Salutary effects of high-intensity interval training in persons with elevated cardiovascular risk

Healthy adults

In healthy adults, a meta-analysis that included 723 healthy adults aged 18–45 years old from 28 controlled trials of 3–24 weeks’ duration showed a large absolute increase in peak VO₂ of 4.9 mL/kg/minute following HIIT, which was greater than that seen with traditional MICT⁹. Larger increases were observed among individuals with lower baseline fitness and in interventions longer than 10 weeks. Improved skeletal muscle mitochondrial function and pulmonary oxygen uptake kinetics have been demonstrated after only six HIIT sessions over 2 weeks in healthy untrained men¹⁰. Although occasional studies have failed to show superior effects of HIIT over MICT on peak VO₂, these studies generally employed a program duration shorter than 10 weeks³. Because equivalent energy expenditure can be accomplished in less time with HIIT than with MICT, this may allow shorter exercise sessions with HIIT, thereby improving adherence.

Obesity

Given the frequent association of obesity with low fitness and with CV risk factors such as hypertension, glucose intolerance, and dyslipidemia, a strong rationale exists for aerobic exercise training in such individuals. In three studies 3–6 months in duration, similar improvements in body mass index and waist circumference were observed in overweight/obese participants following both MICT and HIIT^11–13. The equivalent anthropometric changes might be attributed to the similar total energy expenditure with the two programs in those studies.

Hypertension

Traditional MICT exerts significant reduction of BP in hypertensive adults, especially those with suboptimal baseline BP control¹⁴. In such individuals who were not receiving antihypertensive drugs, HIIT for ≥12 weeks appears to provide a similar antihypertensive effect³. For example, 16 weeks of MICT or HIIT led to similar reductions of systolic (10 mmHg) and diastolic (6 mmHg) BP in middle-aged adults with elevated BP at baseline¹³. A 12-week HIIT program in overweight/obese adolescents with borderline hypertension also elicited significant reductions in both systolic BP (9 mmHg) and diastolic BP (6 mmHg)¹⁵.

Lipids

Among individuals with dyslipidemia, traditional MICT typically elicits modest increases in high-density lipoprotein cholesterol (HDL-C) but exerts no consistent effect on low-density lipoprotein cholesterol or triglycerides¹⁶. Similar effects on blood lipids are observed with HIIT¹⁷. Modest increases of HDL-C with HIIT required 8 or more weeks of training and occurred in only 3 of 10 such studies¹⁷. Given these inconsistent effects on HDL-C without benefit on other lipid fractions, neither HIIT nor MICT can generally be recommended as primary therapy for the treatment of dyslipidemia.

Glucose metabolism

Substantial evidence suggests that HIIT improves glucose metabolism to a similar or greater extent than does MICT. Augmented insulin sensitivity occurs as early as 2 weeks after the initiation of HIIT¹⁸ and has been shown in both healthy adults¹⁹ and those with metabolic syndrome¹³. Improved oral glucose tolerance test results have been consistently reported after HIIT^3,18,20. Fasting blood glucose did not change in studies of less than 12 weeks’ duration but declined in four of seven longer studies³. Small studies have found improved glycemic control in patients with type 2 diabetes^21–23.

Adults with heart disease

Incontrovertible evidence for the benefits of MICT in patients with CVD has accumulated over the past four decades through hospital-based CR programs involving patients after acute MI, coronary revascularization, valvular surgery, and those with chronic heart failure (CHF). Similar, though less extensively studied, salutary effects of HIIT have been demonstrated in patients with CVD and are reviewed below.

Coronary artery disease. Multiple studies have documented the benefit of HIIT in patients with coronary artery disease (CAD), the most prevalent form of heart disease in developed countries. A meta-analysis of 229 patients with CAD demonstrated a 1.5 mL/kg/minute larger mean increase in peak VO₂ with HIIT than with MICT²⁴. A larger meta-analysis that included 472 CAD patients showed a similarly augmented gain in peak VO₂ (1.8 mL/kg/minute mean difference) compared with MICT²⁵. In this latter analysis, no differences in blood glucose or lipids were observed between the groups. However, resting heart rate (-1.8 beats/minute) and body weight (-0.5 kg) declined slightly after MICT but not HIIT. A recently published randomized trial also showed a significantly larger increase in peak VO₂ after 8 weeks of HIIT compared to MICT (4.5 versus 2.5 mL/kg/minute), respectively²⁶.

Chronic heart failure. Although CR was not approved until 2014 by the Center for Medicare and Medicaid Services for patients with CHF, considerable evidence has accrued on the benefits of HIIT in this population. One of the first studies to examine the effect of HIIT in CHF patients showed a remarkable 46% increase in peak VO₂ in nine older patients (mean 75 years) with post-MI CHF versus an increase of only 14% with MICT²⁷. Favorable left ventricular remodeling and increased left ventricular ejection fraction occurred only after HIIT. Three recent meta-analyses have confirmed a larger increase in peak VO₂ with HIIT than MICT in CHF patients^28–30. Haykowsky et al.²⁸ showed a mean 2.1 mL/kg/minute larger increase in peak VO₂ with HIIT in seven studies encompassing 168 patients. In a meta-analysis by Smart et al.²⁹ involving 212 patients who performed HIIT and 66 who performed MICT, the mean improvement in peak VO₂ was 1.0 mL/kg/minute larger after HIIT. A very large meta-analysis that included 74 exercise-based CR trials involving 5877 participants showed a 23% mean increase in peak VO₂ among patients receiving HIT versus a 13% increase in those undergoing MICT³⁰. Of note, withdrawal from the CR program was lower with HIIT. It should be noted that all of the studies and meta-analyses cited above excluded patients with CHF and preserved ejection fraction (HFpEF), who comprise 30–40% of the CHF population. Studies of HIIT are clearly needed in this latter group.

Heart transplant recipients. Although data remain limited regarding the effects of HIIT in heart transplant recipients, available evidence suggests a similar benefit as seen with MICT. Compared to a usual care control group, 24 stable heart transplant recipients 1–8 years post transplantation demonstrated a 3.6 mL/kg/minute higher peak VO₂ after 1 year of HIIT³¹. In a study of 16 patients ≥12 months post transplantation, 8 weeks of HIIT induced a larger increase in peak VO₂ than did MICT (4.9 versus 2.6 mL/kg/minute)³².

Quality of life

Although quality of life (QOL) is often considered a “softer” outcome variable than changes in physiological indices, it is probably a more relevant variable to patients. In this context, both MICT and HIIT have elicited improvement in QOL in a variety of clinical settings. For example, improvement in QOL after HIIT has been reported in patients with CAD²⁶ and CHF³³, cardiac transplant recipients³², and generally healthy older adults³⁴. Such improvement in QOL may reinforce the patient’s motivation to continue exercise participation.

Safety of HIIT

An important concern in prescribing any exercise program, especially in older adults and patients with CVD or other comorbidities, is safety. To date, the evidence suggests that HIIT is well tolerated to a similar extent as MICT. In the large meta-analysis of CHF patients previously mentioned, no deaths were attributed to exercise training regardless of intensity³⁰. A similar finding was reported in an analysis of 4846 CAD patients from three Norwegian CR centers³⁵. In this study, major complications were one per 129,456 hours of MICT and one per 23,182 hours of HIIT. Nevertheless, HIIT may not be appropriate for frail older adults, those with significant orthopedic, neurological, or balance difficulties, those with marked obesity, or those with severe deconditioning. In such individuals, an initial low-to-moderate-intensity exercise program appears to be preferable.

Mechanistic insights

Given the substantial benefits of HIIT in a wide variety of settings, insights into the biochemical and molecular adaptations accompanying HIIT are worthy of inquiry. In patients with obesity, metabolic syndrome, or CHF, HIIT induced increases in peroxisome proliferator-activated receptor γ co-activator (PGC)-1α, a master regulator of oxidative phenotype^12,13,27 and muscle mitochondrial capacity^10,18. In addition, sarcoplasmic reticulum calcium uptake was augmented by HIIT but not MICT, likely owing to an increased ability to perform high-intensity muscle contractions^12,18,25. Another salutary effect of HIIT is to enhance flow-mediated dilation of the brachial artery, a measure of vascular endothelial function mediated in part by increased nitric oxide availability^12,13,27. Finally, increased cardiac stroke volume has been reported after HIIT in obese women³⁶, sedentary middle-aged adults³⁷, and patients with CHF²⁷.