Gastroenterology
Abstract
BACKGROUND & AIMS
Nonalcoholic fatty liver disease (NAFLD) has been associated with subclinical atherosclerosis in cross-sectional studies. We investigated the longitudinal association of NAFLD with the development of subclinical carotid atherosclerosis.
METHODS
We performed a retrospective cohort study of 8,020 adult men (average age, 49.2 years) without carotid atherosclerosis at baseline who underwent repeated health check-up examinations from January 1, 2005 through December 31, 2013. NAFLD status was diagnosed by ultrasonography and classified into 4 groups based on baseline and follow-up findings: none, developed, regressed, or persistent NAFLD. Subclinical carotid atherosclerosis was measured by ultrasound.
RESULTS
The age-adjusted hazard ratio for subclinical carotid atherosclerosis development comparing participants with persistent NAFLD to those without NAFLD was 1.23 (95% confidence interval [CI], 1.13-1.35; P<.001). The association persisted after adjustment for smoking, alcohol, body mass index, and weight change (hazard ratio, 1.13; 95% CI 1.03-1.25; P=.014), but disappeared after adjustment for metabolic variables. The hazard ratio, comparing subjects with regression of NAFLD vs those with persistent NAFLD, was 0.82 (95% CI, 0.69-0.96; P=.013). The risk of subclinical carotid atherosclerosis development was also higher among participants with high NAFLD fibrosis score, FIB-4 scores, or levels of gamma-glutamyl transferase at baseline.
CONCLUSION
In a large cohort study, persistent NAFLD was associated with an increased risk of subclinical carotid atherosclerosis development. This association was explained by metabolic factors that could be potential mediators of the effect of NAFLD. Markers of liver fibrosis were also associated with subclinical carotid atherosclerosis development. Prospective studies are needed to determine whether treatment of NAFLD can reduce this risk.