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bioRxiv · 10.1101/2025.08.22.671781

Preservation of cerebral vascular and metabolic health with greater cardiorespiratory fitness in coronary artery disease

Sanami, S.·Tremblay, S. A.·Potvin-Jutras, Z.·Rezaei, A.·Sabra, D.·Gagnon, C.·Intzandt, B.·Mainville-Berthiaume, A.·Wright, L.·Gayda, M.·Iglesies-Grau, J.·Nigam, A.·Bherer, L.·Gauthier, C.
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Abstract

BackgroundCoronary artery disease (CAD) is the leading cause of cardiovascular-related death globally. Beyond its cardiac consequences, CAD significantly impacts brain health, causing grey matter atrophy, reduced cerebral blood flow (CBF), impaired cerebrovascular reactivity (CVR), and cognitive decline. Recent evidence also highlights altered cerebral metabolism in CAD, characterized by reduced cerebral metabolic rate of oxygen consumption (CMRO2) and increased oxygen extraction fraction (OEF). Notably, impaired cardiorespiratory fitness, as measured by reduced peak oxygen uptake (VO2peak), is a hallmark of CAD progression and a strong prognostic marker of cardiovascular and neurological outcomes. Although VO2peak is associated with brain structural integrity and cognitive function, its relationship to cerebral vascular and metabolic function in CAD patients remains poorly understood. MethodsThirty-seven healthy individuals (age=65.35 {+/-} 8.31) and thirty-five patients with CAD (age=66.42 {+/-} 9.29) participated in this study. The objective was to determine whether higher cardiorespiratory fitness is associated with markers of cerebral health known to be impaired in CAD, in order to assess the potential of exercise as a strategy to mitigate CAD-related brain alterations. Cerebral vascular and metabolic biomarkers, including CBF, CVR, CMRO2, and OEF, were quantified using calibrated functional magnetic resonance imaging (MRI). Participants also completed a maximal cardiopulmonary exercise test on a bicycle ergometer to determine peak oxygen uptake (VO2peak). ResultsAcross all participants, VO2peak was positively associated with CBF ({beta}=0.32, p=0.02), and CVR ({beta}=0.002, p=0.04), in grey matter, confirming a link between aerobic fitness and vascular health across the cardiovascular health spectrum. However, metabolic markers exhibited group-specific patterns. Specifically, in CAD patients, VO2peak was positively associated with CMRO2 ({beta} = 0.08, p = 0.02), suggesting that reduced CMRO2 in CAD may be partially preserved by greater cardiorespiratory fitness. In contrast, a negative association between VO2peak and OEF was observed exclusively in healthy controls ({beta} = -3.6, p = 0.02), consistent with adaptations in healthy aging being primarily driven by improved CBF without changes in CMRO2. ConclusionThis study shows that higher cardiorespiratory fitness is associated with improved cerebral vascular and metabolic function, with distinct patterns observed between healthy individuals and those with CAD. In patients with CAD, greater fitness appears to preserve cerebral oxygen metabolism, while in healthy individuals, fitness is primarily linked to enhanced perfusion. These findings support the role of aerobic exercise as a promising strategy to counteract CAD-related brain alterations, emphasizing the importance of targeting cardiorespiratory fitness in both prevention and rehabilitation settings.

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Sanami, S., Tremblay, S. A., Potvin-Jutras, Z., Rezaei, A., Sabra, D., Gagnon, C., Intzandt, B., Mainville-Berthiaume, A., Wright, L., Gayda, M., Iglesies-Grau, J., Nigam, A., Bherer, L., Gauthier, C.. 2025-08-27. Preservation of cerebral vascular and metabolic health with greater cardiorespiratory fitness in coronary artery disease. https://doi.org/10.1101/2025.08.22.671781

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