Exercise-induced effects on coronary atherosclerosis assessed by grayscale and radiofrequency intravascular ultrasound

Abstract

Coronary atherosclerosis is a leading cause of morbidity and mortality worldwide. Physical inactivity is an independent risk factor for coronary artery disease, and physically active patients have an improved prognosis compared to sedate patients. Although the clinical relationship between exercise and cardiovascular health is convincing, the pathophysiological mechanisms responsible for improved outcomes in this large patient group are largely unknown. In a randomized controlled trial, we assessed exercise-induced effects on coronary atherosclerosis in 36 patients with established coronary artery disease undergoing stent implantation and optimal medical therapy. Patients exercised for 12 weeks, either following an aerobic interval training protocol, or performing moderate continuous exercise. Coronary atherosclerosis was assessed by grayscale and radiofrequency intravascular ultrasound, quantifying both plaque geometry and tissue characteristics. Our main findings were that with both exercise protocols there was a significant reduction in necrotic core (≈ 3 %) and a strong trend towards a reduction of plaque burden (≈ 10 %) in non-stented coronary segments and in separate atheroma lesions. There were no differences between exercise groups. In a post-hoc analysis of data from the randomized controlled trial, we assessed clinical factors at baseline that potentially were associated with a reduction in necrotic core and plaque burden at follow-up. We found a strong association between the clinical presentation of disease and necrotic core volume reduction after aerobic exercise (p=0.011). The association was in favor of patients with stable coronary artery disease, and necrotic core volume reduction was much more frequent in these patients (17/18) than in patients with unstable coronary artery disease (8/18). There were no significant associations between any clinical baseline explanatory variables and plaque burden reduction at follow-up. In a third study conducted within a subgroup of patients included in the randomized controlled trial, we assessed the reproducibility of intravascular ultrasound data acquisition in stented coronary arteries. This was performed by repeating the intravascular ultrasound pullback twice at the same time-point, thus simulating data collection in a serial imaging study. Our main finding was that the inter-pullback reproducibility of geometrical data was very good for non-stented segments with relative differences between pullbacks < 5 %. For stented segments reproducibility was poorer, though acceptable, and < 10 %. Taken together, the data presented in this thesis strengthens the scientific evidence for beneficial exercise-induced effects on coronary atherosclerosis, not only with respect to atherosclerotic burden, but also with respect to plaque vulnerability. Furthermore, exerciseinduced effects on coronary atherosclerosis may be more beneficial in patients with stable coronary artery disease compared to patients in the early phase after an acute coronary syndrome. Finally, serial intravascular ultrasound imaging in stented coronary arteries seems to be associated with a variability of 5–10 % attributed to the acquisition of images itself, which may have implications for the design of future serial stent studies.