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

•NAFLD is associated with inflammation and subclinical atherosclerosis independent of obesity and metabolic syndrome.•The association between NAFLD, inflammation and subclinical atherosclerosis differs according to gender and race.•With increasing burden of NAFLD, obesity and metabolic syndrome, there is a stepwise increase in the prevalence of inflammation and subclinical atherosclerosis.

IntroductionWe characterized the association of 3 metabolic conditions - obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) - with increased inflammation and subclinical atherosclerosis.MethodsWe 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 ≥ 30 kg/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) ≥2 mg/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.ResultsMean 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 ≥2 mg/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 ≥2 mg/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 ≥2 mg/L and CAC >0.ConclusionNAFLD 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.