Non-alcoholic fatty liver modifies associations of body mass index and waist circumference with cardiometabolic risk: The CARDIA study

Background Non-alcoholic fatty liver disease (NAFLD) is recognized as a prevalent determinant of cardiometabolic diseases. The association between NAFLD and obesity warrants further research on how NAFLD modifies associations between body mass index (BMI) and Waist circumference (WC) with cardiometabolic risk (CMR). Objective This study assessed whether NAFLD modifies associations between BMI and WC with 5-year changes in CMR in 2366 CARDIA study participants. Methods Non-contrast CT was used to quantify liver attenuation, with <= 51 Hounsfield Units (HU) used to define NAFLD in the absence of secondary causes of excess liver fat. The dependent variable was the average Z score of fasting glucose, insulin, triglycerides [log], (-) high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure(SBP). Multivariable linear regression was used to estimate the associations between BMI and WC with CMR. Effect modification by NAFLD was assessed by an interaction term between NAFLD and BMI or WC. Results The final sample had 539 (23%) NAFLD cases. NAFLD modified the association of BMI and WC with CMR (interaction p < 0.0001 for both). BMI and WC were associated with CMR in participants without NAFLD (p < 0.001), but not among those with NAFLD. Participants with NAFLD and normal BMI and WC had CMR estimates that were higher than those without NAFLD in the obese categories. Among those without NAFLD the 5 years CMR change estimate was 0.09 (95% CI: 0.062, 0.125) for BMI >= 30 kg/m(2) compared to -0.06 (-0.092, -0.018) for BMI < 25 kg/m(2), and among those with NAFLD, these estimates were 0.15 (0.108, 0.193) and 0.16 (-0.035, 0.363). Conclusions NAFLD modifies associations of BMI and WC with CMR. Compared with BMI and WC, NAFLD was more strongly associated with CMR. In the presence of NAFLD, BMI and WC were not associated with CMR. These findings have implications for clinical screening guidelines.