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Beta-Blockers Do Not Impair the Cardiovascular Benefits of Endurance Training in Hypertensives

Beta-Blockers Do Not Impair the Cardiovascular Benefits of Endurance Training in Hypertensives

Journal of Human (2007) 21, 486–493 & 2007 Nature Publishing Group All rights reserved 0950-9240/07 $30.00 www.nature.com/jhh ORIGINAL ARTICLE Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives

TH Westhoff1,4, N Franke1,4, S Schmidt1, K Vallbracht-Israng2, W Zidek1, F Dimeo3,5 and M van der Giet1,5 1Medizinische Klinik IV – Nephrology, Charite´ – Campus Benjamin Franklin, Berlin, Germany; 2Department of Cardiology, Charite´ – Campus Virchow Klinikum, Berlin, Germany and 3Medizinische Klinik III – Section of Sports Medicine, Charite´ – Campus Benjamin Franklin, Berlin, Germany

Aerobic physical exercise is broadly recommended as exertion (100 W) and increased -dependent a helpful adjunct to obtain pressure control in (flow-mediated vasodilation, FMD) and hypertension. Beta-blockade interacts with rate, physical performance both in the presence and absence sympathetic tone, maximal workload and local lactate of beta-blockade (Po0.05 each). The extent of ABP production. In the present randomized-controlled study, reduction did not significantly differ in the presence we compared the cardiovascular effects of an endurance or absence of beta-blockade (D systolic ABP 10.6710.5 training programme in elderly hypertensives with or vs 10.678.8 mm Hg, D diastolic ABP 5.778.6 vs without beta-blockers and developed a first approach to 5.874.0 mm Hg). Mean training was signifi- determine a lactate-based training heart rate in presence cantly lower in the patients on beta-blockers (97.277.7 of beta-blockade. Fifty-two patients (23 with beta-block- vs 118.377.5/min, Po0.001). Lactate-based aerobic er, 29 without beta-blocker) X60 years with systolic 24-h endurance training evokes comparable cardiovascular ambulatory (ABP) X140 mm Hg and/or benefits in the presence and absence of beta-blockade antihypertensive treatment were randomly assigned to including a marked improvement of endothelial func- sedentary activity or a heart-rate controlled 12-week tion. In the present study, target training heart rate with treadmill exercise programme (lactate 2.0 mmol/l). In the beta-blockers is about 18% lower than without. exercise group, the training significantly decreased Journal of Human Hypertension (2007) 21, 486–493. systolic and diastolic 24-h ABP, blood pressure on doi:10.1038/sj.jhh.1002173; published online 1 March 2007

Keywords: exercise; blood pressure; endothelial function; beta-blocker

Introduction cardiovascular benefits, however, depends strictly on the concept of the endurance programme. Guide- Aerobic physical exercise is recommended as basic lines recommend modest levels of aerobic exercise lifestyle modification in the treatment of arterial 1,2 on a regular basis, such as walking, jogging or hypertension. Whereas cardiovascular training swimming for 30–45 min, 3–4 times a week.1,5,6 can induce systolic and diastolic blood pressure Training should be performed at 40–60% of maxi- reductions of approximately 3–4 mm Hg in normo- mum O uptake.7 Physical exercise beyond 60% of tensives, this phenomenon is even more pronoun- 2 3 maximal O2 consumption does not lead to further ced in hypertensives. Shear stress – as induced by reductions of blood pressure and might even physical exercise – is a potent stimulus on endo- increase blood pressure in hypertensives.8,9 The thelial cells for an increase in nitrous oxide (NO)- intensity of exercise is generally monitored by heart production leading to improved endothelial func- 4 rate. Adequate training heart rate can be assessed by tion and reduced . The extent of determination of the anaerobic threshold using ventilatory parameters or lactate.10,11 This proce- Correspondence: Dr TH Westhoff, Medizinische Klinik IV – dure, however, is too time-consuming and expen- Nephrology, Charite´ – Campus Benjamin Franklin, Hindenbur- sive to be used in general practice. Therefore, target gamm 30, 12200 Berlin, Germany. heart rates are usually determined on the basis of E-mail: [email protected] empirical experiences. The percentage of maximal Sources of financial support: None. heart rate is the most widely accepted parameter for 4These authors contributed equally to this work. 5These authors contributed equally to this work. the description of training intensities. The American Received 24 August 2006; revised 17 December 2006; accepted 20 College of Sports Medicine and the American January 2007; published online 1 March 2007 Heart Association recommend training intensities Endurance training and beta-blockade TH Westhoff et al 487 between 5512 and 65–85% of maximal heart rate.13 Methods As beta-blockers reduce heart rate both in rest and under exertion, target heart rates might differ from Study population general recommendations.14 Furthermore, acute Patients were recruited from the hypertension out- treatment with beta-blocking modifies local patient clinic of our university hospital and by press muscular metabolic properties and impairs endur- announcement to assess cardiovascular benefits of ance exercise capacity resulting in an increase in exercise training on treated hypertensives. Inclusion perceived exertion, lower VO2max and lower work criteria for the current study were systolic ambula- rate, whereas the influence of chronical administra- tory blood pressure (ABP) X140 mm Hg and/or tion of beta-blockers is discussed controversially.15 It current antihypertensive treatment, age X60 years. has been shown that non-selective beta-blockers can Before the exercise programme, cardiac function increase lactate levels during exercise, for example, was examined by electrocardiogram (ECG) and 16 through b2-associated peripheral . echocardiogram. Exclusion criteria were continuous Furthermore, metoprolol – as a selective b1-selective engagement in physical exercise training 460 min/ antagonist – induces a left-shift of both lactate and week in the past 12 weeks before inclusion in the ventilatory aerobic threshold.17 In a small study of study, symptomatic peripheral arterial occlusive 10 young healthy men, a small dose of bisoprolol disease, aortic insufficiency or stenosis 4stage I, given for 2 weeks reduced the percentage of hypertrophic obstructive cardiomyopathy (HOCM), maximal heart rate at the aerobic and anaerobic congestive (4NYHA II (New York threshold.18 Thus, it may be speculated that cardio- Heart Association, grade II)), uncontrolled cardiac vascular benefits of exercise at a defined heart rate with hemodynamic relevance, systolic differ in the absence and presence of beta-blockade. office BPX180 mm Hg, signs of acute ischemia in The aim of the present study is to determine the exercise , change of antihyper- differential effects of lactate-based exercise prescrip- tensive in the past 6 weeks before tion on hypertensives with or without chronic beta- inclusion or during the follow-up period. Further blockade. indication of hypertension-associated target- In the present study, we compared the cardio- damage was not regarded as exclusion criteria. vascular effects of a heart-rate controlled 12-week According to these criteria, 52 patients (26 male, endurance training programme between elderly 26 female) were enrolled to the study. Patients’ hypertensives with or without beta-blockers and characteristics including concomitant diseases are a sedentary control group. We developed a first presented in Table 1. All patients were treated with approach to determine a lactate-based training heart at least one antihypertensive . Irrespective of rate in the presence of beta-blockade. presence or absence of beta-blockade, patients were

Table 1 Patients’ characteristics (age and number of antihypertensive drugs presented as mean7s.d.)

Exercise Control

All (n ¼ 25) Beta- No beta- All (n ¼ 27) Beta- No beta- blockade blockade blockade blockade (n ¼ 9) (n ¼ 16) (n ¼ 14) (n ¼ 13)

Female 12 (48%) 6 (67%) 6 (38%) 14 (52%) 6 (43%) 8 (62%) Male 13 (52%) 3 (33%) 10 (63%) 13 (48%) 8 (57%) 5 (38%) Age (years) 67.874.7 66.473.4 68.575.2 68.975.2 68.975.2 69.075.3

Concomitant diseases Diabetes mellitus 4 (16%) 0 (0%) 4 (25%) 5 (19%) 4 (29%) 1 (8%) 13 (52%) 5 (56%) 8 (50%) 11 (41%) 7 (50%) 4 (31%) Smoking 3 (12%) 3 (33%) 0 (0%) 2 (7%) 1 (7%) 1 (7%) Family history of 12 (48%) 6 (67%) 6 (38%) 13 (48%) 7 (50%) 6 (46%) Cardiac endorgan damage 14 (56%) 3 (33%) 9 (56%) 13 (48%) 6 (43%) 7 (54%)

Antihypertensive medication Number of 2.471.4 2.971.4 2.171.3 3.271.4 3.971.0 2.271.2 antihypertensive drugs ACE inhibitors 8 (32%) 4 (44%) 4 (25%) 9 (33%) 5 (36%) 4 (31%) receptor 11 (44%) 4 (44%) 7 (44%) 12 (44%) 8 (57%) 4 (31%) blockers -channel blockers 11 (44%) 3 (33%) 8 (50%) 16 (59%) 11 (79%) 5 (38%) 13 (52%) 6 (67%) 7 (44%) 17 (63%) 12 (86%) 5 (38%) Alpha blockers 2 (8%) 0 (0%) 2 (13%) 4 (15%) 2 (14%) 2 (15%) 2 (8%) 1 (11%) 1 (6%) 1 (4%) 1 (7%) 0 (0%)

Abbreviation: ACE, angiotensin-converting enzyme.

Journal of Human Hypertension Endurance training and beta-blockade TH Westhoff et al 488 randomized to exercise or control group. Twenty- progressively increased to 30, 32 and 36 min and five patients were randomised to the exercise group, carried out without interruption. Training intensity 27 were randomized to the control group. Nine corresponded to the speed necessary to reach a patients in the exercise and 14 patients in the lactate concentration of 2.070.5 mmol/l in control group were on beta-blockers. In the exercise blood. Heart rate during training was controlled by group, patients were on metoprolol, bisoprolol or a heart-rate monitor (Polar Sport Tester, Kempele, atenolol. In the control group, two patients were on Finland); blood pressure was measured according , one patient on nebivolol and the other to Riva-Rocci every 5 min with the proband still patients were on metoprolol, bisoprolol and atenolol walking; lactate concentration was controlled every as well. There were no patients on negative chrono- fifth training day. As lactate concentration sank tropic calcium-channel blockers such as verapamil below 1.8 mmol/l or increased beyond 2.2 mmol/l, or . Mean number of antihypertensive target heart rate was adapted until target levels drugs and pattern of antihypertensive medication were reached. If exercise heart rate decreased by is presented in Table 1 for exercise and control more than 5/min as a result of training adaptation, group. The pre-existing antihypertensive medica- treadmill speed was increased by 0.5 km/h or tion remained unchanged throughout the study. elevation was increased by 3% to maintain training Written informed consent was obtained from all intensity. We have previously shown that this participants before inclusion in the study. The study training protocol leads to a substantial increase was approved by the local ethics committee at the of physical performance in short time.20 During Charite´ Berlin. training, patients were continuously supervised by a physician. Patients in the control group did not participate in a structured exercise programme. Protocol Assessment of physical performance and 24-h ABP monitoring were performed before and after the Assessment of endothelial function by flow-mediated observation period. Assessment of physical perfor- dilation mance was carried out by a treadmill stress test Endothelial function was assessed in the brachial using a modified Bruce protocol (begin with 3 km/h, as reported previously.21,22 By means of high- increase of speed by 1.4 km/h after 3 min, thereafter resolution ultrasound, diameter changes in response increase of elevation by 3% at constant speed) under to reactive (flow-mediated vasodilation, continuous ECG monitoring.19 In this protocol, each FMD) and glyceroltrinitrate (GTN), were measured, workload corresponds to an increase of 25 W for according to standard protocols.22–25 Accuracy and a patient of 75 kg weight. Lactate concentration in reproducibility of the method had been documented capillary blood was determined at the end of each previously.21,22 Flow-mediated vasodilation in res- workload and lactate thresholds were determined ponse to reactive hyperaemia (FMD) represents according to Kindermann et al.11 endothelium-dependent vasoreactivity, whereas Twenty-four-hour ABP monitoring was performed vasodilation in response to GTN indicates smooth using Spacelabs 90207 monitors (Spacelabs, Red- muscle-cell function and is independent of endothe- mond, WA, USA). As sports affect night-time lial function.23 The brachial artery was examined by blood pressure (BP) values only marginally and two-dimensional ultrasound images, with a 10-MHz several probands denied to wear their devices at linear array transducer and a standard 128XP/ night because of the sleep-disturbances, only day- 10c-system (Acuson, Mountain View, CA, USA). time (0600–2200) values are presented. There was The transducer was positioned proximal to the one measurement before and after the observation elbow to obtain a longitudinal picture of the brachial period. Intervals between single measurements were artery. Diameters were measured by a computerised set to be 20 min. The follow-up BP and vascular edge-detection programme (Cardiovascular Imaging measurements of the training group were conducted Software, Information-Integrity, Boston, MA, USA); within 2 days after the last training session. the images were acquired ECG-triggered at end- The training programme, consisting of walking on throughout the study. a treadmill according to an interval-training pattern, A resting scan was recorded for 2 min. A pneu- was carried out three times a week for 12 weeks. If matic tourniquet, placed distal of the subject’s patients missed a training session, the programme elbow, was then inflated to a pressure of 300 mm was prolonged until they performed 36 workouts. Hg for 3 min. The release immediately induces The initial duration of training sessions was 30 min. increased blood flow in the subject’s forearm for a During the first week, training consisted of five few seconds, which represents the stimulus for workloads of 3 min; between workloads, patients endothelium-dependent vasodilation. A break of walked with half-speed for 3 min. Exercise duration 10 min with the patient continuously staying in a was gradually increased to 4 Â 5 min/day in the supine position was required before the scan for second week, 3 Â 8 min/day in the third, 3 Â 10 min/ endothelium-independent vasodilation was started. day in the fourth and 2 Â 15 min/day in the fifth After a resting scan of 2 min, 400 mg GTN was week. In the sixth and further weeks, exercise was administered sublingually; the scan was completed

Journal of Human Hypertension Endurance training and beta-blockade TH Westhoff et al 489 5 min after application. The same experienced (body mass index) at baseline and comparison of the person performed all of the scans. The computer- baseline-adjusted change of these parameters were assisted calculation of vessel diameters was performed using an analysis of variance (ANOVA). conducted in a blinded manner as reported Lactate curves of initial treadmill stress tests previously.21,22 FMD represents the percentage of (Figure 1a) were constructed using a third-order diameter increase caused by shear stress compared polynomial regression. Po0.05 was regarded to be with baseline. The nitrous oxide (NO)-independent statistically significant. dilation represents the percentage of diameter increase induced by GTN compared with baseline. Results Statistical analysis Results are presented as mean7s.d. Number of Exercise and control groups were homogeneous antihypertensive drugs in each group is presented for age and number of antihypertensive drugs as as median and range. Comparison of systolic ABP, presented in Table 1 (P40.05 each). At the initial diastolic ABP, BP on exertion, FMD, GTN and BMI examination, diastolic ABP was slightly but signifi-

Figure 1 Effect of beta-blockade on baseline treadmill stress tests. (a, b) Lactate levels (mmol/l) and average lactate curve (polynomial third-order regression), (c, d) physical performance (W), (e, f) perceived exertion according to Borg rating scale (1–20) in dependence of heart rate in absence or presence of beta-blockade. Data derived from baseline stress tests of training and control group.

Journal of Human Hypertension Endurance training and beta-blockade TH Westhoff et al 490 Table 2 Cardiovascular effects of exercise

Exercise group (n ¼ 25) Control (n ¼ 27) Exercise vs control

Baseline Follow-up Delta Baseline Follow-up Delta Baseline Delta (P) (P)

Systolic ABP (mm Hg) 141.7713.5 131.179.4 10.6710.5 137.9711.1 138.2713.5 À0.379.3 0.28 o0.01 Diastolic ABP (mm Hg) 80.278.4 74.477.5 5.875.9 75.377.1 74.778.4 0.675.4 0.03 o0.01 Systolic BP at 100 W 194.3726.9 170.0723.1 24.3726.6 194.6726.4 187.5723.8 7.1721.8 0.35 0.07 (mm Hg) Diastolic BP at 100 W 76.978.4 67.176.2 9.877.0 74.6715.6 70.4711.0 4.278.2 0.10 0.04 (mm Hg) Endothelium-dependent 5.571.7 7.972.9 À2.472.2 6.172.3 6.372.4 À0.273.1 0.98 o0.01 vasodilation (%) Endothelium- 13.076.7 12.876.3 0.275.0 10.175.7 9.373.9 1.275.3 0.58 0.48 independent vasodilation (%) BMI (kg/m2) 27.774.4 27.574.4 À0.270.7 30.174.4 30.374.6 0.370.9 0.07 0.07

Abbreviations: ABP, ambulatory blood pressure; BP, blood pressure; BMI, body mass index; NS, nonsignificant. Delta, change of parameter in the observation period; data presented as mean7s.d.; Po0.05 was regarded significant.

Table 3 Cardiovascular effects of exercise with and without beta-blockade

Patients on beta blockers (n ¼ 9) Patients without beta blockers (n ¼ 16) Beta blockade vs no beta blockade

Baseline Follow-up Delta Baseline Follow-up Delta Baseline Delta (P) (P)

Systolic ABP (mm Hg) 140.4719.9 129.9710.3 10.6713.5 142.478.9 131.879.1 10.678.8 0.74 1.0 Diastolic ABP (mm Hg) 78.3711.3 72.775.2 5.778.6 81.276.4 75.378.5 5.874.0 0.43 0.94 Systolic BP at 100 W 195.0729.5 153.3719.7 41.7731.3 194.0726.9 176.7721.4 17.3721.9 0.94 0.06 (mm Hg) Diastolic BP at 100 W 80.8710.2 69.272.0 11.7710.3 75.377.4 66.377.2 9.075.4 0.18 0.44 (mm Hg) Endothelium-dependent 5.871.9 8.972.3 À3.172.1 5.371.6 7.373.2 À1.972.2 0.53 0.20 vasodilation (%) Endothelium- 14.077.8 13.376.4 0.675.6 12.57 6.2 12.676.4 À0.174.8 0.61 0.75 independent vasodilation (%) BMI (kg/m2) 25.474.9 25.274.7 À0.270.3 28.873.8 28.773.9 À0.270.8 0.07 0.99 Performance at 2 mmol/l 77.1744.7 141.5733.2 64.4754.1 104.6729.6 152.6729.9 48.0728.3 0.08 0.34 lactate (W) Performance at 3 mmol/l 126.9750.2 160.6736.0 47.8752.0 139.7728.4 181.3733.5 41.6722.2 0.43 0.72 lactate (W)

Abbreviations: ABP, ambulatory blood pressure; BP, blood pressure; BMI, body mass index; NS, nonsignificant. Delta, change of parameter in the observation period; data presented as mean7s.d., Po0.05 was regarded significant.

cantly lower in the control than in the exercise tensive drugs, ABP values, BP at exertion, endo- group (75.377.1 vs 80.278.4, P ¼ 0.03; Table 2). thelium-dependent and -independent vasodilation, There was no significant difference for baseline BMI and physical performance as well (P40.05 systolic ABP, systolic BP at 100-W activity, diastolic each, Table 3). BP at 100-W activity, endothelium-dependent vaso- All patients completed the study. Comparison of dilation, endothelium-independent vasodilation the changes of BP in exercise and control group and BMI in exercise and control group (P40.05 showed that the exercise programme resulted in each; Table 2). Furthermore, there were no signifi- a significant decrease of systolic and diastolic ABP cant differences between baseline physical perfor- of 10.6710.5 and 5.875.9 mm Hg, respectively mance at 2 mmol/l lactate (94.3737.6 vs 93.2748.0 (Po0.01, Table 2). Systolic BP on exertion (100 W) W, P ¼ 0.94) and at 3 mmol/l lactate (135.3736.8 vs tended to be largely decreased by 24.3726.6 mm Hg 125.4750.9 W, P ¼ 0.50). Within the exercise group, (P ¼ 0.07, Table 2) and diastolic BP on exertion (100 the beta-blocker- and non-beta-blocker subgroups W) was significantly diminished by 9.877.0 mm Hg were homogeneous for age, number of antihyper- (P ¼ 0.04, Table 2) compared with the changes in

Journal of Human Hypertension Endurance training and beta-blockade TH Westhoff et al 491 the control group. The decrease of BP cannot be ascribed to a reduction of body weight, as BMI was not significantly altered (Table 2). Endothelium- dependent vasodilation, however, significantly improved from 5.571.7 to 7.972.9% (Po0.01). In contrast to endothelium-dependent vasodilation, endothelium-independent vasodilation as induced by application of GTN was not significantly changed (P40.05, Table 2). At the initial treadmill stress test, the average lactate curve of the beta-blocker patients of the whole study population shows a lower slope com- pared with the non-beta-blocker patients. Further- more, there is a left-shift indicating that higher lactate values were reached at lower heart rates (Figure 1a and b). Physical performance and per- ceived exertion were higher at lower heart rates as well (Figure 1c–f). In the exercise group, the beta- blocker patients tended to show lower physical performance at lactate concentrations of 2 mmol/l (P ¼ 0.08, Table 3). Both in the beta-blocker and non- beta-blocker patients, the exercise training evoked significant reductions of systolic ABP, systolic BP on exertion and diastolic BP on exertion (Po0.05 each, Table 3). FMD was significantly increased in both groups (Po0.05, Table 3), whereas GTN was not significantly altered (P40.05, Table 3). Diastolic ABP was significantly reduced in the non-beta- blocker group (Po0.01, Table 3) and tended to be lower in the beta-blocker group without reaching significance (P ¼ 0.08, Table 3). The extent of BP reduction and improvement of endothelial func- tion did not significantly differ between beta-blocker and non-beta-blocker patients (P40.05 each, Table 3). Furthermore, there was no significant impact of the different beta-blocking substances on the decrease of systolic BP (P40.05). Physical performance was increased both in the beta-blocker and non-beta-blocker groups as indicated by the right-shift of average lactate curves (Figure 2a and b), whereas the lactate curve remained unchanged in the control group (Figure 2c). Performance at 2 and 3 mmol/l lactate improved significantly with and without beta-blockade (Po0.05 each, Table 3). There was no significant difference of improvement of performance at these levels between beta-blocker and non-beta-blocker patients (P40.05, Table 3). Figure 2 Effect of exercise training on lactate curves in absence Heart rate was measured every 5 min during a and presence of beta-blockade. Data derived from treadmill stress training session. Calculated for the 12 weeks of tests before and after the training programme from patients with 7 (a) and without (b) beta-blockers. Lactate levels are presented in exercise, mean training heart rate was 97.2 7.7/min mmol/l, lactate curves are constructed by polynomial third-order in the presence of beta-blockade and vs 118.377.5/ regression and (c) patients of the control group at baseline and min in the absence of beta-blockade. This difference follow-up. was highly significant (Po0.001). Mean heart rate at rest was 68.277.5/min in the beta-blocker group and 84.979.4/min in the non-beta-blocker group Discussion (Po0.001). Lactate was measured every fifth train- ing session. Mean lactate concentration did not The present work constitutes the first randomized, differ significantly in the beta-blocker and in the controlled trial on the differential effects of a lactate- non-beta-blocker group (1.970.4 vs 2.170.5 mmol/ based cardiovascular exercise training on BP and l, P40.05). vascular function in the absence and presence of

Journal of Human Hypertension Endurance training and beta-blockade TH Westhoff et al 492 beta-blockade. Our data provide first insight into patients. Endothelium-dependent vasodilation is lactate-based assessment of training heart rates for improved in both groups as well. The reduction hypertensives with beta-blockers. of BP on exertion even tends to be higher in The 12-week exercise programme led to a marked the presence of beta-blockade. The difference only improvement of physical performance as repre- slightly fails to be significant for systolic values. sented by the right shift of the lactate curve. The Thus, it may be summarised that beta-blockers American College of Sports Medicine criticised that do not constitute a drawback for an efficient cardio- in most studies on endurance training, BP was not vascular endurance training. measured by a blinded observer or an automated Regular physical exercise is a helpful adjunct to device and emphasised the need for studies using control BP even in old hypertensives. Our findings 24-h ABP monitoring.26 We complied with this show that exercise can be recommended to patients recommendation and our data objectively present a with beta-blockers as well. Both the reduction of BP significant improvement of daytime ABP. Further- and the improvement of endothelial function more, the exercise programme led to a significant decrease cardiovascular risk. In order to avoid poten- decrease of blood pressure on exertion. A recent tially harmful BP peaks or coronary events under meta-analysis, which involves 72 trials on exercise exertion, stress ECG is recommended before initia- training including 30 hypertensive study groups tion of training in patients at high risk of coronary describes an average decrease of resting BP and artery disease or with high resting blood pressure. daytime ABP of 3.0/2.4 and 3.3/3.5 mm Hg, respec- How to determine the optimum training heart rate tively. The reduction of resting BP was more in the presence of beta-blockade still remains the pronounced in the hypertensive study groups question. In the present study, an average lactate- (À6.9/À4.9 mm Hg) than in others (À1.9/À1.6 mm level of about 2 mmol/l corresponded to a training Hg).3 Compared with these data, our results reveal heart rate of about 97/min at a mean patients’ age of even higher reductions of BP, indicating an efficient 66 years. This heart rate was 18% lower than in training concept. As reflected by the increase of the non-beta-blocker group with patients of compar- FMD, the decrease of BP is associated with an able age. It has to be kept in mind that the study improvement of endothelial function. The lacking population reviewed various types and doses of beta- increase of vasodilation to GTN shows that the blockers. Therefore, this finding has to be regarded improvement of endothelium-dependent vasodila- as a first rough estimation of target heart rate for tion was not based on an alteration of the mechan- cardiovascular endurance training in the presence of ical dilatory properties of the artery. As BMI values beta-blockade. In order to find out whether this heart remained unchanged during the observation period, rate is the optimum training heart rate, further the reduction of BP cannot be attributed to a loss of studies are required, comparing beta-blocker patients body weight. who perform exercise trainings at different target Beta-blockers are known to reduce heart rate by lactate levels with identical doses of beta-blocking 10–20% both in rest and under exertion.14 The drug agents. The following table summarises what the lowers the sympathoadrenergic discharge to the present study adds to our knowledge on the effects heart and circulation, particularly in states of of endurance training in hypertensives. elevated sympathetic tone. In healthy subjects, beta-blockade leads to a decrease of , Summary of the findings of the present study and maximum aerobic performance What is known about endurance training of hypertensives and capacity, whereas the arteriovenous differ- beta-blockade ence increases.27 These effects are shared by all K Depending on the concept of the training program, aerobic types of beta-blockers.28 Our data show that chronic endurance training can lead to a substantial decrease of blood beta-blockade induces a left-shift of physical perfor- pressure in hypertensives. K Percentage of maximal heart rate is the most widely accepted mance, lactate-levels and perceived exertion in parameter for the prescription of training intensities. dependence of heart rate in hypertensives. The K Acute treatment with beta-blocking drugs modifies local training-induced cardiovascular benefits, however, muscular metabolic properties and impairs endurance are not diminished by beta-blockade. Endothelium- exercise capacity resulting in an increase in perceived dependent vasodilation can be elicited by applica- exertion, lower VO2max and lower work rate, whereas the 29 influence of chronical administration of beta-blockers is tion of b2-mimetic drugs (Zitat: Wilkinson et al. ). discussed controversially. In the exercise group, all patients with beta-block- What this study adds to this knowledge ade were on b1-selective drugs. These drugs are supposed to show no interaction with endothelium- K Lactate-based aerobic endurance training evokes comparable cardiovascular benefits in presence and absence of beta- dependent vasodilation. As the exercise-induced blockade and beta-blockade does not attenuate the exercise- improvement of endothelium-dependent vasodila- induced improvement of endothelial function. tion may be of crucial relevance for the BP K Chronic application of beta-blockers induces a left-shift of reduction, this might contribute to the explanation physical performance, lactate-levels, and perceived exertion in dependence of heart rate. of the present findings. K In the present study target training heart rate with beta- Systolic and diastolic ABP decrease by an almost blockers is about 18% lower than without. identical extent in beta-blocker and non-beta-blocker

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