The association of nonalcoholic fatty liver disease, obesity, and metabolic syndrome, with systemic inflammation and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: We characterized the association of 3 metabolic conditions - obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) - with increased inflammation and subclinical atherosclerosis. Methods: We conducted cross-sectional analysis of 3976 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with adequate CT imaging to diagnose NAFLD. Obesity was defined as BMI≥30kg/m², metabolic syndrome by AHA/NHLBI criteria, and NAFLD using non-contrast cardiac CT and a liver/spleen attenuation ratio (L/S)<1. Increased inflammation was defined as high sensitivity C-reactive protein (hsCRP) ≥2mg/L and subclinical atherosclerosis as coronary artery calcium (CAC)>0. We studied the association of a stepwise increase in number of these metabolic conditions (0-3) with increased inflammation and CAC, stratifying results by gender and ethnicity. Results: Mean age of participants was 63 (±10) years, 45% were male, 37% white, 10% Chinese, 30% African American, and 23% were Hispanic. Adjusting for obesity, metabolic syndrome and traditional risk factors, NAFLD was associated with a prevalence odds ratio for hsCRP ≥2mg/L and CAC >0 of 1.47 (1.20-1.79) and 1.37 (1.11-1.68) respectively. There was a positive interaction between female gender and NAFLD in the association with hsCRP ≥2mg/L (p=0.006), with no interaction by race. With increasing number of metabolic conditions, there was a graded increase in prevalence odds ratios of hsCRP ≥2mg/L and CAC >0. Conclusion: NAFLD is associated with increased inflammation and CAC independent of traditional risk factors, obesity and metabolic syndrome. There is a graded association between obesity, metabolic syndrome, and NAFLD with inflammation and CAC.