Postprandial Hypotension Is Associated With More Rapid Gastric Emptying in Healthy Older Individuals

Postprandial Hypotension Is Associated With More Rapid Gastric Emptying in Healthy Older Individuals

JAMDA 16 (2015) 521e523 JAMDA journal homepage: www.jamda.com Brief Report Postprandial Hypotension Is Associated With More Rapid Gastric Emptying ...

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JAMDA 16 (2015) 521e523

JAMDA journal homepage: www.jamda.com

Brief Report

Postprandial Hypotension Is Associated With More Rapid Gastric Emptying in Healthy Older Individuals Laurence G. Trahair BHlthSci (Hons) a, b, Michael Horowitz PhD a, b, Karen L. Jones PhD a, b, * a

Discipline of Medicine, The University of Adelaide, Adelaide, South Australia National Health and Medical Research Council, Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia b

a b s t r a c t Keywords: Postprandial blood pressure hypotension gastric emptying

Background: Postprandial hypotension (PPH) occurs frequently in older individuals with disease and/or living in residential care, but its prevalence in “healthy” older individuals has not been evaluated in large cohorts. PPH is associated with substantial morbidity and increased mortality; current management is suboptimal. Recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is related to the rate of gastric emptying (GE), so that relatively more rapid GE may potentially be a risk factor for PPH. We aimed to determine the prevalence of, and evaluate the association of GE with PPH. Methods: A total of 88 healthy “older”, community-dwelling residents (47 women, 41 men; age 71.0  0.5 years) attended a clinical research laboratory on a single occasion. Individuals consumed a 300 mL drink containing 75 g glucose and 150 mg C13-acetate. Exhaled breath was obtained for analysis of 13 CO2 and calculation of the 50% GE time (T50). BP and heart rate were assessed with an automated device. Results: Eleven (12.8%) of 86 subjects had PPH (2 had diabetes and were excluded). GE was faster in subjects with PPH than the remainder of the group (T50 118.0  9.4 vs 142.3  4.6 minutes, P < .05). Conclusions: We conclude the prevalence of PPH in a cohort of otherwise healthy “older” individuals is 12.8% and PPH is associated with relatively more rapid GE. Therapies that slow GE may be useful in the management of PPH. Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

Postprandial hypotension (PPH) is a clinically important disorder, occurring frequently, predisposing to syncope and falls, and associated with increased mortality.1 The prevalence of PPH in inmates of residential care is 25% to 40% and 20% to 91% in hospitalized geriatric patients.1 No study has hitherto evaluated the prevalence of PPH in “healthy” older individuals, with the exception of small cohorts of “control” subjects.2,3 Although the pathophysiology of PPH is poorly understood, our recent studies indicate that the magnitude of the postprandial fall in BP is dependent on the rate of nutrient entry to the small intestine. For example, in a small cohort of patients with This study was funded by the National Health and Medical Research Council (NHMRC 627189) of Australia. L.G.T. is supported by an Australian Postgraduate Award and a Dawes scholarship from the Royal Adelaide Hospital. K.L.J.’s salary is funded by an NHMRC Senior Career Development Award (627011). M.H. has participated in Advisory Boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca, and has received honoraria for this activity. L.G.T. and K.L.J. have no personal or financial conflict of interest to declare. * Address correspondence to Karen L. Jones, PhD, Discipline of Medicine, The University of Adelaide, Level 6, Eleanor Harrald Building, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia. E-mail address: [email protected] (K.L. Jones). http://dx.doi.org/10.1016/j.jamda.2015.01.097 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

type 2 diabetes, when gastric emptying (GE) of glucose was faster, the magnitude of the hypotensive response was greater4 and, in healthy older individuals, when glucose was infused intraduodenally at rates within the “physiological” range of GE of 1, 2, or 3 kcal/min, there was a substantial fall in systolic blood pressure (BP) in response to the 2 and 3 kcal/min, but not the 1 kcal/min, load.5 Accordingly, given the wide range of normal gastric emptying,6 which is affected little by age,6 relatively more rapid GE may be a risk factor for PPH. This has hitherto not been evaluated and, if so, would have substantial implications for the management of PPH, which is suboptimal.1 In this study we have characterized GE of, and the BP responses to, an oral glucose load in healthy older individuals to (1) determine the prevalence of, and (2) evaluate the association of gastric emptying with, PPH. Materials and Methods Participants Eighty-eight healthy “older” individuals (47 female and 41 male, age 71.0  0.5 years [range: 65e90 years], body mass index [BMI]

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26.0  0.3 kg/m2 [range: 20.3e30.5 kg/m2]) were recruited by advertisements. Demographic information and a medical history were obtained. Individuals with a history of gastrointestinal disease or surgery, known diabetes, significant respiratory or cardiac disease, or alcohol intake (>20 g per day) were excluded. Any medication was withheld for 24 hours before the study. Protocol In each participant, BP and GE were measured concurrently on a single study day, which commenced at 0830 hours after an overnight fast. On arrival, an intravenous cannula was inserted into an antecubital vein for blood sampling while the participant was supine. The participant was then seated and allowed to “rest” for 15 to 30 minutes before consuming a drink containing 75 g glucose and 150 mg C13acetate made up to 300 mL with water within 3 minutes; t ¼ 0 minutes was the time of completion of the drink. BP was measured for 120 minutes and GE for 240 minutes after the drink. Venous blood samples were obtained immediately before the glucose drink, and at regular intervals, for 240 minutes. Results of blood glucose and insulin in this cohort have been reported.7 At t ¼ 240 minutes, the cannula was removed and the participant given a meal before leaving the laboratory. The protocol was approved by the Research Ethics Committee of the Royal Adelaide Hospital, and each participant provided written, informed consent before their inclusion. All studies were carried out in accordance with the Declaration of Helsinki. BP and Heart Rate BP and heart rate (HR) were measured using an automated oscillometric monitor (DINAMAP ProCare 100; GE Medical Systems, Milwaukee, WI), every 3 minutes during the “rest” period, and every 5 minutes from t ¼ 3e118 minutes. Baseline BP was calculated as an average of the measurements obtained at t ¼ 9, t ¼ 6, and t ¼ 3 minutes.5 PPH was defined as a sustained fall in systolic BP of 20 mm Hg, occurring within the first 90 minutes after the drink.1 GE Exhaled breath samples were collected in hermetically sealed 10 mL tubes (Exetainer, Buckinghamshire, England) before ingestion of the drink (t ¼ 3 minutes), every 5 minutes for the first hour, and then every 15 minutes for the subsequent 3 hours, for assessment of GE. The 13CO2 concentration in breath samples was measured by an isotope ratio mass spectrometer (ABCA 20/20; Europa Scientific, Crewe, UK) with an online gas chromatographic purification system. The gastric 50% emptying time (T50) was calculated using the formula described by Ghoos et al.8

glucose measurements) and were excluded from the analysis. Five individuals were taking antihypertensive medication. In 7 individuals, GE data were unavailable, as an appropriate nonlinear regression model fit to the measured 13CO2 concentrations was not feasible. Accordingly, complete data were available in 79 participants. BP and HR Baseline systolic BP was 122.3  1.5 mm Hg. Following the drink, there was a transient, modest rise, followed by a fall (P < .001) in systolic BP. The maximum fall was 14.2  1.0 mm Hg, occurring at 80.1  3.5 minutes. Eleven participants (12.8%) had PPH. Baseline diastolic BP was 69.0  0.8 mm Hg. Following the drink, there was a transient, modest rise, followed by a fall (P < .001) in diastolic BP. The maximum fall was 11.9  0.6 mm Hg, occurring at 65.4  3.6 minutes. Baseline HR was 64.0  0.9 beats per minute. Following the drink there was a prompt, and sustained, rise in HR (P < .05). The maximum increase in HR was 8.3  0.5 beats per minute, occurring at 43.8  4.0 minutes. GE The mean GE 55e256 minutes).

T50

was

138.9



4.2

minutes

(range:

Comparison Between Participants With and Without PPH There was no difference in age (P ¼ .14) or body mass index (BMI) (P ¼ .24) between the groups. Baseline systolic BP was higher in participants with PPH (non-PPH 121.0  1.6 mm Hg vs PPH 131.6  3.8 mm Hg, P < .05), and there was no difference in diastolic BP (non-PPH 68.4  0.9 mm Hg vs PPH 73.0  2.7 mm Hg, P ¼ .14) or HR (non-PPH 63.4  0.9 beats per minute vs PPH 68.1  3.5 beats per minute, P ¼ .22) between the groups. The GE T50 was shorter in those with PPH (non-PPH 142.3  4.6 minutes vs PPH 118.0  9.4 minutes, P < .05) (Figure 1). Relationships Between Variables In the whole group, there was a trend for an inverse relationship between maximum fall in systolic BP and maximum rise in HR (R ¼ 0.20, P ¼ .09), so that when the fall in systolic BP was greater, there tended to be a greater rise in HR. There was no significant

Statistical Analysis BP and HR were analyzed as changes from baseline, and GE as absolute values. Maximum changes in BP and HR were calculated as the greatest change that occurred from baseline. Changes in BP and HR over time were assessed with 1-way analysis of variance. Differences between groups with and without PPH were assessed with Student’s paired t test. Pearson’s correlation was used to evaluate relationships between variables. A P less than .05 was considered significant in all analyses. Data are presented as mean values  SEM. Results The studies were well tolerated and there were no adverse events. Two individuals had diabetes (based on fasting and 2-hour blood

Fig. 1. GE half times (T50) in individuals without (n ¼ 68, C) and with (n ¼ 11, -) PPH (P < .05).

L.G. Trahair et al. / JAMDA 16 (2015) 521e523

relationship between age, BMI, or the maximum fall in systolic and diastolic BP with the GE T50.

Discussion We characterized the BP and GE responses to an oral glucose load in an unselected cohort of 86 healthy individuals older than 65 years; 11 participants (12.8%) had PPH, and GE was faster in this group. Previous studies have evaluated the prevalence of PPH in cohorts in which PPH is likely to be more common, including the frail elderly in residential care facilities, patients with dysautonomia, those with a history of syncope or falls, and patients with hypertension.1 Given the reported high prevalence in these groups, it is not surprising that 12.8% of our healthy older participants had PPH. We did not include a “control” study for logistical reasons, but in healthy young individuals, ingestion of glucose is not associated with a fall in BP.4 Studies to evaluate the association of postprandial changes in BP with symptoms and mortality in healthy older individuals are indicated. We hypothesized that PPH would be associated with relatively more rapid GE, based on the outcome of our previous studies4,5 and this proved to be the case. GE in health exhibits a substantial inter-, but lower intraindividual variation6; more rapid GE has been reported to predispose to PPH and, possibly, the risk of type 2 diabetes.7 Hypertension also has been associated with more rapid GE9 and is a risk factor for PPH,1 as confirmed in the current study. Although the breath test used to quantify GE has been validated against the “gold standard” of scintigraphy,8 the resultant T50 should be regarded as notional. Accordingly, we cannot calculate a GE rate as kcal/min, although our previous studies suggest that the relationship of the postprandial fall in BP with the rate of small intestinal nutrient delivery is nonlinear.5 Our novel observation of an association of PPH with more rapid GE has implications for the management of PPH,

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diseases that are frequently associated with PPH, such as diabetes and Parkinson disease1 are also associated with disordered, albeit more frequently delayed, rather than more rapid, GE, whereas drugs that slow GE, such as the a-glucosidase inhibitor acarbose, may have efficacy in the management of PPH.1 Acknowledgments The authors acknowledge Raj Sardana, Michelle Bound, Kevyn Mejia-Hernandez, and Rachael Tippett for their assistance with data collection, and Max Bellon for his assistance with the C13-breath test analysis. References 1. Trahair LG, Horowitz M, Jones KL. Postprandial hypotension: A systematic review. J Am Med Dir Assoc 2014;15:394e409. 2. Lipsitz LA, Ryan SM, Parker JA, et al. Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension. Circulation 1993;87: 391e400. 3. Van Orshoven NP, Jansen PA, Oudejans I, et al. Postprandial hypotension in clinical geriatric patients and healthy elderly: Prevalence related to patient selection and diagnostic criteria. J Aging Res 2010;2010:243752. 4. Jones KL, Tonkin A, Horowitz M, et al. Rate of gastric emptying is a determinant of postprandial hypotension in non-insulin-dependent diabetes mellitus. Clin Sci (Lond) 1998;94:65e70. 5. Vanis L, Gentilcore D, Rayner CK, et al. Effects of small intestinal glucose load on blood pressure, splanchnic blood flow, glycaemia and GLP-1 release in healthy older subjects. Am J Physiol Regul Integr Comp Physiol 2011;300:R1524eR1531. 6. Kuo P, Rayner CK, Horowitz M. Gastric emptying, diabetes, and aging. Clin Geriatr Med 2007;23:785e808. vi. 7. Trahair LG, Horowitz M, Marathe CS, et al. Impact of gastric emptying to the glycemic and insulinemic responses to a 75-g oral glucose load in older subjects with normal and impaired glucose tolerance. Physiol Rep 2014;2:e12204. 8. Ghoos YF, Maes BD, Geypens BJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology 1993;104:1640e1647. 9. Phillips WT, Salman UA, McMahan CA, Schwartz JG. Accelerated gastric emptying in hypertensive subjects. J Nucl Med 1997;38:207e211.