Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older

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1 (2009) 23, & 2009 Macmillan Publishers Limited All rights reserved /09 $ ORIGINAL ARTICLE Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older P Hiitola 1,2, H Enlund 3, R Kettunen 4, R Sulkava 5,6 and S Hartikainen 7,8,9 1 Department of Social Pharmacy, University of Kuopio, Kuopio, Finland; 2 Kuopio Research Centre of Geriatric Care, Kuopio, Finland; 3 Department of Pharmacy Practice, Kuwait University, Kuwait; 4 Department of Medicine, Paijat-Hame Central Hospital, Lahti, Finland; 5 Division of Geriatrics, School of Public Health and Clinical Nutrition, University of Kuopio, Finland, Finland; 6 Rheumatism Foundation Hospital, Heinola, Finland; 7 Faculty of Pharmacy, University of Kuopio, Kuopio, Finland; 8 Kuopio Research Centre of Geriatric Care, Kuopio, Finland and 9 Leppävirta Health Centre, Leppävirta, Finland This cross-sectional analysis of a population-based cohort investigates the postural changes in blood pressure (BP) and heart rate and assesses the prevalence of orthostatic hypotension (OH) and its associations with the medicines used by an elderly population. The study population (n ¼ 1000) was a random sample of persons aged 75 years or older in the City of Kuopio, Finland. In 2004, altogether, 781 persons participated in the study. After the exclusion of persons living in institutional care (n ¼ 82) and those without orthostatic test (n ¼ 46), the final study population comprised 653 home-dwelling elderly persons. OH was defined as a X20 mm Hg drop of systolic BP or a X10 mm Hg drop of diastolic BP or both 1 or 3 min after standing up from supine position. Systolic BP dropped for more than half of the home-dwelling elderly when they stood up from a supine to a standing position. The total prevalence of OH was 34% (n ¼ 220). No significant gender or age differences were seen. The prevalence of OH was related to the total number of medicines in regular use (Po0.05). OH and postural changes in BP are more common among the home-dwelling elderly than reported in previous studies. The prevalence of OH is related to the number of medicines in regular use. There is an obvious need to measure orthostatic BP of elderly persons, as low BP and OH are important risk factors especially among the frail elderly persons. (2009) 23, 33 39; doi: /jhh ; published online 24 July 2008 Keywords: blood pressure; orthostatic hypotension; pulse pressure; elderly; population-based study Introduction Orthostatic hypotension (OH) is a major health problem in the elderly. It affects 6 30% of homedwelling elderly persons. 1 5 OH is even more prevalent in residential care Postural hypotension and OH are risk factors for dizziness, syncope and falls, which can lead to functional impairment. 1,7,10,12,13 Hospitalization, prolonged bed rest and diseases such as Parkinson s disease are also associated with OH. 6,14,15 OH is a risk factor for stroke, and it is associated with cardiovascular and all-cause mortality. 2,3,16 An association with mortality has been reported even for blood pressure Correspondence: P Hiitola, Department of Social Pharmacy, University of Kuopio, Box 1627, Kuopio 70211, Finland. Paivi.Hiitola@uku.fi Received 22 February 2008; revised 15 June 2008; accepted 18 June 2008; published online 24 July 2008 (BP) drops lower than those fulfilling the OH criteria. 2,16 Orthostatic hypotension can be caused by several medicines, such as antihypertensives, 9 antidepressants, 9,17 a-adrenergic blocking agents 9,14,18 and medication for Parkinson s disease, 6 haemodynamic conditions such as hypovolaemia and cardiac insufficiency, and neurogenic causes such as multiple system atrophy and, for example, diabetic neuropathy. 19 As far as we know, there are no wide populationbased studies concerning the changes in blood and pulse pressures following postural change and the prevalence of OH and its associations with medication in elderly populations. Therefore, the aim of this study was to examine the changes in blood and pulse pressures following postural change to determine the prevalence of OH and to find its associations with the use of medicines in home-dwelling elderly persons aged 75 years or older.

2 34 Materials and methods Postural changes in blood pressure and orthostatic hypotension Study subjects and setting This study is part of the population-based GeMS study (Geriatric Multidisciplinary Strategy for the Good Care of the Elderly), a multidisciplinary health intervention survey focusing on the clinical epidemiology of diseases, functional capacity, medication and use of services in a population of elderly persons aged 75 years or older. The target population comprised all the inhabitants of the City of Kuopio in Eastern Finland, aged 75 years or older on 1 November From this population, a random sample of 1000 persons was drawn. In this cohort, 55 died before the examination, two moved away and 162 persons refused to take part in the survey. The remaining 781 participants attended a structured clinical examination and an interview conducted by a trained nurse. Physiotherapists tested their functional capacity, strength and balance. Of all the examined elderly persons (n ¼ 781), we excluded those in institutional care (n ¼ 82) and the home-dwelling elderly without an orthostatic test (n ¼ 46). This study is based on information from the 653 home-dwelling elderly with an orthostatic test. Of the participants, 70% (n ¼ 454) were females and 30% (n ¼ 199) were males. The mean age of our participants in 2004 was 81 years (range of years). Data collection The basic demographic and clinical data were collected by means of interviews. Trained nurses interviewed the participants about their use of medicines and recorded the medicines they were currently taking. The participants were also asked to bring their prescription forms and medicine containers with them for the interview. If the person him/herself could not answer the questions, a relative or a caregiver gave the required information. If the participant was unable to visit the clinic, a trained nurse made a home visit. Medical records from the municipal health centre, home nursing service, local hospitals and Kuopio University Hospital were also available. Both regularly and irregularly taken prescribed and non-prescribed medicines were recorded. If a medicine was taken daily or at regular intervals, it was recorded as being in regular use. If it was taken only when needed, it was recorded as being in irregular use. The medicines were classified according to the Anatomic Therapeutic Chemical classification system, version 2004, recommended by the World Health Organization for drug utilization studies. 20,21 The criteria for OH were those defined by the American Autonomic Society and the American Academy of Neurology: a systolic BP (SBP) decrease of at least 20 mm Hg (systolic OH) or a diastolic BP (DBP) decrease of at least 10 mm Hg (diastolic OH) within 3 min of standing up. 22 The BP recordings were made after 10 min rest. BP was measured in lying, sitting and standing positions (at 1 and 3 min) by a trained nurse using a calibrated mercury column sphygmomanometer or a calibrated airpressure sphygmomanometer. Pulse pressure was calculated as the difference between SBP and DBP. The largest changes from baseline in SBP and DBP were also examined. The clinical criteria for dementia were those of Diagnostic and Statistical Manual of Mental Disorders-IV. 23 Statistical analysis The data management and analysis were performed using SPSS 14.0 for Windows (Statistical Package for Social Sciences 14.0). Chi-square test was used for analysing the statistical significance of the differences in categorical variables. Non-parametric Mann Whitney U-test was used in analysing the statistical significance of the differences in continuous variables like age and the number of medicines used. The T-test was used for analysing the differences in pulse pressures between the OH groups. Ethical issues Written informed consent was obtained from the study participants or their relatives. The study was approved by the Research Ethics Committee of Northern Savo Hospital District and Kuopio University Hospital. Results There were no statistically significant differences in basic demographic characteristics, body mass index, diseases or BPs between participants having OH and those not having OH (Table 1). Postural changes in BP among all participants In the orthostatic test, SBP did not change in 13% (1 min) and 18% (3 min) of the participants. About 20% of the elderly persons had a rise and 68% (1 min) and 60% (3 min) had a drop in SBP (Figure 1). SBP dropped by 30 mm Hg or more after 1 min in 10% and by mm Hg in 27% of those tested. DBP dropped in 39% (1 min) and in 32% (3 min). The lowest SBP value was 95 mm Hg (1 min) and 100 mm Hg (3 min) and the lowest DBP value 48 mm Hg (1 min) and 50 mm Hg (3 min). The biggest drop in SBP from a supine to a standing position after 1 min of standing was 55 mm Hg and that after 3 min of standing was 50 mm Hg. In DBP, the biggest drop was 20 mm Hg after both 1 and 3 min of standing.

3 Postural changes in blood pressure and orthostatic hypotension Table 1 Characteristics of the study population according to the OH status (n ¼ 653) 35 OH-positive n ¼ 220 (%) OH-negative n ¼ 433 (%) Total n ¼ 653 (%) P-value a Age (46) 228 (53) 328 (50) (31) 128 (29) 197 (30) (23) 77 (18) 128 (20) Sex Male 64 (29) 135 (31) 199 (31) BMI, mean 26.0 (95% CI ) 26.7 (95% CI ) 26.5 (95% CI ) Systolic blood pressure, sitting 145 (95% CI ) 145 (95% CI ) 145 (95% CI ) position, mean (mm Hg) Diastolic blood pressure, sitting 79 (95% CI 77 80) 80 (95% CI 79 81) 80 (95% CI 79 81) position, mean (mm Hg) Dementia 37 (17) 52 (12) 89 (14) Diabetes mellitus 67 (16) 32 (15) 99 (15) Hypertonia 127 (58) 252 (58) 379 (58) Parkinson s disease 6 (3) 5 (1) 11 (2) Abbreviations: BMI, body mass index; CI, confidence interval; OH, orthostatic hypotension. a From the w 2 test (stratified variables) or Mann Whitney U-test (continuous variables). prevalence of a combination of systolic and diastolic OH increased significantly with age (Po0.05). The prevalence of any orthostatic reaction was similar regardless of SBP in a sitting position (Table 2). Systolic OH (3 min) was most common among the participants with SBPX160 mm Hg (20%), and its prevalence decreased in the lower BP groups (7%). The prevalence of diastolic OH (1 min) was more prevalent in the participants whose SBP was o120 mm Hg (18%) in a sitting position, and it decreased in the higher BP groups (6%). Figure 1 Changes in BP after postural changes in all elderly participants (n ¼ 653). BP, blood pressure. Prevalence of orthostatic hypotension Orthostatic hypotension was found in 34% (14% after 1 min only, 4% after 3 min only and 16% both at 1 and 3 min) of this elderly population. The prevalence of only systolic OH was 23% and only diastolic OH 4% and both systolic and diastolic OH 7%. OH was equally common in men and women. The OH criteria were fulfilled by 31% of the persons aged years, 35% of those aged years and 40% of those aged 85 years or older (P ¼ 0.15, age as a continuous variable, P ¼ 0.09). Only the Orthostatic hypotension and the use of medicines The association between the prevalence of OH and the number of regularly used medicines was statistically significant (Po0.05, Table 3). The more medicines there were in regular use, the more common was OH. OH was not associated with the number of irregularly used medicines or total medication. Further analysis showed that OH was not associated with the number of BP-lowering medicines in use or the number of drugs that traditionally have been associated with OH. Neither any particular antihypertensive nor causative medicine was associated with OH. Orthostatic hypotension and heart rate In the orthostatic test, after 1 min of standing, 64% of the participants had no change in their heart rate, 27% showed an increase and 9% showed a decrease in heart rate. After 3 min of standing, the respective proportions were almost identical 66, 25 and 9%. After 1 min of standing, the increases in heart rates between OH-positive and OH-negative

4 Postural changes in blood pressure and orthostatic hypotension 36 Table 2 Prevalence of different types of OH and mean blood pressure drops (mm Hg) by systolic blood pressure in sitting position (n ¼ 653) Type of OH reaction Systolic blood pressure in sitting position (mm Hg) o120 n ¼ n ¼ n ¼ 239 X160 n ¼ 179 Total n ¼ 653 Any OH reaction, n (%) 18 (32) 66 (37) 75 (31) 61 (34) 220 (34) Systolic OH 1 min, n (%) 14 (25) 52 (29) 62 (26) 43 (24) 171 (26) Mean drop (range) 9.5 (15, 35) 9.5 (35, 55) 9.3 (25, 50) 8.1 (33, 50) 9.0 (35, 55) Systolic OH 3 min, n (%) 4 (7) 27 (15) 46 (19) 35 (20) 112 (17) Mean drop (range) 4.4 (20, 25) 5.9 (20, 40) 6.6 (33, 50) 6.6 (30, 45) 6.2 (33, 50) Diastolic OH 1 min, n (%) 10 (18) 23 (13) 14 (6) 11 (6) 58 (9) Mean drop (range) 2.7 (12, 15) 1.4 (36, 15) 0.5 (16, 20) 0.1 (16, 20) 0.8 (36, 20) Diastolic OH 3 min, n (%) 2 (4) 17 (10) 11 (5) 9 (5) 39 (6) Mean drop (range) 0.4 (15, 10) 0.7(18, 16) 0.2 (13, 20) 0.6 (18, 18) 0 (18, 20) Abbreviation: OH, orthostatic hypotension. Table 3 Use of medications and mean numbers (95% CI) of used medicines according to the presence of OH (n ¼ 653) Medical groups (ATC code) OH-positive n ¼ 220 (%) OH-negative n ¼ 433 (%) Total n ¼ 653 (%) P-value a Diuretics (C03) 69 (31) 107 (25) 176 (27) b-blocking agents (C07) 114 (52) 218 (50) 332 (51) Calcium channel blockers (C08) 57 (26) 112 (26) 169 (26) Agents acting on renin angiotensin 69 (31) 159 (37) 228 (35) system (C09) Organic nitrates (C01DA) 59 (27) 116 (27) 175 (27) a-blockers (G04CA) 13 (6) 16 (4) 29 (4) Drugs for Parkinson s disease (N04B) 7 (3) 5 (1) 12 (2) Antipsychotics (N05A) 11 (5) 23 (5) 34 (5) Tricyclic antidepressants (N06AA) 6 (3) 3 (1) 9 (1) Causative medication b 1 70 (44) 123 (44) 193 (44) 2 62 (39) 104 (37) 166 (37) 3 or more medicines 29 (18) 56 (20) 85 (19) Mean (95% CI) 1.31 ( ) 1.17 ( ) 1.22 ( ) Antihypertensives c 1 71 (32) 143 (33) 214 (33) 2 62 (28) 121 (28) 183 (28) 3 or more medicines 36 (17) 70 (16) 106 (16) Mean (95% CI) 1.43 ( ) 1.39 ( ) 1.41 ( ) Regularly used medicines Mean (95% CI) 5.03 ( ) 4.59 ( ) 4.74 ( ) Irregularly used medication Mean (95%) 1.27 ( ) 1.27 ( ) 1.27 ( ) Total medication Mean (95%) 6.30 ( ) 5.86 ( ) 6.01 ( ) Abbreviations: ATC, Anatomic Therapeutic Chemical classification system; CI, confidence interval; OH, orthostatic hypotension. a From the w 2 test (stratified variables) or Mann Whitney U-test (continuous variables). b Causative medication (regular use): antihypertensive, organic nitrates, a-blockers, drugs for Parkinson s disease, antipsychotics and tricyclic antidepressants. c Antihypertensives: diuretic, b-blocking agents, calcium channel blockers and agents acting on renin angiotensin system. participants were not statistically significant (31 vs 24%, P ¼ 0.121). The increase in heart rate was o10 beats per minute in 71% of OH-positive and in 80% of OH-negative participants. In the rest of the participants, the increase in heart rate varied between 10 and 20 beats per minute. Similar results were obtained at 3 min. Pulse pressure was significantly higher in the OH-positive participants than in the OH-negative participants in a supine position (Po0.001), after 1 min of standing (Po0.001) and after 3 min of standing (P ¼ 0.011). The decrease in pulse pressure was more pronounced in the OH-positive than in the OH-negative persons after rising from a supine to a

5 Postural changes in blood pressure and orthostatic hypotension Table 4 Mean pulse pressures in OH-positive and OH-negative participants and changes in pulse pressure during the upright postural changes (mm Hg) 37 OH-positive (n ¼ 218) OH-negative (n ¼ 433) P-value a Supine position o0.001 Sitting position Standing position 1 min o0.001 Standing position 3 min Decrease in pulse pressure from supine 18 3 o0.001 to standing position after 1 min Decrease in pulse pressure from supine to standing position after 3 min 14 2 o0.001 Abbreviation: OH, orthostatic hypotension. a From a T-test. standing position after 1 (Po0.001) and 3 min of standing (Po0.001) (Table 4). Discussion Systolic BP dropped in two-thirds of the homedwelling elderly, and every third had OH. This figure was higher than that in many previous studies. 1,2,5 Orthostatic hypotension and low BP have been found to be associated with dizziness and an increased risk of falling. 1,10,13 Moreover, only scant attention has been paid to a drop of BP too small to fulfill the criteria of orthostatic reaction. It might be that, in frail elderly persons with low BP, even a small drop in BP can be a risk factor for falling. The haemodynamic response to an orthostatic reaction involves many organs. Orthostatic challenges are responsible for blood redistribution in the lower parts of the body and for decreases in BP and cardiac output. 24 In response to that, carotid and aortic wall receptors activate the baroreflex, which reduces parasympathetic and increases sympathetic activity. These autonomic changes cause vasoconstriction, tachycardia and positive inotropy and lead to partial restoration of arterial pressure. In the present study, OH-positive participants showed an increase of heart rate slightly more often than the OH-negative persons, whereas a minority of OH-negative persons maintained their BP by increasing the heart rate. This might indicate that reflex tachycardia is secondary in preventing an orthostatic reaction even in elderly persons. In addition, the heart rate changes in both the groups were minor, less than 10 beats per minute, which might suggest baroreflex impairment. 15 In the present study, pulse pressure in a supine position was higher in OH-positive than in OHnegative subjects. This can be explained by the fact that an increased resting pulse pressure indicates stiffness of the major arteries. Still, after rising to a standing position, the decrease of pulse pressure was also more pronounced in OH-positive than in OH-negative persons. The increased pulse pressure has been associated with a risk of major cardiovascular complications and mortality. 25 However, the mean pressure is not the only factor resulting in a high cardiovascular risk in old patients. Another important finding was that OH in elderly persons is independent of BP in sitting position and that diastolic OH after 1 min of standing was found to be more prevalent in the persons with low BP in a sitting position. This finding is notable because diastolic OH after 1 min predicted cardiovascular mortality in old persons. 3 In addition, a diastolic BP drop, even when it is small enough not to fulfil the criteria of OH, after 1 min of standing up identifies the elderly persons at a high risk for myocardial infarction. 16 This might be due to the load the heart is exposed to upon rising up, and it may provoke coronary insufficiency and a decrease of stroke volume in frail elderly person. Previous studies have reported an increase in the prevalence of OH with advancing age. 1,2 This trend was not very obvious in our study population aged 75 years or older. Only the prevalence of a combination of systolic and diastolic orthostatic reactions increased significantly with advancing age. However, our population was older (mean age 81 years) than many of those previously reported, and they had multiple comorbidities and medications. There was no difference in the prevalence of OH between men and women, which is consistent with the previous studies. We found that a high number of regularly used medicines are associated with OH. Poon and Braun 9 found a relationship between OH and potentially causative medication. In our study, we did not find such an association. However, in our study population, the use of medicines was high; the range of medicines in the regular use was from 0 to 19 and the range of total medicines was from 0 to 23. In old individuals, with numerous medicines in use, it is often impossible to determine whether OH is caused by certain medicines or the underlying diseases or both. To get a proper diagnosis of OH, the methods and protocol of measuring BP should be correct. In clinical practice, the skills and knowledge of nurses are often inadequate for diagnosing OH in elderly patients. 26 In our study, the study nurses were

6 38 instructed and trained to measure BPs accurately. Our study had the limitation that OH testing was performed only once. Furthermore, the time of the day for measuring BP, meals and daily activities differed between persons, which might have influenced our results. The reliability of the collection of medication data was improved by asking the participants to bring their medicine containers and prescription forms with them for the interview, and medication information was also checked from the medical records and caregivers or family members, if needed. Orthostatic hypotension and drops in BP seem to be more common among home-dwelling elderly persons than has previously been reported. Our results suggest the need for testing OH in patients aged 75 years or older regardless of the BP levels in a sitting position. Clinicians should assess medication in persons with OH to prevent risks for falling and cardiovascular hazards. What is known about the topic K Orthostatic hypotension is a major health problem in the elderly and it affects 6 30% of home-dwelling elderly persons. 1 5 K Orthostatic hypotension is a risk factor for dizziness and falls as well for stroke, and it is associated with cardiovascular and all-cause mortality. 2,3,16 Acknowledgements We thank statistician Piia Lavikainen for her help with the statistics and research secretary Päivi Heikura for updating and managing the database. This study was supported by Social Insurance Institution of Finland and City of Kuopio. Conflict of interest None. References Postural changes in blood pressure and orthostatic hypotension What this study adds K This study reports that systolic blood pressure dropped in two-thirds of the home-dwelling elderly when they stood up from a supine to a standing position and every third had orthostatic hypotension. This figure was higher than that in many previous studies. K Pulse pressure in a supine position was higher in OHpositive than in OH-negative subjects, and after rising to a standing position, the decrease of pulse pressure was also more pronounced in OH-positive than in OH-negative persons. K High number of regularly used medicines is associated with orthostatic hypotension. 1 Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS. Orthostatic hypotension in older adults. The Cardiovascular Health Study. For the CHS collaborative research group. Hypertension 1992; 19: Masaki KH, Schatz IJ, Burchfiel CM, Sharp DS, Chiu D, Foley D et al. Orthostatic hypotension predicts mortality in elderly men: The Honolulu Heart Program. Circulation 1998; 98: Luukinen H, Koski K, Laippala P, Kivela SL. Prognosis of diastolic and systolic orthostatic hypotension in older persons. Arch Intern Med 1999; 159: Räihä I, Luutonen S, Piha J, Seppänen A, Toikka T, Sourander L. Prevalence, predisposing factors, and prognostic importance of postural hypotension. 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7 20 WHO. Guidelines for ATC Classification and DDD Assignment. WHO Collaborating Centre for Drug Statistics Methodology: Oslo, National Agency for Medicines. Classification of Medicines (ATC) and Defined Daily Doses (DDD) National Agency for Medicines: Helsinki, The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 1996; 46: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th Postural changes in blood pressure and orthostatic hypotension edn. American Psychiatric Association: Washington, DC, Boddaert J, Tamim H, Verny M, Belmin J. Arterial stiffness is associated with orthostatic hypotension in elderly subjects with history of falls. J Am Geriatr Soc 2004; 52: Blacher J, Staessen JA, Girerd X, Gasowski J, Thijs L, Wang JG et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch Intern Med 2000; 160: Vloet LC, Smits R, Frederiks CM, Hoefnagels WH, Jansen RW. Evaluation of skills and knowledge on orthostatic blood pressure measurements in elderly patients. Age Ageing 2002; 31: