Are three months multidisciplinary lifestyle intervention enough to get benefits on blood pressure in overweight/obese adults ?
Abstract
Keywords
- Exercise
- Lifestyle
- Obesity
- Blood Pressure
- Chronic disease
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INTRODUCTION
Physical activity is considered as one of the most important instruments for primary prevention of hypertension [1]. Since 2003 The National High Blood Pressure Education Program Coordinating Committee [2] and International Society of Hypertension [3] have recommended an approach aimed at improving lifestyle habits (engage in moderate physical activity; maintain normal body weight; limit alcohol consumption; reduce sodium intake; maintain adequate intake of potassium; and consume a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat) and decreasing elevated blood pressure (BP) levels for those with high normal BP or hypertension.
The WHO (World Health Organization) has reported that attributable mortality worldwide is greater for hypertension than for many traditional cardiovascular disease (Cardio Vascular Diseases, or CVD) risk factors (e.g., tobacco, abnormal lipids, undesirable body mass index (BMI) [4]. Normally physical exercise can cause an acute increase in both metabolic activity and systolic BP (SBP), while the diastolic BP (DBP) values lower slightly or are unchanged [5]. Some authors have underlined that an insufficient increase or drop in BP noted during incremental exercise testing could be associated with underlying cardiac and CVD [5]. On the other hand, it has been shown that a BP reduction of 5 mmHg is linked with stroke and heart disease reduction of 15%-20% [6]. The positive BP effects of physical exercise, including significant reductions in clinic systolic SBP, DBP and daytime ambulatory systolic (or DAYSBP) and diastolic (or DAYBP) BP have already been documented [7]. Further, Taylor [8] has suggested that in older sedentary men with stage 1 or 2 hypertension, the reduction in BP load from an acute exercise bout of just 45 minutes is immediately apparent and can persist for 24 hours. This phenomenon occurs through adjustments in the neuro-humoral mechanisms and could have an important clinical impact on cardiovascular health.
Prehypertension, well defined as SBP between 120 and 139 mmHg and/or DBP between 80 and 89 mmHg, requires health-promoting lifestyle modifications to prevent the progressive rise in BP values and cardiovascular disease.
Moreover, lifestyle modifications are essential for overweight/obesity and high BP prevention: these are generally the initial steps in diseases management. Multidisciplinary management of chronic metabolic diseases (e.g. diabetes, overweight and obesity) [9] are the recommended methodology: multidisciplinary interventions and exercise have been demonstrated to be effective in adults [10] and children [12] on ameliorate microcirculatory function, glycometabolic control, systemic blood pressure and exercise measures. Martinez Aguirre-Betolaza et al. [13] have stated that supervised exercise and a healthy diet may produce a significant improvement in the autonomic nervous system functioning, reducing heart rate and blood pressure.
Once cardiovascular risk factors are evaluated in patients with hypertension, it is essential to pay attention to lifestyles and behavioral habits that favorably affect BP levels and reduce the overall risk of cardiovascular disease [1]. Cardoso et al. [14] have observed that BP values are lower when evaluated after exercise with respect to BP measured before exercise sessions or on day without exercise. In order to be clinically relevant, BP reduction after exercise must have a considerable effect and it should be maintained for a long period of time under ambulatory conditions [14].
Some authors have already well clarified the Post-Exercise Hypotension (PEH) phenomenon as an acute physical exercise effect characterized by a sustained decrease in BP after a single bouts of exercise; the duration of PEH occurs from 10 minutes and persists until 24h after a bout of exercise [15]. An acute exercise session can promote the lowering of clinical BP during the post-exercise period in both hypertensive and normotensive subjects [16].
Although the effect of a single period of aerobic exercise on post-exercise DAYBP has been widely studied [17,18] discordant opinions remain when these effects are studied in different groups, for example normotensive or hypertensive subjects. Some authors have found support for the physical exercise effects on BP values detected in normotensive subjects after training [17], while others have not observed any change in post-exercise BP values of such subjects [19]. On the other hand, some studies which involved hypertensive subjects have demonstrated significant post-exercise ambulatory BP decreases [8,18-20].
To our knowledge, among the aspects not yet fully clarified were the exact time span within which benefits can be observed on pressure values induced by physical exercise and the different, specific, characteristics of the exercise (such as type, intensity, training length and muscle groups involved) that might also be important in determining post-exercise hypotension.
After aerobic exercise some authors have observed neural mechanism as a reduced sympathetic nerve muscle activity, cardiac autonomic balance and increased baroreflex sensitivity, as well as heart rate variability. Conversely, other studies that used exercise strength or maximum aerobic exercise have observed an increase in cardiac sympathy and vasomotor modulation, decreased parasympathetic modulation, and/or attenuation of baroreflex sensitivity [21]. Other evidence has shown an important mechanism working in the nervous system to adjust post exercise hypotension [22]. Though these effects require further studies to be fully understood, it seems to be widespread agreement among some authors that a single aerobic exercise episode decreases arterial pressure during the post-exercise period, especially in hypertensive subjects. Furthermore, this effect lasts for several hours and therefore it has clinical significance for hypertensive patients. Regarding PA type and intensity. Quinn et al. [18] observed greater hypotensive effects after heavy exercise compared to light exercise. In contrast with this observation, other authors have found that low-intensity exercise results in greater post-exercise hypotension: Park et al. [20] reported that post-exercise ambulatory hypotension lasted longer when the same exercise was divided into multiple short periods than when exercise was continuous.
Some authors argue that endurance training, compared to other types of training, reduces BP values more in hypertensive participants (8.3/5.2 mmHg) and that the regular practice of lower intensity (and duration) physical activity, although it reduces BP less than moderate or high-intensity exercise, is associated with at least a 15% decrease in mortality [23]. This evidence suggests that people with high BP should be advised to participate in at least 30 minutes of dynamic aerobic exercise (as walking, cycling, etc.) at moderate intensity, on 5–7 days weekly. Performance of resistance exercises on 2 - 3 days per week can also be advised. For additional benefit in healthy adults, a gradual increase in aerobic physical activity to 300 minutes a week of moderate intensity or 150 minutes a week of vigorous intensity aerobic physical activity, or an equivalent combination thereof, is recommended [16].
The American College of Sports Medicine guidelines proposes exercise programs for the person with hypertension that provides ≥ 30 min of accumulated physical activity on most days of the week at 40 to 60 % of maximum capacity [16]. Because a single bout of exercise can cause an acute reduction in BP that lasts many hours (e.g., Post Exercise Hypotension or PEH) thus augmenting or contributing to the reductions in BP resulting from exercise training [24], consideration should be given to daily or near-daily exercise. Some authors have explained that the acute and chronic depressor effects of dynamic exercise are a low-threshold phenomenon: the hypotensive responses are noted at an exercise intensity of 40% of maximum oxygen consumption [25]. Additionally, it seems that it’s possible to have this hypotensive effects related to physical exercise after only a few sessions of aerobic activity [26].
In overweight/obese adults the optimal exercise-training characteristics for reducing blood pressure (BP) are unclear to date. Some authors have stated that high-intensity interval training [27] and aerobic exercise programs [13] are to be considered as a treatment option for BP management.
To our knowledge, the exact magnitude of reduction in BP following exercise training is unclear to date. In this study we try to give very detailed data in a methodical assessment of blood pressure before and after exercise sessions.
Speculating that a multidisciplinary lifestyle intervention ameliorates some health-related variables, particularly blood pressure values, we try to explain if a few weeks of exercise is enough to achieve benefits on blood pressure in an overweight / obese adult group. This short term, retrospective study aims to show the effects of a multidisciplinary lifestyle intervention on some health-related measures. Particularly, it tries to contribute to the understanding of the exercise time-related effects on BP.
MATERIALS AND METHODS
Participants
The study involved 378 subjects (women n=226, man n=152, age median=52, min=18, max=75) affected by overweight/obesity (n=253, BMI median=33.9, min=24, max=52.3) or type 2 diabetes (n=125, BMI median=31.1, min=20.6, max=44.3) enrolled among the patients whom participated in C.U.R.I.A.Mo. (Centro Universitario Ricerca Interdipartimentale Attività Motoria) trial between January 2011 and December 2014. Inclusion criteria were: age between 18 and 75 years, BMI >27 kg/m2. Exclusion criteria are: concomitant diseases contraindicating physical exercise and failure to sign written informed consent. The C.U.R.I.A.Mo. trial was registered in the Australian New Zealand Clinical Trials Registry, ACTRN12611000255987 and it approved by the local Ethics Committee (CEAS Umbria Region, HREC number 1/10/1633).
Basing on DAYBP values, according to pharmacological treatment and ESH/ESC classification of BP levels (table 1) [28] the 378 participants - whose baseline sociodemographic data are reported in table 2 - will be allocated into resultant subgroups (table 3):
1) normotensive subjects group presenting SBP value < 120 mmHg and DBP value < 80 mmHg (n=89, mean SBP = 120 mmHg, min 100 - max 135; mean DBP 75 mmHg, min 55 - max 80) and no taking medications; 2) hypertensive subjects group, presenting SBP >140 mmHg and/or DBP >90 mmHg, or being on antihypertensive treatment (n=289, mean SBP 140 mmHg, min 100 - max 170; mean DBP 85 mmHg, min 60 - max 110); this group involved also the subjects presenting SBP > 140 and/or DBP> 90 and which are not in antihypertensive medicinal product regimen. To avoid the drug masking-effect, patients with normal high blood pressure who followed a pharmacological therapy with anti-hypertensive drugs were included in the group of hypertensive patients.
According to Center for Chronic Disease Prevention and Health Promotion BMI classification [29] participants’ sociodemographic data were presented into BMI subgroups (table 3), as follow: normal weight, BMI 18.5 – 24.9 (Norm); overweight, BMI<29.9 (Over); obese, BMI ≥30 (Ob) groups.
All subjects underwent to the C.U.R.I.A.Mo. lifestyle intervention program, lasting three month, that included [30]: 1) a first medical examination with the endocrinologist, to clinically evaluate the disease and any complications; 2) an interview with a psychologist to increase the subject’s motivation; 3) a nutritional interview to assess the nutritional behavior of the participants and to improve the Mediterranean diet adherence; 4) an individualized program consisting of 25 sessions (two per week) of structured indoor exercise, preceded by the medical specialist in sport medicine evaluation, to asses physical exercise measures.
Structured, mixed, indoor exercise program was supervised by a graduate in Sport Science with a maximum attendance of 5 patient/group, twice a week for three months. Each of 25 sessions lasts 90 minutes (60 minutes of aerobic workout and 30 minutes of circuit training for muscular strength and flexibility exercises). The aerobic workout was performed using ergometers (treadmill, ciclo- and arm ergometer) with work intensity gradually increased from 50% up to 70% of heart rate reserve. The workout for muscular strength will use isotonic machines for training of the lower and upper limbs, with gradual increase from 50 % of 1 repetition maximum (RM) estimated before starting the program. Two sets of 20 repetitions have been carried out for each exercise, with 45 seconds of rest between sets and exercises. Machine loads was gradually increased (every three weeks if it’s possible), according to the individual performance and capacity.
Definitions and classification of office blood pressure levels (mmHg). Adapted from 2018 ESH/ESC Guidelines for the management of arterial hypertension [28].
| Blood Pressure Category | Systolic BP | Conjunction | Diastolic BP |
|---|---|---|---|
| Optimal | <120 | and | <80 |
| Normal | 120–129 | and/or | 80–84 |
| High normal | 130–139 | and/or | 85–89 |
| Grade 1 hypertension | 140–159 | and/or | 90–99 |
| Grade 2 hypertension | 160–179 | and/or | 100-109 |
| Grade 3 hypertension | ≥180 | and/or | ≥110 |
| Isolated systolic hypertension | ≥140 | and | <90 |
Participants sociodemographic data.
| Indicator | Women | Man | ||||
|---|---|---|---|---|---|---|
| All=226 | Normo=70 | Hyper=156 | All=152 | Normo=19 | Hyper=133 | |
| Age | 49.34 ± 12.63 | 39.47±11.52 | 53.76±10.43 | 52.88±11.08 | 45.21±16.48 | 53.97±9.69 |
| Body weight (kg) | 89.7 ± 15.06 | 90.39±14.03 | 89.39±15.54 | 103.84±18.32 | 101.9±17.07 | 104.12±18.54 |
| BMI (Kg/m2) | 33.70 ± 4.95 | 34.04±4.60 | 33.54±5.10 | 33.52±5.15 | 32.18±4.25 | 33.71±5.25 |
| WC (cm) | 108.18± 11.51 | 107.06±11.96 | 108.69±11.31 | 115.03±12.56 | 112.05±10.86 | 115.46±12.76 |
| WHTR (cm) | 0.664±0.07 | 0.659±0.07 | 0.667±0.07 | 0.654±0.07 | 0.657±0.070 | 0.657±.0.7 |
| DAYSBP (mmHg) | 131.26± 12,62 | 121±8.49 | 135.57±11.55 | 136.65±14.11 | 121.05±7.56 | 121.05±7.56 |
| DAYDBP (mmHg) | 79.88± 8.75 | 73.15±6.59 | 82.7±7.97 | 83.78±9.85 | 73.16±7.49 | 85.3±9.2 |
Measures
During C.U.R.I.A.Mo. lifestyle intervention anthropometric measures such as height (expressed in cm), body weight (expressed in Kg), Body Mass Index (or BMI, expressed in Kg/m2), waist circumference (or WC, expressed in cm), body composition (as fat and muscle mass, expressed in %) and the waist-to-height ratio index (or WHTR) were evaluated. BP values as DAYSBP, DAYDBP, SBP and DBP (expressed in mmHg) were measured. Furthermore, physical exercise measures as maximum dynamic muscle strength (expressed in Kg), aerobic capacity or VO2max (expressed in in ml/O2/Kg/min) and flexibility (expressed in cm) were measured. All the variables were measured at the beginning and after three-months of intervention, as described below.
• Anthropometric measures, such as body weight and body composition, were performed during first medical examination, using Bioelectric Impendence Technology (BIA) trough body composition analyzer (BC-420MA TANITA, Tokyo, Japan). BMI was calculated as weight over height squared. WHTR, an anthropometric index for measuring central adiposity used to identify cardio metabolic risk as well as WC and BMI, was calculated dividing WC by height [31].
• BP values were measured through a mercury-free sphygmomanometer (UM-101, A&D Medical, Italy), using a properly sized BP cuff. During first medical examination ambulatory BP values (DAYBP) were measured for three times, one minute lasting between consecutive measurement and after 5 minutes of sitting at rest, on the right upper arm using an appropriate sized cuff. Furthermore, BP values were evaluated during three months exercise intervention program, at the beginning (or T0 value), every three weeks (T1, T2, T3) in correspondence of the exercise intensity increase and at the end (T4 values). To evaluate the exercise effects BP, these values were evaluated before (PRE) and after (POST) exercise sessions. We used an upper arm BP monitor (AND A&D Medical, Model UA-787Plus).
• Physical exercise measures, as the maximum dynamic muscle strength and VO2max, was estimated before starting the training program (during the medical specialist in sport medicine evaluation) and after three-months, as follows. During the first week (sessions n°1 and n°2) all the patients participated at pre-training sessions in the exercise laboratory of C.U.R.I.A.Mo. and they received the indications for the correct performance of full program and exercises. In the workouts n°3, n°4 and n°25 we used isotonic machines (Lat machine, Chest Press, Leg Extension and Leg Press Technogym, Cesena, Italy) to evaluate the maximum dynamic force of extensor muscles of the leg and the flexor and extensor muscles of the arms. To estimate the 1RM we used the Brzycki 1-RM prediction equation [32]. A single test’s session was composed of warm up period and (at least) 10 repetitions for each exercise, using the load/resistance detected during the familiarization session. The resistance was progressively increased until the subjects could perform 12 or fewer repetitions, for each exercise, in order to carry out the test correctly. Maximum oxygen consumption (VO2max) was estimated through the Rockport fitness walking test, one of the most tests used to estimate VO2max in sedentary people and a valid predictor of VO2max [33].
Selected data of study participants.
| All | Women | Man | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BP | Patol | BMI | n | Age | BP | Patol | BMI | n | Age | BP | Patol | BMI | n | Age | ||||||
| Median | Min | Max | Median | Min | Max | Median | Min | Max | ||||||||||||
| Normo | Obesity | Norm | 1 | 56.0 | 56 | 56 | Normo | Obesity | Norm | 1 | 56.0 | 56 | 56 | Normo | Obesity | Norm | 0 | / | / | / |
| Over | 12 | 47.0 | 19 | 68 | Over | 8 | 45.0 | 19 | 59 | Over | 4 | 61.5 | 32 | 68 | ||||||
| Ob | 67 | 38.0 | 18 | 61 | Ob | 56 | 38.0 | 18 | 61 | Ob | 11 | 37.0 | 18 | 60 | ||||||
| Total | 80 | 38.0 | 18 | 68 | Total | 65 | 38.0 | 18 | 61 | Total | 15 | 37.0 | 18 | 68 | ||||||
| Diabetes | Norm | 1 | 54.0 | 54 | 54 | Diabetes | Norm | 0 | / | / | / | Diabetes | Norm | 1 | 54.0 | 54 | 54 | |||
| Over | 3 | 61.0 | 45 | 67 | Over | 1 | 45.0 | 45 | 45 | Over | 2 | 64.0 | 61 | 67 | ||||||
| Ob | 5 | 47.0 | 41 | 66 | Ob | 4 | 56.0 | 41 | 66 | Ob | 1 | 44.0 | 44 | 44 | ||||||
| Total | 9 | 54.0 | 41 | 67 | Total | 5 | 47.0 | 41 | 66 | Total | 4 | 57.5 | 44 | 67 | ||||||
| All | Norm | 2 | 55.0 | 54 | 56 | All | Norm | 1 | 56.0 | 56 | 56 | All | Norm | 1 | 54.0 | 54 | 54 | |||
| Over | 15 | 47.0 | 19 | 68 | Over | 9 | 45.0 | 19 | 59 | Over | 6 | 62.0 | 32 | 68 | ||||||
| Ob | 72 | 38.0 | 18 | 66 | Ob | 60 | 38.5 | 18 | 66 | Ob | 12 | 37.0 | 18 | 60 | ||||||
| Total | 89 | 40.0 | 18 | 68 | Total | 70 | 39.5 | 18 | 66 | Total | 19 | 44.0 | 18 | 68 | ||||||
| Hyper | Obesity | Norm | 2 | 48.0 | 46 | 50 | Hyper | Obesity | Norm | 1 | 50.0 | 50 | 50 | Hyper | Obesity | Norm | 1 | 46.0 | 46 | 46 |
| Over | 21 | 55.0 | 39 | 73 | Over | 15 | 60.0 | 39 | 73 | Over | 6 | 54.5 | 50 | 65 | ||||||
| Ob | 150 | 51.0 | 19 | 74 | Ob | 88 | 51.0 | 19 | 74 | Ob | 62 | 51.0 | 25 | 70 | ||||||
| Total | 173 | 51.0 | 19 | 74 | Total | 104 | 51.5 | 19 | 74 | Total | 69 | 51.0 | 25 | 70 | ||||||
| Diabetes | Norm | 6 | 59.0 | 40 | 70 | Diabetes | Norm | 2 | 49.0 | 40 | 58 | Diabetes | Norm | 4 | 61.5 | 55 | 70 | |||
| Over | 38 | 59.5 | 46 | 75 | Over | 18 | 59.0 | 51 | 71 | Over | 20 | 60.0 | 46 | 75 | ||||||
| Ob | 72 | 58.0 | 33 | 71 | Ob | 32 | 59.0 | 35 | 71 | Ob | 40 | 57.0 | 33 | 68 | ||||||
| Total | 116 | 58.5 | 33 | 75 | Total | 52 | 59.0 | 35 | 71 | Total | 64 | 58.0 | 33 | 75 | ||||||
| All | Norm | 8 | 56.5 | 40 | 70 | All | Norm | 3 | 50.0 | 40 | 58 | All | Norm | 5 | 60.0 | 46 | 70 | |||
| Over | 59 | 59.0 | 39 | 75 | Over | 33 | 59.0 | 39 | 73 | Over | 26 | 59.0 | 46 | 75 | ||||||
| Ob | 222 | 53.0 | 19 | 74 | Ob | 120 | 53.0 | 19 | 74 | Ob | 102 | 53.5 | 25 | 70 | ||||||
| Total | 289 | 55.0 | 19 | 75 | Total | 156 | 55.0 | 19 | 74 | Total | 133 | 55.0 | 25 | 75 | ||||||
During this test we indicate to patient to walk for a mile as quickly as possible. The following equation was used to predict the VO2max estimated values:
VO2 max (ml/Kg/min)=132.853 - (0.0769 x weight in kg) - (0.3877 x age in years) + (6.315 x gender) - 188 (3.2649 x total time in minutes) - (0.1565 x final heart rate).
Flexibility was evaluated through a bending test called Sit & Reach [34], conducted both in horizontal (HB) and vertical position (VB).
Statistical Analysis
Evaluation of normality was conducted using Kolmogorov - Smirnov test to assess the normal distribution of data. At first non-normally distributed variables were transformed using Box-Cox transformation, to better approximate the Gaussian distribution. Due to their asymmetry data are shown as median (min/max). An independent samples T-Test was performed to evaluate if two studied subgroups (normo- and hypertensive subjects) presented differences at baseline. A Student T-test for paired sample was used to compare all measures (anthropometry, BP and exercise program) before and after treatment (T0 vs. T4), in whole sample and in the two subgroups (normotensive and hypertensive subjects groups) according to baseline DAYBP values. P≤0.05 value was used to established statistical significance. The treatment effects value (delta changes) are obtained by subtracting the pre-exercise from the post-exercise values. A mixed model analysis of variance for repeated measures (T0,T1,T2,T3,T4) was conducted to estimate the physical activity effects on systolic SBP and DBP during (in every training step corresponding to the exercise intensity increase) and after the exercise intervention program. Furthermore, a post-hoc multiple comparison tests (tables 7 and
8) was conducted to determine which specific means differed from which others. Data extraction was conducted by graduates in Sport Science and the data was collected and extracted to Microsoft Excel spread sheets. Finally, all the analyses were performed using IBM SPSS® Statistics software package version 22.0.
Physical activity chronic effects.
| Indicator | Overall | Normo | Hyper | ||||||
|---|---|---|---|---|---|---|---|---|---|
| T0 | T4 | p | T0 | T4 | p | T0 | T4 | p | |
| Body weight (Kg) | 93.35 (55.4/150.8) | 90.45 (54.7/145.6) | ** | 89.6 (60.5/125.50) | 86.8 (58.7/124.2) | ** | 95.1 (55.4/150.8) | 91.7 (54.7/145.6) | ** |
| BMI (Kg/m2) | 33.4 (20.6/52.3) | 32.3 (20.3/49) | ** | 33.4 (24.2/48.8) | 32.6 (23.4/48.3) | ** | 33.3 (20.6/52.3) | 32.2 (20.3/49) | ** |
| WC (cm) | 110 (82/147) | 106 (82/147) | ** | 108 (84/140) | 103 (80/133) | ** | 111 (82/147) | 107 (79/146) | ** |
| WHTR (cm) | 0.655 (0.47-0.85) | 0.632 (0.46-0.79) | ** | 0.659 (0.49- 0.83) | 0.623 (0.46-0.78) | ** | 0.655 (0.47-0.85) | 0.634 (0.46-0.79) | ** |
| DAYSBP (mmHg) | 130 (100/170) | 125 (90/170) | ** | 120 (100/135) | 117.5 (90/135) | * | 140 (100/170) | 130 (100/170) | ** |
| DAYDBP (mmHg) | 80 (55/110) | 75 (50/110) | ** | 75 (55/80) | 70 (50/90) | * | 85 (60/110) | 80 (50/110) | ** |
| SBPPRE | 133 (99/198) | 128.5 (102/174.5) | ** | 126 (99/160) | 122.5 (102/151) | NS | 136 (103/198) | 131.4 (102/174.5) | ** |
| SBPPOST | 125 (89/186) | 120 (94/168.7) | ** | 122 (98/149) | 118 (95/140) | ** | 126 (89/186) | 121 (94/168.7) | ** |
| DBPPRE | 84 (54/116) | 81 (60.5/116.7) | ** | 81 (58/105) | 79.5 (62.3/98.5) | ** | 85 (54/116) | 81.5 (60.5/116.7) | ** |
| DBPPOST | 80 (53/115) | 77 (59/104.3) | ** | 78 (53/97) | 76 (59.3/93.5) | ** | 81 (57/115) | 77.4 (59/104.3) | ** |
| VB (cm) | -8 (-39/23) | -4 (-37/38) | ** | -6 (-33/16) | -3.5 (-27/37) | ** | -9 (-39/23) | -5 (-37/38) | ** |
| HB (cm) | 27 (-23/54) | 30 (3/54) | ** | 30.5 (-3/54) | 33 (4/53) | ** | 26 (-23/49) | 29 (3/54) | ** |
| LAT (Kg) | 36.3 (18.6/95.4) | 46 (25.7/90) | ** | 36 (18.6/57.6) | 45 (27.5/76.7) | ** | 37.15 (18.6/95.4) | 46.7 (25.7/90) | ** |
| CHEST (Kg) | 26.3 (10/64.8) | 36 (14.5/80.7) | ** | 24.8 (10/50.4) | 34.1 (21.6/61.2) | ** | 26.85 (10/64.8) | 37.2 (14.5/80.7) | ** |
| Leg Press (Kg) | 158.5 (80/300.5) | 194.2 (102.9/346.8) | ** | 149 (86.9/295.1) | 192.45 (111.1/298) | ** | 158.5 (80/300.5) | 194.5 (102.9/346.8) | ** |
| Leg Ext (Kg) | 28.8 (11.6/86.4) | 43.5 (18.5/103.4) | ** | 30 (14.4/57.6) | 47.8 (27.7/79.2) | ** | 28.8 (11.6/86.4) | 43.3 (18.5/103.4) | ** |
| VO2MAX (mm/Kg/min) | 19.65 (5/43.9) | 26.9 (4.8/49.7) | ** | 22.9 (5/43.9) | 29.4 (10.9/49.7) | ** | 18.5 (5/42.3) | 25.7 (4.8/47.7) | ** |
Systolic Blood Pressure (SBP) values, PRE-and POST-exercise, at baseline (T0), every three weeks (T1, T2, T3) and at the end (T4) of intensive exercise program.
| Time | Variable | All | Normo | Hyper | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| median | min | max | median | min | max | median | min | max | ||
| 0 | SBP PRE | 133 | 99 | 198 | 126 | 99 | 160 | 136 | 103 | 198 |
| SBP POST | 125 | 89 | 186 | 122 | 98 | 149 | 126 | 89 | 186 | |
| 1 | SBP PRE | 132 | 102 | 194 | 124 | 105.7 | 155.5 | 134 | 102 | 194 |
| SBP POST | 123 | 84.5 | 179 | 122 | 94 | 150 | 123 | 84.5 | 179 | |
| 2 | SBP PRE | 130.85 | 96.7 | 186.5 | 123 | 96.7 | 151 | 133.7 | 102.3 | 186.5 |
| SBP POST | 120.7 | 87 | 170.3 | 117.3 | 87 | 141.7 | 121.4 | 91.7 | 170.3 | |
| 3 | SBP PRE | 129.6 | 95 | 190 | 124 | 102 | 151 | 132 | 95 | 190 |
| SBP POST | 120 | 89 | 170 | 118.3 | 95.3 | 146 | 120.5 | 89 | 170 | |
| 4 | SBP PRE | 128.5 | 102 | 174.5 | 122.5 | 102 | 151 | 131.4 | 102 | 174.5 |
| SBP POST | 120 | 94 | 168.7 | 118 | 95 | 140 | 121 | 94 | 168.7 | |
Diastolic Blood Pressure (SBP) values, PRE- and POST- exercise, at baseline (T0), every three weeks (T1, T2, T3) and at the end (T4) of intensive exercise program.
| Time | Variable | All | Normo | Hyper | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| median | min | max | median | min | max | median | min | max | ||
| 0 | DBP PRE | 84 | 54 | 116 | 81 | 58 | 105 | 85 | 54 | 116 |
| DBP POST | 80 | 53 | 115 | 78 | 53 | 97 | 81 | 57 | 115 | |
| 1 | DBP PRE | 83 | 57.5 | 113 | 80 | 63 | 99.5 | 84 | 57.5 | 113 |
| DBP POST | 78.5 | 58 | 107.5 | 78 | 63 | 93.7 | 79 | 58 | 107.5 | |
| 2 | DBP PRE | 82 | 59.5 | 111.7 | 79.3 | 65 | 99 | 82.3 | 59.5 | 111.7 |
| DBP POST | 78 | 56 | 107 | 76.7 | 56 | 93.3 | 78 | 58.7 | 107 | |
| 3 | DBP PRE | 80.5 | 59 | 113 | 78.7 | 63.3 | 94 | 81 | 59 | 113 |
| DBP POST | 76.3 | 56 | 106 | 76 | 60.3 | 91.7 | 76.3 | 56 | 106 | |
| 4 | DBP PRE | 81 | 60.5 | 116.7 | 79.5 | 62.3 | 98.5 | 81.85 | 60.5 | 116.7 |
| DBP POST | 77 | 59 | 104.3 | 76 | 59.3 | 93.5 | 77.4 | 59 | 104.3 | |
Post hoc analysis of systolic blood pressure (SBP) post-exercise.
| Time | SBP POST | SBP POST | |||
|---|---|---|---|---|---|
| Normo (mmHg) | Hyper (mmHg) | ||||
| Mean Diff | p | Mean Diff | p | ||
| 0 | 1 | 0,1 | NS | 2,3 | ** |
| 2 | 3,1 | ** | 3,6 | ** | |
| 3 | 2,9 | * | 4,9 | ** | |
| 4 | 3,2 | ** | 4,9 | ** | |
| 1 | 0 | -0,1 | NS | -2,3 | ** |
| 2 | 3,1 | * | 1,3 | NS | |
| 3 | 2,9 | * | 2,6 | ** | |
| 4 | 3,2 | * | 2,6 | ** | |
| 2 | 0 | -3,1 | ** | -3,6 | ** |
| 1 | -3,1 | * | -1,3 | NS | |
| 3 | -0,2 | NS | 1,3 | * | |
| 4 | 0,1 | NS | 1,3 | NS | |
| 3 | 0 | -2,9 | * | -4,9 | ** |
| 1 | -2,9 | * | -2,6 | ** | |
| 2 | 0,2 | NS | -1,3 | NS | |
| 4 | 0,3 | NS | 0,0 | NS | |
| 4 | 0 | -3,2 | ** | -4,9 | ** |
| 1 | -3,2 | * | -2,6 | ** | |
| 2 | -0,1 | NS | -1,3 | NS | |
| 3 | -0,3 | NS | 0,0 | NS | |
Post hoc analysis of diastolic blood pressure (DBP) post-exercise.
| Time | DBP POST | DBP POST | ||||
|---|---|---|---|---|---|---|
| Normo (mmHg) | Hyper (mmHg) | |||||
| Mean Diff | p | Mean Diff | p | |||
| 0 | 1 | -0,2 | NS | 1,1 | * | |
| 2 | 1,0 | NS | 1,9 | ** | ||
| 3 | 2,5 | ** | 3,5 | ** | ||
| 4 | 1,8 | NS | 3,5 | ** | ||
| 1 | 0 | 0,2 | NS | -1,1 | * | |
| 2 | 1,2 | NS | 0,7 | NS | ||
| 3 | 2,7 | ** | 2,3 | ** | ||
| 4 | 2,0 | ** | 2,4 | ** | ||
| 2 | 0 | -1,0 | NS | -1,9 | ** | |
| 1 | -1,2 | NS | -0,7 | NS | ||
| 3 | 1,5 | * | 1,6 | ** | ||
| 4 | 0,8 | NS | 1,7 | ** | ||
| 3 | 0 | -2,5 | ** | -3,5 | ** | |
| 1 | -2,7 | ** | -2,3 | ** | ||
| 2 | -1,5 | * | -1,6 | ** | ||
| 4 | -0,7 | NS | 0,1 | NS | ||
| 4 | 0 | -1,8 | NS | -3,5 | ** | |
| 1 | -2,0 | ** | -2,4 | ** | ||
| 2 | -0,8 | NS | -1,7 | ** | ||
| 3 | 0,7 | NS | -0,1 | NS | ||
Systolic Blood Pressure mean values before (upper panel) and after (bottom panel) exercise sessions.
Diastolic Blood Pressure mean values before (upper panel) and after (bottom panel) exercise sessions.
RESULTS
At the end of the intervention period (T4), in all subjects anthropometric parameters such as body weight, BMI, WC, WHTR index significantly improved as compared to baseline (Table 4). Similarly, physical exercise measures such as flexibility (both in vertical and horizontal position), maximum dynamic muscle strength of upper (Lat machine, or LAT; chest press, or CHEST) and lower limbs (LEG PRESS and leg extension, or LEG EXT) and VO2 max showed a statistically significant (p<0.01) improvement. Finally, DAYSBP and DAYDBP as well as BP values PRE- and POST-exercise significantly decreased at the end of the intervention period as compared to baseline. No statistically significant difference was found between males and females in all variables (data not shown).
The improvement of the anthropometric and exercise parameters observed at T4 in the whole group was also observed when subjects were split in normotensive and hypertensive groups. In particular, with regard to BP data, the comparison of data between normotensive and hypertensive groups indicated that, with the exception of SBPPRE in the normotensive group, DAYBP, DAYDBP, DBPPRE, DBPPOST and SBPPRE significantly decreased at T4. In fact, the average DAYSBP decrease was of 10 mmHg in the hypertensive subjects and 2.5 mmHg in the normotensive subjects, respectively. The DAYDBP drop was of 5 mmHg in both groups.
The repeated measures analysis of variance with a within subjects factor (time) and between subjects factor (group) showed that BP values measured in the gym during physical activity sessions decreased significantly during the exercise treatment period, both in the normotensive and hypertensive groups, although to a greater extent in the hypertensive group, confirming the result obtained from the analysis of the whole sample. Therefore, exercise-related effects on BP were observed over the 3-month intervention period within subjects (p<0.0001), with no difference between groups (p>0.05).
In the whole group, post-exercise SBP and DBP decreased form baseline to T4 by 5 mmHg (from 125 to 120 mmHg) and by 3 mmHg (from 80 to 77 mmHg), respectively, after the training period (Tables 5 and 6). Between group comparisons indicated that, in the hypertensive subjects, post-exercise SBP and DBP values decreased (5.0 and 3.6 mmHg, respectively) more than those in the normotensive group (4.0 and 2.0 mmHg, respectively). Overall, in the normotensive group, the drop in BP was mainly evident in the 2nd and the 4th training period, whereas in the hypertensive group the decrease in BP values was more continuous from baseline to T4 with a greater drop in the second training period (fig. 1 and 2). BP values showed a statistically significant decrease in DAYSBP and DAYDBP, as well as in BP values PRE- and POST-exercise.
DISCUSSION
The main aim of the study was to establish whether a lifestyle intervention based on the combination of diet, increased physical activity, and behaviour modification [30] might have improved health-related variables, particularly blood pressure, in overweight/obese adult subjects. Among the participants at C.U.R.I.A.Mo. trial, we recruited 378 people with overweight/obesity and/or type 2 diabetes, allocated to normotensive or hypertensive groups, to take part in a multidisciplinary intervention including physical exercise sessions. The results demonstrate that a three-month period lifestyle multidisciplinary intervention is associated with a significant improvement in CV risk factor such as reduction in BMI, WC, WHTR index and BP values. In addition, it is worth pointing out that the improvement in BP values started to become evident after only a few weeks into the intervention. To the best of our knowledge, the present study is the first structured lifestyle multidisciplinary intervention involving people with obesity and/or type 2 diabetes, focused on physical exercise-induced effects on BP. Wang et al. [35] found similar results in overweight women following 10 weeks of supervised exercise training. In our study, we observed an initial BP decrease after only three weeks (T1, Figure 1 and Figure 2), both in normotensive and hypertensive subjects with overweight/obesity.
Cardoso et al. have reviewed the current literature on the acute and chronic effects of aerobic and resistance exercise on ambulatory blood pressure in normotensive and hypertensive subjects and found that a single episode of aerobic exercise reduces ambulatory blood pressure in hypertensive patients. They also pointed out that blood pressure levels decrease soon after exercise in comparison to blood pressure measured before exercise or on a control day when no exercise is performed [14]. However, to be clinically relevant, the reduction of BP after exercise must have a considerable effect and must be maintained for a long period of time under ambulatory conditions. In the present study, post-exercise SBP and DBP decreased and remained lower than pre-exercise measurements up to the end of the three-month period of observation (T4). Other studies of the C.U.R.I.A.Mo. research group have shown that BP reductions observed at three-months in daytime ambulatory SBP and DBP in BP can be maintained over a two-year follow-up visits, provided the lifestyle changes of the multidisciplinary intervention are maintained [10].
It is known that a clinically meaningful BP reduction, as used in many hypertension trials, is arbitrarily defined as an absolute SBP and DBP reduction of 3 mmHg or more because this significantly reduces the incidence of CVD in both hypertensive and normotensive individuals [36]. Hess et al. reported that after 6 weeks of isometric training exercise, reductions in SBP were similar to the antihypertensive effects observed in monotherapy of 5-7 mm Hg [37]. In the present study we observed BP value reductions after three weeks (T1) of exercise. Furthermore, as shown in tables 3a and 3b, BP values were positively affected by every single session of mixed type exercise (reduction of PRE-POST exercise of systolic and diastolic pressure values). Considering that a single training period of the type presented may cause a sustained decrease of BP (acute effect) that lasts for a few hours after training, it is strongly recommended to exercise several times a week (better if daily). Based on these results we can conclude that just four sessions of supervised exercise (twice a week) are enough to begin to get benefits on BP value reductions both in “normotensive” and “hypertensive” people.
According to Martinez Aguirre-Betolaza et al. [13] better BP improvements in overweight/obese people with hypertension are achieved when the exercise training is individually designed and supervised, empowering the existing exercise recommendations. In that context, the results of the present study are in line with those of Martinez Aguirre-Betolaza et al. [13], and contributes to scientific evidence by using a specific multidisciplinary clinical program, including a structured exercise program individualized for type, frequency and intensity in order to effectively counteract hypertension and overweight/obesity. In addition, exercise was supervised by exercise physiologists with an Exercise Sport Science degree and endocrinologists. For that reason, the present study may not be replicable in a simple ambulatory counselling setting aimed at increasing regular exercise if devoid of specific instrument, machines, and especially a team of highly qualified personnel including graduates in Sport Science [38,39].
The mechanisms responsible for BP reduction in our study are not clear. However, considering that hypertension is a multifactorial disease, it is possible that different mechanisms may mediate the hypotensive effects of mixed exercise training. Among the possible mechanisms we mention a reduction of vascular resistance, in which the sympathetic nervous system and the renin-angiotensin system appear to be involved [40] as well as body weight and fat mass loss.
Despite the novelty of our results, we should acknowledge a few limitations of our study. First, the intervention included food habits, Mediterranean diet adherence and psychological and motivational interviews. However, it needs to be recognized that the relative impact of the single components of the intervention on BP values of people affected by overweight/obesity or type 2 diabetes cannot be understood from our study [41]. Generally, we believe that the exercise program (25 sessions of 90 minutes each) has played a major role in the outcomes as compared with nutritional (3 meetings of one hour each) and psychological (2 meetings of 45 minutes each) interviews. Second, despite the fact that our intervention is a multidisciplinary one, we focused in this analysis mainly on the role of supervised exercise. Third, the results of the other variables related to nutritional and psychological intervention are not reported. Finally, the study lacks a control group because this was not included in C.U.R.I.A.Mo. clinical trial.
CONCLUSION
These results demonstrate that an intensive lifestyle intervention including a regular practice of supervised exercise should be recommended for overweight/obese adults with high BP value to obtain improvements on body weight, body composition, BP value, muscular strength, flexibility and maximum oxygen consumption. Beneficial effects of exercise on BP value reductions can be seen in as little as 2 to 3 weeks after starting the exercise program. Future studies will be needed to better understand the combined effects associated with exercise, nutritional and motivational counselling on blood pressure in people affected by overweight/obesity or type 2 diabetes.
REFERENCES
- Sharman JE, La Gerche A and Coombes JS. Exercise and cardiovascular risk in patients with hypertension. Am J Hypertens 2015; 28: 147–158.
- Whelton PK, He J, Appel LJ et al, for the National High Blood Pressure Education Program Coordinating Committee. Primary Prevention of Hypertension Clinical and Public Health Advisory From the National High Blood Pressure Education Program. JAMA 2002; 288: 1882–1888.
- Unger, T. et al. (2020). 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. Hypertension. doi: 10.1161/hypertensionaha.120.15026
- Lee IM, Shiroma EJ, Lobelo F et al. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012; 380: 219–229.
- Fletcher GF, Ades PA, Kligfield P et al. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation 2013; 128: 873–934.
- Mancia G, Fagard R, Narkiewicz K et al. ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159–219.
- Cornelissen VA, Buys R and Smart NA. Endurance exercise beneficially affects ambulatory blood pressure: a systematic review and meta-analysis. J Hypertens 2013; 31: 639–648.
- Taylor-Tolbert NS, Dengel DR, Brown MD et al. Ambulatory blood pressure after acute exercise in older men with essential hypertension. Am J Hypertens 2000; 13: 44–51.
- Semlitsch T; Stigler FL; Jeitler K; Horvath K; Siebenhofer A. Management of overweight and obesity in primary care—A systematic overview of international evidence-based guidelines. Obesity Reviews. 2019; 20: 1218–1230.
- Sbroma Tomaro E, Pippi R, Reginato E, et al. Intensive lifestyle intervention is particularly advantageous in poorly controlled type 2 diabetes. Nutr Metab Cardiovasc Dis. 2017; 27(8): 688–694. doi: 10.1016/j.numecd.2017.06.009.
- Russo A, Pirisinu I, Vacca C, Reginato E, Tomaro ES, Pippi R, Aiello C, Talesa VN, De Feo P, Romani R. An intensive lifestyle intervention reduces circulating low-density lipoprotein and increases human paraoxonase activity in obese subjects. Obesity oxidised Research and Clinical Practice 2018, 12(1), 108-114.
- Ranucci C, Pippi R, Buratta L, et al. Effects of an Intensive Lifestyle Intervention to Treat Overweight/Obese Children and Adolescents. Biomed Res Int. 2017; 2017: 8573725. doi: 10.1155/2017/8573725.
- MartinezAguirre-Betolaza, A., Mujika, I., Fryer, S.M. et al. Effects of different aerobic exercise programs on cardiac autonomic modulation and hemodynamics in hypertension: data from EXERDIET-HTA randomized trial. J Hum Hypertens (2020). https://doi.org/10.1038/s41371-020-0298-4.
- Cardoso CG, Gomides RS, Queiroz ACC, et al. Acute and Chronic Effects of Aerobic and Resistance Exercise on Ambulatory Blood Pressure. Clinics 2010; 65: 317–325.
- Ciolac EG, Guimaraes GV, D’Avila VM et al. Acute aerobic exercise reduces 24-h ambulatory blood pressure levels in longterm-treated hypertensive patients. Clinics (Sao Paulo) 2008; 63: 753–8.
- Pescatello LS, Franklin BA, Fagard R et al. American College of Sports Medicine position stand. Exercise and hypertension. Med Sci Sports Exerc 2004; 36: 533–53.
- Bermudes AM, Vassallo DV, Vasquez EC et al. Ambulatory blood pressure monitoring in normotensive individuals undergoing two single exercise sessions: resistive exercise training and aerobic exercise training. Arq Bras Cardiol 2004; 82: 65–71.
- Quinn TJ. Twenty-four hour, ambulatory blood pressure responses following acute exercise: impact of exercise intensity. J Hum Hypertens 2000; 14: 547–53.
- Wallace JP, Bogle PG, King BA et al. A comparison of 24-h average blood pressures and blood pressure load following exercise. Am J Hypertens 1997; 10: 728–34.
- Park S, Rink LD and Wallace JP. Accumulation of physical activity leads to a greater blood pressure reduction than a single continuous session, in prehypertension. J Hypertens 2006; 24: 1761–70.
- Bisquolo VA, Cardoso CG Jr., Ortega KC et al. Previous Exercise Attenuates Muscle Sympathetic Activity and Increases Blood Flow During Acute Euglycemic. J Appl Physiol 2005; 98: 866–71.
- Maria do Socorro Brasileiro-Santos Amilton da Cruz Santos. Neural mechanisms and post-exercise hypotension: The importance of experimental studies. Motriz, Rio Claro 2017; 23: e101622.
- Rossi A, Dikareva A, Bacon SL et al. The impact of physical activity on mortality in patients with high blood pressure: a systematic review. JHypertens 2012; 30: 1277–1288.
- Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001; 33: S438–45.
- Kenney MJ and Seals DR. Postexercise hypotension: key features, mechanisms, and clinical significance. Hypertension 1993; 22: 653–664.
- Pescatello LS, Fargo AE, Leach CN, et al. Short-term effect of dynamic exercise on arterial blood pressure. Circulation 1991; 83: 1557–1561.
- Clark T. et al. High-intensity interval training for reducing blood pressure: a randomized trial vs. moderate-intensity continuous training in males with overweight or obesity. Hypertension Research (2020) 43:396–403. https://doi.org/10.1038/s41440-019-0392-6.
- Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39 (33): 3021–3104.
- https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/index.html . Accessed 29.05.2020.
- De Feo P, Fatone C, Burani P, et al. An innovative model for changing the lifestyles of persons with obesity and/or Type 2 diabetes mellitus. J Endocrinol Invest 2011; 34: e349.
- Lee CM, Huxley RR, Wildman RP, et al. Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis. J Clin Epidemiol 2008; 61(7): 646–653.
- Do Nascimento MA, Serpeloni Cyrino E, Nakamura FY, et al. Validation of the Brzycki equation for the estimation of 1-RM in the bench press. Rev Bras Med Esporte 2007; 13: 40e-42e
- Weiglein L, Herrick J, Kirk S et al. The 1-mile walk test is a valid predictor of VO2max and is a reliable 476 alternative fitness test to the 1.5-mile run in U.S. Air Force males. Mil Med 2011; 176(6): 669–673.
- Mayorga-Vega D, Merino-Marban R and Viciana J. Criterion-related validity of sit-and-reach tests for estimating hamstring and lumbar extensibility: a meta-analysis. J Sports Sci Med 2014; 13: 1–14.
- Wang J, Tan S, Cao L. Exercise training at the maximal fat oxidation intensity improved health-related physical fitness in overweight middle-aged women. J Exerc Sci Fit. 2015; 13(2): 111–116. doi: 10.1016/j.jesf.2015.08.003.
- Collaboration BPLTT: Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 362: 1527-1535, 2003.
- Hess NC, Carlson DJ, Inder JD, Jesulola E, McFarlane JR, Smart NA. Clinically meaningful blood pressure reductions with low intensity isometric handgrip exercise. A randomized trial. Physiol Res. 2016; 65(3): 461–468. doi: 10.33549/physiolres.933120.
- Ortenburger D, Rodziewicz-Gruhn J, Wąsik J, Marfina O, Polina N. Selected problems of the relation between pain-immunity and depression. Phys Activ Rev 2017, 5: 74-77. doi: 10.16926/par.2017.05.10
- Szerla M, Wąsik J, Ortenburger D, Gwara M, Trybulec B. Optimization of quality of functional improvement – aspects of psychomedical treatment. Med Stud 2016; 32(2): 150–156. doi: 10.5114/ms.2016.61105
- Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension 2005; 46: 667–675.
- Delgado-Floody P, Alvarez C, Caamano-Navarrete F, Jerez-Mayorga D, Latorre-Román P. Influence of Mediterranean diet adherence, physical activity patterns, and weight status on cardiovascular response to cardiorespiratory fitness test in Chilean school children. Nutrition 2020; 71: 110621. doi: 10.1016/j.nut.2019.110621.
Article information
Phys Act Rev. 2021;9(1):40-53.DOI: 10.16926/par.2021.09.06
