romero-Ortuno R, Cogan L, Fan CW, Kenny RA (2010) Intolerance to initial orthostasis relates to systolic BP changes in elders. Clin Auton Res 20:39–45 66. Romero-Ortuno R, Cogan L, Foran T, Kenny RA, Fan CW (2011) Continuous noninvasive orthostatic blood pressure measurements and their relationship with orthostatic intolerance, falls, and frailty in older people. J Am Geriatr Soc 59:655–665 67. Romero-Ortuno R, Cogan L, O’Shea D, Lawlor BA, Kenny RA (2011) Orthostatic haemodynamics may be impaired in frailty. Age Ageing 40:576–583 68. Rongen GA, Bos WJ, Lenders JW, van Montfrans GA, van Lier HJ, van Goudoever J, Wesseling KH, Thien T (1995) Comparison of intrabrachial and finger blood pressure in healthy elderly volunteers. Am J Hypertens 8:237–248 69. Rubenstein LZ (2006) Falls in older people: epidemiology, risk factors and strategies for prevention. Age Ageing 35(Suppl 2):ii37–ii41 70. Rubenstein LZ, Josephson KR (2002) The epidemiology of falls and syncope. Clin Geriatr Med 18:141–158 71. Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, Breteler MM (2005) Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 57:789–794 72. Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS (1992) Orthostatic hypotension in older adults. The cardiovascular health study. CHS collaborative research group. Hypertension 19:508–519 73. Sahota IS, Ravensbergen HR, McGrath MS, Claydon VE (2012) Cerebrovascular responses to orthostatic stress after spinal cord injury. J Neurotrauma 29:2446–2456 74. Sato T, Nishinaga M, Kawamoto A, Ozawa T, Takatsuji H (1993) Accuracy of a continuous blood pressure monitor based on arterial tonometry. Hypertension 21:866–874 75. Schondorf R, Benoit J, Stein R (2001) Cerebral autoregulation in orthostatic intolerance. Ann N Y Acad Sci 940:514–526 76. Schutte AE, Huisman HW, van Rooyen JM, Malan NT, Schutte R (2004) Validation of the Finometer device for measurement of blood pressure in black women. J Hum Hypertens 18:79–84 77. Shibao C, Grijalva CG, Raj SR, Biaggioni I, Griffin MR (2007) Orthostatic hypotension-related hospitalizations in the United States. Am J Med 120:975–980 78. Sorond FA, Galica A, Serrador JM, Kiely DK, Iloputaife I, Cupples LA, Lipsitz LA (2010) Cerebrovascular hemodynamics, gait, and falls in an elderly population: MOBILIZE Boston study. Neurology 74:1627–1633 79. Sorond FA, Serrador JM, Jones RN, Shaffer ML, Lipsitz LA (2009) The sit-to-stand technique for the measurement of dynamic cerebral autoregulation. Ultrasound Med Biol 35:21–29 80. Sprangers RL, Wesseling KH, Imholz AL, Imholz BP, Wieling W (1991) Initial blood pressure fall on stand up and exercise

Clin Auton Res (2014) 24:3–13

81.

82.

83.

84.

85. 86.

87. 88.

89.

90.

explained by changes in total peripheral resistance. J Appl Physiol 70:523–530 Steiner LA, Johnston AJ, Salvador R, Czosnyka M, Menon DK (2003) Validation of a tonometric noninvasive arterial blood pressure monitor in the intensive care setting. Anaesthesia 58:448–454 Stevens JA, Corso PS, Finkelstein EA, Miller TR (2006) The costs of fatal and non-fatal falls among older adults. Inj Prev 12:290–295 Stevens PM (1966) Cardiovascular dynamics during orthostasis and the influence of intravascular instrumentation. Am J Cardiol 17:211–218 Stewart JM, Clarke D (2011) ‘‘He’s dizzy when he stands up’’: an introduction to initial orthostatic hypotension. J Pediatr 158:499–504 Streeten DH, Anderson GH Jr (1992) Delayed orthostatic intolerance. Arch Intern Med 152:1066–1072 Tanaka H, Sjoberg BJ, Thulesius O (1996) Cardiac output and blood pressure during active and passive standing. Clin Physiol 16:157–170 Thijs RD, Bloem BR, van Dijk JG (2009) Falls, faints, fits and funny turns. J Neurol 256:155–167 Thomas KN, Cotter JD, Galvin SD, Williams MJ, Willie CK, Ainslie PN (2009) Initial orthostatic hypotension is unrelated to orthostatic tolerance in healthy young subjects. J Appl Physiol 107:506–517 Tinetti ME, Baker DI, McAvay G, Claus EB, Garrett P, Gottschalk M, Koch ML, Trainor K, Horwitz RI (1994) A multifactorial intervention to reduce the risk of falling among elderly people living in the community. N Engl J Med 331:821–827 Tromp AM, Pluijm SM, Smit JH, Deeg DJ, Bouter LM, Lips P (2001) Fall-risk screening test: a prospective study on predictors

13

91.

92.

93.

94.

95.

96.

97.

98.

99.

for falls in community-dwelling elderly. J Clin Epidemiol 54:837–844 Ungar A, Galizia G, Morrione A, Mussi C, Noro G, Ghirelli L, Masotti G, Rengo F, Marchionni N, Abete P (2011) Two-year morbidity and mortality in elderly patients with syncope. Age Ageing 40:696–702 van der Velde N, van den Meiracker AH, Stricker BH, van der Cammen TJ (2007) Measuring orthostatic hypotension with the Finometer device: is a blood pressure drop of one heartbeat clinically relevant? Blood Press Monit 12:167–171 Wieling W, Harms MP, Kortz RA, Linzer M (2001) Initial orthostatic hypotension as a cause of recurrent syncope: a case report. Clin Auton Res 11:269–270 Wieling W, Krediet CT, van Dijk N, Linzer M, Tschakovsky ME (2007) Initial orthostatic hypotension: review of a forgotten condition. Clin Sci (Lond) 112:157–165 Wieling W, Schatz IJ (2009) The consensus statement on the definition of orthostatic hypotension: a revisit after 13 years. J Hypertens 27:935–938 Wieling W, Thijs RD, van Dijk N, Wilde AA, Benditt DG, van Dijk JG (2009) Symptoms and signs of syncope: a review of the link between physiology and clinical clues. Brain 132:2630–2642 Winker R, Prager W, Haider A, Salameh B, Rudiger HW (2005) Schellong test in orthostatic dysregulation: a comparison with tilt-table testing. Wien Klin Wochenschr 117:36–41 World Health Organization (2007) WHO global report on falls prevention in older age. In: Salas-Rojas C (ed) World Health Organization, Geneva, p 53 Zorn EA, Wilson MB, Angel JJ, Zanella J, Alpert BS (1997) Validation of an automated arterial tonometry monitor using Association for the Advancement of Medical Instrumentation standards. Blood Press Monit 2:185–188

123