Nicorandil in Atherosclerosis Risk in Patients With Rheumatoid Arthritis

RA is associated with significant risk of cardiovascular (CV) disease. Atherosclerosis isnotably accelerated in RA patients, driven by a combination of chronic systemicinflammation, endothelial dysfunction, and traditional CV risk factors includinghypertension, dyslipidemia, and insulin resistance.the conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs), effectivelycontrol joint inflammation and disease activity, but doesnot affect the risk ofatherosclerosis.Nicorandil is a hybrid drug that combines nitrate‐like vasodilatory properties with theactivation of ATP‐sensitive potassium (K_ATP) channels. It has been extensively studiedin cardiovascular medicine for its vasodilatory, anti‐ischemic, andendothelial‐stabilizing effects. Recent preclinical and clinical evidence suggests thatnicorandil also possesses anti‐inflammatory properties, making it a promising candidatefor vascular protection in inflammatory conditions such as RA.Carotid intima‐media thickness (CIMT) is a validated, non‐invasive imaging biomarker forsubclinical atherosclerosis. It reflects structural arterial changes and is predictive offuture cardiovascular events. In RA, CIMT is frequently elevated even in the absence ofovert CV disease, correlating with disease duration, activity, and systemic inflammation.Changes in CIMT serve as a surrogate endpoint for evaluating the progression orregression of atherosclerosis in interventional trials.Lipoprotein(a) [Lp(a)] has emerged as a promising biomarker for predictingatherosclerotic risk. Elevated Lp(a) levels contribute to accelerated atherogenesis bypromoting endothelial dysfunction, oxidative stress, and recruitment of pro‐inflammatoryimmune cells within the vascular wall. Patients with RA often exhibit elevated Lp(a)levels compared to healthy individuals, which has been associated with a higher risk ofatherosclerosis. Among autoimmune disorders, RA exhibits the strongest association withelevated Lp(a) in the context of atherosclerosis.both will be used to assess risk reduction.