Lipid metabolism at the intersection of rheumatoid arthritis and atherosclerosis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic, symmetric polyarticular synovitis, with a global prevalence of approximately 0.5%-1%. Its pathogenesis involves a complex interplay of genetic and environmental factors, as well as abnormal immune activation. RA patients face a significantly increased risk of cardiovascular disease, with atherosclerosis (AS) and its complications being the leading cause of mortality. Chronic systemic inflammation has long been considered the core pathological bridge linking RA and AS, whereby inflammatory cytokines drive cardiovascular events by impairing endothelial function and promoting arterial plaque formation and destabilization. However, recent research has yielded critical breakthroughs, revealing that dyslipidemia plays a vital role in RA pathogenesis and its comorbidity with AS. It goes beyond a traditional secondary effect, serving as an active participant intertwined with the immune-inflammatory network. This review specifically focuses on lipid-immune crosstalk in RA-AS comorbidity. To this end, we aim to systematically outline the epidemiological evidence for this association, summarize current clinical management strategies and their impact on cardiovascular risk, analyze shared risk factors, and explore in depth the central role of lipid metabolism in their shared pathophysiological mechanisms. We focus on cutting-edge topics such as the "lipid paradox" phenomenon, lipoprotein dysfunction, lipid metabolic dysregulation in macrophages and the imbalance of bioactive lipid mediators to provide a comprehensive perspective and theoretical basis for understanding their common pathophysiological pathways and developing novel therapeutic strategies targeting the metabolism-immune axis.