jfa journal

AND option

OR option

MUSCLE LOSS IS ASSOCIATED WITH RISK OF ORTHOSTATIC HYPOTENSION IN OLDER MEN AND WOMEN

 

M.J. Benton, A.L. Silva-Smith, J.M. Spicher

University of Colorado Colorado Springs, Colorado Springs, CO, USA.
Corresponding author: Melissa J. Benton, PhD, RN, Helen & Arthur E. Johnson Beth-El College of Nursing & Health Sciences, University of Colorado Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, phone: +1-719-255-4140, email: mbenton@uccs.edu

J Frailty Aging 2020;in press
Published online December 23, 2020, http://dx.doi.org/10.14283/jfa.2020.72


Abstract

Background: Muscle provides a reservoir for water to maintain fluid volume and blood pressure, so older adults may be at risk for orthostatic hypotension due to muscle loss with age. Objectives: To evaluate the association between muscle loss with age and postural blood pressure. Design: Longitudinal comparison of overnight changes in hydration, postural blood pressure, and strength. Setting: Community field study. Participants: Sixty-nine men and women (76.0 ± 0.8 years) with low (Low) or normal (Normal) muscle based on the Lean Mass Index. Measurements: Body composition was measured with bioelectrical impedance analysis. Postural blood pressure was measured sequentially (lying, sitting, standing). Strength was measured with a handgrip dynamometer, Arm Curl test, and Chair Stand test. Results: On Day 1, Low had less hydration and a significant drop in postural systolic blood pressure compared to Normal (lying to standing: -11.06 ± 2.36 vs. +1.14 ± 2.20 mmHg, p < 0.001). Overnight, both groups lost significant total body water, while fluid volume was unchanged. On Day 2, both groups experienced significant drops in postural systolic blood pressure, although the drop in Low was more profound and significantly greater than Normal (lying to standing: -16.85 ± 2.50 vs. -3.89 ± 2.52 mmHg, p = 0.001). On both days, Normal compensated for postural changes with increases in postural diastolic blood pressure not observed in Low. Only Low experienced significant overnight decreases in all strength measures. Conclusions: In older men and women, muscle loss with age is accompanied by loss of hydration and less stable early morning postural systolic blood pressure that increase risk for orthostatic hypotension and can also increase risk for falls.

Key words: Orthostatic hypotension, postural blood pressure, lean mass index, hydration, strength.


 

Introduction

Orthostatic hypotension (OH) increases risk for cognitive impairment, disability, and mortality (1-4). Generally, among older adults, the prevalence of OH is greater than 20% (5). However, among those with a history of falls, prevalence can exceed 50% (6). Finally, frailty and OH are associated, and among frail older adults, prevalence can be as high as 66% (4).
The criteria for OH are a decrease in postural systolic blood pressure of ≥ 20 mmHg or a decrease in postural diastolic blood pressure of ≥ 10 mmHg within three minutes of standing (7). Older adults who meet this criteria have been found to be weaker, slower, and have diminished physical function compared to those without OH (8). Notably, these characteristics are diagnostic of frailty (9), and related to sarcopenia or muscle loss with age (10).
Muscle provides a reservoir for water to maintain fluid volume and blood pressure (11), so older adults with low muscle mass may be at risk for OH, especially when oral intake is diminished, such as the overnight period. We previously demonstrated that older women with less muscle mass also have less total body water and intramuscular water compared to those with greater muscle mass, and these differences are reflected by more unstable systolic and diastolic postural blood pressure that meets the criteria for OH (12). By comparison, men have greater muscle mass, experience less loss with age, and have a lower prevalence of OH (2, 13). Nonetheless, men are at risk for OH and to our knowledge, the association between muscle, hydration, and postural blood pressure has not yet been evaluated among older men. Therefore, the objective of this study was to answer the question: Is muscle loss with age associated with risk of OH in both older men and women? To do so, we compared overnight changes in hydration, postural blood pressure, and strength in community-dwelling older men and women.

 

Methods

Participants

Men and women were recruited who were age 65 years or older, non-smokers, able to stand up independently, and able to ambulate independently or with an assistive device such as a cane or walker. Because our variable of interest was hydration, participants were excluded if they were currently using diuretic medications, or had any condition that could influence hydration including fever, nausea, vomiting or diarrhea; hemodialysis or peritoneal dialysis; or had been hospitalized within the last month.

Ethics

The university Institutional Review Board approved the study and all participants gave written informed consent prior to enrollment.

Design

Participants completed two identical measurement sessions in their own homes on consecutive days. Baseline (Day 1) measurements were completed in a euhydrated state (normal food and fluid intake) between 10:00 am – 4:00 pm when older adults are most well hydrated based on their 24-hour fluid consumption patterns (14). The second (Day 2) measurement session was completed the next morning, within 30 minutes of waking with participants in a fasted state (no food or fluids for at least 8 hours). All data were collected by the same researcher.

Measurements

Lean mass and hydration were measured using multifrequency bioelectrical impedance analysis (Quadscan 4000, Bodystat, UK). Participants remained supine for at least 5 minutes prior to measurement. Bioelectrical impedance analysis is valid, reliable, and accurate despite hydration status (15).
Postural blood pressure was measured using a digital blood pressure monitor (Omron Healthcare, Japan). Three sequential measurements were taken (lying, sitting, standing). The initial (lying) measurement was taken after completion of lean mass and hydration measurement, so participants had been resting for at least 5 minutes. The second (sitting) measurement was taken 1 minute after sitting upright with both feet flat on the floor. The third (standing) measurement was taken 1 minute after standing erect.
Handgrip strength was measured to the nearest 0.1 kg using a digital grip dynamometer (Takei Scientific Instruments, Japan). Participants sat with the device in their dominant hand, their arm supported on a stable surface, their wrist in a neutral position, and their elbow at a 90° angle. They squeezed the device one time as hard as possible for 3 seconds. Handgrip strength has been validated using manual upper extremity muscle strength testing as the criterion measure (16), and reliability has been established in multiple studies with intra-class correlation coefficients exceeding 0.80 (17). Moreover, handgrip dynamometry has strong predictive validity for cognitive, physical, and functional decline in older adults (18).
Upper and lower body strength was measured using the Arm Curl and Chair Stand tests. For the Arm Curl, participants sat with a 5-lb (women) or 8-lb (men) dumbbell in their dominant hand. They repeatedly raised and lowered it through a full range of motion for 30 seconds. For the Chair Stand test, participants remained seated with both arms folded across their chest. They repeatedly stood up to a fully erect position and sat down again for 30 seconds. Criterion validity for the 30-second Arm Curl and Chair Stand tests has been determined using laboratory measurement of maximal upper and lower body strength (chest and leg press), and test-retest reliability has been well established with intra-class correlation coefficients exceeding 0.80 (19-21).

Grouping for Analysis

Participants were grouped by lean mass relative to height (kg/m2) using the Lean Mass Index (LMI). Low muscle mass (Low) was defined as women <15.0 kg/m2 and men <19.0 kg/m2, and normal muscle mass (Normal) was defined as women ≥15.0 kg/m2 and men ≥19.0 kg/m2, 22).

Statistical Analysis

Data were analyzed using SPSS version 25 (IBM, USA). Analysis of variance (ANOVA) was used to identify individual between-group differences, and repeated measures ANOVA was used to evaluate between and within-group differences over time (Day 1 vs. Day 2 measurements). An additional multivariate analysis using age as a covariate was conducted to assess the influence of age on postural blood pressure changes. Chi-square analysis was used to evaluate between-group differences in gender, and Spearman correlation analysis was used to evaluate the influence of gender on postural blood pressure changes. Significance was determined as p < 0.05 and data were reported as mean ± standard error with 95% confidence intervals. Effect sizes were calculated as eta squared (η2) and interpreted as small (≥ 0.01), medium (≥ 0.06), and large (≥ 0.14) effects. Sample size calculation determined that 64 participants were adequate for a two-group ANOVA with a significance level of 0.05, 80% power, and a medium effect size.

 

Results

Sixty-nine men (n = 37) and women (n = 32) completed the study. Overall, they were 76 ± 0.8 years of age with an average body mass index (BMI) of 26.0 ± 0.5 kg/m2 (Table 1). There were no differences between genders for age, BMI, or resting (lying) blood pressure, and correlation analysis identified no influence of gender on postural blood pressure changes, so men and women were combined for analysis based on LMI. In total, 34 participants met the criteria for Low muscle mass. Nineteen (55%) were males and 15 (45%) were females.

Table 1
Participant characteristics at baseline (Day 1)

Note: Data reported as Mean ± SE, [95% CI], (η2) = effect size (eta squared); Low = Low muscle group; Normal = Normal muscle group; M = Male; F = Female; *Between-group differences in co-morbidities calculated using Fisher’s Exact Test.

At baseline (Day 1), participants in the Low group were significantly older, with lower body mass and BMI. They also had less lean mass that was accompanied by significantly less total body water, fluid volume, and intramuscular water. Although resting systolic blood pressure did not differ between groups, those in the Low group had significantly lower resting diastolic blood pressure, as well as significantly lower systolic and diastolic blood pressure when repositioned to sitting and standing postures (Table 1). In addition, during postural changes the Low group experienced a significant decrease in systolic blood pressure compared to the Normal group, which remained relatively stable (lying to standing: -11.06 ± 2.36 vs. +1.14 ± 2.20 mmHg, p < 0.001, η2 = 0.18) (Figure 1A). At the same time, a difference in diastolic blood pressure was observed. Specifically, the Normal group compensated for postural changes by increasing diastolic blood pressure, while the Low group did not (lying to standing: +5.14 ± 1.38 mmHg vs. +0.56 ± 1.49 mmHg; p = 0.027, η2 = 0.07). When age was included as a covariate, between-group differences in postural systolic blood pressure were somewhat attenuated (adjusted p = 0.003), while between-group differences in postural diastolic blood pressure were no longer significant.

Figure 1
Postural blood pressure changes on Day 1 (A) when participants were normally hydrated and Day 2 (B) when participants had fasted overnight. On both days, participants with low muscle had significant drops in systolic BP (Day 1: -11.06 ± 2.36 mmHg, p < 0.001; Day 2: -16.85 ± 2.50 mmHg, p < 0.001) that were not observed in those with normal muscle (Day1: +1.14 ± 2.20 mmHg; Day 2: -3.89 ± 2.52 mmHg). In contrast, participants in the normal muscle group compensated for postural changes with increases in diastolic BP (Day 1: +5.14 ± 1.38 mmHg, p = 0.027; Day 2: +5.37 ± 1.17 mmHg, p = 0.009) that were not observed in the low muscle group (Day 1: +0.56 ± 1.49 mmHg; Day 2: -0.03 ± 1.67 mmHg)

 

Overnight, both groups lost significant but similar amounts of total body water (p < 0.001), although only the Normal group lost significant amounts of intramuscular water (p = 0.038). Fluid volume remained stable in both groups (Table 2, Figure 2). This change in hydration was manifested as significant (p < 0.001) overnight decreases in both body mass (Low: -0.85 ± 0.07 kg; Normal: -0.97 ± 0.26 kg) and lean mass (Low: -1.08 ± 0.13 kg; Normal: -1.09 ± 0.16 kg). However, there were no between-group differences in any of these overnight changes. By comparison, significant between and within-group differences were observed in postural blood pressure (Figure 1B). On Day 2, systolic blood pressure decreased significantly (p < 0.001) during postural changes from lying to standing in both groups. However, the decrease in the Low group was even more profound than on Day 1 and significantly greater than that observed in the Normal group (lying to standing: -16.85 ± 2.50 vs. -3.89 ± 2.52 mmHg, p = 0.001, η2 = 0.18). Furthermore, as was observed on Day 1, the Normal group again compensated for postural changes with an increase in diastolic blood pressure that was significantly greater than the Low group that again remained stable (lying to standing: +5.37 ± 1.17 vs. -0.03 ± 1.67 mmHg, p = 0.009, η2 = 0.17). When age was included as a covariate, between-group differences in postural blood pressure were again somewhat attenuated (systolic blood pressure: adjusted p = 0.004; diastolic blood pressure: adjusted p = 0.040). Overall, on Day 2, 44.1% (n = 15) of the Low group met the criteria for OH (decrease in postural systolic blood pressure of ≥ 20 mmHg or decrease in postural diastolic blood pressure of ≥ 10 mmHg) compared to only 8.6% (n = 3) of the Normal group (p = 0.001).

Table 2
Overnight changes in mass, hydration, and strength in participants with Low and Normal muscle

Note: Data reported as Mean ± SE, [95% CI], (η2) = effect size (eta squared); Low = Low muscle group; Normal = Normal muscle group

Significant overnight changes in strength that favored older adults in the Normal group also occurred. On Day 1, handgrip strength was similar between groups (Low: 24.5 ± 1.6 kg; Normal: 22.5 ± 1.6 kg) (Table 1). Overnight, a significant between-group difference was observed (Table 2). Participants in the Low group experienced a significant decrease in handgrip strength (-2.42 ± 0.48 kg; p = 0.001) that was not observed in the Normal group (-0.76 ± 0.77 kg). A similar pattern was also observed in lower body strength. For lower body strength measured as the Chair Stand test, both groups were initially similar (Low: 11.6 ± 0.8 repetitions; Normal: 10.6 ± 0.7 repetitions). Overnight, a significant decrease in lower body strength was observed in the Low group (-1.42 ± 0.41 repetitions, p = 0.001) that was not observed in the Normal group (-0.43 ± 0.22 repetitions), and that resulted in a statistically significant difference between groups (p = 0.034). Finally, Arm Curl scores were initially similar between groups (Low: 14.5 ± 0.5 repetitions; Normal: 14.8 ± 0.8 repetitions). Overnight, a significant decrease was observed in both groups (Low: -2.67 ± 0.40 repetitions; p < 0.001; Normal: -0.91 ± 0.37 repetitions, p = 0.017), although the decrease in the Low group was statistically greater than that observed in the Normal group (p = 0.002).

Figure 2
Overnight changes in hydration between participants with Low and Normal muscle. Both groups lost similar and significant amounts of total body waster (p < 0.001), while only the Normal group lost significant amounts of intramuscular water (p = 0.038). Fluid volume remained stable in both groups

 

Discussion

To our knowledge, this is the first study to evaluate postural blood pressure changes in men and women using muscle as the criterion for evaluation. Based on our findings, muscle loss with age is associated with risk for OH in both men and women. Although the average drop in postural systolic blood pressure of 17 mmHg that we observed in participants with low muscle mass was less than the ≥ 20 mmHg decrease needed to meet the definition of OH, the differences between older men and women with low compared to normal muscle mass were statistically significant with large effect sizes. Hence, we believe our findings reflect a clear association with muscle loss, especially as we found a statistically greater prevalence of participants that met the diagnostic criteria for OH among participants with low muscle mass (44.1%) compared to those with normal muscle mass (8.6%). Furthermore, we found no relationship with gender, indicating that both men and women are equally susceptible despite differences in absolute and relative lean mass.
Poor nutrition, which increases the risk for muscle loss and frailty in older adults, has previously been found to be associated with OH (23). This is consistent with the differences in body composition observed among our participants, in which those with low muscle were also observed to have significantly less fat and an overall lower BMI compared to those with normal muscle. Some previous research has demonstrated a negative association between BMI and OH, such that older adults with OH had lower BMI levels than those without OH (4, 24). However, average BMI values were in the overweight category and in one study, differences were not statistically significant (4). The association between OH and BMI is not clear. In other previous reports of normal (25) and overweight (2) older adults with and without OH, there were no differences based on BMI. Furthermore, in a comparison of OH prevalence among robust, pre-frail, and frail older adults, the prevalence of OH and participant age increased significantly with level of frailty, but there was no difference in BMI, which was in the overweight category for all participants (26). We believe the link between frailty and OH may lie in the influence of lean (muscle) mass. This is a gap in the literature and should be explored.
In addition to greater instability in postural blood pressure, participants with low muscle experienced greater overnight losses of strength compared to those with normal muscle. When loss of strength, especially in the lower body, is accompanied by severe early morning drops in postural blood pressure, this increases risk for falls in the early morning when between 30 to 50% of falls are reported to occur (27). Falls are of concern among older adults with OH, who have a greater than 50% higher risk of a first fall than older adults without OH (28). Treatment of OH is frequently driven by concerns regarding potential injuries due to falls. Unfortunately, first line treatment often focuses on medication reduction, including cardiovascular medications such as antihypertensives (29). This creates a burden for patients who must choose between the risks associated with OH and potential risks associated with discontinuance of medications. Cardiovascular medications optimize blood pressure control and reduce the risk of stroke, myocardial infarction, renal dysfunction, and complications of diabetes (30). Furthermore, abrupt discontinuation of blood pressure-lowering medications, can place patients at risk for an acute stroke or cardiovascular event (31). Non-pharmacological strategies for management of OH are available, but evidence indicates that they are minimally effective (32), and not generally acceptable to older adults with OH (33).
Increasing muscle mass may represent a novel strategy for OH that has not previously been considered. Although frailty is associated with OH (4), we can find no studies in which body composition has been included in the assessment of older adults with OH. Nonetheless, decreased fluid volume and deconditioning are recognized factors in the etiology of OH (34). Muscle, as a repository for body fluids, enhances fluid volume. As observed in our participants, those with greater muscle had significantly greater reserves of water. Furthermore, there was a non-selective loss of fluid overnight of approximately one liter that did not differ between those with low and normal muscle mass. This non-selective fluid loss is consistent with what we previously observed in older women (12). Our interpretation is that individuals with limited fluid reserves due to reduced amounts of muscle cannot compensate for fluids losses during periods of low intake. Hence, in our study, when muscle tissue apparently “donated” intramuscular water to maintain overall fluid volume during the overnight period, those with low muscle mass were seen to be at greater risk for unstable postural blood pressure and loss of strength compared to those with greater muscle mass and the fluid reserves that accompany it.
Resistance training may represent a feasible non-pharmacologic approach to blood pressure management in the context of OH. However, evidence is limited. We identified only one resistance training program for patients with OH by Zion and colleagues (35), and it did not successfully improve blood pressure. However, the duration was only 8 weeks and elastic bands were used for training. While elastic bands can provide adequate resistance to stimulate muscle hypertrophy, their use in research has been limited. Krause and colleagues reported use of elastic bands to increase muscle mass in healthy older adults, but the training program was 12 weeks long and all training was supervised (36). Unfortunately, Zion and colleagues did not measure body composition (35), but it seems likely that their shorter, unsupervised program was not sufficient to increase muscle mass and therefore had no effect on blood pressure. Evidently, more research is needed.
We recognize that the fact that we did not control for medications other than diuretics may be considered a study weakness. However, we also recognize that use of medications is increasing, especially use of multiple medications. In the United States, approximately 90% of older adults report use of at least one medication, while approximately 40% report polypharmacy (use of 5 or more medications) (37, 38). For the current study, we used a pragmatic approach with the intent of evaluating older adults under real-world conditions in their own homes, and those conditions include use of regularly prescribed medications. Furthermore, previous research demonstrates that medications do not have a significant influence on OH (39, 40). In older men and women no association has been found between OH and either the number or type of medications, including antihypertensives, diuretics, antipsychotics, antidepressants, and drugs for Parkinson’s disease (39, 40). Nonetheless, there are numerous other types of medications that may influence OH that have not been evaluated.
In conclusion, our findings support a role for muscle in maintaining stable postural blood pressure and decreasing risk for OH. Although more research is evidently needed, in these older adults, muscle loss with age was accompanied by loss of hydration and less stable early morning systolic blood pressure that may increase risk for falls. Resistance exercise to increase muscle mass may provide a novel therapeutic strategy that should be explored.

Acknowledgements: The authors thank Andrew Quinonez for assistance with graphic design to format the figures for publication.
Funding: No funding was received for this study.
Conflicts of Interest: All authors declare no conflict of interest.
 

References

1. Iseli R, Nguyen VTV, Sharmin S, Reijnierse EM, Lim WK, and Maier AB, Orthostatic hypotension and cognition in older adults: A systematic review and meta-analysis. Exp Gerontol 2019;120:40-49.
2. Suemoto CK, Baena CP, Mill JG, Santos IS, Lotufo PA, and Bensenor I, Orthostatic Hypotension and Cognitive Function: Cross-sectional Results From the ELSA-Brasil Study. J Gerontol A Biol Sci Med Sci 2019;74:358-365.
3. Shaw BH, Borrel D, Sabbaghan K, et al., Relationships between orthostatic hypotension, frailty, falling and mortality in elderly care home residents. BMC Geriatr 2019;19:80.
4. Liguori I, Russo G, Coscia V, et al., Orthostatic Hypotension in the Elderly: A Marker of Clinical Frailty? J Am Med Dir Assoc 2018;19:779-785.
5. Saedon NI, Pin Tan M, and Frith J, The Prevalence of Orthostatic Hypotension: A Systematic Review and Meta-Analysis. J Gerontol A Biol Sci Med Sci 2020;75:117-122.
6. McDonald C, Pearce M, Kerr SR, and Newton J, A prospective study of the association between orthostatic hypotension and falls: definition matters. Age Ageing 2017;46:439-445.
7. Freeman R, Wieling W, Axelrod FB, et al., Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011;21:69-72.
8. Mol A, Reijnierse EM, Bui Hoang PTS, van Wezel RJA, Meskers CGM, and Maier AB, Orthostatic hypotension and physical functioning in older adults: A systematic review and meta-analysis. Ageing Res Rev 2018;48:122-144.
9. Fried LP, Tangen CM, Walston J, et al., Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-56.
10. Batsis JA, Mackenzie TA, Lopez-Jimenez F, and Bartels SJ, Sarcopenia, sarcopenic obesity, and functional impairments in older adults: National Health and Nutrition Examination Surveys 1999-2004. Nutr Res 2015;35:1031-9.
11. Lundvall J and Lanne T, Large capacity in man for effective plasma volume control in hypovolaemia via fluid transfer from tissue to blood. Acta Physiol Scand 1989;137:513-20.
12. Benton MJ and Schlairet MC, Lean mass influences overnight changes in hydration, blood pressure and strength in community-dwelling older women. Blood Press 2016;25:269-75.
13. Chumlea WC, Guo SS, Kuczmarski RJ, et al., Body composition estimates from NHANES III bioelectrical impedance data. Int J Obes Relat Metab Disord 2002;26:1596-609.
14. de Castro JM, Age-related changes in natural spontaneous fluid ingestion and thirst in humans. J Gerontol 1992;47:P321-30.
15. Shanholtzer BA and Patterson SM, Use of bioelectrical impedance in hydration status assessment: reliability of a new tool in psychophysiology research. Int J Psychophysiol 2003;49:217-26.
16. Bohannon RW, Hand-grip dynamometry provides a valid indication of upper extremity strength impairment in home care patients. J Hand Ther 1998;11:258-60.
17. Bohannon RW, Test-Retest Reliability of Measurements of Hand-Grip Strength Obtained by Dynamometry from Older Adults: A Systematic Review of Research in the PubMed Database. J Frailty Aging 2017;6:83-87.
18. Rijk JM, Roos PR, Deckx L, van den Akker M, and Buntinx F, Prognostic value of handgrip strength in people aged 60 years and older: A systematic review and meta-analysis. Geriatr Gerontol Int 2016;16:5-20.
19. Rikli RE and Jones CJ, Development and validation of a functional fitness test for community-residing older adults. Journal of Aging and Physical Activity 1999;7:127-159.
20. Benton MJ and Alexander JL, Validation of functional fitness tests as surrogates for strength measurement in frail, older adults with chronic obstructive pulmonary disease. Am J Phys Med Rehabil 2009;88:579-83; quiz 584-6, 590.
21. Rikli RE and Jones CJ, Development and validation of criterion-referenced clinically relevant fitness standards for maintaining physical independence in later years. Gerontologist 2013;53:255-67.
22. Schutz Y, Kyle UU, and Pichard C, Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y. Int J Obes Relat Metab Disord 2002;26:953-60.
23. Kocyigit SE, Soysal P, Ates Bulut E, and Isik AT, Malnutrition and Malnutrition Risk Can Be Associated with Systolic Orthostatic Hypotension in Older Adults. J Nutr Health Aging 2018;22:928-933.
24. Applegate WB, Davis BR, Black HR, Smith WM, Miller ST, and Burlando AJ, Prevalence of postural hypotension at baseline in the Systolic Hypertension in the Elderly Program (SHEP) cohort. J Am Geriatr Soc 1991;39:1057-64.
25. Chen L, Xu Y, Chen XJ, Lee WJ, and Chen LK, Association between Orthostatic Hypotension and Frailty in Hospitalized Older Patients: a Geriatric Syndrome More Than a Cardiovascular Condition. J Nutr Health Aging 2019;23:318-322.
26. Kocyigit SE, Soysal P, Bulut EA, Aydin AE, Dokuzlar O, and Isik AT, What is the relationship between frailty and orthostatic hypotension in older adults? J Geriatr Cardiol 2019;16:272-279.
27. Lopez-Soto PJ, Smolensky MH, Sackett-Lundeen LL, et al., Temporal Patterns of In-Hospital Falls of Elderly Patients. Nurs Res 2016;65:435-445.
28. Hartog LC, Schrijnders D, Landman GWD, et al., Is orthostatic hypotension related to falling? A meta-analysis of individual patient data of prospective observational studies. Age Ageing 2017;46:568-575.
29. Shibao C, Lipsitz LA, Biaggioni I, and American Society of Hypertension Writing G, Evaluation and treatment of orthostatic hypotension. J Am Soc Hypertens 2013;7:317-24.
30. Arnett DK, Blumenthal RS, Albert MA, et al., 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation 2019:CIR0000000000000678.
31. Karachalios GN, Charalabopoulos A, Papalimneou V, et al., Withdrawal syndrome following cessation of antihypertensive drug therapy. Int J Clin Pract 2005;59:562-70.
32. Newton JL and Frith J, The efficacy of nonpharmacologic intervention for orthostatic hypotension associated with aging. Neurology 2018;91:e652-e656.
33. Robinson LJ, Pearce RM, and Frith J, Acceptability of non-drug therapies in older people with orthostatic hypotension: a qualitative study. BMC Geriatr 2018;18:315.
34. Tzur I, Izhakian S, and Gorelik O, Orthostatic hypotension: definition, classification and evaluation. Blood Press 2019;28:146-156.
35. Zion AS, De Meersman R, Diamond BE, and Bloomfield DM, A home-based resistance-training program using elastic bands for elderly patients with orthostatic hypotension. Clin Auton Res 2003;13:286-92.
36. Krause M, Crognale D, Cogan K, et al., The effects of a combined bodyweight-based and elastic bands resistance training, with or without protein supplementation, on muscle mass, signaling and heat shock response in healthy older people. Exp Gerontol 2019;115:104-113.
37. Kantor ED, Rehm CD, Haas JS, Chan AT, and Giovannucci EL, Trends in Prescription Drug Use Among Adults in the United States From 1999-2012. JAMA 2015;314:1818-31.
38. Oktora MP, Denig P, Bos JHJ, Schuiling-Veninga CCM, and Hak E, Trends in polypharmacy and dispensed drugs among adults in the Netherlands as compared to the United States. PLoS One 2019;14:e0214240.
39. Jodaitis L, Vaillant F, Snacken M, et al., Orthostatic hypotension and associated conditions in geriatric inpatients. Acta Clin Belg 2015;70:251-8.
40. Luukkonen A, Tiihonen M, Rissanen T, Hartikainen S, and Nykanen I, Orthostatic Hypotension and Associated Factors among Home Care Clients Aged 75 Years or Older – A Population-Based Study. J Nutr Health Aging 2018;22:154-158.