ObjectiveWe investigated if the differences in liver fat content would predict the development of non-fatal and fatal atherosclerotic endpoints (coronary heart disease and stroke).Design, setting and participantsOur study group is a population-based, randomly recruited cohort (Oulu Project Elucidating Risk of Atherosclerosis, OPERA), initiated in 1991. The cohort consisted of 988 middle-aged Finnish participants.InterventionTotal mortality and hospital events were followed up to 2009 based on the registry of the National Institute for Health and Welfare and the National death registry.Main outcome measureThe severity of hepatic steatosis was measured by ultrasound and divided into three groups (0–2). Cox regression analysis was used in the statistical analysis.ResultsIn the follow-up of years 1991–2009, 13.5% of the participants with non-fatty liver, 24.2% of participants having moderate liver fat content and 29.2% of the participants having severe fatty liver experienced a cardiovascular event during the follow-up time (p<0.001). Severe liver fat content predicted the risk for future risk of cardiovascular event even when adjusted for age, gender and study group (HR 1.92, CI 1.32 to 2.80, p<0.01). When further adjustments for smoking, alcohol consumption, low-density lipoprotein-cholesterol, body mass index and systolic blood pressure were conducted, the risk still remained statistically significant (HR 1.74, CI 1.16 to 2.63, p<0.01). Statistical significance disappeared with further adjustment for QUICKI.ConclusionsLiver fat content increases the risk of future cardiovascular disease event in long-term follow-up but it is seems to be dependent on insulin sensitivity.