Exercise and brain health in patients with coronary artery disease: study protocol for the HEART-BRAIN randomized controlled trial
Authors: Toval Angel , Solis-Urra Patricio , Bakker Esmée A , Sánchez-Aranda Lucía , Fernández-Ortega Javier , Prieto Carlos , Alonso-Cuenca Rosa María , González-García Alberto , Martín-Fuentes Isabel , Fernandez-Gamez Beatriz , Olvera-Rojas Marcos , Pulido Andrea Coca- , Bellón Darío , Sclafani Alessandro , Sanchez-Martinez Javier , Rivera-López Ricardo , Herrera-Gómez Norberto , Peñafiel-Burkhardt Rafael , López-Espinosa Víctor , Pérez Sara Corpas- , García-Ortega María Belén , Vega-Cordoba Alejandro , Barranco-Moreno Emilio J. , Morales-Navarro Francisco J. , Nieves Raúl , Caro-Rus Alfredo , Amaro-Gahete Francisco J. , Mora-Gonzalez Jose , Vidal-Almela Sol , Carlén Anna , Migueles Jairo H. , Erickson Kirk I. , Moreno-Escobar Eduardo , García-Orta Rocío , Esteban-Cornejo Irene , Ortega Francisco B. 
Published: May 2024

Introduction

Patients with coronary artery disease (CAD), also called coronary heart disease, have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. There is a need to identify effective and sustainable strategies to improve brain health in individuals with CAD, in which physical exercise could play a major role. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of exercise, including different types, on brain health outcomes in patients with CAD, and the underlying mechanisms.

Methods

This three-arm, single-blinded RCT will include 90 adults with CAD, aged 50-75 years. The participants will be randomized into: 1) control group - usual care (n=30), including periodic medical visits and medication management, 2) aerobic high-intensity interval training (HIIT) (n=30), or 3) aerobic HIIT combined with resistance exercise training (n=30). The intervention will last 12 weeks, offering 3 sessions (45min each) per week to the exercise groups, and the study outcomes will be assessed at baseline and after the intervention. The primary outcome of the study is to determine changes in global and regional cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes will be evaluated, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior).

Conclusions

The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results might have important clinical implications by increasing the evidence on the effectiveness of exercise-based preventive strategies that could delay cognitive decline in this high-risk CAD population. Our findings will be relevant for patients with CAD, researchers and healthcare providers involved in CAD-related clinical care.