Persistent Nonalcoholic Fatty Liver Disease Increases Risk for Carotid Atherosclerosis.
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.



We performed a retrospective cohort study of 8020 adult men (average age, 49.2 y) 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.



The age-adjusted hazard ratio for subclinical carotid atherosclerosis development comparing participants with persistent NAFLD with 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 also was higher among participants with a high NAFLD fibrosis score, fibrosis-4 scores, or levels of γ-glutamyl transferase at baseline.



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 also were associated with subclinical carotid atherosclerosis development. Prospective studies are needed to determine whether treatment of NAFLD can reduce this risk.
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Dong Hyun
DH
Sinn
Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Soo Jin
SJ
Cho
Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Seonhye
S
Gu
Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Donghyeong
D
Seong
Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Danbee
D
Kang
Department of Otorhinolaryngology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hyunkyoung
H
Kim
Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Medical Informatics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Byoung-Kee
BK
Yi
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Seung Woon
SW
Paik
Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Eliseo
E
Guallar
Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Juhee
J
Cho
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: gy.gwak@samsung.com.
Geum-Youn
GY
Gwak
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002340:Carotid Artery Diseases / Q000209:etiology*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors
D015415:Biomarkers
Chronic Liver Disease; GGT; Intima-Media Thickness; Liver Steatosis