Patients who adhere to more comprehensive professional lifestyle intervention (ie, smoking cessation, adequately designed and supervised exercise program, and diet recommendations) have a 54% lower risk of recurrent events 6 mo after a myocardial infarction (MI),1 and their quality of life and longevity increase.2
Previous studies support the beneficial effect of the Mediterranean diet (Mediet) combined with regular exercise for the primary prevention of cardiovascular disease3 and reduction of cardiovascular risk4,5 despite the amount of interstudy heterogeneity observed.6 However, a recent meta-analysis has demonstrated no improvement in all-cause mortality among patients participating in an exercise-based cardiac rehabilitation program when compared with the nonexercise control group.7 Data from studies included in this review were based on a wide range of clinical environments and the intervention ranged greatly in quality (ie, participants may not have received an adequate dose of exercise).7 High-intensity aerobic interval training (HIIT) has been found to be more effective than moderate-intensity continuous aerobic exercise training in improving cardiac and vascular functions, aerobic capacity, post-exercise heart rate recovery, and psychological states in patients with coronary artery disease (CAD).8–14 Nevertheless, the SAINTEX-CAD study observed similar improvement in exercise capacity and peripheral function after 12-wk HIIT and moderate-intensity continuous aerobic exercise training intervention in patients with CAD,15 and a systematic review found that the superiority of HIIT disappeared when isocaloric protocols were applied in these patients.16
On the contrary, low-volume HIIT protocols are time-efficient strategies that have been shown to be effective in both healthy populations17–19 and individuals with health conditions such as CAD,20 type II diabetes mellitus,21–23 and primary hypertension.24 Since lack of time is one of the more common barriers for people considering initiation of a supervised exercise program, low-volume HIIT could be an interesting strategy if the resultant physiological benefits are comparable with high-volume HIIT.
It is very well known that higher cardiorespiratory fitness (CRF) (ie, peak oxygen uptake,
O2peak) is linked with a lower risk of early death after a first MI25 and also the importance of the fat-but-fit paradigm on mortality risk among patients with CAD.26 Therefore, the purpose of this study was to analyze the changes in CRF and body composition following 2 different (low-volume vs high-volume) 16-wk HIIT programs performed 2 d/wk compared with an attention control (AC) group, all combined with Mediet recommendations, in patients after an MI. We hypothesized that low-volume HIIT would provide sufficient stimulus for similar improvements as high-volume HIIT on CRF and body composition.
The INTERFARCT study is a single-blind, randomized-controlled, 3-arm parallel trial comparing the effects of 2 different 16-wk HIIT exercise programs (performed 2 d/wk) combined with Mediet recommendations in patients after an MI (ClinicalTrials.gov ID: NCT02876952). The study complied with the World Medical Association Declaration of Helsinki on ethics in medical research. The protocol and informed consent procedures were approved by the ethics committee of the university (UPV/EHU, CEISH, 2016) and the ethics committee of clinical investigation of the hospital (CEIC 1462), and all participants provided written informed consent before the clinical and physiological examination. The Cardiology staff was blinded to the participant randomization process. The design, selection criteria, and procedures for the INTERFARCT study have been detailed previously.27
Two hundred twenty-four patients were evaluated for eligibility (see Supplemental Digital Content 1, available at: http://links.lww.com/JCRP/A126). However, after exclusion for not meeting the inclusion criteria and/or refusal to participate, only 70 non-Hispanic white patients (n = 59 men and n = 11 women) with a diagnosis of MI according to criteria of “third universal definition of myocardial infarction” and clinical classification of MI type 1, called “spontaneous myocardial infarction,”28 were enrolled in the study from February 2016 to December 2017.
The measurements for the study were taken before (T1) and after (T2) the intervention period (16 wk) (see Supplemental Digital Content 1, available at: http://links.lww.com/JCRP/A126). The post-intervention assessment procedures were scheduled the following week after finishing the 16-wk intervention period.
ANTHROPOMETRY AND BODY COMPOSITION
Stature, total body mass, and waist and hip circumferences were measured with models 213, 869, and 200 (SECA), respectively, before the cardiopulmonary exercise test to calculate the waist to hip ratio (WHR). Furthermore, bioelectrical impedance BF 350 (Tanita) was used to estimate fat-free mass and fat body mass.
As described previously,27 a peak, gradual, and symptom-limited cardiopulmonary exercise test (ie, starting at 0 W with 10-W/min increments) on a cycle ergometer Excalibur Sport Cycle (Lode) was performed. Twelve-lead electrocardiogram monitoring and breath-by-breath gas exchange measurements Ref. USM001 V1.0 (Ergocard Medisoft) were recorded continuously, and blood pressure was measured every 2 min. Achievement of
O2peak criteria has previously been defined.29 Ventilatory thresholds (ie, VT1 and VT2) were assessed by standardized methods using ventilatory equivalents.29 The 3 exercise intensity domains (ie, R1—light to moderate; R2—moderate to high; and R3—high to severe) were determined with the 2 VT or percentages of heart rate reserve when VT2 was not possible to identify.27,29
All participants received Mediet pattern recommendations.27 The AC group was encouraged to maintain regular physical activity in order to keep ethical procedures regarding health.27,30,31 The training intervention for low- and high-volume HIIT was previously described.27 In short, the participants trained for 2 nonconsecutive d/wk for 16 wk, under the supervision of an exercise specialist. The principal portion of the training session consisted of aerobic exercises; that is, 1 d/wk on the treadmill (intervals of 4 min at R3, followed by 3 min at R2), and the second one on the exercise bike (intervals of 30 sec at R3, followed by 60 sec at R2) developing progressively both the volume (ie, 20-40 min in the high-volume HIIT groups, whereas in the low-volume HIIT group, the duration was always 20 min) and intensity (BH Fitness equipment). Intensity was individually tailored to heart rate at moderate (R2) or vigorous (R3) intensity, adjusting the speed and incline of the treadmill, or the power (W) and speed on the exercise bike, to achieve the planned target heart rate. Supervised exercise training protocols have been previously explained in full.27
Considering the mean
O2peak (1.9 L·min−1; 6.6 metabolic equivalents [METs]) at baseline for all participants, the total work performed by the 2 exercise groups was calculated as the total amount of energy expended during the different aerobic exercise programs over a period of 1 wk from the combination of frequency, intensity, type, and time.32 Thus, the moderate intensity at R2 was taken as 70% of
O2peak (1.3 L·min−1 or 4.6 METs) and the high intensity at R3 as 90% of
O2peak (1.7 L·min−1 or 5.9 METs). As such, the low- and high-volume HIIT groups performed 20 and 40 min 2 d/wk, respectively; exercising 1 d on the treadmill (low-volume HIIT: 2 × 4 min at R3 and 12 min at R2; high-volume HIIT: 4 × 4 min at R3 and 24 min at R2, representing ∼131 kcal and ∼263 kcal, respectively) and 1 d on the exercise bike (low-volume HIIT: 8 × 30 sec at R3 and 16 min at R2; high-volume HIIT: 16 × 30 sec at R3 and 32 min at R2, representing ∼104 kcal and ∼210 kcal, respectively). In all, it represented ∼235 kcal/wk for low-volume HIIT versus ∼473 kcal/wk for high-volume HIIT. Compliance for the exercise intervention was defined as ≥80% of the 32 sessions.
The required sample size was determined for the primary outcome variable (
O2peak). It was identified that adequate power (0.80) to evaluate differences in our design consisting of 3 experimental groups would be achieved with 177 people (50 in each group, α = .05, effect size [ES] f = 0.23).27 As the sample size was too small (n = 70) to have adequate power for statistical significance, the current report is considered a pilot study. Descriptive statistics were calculated for all variables. Data are expressed as means ± standard and the range. All variables that were not normally distributed using a Kolmogorov-Smirnov test were log transformed prior to any analysis. Analysis of variance was used to determine whether there were significant pre-intervention differences among groups. The comparison of frequencies in categorical variables among groups was performed using the χ2 test. A 2-sample t test was used to determine whether there was a significant difference in the recorded data between pre- and post-intervention within each group. Analysis of covariance was used to examine the delta (Δ) score classified by group (AC, high-volume HIIT, low-volume HIIT), adjusting the analysis for age, sex, and initial value of each of the dependent variables. Helmert contrasts were performed to analyze the differences between the 2 exercise groups pooled together and the AC group. The Bonferroni correction was used to determine the level of significance when a significant main effect was found. Data were analyzed according to the intention-to-treat principle. Statistical significance was set at P < .05. All statistical analyses were performed with SPSS version 22.0.
BASELINE CHARACTERISTICS (T1)
Participants and medications were classified by group and are presented in Table 1. The mean age of participants was 58.4 ± 8.5 yr, with fewer women (16%) than men (84%). At T1, 84% of participants suffered from hypertension, 29% from type 2 diabetes mellitus, 89% from dyslipidemia, 80% were smokers, 13% had sleep apnea, and 38% were consuming >14 drinks/wk of alcohol. For participants of the present study,
O2peak values (23.1 ± 7.4 mL˙kg−1˙min−1) were all <40th percentile according to the Fitness Registry and Importance of Exercise National Database (FRIEND) reference standards.33 All participants (N = 70) were undergoing pharmacological treatment, irrespective of groups (91% β-blockers, 87% angiotensin-converting enzyme inhibitors/angiotensin receptor antagonist, 94% aspirin, 57% clopidogrel or similar, 4% anticoagulants, 18% calcium antagonists, 21% diuretics, 99% statins, and 23% hypoglycemic agents). There were no significant between-group differences observed for body composition, anthropometrics, CRF, and pharmacologic treatment (P > .05). There was only one difference in resting systolic blood pressure (mm Hg), with smaller (P = .003) values in the AC group compared with high-volume HIIT groups (mean difference = 13 mm Hg; 95% CI, 4-23).
FOLLOW-UP CHANGES (T2)
At T2, 15 participants had dropped out. Therefore, the total sample for statistical analysis after intervention was 55 (see Supplemental Digital Content 1, available at: http://links.lww.com/JCRP/A126). At follow-up, some anthropometric changes were shown in the exercise groups (Table 2). Both groups reduced waist circumference significantly (low-volume HIIT, Δ = −4%, P < .05; high-volume HIIT, Δ = −2%, P <.001). The WHR decreased only in the low-volume HIIT group (Δ = −4%, P < .01). Body mass, fat-free mass, and fat body mass did not show any significant change at T2. Following the Bonferroni correction, there were no significant between-group differences in any anthropometric and body composition variables.
Regarding physiological changes related to CRF, as shown in Table 2,
O2peak (mL˙kg−1˙min−1) increased significantly at T2 (low-volume HIIT, Δ = 15%, P < .01; high-volume HIIT, Δ = 22%, P < .001). Furthermore, both groups increased ≥1 MET after intervention (Table 2). However, improvements in VT (mL˙kg−1˙min−1) with higher values were observed only in the high-volume HIIT group for VT1 (Δ 1= 2%, P = .009) and for VT2 (Δ = 16%, P = .003). A significant increase was also observed following training for exercise groups in cardiopulmonary exercise test duration (low-volume HIIT, Δ = 17%, P < .001; high-volume HIIT, Δ = 14%, P < .001) and peak power on the cycle ergometer (Wpeak) (low-volume HIIT, Δ = 18%, P < .001; high-volume HIIT, Δ = 15%, P < .001). In contrast, no significant changes were seen in the AC group for any of the physiological variables studied. Following the Bonferroni correction, there were significant between-group differences. Thus, the HIIT groups showed significant improvement in
O2peak (P < .001) compared with the AC group (low-volume HIIT, difference = 3.0 mL˙kg−1˙min−1; 95% CI, −1.6 to 7.5; high-volume HIIT, difference = 4.5 mL˙kg−1˙min−1; 95% CI, 0.1-9.1) (P < .001). There were also improvements in the secondary variables such as peak power (low-volume HIIT, difference = 22.2 Wpeak; 95% CI, 4.5-39.9; high-volume HIIT, difference = 20.8 Wpeak; 95% CI, 3.4-38.3) and exercise duration (low-volume HIIT, difference = 2.2 min; 95% CI, 0.5-4.0; high-volume HIIT, difference = 2.1 min; 95% CI, 0.3-3.8). No significant differences between HIIT groups were found in any of the studied variables.
Angiotensin-converting enzyme inhibitors/angiotensin receptor antagonist dose was changed in 5 participants during the intervention period: reduced in 3 participants in the low-volume HIIT group and 2 participants in the high-volume HIIT group. β-Blocker dose was not changed in any of the participants.
During the intervention and training sessions, there were no adverse events reported.
The present study examined the effects of low- and high-volume HIIT in comparison with AC, combined with Mediet recommendations in all 3 groups, on body composition and CRF in patients after an MI. Primarily, this study showed that both HIIT exercise protocols induced positive changes in CRF and waist circumference to a similar extent, supporting the efficiency of low-volume HIIT. However, significant improvements in VT1 and VT2 values (submaximal aerobic variables) were observed only in the high-volume HIIT group, highlighting its greater benefits. No improvements were found, however, in body composition and CRF for the AC group, suggesting that supervised exercise programs lead to better health-related results than physical activity recommendations alone.
Bearing in mind the link between CRF and survival time following an MI,34 one of the main challenges in secondary prevention after an acute MI is to improve CRF. Therefore, finding the most efficient way to achieve this (ie, the precision of exercise-based strategies applying the frequency, intensity, type, time principle) is a clinically relevant concern.32 In the present study, both HIIT groups responded to the exercise dose to improve CRF (ie, relative
O2peak) post-training (low-volume HIIT, Δ = 15%, P < .01; high-volume HIIT, Δ = 22%, P < .001), with a nonsignificant between-group difference (P = .016, ES = 0.114; Table 2), even with an exercise-volume difference between groups of 50% (ie, low-volume = 20 min vs high-volume = 40 min). Previous studies on individuals with CAD have found that for a fixed volume of exercise, the intensity is positively associated with greater improvement in CRF compared with a lower-intensity load.11,35,36 This confirms that lower exercise intensities may not be sufficient to improve CRF in a substantial proportion of sedentary adults.37 However, the current study has indeed provided evidence whether exercise associated with CRF response is more dependent on exercise volume or intensity. Thus, a low-volume HIIT program (ie, <10 min/session exercising at high-intensity zone) performed 2 d/wk seems to be an efficient stimulus to obtain a clinically relevant CRF improvement in individuals after an MI. This result reinforces the idea of less is more in this population, after observing similar results in obese participants with primary hypertension with no previous cardiovascular event.24
The mechanisms underlying the beneficial effect of low-volume HIIT could be multifactorial (ie, skeletal muscle and cardiovascular system).38,39 Thus, studies specifically applying low-volume HIIT in different populations following training have shown increases in regulators of mitochondrial biogenesis via coactivation of transcription factors linked to mitochondrial gene expression,19 positive changes in the myocardial mass leading to physiological cardiac hypertrophy,40 better autonomic profile,41 and even improvements in endothelium-dependent brachial artery flow-mediated dilation and significant outward artery modeling.23 Following these results and observations, it seems clear that low-volume HIIT may represent a safe, potent, and time-efficient exercise strategy in clinical practices such as cardiac rehabilitation programs. This would also facilitate concurrent resistance training and low-volume HIIT in the same session, as recommended by international consensus.42
On the contrary, the fact that, after the intervention, nonsignificant improvements related to CRF were found in the AC group shows that general physical activity recommendations for this population may not be enough to improve CRF. This evidence demonstrates that supervised and individually designed exercise led by qualified exercise specialists is of clinical relevance. Our results are reinforced even more after analyzing other variables related to CRF, such as MET, total exercise time on the cardiopulmonary exercise test (min), and power (Wpeak) (Table 2). Thus, only the supervised exercise groups presented positive and significant changes after the intervention in the aforementioned variables. Furthermore, it is particularly noteworthy that both HIIT groups incremented ≥1 MET after intervention (low-volume HIIT, 6.6 vs 7.6; and high-volume HIIT, 6.6 vs 8; P < .05; Table 2), knowing that each 1-MET increment in CRF is associated with a 13% and 15% lower risk of all-cause and cardiovascular disease mortality, respectively.34 The need to measure CRF in clinical practice and cardiac rehabilitation programs is, therefore, highlighted not only to characterize the health risk of the patients but also to determine the treatment efficiency after the exercise intervention.
It is well known that
O2peak, VT1, and VT2 are the gold standard references for the assessment of CRF.29 Therefore, another interesting result was that VT only improved in the high-volume HIIT group but not in the low-volume HIIT group (Table 2). This result could be justified by superior exercise volume at intensities relative to VT in the high-volume group compared with the low-volume HIIT group (24 min/wk vs 12 min/wk at intensities >VT2, respectively). It is likely, therefore, that a minimum necessary training load, and not only high intensity, will be necessary to stimulate change in submaximal variables such as VT.43
The significant and positive changes observed in waist circumference (ie, decrease) for both HIIT groups and no changes in the AC group demonstrate the following: (1) the effectiveness of supervised HIIT training to improve one of the most common indices of visceral adiposity associated with systemic inflammation and cardiovascular risk44; and (2) the likely need to also include a stricter diet intervention (ie, individual calorie intake design and not only counseling). Adding to that, we should support the fat-but-fit paradigm in this population, knowing that a medium-high CRF level may attenuate the adverse consequences of obesity on health.26
The results of this study should be interpreted within the context of its limitations. The first one consists of the relatively small sample size, not reaching a priori statistical power for the study. However, taking into account the estimated ES with such a small sample per group, we do find that our results are very promising. Second, we required participants in the AC group to follow-up on the physical activity recommendations and to keep a daily record of their performed physical activity; however, most of them either did not record any activity or did not comply with the recommendations.
This study suggests that a 16-wk intervention with 2 d/wk of different HIIT volumes with Mediet recommendations could equally improve CRF and reduce waist circumference after an MI. Low-volume HIIT may be a potent and time-efficient exercise training strategy to induce CRF in this population. In clinical practice, supervised and individually designed exercise and diet by specialists should be prescribed rather than just generally recommended.
The trial was supported by the Santiago Apostol Hospital (Miranda de Ebro, Burgos, Spain) and the Department of Physical Education and Sport (University of the Basque Country, UPV/EHU). The authors give special thanks to Jessica Werdenberg for proofreading the manuscript and to all the participants of the study.
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