Associations of cardiorespiratory fitness indicators with brain volumes and cognitive function in patients with coronary artery disease – findings from the Heart-Brain trial

Abstract Aim Patients with coronary artery disease (CAD) are at risk of accelerated cognitive decline. We aimed to explore how different cardiorespiratory fitness (CRF) indicators associate with brain structure and cognitive function in these patients. Methods We studied 105 stable CAD patients (62.1±6.6 years, 21% female), using baseline data from the randomized controlled Heart-Brain trial. Time-to-exhaustion (TTE), peak oxygen uptake (VO2peak), ventilatory anaerobic threshold (VAT), oxygen uptake efficiency slope (OUES), peak O2-pulse and 60-s heart rate recovery (HRrec) were determined from cardiopulmonary exercise tests. From magnetic resonance imaging, we extracted brain volumes (total-, grey-, and white matter volumes [TBV, GMV and WMV]) and hippocampal volume (HV), and calculated the difference between estimated and chronological brain age (brainPAD). Episodic memory, processing speed, working memory, executive function/attentional control and general cognition were evaluated. Results TTE, VO2peak and OUES were positively associated with TBV (βstd 0.15 to 0.19, p<0.05) and HV (βstd 0.23 to 0.36, p<0.05). Higher OUES, HRrec and O2-pulse were associated with lower brainPAD (βstd -0.23 to -0.32, p<0.05). Higher VAT was associated with better working memory (βstd=0.26, p=0.023), and higher OUES with better executive function/attentional control (βstd=0.20, p=0.021). Hippocampal atrophy was more prevalent in lower vs middle/upper VO2peak tertile (p=0.001). Conclusion In CAD patients, both maximal and submaximal CRF-indicators were associated with larger brain volumes, with stronger region-specific association with HV, and younger physiological appearance of the brain, while associations with cognitive functions were fewer and weaker. Our findings support CRF as a biomarker of structural brain health in CAD patients.