Citation for published version (APA): Hartog, L. (2017). Orthostatic hypotension in elderly patients. [Groningen]: Rijksuniversiteit Groningen

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1 University of Groningen Orthostatic hypotension in elderly patients. Hartog, Laura IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2017 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Hartog, L. (2017). Orthostatic hypotension in elderly patients. [Groningen]: Rijksuniversiteit Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 CHAPTER 6 The association between orthostatic hypotension, falling and successful rehabilitation in a nursing home population Published as: Hartog LC, Cimzar-Sweelssen M, Knipscheer A, Groenier KH, Kleefstra N, Bilo HJG, Van Hateren KJJ. The association between Orthostatic hypotension, Falling and Successful Rehabilitation in a nursing home population. Archives of Gerontology and Geriatrics 2015; 61 (2):190-6.

3 Chapter 6 ABSTRACT urpose o the stud : Our objectives were to identify the prevalence of orthostatic hypotension (OH) in frail, elderly nursing home residents, and assess its possible association with falling and chances of successful rehabilitation. Materials and Methods: A prospective observational cohort study. A total of 290 patients participated in this study, of which 128 were admitted to the rehabilitation department. OH was defined as a drop in systolic blood pressure of > 20 mmhg and diastolic blood pressure of > 10 mmhg after postural change within 3 minutes. The analyses regarding falling and successful rehabilitation were only performed in the rehabilitation group. Multivariate binary logistic regression analyses were used to describe risk factors related with falling. Cox proportional hazard modeling was used to investigate the relation between OH and the time to successful rehabilitation. esults: The prevalence of OH in the studied nursing home population was 36.6% (95%CI (confidence interval): 31.1%-42.1%). The prevalence varied from 28.6% (95%CI:16.8%- 40.4%) in somatic patients, 36.7% (95%CI: 28.4%-45.1) in rehabilitation patients, to 40.6% (95%CI: 31.3%-50.0%) in psychogeriatric patients. The association between orthostatic hypotension and previous falling was not significant; Odds ratio 0.66 (95%CI: ). The Hazard ratio of the relationship between OH and successful rehabilitation was 2.88 (95% CI: ). onclusions: OH is highly prevalent in nursing home residents. Surprisingly, patients with OH were found to have a higher chance of successful rehabilitation compared to patients without OH. If confirmed in other studies, these results may change our view of the implications of OH. 86

4 rthostatic h potension alling and rehabilitation INTRODUCTION Orthostatic hypotension (OH) is frequently seen in the elderly population, and its prevalence increases with advancing age [1]. The etiology of OH is multifactorial; decrease of baroreceptor sensitivity, pure autonomic failure, and use of different medications like antihypertensive medications or antipsychotics are all considered being possible causes [2, 3]. Presence of OH increases the risk of cardiovascular disease and all-cause mortality in elderly people [4-7]. Furthermore, morbidity associated with OH is not limited to cardiovascular disease; some studies strongly suggest OH to be associated with falls, which in turn can lead to serious morbidity [8-10]. Most studies, which reported a positive association between falls and OH, were performed in nursing homes [11-13]. As the prevalence of OH in nursing home populations is high, and associations with fall incidents were observed in these populations, OH may be an important prognostic factor for chances of rehabilitation in nursing home patients. Although a few studies reported prevalence of OH in frail, elderly nursing home residents [11, 14, 15], the prevalence in these studies varied widely from 18-50% and the actual prevalence in different patient categories, such as psychogeriatric, somatic and rehabilitation patients, in nursing homes is unknown. In the current observational study we aimed to investigate the prevalence of OH and its association with previous fall incidents in different nursing home patient groups. Furthermore, we aimed to explore the influence of OH on the chances of successful rehabilitation. We hypothesized that the presence of OH would negatively influence the time to successful rehabilitation. 6 MATERIALS AND METHODS tud population For this prospective observational cohort study, patients were recruited from a nursing home facility in the northeastern region of the Netherlands (TriviumMeulenbeltZorg, Hengelo). Recruitment and all study procedures for patients on the somatic and psychogeriatric departments took place between September 2010 and December For patients on the rehabilitation department recruitment and all study procedures took place between September 2010 and December 2011, mostly within the first weeks of admission. Patients at the psychogeriatric department were diagnosed with severe to very severe dementia and behavioral disorders. Patients at the somatic department received prolonged or permanent care whereas patients at the rehabilitation department were rehabilitated to return to home as soon as possible. Exclusion criteria were a life expectancy of less than 4 weeks or admission to the hospice department. 87

5 Chapter 6 ata collection Baseline data involved demographic characteristics, a full medical history including a history of cardiovascular disease, diabetes mellitus, hypertension, falls in the previous year (yes of no), and medication use. All patients were subjected to questionnaires and blood pressure measurements. The activities of daily living were measured with the Barthel-Index [16]. Body mass index was calculated by measuring body weight and height. Blood pressure was measured following a standardized protocol, using an automated sphygmomanometer (Omron M6) [17]. Trained medical staff performed all tests. Blood pressure was measured two times in supine position after 5 minutes of rest, and two times each at 1 and 3 minutes after postural change. The forearm of the patient was supported at heart level during the measurements in upright position [18]. The postural change was from supine to standing position, with the exception of patients who were unable to stand. For these patients the postural change was from lying to sitting position. OH was defined as a drop in systolic blood pressure (SBP) of > 20 mmhg or diastolic blood pressure (DBP) of > 10 mmhg after postural change compared to the mean value of the baseline measurements in supine position [1]. Characteristic symptoms of OH like light-headedness, syncope, or dizziness after postural change were questioned and the combination of OH and orthostatic complaints was described as symptomatic OH. Successful rehabilitation was defined as discharge to patients own homes or to an adapted home for the elderly, where they functioned self-reliant. tatistical anal ses Continuous variables are presented as mean and standard deviation for normally distributed variables, or as median and interquartile range for non-normally distributed variables. Univariate binary logistic regression analyses were performed to assess the association of OH, orthostatic complaints or symptomatic OH and the baseline characteristics. Subsequently, multivariate binary logistic regression analyses were used to describe risk factors associated with falling. In the multivariate binary logistic regression analyses we adjusted for age, gender, body mass index (BMI), a history of diabetes mellitus, the score on the Barthel questionnaire, previous macrovascular complications, and the use of antihypertensive medication. Cox proportional hazard modeling was used to investigate the relation between OH, orthostatic complaints, or symptomatic OH and successful rehabilitation. Since not all blood pressure measurements were performed in the first week of rehabilitation; time to successful rehabilitation started on the day of OH blood pressure measurement. In the multivariate Cox regression models we adjusted for the same variables as in the multivariate binary logistic analyses, including mean systolic blood pressure. The Schoenfeld residual plots were inspected for each predictor variable to check the assumption of proportional hazards. The analyses regarding falling and successful rehabilitation were only performed in the rehabilitation group. P values less than 0.05 were considered statistically significant. 88

6 rthostatic h potension alling and rehabilitation All statistical analyses were performed using SPSS software (version 22). The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement was used to describe this observational cohort study [19]. thical approval and linical rial registration This study was performed in accordance with the Declaration of Helsinki. According to Dutch guidelines this study did not fall under the scope of the Medical Research Involving Human Subjects Act, and therefore this study did not need a formal approval of an accredited medical ethics committee. Written informed consent was obtained for all patients by the participating medical doctor or nurse. All data were analyzed anonymously. The study was registered on ClinicalTrials.gov (NCT ). RESULTS A total of 290 patients was included in this cohort, 106 patients at the psychogeriatric department, 56 patients at the somatic department, and 128 patients at the rehabilitation department. The baseline characteristics are presented in table 1. Mean age of the total study population was 80.9 (+ 9.9) years. OH was present in 106 out of 290 patients, resulting in a prevalence of 36.6% (95%CI (confidence interval): 31.1%-42.1%). The prevalence ranged from 28.6% (95%CI: 16.8%-40.4%) on the somatic department, to 36.7% (95% CI: 28.4% to 45.1) and 40.6% (95% CI: 31.3% to 50.0%) on the rehabilitation and the psychogeriatric departments, respectively. The intended postural change could be performed from lying to standing in 35.7% of the somatic patients, 86.7% of the rehabilitation patients, and 66.0% of the psychogeriatric patients. The remaining patients performed the postural change from lying to sitting. The results of the univariate regression analyses are presented in appendix table A1 and A2. Both age and mean supine systolic blood pressure were related to OH. Mean systolic blood pressure was higher in the OH group. A total of 59 (20.3%) patients had fallen at least once in the previous year. A correlation between falls in the last year and symptomatic OH was seen, whereas the presence of OH and orthostatic complaints were not correlated. 6 89

7 Chapter 6 Table 1. Baseline characteristics total population and different groups of patients. Total Psychogeriatric department Somatic department Rehabilitation department Characteristic N=290 N=106 N=56 N=128 Demographics Age 80.8 (9.9) 82.9 (8.9) 77.1 (14.1) 80.7 (7.9) Female Gender 206 (71.0) 78 (73.6) 36 (64.3) 92 (71.9) Mean body mass index, kg/m (5.4) 25.9 (5.2) 28.2 (5.8) 25.9 (5.3) Hypertension 226 (77.9) 79 (74.5) 42 (75) 105 (82.0) History of CVD 131 (45.2) 48 (45.3) 32 (57.1) 51 (39.8) Diabetes mellitus 104 (35.0) 30 (28.3) 19 (33.9) 55 (43.0) Dementia 121 (41.7) 100 (94.3) 12 (21.4) 9 (7.0) Currrent smoker 32 (11.0) 8 (7.5) 12 (21.4) 12 (9.4) Measurements Consumption meal or drink 194 (66.9) 77 (72.6) 30 (53.6) 87 (68.0) Mean SBP lying 147 (22) (21.0) 147 (25) (22.2) Mean DBP lying 74 (11) 76.6 (11.4) 75 (13) 72.4 (9.8) Mean pulse frequency 74 (13) 72.4 (14.1) 74 (13) 75.4 (12.3) Falls last year 59 (20.3) 8 (7.5) 4 (7.1) 47 (36.7) Orthostatic hypotension 106 (36.6) 43 (40.6) 16 (28.6) 47 (36.7) Orthostatic complaints 71 (24.7) 26 (24.5) 11 (19.6) 34 (26.6) Score Barthel questionnaire 10 (6-15) 9 (4-14) 6 (2-12) 13 (9-16) Medication Mean number of agents 8.7 (3.5) 8.5 (3.0) 9.5 (4.2) 8.6 (3.6) Antihypertensive medication - Diuretics - Beta blockers - Calcium channel blockers - ACE inhibitors 194 (66.9) 128 (44.1) 85 (29.3) 42 (14.5) 100 (34.5) 68 (64.2) 43 (40.6) 23 (21.7) 13 (12.3) 42 (39.6) 35 (62.5) 23 (41.1) 17 (30.4) 8 (14.3) 15 (26.8) 91 (71.1) 62 (48.4) 45 (35.2) 21 (16.4) 43 (33.6) Benzodiazepines 150 (51.7) 52 (49.1) 34 (60.7) 64 (50) Antipsychotics 59 (20.3) 34 (32.1) 11 (19.6) 14 (10.9) Antidepressants 69 (23.8) 32 (30.2) 18 (32.1) 19 (14.8) Opioids 32 (11.0) 10 (9.4) 9 (16.1) 13 (10.2) Data are means (± SD), medians (interquartile range) or n (%). CVD = Cardio vascular disease. SBP = systolic blood pressure. DBP = diastolic blood pressure. 90

8 rthostatic h potension alling and rehabilitation revious all incidents Because 80% of all patients who had fallen at least once in the previous year were admitted at the rehabilitation ward, multivariate analyses on the risk of previous falls were only performed in the rehabilitation group (table 2). In the multivariate analyses no significant relation was found between OH or orthostatic complaints and reported previous falling. The relationship between symptomatic OH and previous falls was also not significant; adjusted Odds ratio 2.1 (95% CI: ). Adjustment for the postural position (standing or sitting) did not influence the results (data not shown). uccess ul rehabilitation A total of 128 patients were admitted to the rehabilitation department. During a median follow-up period of 2.6 months (IQR ), 106 patients were successfully rehabilitated. 94 patients were discharged to their own homes, and 12 patients were discharged to an adapted home for the elderly. Two patients died during admission. Median time between admission to the rehabilitation department and blood pressure measurements was 1.1 month (IQR ). Table 3 presents the results of the Cox regression analyses, and figure 1 shows the cumulative proportion of successful rehabilitation curve. The chance of successful rehabilitation was 188% (95%CI: 77%-469%) higher for patients with OH compared to those without, when adjusted for orthostatic complaints and selected confounders. Also without adjustment for orthostatic complaints the chance of successful rehabilitation was higher for patients with OH. This relation was also significant when it was adjusted only for age and gender (HR 1.71 [95%CI ]). Higher scores on the Barthel questionnaire were also related to successful rehabilitation in all multivariate models. A history of diabetes mellitus was inversely related to successful rehabilitation. The plots of the Schoenfeld residues showed that the assumptions of proportional hazards were met. Some post-hoc analyses were performed. As the postural position (standing or sitting), reason for admission, and the discharge destination (own home or adapted home for the elderly) may have influenced the results, we performed additional cox regression analyses in which we additionally adjusted for these variables. Results did not relevantly change (data not shown). As blood pressure may be a marker of frailty in old age [20], we performed post-hoc analyses in which we tested for interaction with blood pressure by analyzing different systolic blood pressure subgroups ( mmhg, mmhg, and mmhg). The HR s for each subgroup were 2.95 (95%CI: ), 3.04 (95% CI: , and 1.95 (95%CI: ), respectively. OH was only significantly related to successful rehabilitation in the group with blood pressure values between mmhg (p=0.001). Figure 1 shows the cumulative proportion of successful rehabilitation curves for the total cohort and each of the subgroups. 6 91

9 Chapter 6 Table 2. Adjusted odds ratios for the effect of clinical variables on the risk of previous fall incidents in the rehabilitation patient group (n=128). The odds ratios can be interpreted as a measure of the association of the various variables to previous fall incidents (the dependent variables). Previous fall incidents in last year as the dependent variable Model 1 Model 2 Model 3 Model 4 Odds ratio (95% CI) Odds ratio (95% CI) Odds ratio (95% CI) OH 0.66 ( ) ( ) - Orthostatic complaints ( ) 1.35 ( ) - Symptomatic OH ( ) Age 1.02 ( ) 1.02 ( ) 1.02 ( ) 1.02 ( ) Gender, female vs male 0.55 ( ) 0.53 ( ) 0.55 ( ) 0.53 ( ) Body Mass Index 0.99 ( ) 0.99 ( ) 0.99 ( ) 0.99 ( ) DM, DM vs control 0.78 ( ) 0.79 ( ) 0.79 ( ) 0.79 ( ) Score Barthel questionnaire 1.03 ( ) 1.04 ( ) 1.04 ( ) 1.04 ( ) History of CVD disease 0.43 ( ) 0.45 ( ) 0.46 ( ) 0.45 ( ) Antihypertensive medication 1.02 ( ) 0.92 ( ) 0.97 ( ) 0.91 ( ) Model 1 was adjusted for OH, model 2 for orthostatic complaints, model 3 for OH and orthostatic complaints, and model 4 for symptomatic orthostatic hypotension. All models were additionally adjusted for the following possible predictors of fall incidents: age, gender, BMI, diabetes mellitus, score Barthel questionnaire, previous macro vascular complications, and use of antihypertensive medications. The ORs can be interpreted as a measure of the association of the various variables to previous fall incidents. OH = orthostatic hypotension. CVD = Cardio vascular disease. 92

10 rthostatic h potension alling and rehabilitation Table 3. Cox regression analyses; hazard ratios for successful rehabilitation in the rehabilitation patient group (n=128). Model 1 Model 2 Model 3 Model 4 HR (95% CI) HR (95% CI) HR (95% CI) HR (95% CI) OH 2.65 ( ) ( ) - Orthostatic complaints ( ) 0.79 ( ) - Symptomatic OH ( ) Age 1.01 ( ) 1.01 ( ) 1.01 ( ) 1.01 ( ) Gender, female vs male 1.37 ( ) 1.38 ( ) 1.37 ( ) 1.40 ( ) BMI 1.05 ( ) 1.04 ( ) 1.05 ( ) 1.04 ( ) Score Barthel questionnaire 1.16 ( ) 1.14 ( ) 1.16 ( ) 1.14 ( ) Antihypertensive medication 0.95 ( ) 1.01 ( ) 0.96 ( ) 1.02 ( ) History of CVD disease 1.39 ( ) 1.33 ( ) 1.39 ( ) 1.35 ( ) T2DM, DM vs control 0.60 ( ) 0.59 ( ) 0.61 ( ) 0.59 ( ) Mean SBP lying 1.01 ( ) 1.01 ( ) 1.01 ( ) 1.01 ( ) Hazard ratios for successful rehabiliation. All models were additionally adjusted for the following possible predictors of fall incidents: age, gender, BMI, diabetes mellitus, score Barthel questionnaire, previous macro vascular complications, mean SBP lying, and the number of antihypertensive medications used. OH = orthostatic hypotension. CVD = Cardio vascular disease. SBP = systolic blood pressure. 6 93

11 Chapter 6 Figure 1. Cumulative proportion of successful rehabilitation (Survival curves) for the total cohort (A), subgroups with systolic blood pressure mmHg (B), mmhg (C), and mmhg (D). DISCUSSION In the present study, the overall prevalence of OH in nursing home residents was 36.6%, varying from 28.6% at the somatic department, to 36.7% at the rehabilitation department, and 40.6% at the psychogeriatric department. No significant correlation was found between reported previous falling and OH or orthostatic complaints. Finally, the chance of successful rehabilitation was higher for patients with OH compared to patients without. revalence The prevalence of OH in this study proved to be higher than in community-dwelling elderly of the same age [6, 21, 22]. In contrast, the prevalence was lower compared to a prospective 94

12 rthostatic h potension alling and rehabilitation study by Ooi et al. amongst nursing home residents. In this study, OH in frail, elderly nursing home residents occurred in more than 50% [14]. The most important difference with the current study could be the timing of the measurements. In the study by Ooi et al. the prevalence of OH was highest before breakfast, while in the present study two third of the patients had already eaten when measured. The prevalence of OH was lowest in the group of somatic patients. Because only 35.7% of these patients could perform the postural change from lying to standing, the actual number of patients with OH could be underestimated in this group of patients. revious all incidents No significant correlation was found between reported previous falling and OH or orthostatic complaints. In a previous review and meta-analysis, no significant conclusions could be drawn concerning the relationship between OH and falling [10, 23]. In a prospective study of over 800 elderly patients, OH was not associated with subsequent falls. However, patients with OH and a history of previous falling had an increased risk of recurrent falls [12]. Romero- Ortuno et al. did find a correlation between initial OH, defined as blood pressure decrease of more than 40 mmhg in systolic or more than 20 mmhg in diastolic blood pressure within 15 seconds after standing with symptoms, and falls [24]. Furthermore, a strong correlation was found between initial OH and orthostatic complaints, but not between OH and complaints. Possibly, the current definition of OH is incorrect with regard to the relationship between OH and falling. Orthostatic complains may be more relevant than OH on itself [25]. 6 is o success ul rehabilitation A rather counterintuitive association between OH and the hazard of successful rehabilitation was observed in the present study. As far as we are aware, there is only one study that has described functional outcome of patients undergoing rehabilitation stratified according to OH. Functional outcome was not different between stroke patients with and without OH [26]. Cox regression analyses were not performed in this study. We hypothesized about possible explanations for the positive relationship between OH and successful rehabilitation. Firstly, we tested for interaction with blood pressure, as lower values are a marker of frailty in old age. Results of these additional analyses showed that OH was only significantly related to a higher chance of successful rehabilitation in patients with SBP values between 130 and 160 mmhg (possibly because of the higher number of events in this group). Still, this is no explanation for the remarkable association. As OH is related to reduced standing balance [27], the homes and home environment of patients with OH may be more adapted to their disabilities, or patients with OH may be used to a less active life, resulting in a quicker achievement of their rehabilitation targets. However, the Barthel index was positively correlated with successful rehabilitation. This argues against 95

13 Chapter 6 the above-mentioned arguments as patients with higher scores on the Barthel index are more independent. Finally, the result could be a matter of coincidence as the study group is rather small. i itations The current study has some limitations. The main limitation is its observational design; therefore, establishing a causal relation is not possible. Besides, two important types of bias occurred in this study; selection and recall bias. Patients in a nursing home on a rehabilitation department are mainly rehabilitating after a fracture or fall, which creates bias with respect to falling and OH. Recall problems were caused because all previous fall incidents were retrospectively assessed. The information regarding previous falls was based on questioning patients or participants. It is very likely that the actual number of patients with previous fall incidents was higher. Another limitation is the definition of successful rehabilitation. This was defined as discharge to home or a home for the elderly, where they functioned self-reliant. As a consequence, patients with a worse outcome after rehabilitation but with a highly adapted home environment (e.g. stairlift, homecare, meal service) may be quickly sent home. Finally, a limitation of this study is the variation of point of time of the blood pressure measurements. Not all measurements were performed in the first weeks of rehabilitation. The actual number of patients with OH could be underestimated by this variation. In the cox regression analyses, time to successful rehabilitation started on the day of OH blood pressure measurement. We also performed the same analyses stratified according to timing of blood pressure measurements: hazard ratios were 3.66 (95%CI ) for measurements < 30 days and 2.60 (95%CI ) for measurements > 30 days after admission. Because we are investigating OH in relation to successful rehabilitation, the time at risk started at the date of OH measurement. CONCLUSIONS More than one third of the nursing home residents were diagnosed with OH. There was no significant correlation between reported previous falls and OH or orthostatic complaints. Remarkably, patients with OH were found to have a higher chance of successful rehabilitation compared to patients without OH. Confirmation of this rather remarkable and counterintuitive finding in other studies is necessary, preferably performed in prospective studies. 96

14 rthostatic h potension alling and rehabilitation REFERENCES 1. Lahrmann H, Cortelli P, Hilz M, et al. EFNS guidelines on the diagnosis and management of orthostatic hypotension. European journal of neurology : the official journal of the European Federation of Neurological Societies Sep;13(9): Medow MS, Stewart JM, Sanyal S, et al. Pathophysiology, diagnosis, and treatment of orthostatic hypotension and vasovagal syncope. Cardiology in review Jan-Feb;16(1): Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Archives of internal medicine Nov 23;169(21): Verwoert GC, Mattace-Raso FU, Hofman A, et al. Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study. Journal of the American Geriatrics Society Oct;56(10): Xin W, Lin Z, Mi S. Orthostatic hypotension and mortality risk: a meta-analysis of cohort studies. Heart Mar;100(5): Masaki KH, Schatz IJ, Burchfiel CM, et al. Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program. Circulation Nov 24;98(21): Rose KM, Tyroler HA, Nardo CJ, et al. Orthostatic hypotension and the incidence of coronary heart disease: the Atherosclerosis Risk in Communities study. American journal of hypertension Jun;13(6 Pt 1): Benvenuto LJ, Krakoff LR. Morbidity and mortality of orthostatic hypotension: implications for management of cardiovascular disease. American journal of hypertension Feb;24(2): Scheffer AC, van Hensbroek PB, van Dijk N, et al. Risk factors associated with visiting or not visiting the accident & emergency department after a fall. BMC health services research. 2013;13: Shaw BH, Claydon VE. The relationship between orthostatic hypotension and falling in older adults. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Feb;24(1): Graafmans WC, Ooms ME, Hofstee HM, et al. Falls in the elderly: a prospective study of risk factors and risk profiles. American journal of epidemiology Jun 1;143(11): Ooi WL, Hossain M, Lipsitz LA. The association between orthostatic hypotension and recurrent falls in nursing home residents. The American journal of medicine Feb;108(2): Rubenstein LZ, Josephson KR, Robbins AS. Falls in the nursing home. Annals of internal medicine Sep 15;121(6): Ooi WL, Barrett S, Hossain M, Kelley-Gagnon M, Lipsitz LA. Patterns of orthostatic blood pressure change and their clinical correlates in a frail, elderly population. Jama Apr 23-30;277(16): Valbusa F, Labat C, Salvi P, et al. Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study. Journal of hypertension Jan;30(1): Sainsbury A, Seebass G, Bansal A, Young JB. Reliability of the Barthel Index when used with older people. Age and ageing May;34(3): Altunkan S, Iliman N, Altunkan E. Validation of the Omron M6 (HEM-7001-E) upper arm blood pressure measuring device according to the International Protocol in elderly patients. Blood pressure monitoring Apr;13(2): Mariotti G, Alli C, Avanzini F, et al. Arm position as a source of error in blood pressure measurement. Clinical cardiology Oct;10(10): von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies. International journal of surgery Jul

15 Chapter van Hateren KJ, Landman GW, Kleefstra N, et al. Lower blood pressure associated with higher mortality in elderly diabetic patients (ZODIAC-12). Age and ageing Sep;39(5): Luukinen H, Koski K, Laippala P, Kivela SL. Prognosis of diastolic and systolic orthostatic hypotension in older persons. Archives of internal medicine Feb 8;159(3): Rutan GH, Hermanson B, Bild DE, et al. Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension Jun;19(6 Pt 1): Angelousi A, Girerd N, Benetos A, et al. Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis. Journal of hypertension Aug;32(8): ; discussion Romero-Ortuno R, Cogan L, Foran T, Kenny RA, Fan CW. Continuous noninvasive orthostatic blood pressure measurements and their relationship with orthostatic intolerance, falls, and frailty in older people. Journal of the American Geriatrics Society Apr;59(4): van Hateren KJ, Kleefstra N, Blanker MH, et al. Orthostatic hypotension, diabetes, and falling in older patients: a cross-sectional study. The British journal of general practice : the journal of the Royal College of General Practitioners Oct;62(603):e Kong KH, Chuo AM. Incidence and outcome of orthostatic hypotension in stroke patients undergoing rehabilitation. Archives of physical medicine and rehabilitation Apr;84(4): Pasma JH, Bijlsma AY, Klip JM, et al. Blood pressure associates with standing balance in elderly outpatients. PloS one. 2014;9(9):e

16 rthostatic h potension alling and rehabilitation SUPPLEMENTAL DATA Table A1. Univariate logistic regression analyses with OH, orthostatic complaints and symptomatic OH as dependent variables. Total OR (95%CI) OR (95%CI) OR (95%CI) Characteristic N=290 rthostatic co plaints pto atic Demographics Age 80.8 (9.9) 1.04 ( ) 1.00 ( ) 1.01 ( ) Gender (% female) 206/290 (71.0) 1.18 ( ) 0.79 ( ) 1.00 ( ) Mean body mass index, kg/m (5.4) 0.99 ( ) 1.00 ( ) 1.02 ( ) Hypertension 226/290 (77.9) 1.63 ( ) 1.75 ( ) 1.53 ( ) History of CVD disease 131/290 (45.2) 1.21 ( ) 0.64 ( ) 0.74 ( ) Diabetes mellitus 104/290 (35.0) 1.29 ( ) 1.42 ( ) 1.53 ( ) Dementia 121/290 (41.7) 1.18 ( ) 0.82 ( ) 0.54 ( ) Currrent smoker 32/290 (11.0) 0.54 ( ) 0.68 ( ) 0.53 ( ) Measurements Consumption meal or drink 194/290 (66.9) 0.63 ( ) 0.97 ( ) 0.65 ( ) Mean SBP lying 147 (22) 1.01 ( ) 0.99 ( ) 1.01 ( ) Mean DBP lying 74 (11) 1.02 ( ) 1.01 ( ) 1.02 ( ) Mean pulse frequency 74 (13) 0.98 ( ) 1.01 ( ) 1.00 ( ) Falls last year 59/290 (20.3) 0.95 ( ) 1.62 ( ) 2.42 ( ) Orthostatic hypotension 106/290 (36.6) NA 1.48 ( ) NA Orthostatic complaints 71/288 (24.7) 1.48 ( ) NA NA Score Barthel questionnaire 10 (6-15) 0.98 ( ) 1.01 ( ) 1.02 ( ) Medication Mean number of agents 8.7 (3.5) 1.03 ( ) 0.97 ( ) 0.99 ( ) Antihypertensive medication 194/290 (66.9) 1.32 ( ) 1.25 ( ) 0.76 ( ) - Diuretics 128/290 (44.1) 1.37 ( ) 1.77 ( ) 1.40 ( ) - Beta blockers 85/290 (29.3) 0.99 ( ) 0.77 ( ) 0.99 ( ) - Calcium channel blockers 42/290 (14.5) 1.36 ( ) 0.95 ( ) 0.86 ( ) - ACE inhibitors 100/290 (34.5) 1.34 ( ) 1.24 ( ) 0.76 ( ) Benzodiazepines 150/290 (51.7) 0.75 ( ) 0.96 ( ) 0.86 ( ) Antipsychotics 59/290 (20.3) 1.14 ( ) 0.58 ( ) 0.73 ( ) Antidepressants 69/290 (23.8) 0.83 ( ) 0.83 ( ) 0.93 ( ) Opioids 32/290 (11.0) 1.87 ( ) 0.84 ( ) 1.65 ( ) Baseline characteristics and results of univariate logistic regression analyses with orthostatic hypotension (OH), orthostatic complaints, and symptomatic OH as dependent variables. Data are means (SD), medians (interquartile range) or n (%). 6 99

17 Chapter 6 Table A2. Rehabilitation department: Univariate logistic regression analyses with OH, orthostatic complaints, and falls last year as dependent variables. Rehabilitation department OR (95%CI) OR (95%CI) OR (95%CI) Characteristic N=128 rthostatic co plaints alls last ear Demographics Age 80.7 (7.9) 1.01 ( ) 0.96 ( ) 1.02 ( ) Female Gender 92 (71.9) 1.57 ( ) 0.89 ( ) 0.47 ( ) Mean body mass index, kg/m (5.3) 1.01 ( ) 1.03 ( ) 0.99 ( ) Hypertension 105 (82.0) 2.40 ( ) 4.60 ( ) 0.57 ( ) History of CVD 51 (39.8) 1.20 ( ) 0.45 ( ) 0.43 ( ) Diabetes mellitus 55 (43.0) 1.12 ( ) 0.91 ( ) 0.64 ( ) Dementia 9 (7.0) 2.29 ( ) 0.33 ( ) 0.85 ( ) Currrent smoker 12 (9.4) 0.55 ( ) 0.53 ( ) 0.85 ( ) Measurements Mean SBP lying (22.2) 1.00 ( ) 0.99 ( ) 1.01 ( ) Mean DBP lying 72.4 (9.8) 1.02 ( ) 1.01 ( ) 0.99 ( ) Mean pulse frequency 75.4 (12.3) 0.98 ( ) 0.99 ( ) 0.99 ( ) Falls last year 47 (36.7) 0.62 ( ) 1.29 ( ) NA Orthostatic hypotension 47 (36.7) NA 2.13 ( ) 0.62 ( ) Orthostatic complaints 34 (26.6) 2.13 ( ) NA 1.29 ( ) Score Barthel questionnaire 13 (9-16) 0.98 ( ) 0.98 ( ) 1.06 ( ) Medication Mean number of agents 8.6 (3.6) 1.08 ( ) 1.03 ( ) 0.98 ( ) Antihypertensive medication - Diuretics - Beta blockers - Calcium channel blockers - ACE inhibitors 91 (71.1) 62 (48.4) 45 (35.2) 21 (16.4) 43 (33.6) 1.85 ( ) 2.34 ( ) 0.93 ( ) 1.37 ( ) 1.39 ( ) 1.45 ( ) 1.77 ( ) 1.20 ( ) 1.48 ( ) 0.93 ( ) 0.94 ( ) 0.90 ( ) 1.07 ( ) 0.48 ( ) 0.76 ( ) Benzodiazepines 64 (50) 0.82 ( ) 1.62 ( ) 1.22 ( ) Antipsychotics 14 (10.9) 0.95 ( ) 0.73 ( ) 0.43 ( ) Antidepressants 19 (14.8) 1.01 ( ) 0.99 ( ) 1.01 ( ) Opioids 13 (10.2) 3.12 ( ) 1.85 ( ) 0.74 ( ) Baseline characteristics and results of univariate logistic regression analyses with orthostatic hypotension (OH), orthostatic complaints, and Falls last year as dependent variables. Data are means (SD), medians (interquartile range) or n (%). CVD = Cardio vascular disease. SBP = systolic blood pressure. DBP = diastolic blood pressure. 100