Effects of High-Intensity Interval Training on Coronary Atheromatous Plaques: Results from a randomized clinical trial

Abstract

Atherosclerosis is a chronic, progressive disease characterized by the deposition of cholesterol and various inflammatory cells within the vessel walls, leading to fatty deposits (plaques) and calcifications. When the coronary arteries, which supply blood to the heart muscle, are affected, it can result in lumen narrowing with reduced coronary artery flow. Plaque size and composition are important predictors of coronary heart disease progression, symptoms, and outcomes. Large plaques with high lipid content are particularly vulnerable, as they carry an increased risk of rupture and the formation of blood clots with the risk of myocardial infarction. Healthy lifestyle is of importance to prevent plaque progression. Physical fitness, expressed as maximal oxygen uptake, has been demonstrated to be an independent prognostic factor for the development and prognosis of coronary artery disease. Accordingly, regular exercise is an essential part of the preventive strategy, and participation in exercise-based cardiac rehabilitation is strongly recommended in current guidelines. Although numerous beneficial effects of exercise on the heart are described, knowledge of how physical exercise affects coronary plaques remains limited. This thesis is based on a clinical, randomized, controlled exercise study, "Impact of cardiac exercise training on lipid content in coronary atheromatous plaques evaluated by near-infrared spectroscopy: A randomized trial (CENIT)," which aimed to investigate the effects of high-intensity interval training (HIIT) on coronary plaques in patients with stable coronary artery disease undergoing Percutaneous Coronary Intervention (PCI). Intracoronary imaging was performed using near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). After PCI, a baseline cardiopulmonary exercise test was performed to measure maximum heart rate and oxygen uptake. Patients were randomly assigned to either the intervention group, which participated in twice-weekly supervised HIIT sessions, or the control group, which followed the current preventive treatment guidelines without additional monitoring. In addition to receiving guidance on supplementary strength training, the intervention group was provided with an activity monitor to motivate and encourage increased exercise volume. After a 6-month followup period, intravascular imaging, blood sampling, exercise tests, and clinical data were repeated. The thesis consists of three articles: Article I: In this study, we examined the impact of HIIT on plaque composition in coronary arteries. Using intracoronary imaging with NIRS, plaque lipid content was measured at study initiation and after six months. When comparing changes in lipid content, no significant group differences were detected. There was a significant correlation between increase in oxygen uptake (independent of group allocation) and reduction in plaque lipid content. Article II: In this study, we investigated how regular HIIT affects plaque geometry within coronary arteries. Using IVUS, plaque volume was measured at the study initiation and again after a six-months period. A significant distinction emerged after comparing the changes in plaque volume between the groups. A favorable plaque regression was demonstrated in the group following HIIT, as opposed to a non-significant increase in plaque volume in the control group. Article III: In this study, we analyzed baseline data from the CENIT population to explore a potential association between circulating lipoprotein subfractions assessed by nuclear magnetic resonance spectroscopy and coronary plaque composition assessed by near-infrared spectroscopy. Lp(a) and free cholesterol in the smallest HDL subfractions (HDL-4) exhibited the strongest potential for predicting lipid content in coronary plaques. However, after adjusting for cardiovascular risk factors in the model, none of the lipoprotein subfractions were significantly associated with lipid content in coronary plaques. In summary, these studies demonstrate that supervised HIIT has beneficial effects on coronary artery disease, comprising both plaque regression and, to some extent, plaque stabilization, at least in patients improving their cardiopulmonary fitness. The prevalence of lipid-rich coronary plaques in our study population could not be denoted using circulating lipoprotein subfractions. The results of these studies contribute to a greater understanding of the underlying mechanisms concerning the effect of exercise on coronary plaques and strengthen the scientific evidence for recommending exercise as medicine for patients with stable coronary artery disease. “The heart cannot see what shoes you are wearing, but it can feel the effects.” Andre Le Gerche