Atherosclerosis 203 (2009) 581–586 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis The severity of nonalcoholic fatty liver disease is associated with increased cardiovascular risk in a large cohort of non-obese Asian subjects Ki Chul Sung a,∗,1 , Marno C. Ryan b , Andrew M. Wilson b,1 a Division of Cardiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Pyung Dong, Jongro-Ku, Seoul 110-746, South Korea b University of Melbourne, Department of Medicine, St Vincent’s Hospital, Melbourne, Australia article info Article history: Received 18 May 2008 Received in revised form 14 July 2008 Accepted 21 July 2008 Available online 31 July 2008 Keywords: Cardiovascular risk factor CRP Metabolic syndrome Framingham risk score Hepatic steatosis abstract Backgrounds: Nonalcoholic fatty liver disease (NAFLD) has been linked to cardiovascular disease (CVD) but it is largely unknown if such a relationship between NAFLD and CVD risk relates to severity of liver disease or if it is independent. We aimed to study the severity of NAFLD in a well characterized non-obese population and to compare this to prevalence of CVD risk factors and Framingham risk score. Methods: This study included 30,172 subjects. Based on the presence or absence of steatosis on ultra- sound and serum alanine aminotransferase (ALT), subjects were divided into controls, an increased serum ALT group without steatosis and a group with presumed nonalcoholic fatty liver disease (NAFLD), which included a steatosis alone group and a group with presumed nonalcoholic steatohepatitis (NASH) with steatosis and an elevated ALT. Results: The odds ratio for 10-year risk by total Framingham risk scores ≥10% was 5.3 times higher in NASH groups. The prevalence of diabetes, hypertension, elevated CRP and metabolic syndrome were all increased up to 15-fold over controls, independent of age, BMI, smoking and exercise habits. Overall CVD risk was significantly greater in NASH than in either steatosis or raised ALT alone. Conclusion: Young, non-obese subjects with NAFLD are at significantly increased CVD risk, especially those with NASH. As well as specific therapy for liver disease, a diagnosis of NAFLD should lead to targeted risk assessment and risk factor modification. © 2008 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from simple steatosis to nonalcoholic steatohep- atitis (NASH), which can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma [1,2]. NAFLD is the most common cause of abnormal liver function tests in clinical practice. Increas- ing evidence has linked NAFLD to insulin resistance, possibly via common pathogenic factors. Recent data has linked abnormal liver function tests, particularly alanine aminotransferase (ALT) to the Abbreviations: NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; BMI, body mass index; WC, waist circumference; NASH, nonal- coholic steatohepatitis; HCV Ab, hepatitis C antibody; HBsAg, hepatitis B surface antigen; HBsAb, hepatitis B core antibody; ALT, alanine aminotransferase; S.D., stan- dard deviation; ANOVA, analysis of variance; OR, odds ratio. ∗ Corresponding author. Tel.: +82 2 2001 2401; fax: +82 2 2001 2400. E-mail address: kcmd.sung@samsung.com (K.C. Sung). 1 These authors contributed equally to this article. presence of atherosclerosis and to CVD risk [3]. This has also been extrapolated to link NAFLD to CVD [4,5]. However, these studies have been mostly relatively small and have not focused on excluding patients with confounding factors, particularly viral hepatitis and obesity. The current study was initiated to address some of these issues by taking advantage of a database obtained from a large group of apparently healthy, non-obese, relatively young subjects, with extensive clinical characterization including hepatic ultrasound, anthrompometry and screening for viral hepatitis and alcohol intake. The hypothesis of this study was that a clinical diagnosis of NASH would be associated with increased CVD risk. The primary goal of our analysis was to evaluate the relationship between the diagno- sis and severity of NAFLD and the cardiovascular risk factors and predicted risk using the Framingham risk score corrected for other potential confounding factors. We also aimed to assess whether the clinical diagnosis of NASH was adverse when compared to steatosis or raised ALT alone. 0021-9150/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2008.07.024