Effect of circulating irisin level on clinical outcome in obesity-associated atherosclerosis

Aims: To investigate the association between circulating irisin levels, metabolic profiles, and clinical outcomes in obesity-associated atherosclerosis.Methods: This retrospective study included 220 patients admitted to the Department of Cardiology between January 2022 and January 2025, stratified into four groups based on body mass index and atherosclerosis status.Fasting blood samples were analyzed for serum irisin, glucose, HbA1c, insulin (HOMA-IR), and lipid profiles, including small dense LDL.Echocardiography was performed to assess cardiac structure and function, while carotid ultrasonography was used to quantify intima-media thickness and plaque burden; severe atherosclerosis was defined as a plaque area > 30 mm 2 .Patients were prospectively followed up for major adverse cardiovascular events (MACE), which were adjudicated by an independent blinded committee.Results: Serum irisin levels were highest in normal-weight controls and progressively decreased across the overweight and atherosclerotic groups (P < 0.05).Concomitantly, fasting glucose, HbA1c, and HOMA-IR increased in a stepwise manner, with the most significant derangements observed in overweight patients with atherosclerosis.Dyslipidemia was characterized by elevated total cholesterol, LDL-C, and triglycerides, along with reduced HDL-C, particularly in groups with vascular disease.Cardiac structural remodeling was evident, with progressive increases in left ventricular (LV) mass and left atrial size, reductions in ejection fraction and global longitudinal strain, and worsening diastolic indices (all P < 0.001).The incidence of MACE increased from 3.6% in Group A to 45.5% in Group D (P < 0.001).Cox regression analysis identified age, BMI, diabetes, and LDL-C as independent risk factors, whereas each 1 ng/mL increase in irisin was associated with a 26% reduction in MACE risk.Logistic regression further revealed that low irisin was the strongest predictor of severe atherosclerosis (OR 0.128, 95% CI 0.058-0.283,P < 0.001).Conclusion: Low circulating irisin is an independent predictor of severe atherosclerosis and adverse cardiovascular outcome in patients with obesity-associated vascular disease.