Effects of HIIT and HIIT plus Resistance Training on Cerebral Blood Flow and Other Health Outcomes in Individuals with Coronary Artery Disease: The Heart-Brain Randomized Controlled Trial

Abstract Background Individuals with coronary artery disease (CAD) are at higher risk of cognitive decline and dementia, in which gray matter cerebral blood flow (CBF) plays a critical role. This study investigated the effects of High Intensity Interval Training (HIIT) and HIIT plus resistance training (RT) on CBF and other health outcomes in individuals with CAD. Methods This trial included 105 participants with CAD (age 62.1±6.6 years, 21% women) randomly assigned to HIIT+RT (n=37), HIIT (n=35) or usual care (n=33). The primary outcome was the change in global CBF from baseline to 12-week follow-up. Secondary outcomes included: region-specific CBF (hippocampus, precuneus, and anterior/posterior cingulate cortex), cognitive function (general cognition, episodic memory, processing speed, working memory and executive function/attentional control), peak oxygen uptake (VO 2 peak), muscular fitness (30s sit-to-stand) and body composition [weight, body mass index (BMI), and fat and muscle mass). Data were analyzed using available-case intention-to-treat constrained (baseline-adjusted) linear mixed models. Predefined subgroup analyses were conducted for age, sex, education, and baseline level of the outcome studied. Results No significant between-group differences were observed in CBF changes in the whole sample. However, participants with lower CBF at baseline showed greater CBF increases in the HIIT group compared to both usual care (+7.1 ml/100g/min, P=0.02) and HIIT+RT (+5.53 ml/100g/min, P=0.04). No effects were observed on regional CBF or cognition. Both exercise groups improved VO 2 peak compared to usual care (HIIT+RT: +2.6; HIIT: +2.5 mL/kg/min, both P<0.001). Only HIIT+RT increased muscular fitness (vs usual care: +3.3; vs HIIT: +3.1 repetitions, both P<0.001), and only HIIT decreased BMI (vs usual care: -0.47; vs HIIT+RT: -0.44 kg/m 2 , both P≤0.03). No life-threatening events or deaths occurred during 1995 training sessions in the exercise groups, nor in the usual care group. Conclusion Twelve weeks of HIIT+RT or HIIT did not increase CBF in the whole sample with CAD, but HIIT effectively increased CBF in those who had poorer CBF at baseline. While no cognitive benefits were observed, we found exercise-specific improvements in other clinically relevant outcomes, such as VO₂peak, muscular fitness, and BMI. Clinical Perspective What’s new? This study investigated the effectiveness of two high intensity interval training (HIIT)-based programs on cerebral blood flow (CBF), cognition and other clinically relevant outcomes in individuals with coronary artery disease (CAD). This is particularly important given the accelerated cognitive decline, dementia risk, and inherent poorer cardiovascular health in individuals with CAD. This study introduces a novel exercise model by adapting the traditional 4×4 HIIT into a 3×4 format plus 2 rounds of 8 resistance exercises. The program is time-efficient (3 sessions/week of 45 minutes) and aligns with the World Health Organization recommendations, the American and European clinical guidelines for CAD management, and American College of Sports Medicine recommendations on resistance training prescription. What are the clinical implications? HIIT alone was effective in increasing CBF only in individuals with low levels of CBF at baseline, and in reducing BMI in the whole sample. Both HIIT+RT and HIIT equally improved cardiorespiratory fitness, whereas the HIIT+RT additionally improved muscular fitness. Both HIIT+RT and HIIT were safe in this population with CAD, with no major adverse events or death occurring during roughly 2000 sessions.