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Low plasma high-density lipoprotein (HDL)-cholesterol is a major risk factor for cardiovascular diseases. We investigated whether HDL-cholesterol levels had a prognostic value in patients with mild left ventricular dysfunction, irrespective of the presence of coronary disease.The study included 686 consecutive patients hospitalized between January 2002 and December 2006 because of left ventricular dysfunction. All patients completed a lipid profile and underwent coronary angiography. Patients were followed for a mean period of 23 months, during which major events were recorded.Seventy-three percent of patients were New York Heart Association (NYHA) class I–II, with the mean values of left ventricular ejection fraction and left ventricular end-diastolic diameter being, respectively, 36.3 ± 8.6% and 58.3 ± 7.9 mm. Half of the patients (52%) had HDL values less than 40 mg/dl, 28% presented with HDL less than 35 mg/dl. In multivariable analysis, patients with HDL-cholesterol concentration less than 40 mg/dl showed higher risk for cumulative mortality (HR 1.77, P < 0.05) and for cardiac death (HR 2.06, P < 0.05). This higher risk was also observed in patients with low HDL-cholesterol levels but without significant coronary stenosis. The inclusion of the C-reactive protein (CRP) inflammation marker into the model highly improved the power of death prediction.In patients with left ventricular dysfunction, regardless of the presence of coronary atherosclerosis, lower HDL-cholesterol was a strong and independent predictor of both cardiac and all-cause death.