Iron Balance and Cardiovascular Health: The Double-Edged Role of Deficiency and Overload.

Cardiovascular disease is the leading cause of death worldwide, accounting for about a third of all deaths. Traditional risk factors like hypertension, diabetes, dyslipidemia, and obesity are well known, but iron also plays a crucial role in heart health. Iron is essential for oxygen transport, mitochondrial function, and heart muscle activity, and both deficiency and overload can harm cardiovascular outcomes. This review examines studies on iron metabolism, regulation via the hepcidin-ferroportin pathway, myocardial energy, oxidative stress, and clinical trials of iron supplementation or reduction in heart failure, chronic kidney disease, the elderly, women, and athletes. Iron deficiency affects over 60% of heart failure patients, leading to reduced energy, lower exercise capacity, and higher morbidity. Intravenous iron improves functional capacity, quality of life, and reduces hospitalizations, especially in patients with low transferrin saturation. Iron overload, on the other hand, increases oxidative stress, arrhythmias, and cardiomyopathy. Evidence shows a U-shaped relationship between iron and cardiovascular outcomes, emphasizing the importance of markers like transferrin saturation, soluble transferrin receptor, and hepcidin. Iron imbalance contributes to cardiovascular disease. Targeted assessment and treatment, including supplementation for deficiency and chelation or phlebotomy for overload, may improve outcomes. The ultimate aim of this review is to enhance perioperative management and long-term results for this highly vulnerable population by synthesizing current insights and addressing knowledge gaps.