High-intensity interval training improves metabolic syndrome and body composition in outpatient cardiac rehabilitation patients with myocardial infarction

This was a retrospective cohort study of 391 consecutive MI patients enrolled in early outpatient cardiac rehabilitation (CR) at Mayo Clinic, Rochester, MN between September 1st, 2015 and February 28th, 2018. Of 391 patients, 174 MI patients presented with MetS. Patients meeting the following inclusion criteria were included: (1) diagnosed with both MI and MetS, (2) completion of 36 sessions of supervised outpatient cardiac rehabilitation, (3) pre- and post-CR blood lipids and fasting blood glucose tests, and (4) completed pre- and post-CR dual energy X-ray absorptiometry. The cardiac rehabilitation program at Mayo Clinic is a multidisciplinary health care program that includes a highly supervised exercise program (36 exercise sessions), patient education and wellness programs, nutrition and smoking cessation counseling, stress management, and psychological and pharmacological counseling. A standard 36 sessions of CR usually lasts 12 weeks (three sessions per week). Of the 56 eligible patients who met all the inclusion criteria, 42 engaged in HIIT and 14 in MICT (Fig. 1). All aspects of this study conformed to the principles outlined in the Declaration of Helsinki and were approved by the Mayo Clinic Institutional Review Board. All participants agreed to use of their medical records for research purposes.

Patients performed an average of three supervised HIIT or MICT sessions/week on a treadmill, cycle ergometer, or recumbent stepper in the CR center and were prescribed 3 days of self-guided exercise at home. In the 1st week, all patients performed MICT, after that, if patients were able to exercise for ≥ 20 min at a rating of perceived exertion (RPE: Borg 6–20) of 12–14, they self-determined to continue MICT or transition to HIIT. The HIIT sessions were characterized by brief, intermittent bouts of high-intensity exercise interspersed with periods of low-intensity exercise (active recovery). Because most patients are prescribed heart rate modulating pharmacotherapy after MI and to maximize generalizability and real-world applicability, the intensity of HIIT was prescribed using RPE. These patients began with four high-intensity intervals of 30–60 s at an RPE of 15–17 interspersed with 1–5 min of low-intensity intervals at an RPE < 14, progressing to 5–8 high-intensity intervals of 2–4 min during 20–45 min of training according to the American College of Sports Medicine (ACSM) guidelines [11]. HIIT was performed only during supervised sessions with frequency not exceeding 3 days/week (non-consecutive days). MICT was performed for 20–45 min at an RPE of 12–14. Heart rate (HR) and rhythm were continuously monitored via a 3-lead electrocardiogram (Q-Tel telemonitoring system, Welch Allyn, USA) with blood pressure (systolic [SBP] and diastolic [DBP]) measured by manual sphygmomanometry. Heart rate (HR) data were retrieved from the exercise session report of each patient, which provided documentation on HRs at specific time-points including: (a) before and after each exercise training session for both HIIT and MICT groups, (b) at the end of the second and third intervals for HIIT, and (c) at the mid-point and end of exercise for MICT. Average HR was calculated by averaging HR values that were documented during exercise. The average metabolic equivalent (MET) and exercise time for each exercise session were reported by the Q-Tel telemonitoring system and documented in exercise session reports. Energy expenditure (EE) was calculated according to the equation: calories = [METs × body weight in kilograms × 3.5]/200 × exercise time, as described previously [12].

The definition of metabolic syndrome (MetS) is based on the revised National Cholesterol Education Program’s Adult Treatment Panel III (ATP III) [1]. An ATP III MetS score was calculated as the sum of the ATP III MetS criteria at baseline and completion of CR.

Metabolic syndrome z-score is a continuous score of each MetS variable defined by ATP III, and was calculated from modified z-scores of the following variables: [13] waist circumference; SBP; DBP; triglycerides (TG); fasting blood glucose (FBG); ATP III criteria, and standard deviations (denominator of each factor in the formula) using baseline data from the entire study cohort (N = 56): Metabolic syndrome z-score = [(50-HDL)/9.9] + [(TG-150)/69.8] + [(FBG-100)/24.5] + [(WC-88)/10.3] + [(SBP-130)/16.0] + [(DBP-85)/11.2].

Dual-energy X-ray absorptiometry (Lunar iDXA Series X, Madison, WI, USA) was conducted by trained radiology technicians using standardized procedures as described previously [14]. The scans were performed within 1 week prior to starting and 1 week after completion of CR. Scans were used to measure total body mass, body fat mass, body lean mass, body fat percentage, and abdominal region fat percentage (the area between the ribs and pelvis). Percentages of the total were calculated accordingly. The scanner was calibrated daily against a manufacturer supplied standard calibration block to control for possible baseline drift. Height was measured using a stadiometer.

Dietary assessment was performed using the Rate-Your-Plate (RYP) questionnaire as previously described [15] during the first and last CR session.

Due to the known influence of statin therapy on blood lipids and body composition, we retrieved and analyzed statin therapy intensity data for each patient. Statin therapy intensity was assessed within 1 week prior to the start and within 1 week after the completion of CR and stratified using ACC/AHA guidelines [16]. Statin intensity therapy is defined as a pseudo-continuous variable, 3 = high intensity, 2 = moderate intensity, 1 = low intensity, and 0 = none.

Exercise capacity was evaluated at the beginning and completion of 36 sessions of CR via standard exercise stress test, cardiopulmonary exercise test (CPET) or 6 min walk test (6 MWT). The protocols of pre- and post-intervention were the same for each patient. In the present study, exercise capacity was represented as peak oxygen consumed (VO₂peak, ml/kg/min) that was directly measured by performing CPET (HIIT = 28; MICT = 9), the VO₂peak calculated by the equation VO₂peak = 3.5 ml/kg/min * peak metabolic equivalents (METs) that was determined by standard exercise stress test (HIIT = 8; MICT = 3), or the VO₂peak calculated from the equation VO₂peak = 4.9486 + 0.023 * walk distance (meters) that was determined via using 6 MWT (HIIT = 6; MICT = 2) as described previously [17].

To determine if there was a difference in HIIT- and MICT-induced psychological response, we retrieved Patient Health Questionnaire 9 (PHQ-9) data that was collected monthly for patients to assess patient’s depressive symptoms. The PHQ-9 test was conducted as described previously [18].

The primary outcomes of this study were the mean differences in metabolic syndrome variables from baseline through 36 sessions of CR between groups. A secondary outcome of interest was the mean difference in body composition, including total body fat mass, body fat percentage, abdominal fat percentage, and body lean mass between groups.

Baseline data are presented as frequency and percentage for categorical variables and compared between groups using the Pearson Chi-square test or Fisher exact test. Continuous data are presented as mean and standard deviation and compared between groups using two-sample t-test or non-parametric Wilcoxon rank-sum test, as appropriate depending on the distribution. Prior to analyses, normality was evaluated and the distribution of changes looked approximately normal. Analysis of covariance (ANCOVA) was used to compare the change in each parameter of interest between groups. In this analysis, change was modeled as the outcome in a linear regression model and group effects were tested with adjustment for the baseline value of the parameter being tested. These analyses were repeated in a matched subset of each group to control for potential differences in exercise duration, exercise intensity, and exercise energy expenditure. In order to assess differences over time between groups, a repeated measures analysis of variance (ANOVA) was used. In this analysis, measurements at each week were used to examine the interaction of time and group and tested the differences in effects over time between groups. Energy expenditure and METs were log transformed in these analyses to approximate normality prior to analysis. Means and confidence intervals were back-transformed to the original scale for presentation. Comparisons at each week used the method of Scheffe to adjust P-values for multiple comparisons. SAS version 9.4 (Cary, NC) was used for analyses and Two-sided P-values ≤ .05 were considered to be statistically significant.

Baseline characteristics were not different between groups (Table 1): age (69 ± 14 vs. 68 ± 10 years P = .78), female (36% vs. 36%, P > .99), body weight (91.2 ± 14.4 vs. 91.5 ± 16.3 kg P = .95), height (170 ± 10 vs. 171 ± 9 cm P = .84), and BMI (31.5 ± 4.2 vs. 31.3 ± 4.7 kg/m² P = .90). Comorbidities and medications were also not different between groups (P > .05). Percentage of PCI (50% vs. 57%) and CABG (14% vs. 14%) were not different between groups (P = .64, P > .99 respectively). Twenty-five patients suffered one-vessel disease (MICT = 6, 42%; HIIT = 17, 40%; P = .88), 17 patients suffered two-vessel disease (MICT = 4, 29%; HIIT = 12, 31%; P = .99), 14 patients suffered three-vessel disease (MICT = 4, 29%; HIIT = 13, 31%; P = .74). The number of days between patients’ MI event and the beginning of CR was also not different between groups (14 ± 4 vs. 14 ± 11 days, P = .34). The VO₂peak at baseline was not significantly different between groups (23.7 ± 7.1 vs. 23.0 ± 6.3 ml/kg/min, P = .73).

The HIIT group demonstrated significantly higher average HR, average exercise intensity, longer duration of exercise, and higher energy expenditure per session at each time point compared to MICT group (P < .05), while the average exercise intensity (P = .40), duration of exercise at 12-weeks (P = .39), and energy expenditure at 2-weeks (P = .09) and 12-weeks (P = .37) were not different between groups. Further, there were no differences between groups in average HR (P = .81), average exercise intensity (P = .40), duration of exercise (P = .68), energy expenditure per session (P = .37) across groups over time (Fig. 2).

Compared to MICT, the HIIT group demonstrated greater reductions in MetS presence (relative risk = 0.5, 95% confidence interval 0.33–0.75, P < .001), MetS z-score (− 3.6 ± 2.9 vs. − 0.8 ± 3.8, P < .001), ATP III MetS scores (P = .005) and improvements in individual MetS variables, including, waist circumference (P = .01), FBG (P < .001), TG (P = .001) and DBP (P = .001). The changes in HDL-C and SBP were not different between groups (Table 2).

The HIIT group demonstrated greater improvements in total body fat mass (P = .002), body fat percentage (P = .002), abdominal fat percentage (P = .004), and body lean mass (P = .01) compared to MICT (Fig. 3).

Due to the difference in exercise energy expenditure between HIIT and MICT, we matched HIIT and MICT participants for exercise energy expenditure. In this sub-group analysis, the HIIT group demonstrated greater improvements in MetS z-score (P < .001), ATP III MetS score (P = .005), and MetS variables (including FBG (P = .002), TG (P = .008), DBP (P < .001), total body fat mass (P = .02), body fat percentage (P = .01), body lean mass (P = .03), and abdominal fat percentage (P = .01) compared to MICT, with no differences in RYP scores (P = .95) and average statin therapy intensity between groups from baseline to follow-up (P = .23) (Table 3).