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Alcohol and psychotropic drugs: risk factors for orthostatic hypotension in elderly fallers

Journal of Human Hypertension volume 31, pages 299–304 (2017)Cite this article

Subjects

Abstract

We assess orthostatic hypotension (OH) prevalence in elderly fallers and determine OH-associated risk factors in this patient population. A monocentric prospective study at Lille University Hospital Falls Clinic included 833 consecutive patients who had fallen or were at high risk of falls and who were assessed for the presence of OH. Among 833 patients aged 80.4±7.4 years, OH was found in 199 subjects (23.9% of cases). Multivariate analysis showed that selective serotonin reuptake inhibitors (odds ratio (OR) 2.42, 95% confidence interval (CI): 1.56–3.75), serotonin-norepinephrine reuptake inhibitors (OR 5.37, 95% CI: 1.93–14.97), Parkinsonian syndrome (OR 2.54, 95% CI: 1.54–4.19), excessive alcohol consumption (OR 2.17, 95% CI: 1.32–3.56), meprobamate (OR 2.65, 95% CI: 1.12–6.25) and calcium channel blockers (OR 1.79, 95% CI: 1.16–2.76) were all risk factors for OH. In contrast, angiotensin receptor blockers (OR 0.52, 95% CI: 0.30–0.91) appeared to be protective factors against OH. This study demonstrates that a systematic investigation should be made in all elderly fallers and those at high risk of falls to detect the presence of OH. In OH patients, in addition to the usual predisposing factors, excessive alcohol consumption and psychotropic drug intake—in particular, the intake of serotonergic antidepressants—should be taken into account as potential risk factors.

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Introduction

Falls are the fifth most common cause of death in elderly subjects1 and, in persons aged over 65 years, are the primary cause of accidental death in France.2 Each year, one-third of the elderly population living at home and 50% of institutionalized elderly persons suffer from falls.1 In this older age group, the risk factors for falls are frequently numerous, and the risk of falling increases in proportion to the number of risk factors involved.3, 4 Orthostatic hypotension (OH) has been reported in the literature as constituting one of the main risk factors for falls,3, 4 although this observation has recently been questioned.5 The primary objective of the present study was therefore to assess the prevalence of OH in an elderly fall population. The secondary objectives were to determine the risk factors associated with OH and to evaluate the respective cases at 6 months of follow-up.

Patients and methods

Subjects

Eight hundred and thirty-three out of the 884 patients who had consecutively attended the Lille University Hospital Falls Clinic between January 1996 and December 2008 and who had been examined for the presence of OH were included in the study.

Data collection

Each patient was successively examined by a multidisciplinary team consisting of a geriatrician, a neurologist and a physiotherapist.6 The examining physicians entered their observations in a prospective manner into a single standardized medical file. After this initial assessment, the staff recommended appropriate interventions: physiotherapy; feet care; medication changes; further investigations; environmental changes, including footwear; and personal alarm. A general report was compiled by the geriatrician and sent to the patient’s family physician and also to the patient if so requested. It included the intrinsic and extrinsic risk factors for falls that had been determined for each case, proposals regarding the type of functional and environmental therapy, and additional examinations. Six months later, the patient was requested to attend geriatric consultation, at which time the evolution of each case and follow-up of the various recommendations were assessed.

The following data were recorded for each patient: age and gender; weight and height; place of residence; medical history; usual treatment (number and names of drugs prescribed and drug classes); alcohol consumption when considered to be excessive on the basis of a weekly intake of over 21 units for males and 14 units for females, each glass being equal to 10 grams of pure alcohol; number of falls and circumstances under which they had taken place in the 6 months prior to consultation; the fear of falling as expressed by the patient himself or herself; the environmental risk factors (that is, the patient’s everyday living conditions) and the use or lack of use of a walking aid. Autonomy was measured using the Katz Index of Independence in activities of daily living scale. Cognitive function was assessed using Folstein’s mini-mental state examination. Patients with an mini-mental state examination score of below 25 and subjects in whom dementia had been diagnosed prior to consultation were all considered as suffering from dementia. All patients were screened for major depression. A diagnosis of depression was considered made in the presence of major depressive symptoms as defined in the diagnosis manual of mental disorders or when history of depression was reported by the patient or by his or her general practitioner. Balance disorder was defined as the presence of instability or imbalance when standing upright in a bipodal position, with feet together and eyes open or closed, or by an absence of postural reaction upon sternal pressure. A unipodal balance test (less than or more than 5 s) was also carried out. The data obtained from the clinical examination and the description of gait provided by the three examining physicians enabled the gait disorders to be classified in a retrospective manner for each patient according to the classification proposed by Alexander and Goldberg.7 Gait was also evaluated via the Timed Up-and-Go Test (less than or more than 20 s).

Measurement of Blood Pressure (BP) and definition of orthostatic hypotension

Testing for the presence of OH was systematically carried out during the consultation. After a resting time of 10 min in a lying position, one reading of supine BP was taken on the right arm, and then another was taken on the left arm. Then a third reading of the highest BP was taken on the side. This third BP was considered as the baseline value. BP and heart rate measurements were repeated after 1 and 3 min of standing. Between 1995 and 2005, upper arm BP was measured using an auscultatory method with the help of a conventional mercury sphygmomanometer. Since 2006, an aneroid sphygmomanometer or a BP monitor (DATASCOPE Duo BP Monitor, Mindray DS USA, Inc.) has been used for OH testing.

OH was defined as a drop of at least 20 mm Hg in systolic BP and/or a drop of at least 10 mm Hg in diastolic BP within 3 min of standing up.8 All patients were asked about the most common symptoms of OH (at home). It included feeling lightheaded or dizzy, blurry vision, weakness, and fainting when they stood up after sitting or lying down. Each patient was questioned about the occurrence of one or several falls directly after standing up, that is, events suggestive of OH.

Statistical analysis

The numerical variables were expressed in terms of the mean and standard deviation, and the qualitative parameters were expressed as frequencies and percentages. A comparison between the numerical variables of the OH and the non-OH subjects was made using Student’s t-test, whereas a comparison between qualitative parameters was carried out using the χ2 test or Fisher’s exact test when the cell count was less than 5. An analysis was made of the association between the detection of OH during consultation and the patient’s specific drug intake (that is, the number of drugs taken and main drug classes reported in the literature as being associated with OH).

A multivariate regression was performed to identify the determinantal factors of OH. All the variables with a significance level of less than 0.2 as determined using bivariate analysis were introduced in a logistic regression model with step-by-step selection using a bootstrap resampling method, and the results were presented in the form of an odds ratio with a confidence interval of 95%.

The statistical analyses were performed using the SAS software, version 9.2 (SAS Institute Inc., Cary, NC, USA). The level of significance was set at 5%.

Results

The average age of the 833 patients was 80.4±7.4 years; the sex ratio amounted to 2.7:1 (females/males). The mean activities of daily living score was 5.1±1.2. The characteristics of the patient population have been presented in Tables 1 and 2. The median number of falls during the 6 months preceding the consultation was 3. Eighty-six per cent of patients had fallen at least once, with the majority of subjects having fallen more than once (69% of the total population). Two out of the 833 patients examined for OH were unable to recall the number of falls experienced over the previous 6 months.

Table 1 Comparison of characteristics of the study population tested for the presence of OH
Full size table
Table 2 Characteristics of the therapeutic agents administered to the study population tested for the presence of OH
Full size table

Orthostatic hypotension

Among the 833 patients examined, 199 subjects tested positive for OH (23.9%). A higher incidence of OH was detected among males; it was more frequently found in the patients who required assistance in activities of daily living. OH was significantly more frequently diagnosed when patients reported suggestive symptoms of OH at home. Bivariate analysis (Tables 1 and 2) showed an association between OH and depression (P<0.0001), diabetes, excessive alcohol consumption and active tobacco smoking. It was also observed that parkinsonism and the intake of L-3,4-dihydroxyphenylalanine (L-DOPA) or dopaminergic agonists were associated with OH.

The number of drugs taken was found to be significantly associated with OH (P<0.0001). However, the number of antihypertensive drugs used had no influence on the development of OH. Among the antihypertensive agents, only calcium channel blockers (P=0.02) were found to be positively associated with OH, whereas angiotensin receptor blockers (ARBs) and centrally acting antihypertensive agents were negatively associated with OH. Intake of psychotropic drugs (P=0.006)—in particular, meprobamate, benzodiazepines and antidepressants—including selective serotonin reuptake inhibitors (SRIs) (P<0.0001), serotonin-norepinephrine reuptake inhibitors (P=0.002) and tricyclic antidepressants (P=0.03), was found to be positively related to OH (P<0.0001).

Multivariate analysis (Table 3) showed that ARBs antihypertensive agents appeared to constitute protective factors against OH, whereas the presence of diabetes, parkinsonism and excessive alcohol consumption and the intake of serotonergic antidepressants, meprobamate and calcium channel blockers were risk factors for OH.

Table 3 Results of multivariate analysis
Full size table

Follow-up at 6 months

Six months after the initial consultation, 536 patients out of the 833 who had been tested for the presence or absence of OH attended follow-up. The median number of falls in the 6 months following consultation amounted to zero (compared with the three initially reported). Three hundred and thirty-six patients (62.7%) had not experienced any falls during the 6-month period. For the patients presenting with OH, fall recurrence was higher than for the subjects without OH (P=0.02). However, no significant difference between these 2 groups was found at 6 months in terms of fracture events, hospitalization, institutionalization or mortality rate. These results have been presented in Table 1.

Discussion

The prevalence of OH amounted to 23.9% among these elderly fallers or subjects at risk of falls. Although not regularly taken into account as factors associated with OH, habitual and excessive consumption of alcohol (according to the WHO definition) and the intake of serotonergic antidepressant seemed to be correlated with OH in the present study population. Among the different antihypertensive agents, only calcium channel blockers were found to be associated with OH, whereas ARBs appeared to have a protective effect.

A higher incidence of OH has been observed in institutionalized subjects (around 50%) and in hospitalized short-stay geriatric patients (70%) than in community-dwelling patients (5–15%).9, 10 In the present study, the incidence of OH among relatively independent elderly subjects—either fallers or subjects at high risk of falls—who attended the multidisciplinary Falls Clinic in Lille amounted to 23.9%, whereas in the literature, the prevalence of OH among elderly fallers has been reported as ranging between 19 and 50%.11, 12, 13 It was therefore difficult to compare the present results with those in the literature, as the distinct differences in the various studies regarding the prevalence of and the risk factors associated with OH are to a large extent explained by the differences in the selected characteristics of the study population and the specific methodology adopted.14

The pathologies commonly described in the literature as associated with OH, such as parkinsonism, diabetes (although this association is not always consistently observed) and depression, were also found in the present study. Acute alcohol consumption is reported to decrease the mean arterial pressure during orthostatic challenge,15 but the association between chronic alcohol consumption and OH has been less frequently reported.16

The iatrogenic etiology of OH has often been described in elderly subjects. In the literature and again in the present study, OH has been found to be significantly associated with the number of drugs administered.17, 18 However, although a link has been reported between OH and the intake of certain types of drugs, such as class III analgesics, nitrate derivatives, or alpha-blockers for the treatment of urinary disorders, this association was not found in the present study.

The association between OH and psychotropic drug intake is well known, in particular, regarding tricyclic antidepressants,19 anxiolytics and/or sedatives.5, 20 This was also observed in the present study, although a link between OH and the use of non-benzodiazepine hypnotic agents was not found. To the best of our knowledge, unlike benzodiazepines, short-acting hypnosedatives zopiclone and zolpidem have never been reported as causes of OH. Clinically significant OH has been reported not only with tricyclic antidepressants and the older monoamine oxidase inhibitors but also with selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, although less frequently.17, 19, 21, 22 In the present study, a highly significant association between serotonergic antidepressants and OH was found. The mechanism by which SRIs may cause OH is not elucidated. However, several studies have provided evidence that fluoxetine and citalopram directly inhibit Ca2+ entry into vascular and intestinal smooth muscles, resulting in vasodilation and intestinal relaxation effects, which could play a role in postural BP regulation.19, 22 In addition to OH, SRIs also increase the risk of falling because of their potentially sedative effect and their known negative effect on the quality of sleep (insomnia and nycturia).19

Absence of an association between BP levels and OH was not an expected result. A few years ago, we highlighted, as did most of the others studies, an association between systolic BP and OH.23 But the link between hypertension and OH is complex; many comorbidities and medications can interfere with the BP level and regulation of BP. A number of diseases, including diabetes, any circulatory disease, coronary heart disease, high BP, thyroid disease, eye disease, arthritis, cancer, depression and chronic obstructive pulmonary disease, increase odds of having OH in elderly women.24 And although the mechanism of action of antihypertensive drugs may, in theory, induce OH, the data in the literature remain controversial.9 In the present study too, we did not observe any relationship between the intake of an antihypertensive treatment and the presence of OH. This result is in agreement with several previous studies.25, 26, 27 Among very old individuals living in nursing homes (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Elderly Populations—Partage study), history of hypertension, number of patients treated for hypertension and the number of antihypertensive drugs were not associated with OH. A strong correlation between OH and basal arterial BP has been reported in many studies; despite this, we didn’t confirm this result. In several studies, it has been observed that old well treated hypertensive patients had a lower risk of OH than did patients having uncontrolled hypertension.5, 25, 28 The underlying mechanisms for these observations are not known but may potentially involve baroreflex, as a decrease in baroreflex-mediated cardioacceleration and vasoconstriction has been associated with aging and hypertension, which greatly increase the risk of OH in older adults. Moreover, it has been shown that the treatment of hypertension in older adults using an angiotensin-converting enzyme inhibitor-based regimen improves cerebral blood flow.29

Only calcium channel blockers were found to be associated with OH in this study, whereas ARBs and centrally acting antihypertensive agents appeared to play a protective role against the development of OH. Although a low incidence of OH has been reported among users of centrally acting antihypertensive drugs,30 to the authors’ knowledge, no study has yet been published on the protective effect of these agents against OH. A low incidence of OH has also been observed among patients receiving valsartan and candesartan.31, 32 In the Partage study, the subjects presenting with OH had been less frequently treated with ARBs.28 Federowski et al. provide interesting data suggesting that angiotensin-converting-enzyme inhibition appeared to protect hypertensive individuals from OH.33 The potential protective effect of angiotensin-converting-enzyme inhibitors and ARBs against OH could be mediated by improved baroreflex sensitivity in elderly hypertensives on these medications, modulating the renin-angiotensin-aldosterone system, as seen with lisinopril, compared with nifedipine.34 These classes of antihypertensive drugs should therefore be considered in the treatment of elderly hypertensive patients presenting with other risk factors for OH (for example, diabetes and Parkinson’s disease).

OH is commonly viewed as a factor that increases the risk of falls. Assessment and treatment of postural hypotension are parts of recommendations issued by the French Health Authorities as well as by the American Geriatrics Society and the British Geriatrics Society35 for elderly persons who experience repeated falls. However, the findings in the literature on this subject remain controversial.9 In the present study, several arguments can be put forward in favor of such a link. For instance, it was observed that the subjects in whom OH had been detected at the time of consultation were often those who had experienced a number of falls during the 6 months prior to the study (P=0.02), and it was this group of patients that also had a higher risk of falling than non-OH patients during the 6 months following consultation. Finally, in the present study, fallers who reported symptoms of OH at home (that is, on standing upright from a decubitus position) had more often a positive OH test at the time of consultation.

A limitation could be the definition of depression used in this study. Although we didn’t use a systematically specific depression scale (like the Geriatric Depression Scale), all patients were screened for major depression. A diagnosis of depression was considered made in the presence of major depressive symptoms as defined in the Diagnosis Manual of Mental Disorders or when a history of depression was reported by the patient or by his or her general practitioner. Among the 833 patients, the geriatrician proposed introducing an antidepressant treatment for 21 patients and withdrawing an antidepressant treatment from 25 patients.

The formal ‘white coat’ may have a negative effect on certain patients—an aspect that could have also explained the relatively high average figures for Systolic BP (148 mm Hg) that were found in the present study population. It should also be mentioned that one of the drawbacks of the present study was that OH testing was only carried out once. However, the intraindividual reproducibility for the orthostatic test is relatively poor. Several studies have in fact shown that BP response during the test may vary considerably in the same patient from one day to another and even from one hour to the next.23 Thus, had the orthostatic test been repeated in the present study, the patient population characterized as having OH might have differed. Although standardized BP measurement included this resting time for, ideally, 10 min before OH testing in research studies (ours included), the OH testing in clinical daily practice did not often respect this resting time owing to the constraints of limited consultation time per patient.

Lastly, although 6 months of follow-up may be of value for the assessment of fall recurrence, it is evidently too short a period of time to examine other factors such as the risk of institutionalization or the risk of mortality.

In conclusion, the relatively high incidence of OH found in this study shows the interest of carrying out a systematic investigation for the presence or absence of OH in any fall patient or subject at risk of falling. Testing for OH may be carried out by any family physician. When investigating the etiology of OH, in addition to the ‘usual’ predisposing factors, the physician should bear in mind that habitual and excessive consumption of alcohol and the intake of antidepressants—in particular, serotonergic antidepressants—may also contribute to its development.

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Acknowledgements

The authors would like to thank the IRA Group, Lille Faculty of Medicine, for their invaluable assistance and Mrs Marilyn Schreier for reviewing the English. This study has not received any external financing.

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Affiliations

  1. Gerontology Clinic, Les Bateliers Geriatric Hospital, Lille University Hospital, Lille, France

    C Gaxatte, O Lathuillerie, M-H Destailleur, E Boulanger & F Puisieux

  2. IRA Group, Lille Faculty of Medicine, University of Lille 2, Lille, France

    E Faraj

  3. Department of Biostatistics, CHRU Lille, EA2694, Univ Lille Nord de France, Lille, France

    J Salleron

  4. Neurology Department, EA1046, University of Lille 2, Lille University Hospital, Lille, France

    V Deramecourt

  5. Rehabilitation Clinic, Les Bateliers Geriatric Hospital, Lille University Hospital, Lille, France

    V Pardessus

  6. Biology of Aging, EA2693, University of Lille 2, Lille, France

    E Boulanger

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Gaxatte, C., Faraj, E., Lathuillerie, O. et al. Alcohol and psychotropic drugs: risk factors for orthostatic hypotension in elderly fallers. J Hum Hypertens 31, 299–304 (2017). https://doi.org/10.1038/jhh.2013.82

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Keywords

  • risk factor
  • fall
  • orthostatic hypotension
  • alcohol consumption
  • serotonin reuptake inhibitor
  • antidepressant

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