Nonalcoholic fatty liver disease and serum lipoproteins: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE

While nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome, it is not known if NAFLD plays an independent role in the atherogenic dyslipidemia phenotype.

METHODS AND RESULTS

The Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based prospective cohort study of adults free of clinical cardiovascular disease at enrollment. We tested for a relationship between NAFLD, defined as a liver/spleen (L/S) attenuation ratio of <1 on a non-contrast cardiac CT scan, and multiple measures of fasting serum lipoprotein size, cholesterol and particle concentrations. NAFLD was present in 569 (17%) of 3362 participants. After adjustment for multiple metabolic risk factors, adiposity and measures of insulin resistance (HOMA-IR), NAFLD was independently associated with higher fasting serum triglycerides and lower serum HDL-C. Despite a lack of association with LDL-C, NAFLD was associated with higher LDL particle concentration and lower LDL particle size. Modeling the L/S ratio as a continuous variable, a severity dependent association was observed between atherogenic lipoprotein abnormalities and NAFLD.

CONCLUSION

In a large, multi-ethnic, gender balanced cohort, CT-diagnosed NAFLD was associated with the atherogenic dyslipidemia phenotype in a dose dependent fashion. These relationships persisted after adjustment for several metabolic risk factors and HOMA-IR, suggesting a possible independent pathophysiologic role between NAFLD and dyslipidemia.