Reference
Hearon CM Jr, Dias KA, MacNamara JP, et al. 1 year HIIT and omega-3 fatty acids to improve cardiometabolic risk in stage-A heart failure. JACC Heart Fail. 2022;10(4):238-249.
Study Objective
To determine if 1 year of high-intensity interval training (HIIT) and omega-3 fatty acid supplementation would improve fitness, cardiovascular function and/or structure, and body composition in obese, middle-aged adults who are at high risk of heart failure (stage A)
Key Takeaway
One year of HIIT training can induce favorable changes in biomarkers of heart health in a population of obese, middle-aged subjects with biomarkers of early cardiac damage.
Design
Prospective, parallel-group, randomized, attention-controlled, and placebo-controlled clinical trial
Participants
Investigators allocated 80 subjects (aged 40–55 years) to either a HIIT training group or to no exercise program as a control. Of the original 80 participants, 56 completed the trial.
In the control group of 34 subjects, 7 withdrew due to time commitment or loss to follow-up. In the HIIT group, 17 withdrew due to time commitment, loss to follow-up, or aversion to exercise.
The attention-control group was allowed to do yoga, stretching, and strength training. Neither group received dietary interventions or guidelines.
Inclusion criteria: All subjects were aged 40 to 55 years. They were at risk of stage A heart failure (HF), per the American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) definition. These are people at high risk of heart failure due to obesity (as defined by body mass index [BMI] of 30 or greater), visceral obesity (visceral fat content >2 kg), and the elevation of certain cardiac biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP >40 pg/mL), or high-sensitivity cardiac troponin (cTnT, >0.6 pg/mL).
There were extensive exclusion criteria, some of which would appear to limit participants’ ability to engage in a HIIT program, and others would seem to imply a stage of heart failure beyond the ACCF/AHA “A” stage, or would herald the possibility of a cardiac event during the program. These included: hypertension, heart failure (not stated but most likely meaning beyond stage A), moderate to severe chronic obstructive pulmonary disease, restrictive pulmonary disease–asthma as the 1 listed in the patient population section, external angina or previous myocardial infarction, valvular heart disease, history of atrial fibrillation, previous transient ischemic attack/stroke, and treatment for obstructive sleep apnea. Participants could use medication for hypertension, such as angiotensin-converting enzyme (ACE) inhibitors or diuretics, but could not use beta blockers during maximal exercise testing.
Interventions
In the intervention group, exercise training for each subject was prescribed based on heart rate (HR). The goal was to increase the duration and intensity of exercise over the 1 year. Workouts, which were on a cycle ergometer, varied in duration (30 to 60 minutes) and varied in intensity (continuous pace, aerobic intervals, recovery sessions). Frequency was 3 to 4 times per week. HR was recorded.
A control group was defined as those not participating in the HIIT activity versus those who did so for 1 year. Other forms of exercise were allowed.
Within both the control (no HIIT) and activity/intervention (HIIT) group, there was a subgroup that received 1.6 g/day of omega-3 fatty acids and a placebo group that received 1.6 g/day of olive oil (encapsulation). Thus, there were 4 distinct groups.
Study Parameters Assessed
The researchers looked at cardiometabolic factors and exercise results, as well as changes to left ventricular structure. Specifically, they examined the size of the left ventricle to determine if cardio-dilatory compensations were occurring, which can lead to cardiac performance increases in the short term.
Additionally, researchers took the following as outcome variables in exercise: heart rate, mean arterial blood pressure during exercise, cardiac output, stroke volume, respiratory exchange ratio, oxygen uptake (VO2). Peak VO2 was defined as the highest oxygen uptake measured from at least a 30-second Douglas bag (holds expired air) collection.
Structurally, they measured: left ventricular (LV) mass, LV volume (magnetic resonance imaging [MRI], transthoracic echocardiograph); myocardial triglyceride content (magnetic resonance spectroscopy); arterial stiffness/function (central pulsed-wave velocity; augmentation index), and body composition (dual x-ray absorptiometry scan). This test used tonometry to see the reflection of wave energy—an indirect measurement of arterial stiffness. The carotid arteries were measured with Doppler ultrasound for stiffness as well.
Primary Outcomes
- Body composition
- Myocardial triglyceride concentration
- Maximal exercise capacity
- Cardiac remodeling and vascular stiffness and function
Key Findings
There was no independent or interaction effect of omega-3 fatty acid supplementation on any primary outcome variable, in either group.
When comparing HIIT to non-HIIT groups for body composition and myocardial triglyceride concentration: There was a moderate decrease in fat mass in the exercise group (a loss of 2.63 kg; P=0.018). The loss of visceral adiposity varied and was not statistically significant, at a 0.13 kg loss (95% CI, P=0.149).
As far as reductions in myocardial triglyceride (TG), there were none. The researchers caution that since only 39 patients had interpretable pre- and post-MRI spectroscopy measures for myocardial TG, this outcome lacks statistical power. These 39 patients were spread out into 4 subgroups (HIIT plus omega-3; HIIT with placebo; control plus omega-3; control with placebo). Further studies are needed to make any determination of this parameter.
Findings on maximal exercise capacity: HIIT for 1 year increased absolute peak VO2 (highest oxygen uptake). This was significant (95% CI, P<0.001). The researchers attributed this to an increase in peak cardiac output and stroke volume.
Findings on cardiac remodeling and vascular stiffness and function: intervention resulted in 1 year of HIIT-induced cardiac remodeling (physiologic), which included increased left ventricle mass of an average of 9.40 g (95% CI, P<0.001); and increased left ventricular end diastolic volume (better filling of ventricle) for an average of 12.33 mL (95% CI, P<0.001).
There was no effect on either arterial stiffness or on carotid stiffness. There was a reduction in pulsed-wave augmentation index (4.81% reduction; 95% CI, P=0.009).
Transparency
The American Heart Association Strategically Focused Research Network supported the study. The authors report that they have no relationships relevant to the contents of the paper that need to be disclosed.
Practice Implications & Limitations
This study demonstrates in a very precise way the benefits of exercise in those at very high risk of heart failure/early heart failure. The actual study population is important to consider. These were individuals 40 to 55 years of age who were obese. They were included in this study because they had NT-proBNP elevations, and/or high-sensitivity cardiac troponin. NT-proBNP is considered a valid marker of heart disease, and individuals with normal levels can be considered not to have heart failure.1
Brain natriuretic peptide (BNP) is a heart-protective substance that works against the neural-hormonal effects of renin (which include sympathetic overactivation, increased vessel tone, and increased risk of destabilizing electrical cardiac events).2 Troponin (TnT) is a biomarker for early heart damage.3 Early damage can occur with various degenerative processes and progress slowly, resulting in much lower TnT levels than a myocardial infarction. Uncoupling, damaging forms of oxidative stress, mitochondrial fission, and attrition of mitochondria are all sure signs of a rapidly aging heart and examples of a slow, degenerative process.5
This study makes an important point that even in those who have signs of early heart damage, there remains the ability to recondition the heart, improve oxygen utilization, physiologically remodel the heart to be stronger, and even lose some overall adipose tissue.
What is somewhat quizzical is that the HIIT program did not really impact visceral adipose tissue. This means that a major risk factor for cardiac death remains in place. The obesity and visceral fat accumulation would imply that metabolic syndrome and insulin resistance are issues for many of the study subjects.
The HIIT regimen did not decrease arterial stiffness either. In contrast to what may be expected, omega-3 fatty acid supplementation made no difference in arterial stiffness in either the HIIT group or the control group. The 1.6 g per day is lower than what might be used in a more aggressive protocol, and the quality of this supplement is hard to determine, but the null effect is noteworthy.
This study makes an important point that even in those who have signs of early heart damage, there remains the ability to recondition the heart, improve oxygen utilization, physiologically remodel the heart to be stronger, and even lose some overall adipose tissue.
This study suggests that it is not too late for middle-aged patients to increase the strength of their cardiac pump with proper exercise. Ultimately, it demonstrates that they have not lost the plasticity and potential for adaptive remodeling of the heart.
Visceral fat contributes to cardiovascular risk, including heart failure. The lack of reduction in visceral fat with HIIT implies that we should not expect some processes such as inflammation, lipid peroxidation, and perhaps dysglycemia to change with HIIT, at least to the extent that these are associated with the visceral fat of any given patient.
Exercise, however, may have other benefits. Exercise causes the release of protective molecules, the sestrins, from the heart. The mild stress of exercise has a pre-conditioning effect and an adaptive one.5,6 It would be interesting to observe the adaptive changes due to sestrin release that take place, along with other, possibly hermetic effects, with a HIIT regimen.7
This study should temper our confidence in omega-3 fatty acid supplementation as a standalone treatment. In addition to exercise, diet can help control blood parameters related to higher risk of heart failure. It is clear that diet—both the elimination of lipid-raising, pro-oxidative, and glycemic-dysregulating foods and the addition of protective, antioxidant-bearing, and anti-inflammatory foods—is an essential element of a treatment plan. Diet combined with HIIT training could create comprehensive change in a direction away from heart failure and toward heart health.
