Evaluation of Ferroptosis-Related Biomarkers in Individuals With Coronary Artery Disease: The Impact of Cardiac Rehabilitation
Coronary artery disease (CAD) remains a major global health concern and is the leading cause of cardiovascular mortality worldwide. Cardiac rehabilitation (CR) is a comprehensive, evidence-based intervention that integrates exercise training with optimal medical management and has been shown to improve clinical outcomes in patients with CAD. The primary objective of this study is to investigate the effects of cardiac rehabilitation on ferroptosis, an iron-dependent form of regulated cell death, in patients with coronary artery disease. A total of 90 participants will be enrolled in the study after providing written informed consent. The study population will consist of three groups: 30 patients with CAD who participate in a cardiac rehabilitation program, 30 patients with CAD who voluntarily decline participation in cardiac rehabilitation, and 30 age- and sex-matched healthy volunteers without any known chronic disease. Peripheral venous blood samples will be collected from patients undergoing cardiac rehabilitation both before the initiation of the rehabilitation program and upon its completion. A single blood sample will be obtained from patients who decline participation in cardiac rehabilitation and from healthy control participants. To evaluate ferroptosis-related molecular alterations, the expression levels of the ferroptosis-associated genes GPX4, SLC7A11, ACSL4, FSP1, NRF2, TFRC, and NCOA4 will be analyzed. In addition, serum concentrations of ferroptosis-related biomarkers, including free iron, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and GPX4 protein, will be measured. The molecular and biochemical parameters will be compared among the three study groups, and changes in ferroptosis-related biomarkers before and after the cardiac rehabilitation program will be evaluated in patients undergoing cardiac rehabilitation.
⁃ Patients With Coronary Artery Disease (CAD):
• Age between 18 and 75 years.
• Diagnosis of coronary artery disease within the previous 3 months.
• Eligible to participate in a cardiac rehabilitation program or voluntarily decline participation in the cardiac rehabilitation program.
• Peak exercise capacity of ≥5 metabolic equivalents (METs).
• Able to undergo cardiopulmonary exercise testing (CPET).
• Able to understand the study procedures and provide written informed consent.
⁃ Healthy Controls:
• Age between 18 and 75 years.
• No history of coronary artery disease or other cardiovascular diseases.
• No history of chronic systemic diseases, including diabetes mellitus, hypertension, chronic kidney disease, chronic liver disease, inflammatory or autoimmune diseases, or malignancy.
• Not receiving regular medication.
• Able to provide written informed consent.