Different patterns of orthostatic hypotension in older patients with unexplained falls or syncope: orthostatic hypotension patterns in older people

  • Elizabeth J. Roosendaal
  • Simone J. Moeskops
  • Tjeerd Germans
  • Jaap H. Ruiter
  • René W. M. M. Jansen
Research Paper

Abstract

Purpose

To evaluate different patterns of orthostatic hypotension (OH) and its relation to mortality in older patients with unexplained falls or syncope.

Methods

This is an observational cohort study in consecutive patients aged ≥ 65 years with unexplained falls or syncope at a Fall Syncope day clinic November 2011 until May 2016. OH is defined as a decrease in systolic blood pressure (BP) ≥ 20 mmHg and/or in diastolic BP ≥ 10 mmHg during standing test. Main outcomes are the baseline characteristics and prevalence of patients with classical OH (decrease BP until 3 min), delayed OH (decrease of BP from 5 to 10 min) and continuous OH (decrease of BP for 10 min). Secondary outcome is the relation between different OH patterns and mortality.

Results

Of 374 patients with a mean age of 80 year (SD 6.6), 56% of the patients had OH: 16% had classical OH, 8% delayed OH, 32% had continuous OH and 44% had no OH. Patients with continuous OH and patients with delayed OH tended to have a higher mortality compared to patients with classical OH, 14 vs. 5% (P = 0.07) and 17 vs. 5% (P = 0.06). This possible relation between OH patterns and mortality could not be confirmed in multivariate analysis.

Conclusions

In these very old patients, there are various patterns of decline in standing BP. Delayed and continuous OH will be missed if BP is measured only for 3 min during standing. This is important because patients with continuous OH and delayed OH might have a relation with mortality. Our results encourage additional studies investigating the relation between different OH patterns and mortality.

Keywords

Syncope Falls Elderly Continuous Orthostatic hypotension Mortality 

Introduction

Orthostatic hypotension (OH) is a common disorder in the elderly leading to falls and syncope [1, 2]. A fall is often a manifestation of a syncope that is defined as ‘a transient loss of consciousness due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery’ [3]. The incidence of syncope is increasing with age and may cause physical injury and a decrease in quality of life [4, 5, 6]. Previous studies have demonstrated that syncope can present as a fall [3, 7, 8]. Discrimination between both conditions is difficult since memory loss of the transient loss of consciousness often occurs and a fall frequently happens in the absence of eyewitnesses [8, 9]. Furthermore, we recently described that cognitive disorders are very common in older patients with syncope [10].

Several years ago, we developed a multidisciplinary pathway for the combined evaluation of unexplained non-accidental falls and syncope. With the collaboration of cardiologists, neurologists and geriatricians we achieved one or more possible explanations for patients with a syncope in 94% [8].

The most common diagnoses of syncope in elderly adults are OH, cardiac arrhythmias, carotid sinus syndrome, and various forms of neurally mediated syncope [3]. OH is defined as an abnormal decrease in systolic blood pressure (SBP) on standing [3]. OH can be divided into different clinical syndromes. The classical OH is the most common form in clinical practices and is defined as a decrease in SBP ≥ 20 mmHg and/or in diastolic blood pressure (DBP) ≥ 10 mmHg within 3 min of standing [3]. Delayed OH, which is defined as a slow progressive decreasing blood pressure (BP) after 3 min of erect posture, is more common in the elderly than previously thought [3, 11]. Current ESC guidelines advice to measure BP during standing for only 3 min, in which the delayed form of OH will be missed [12].

The presence of OH is associated with stroke [13, 14, 15], heart failure [13, 15, 16, 17], device implantation [14], cardiovascular mortality [15, 18] and coronary heart disease [15, 19]. With so many cardiovascular events, Ruwald et al. suggested that OH is a first symptom of an underlying cardiovascular disease [14]. On the other hand, OH is also associated with autonomic failure [20]. This suggests that different mechanisms ultimately result in OH and therefore different patterns of OH exist [21, 22, 23]. Since OH is associated with increased mortality, it is important to evaluate whether this is related to a specific pattern of OH [13, 14, 15, 24]. Most research is performed on patients with OH, but without further differentiation of OH patterns or only one OH pattern has been studied. Further, most research about OH has been performed in younger patients. Therefore, more information on OH patterns is needed about the very elderly.

The main objective of this study was to determine the prevalence of the different patterns of OH. Secondly, we explored the characteristics of very elderly patients with OH with unexplained fall or syncope. In addition, we investigated the relation between different OH patterns and mortality. Our hypotheses were that half of the patient would be diagnosed with OH and that these patients have more often cardiovascular comorbidities. Further, we hypothesized that patients with OH would have a higher mortality rate compared to patients without OH.

Methods

We conducted a retrospective observational cohort study at the Fall and Syncope day Clinic (FSC) of the Northwest clinics, Alkmaar, the Netherlands from November 2011 until May 2016. The FSC is a multidisciplinary day clinic of the department of geriatric medicine were unexplained falls or syncope are analysed. Both general practitioners (GP) and specialists can refer patients to the FSC. At the FSC, there is a close collaboration of the geriatrician, cardiologist, neurologist, old age psychiatrist and paramedics to determine causes of falls or syncope. Inclusion criteria for this study were consecutive patients aged ≥ 65 years with unexplained falls or syncope. This included patients with a fall alone and patients with syncope, who also experienced a fall due loss of muscle tone due loss of consciousness. Patients without complete standing BP measurements were excluded. Main outcomes were the prevalence of different OH patterns and the description of the characteristics of the patients with the different OH patterns. Secondary outcome included the relation of different OH patterns and mortality.

Specific patient consent and ethical board approval were not requested, since this study used archival data of standard geriatric evaluations and had no implications on therapeutic decisions.

The method and data collection have been described previously [7]. In brief, all patients were seen and fully examined during 2 days at the FSC. On the first day, patients underwent a comprehensive geriatric assessment, including full clinical history, medication review, physical- and cognitive examination. Information about clinical history and comorbidities were extracted from the referral letter of the GP and the hospital records. The number of comorbidities was measured with the Charlson index [25]. Patients with eGFR ≥ 60 mL/min were classified as having a normal kidney function and patients with an eGFR < 60 mL/min as having a decreased kidney function [26]. With laboratory test hemoglobulin was measured and anemia was determined as a hemoglobulin < 7.5 mmol/L (female) and < 8.5 mmol/L (male) [27]. A nurse practitioner investigated functional state with the KATZ-ADL [28]. A patient was called ADL dependent if one of the six items was scored as dependent. The physician divided the patients in a fall- or syncope group, based on the clinical history and witness account. If there was no loss of consciousness, patients were assigned to the fall group. If there was clinical evidence for loss of consciousness patients were assigned to the syncope group. More extensive orthostatic- and postprandial BP measurements were taken 1 week later in the morning after an overnight fast. BP was measured by a trained nurse with a Welch Allyn vital signs monitor 300 devices in a quiet room with a pleasant room temperature of 21–24 °C. BP was measured on the right upper arm after at least 10 min of supine position and then after 1, 3, 5, 7, 9 and 10 min of active standing. During the standing test patients were diagnosed with classical OH and delayed OH according to the international consensus criteria. Classical OH is defined as a decrease in SBP ≥ 20 mmHg and/or DBP ≥ 10 mmHg within 3 min of standing followed by a recovery of SBP [3]. Delayed OH is defined as a slow progressive decreasing SBP ≥ 20 mmHg and/or DBP ≥ 10 mmHg after 3 min of erect posture [3, 29]. However, some patients were classified as both classical OH and delayed OH. Therefore, we classified these patients as continuous OH: a decreased SBP ≥ 20 mmHg/or DBP ≥ 10 mmHg within 3 min and after 3 min for the remaining 10 min standing period.

All the hospital records of the included patients were reviewed on September 1, 2016 to determine if a patient had died. We had no access to the national death registration (Centraal Bureau voor de Statistiek, Heerlen, the Netherlands). However, in case of a death at home, the GP sends this information to the hospital where the hospital records are adjusted. So, in general nearly all deaths of patients were recorded in the hospital records which we used to analyse mortality.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics 20.0. (SPSS, Inc., Chicago, IL, USA).

Nominal and ordinal variables were described using frequency tables, mode and median. Normality of continuous variables was tested with the Kolmogorov–Smirnov test and presented as means and standard deviations (SD) or median and interquartile range (IQR). Each OH pattern was analysed as a nominal variable. The χ2 test or Mann–Whitney U test was performed to compare each BP pattern reciprocally, especially concerning different characteristics and death. The χ2 test and Kruskal–Wallis test were performed to investigate if a significant difference existed between the BP pattern groups. To identify whether the relationship between OH patterns and mortality was independent for potential confounders, the Cox-proportional hazard analysis were adjusted for different risk factors known to affect mortality, expert opinion and variables associated with mortality during univariate analysis. The Cox-proportional hazard analysis was used to estimate the hazard ratio (HR) with corresponding 95% confidence intervals (CI). A P value less then 0.05 was considered significant.

Results

A total of 430 patient records were reviewed for this study. Of these patients, 56 (13%) were excluded because of: age (n = 12), presentation without an unexplained fall or syncope (n = 21) or incomplete BP measurements (n = 23). In the last group for seven patients the second day was cancelled because of hospital admission (n = 2), moving away (n = 1), short life expectancy (n = 1) or unclear (n = 3). For nine patients BP measurements were discontinued because of pain, lack of strength or fear. In seven patients BP measurements were done but not noted. Of 23 excluded patients, five patients died but the reasons for incomplete BP measurements were different. The remaining 374 patients were included in this study as presented in Fig. 1. We included a very elderly population with a mean age of 80 years (SD 6.6) with multiple comorbidities (mean 11, SD 6), mainly consisting of females (68%). The mean number of medications use was 7.1 (SD 3.7). 23% of the patients were dependent of care for activities of daily living (ADL), and 40% for instrumental ADL. Half of the patients used a walking device. The mean duration of follow-up was 30 months (SD 16). Patients with syncope had more often heart failure (P = 0.02), orthostatic hypotension (P = 0.001) and were more often iADL dependent (P = 0.02) compared to patients with falls.
Fig. 1

Flowchart study population at the Fall and Syncope Day Clinic. OH orthostatic hypotension, BP blood pressure

A total of 209 patients (56%) were diagnosed with OH. We divided the patients with OH into three groups based on the results of the standing test: classical OH, delayed OH and continuous OH. Table 1 shows the baseline characteristics of patients with different BP patterns. Figure 2 presents the different BP patterns during standing test. Of all 374 patients, 44% had no OH, 16% had classical OH, 8% had the delayed form and the continuous form was diagnosed in 32%, as shown in Table 1. Patients without OH, classical OH, delayed OH or continuous OH differed significant in Charlson Index (P = 0.03), diabetes mellitus (P = 0.04) and congestive heart failure (P = 0.04). This difference was mostly due the high rates in patients with delayed OH compared to the other groups. In our study population, 67% of the patients had a history of hypertension en 68% used anti-hypertensive drugs. Patients with delayed OH had higher rates of hypertension and use of anti-hypertensive drugs: 83% resp 81%. Patients with continuous OH were, compared to patients with classical OH, more often diagnosed with dementia (P = 0.02) and heart failure (P = 0.05). Last, patients with different BP patterns differed significant in baseline SBP with the highest SBP in patients with continuous OH (157 mmHg) and the lowest SBP in patients without OH (147 mmHg) (P < 0.001). Patients with different BP patterns did not differ concerning age, comorbidity and number of medication as presented in Table 1.
Table 1

Baseline characteristics of the study subjects

 

All subjects

n = 374

Subjects without OH

n = 165 (44%)

Subjects with classical OH

n = 60 (16%)

Subjects with delayed OH

n = 29 (8%)

Subjects with continuous OH

n = 120 (32%)

P value

Man, n (%)

118 (32)

45 (27)

20 (33)

10 (35)

43 (36)

0.45

Age, years, median (IQR)

80 (10)

80 (10)

79 (12)

80 (9)

79 (9)

0.87

Body Mass Index, kg/m2, median (IQR)

25.5 (5.1)

25.6 (5.5)

25.7 (4.8)

25.1 (5.4)

25.3 (4.8)

0.48

Number of comorbidities, median (IQR)

10 (7)

10 (5)

10 (6)

13 (8)

11 (8)

0.31

Charlson Index, median (IQR)

1 (2)

1 (2)

1 (2)

2 (1)

1 (2)

0.03

Hypertension, n (%)

251 (67)

109 (66)

41 (68)

24 (81)

77 (64)

0.28

Hypercholesterolemia, n (%)

88 (24)

37 (22)

18 (30)

8 (28)

25 (21)

0.52

Diabetes mellitus, n (%)

77 (21)

24 (15)

13 (22)

10 (35)

30 (25)

0.04

CVA, n (%)

89 (24)

40 (24)

15 (25)

7 (24)

27 (23)

0.98

Ischemic heart disorder, n (%)

97 (26)

35 (21)

15 (25)

9 (31)

38 (32)

0.22

Myocardial infarction, n (%)

36 (10)

12 (7)

5 (8)

2 (7)

17 (14)

0.22

Angina pectoris, n (%)

66 (18)

27 (16)

12 (20)

8 (28)

19 (16)

0.46

Atrial fibrillation, n (%)

86 (23)

38 (23)

15 (25)

9 (31)

24 (20)

0.61

Congestive heart failure, n (%)

34 (9)

15 (9)

1 (2)

6 (21)

12 (10)

0.04

Bypass, PTA or stent, n (%)

45 (12)

17 (10)

7 (12)

3 (10)

18 (15)

0.66

Anemia, n (%)

108 (29)

40 (24)

20 (33)

7 (24)

41 (34)

0.25

Renal function < 60 mL/min

119 (32)

50 (30)

17 (28)

11 (38)

41 (34)

0.70

ADL dependent, n (%)

87 (23)

39 (21)

13 (21)

12 (35)

28 (23)

0.33

iADL dependent, n (%)

151 (40)

69 (38)

24 (38)

16 (47)

51 (41)

0.73

SBP supine, mmHg, median (range)

152 (101–212)

147 (101–199)

153 (109–210)

152 (115–184)

157 (114–212)

< 0.001

DBP supine, mmHg, median (range)

81 (50–122)

81 (50–108)

81 (50–122)

83 (66–102)

82 (54–120)

0.23

HR supine, beats/min, median (range)

68 (46–101)

68 (46–100)

66 (48–101)

70 (49–92)

70 (48–98)

0.27

Number of medications, median (range)

7 (0–23)

6 (0–23)

7 (0–17)

8 (3–19)

7 (0–20)

0.13

Antihypertensives, n (%)

255 (68)

109 (66)

45 (75)

24 (83)

77 (64)

0.15

CVA cerebral vascular accident, PTA percutaneous transluminal angioplasty, COPD chronic obstructive pulmonary disease, SBP systolic blood pressure, DBP diastolic blood pressure, HR heart rate

Fig. 2

Blood pressure patterns during standing test

Overall, 13% of the 374 patients died in the period between their visit of the FSC and September 1 2016, when the hospital records were reviewed for mortality. Mortality rates between patients with OH and without OH were equal (12 vs. 13%). In the delayed group five patients died (17%) compared to three patients (5%) with classical OH (P = 0.06). 17 patients with continuous OH died (14%) compared to 3 patients (5%) with classical OH, but this difference did not reach statistical significance (P = 0.07) (Table 2). However, we also performed a multivariate Cox proportional hazard analysis with five variables including the four BP patterns (no OH, classical OH, delayed OH and continuous OH) and based on the univariate analysis: congestive heart failure, anemia, gender and the Charlson Index. Mortality was strongly related to congestive heart failure (HR 3.09, 95% CI 1.48–6.45, P = 0.002) and female gender (HR 2.04, 95% CI 1.09–3.80, P = 0.03), but not to different OH patterns (Table 3).
Table 2

Mortality rates of different OH patterns and comparison between patterns

 

n (%)

 

All subjects

47 (13)

 

No OH

22 (13)

 

Classical OH

3 (5)

 

Delayed OH

5 (17)

vs. Classical OH (P = 0.06)

Continuous OH

17 (14)

vs. Classical OH (P = 0.07)

OH orthostatic hypotension

Table 3

Analysis of death in 374 patients with Cox proportional hazard regression model

 

Univariate analysis

Multivariate analysis

HR (95% CI)

P value

HR (95% CI)

P value

Female gender

2.53 (1.42–4.49)

0.002

2.04 (1.09–3.80)

0.03

Charlson Index

1.30 (1.12–1.50)

< 0.001

1.11 (0.95–1.31)

0.19

Congestive heart failure

4.93 (2.57–9.48)

< 0.001

3.09 (1.48–6.45)

0.002

Anemia

2.39 (1.35–4.24)

0.003

1.54 (0.82–2.92)

0.18

BP pattern

 Classical OH

0.40 (0.12–1.33)

0.13

0.33 (0.08–1.41)

0.14

 Delayed OH

1.45 (0.55–3.84)

0.45

1.22 (0.45–3.30)

0.70

 Continuous OH

1.07 (0.57–2.01)

0.84

0.96 (0.51–1.82)

0.90

The total number of events is 47

HR hazard ratio, BP blood pressure, OH orthostatic hypotension

Discussion

In this paper, we present different patterns of OH in relation to mortality in a very large cohort of 374 very elderly patients with unexplained fall or syncope. The mean age of the patients was 80 years and 56% were diagnosed with OH. We discovered a continuous pattern of OH during 10 min in the standing position without any indication of recovery, which was more prevalent than the classical form of OH (32 vs. 16%). However, continuous OH remains undiagnosed when using current standard OH measurements according to the ESC syncope guidelines of 2009 and the recent update in 2018 [12].

Different OH patterns

The overall prevalence of OH of 56% in our study population is in line with other studies [30, 31]. A large proportion of our study population (32%) had a prolonged BP drop during standing test which we described as continuous OH. Compared to patients with classical OH, these patients were more often diagnosed with dementia and heart failure and their mortality rate tended to be higher. To our knowledge, a prolonged BP drop during standing test has only been described earlier in patients with multiple system atrophy and Parkinson diseases [2, 21]. Finucane et al. described a significant relation between sustained OH and an increased risk of falls [1]. Sustained OH is defined as a BP drop without recovery in 40–110 s. Since patients with classical OH have a recovery of BP around 1 min, this group with sustained OH are comparable with our patients which we classified as continuous OH. Therefore, continuous OH seems to be a clinically important pattern of OH but more research is needed.

The 8% prevalence of delayed OH in our patients is remarkably similar to the 7.2% reported by Naschitz et al. [32]. Delayed OH is also described in patients with autonomic failure [23]. Interestingly, we found no other studies with a prevalence rate of delayed OH in patients of 65 years or older with unexplained fall or syncope. We discovered an elevated prevalence of diabetic mellitus, heart failure and hypertension in patients with delayed OH. This could suggest that delayed OH is associated with heart failure, as suggested earlier by Magnusson [16]. In delayed OH, cardiac impairment seems to be involved together with chronotropic and vascular impairment. Also, delayed OH could give an elevated mortality rate due cardiovascular impairment.

Mortality

We discovered that patients with continuous OH had a tendency for increased mortality compared to patients with classical OH. However, the Cox regression analysis did not show an association between a specific OH pattern and mortality. Other investigators discovered an increased mortality in patients with failure to recovery of BP after 1 min of standing. They stated that the duration of the BP drop influences mortality [33]. The absence of any recovery of BP during standing test in patients with continuous OH could result from impaired BP regulation due autonomic failure. This could limit cerebral circulation that might cause cerebrovascular damage and subsequent increased mortality. Autonomic failure is indeed associated with increased mortality [34]. Further research is required to examine the clinical relevance of patients with continuous OH and its relationship with autonomic failure and mortality.

It is difficult to subdivide patients with OH in three different groups since so many pathophysiology mechanisms can cause OH [22, 35]. Some even suggest that all OH patterns are a pre-stage of classic OH [21, 23]. Also, there are age-related differences of BP decline during standing test [36]. However, since we discovered different mortality rates it will be important to investigate the characteristics of patients with different OH patterns and the underlying pathophysiology.

Five patients died in the exclusion group. This could have influenced the outcomes if all patients had the same OH pattern. This is less likely due the different reasons of incomplete BP measurement. However, since the amount of death was small in each OH pattern group, some small changes could influence the outcome. This could have happened because of incomplete hospital records in case a patient has died at home, and the hospital record was not adjusted. Mortality was not elevated in all patients with OH compared to patients without OH. However, mortality rates differed between the OH patterns. Therefore, it is important to further investigate whether a specific OH pattern is associated with increased mortality.

Cardiovascular risks

We discovered that all patients with different patterns of OH had a higher baseline SBP and DBP compared to patients without OH. Hypertension is associated with OH and therefore hypertension must be treated according to the current guidelines [32, 37, 38]. Also, congestive heart failure was frequently seen in patients with OH in our study population which is in line with other investigations [13, 15, 17]. Especially, patients with diastolic dysfunction have a greater stiffness of the heart and therefore the cardiac output is more pre-load dependent [16]. With standing the atrial BP drops and might decrease cardiac output causing a reduced cerebral perfusion [20, 39]. Because the prevalence of elderly people with diastolic dysfunction is increasing due to the increasing life expectancy and hypertension, more research on the clinical relevance of different OH patterns and heart failure, especially diastolic dysfunction of the heart, is warranted [40, 41]. Since we do not know the timing of different cardiovascular comorbidities we were not able to discuss causality. All variables were diagnosed before by the GP or specialist, but because of our study design we have no information whether OH was caused by comorbidity, for example heart failure.

Fall and syncope

In our study we analysed patients with a fall only and patients with syncope and falls together. However, patients with syncope have more often heart failure, OH and are more often iADL dependent. On the other hand, the distinction between loss of consciousness is difficult. For example, cognitive disorders are common at our FSC, patients can have amnesia for loss of consciousness and in most patients there were no eye-witnesses of the fall [10, 42]. Therefore, in this study we merged both groups.

BP measurements

Since BP measurements were done once every 1 or 2 min, we may have underestimated the prevalence of OH compared to beat-to-beat BP measurement and we were less able to describe the OH patterns precisely [43]. Some investigators suggested that a lower cut-off point in BP decrease (SBP ≥ 10 mmHg and DBP ≥ 5 mmHg) has clinical implications while others suggested a higher cut-off (a decrease of SBP ≥ 30 mmHg) is needed to reduce false-positive outcomes [44, 45]. So, the cut-off point for OH is debatable. Also, the length of BP measurement with the standing test can be discussed. Gibbons et al. found a decrease in BP after 10 min of standing in a substantially 39% of the patients with OH [11]. Therefore, it is likely that patients without OH according to current ESC guidelines might have had delayed OH after 10 min of upright posture.

Limitations

Our study has some limitations due the observational study design. We were not able to perform more analyses within each OH pattern group due the number of patients in each group, especially the small numbers of death. We were depending on the hospital records for death. Therefore, we could have missed a death which could alter our results. Further, the results of the Cox-proportional hazard analysis were limited due the small number of events. Therefore, we had to exclude variables in the analysis which could influence mortality. Also, we used comorbidities noted in the referral letter of the GP and in the hospital record and therefore comorbidity could be under- and overestimated as well.

Conclusion

In conclusion, in this study of very elderly patients with unexplained falls or syncope we identified a new pattern of OH with a prolonged BP drop after standing which we called continuous OH. This continuous form of OH was more prevalent than the classical form. Both continuous OH and delayed OH tended to have a higher mortality rate compared to classical OH, but they remain undiagnosed when using current ESC syncope guidelines to diagnose OH. Our results encourage additional studies investigating the relation between different OH patterns and mortality. We advocate to measure BP for at least 10 min during the standing test to detect delayed OH and continuous OH.

Notes

Acknowledgements

We thank Els Doejaaren for her help with collecting the data and T. van der Ploeg, statistician, for his assistance with the statistical analysis of the data.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© European Geriatric Medicine Society 2018

Authors and Affiliations

  1. 1.Department of Geriatric MedicineNorthwest ClinicsAlkmaarThe Netherlands
  2. 2.Department of CardiologyNorthwest ClinicsAlkmaarThe Netherlands

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