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Morning versus Evening Aerobic Training Effects on Blood Pressure in Treated Hypertension

BRITO, LEANDRO C.1; PEÇANHA, TIAGO1; FECCHIO, RAFAEL Y.1; REZENDE, RAFAEL A.2; SOUSA, PATRÍCIA1; DA SILVA-JÚNIOR, NATAN1; ABREU, ANDREA3; SILVA, GIOVÂNIO3; MION-JUNIOR, DÉCIO3; HALLIWILL, JOHN R.4; FORJAZ, CLAUDIA L. M.1

Author Information
Medicine & Science in Sports & Exercise: April 2019 - Volume 51 - Issue 4 - p 653-662
doi: 10.1249/MSS.0000000000001852

Abstract

Hypertension is estimated to affect 1 billion persons worldwide and is considered one of the most important cardiovascular risk factors, being responsible for 8 million deaths per year, mainly due to cardiovascular causes such as stroke, myocardium infarction, or sudden death (1). Although antihypertensive medications may control blood pressure (BP) (2), low physical activity is an independent risk factor for cardiovascular morbidity and mortality even in treated hypertensives (3). Thus, the increase of physical activity levels, mainly by performing aerobic training, is recommended as a complementary therapy to medication in hypertension (4,5).

The hypotensive effect of aerobic training has been extensively reported in literature. A classic meta-analysis (6) that included 26 randomized controlled trials with hypertensives concluded that aerobic training decreases systolic BP (SBP) by −8 mm Hg (−11 to −6 mm Hg) and diastolic BP (DBP) by −5 mm Hg (−7 to −3 mm Hg), with the greater reductions obtained with training sessions conducted 2–3 times per week, lasting 30–45 min and with moderate intensity. However, despite this well-known chronic hypotensive effect (evidence category A) (7), BP reductions after aerobic training vary across studies, and some factors, such as higher initial BP, moderate to high training intensities, and concomitant diet-induced weight-loss, have been identified as promoters of greater BP decrease (6,8). Further, up to 25% of hypertensives appear to be nonresponders to exercise and do not demonstrate BP decreases because of genetic characteristic and/or other unrecognized factors (9). For these reasons, other factors that potentiate the hypotensive effect of aerobic training must be investigated.

Along these lines, the time of day at which aerobic training is performed may influence BP reductions after training. The BP decrease that occurs after a single session of aerobic exercise has been shown to be greater when exercise was performed in the evening than in the morning (10,11). In addition, acute and chronic hypotensive effects of aerobic exercise are highly correlated (12,13), consistent with the concept that the chronic effects of training may result from the sum of its acute effects (12–14). This suggests a novel concept that aerobic training performed in the evening might potentiate chronic BP reductions. In further support of this concept, the greater BP decrease observed after an acute session of evening aerobic exercise has been attributed to a greater decrease in systemic vascular resistance (SVR) (10), which is also the main mechanism responsible for BP reductions after aerobic training (i.e., a decrease in SVR explains the training-induced decrease in BP) (15).

Despite this background suggesting a better benefit of evening aerobic training for hypertensives, to the best of our knowledge, no previous study has compared the hypotensive effects of aerobic training performed at different times of day. Thus, this study was designed to compare the effects of 10 wk of aerobic training, performed in the morning versus in the evening, on clinic and ambulatory BP as well as on hemodynamic and autonomic mechanisms. The hypothesis was that clinic and ambulatory BP would decrease after training performed at both times of day due to a decrease in SVR, but these reductions would be greater after the evening than the morning training (MT).

METHODS

Study participants

The subjects were recruited through advertisements at the university campus and social media as well as in hypertension awareness campaigns conducted at different regions of the city of São Paulo, Brazil. To participate, subjects needed to be men, between 30 and 65 yr of age, and with resting SBP and DBP lower than 160 and 105 mm Hg, respectively, while receiving antihypertensive drugs for at least 4 months. Exclusion criteria included the following: (i) participation in regular exercise more than once a week; (ii) presence of secondary hypertension and/or target-organ damage; (iii) presence of morningness or eveningness chronotypes (i.e., scores <42 or >58, respectively, in the Horne and Ostberg questionnaire) (16); (iv) presence of obesity stage 2 or greater (i.e., body mass index—BMI ≥ 35 kg·m−2) (17); (v) presence of other cardiovascular disease besides hypertension; (vi) insulin use; (vi) use of medications that directly affect cardiac autonomic modulation assessment, such as beta-blockers and nondihydropyridine calcium channel blockers; (vii) presence of any cardiovascular abnormality in resting or exercise ECG; and (viii) unavailability for participating either in the morning or evening training (ET). In addition, if doses and/or type of antihypertensive drugs changed during the study, the subject was excluded.

This study followed the principles in the Declaration of Helsinki, has been approved by the Research Ethical Committee of the School of Physical Education and Sport of the University of São Paulo (no. 966.072), and was registered at the Brazilian Clinical Trials (www.ensaiosclinicos.gov.br/rg/RBR-7q7pz7/).

Preliminary exams

Subjects who agreed to participate signed the informed consent and underwent preliminary exams to verify whether they fulfill the study criteria. Medical history was investigated in a detailed interview with a physician. Resting auscultatory BP was measured three times after 5 min of seated rest with a mercury sphygmomanometer (Uniteq, São Paulo, Brazil). This procedure was repeated in two visits, and the mean BP of the six measures was calculated (4,5). Body weight and height were measured (Filizola S.A., Personal, Campo Grande, Brazil), and BMI was calculated. Chronotype status was confirmed using the Horne and Ostberg questionnaire (16). The presence of target-organ damage and possibility of secondary hypertension were assessed through a detailed screening, including blood and urine analyses (5). ECG at rest and during maximal exercise test were analyzed for exclusion of cardiac abnormalities (18).

Study design and experimental protocol

This was a randomized controlled trial designed to compare the effects of morning and evening aerobic training on clinic and ambulatory BP, as the primary outcomes, and on hemodynamic and autonomic mechanisms, as the secondary outcomes. For that, the subjects were randomly allocated to one of three groups: MT (7:00–9:00 am), ET (6:00–8:00 pm), or control (C) group. Half of the subjects from the C group were randomly assigned to participate in the control intervention at 7:00–9:00 am and the other half at 6:00–8:00 pm to assure the circadian exposition. These specific periods were chosen because they overlap the morning increase (7:00–9:00 am) and the evening decrease (6:00–8:00 pm) of BP (19). In addition, acute postexercise hypotension has been reported to be different between exercises conducted at these specific periods (10). Thus, these aspects suggest that the times chosen are more likely to reveal any possible effect of time of day on training responses.

Randomization for the groups was conducted by chance, using a blocking method. Every three subjects who entered the study drew a number from a bag to determine their groups: MT, ET, or C. Then the subject who took the C group did a new raffle to be allocated in either the morning or the evening to perform the control intervention. In the next three subjects’ randomization block, the subject sorted for the C group performed the control intervention in the other time of day. This process was supervised by a blinded researcher. Interventions in all groups (MT, ET, and C) occurred 3 times per week for 10 wk and were supervised by a bachelor in physical education. After this period, all subjects were reevaluated (see Figure, Supplemental Digital Content 1, Study flowchart: enrollment, randomization, interventions and follow-up, http://links.lww.com/MSS/B459).

Initial and final evaluations were composed by 1) two maximal cardiopulmonary exercise tests conducted in a random order and separated by at least 3 d: one in the morning (7:00–9:00 am) and one in the evening (8:00–10:00 pm); and 2) two resting cardiovascular evaluations conducted in the same day, the first in the morning (7:00–9:00 am) and the second in the evening (6:00–8:00 pm), and at least 3 d after the last maximal exercise test. Final evaluations were initiated 3–4 d after the last training session.

Before all evaluations, the subjects were instructed to avoid physical efforts and alcoholic beverages for the previous 24 h and to take their antihypertensive medication as usual. Laboratory temperature was kept between 20°C and 22°C, and the windows were uncovered assuring luminosity as a time clue for circadian adjustments (20).

For the maximal cardiopulmonary exercise tests, subjects were instructed to have a light meal 2 h before. The tests were conducted on a cycle ergometer, initiating with a 3-min warm-up at 30 W, followed by 15-W increases every minute until the subjects were unable to maintain 60 rpm. ECG and V˙O2 were continuously measured and BP was measured every 2 min.

For the resting cardiovascular assessments, subjects were instructed to arrive at the laboratory after an overnight fast for the evaluation at 7:00–9:00 am, and with at least 4 h fasting for the evaluation at 6:00–8:00 pm. Thirty minutes before the assessments, the subjects received a standardized meal (two cereal bars: approximately 148 kcal, with 84% carbohydrate, 8% protein, and 7% fat each; and 50 mL of juice: approximately 27 kcal with 100% carbohydrate). Then they rested in the seated position for a total of 40 min. ECG, beat-by-beat BP, and breath-by-breath respiratory signals were registered from minutes 10 to 20 for autonomic evaluation. Auscultatory BP, HR, and cardiac output (CO) were measured in triplicate between minutes 20 and 40. In addition, after the evening assessments, an ambulatory BP monitor was positioned on the subjects’ nondominant arm and was removed after 24 h of recording.

Intervention

The training groups (MT and ET) performed progressive aerobic training only on cycle ergometer (CEFISE, Biotec 2100, Campinas, Brazil). Over the first 4 wk of training, exercise duration increased from 30 to 45 min. From the fifth week, intensity increased progressively every 2 wk from the HR at the anaerobic threshold to the HR 10% below the respiratory compensation point. This training protocol has shown to decrease BP and improve cardiovascular autonomic regulation in hypertensives (21). Training intensity was set up based on the maximal cardiopulmonary exercise test executed at the same time of day as the training sessions. During the training sessions, HR was continuously monitored (Polar A3tm, Kempele, Finland), and workload was adjusted to achieve the target HR. The subjects from the C group performed stretching exercises for 30 min. All subjects were instructed to keep the same routine throughout the study and not to participate in any other regular exercise program.

Measurements

During the maximal cardiopulmonary exercise tests, ECG was continuously registered (EMG System do Brazil, EMG, 030110/00B, São Paulo, Brazil), and auscultatory BP was measured with a mercury column (Uniteq). Oxygen uptake (V˙O2) was measured by a metabolic cart (CPX Ultima, Medical Graphics Corporation, St. Paul, MN) and analyzed in averages of 30 s. Anaerobic threshold and respiratory compensation point were determined in accordance with Skinner and McLellan’s criteria (22) by two different evaluators, and a third one was consulted to solve discrepancies.

During resting cardiovascular evaluations, the same experienced researcher, who was not blinded to the study group, made all auscultatory BP measurements using a mercury column (Uniteq). ECG (EMG System do Brazil, EMG 030110/00B) was continuously obtained and HR registered. CO was estimated by the indirect Fick method of CO2 rebreathing technique (23) using a metabolic cart (CPX Ultima, Medical Graphics Corporation) as previously reported (10). Stroke volume (SV) and SVR were calculated as follows: SV = CO/HR and SVR = mean BP/CO. The coefficients of variation of these measures in our laboratory are 8.9% for CO, 12.7% for SVR, and 11.1% for SV. As BP, HR, and CO were assessed in triplicate, the averages of these values were used for analyses.

Cardiovascular autonomic modulation was assessed by the spectral analysis of HR and BP variability. R-R intervals measured by ECG, beat-by-beat BP obtained by photoplethysmography (Finometer, Finapres Medical System, Arnhem, The Netherlands), and breath-by-breath respiratory signal assessed by a thoracic piezoelectric belt (UFI, Pneumotrace2, Morro Bay, CA) were continuously registered for 10 min through a data acquisition system (Windaq, Dataq Instruments, Akron, OH) with a sampling rate of 500 Hz per channel. These signals were exported to the software for analysis (Heart Scope II, v. 1.3.0.1; A.M.P.S. LLC, New York, NY). HR and BP variability was assessed by autoregressive analysis carried out in stationary segments of 300 beats. Cardiac sympathovagal balance was represented by the ratio between low- and high-frequency components of the HR variability (LF/HF) and vasomotor sympathetic modulation by the total variance of SBP variability (TVSBP). The oscillatory components of the time series were modeled by the Levinson–Durbin recursion, and the model order was chosen according to Akaike’s criterion (24), as previously described by the Task Force (25). Cardiac baroreflex sensitivity (cBRS) was assessed using the sequence technique as previously describe (26).

Ambulatory BP was recorded every 15 min for 24 h through an oscillometric device (Spacelabs 90207; Spacelabs, Inc., Redmond, WA). All subjects were instructed to avoid exercise and to keep similar daily routines during both initial and final evaluations. Only records with more than 85% of successful measures were analyzed. Data were averaged across time to provide the following measures: 24 h (all measurements), awake (all measurements taken while the subjects reported to be awaked), and asleep (all measurements taken while the subjects reported to be sleeping).

Statistical analysis

Considering a medium effect size (ES) (Cohen’s f of 0.30) for clinic SBP, a power of 0.80, and an α of 0.05 for a between–within ANOVA with three groups, the minimal sample size required for this study was 30 subjects (i.e., 10 per group) (G*Power v. 3.1.9.2, Universität Kiel, Germany). For the other variables, posteriori power analyses were conducted, and a power above 0.80 was also found for almost all analyses (22 analyses), except for asleep and 24-h SBP (β = 0.75 and 0.57, respectively), awake DBP (β = 0.65), DBP measured at the morning evaluation (β = 0.77), and HR, DBP, and TVSBP measured at the evening evaluation (β = 0.77, 0.39, and 0.05, respectively).

As this study intended to compare MT and ET efficacy and not efficiency, only data from the subjects who complete at least 75% of the intervention sessions were analyzed (i.e., non–intention-to-treat analysis).

The normality of data for each group was checked by the Shapiro–Wilk test (SPSS for windows; IBM, Chicago, IL). When a normal distribution was not observed, data were natural log-transformed (ln) and normality was achieved. The homogeneity among the groups was tested by the Levene test (SPSS for windows, IBM).

Data analysis was separately applied for each assessment period (7:00–9:00 am and 6:00–8:00 pm). A two-way between–within ANOVA (3 × 2) was used, considering group (MT, ET, and C) as the between factor and study phase (initial vs final) as the within factor. Post hoc comparisons were made using the Newman–Keuls test (Statistic for windows, Statsoft, USA). ANCOVA considering initial values as covariate was also used, but as results were similar to the ANOVA, they were not shown. For all analyses, P ≤ 0.05 was set as significant, and data are shown as mean ± SD. As a complementary analysis for clinic BP, the ES between the group responses at final evaluation (Final values) were calculated using the Cohen’s d and were classified as small (ES ≤ 0.49), medium (ES 0.50–0.79), or large (ES ≥ 0.80) (27).

RESULTS

A total of 210 subjects were interviewed, and 88 signed the consent to participate and underwent the preliminary exams. Twenty-one subjects did not fulfill the study criteria, and an additional 11 dropped out during the initial evaluation. Therefore, 56 subjects were randomized into the groups (MT = 18, ET = 18, and C = 20). During the interventions, 3 subjects from each training groups dropped out. Therefore, 50 subjects (MT = 15, ET = 15, and C = 20) finished the study and had their data analyzed (see Figure, Supplemental Digital Content 1, Study flowchart: enrollment, randomization, interventions and follow-up, http://links.lww.com/MSS/B459).

Subjects’ characteristics

The groups were well matched for age, anthropometrics, rest BP, chronotype, comorbidity, and antihypertensive drugs (Table 1). Adherence to training sessions was high and similar among the groups (MT = 95.3% ± 4.3%, ET = 96.9% ± 4.4%, and C = 95.7% ± 4.2%; P = 0.43).

TABLE 1
TABLE 1:
Baseline characteristics of the three groups: aerobic training in the morning (MT), aerobic training in the evening (ET), and control (C).

Exercise intensity was similar throughout the MT and ET (first training session: MT = 103.7% ± 5.4% vs ET = 102.6% ± 4.9% of HR of anaerobic threshold, P = 0.87; last training session: MT = 90.4% ± 3.3% vs ET = 89.2% ± 6.2% of HR of respiratory compensation point, P = 0.63). Absolute mean values of HR and workload throughout the training sessions were also similar between MT and ET (MT = 117 ± 9 vs ET = 124 ± 15 bpm, P = 0.20 and MT = 61 ± 15 vs ET = 57 ± 13 W, P = 0.32).

Weight did not change in neither group throughout the study (MT = 88.0 ± 12.3 vs 87.1 ± 12.0 kg; ET = 89.1 ± 14.9 vs 89.4 ± 14.3 kg; and C = 88.2 ± 15.9 vs 88.4 ± 15.7 kg, P = 0.23). V˙O2peak increased significant and similarly after the MT and ET at both morning and evening tests, and it did not change after the C (morning tests: MT = 21.4 ± 3.2 vs 23.1 ± 3.4 mL·kg−1·min−1; ET = 21.4 ± 3.4 vs 23.0 ± 4.6 mL·kg−1·min−1; and C = 21.1 ± 4.3 vs 21.0 ± 4.0 mL·kg−1·min−1, P = 0.05; and evening tests: MT = 22.2 ± 3.2 vs 24.5 ± 3.9 mL·kg−1·min−1; ET 21.0 ± 4.1 vs 23.3 ± 3.8 mL·kg−1·min−1; C = 21.7 ± 4.3 vs 21.7 ± 2.9 mL·kg−1·min−1, P = 0.03).

Clinic and ambulatory BP

All results of clinic BP are shown in Figure 1. For the morning evaluation, SBP decreased after MT and ET and did not change after C. Only the decrease after ET was different from C and greater than MT. The ES for ET versus C was medium (−0.63, CI = −1.03 to +0.07). For the evening evaluation, SBP decreased only after the ET, and this decrease was significantly different than MT and C. The ES values for ET versus C and ET versus MT were medium (−0.50, CI = −1.17 to +0.19; and −0.61, CI = −1.33 to +0.13, respectively). At both morning and evening evaluations, DBP decreased only after ET, but these reductions were not different from C. The ES values for ET versus C at both morning and evening evaluations were small (−0.36, CI = −1.04 to +0.34 and −0.29, CI = −0.97 to +0.41, respectively).

FIGURE 1
FIGURE 1:
Clinic BP assessed at the initial and the final evaluations in the three groups: aerobic training in the morning (MT = Δ ─), aerobic training in the evening (ET = ▴ ─), and control (C = □ —). Morning assessments (7:00–9:00 am): (A) SBP; (B) ES and confidence interval between groups of SBP; (C) DBP; (D) ES and confidence interval between groups of DBP. Evening assessments (6:00–8:00 pm): (E) SBP; (F) ES and confidence interval between groups SBP; (G) DBP; (H) ES and confidence interval between groups of DBP. *Different from initial evaluation in the same group (P ≤ 0.05). #Different from the C group at the same evaluation (P ≤ 0.05). †Different from MT at the same evaluation (P ≤ 0.05).

Ambulatory SBP did not change in any of the three groups whether presented as 24-h, awake, or asleep averages. Likewise, awake DBP also did not change. By contrast, 24-h and asleep DBP decreased only after ET, and these decreases were significantly different from MT and C (Fig. 2).

FIGURE 2
FIGURE 2:
Ambulatory BP at the initial and the final evaluations in the three groups: aerobic training in the morning (MT = Δ ─), aerobic training in the evening (ET = ▴ ─), and control (C = □ —): (A) 24-h SBP; (B) 24-h DBP; (C) awake SBP; (D) awake DBP; (E) asleep SBP; and (F) asleep DBP. Data = mean ± SD. *Different from initial evaluation in the same group (P ≤ 0.05). #Different from the C group at the same evaluation (P ≤ 0.05). †Different from MT at the same evaluation (P ≤ 0.05).

Hemodynamics and cardiovascular autonomic

All hemodynamic and autonomic variables are presented in Table 2, where significance levels are also shown. For morning evaluations (7:00–9:00 am), mean BP decreased only after ET, and this reduction was greater than after C and MT. CO did not change in any group, whereas SVR decreased after ET and MT, but only the decrease after ET was different from C. SV increased only after ET, and the response was different from after C, whereas HR decreased similarly after MT and ET, with both being different from after C. LF/HF measured after ET and MT were lower than after C. TVSBP increased after C and decreased only after ET, with responses after MT being different from and C and responses after ET different from C and MT. cBRS increased after MT and ET, with both increases being different from after C and the increase after ET greater than MT.

TABLE 2
TABLE 2:
Hemodynamic and cardiovascular autonomic variables evaluated in the morning (7:00–9:00 am) and in the evening (6:00–8:00 pm) at the initial and the final evaluation in the three groups: aerobic training in the morning (MT), aerobic training in the evening (ET), and control (C).

For the evening evaluations (6:00–8:00 pm), mean BP decreased only after ET, and this response was different than after C and MT. CO did not change in all groups, whereas SVR diminished only after ET, and this response was different than after C and MT. SV increased only after ET, and this response was different than after C, whereas HR decreased after MT and ET but only HR response after ET was different from after C. LF/HF and TVSBP did not change in any group. cBRS measured after ET was higher than after MT and C.

DISCUSSION

The main findings of the present study were that, in treated hypertensive men, only aerobic training performed in the evening produced clinic and ambulatory hypotensive effects. In addition, this hypotensive effect of evening exercise was accompanied by reductions in SVR and TVSBP and increases in cBRS.

After MT, only SBP assessed in the morning evaluation decreased significantly in comparison with the initial values. However, this response was not different from after C, indicating that this decrease in BP cannot be considered as a real hypotensive effect of MT. In addition, the ES of this comparison was really small (−0.09 vs C, Fig. 1B). Finally, as can be seen in Figure 3A and B, only 53% and 20% of the subjects responded to MT with a decrease in SBP above 4.7 mm Hg (i.e., the minimal detectable change calculated based on resting BP measurements) for morning and evening evaluations, respectively. On the other hand, clinic SBP decreases observed after ET in both evaluations, morning and evening, were significantly different from C and also from MT, showing a real hypotensive effect of the ET. In addition, decrease of SBP after ET presented medium ES (−0.63 vs C, Figure 1B), and individual data shown in Figure 3 demonstrate that most of the subjects (60% for evening assessment) decreased SBP above the minimal detected change after ET. Interestingly, only ET produced a significant decrease in 24-h and asleep DBP, and these responses differed from C and MT, also showing a real ambulatory hypotensive effect of ET. On the basis of these results, the present study showed that only ET decreased clinic and ambulatory BP in treated hypertensive men.

FIGURE 3
FIGURE 3:
Individual data of clinic SBP responses in the MT, ET, and Control (C) groups: dashed line (−−−−) as representative of minimal detectable change of SBP (−4.7 mm Hg). A. Effect after MT evaluated at 7:00–9:00 am. B. Effect after MT evaluated at 6:00–8:00 pm. C. Effect after ET evaluated at 7:00–9:00 am. D. Effect after ET evaluated at 6:00–8:00 pm. E. Effect after C evaluated at 7:00–9:00 am. F. Effect after C evaluated at 6:00–8:00 pm.

The clinic SBP/DBP decreases observed after ET were −5 ± 6/−3 ± 3 in the morning evaluations and −8 ± 7/−4 ± 3 mm Hg in the evening evaluations. In addition, the magnitude of 24-h and asleep DBP decreases observed in the present study were −3 ± 5 and −3 ± 4 mm Hg, respectively. These magnitudes might seem small at first, but they are within those reported in previous meta-analysis for aerobic training in hypertensives (i.e., clinic SBP/DBP decreases of −8 [−11 to −6]/−5 [−7 to −3] mm Hg, 24-h DBP decrease of −3 [−4 to −2] mm Hg, and asleep DBP decrease of −2 [−2 to −1] mm Hg) (6,8).

An intriguing result of the present study was the absence of BP reduction after MT. Few studies in literature reported the time of day at which training was conducted. In our literature search, only two studies reported the exact time of day of training, in one of them the subjects trained in the morning (28) and in the other part the subjects trained in the morning and the other part in the evening (29). Both studies did not report BP decrease after training, showing previous evidence of the lack of hypotensive effect with training in the morning. The reasons for the absence of hypotensive effect after MT are not clear, but a possible explanation may be the use of antihypertensive drugs. Previous study with animals found no additional decrease in BP when aerobic exercise was combined with antihypertensive treatment in comparison with medication treatment alone (30). In addition, the hypotensive effects of training are supposed to be lower when BP levels are lower (6,8). Antihypertensive drugs present their greatest activity until ~3 h after their ingestion (31). In the present study, all subjects took medications in the morning and only approximately 50% of them also took medications in the evening. Thus, all subjects in the MT went to training sessions under the greatest activity of antihypertensives, whereas only some subjects were under this greatest effect at the ET. Then it is possible to suppose that the concomitant action of medication might have blunted the hypotensive effect of aerobic training when training sessions were performed in the morning. However, these are only hypotheses that should be tested with an appropriate study design.

The absence of decrease in clinic DBP and in awake BP might also be unexpected. However, the effects of aerobic training on clinic DBP are usually lower when compared with SBP because many studies included in meta-analysis have not reported any diastolic hypotensive effect of aerobic training (6,8). Concerning awake BP, the same rational regarding the use of antihypertensives might be used because all subjects were under antihypertensive effects during the daytime, which might have mitigated the hypotensive effect of both training regimens. Actually, some previous studies with treated hypertensives also did not find reduction in ambulatory BP in treated hypertensives (32).

Regarding hemodynamic and autonomic results, as expected, at both time evaluations (morning and evening), BP reductions induced by ET were accompanied by a reduction in SVR (15). Among the possible mechanisms for reduced SVR, a reduction in sympathetic activity after aerobic training has been reported (33). In accordance, the current study observed a decrease in vasomotor sympathetic modulation, assessed by TVSBP (34). The new contribution of the present study was to show that these effects, i.e., the decrease of SVR and sympathetic vasomotor modulation as well as the increase of cBRS, were more evident after the aerobic training performed in the evening. It is interesting to note that a previous study reported that autonomic changes precede BP decrease induced by training in hypertensives rats (35), which may explain why MT have not produce a decrease in BP despite its effects on autonomic variables.

As expected, both trainings did not change CO but decreased HR (15), which was accompanied by a slightly change in LF/HF, especially in morning assessments. Previous studies (36,37) have also observed HR decrease after training accompanied by small changes in LF/HF, and the explanation for not observing greater effects on HR variability is mainly the fact that this assessment reflects cardiac autonomic modulation and not activity (25). In addition, the presence of antihypertensive treatment is also a possible explanation because some antihypertensives drugs, widely used in the current sample, such as angiotensin receptor type I blockers (47% of the subjects) and angiotensin-converting enzyme inhibitors (40% of the subjects), may have a chronic effect on HR variability (38) that might have masked the effect of training. It is interesting to observe that HR decrease was accompanied by an increase in cBRS, as previously reported (33). However, the novelty of the current study was to show that this effect on cBRS is more evident when training is conducted in the evening than in the morning. In addition, as cBRS was increased while HR decreased in the presence of BP maintenance after MT or decrease after ET, these results suggest that baroreflex set point was changed by training, especially after ET, which should be investigated in the future.

As clinical perspective, the greater hypotensive effect induced by ET may have clinical importance because a decrease of 3 mm Hg in clinic SBP has been associated with an 8% lower risk for stroke and 5% for coronary heart disease mortality (39). In addition, ambulatory BP and especially asleep BP are related to end-target damage and cardiovascular risk in hypertension (40). Thus, by decreasing asleep BP, ET may reduce hypertension consequences. Nevertheless, it is also interesting to highlight that cBRS is independently associated with mortality (41). Thus, as ET and MT increased cBRS, training at both times of day may have benefits on cardiovascular risk. The present results extend previous knowledge by showing that the clinical benefits of aerobic training in treated hypertensive men are especially greater when training is conducted in the evening. Therefore, training at this time of day may be especially recommended for those hypertensives who need a more intensive treatment, such as those with higher cardiovascular risk, resistant hypertension, or nondipper hypertension.

Although the present study has not revealed a significant hypotensive effect of MT, some variables related to BP control (such as HR, LF/HF, TVSBP, and cBRS) improved in the MT, suggesting that training at this time of day might also bring cardiovascular benefits. In addition, a nonsignificant decrease in BP in comparison with C was observed, suggesting that MT may decrease BP with a greater stimulus. As discussed before, experimental data suggest that autonomic adaptations precede the hypotensive effects of aerobic training (35); thus, a longer period of training may lead to a significant reduction of BP after MT. In addition, a greater weekly frequency and/or a higher intensity or duration may produce a quicker adaptation leading to BP reduction after MT. These hypotheses should be tested in the future.

We acknowledge that we limited our investigation to sedentary middle-age men, excluded extreme chronotypes, and limit training to 10 wk. Thus, it is necessary caution when generalizing the results to other conditions to lifelong exercisers, extreme morningness or eveningness chronotypes, other age-groups, or women. There is evidence that BP responses to training (42) vary between genders. As this is the first study investigating time of day influence on BP, only men were studied, and future studies should investigate women. Another potential confounder might be the antihypertensive medication use because some drugs are more likely to effect on exercise responses than others. Along this line, subjects receiving beta-blocker and nondihydropyridine calcium channel blockers did not participate in the study because of the direct effect of these drugs on HR variability assessed by spectral analysis. We are unable to say how subjects using these medications would have responded to either morning or ET. Evaluators not blinded to interventions may be considered a limitation; however, the same highly experienced evaluator performed all measurements, which minimizes the limitation (43). V˙O2peak was measured with cycle ergometer tests, and greater values may be achieved with treadmill tests. However, as training was conducted exclusively with cycling, testing with this ergometer is better to establish exercise intensity and to reveal the effects of training. Despite exercise and diet may change body composition and, consequently, decrease BP, diet was not controlled but the subjects were instructed to keep their eating habits. As their weight did not change, alterations in body composition are unlikely to have affected the results. Subjects’ physical activity was not monitored, but they were instructed to keep their daily routines throughout the study. Training exclusively in the morning or the evening was applied. As time of day has influenced training responses, future studies should investigate whether these effects are also different with training schedules combining training at different times of day (within the same day or in different days of the week). Finally, power analyses revealed low power (<0.50) for DBP and TVSBP evaluated at evening, increasing the chance of type II error for these variables. However, these variables did not reveal significant differences from C.

In conclusion, in treated hypertensive men, aerobic training performed in the evening decreased clinic and ambulatory BP because of reductions in vasomotor sympathetic modulation and SVR. In addition, aerobic training conducted at both morning and evening increased baroreflex sensitivity with a greater effect after ET.

The authors thank Fundaão de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/21676-6), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 304003/2014-0), and Coordenaão de Aperfeioamento Pessoal de Nivel Superior–Brasil (CAPES, financial code 001) for financial support. The authors also thank all volunteers for participating.

There is no conflict of interest. This study had no endorsement by the American College of Sports Medicine. All data are original, and none of them were fabricated or manipulated.

REFERENCES

1. Lawes CM, Vander Hoorn S, Rodgers A, International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371(9623):1513–8.
2. Yusuf S, Sleight P, Heart Outcomes Prevention Evaluation Study I Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145–53.
3. Ratnaparkhe V, Bhangale A. Left ventricular diastolic dysfunction in primary hypertension and its relation with leisure time physical activity. J Assoc Physicians India. 2015;63(7):20–4.
4. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–52.
5. Malachias MVB, Paulo César Veiga Jardim PCV Júnior, Almeida FA, Lima E Júnior, Feitosa GS. 7th Brazilian guideline of arterial hypertension: chapter 7—pharmacological treatment. Arq Bras Cardiol. 2016;107(3 Suppl 3):35–43.
6. Cornelissen VA, Smart NA. Exercise training for blood pressure: a systematic review and meta-analysis. J Am Heart Assoc. 2013;2(1):e004473.
7. Pescatello LS, Franklin BA, Fagard R, Farquhar WB, Kelley GA, Ray CA. Exercise and hypertension. Med Sci Sports Exerc. 2004;36(3):533–53.
8. Sosner P, Guiraud T, Gremeaux V, Arvisais D, Herpin D, Bosquet L. The ambulatory hypotensive effect of aerobic training: a reappraisal through a meta-analysis of selected moderators. Scand J Med Sci Sports. 2017;27(3):327–41.
9. Hagberg JM, Park JJ, Brown MD. The role of exercise training in the treatment of hypertension: an update. Sports Med. 2000;30(3):193–206.
10. de Brito LC, Rezende RA, da Silva Junior ND, et al. Post-exercise hypotension and its mechanisms differ after morning and evening exercise: a randomized crossover study. PLoS One. 2015;10(7):e0132458.
11. Park S, Jastremski CA, Wallace JP. Time of day for exercise on blood pressure reduction in dipping and nondipping hypertension. J Hum Hypertens. 2005;19(8):597–605.
12. Gkaliagkousi E, Gavriilaki E, Douma S. Effects of acute and chronic exercise in patients with essential hypertension: benefits and risks. Am J Hypertens. 2015;28(4):429–39.
13. Liu S, Goodman J, Nolan R, Lacombe S, Thomas SG. Blood pressure responses to acute and chronic exercise are related in prehypertension. Med Sci Sports Exerc. 2012;44(9):1644–52.
14. da Nobrega AC. The subacute effects of exercise: concept, characteristics, and clinical implications. Exerc Sport Sci Rev. 2005;33(2):84–7.
15. Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension. 2005;46(4):667–75.
16. Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol. 1976;4(2):97–110.
17. National Institutes of Health. The practical guide identification, evaluation, and treatment of overweight and obesity in adults. NIH Publication. 2000;(00_4084):1–75.
18. Sociedade Brasileira de Cardiologia S. III Diretrizes da Sociedade Brasileira de Cardiologia Sobre Teste Ergométrico. Arq Bras Cardiol. 2010;95(5 supl. 1):1–26.
19. Portaluppi FS, Smolensky M. H. Circadians rhythms and enviromental determinants of blood pressure regulation in normal and hypertensive conditions. In: Press H, editor. Blood Pressure Monitoring in Cardiovascular Medicine and Therapeutics. Totowa: Humana Press; 2007. pp. 133–56.
20. Golombek DA, Rosenstein RE. Physiology of circadian entrainment. Physiol Rev. 2010;90(3):1063–102.
21. Pitsavos C, Chrysohoou C, Koutroumbi M, et al. The impact of moderate aerobic physical training on left ventricular mass, exercise capacity and blood pressure response during treadmill testing in borderline and mildly hypertensive males. Hellenic J Cardiol. 2011;52(1):6–14.
22. Skinner JS, McLellan TM. The transition from aerobic to anaerobic metabolism. Res Q Exerc Sport. 1980;51(1):234–48.
23. Collier CR. Determination of mixed venous CO2 tensions by rebreathing. J Appl Physiol. 1956;9(1):25–9.
24. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84(2):482–92.
25. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93(5):1043–65.
26. Parati G, Di Rienzo M, Bertinieri G, et al. Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans. Hypertension. 1988;12(2):214–22.
27. Cohen J. CHAPTER 1 - The Concepts of Power Analysis. In: Statistical Power Analysis for the Behavioral Sciences (Revised Edition). Academic Press; 1977. pp. 1–17.
28. Dalleck LC, Allen BA, Hanson BA, Borresen EC, Erickson ME, De Lap SL. Dose-response relationship between moderate-intensity exercise duration and coronary heart disease risk factors in postmenopausal women. J Womens Health (Larchmt). 2009;18(1):105–13.
29. Finucane FM, Sharp SJ, Purslow LR, et al. The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial. Diabetologia. 2010;53(4):624–31.
30. Azevedo LF, Brum PC, Mattos KC, et al. Effects of losartan combined with exercise training in spontaneously hypertensive rats. Braz J Med Biol Res. 2003;36(11):1595–603.
31. Tanigawara Y, Yoshihara K, Kuramoto K, Arakawa K. Comparative pharmacodynamics of olmesartan and azelnidipine in patients with hypertension: a population pharmacokinetic/pharmacodynamic analysis. Drug Metab Pharmacokinet. 2009;24(4):376–88.
32. Guimaraes GV, Ciolac EG, Carvalho VO, D’Avila VM, Bortolotto LA, Bocchi EA. Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertens Res. 2010;33(6):627–32.
33. Laterza MC, de Matos LD, Trombetta IC, et al. Exercise training restores baroreflex sensitivity in never-treated hypertensive patients. Hypertension. 2007;49(6):1298–306.
34. Izdebska E, Cybulska I, Izdebskir J, Makowiecka-Ciesla M, Trzebski A. Effects of moderate physical training on blood pressure variability and hemodynamic pattern in mildly hypertensive subjects. J Physiol Pharmacol. 2004;55(4):713–24.
35. Masson GS, Costa TS, Yshii L, et al. Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity. PloS one. 2014;9(5):e94927.
36. Hua LP, Brown CA, Hains SJ, Godwin M, Parlow JL. Effects of low-intensity exercise conditioning on blood pressure, heart rate, and autonomic modulation of heart rate in men and women with hypertension. Biol Res Nurs. 2009;11(2):129–43.
37. Pattyn N, Beckers PJ, Cornelissen VA, et al. The effect of aerobic interval training and continuous training on exercise capacity and its determinants. Acta Cardiol. 2017;72(3):328–40.
38. Shehab A, Elnour AA, Struthers AD. A randomised, controlled, double-blind, cross-over pilot study assessing the effects of spironolactone, losartan and their combination on heart rate variability and QT dispersion in patients with chronic heart failure. Cardiovasc J Afr. 2008;19(6):292–6.
39. Stamler R. Implications of the INTERSALT study. Hypertension. 1991;17(1 Suppl):I16–20.
40. Hughes JW, Kobayashi I, Deichert NT. Ethnic differences in sleep quality accompany ethnic differences in night-time blood pressure dipping. Am J Hypertens. 2007;20(10):1104–10.
41. La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet. 1998;351(9101):478–84.
42. Collier SR, Frechette V, Sandberg K, et al. Sex differences in resting hemodynamics and arterial stiffness following 4 weeks of resistance versus aerobic exercise training in individuals with pre-hypertension to stage 1 hypertension. Biol Sex Differ. 2011;2(1):9.
43. Mancia G, Zanchetti A. One hundred years of auscultatory blood pressure: commemorating N. S. Korotkoff. J Hypertens. 2005;23(1):1–2.
Keywords:

CIRCADIAN RHYTHM; PHYSICAL ACTIVITY; HYPERTENSION; AMBULATORY BLOOD PRESSURE; VASCULAR RESISTANCE; BAROREFLEX CONTROL

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