Nonalcoholic Fatty Liver Disease in Non-Obese Subjects With Abdominal Obesity is Associated With A Higher Risk of Advanced Cardiovascular Disease: A 14 Year Prospective Cohort Study

Abstract Background Obese nonalcoholic fatty liver disease (NAFLD) is closely associated with an increased risk of cardiovascular disease (CVD). However, the association between non-obese NAFLD and the incidence of CVD is still unclear and little is known about deleterious factors related to their inter-relationship. Here, we investigated the effects of abdominal obesity (AO) and/or NAFLD on CVD risk.Methods We enrolled 8,422 patients who did not have CVD or consume excessive amounts of alcohol at baseline from the Korean Genome and Epidemiology Study (KoGES). NAFLD was defined using the Fatty Liver Index (FLI). Obesity was defined as a body mass index (BMI) ≥25 kg/m2, and AO was defined as a waist circumference (WC) ≥90 cm in men and ≥85 cm in women. Subjects were sub-divided into eight groups depending on whether they were obese, AO, and/or NAFLD.Results In the full cohort, during a median 11.6 years of follow-up period, the incidence rate (IR) of CVD was 8.07%. The IR of CVD in participants with NAFLD was 1.9-fold higher than in those without NAFLD. The IR per 1,000 person-years for CVD was highest in the non-obese abdominal obesity subjects with NAFLD (15.76 [95% confidence interval (CI), 11.76–20.69]). Compared with participants who did not have obesity, AO, or NAFLD, the adjusted hazard ratio for CVD was 1.67 (95% CI: 1.16–2.41) in non-obese NAFLD patients with AO, 1.60 (95% CI: 1.21–2.11) in NAFLD patients with obesity and AO, and 0.54 (95% CI: 0.32–0.91) in obese subjects without either NAFLD or AO.Conclusions The co-occurrence of AO with NAFLD appears to be strongly associated with an increased risk of CVD regardless of obesity; but its risk is higher in non-obese subjects. By contrast, obese individuals without AO or NAFLD appear to be at lower risk. Therefore, early prevention and control of AO and NAFLD is an important means of reducing the risk of CVD, even in subjects with a normal BMI.