Cardiovascular risk in systemic lupus erythematosus: beyond Framingham to emerging risk prediction tools and therapeutic approaches

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation and persistent inflammation. Although the prognosis of patients with SLE has improved substantially over the past few decades, these patients remain at markedly increased risk of cardiovascular disease (CVD) and major adverse cardiovascular events (MACE) compared with the general population. This excess risk is not fully explained by traditional cardiovascular risk factors captured by the Framingham Risk Score (FRS). Emerging evidence suggests that SLE disease activity, cumulative organ damage, medication exposure, and the presence of antiphospholipid antibodies (aPL) contribute significantly. In this review, we examine studies that have investigated these risk factors, including proposals to adopt alternative risk scores and mechanisms underlying the accelerated atherosclerosis in SLE. We also summarize evidence on the role of hydroxychloroquine, statins, acetylsalicylic acid (ASA) and emerging therapies such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) agonists in mitigating cardiovascular risk. Current challenges include the lack of reliable strategies to identify high-risk patients and limited understanding of the pathophysiologic mechanisms driving accelerated atherosclerosis. Addressing these gaps is critical to developing more effective therapeutic strategies, alongside aggressive management of both traditional and non-traditional risk factors, to reduce the burden of CVD in SLE.