Abstract P136: Non-alcoholic Fatty Liver Disease Fibrosis Score Predicts The Development Of Carotid Atherosclerosis: The Strong Heart Family Study
Authors: Zhang Ying , Stoner Julie , Umans Jason G , Roman Mary J , Dvorak Justin , Ali Tauqeer , Lee Elisa T , Wang Wenyu , MacCluer Jean , BEST Lyle G , Howard Barbara V , Devereux Richard B , Cole Shelley 
Published: March 2020

Introduction:
About 30% of all U.S. adults and 70-80% of those with Type 2 diabetes mellitus (T2DM) have non-alcoholic fatty liver disease (NAFLD). Atherosclerotic cardiovascular disease (CVD) is more common among NAFLD patients, albeit with limited evidence from large prospective studies.

Hypothesis:
American Indians (AI) with NAFLD would be more likely to develop carotid atherosclerosis given their high prevalence of obesity and T2DM.

Methods:
The Strong Heart Family Study (SHFS) is a population-based family study of CVD and its risk factors in AI. Participants (n=2786; 59.6% female, mean age 40.8 ±17.3 y) were recruited from 12 tribes in 3 regions: Arizona, North/South Dakota, and Oklahoma. Carotid ultrasound-assessed plaque and plaque score were obtained at the baseline examination in 2001-03, and again in surviving participants (n=2406) from 2006 to 2009. NAFLD prevalence was estimated using hepatic steatosis index (HSI). NAFLD fibrosis score was used to separate NAFLD patients with or without advanced fibrosis. HSI is calculated using serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), BMI, diabetes status, and sex, while the NAFLD fibrosis score is derived from age, BMI, diabetes status, ALT, AST, platelet count, and serum albumin. Plaque progression was defined as any increase in plaque score (0 to 8 carotid segments with plaque) from baseline to the second examination. Frailty model was used in data analyses to account for the relatedness among family members.

Results:
Mean BMI of participants was 31.3 ± 7.5 kg/m
2
, 19% had T2DM, 32.6% were hypertensive, and 36.3% were current smokers. NAFLD prevalence (HSI > 36) was 78%, while 6% did not have NAFLD (HSI < 30) and 16% participants were in an intermediate category (HSI 30-36). Among participants with NAFLD (n=2096), three fibrosis classes were defined by NAFLD fibrosis scores: 1 no to moderate fibrosis (61%, fibrosis score < -1.455), 2 indeterminate (31%, -1.455 ≤ fibrosis score ≤ 0.676), and 3 cirrhosis or severe cirrhosis (8%, fibrosis score > 0.676). About 31% of participants had carotid atherosclerosis (plaque score ≥ 1) at baseline. About 14% of the 2252 participants who had two carotid ultrasound evaluations had plaque progression and 19% of those without carotid atherosclerosis at baseline (n=1571) had incident plaque at the second visit. Compared to those with no to moderate fibrosis, those who had cirrhosis or severe cirrhosis had higher risks of plaque progression with a hazard ratio (HR, 95% CI) of 1.8 (1.1-2.9, P=0.026), and of incident plaque with a HR (95% CI) of 2.6 (1.5-4.6, P=0.0009), adjusted for sex, smoking, hypertension, albuminuria, LDL-C, and HDL-C. Similar results were found among participants with intermediate fibrosis scores.

Conclusions:
The prevalence of HSI-defined NAFLD is high in AI. NAFLD fibrosis score predicts both incident and progressive carotid atherosclerosis.