This study was designed to evaluate the relationship between plasma leptin and prognosis in patients with angiographically confirmed coronary atherosclerosis. Experimental studies suggest that leptin, an adipose tissue-derived hormone, exerts important cardiovascular effects. Study subjects were recruited prospectively from a cohort of patients undergoing clinically indicated coronary angiography (n=382). The median duration of follow-up was four years. Follow-up information was available for 361 patients. The combined end point of cardiac death, myocardial infarction(MI), cerebrovascular accident, or re-vascularization occurred in 44 subjects. In the simple Cox model, leptin had a significant(p< 0.001) non-linear/cubic univariate relationship with the combined end point. Other variables associated with prognosis in the univariate analysis were body mass index (BMI), prior MI, insulin resistance, Creactive protein(CRP), fibrinogen, and number of coronary vessels with >50%stenosis. A positive relationship between leptin and prognosis was also seen when leptin levels were split by quintiles, with a hazard ratio of 6.46 for the highest quintile. The only two variables significantly associated with the combined end point in the multivariate Cox model were leptin(p= 0.004) and number of coronary vessels with >50%stenosis(p< 0.001). A similar relationship between leptin and prognosis was observedwhen leptinwas adjusted forBMI. In patientswith angiographically confirmed coronary atherosclerosis, leptin is a novel predictor of future cardiovascular events independent of other risk factors, including lipid status and CRP. This study was designed to evaluate the relationship between plasma leptin and prognosis in patients with angiographically confirmed coronary atherosclerosis. Experimental studies suggest that leptin, an adipose tissue-derived hormone, exerts important cardiovascular effects. clinically indicated coronary angiography (n = 382). The median duration of follow-up was four years. Follow-up information was available for 361 patients. The combined end point of cardiac death, myocardial infarction (MI), cerebrovascular accident, or re -vascularization occurred in 44 subjects. In the simple Cox model, leptin had a significant (p <0.001) non-linear / cubic univariate relationship with the combined end point. Other variables associated with prognosis in the univariate analysis were body mass index (BMI ) prior MI, insulin resistance, Creactive protein (CRP), fibrinogen, and number of coronary vessels with> 50% stenosis. A po sitive relationship between leptin and prognosis was also seen when leptin levels were split by quintiles, with a hazard ratio of 6.46 for the highest quintile. The only two variables significantly associated with the combined end point in the multivariate Cox model were leptin (p = 0.004 ) and number of coronary vessels with> 50% stenosis (p <0.001). A similar relationship between leptin and prognosis was observed with leptin was adjusted for BMI. In patients with angiographically confirmed coronary atherosclerosis, leptin is a novel predictor of future cardiovascular events independent of other risk Factors, including lipid status and CRP.