Ambulatory blood pressure monitoring and postprandial ... - Nature

Journal of Human Hypertension (1998) 12, 161–165  1998 Stockton Press. All rights reserved 0950-9240/98 $12.00

ORIGINAL ARTICLE

Ambulatory blood pressure monitoring and postprandial hypotension in elderly patients with isolated systolic hypertension T Grodzicki1, M Rajzer2, R Fagard3, ET O’Brien4, L Thijs3, D Clement5, C Davidson6, P Palatini7, G Parati8, J Kocemba1 and JA Staessen3, on behalf of the Systolic Hypertension in Europe (SYST-EUR) Trial Investigators 1

Department of Gerontology and Family Medicine, Jagiellonian University, Cracow, Poland; 21st Department of Cardiology, Jagiellonian University, Cracow, Poland; 3Syst-Eur Coordinating Office, Universitaire Ziekenhuizon UZ Gasthuisberg, Leuven, Belgium; 4Blood Pressure Unit, Beamont Hospital, Dublin, Ireland; 5Department of Cardiology and Angiology, University Hospital, Gent, Belgium; 6Royal County Hospital, Brighton, UK; 7Policlinico, Padua, Italy; 8Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, Milan, Italy

The present analysis was undertaken to evaluate postprandial (PP) changes in blood pressure (BP) assessed with ambulatory BP monitoring (ABPM) in elderly subjects with isolated systolic hypertension (ISH) on conventional measurement. A total of 530 patients (335 women and 195 men, aged 60–100 years, median 70 years) who performed an ABPM during the placebo runin period of the Syst-Eur trial were included into the analysis. The PP changes in BP and heart rate (HR) were calculated by subtracting the mean systolic BP (SBP), diastolic BP (DBP) and HR in the 2 h preceding the main meal from the corresponding means covering the 2 h after the meal. The reproducibility of the postprandial fall in BP and heart rate (PPH) was assessed by contrasting the first and second ABPM in a subgroup of 147 patients who performed two ABPM’s during the placebo run-in period. The mean SBP and DBP decreased and reached the nadir 2 h after the main meal while HR did not change. When PPH was assessed by comparing BP

in the 2 h before and after the meal, both SBP and DBP decreased significantly (respectively −6.6 mm Hg, −5.4 mm Hg; P ⬍ 0.001). In 67.6% of all patients a decrease in SBP was observed and in 24.1% it exceeded 16 mm Hg. The corresponding values for DBP were 71.3% and 24.5% (DBP decreased more than 12 mm Hg). A greater fall in DBP was associated with a greater decrease in HR (r = 0.20, P ⬍ 0.001), while changes in SBP and HR were not interrelated. Regression analysis did not identify any significant covariate of PPH. Group means of PPH could be reproduced without significant changes in their values, but the within-subject reproducibility of the PP changes was low. There were no differences in PPH according to the place of residence of the patients. In conclusion, the descriptive analysis of the meal-induced changes in ABPM in elderly subjects with ISH showed that in every day circumstances most of them experience falls in both SBP and DBP within 2 h after the meal.

Keywords: postprandial hypotension; isolated systolic hypertension; elderly; ambulatory blood pressure monitoring; SYSTEUR

Introduction Significant reductions in blood pressure (BP) after mixed-meals or oral glucose have been observed in elderly healthy, hypertensive or diabetic patients, and in patients with Parkinson’s disease or autonomic insufficiency.1–3 Although the underlying mechanisms are not well established, the increase in concentration of vasoactive gastrointestinal peptides or insulin-related vasodilatation have been Correspondence: Dr Tomasz Grodzicki, Dept of Gerontology and Family Medicine, School of Medicine, Jagiellonian University, Wielicka 267, 30-663 Cracow, Poland Received 3 May 1997; revised and accepted 13 October 1997

suggested as a reason of this phenomenon.1,4 Ageassociated cardiovascular changes such as arterial stiffness and left ventricular diastolic dysfunction may cumulatively produce alterations in BP regulatory mechanisms that impair an older person’s ability to adapt to hypotensive stress.5 Moreover, the blunted baroreceptor reaction in elderly hypertensive patients may be partially responsible for profound postprandial hypotention. It has been demonstrated that patients with a history of falls or syncope present with a more distinct BP decrease after meals.6 Isolated systolic hypertension (ISH) remains an important feature of aging associated with a diminished baroreceptor function and susceptibility to

ABPM and postprandial BP in isolated systolic hypertension T Grodzicki et al

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orthostatic hypotention.7 Nowadays, 24-h ambulatory BP monitoring (ABPM) is used widely in research and everyday clinical practice and remains the method of choice to evaluate fluctuations in BP in hypertensive and normotensive subjects. As to the best of our knowledge the literature describing the influence of meals on the 24-h BP profile is scarce, it seemed interesting to undertake the present analysis to evaluate changes in BP in patients with ISH in relation to the main meal.

Patients and methods The protocol of the multicentre SYST-EUR trial and its side-project on ABPM has been published elsewhere.8,9 After discontinuation of all anti-hypertensive drugs, the participants (⭓60 years) first entered a single-blind period on placebo, during which eligible patients maintained a sitting systolic BP (SBP) of 160–219 mm Hg and a diastolic BP (DBP) below 95 mm Hg on conventional measurement. Ambulatory pressure was recorded non-invasively at intervals not greater than 30 min. A total of 578 patients included into the SYST-EUR (on August 1995) had their ABPM measured at least once during the placebo run-in period phase. Of these 48 were excluded from the analysis because their ABPM recordings were incomplete (n = 26), the time of the main meal was missing (n = 18) or BP measurements during 1 h preceding or after meal were missing (n = 4). The ABPM recordings of the remaining 530 patients were included into analysis. In a subgroup of 147 patients ABPM had been repeated during the baseline period on placebo. The postprandial change in BP and heart rate (HR) was calculated by subtracting the mean SBP, DBP and HR in the 2 h preceding the main meal (according to the patients’ diaries) from the corresponding means from the 2 h after the main meal. All analyses were performed in the entire group of patients (n = 530) and separately in subjects taking their main meal between 11.00 am and 2.00 pm (n = 296), and between 5.00 pm and 8.00 pm (n = 130). Statistical analysis Database management and statistical analyses were performed with the SAS software (The SAS institute Inc, Cary, NC, USA). Unless otherwise indicated the standard deviation (s.d.) was used to report the spread of the results. In order to identify factors that may contribute to the postprandial BP fall, a subgroup and single and multiple linear regression analyses were performed. For multiple means comparisons Ducan’s test was used. The reproducibility of the postprandial changes in BP was assessed by contrasting the first and second BP monitoring. The repeatability coefficients were calculated as 2 s.d. of the differences between repeated measurements. To allow comparisons between various measurements the repeatibility coefficients were expressed as percentages of nearly maximal biological variation, ie, four times the s.d. of the averaged duplicate measurements.

Figure 1 Means of SBP, DBP and heart rate before and after main meal.

Results The ABPM recordings of 530 patients were included into analysis. This group consisted of 335 women and 195 men, aged 60–100 years (median 70 years), with mean body mass index of 26.9 ± 4.2 kg/m2 (women) and 26.2 ± 3.4 kg/m2 (men). Cardiovascular complications were present in 27% of the patients. The main meal was taken between 10.30 am and 11.00 pm, but 95% of patients took their main meal between 11.45 am and 7.00 pm. In the entire group SBP and DBP decreased after the main meal reaching a minimum 1–2 h after the main meal. Heart rate was similar before and after the main meal (Figure 1). When the postprandial change in BP was assessed by comparing the average BP in the 2 h before and after the meal both SBP and DBP decreased significantly but HR remained unchanged (Table 1). The analysis of these changes according to the time of the main meal did not reveal any differences between subjects who had their main meal in the afternoon or in the evening. The Table 1 Postprandial changes in systolic (SBP), diastolic (DBP) blood pressure and heart rate (HR)

SBP (mm Hg) DBP (mm Hg) Pulse rate (bpm) ***P ⬍ 0.001.

Mean ± s.d.

Confidence interval

−6.6 ± 13.8*** −5.4 ± 10.9*** −0.1 ± 8.7

−7.77; −5.43 −6.33; −4.47 −0.84; +0.64


Table 2 Reproducibility of the postprandial changes in blood pressure and pulse rate Change (mm Hg)

Consistency (mm Hg)

Repeatability (mm Hg) (%)

−0.5 −1.0 −1.6

9.3 (0.6–31.3) 7.2 (0.7–28.1) 5.7 (0.8–23.1)

29 (68%) 25 (70%) 24 (79%)

SBP DBP Heart rate

Change = mean difference between duplicate recordings taking into account the sign of the difference. Consistency = median difference between duplicate recordings, disregarding the sign of the difference (5th and 95th percentile range in parentheses). Repeatability = twice the standard deviation of the changes between repeated recordings (percent of maximal variation in parentheses).

Figure 2 Histogram of the postprandial changes in SBP.

histogram of postprandial fluctuations demonstrates that in 67.6% of the patients a decrease in SBP was observed and 24.1% showed a decrease of more than 16 mm Hg (Figure 2). The analysis of the DBP changes shows that in 71.3% DBP decreased and in 24.5% this decrease exceeded 12 mm Hg (Figure 3). Single correlations between changes in BP and HR in the entire group demonstrated that a greater fall in DBP was associated with a greater decrease in HR (r = 0.20, P ⬍ 0.001). In contrast, changes in SBP and HR were not interrelated. Subgroup and regression analysis did not identify any significant covariate of the postprandial changes in BP and pulse rate. In both analyses the following variables were included: age, gender, body mass index, level of BP (and pulse pressure) on conventional measurement, the orthostatic change in BP, the nocturnal fall in BP, the 24-h and daytime s.d. of BP (with exclusion of the 2 h before and after the main meal), the presence of cardiovascular complications, drinking and smoking habits (discrete and continuous), log serum activity of gammaglutamyltranspeptydase, presence of diabetes mel-

litus, R-wave amplitude in aVL and the Sokolov index (SV1 + RV5), and anti-hypertensive treatment in the 6 months preceeding enrolment in the study. Group means of postprandial changes in SBP, DBP and HR could be reproduced without significant changes in their values (Table 2). However, the within-subject reproducibility of the postprandial changes was rather low as expressed by the high repeatability coefficients. The reproducibility of the postprandial BP and HR changes did not differ between patients who took their meal in the afternoon or evening. The postprandial changes in BP and HR were also analysed according to the place of residence (Table 3). Although patients from Southern Europe (n = 166) showed a higher decrease in SBP (−8.1 ± mm Hg) and DBP (−6.4 ± mm Hg) in comparison with patients living in Northern Europe (n = 340) (respectively, −5.9 ± mm Hg, −5.1 ± mm Hg), the differences between these falls did not achieve statistical significance.

Discussion The analysis of ambulatory BP recordings in 530 elderly patients with isolated systolic hypertension Table 3 Average postprandial fall in systolic (SBP), diastolic (DBP) blood pressure and heart rate (HR) according to the place of residence Country

Finland Netherlands Slovenia Ireland UK Belgium Italy Greece Germany Poland Spain Portugal Northern Europe Southern Europe

Figure 3 Histogram of the postprandial changes in DBP.

n

SBP (mm Hg)

DBP (mm Hg)

HR (bpm)

142 15 18 34 76 45 109 9 3 25 44 4 340 166

−4.1 −5.8 −6.4 −6.6 −6.9 −7.2 −7.4 −8.1 −8.9 −9.3 −9.7 −12.0 −5.9 −8.1

−4.9 −5.9 −4.2 −4.1 −6.1 −4.5 −5.2 −8.7 −6.6 −4.7 −9.0 −2.9 −5.1 −6.4

−1.1 −1.4 −4.3 +3.4 +1.7 +1.0 −0.2 −3.1 −2.0 +0.7 −1.7 +6.4 +0.3 −0.6

Southern Europe = Italy, Portugal, Spain, Greece. Northern Europe = Finland, Netherlands, Ireland, UK, Belgium, Germany, Poland.

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showed that within 2 h after the main meal about 70% of subjects experienced a decrease in BP. In nearly one-quarter of them this decrease exceeded 16 mm Hg for systolic or 12 mm Hg for diastolic BP. At the same time, an average heart rate did not show significant changes. The epidemiological prevalence and magnitude of meal-induced changes in BP remains unknown.10 As it has been shown in clinical studies BP reaches a nadir between 30 and 60 min after the meal, but it may appear as early as after 15 min or as late as after 75 min.1,10 BP was taken every 30 min, but the time of first measurement did not necessarily coincide with the beginning of the main meal. Therefore we chose the 2-h period after the meal as a postprandial period and compared the latter with the 2-h period before the meal. Diurnal profile of BP according to the age has been recently studied in the population-based studies such as the Belgian Population Study,11 PAMELA study12 and Ohasama study.13 Unfortunately, none of these trials addressed the problem of mealinduced changes in BP profile nor evaluated subjects with isolated systolic hypertension as a separate group. Nevertheless all these studies have shown that older, in comparison with younger subjects, presented with higher BP variability. Furthermore the analysis of the BP curves from the Belgian Study and the PAMELA survey demonstrated that a dip in both systolic and diastolic BP was observed in the early afternoon hours.11,12 However, data provided in both papers does not allow us to conclude with certainty that it was related to the mid-day meal or to the other factors. Nakajima et al14 reported changes in the ABPM related to the standardised meal. The authors in a ‘Letter to the Editor’ demonstrated that a postprandial fall occurred in 18 (36%) of 50 middle-age hypertensive subjects. The reproducibility of the postprandial decrease in BP in the present patients with ISH was high in the group analysis but much worse for individual patients. In a study by Jansen et al15 who evaluated the reproducibility of postprandial BP changes in 22 nursing home residents after a standardised meal, on two occasions the mean intra-class correlation was significant for both SBP and DBP. In our group ABPM was performed in the everyday life. The timing, composition and temperature of the meals etc might therefore influence the intra-individual reproducibility of BP postprandial changes. As we were concerned that nutritional habits might differ between countries, we analysed the postprandial fall according to the place of residence, but the magnitude of the meal-induced fall was similar across Europe. In conclusion, about 70% of elderly patients with ISH experience a postprandial fall in BP measured in everyday circumstances, and in one-quarter of them a decrease of more than 16 mm Hg in SBP or 12 mm Hg in DBP occurred. Follow-up of these patients in the SYST-EUR trial may demonstrate whether those with the more pronounced postprandial decrease in BP are at higher cardiovascular risk.

Acknowledgements The SYST-EUR trial is a concerted action of the European Union’s BIOMED Research Program. It is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. The trial is supported by Bayer AG (Wuppertal, Germany) and the National Fund for Scientific Research (Brussels, Belgium). Study medication is donated by Bayer AG and Merck Sharpe and Dohme Inc (West Point, PA, USA). Participating centres On 15 May, 1996, the following centres with randomised patients participated in the project on 24h ambulatory blood pressure monitoring: Belgium Leszek Bieniaszewski, Hilde Celis, Robert Fagard, Jan A Staessen, Roger Van Hoof (Leuven), Paul De Cort (Kumtich), Dirk Staessen, Jan A Staessen (Mechelen) Bulgaria Boyan Shahov (Sofia) Estonia Tovio Laks (Tallinn) Finland ¨ Kari Halonen (Kunsankoski), Tapio Hakamaki, Aapo ¨¨ Lehtonen (Turku), Matti Jaaskivi, Liisa Tiito-Wiht, Cinzia Sarti (Vantaa), Pavla Kivinen (Kuopio), Erkki ¨ Lehtomaki (Tampere), Reijo Tilvis, Hannu Vanhanen (Helsinki), Hannu Wallinhiemo (Hensinki) Germany Eberhard Ritz (Heidelberg) Greece Aris D Efstratopoulos (Athens) Ireland Neil Atkins, Eoin T O’Brien (Dublin) Israel ´ Joseph Rosenfeld, Jose Zabludowski (Petha Tiqva), Serge Zerapha (Givataim) Italy Alfredo Bossini (Rome), Roberto Fogari (Pavia), Giuliana Ginocchio, Paolo Palatini (Padova), Salvatore Lattuada (Milan), Giuseppe Maiorano (Bari), Anna Pirrelli (Bari), Antonio Salvetti (Pisa), Laura Terzoli (Milan), Alvaro Vaccarella (Casatenovo) Netherlands Peter de Leeuw (Maastricht), Anton H van den Meiracker (Rotterdam), Arend J J Woittiez (Almelo) Poland Kalina Kawecka-Jaszcz (Cracow), Jozef Kocemba (Cracow) Portugal Gago Leira (Faro) Slovenia Jurij Dobovisek (Ljubljana) Spain Blas Gil-Extremera (Granada), Rafael Marin


´ (Oviedo), Joan Ocon-Pujadas (Barcelona), Josep ´ ´ Redon (Sagunto), Jose L Rodicio (Madrid) UK ` Garreth Beevers, Michele Beevers (Birmingham), Christopher J Bulpitt (London), Christopher Davidson (Brighton), Pandita Gunawardena (London), John Webster (Aberdeen)

Committees and Coordination Data Monitoring Committee Christopher J Bulpitt, Astrid E Fletcher, Jan A Staessen, Lutgarde Thijs Endpoint Committee Peter de Leeuw, Robert Fagard, Gastone Leonetti, James C Petrie Ethics Committee ¨ Willem H Birkenhager, Collin T Dollery, Robert Fagard EU SYST-EUR Liaison Committee ¨ Willem H Birkenhager, Fernando De Padua, Collin T Dollery, Aris D Efstratopoulos, Robert Fagard, Françoise Forette, Detlev Ganten, Eoin T O’Brien, ´ Kevin O’Malley, Jose L Rodicio, Jaakko Tuomilehto, Christian van Ypersele, Alberto Zanchetti Publlication Committee ¨ Willem H Birkenhager, Christopher J Bulpitt, Jan A Staessen, Alberto Zanchetti Steering Committee Paul De Cort, Robert Fagard, Françoise Forette, Kalina Kawecka-Jaszcz, Gastone Leonetti, Choudomir ´ Nachev, Eoin T O’Brien, Jose L Rodico, Joseph Rosenfeld, Jaakko Tuomilehto, John Webster, Yair Yodfat Trial Coordinators Robert Fagard, Jan A Staessen Coordinators of the Project on Ambulatory Blood Pressure Monitoring Denis Clement, Eoin T O’Brien, Giuseppe Mancia, Gianfranco Parati, Jan A Staessen, Lutgarde Thijs Coordinator of the Project on Vascular Dementia Françoise Forette Coordinators of the Project on Quality of Life Christopher J Bulpitt, Astrid E Fletcher

Coordinator of General Practices Hilde Celis

References 1 Mathias CJ. Postprandial hypotension. Pathophysiological mechanisms and clinical implications in different disorders. Hypertension 1991; 18: 694 –704. 2 Haigh RA et al. Possible impairment of the sympathetic nervous system response to postprandial hypotension in elderly hypertensive patients. J Hum Hypertens 1991; 5: 83–89. 3 Lipsitz LA, Nyquist RP, Wei JY, Rowe JW. Postprandial reduction in blood pressure in the elderly. N Engl J Med 1983; 309: 81–81. 4 Jansen RWMM, Hoefnagels WHL. Hormonal mechanisms of postprandial hypotension. J Am Geriatr Soc 1991; 39: 1201–1207. 5 Messerli FH, Grodzicki T. Hypertension in the elderly. In: Messerli FH (ed) Cardiovascular Disease in the Elderly. Kluwer Academic Publishers: Boston, 1993, pp 121–144. 6 Jansen RWMM et al. Postprandial hypotension in elderly patients with unexplained syncope. Arch Intern Med 1995; 155: 945–952. 7 Vanhanen H et al. Associations of orthostatic blood pressure fall in older patients with isolated systolic hypertension. J Hypertens 1996; 14: 943–949. 8 Amery A et al. Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol and organization. Aging 1991; 3: 287–302. 9 Staessen J et al. Twenty-four hour blood pressure monitoring in the Syst-Eur trial. Aging 1992; 4: 85–91. 10 Jansen RWMM, Lipsitz LA. Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann Intern Med 1995; 122: 286–295. 11 Staessen JA et al. An epidemiological approach to ambulatory blood pressure monitoring: the Belgian Population Study. Blood Press Monit 1996; 1: 13–26. 12 Mancia G et al. Ambulatory blood pressure normality: results from the PAMELA study. J Hypertens 1995; 13: 1377–1390. 13 Imai Y et al. Ambulatory blood pressure of adults in Ohasama, Japan. Hypertension 1993; 22: 900–912. 14 Nakajima S et al. Ambulatory blood pressure and postprandial hypotension. Am Heart J 1992; 124: 1669– 1671. 15 Jansen RWMM, Kelley-Gagnon MM, Lipsitz LA. Intraindividual reproducibility of postprandial and orthostatic blood pressure changes in older nursinghome patients: relationship with chronic use of cardiovascular medications. J Am Geriatr Soc 1996; 44: 383–389.

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