Background The effect of physical exercise on lipid content of coronary artery plaques is unknown. With near infrared spectroscopy we measured the effect of high intensity interval training (HIIT) on lipid content in coronary plaques in patients with stable coronary artery disease following percutaneous coronary intervention. Methods and Results In CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near-Infrared Spectroscopy) 60 patients were randomized to 6 months supervised HIIT or to a control group. The primary end point was change in lipid content measured as maximum lipid core burden index at 4 mm (maxLCBI_4mm). A predefined cutoff of maxLCBI_4mm >100 was required for inclusion in the analysis. Forty-nine patients (HIIT=20, usual care=29) had maxLCBI_4mm >100 at baseline. Change in maxLCBI_4mm did not differ between groups (-1.2, 95% CI, -65.8 to 63.4, P=0.97). The estimated reduction in maxLCBI_4mm was -47.7 (95% CI, -100.3 to 5.0, P=0.075) and -46.5 (95% CI, -87.5 to -5.4, P=0.027) after HIIT and in controls, respectively. A negative correlation was observed between change in peak oxygen uptake (VO_2peak) and change in lipid content (Spearman's correlation -0.44, P=0.009). With an increase in VO_2peak above 1 metabolic equivalent task, maxLCBI_4mm was on average reduced by 142 (-8 to -262), whereas the change was -3.2 (154 to -255) with increased VO_2peak below 1 metabolic equivalent task. Conclusions Six months of HIIT following percutaneous coronary intervention did not reduce lipid content in coronary plaques compared with usual care. A moderate negative correlation between increase in VO_2peak and change in lipid content generates the hypothesis that exercise with a subsequent increase in fitness may reduce lipid content in coronary atheromatous plaques. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02494947.

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