Cardiovascular Disease as a Multisystem Disorder: Integrating Inflammation, Metabolism, and Organ Crosstalk

Historically, cardiovascular disease (CVD) has often been regarded as a primarily cardiac condition. Nevertheless, recent research data suggests that this disease should be considered a multifactorial and multisystem one. In this narrative review, available evidence related to inflammatory processes, metabolic disorders, neurohormonal signaling, endothelial dysfunction, and communication between organs will be summarized to illustrate the pathophysiology of CVD. A structured search of available literature was performed using the PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases. Only articles from 2010 to 2025 were considered to ensure that the latest developments were accounted for. The selected literature includes clinical trials, observational studies, and reviews. The analysis suggests, that all cardiovascular disorders, including heart failure, coronary artery disease, atrial fibrillation, and hypertension, have common systemic mechanisms, namely, chronic inflammation, immunological dysregulation, insulin resistance, and neurohormonal stimulation. Moreover, complex relationships exist between the heart, kidneys, liver, gastrointestinal tract, adipose tissue, and the brain, and they can lead to the aggravation of disease course. Despite promising results obtained within an integrated approach, several difficulties need to be acknowledged, among which, clinical translational issues and lack of systems-level clinical trials are of primary importance.