BACKGROUND: In patients with carotid stenosis, we prospectively investigated the association of novel adipokines, apelin and visfatin, with gray-scale median (GSM) score, a valid index of carotid plaque vulnerability. We also assessed the impact of atorvastatin therapy on the above biochemical and imaging markers.MATERIALS AND METHODS: Seventy-four overweight [body-mass index (BMI) > 25 kg/m(2) , fat-mass > 30%], statin-free patients, with carotid stenosis, but without indications for intervention were enrolled. Thirty-eight age-, sex- and BMI-matched healthy subjects served as healthy controls (HC). All patients received gradual titrated (10-80 mg) atorvastatin therapy to target LDL-C < 100 mg/dL. GSM score, blood pressure (BP), fat-mass, lipid profile, and serum high-sensitivity C-reactive protein (hsCRP), apelin and visfatin levels were obtained at baseline and after 24 months.RESULTS: At baseline, patients with carotid atherosclerosis had worse lipid profile, lower apelin and higher systolic BP, hsCRP, visfatin levels compared with HC (P < 0·05). Notably, decreased apelin (P < 0·001) and GSM score (P = 0·010), while increased visfatin (P = 0·019) and hsCRP (P = 0·039) levels were found in symptomatic rather than asymptomatic patients. At baseline, GSM score correlated with fat-mass, BMI, LDL-C, visfatin and apelin (P < 0·05). Apelin, visfatin and fat-mass remained independent determinants of baseline GSM score (R(2) = 0·391, P = 0·007). In parallel, we found that apelin increment and LDL-C reduction were independently associated with the atorvastatin-induced GSM increase (R(2) = 0·411, P = 0·011).CONCLUSION: Increased fat-mass, low apelin and high visfatin serum levels seem to correlate with carotid plaque vulnerability in patients with carotid stenosis. The atorvastatin-induced modification of apelin and LDL-C may beneficially affect carotid plaque stability.