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Background: Coronary heart disease (CHD) is frequently associated with cognitive impairment (CI), whereas physical exercise may improve cognition. To date, the cognitive profile of physically active CHD patients remains poorly understood. Physical activity and cognition has been associated with neurotrophic biomarkers that are positively modulated by a higher cardiorespiratory fitness (V̇ O 2 peak) and/or active lifestyle. This study aimed to compare the cognitive functions, V̇ O 2 peak and trophic biomarkers in physically active CHD patients vs healthy controls., Methods: Thirty-nine CHD patients and 20 controls performed a cardiopulmonary exercise test, a neuropsychological assessment (short-term and working memory, processing speed, executive functions, and long-term verbal memory), and a blood draw to measure brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF1), and cathepsin B (CTSB) plasma concentrations. Physical activity was also measured with an accelerometer for 1 week., Results: Compared to controls, CHD patients had lower V̇ O 2 peak (22.2 vs 29.3 mL/min/kg, p < 0.001), but similar moderate to vigorous physical activity levels (27.5 vs 34.4 min/day, p = 0.114). CHD patients had poorer performances for executive functions (0.198 vs -0.370, p = 0.004) and processing speed (0.150 vs -0.293, p = 0.025), as well as lower BDNF concentrations (166.4 vs 300.2 ng/ml, p = 0.027), but similar IGF-1 and CTSB concentrations (p > 0.05) when compared to controls. BDNF was an independent predictor of processing speed in CHD, and IGF-1 and BDNF were independent predictors of verbal memory in healthy controls., Conclusion: Despite similar physical activity levels, fit CHD patients had lower V̇ O 2 peak values, cognitive performances (executive functions and processing speed) and BDNF concentrations when compared to controls., (Copyright © 2022 Elsevier B.V. All rights reserved.)