Non-alcoholic steatohepatitis and progression of carotid atherosclerosis in patients with type 2 diabetes: a Korean cohort study

Abstract

Background: There is increasing concern regarding cardiovascular risk in individuals with non-alcoholic fatty liver disease. This study was conducted to evaluate whether hepatic steatosis with or without fibrosis is associated with the progression of carotid atherosclerosis in patients with type 2 diabetes. Methods: From a longitudinal cohort, we enrolled 1120 patients with type 2 diabetes who underwent repeated carotid artery ultrasonography every 1-2 years. Ultrasonographic findings at baseline and after 6-8 years were compared. Presence of hepatic steatosis was mainly assessed by abdominal ultrasonography; patients with hepatic steatosis were further evaluated for hepatic fibrosis according to fibrosis-4 index. We investigated the association between liver status and atherosclerosis progression. Results: Of 1120 patients, 636 (56.8%) were classified as having hepatic steatosis at baseline. After 6-8 years, 431 (38.5%) showed atherosclerosis progression. Hepatic steatosis was significantly associated with atherosclerosis progression (adjusted odds ratio[AOR]: 1.370, 95% CI 1.025-1.832; p < 0.05). Among patients with hepatic steatosis, only individuals with fibrosis showed significant association with atherosclerosis progression (AOR: 1.615, 95% CI 1.005-2.598; p < 0.05). The association between hepatic fibrosis and atherosclerosis progression was significant in all metabolic subgroups regardless of age, body mass index, presence of metabolic syndrome, or insulin sensitivity (all p < 0.05). Furthermore, subjects with hepatic steatosis & fibrosis and ≥ 4 components of metabolic syndrome criteria showed markedly increased risk of atherosclerosis progression (AOR: 2.430, 95% CI 1.087-5.458; p < 0.05). Conclusions: Hepatic steatosis with fibrosis is independently associated with the progression of carotid atherosclerosis in patients with type 2 diabetes.

Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study

“…Several lines of evidence have shown that NAFLD is associated with an increased risk of cardiovascular events in T2DM patients. Lee et al showed that NAFLD was independently associated with progression of carotid intima-media thickness, as a well-established surrogate marker of subclinical atherosclerosis, in T2DM patients [ 21 ]. In an observational study of 2103 T2DM patients, NAFLD was associated with an increased incidence of cardiovascular events after adjustment for multiple risk factors (HR 1.96, 95% CI 1.4–2.7) [ 22 ].…”

High NAFLD fibrosis score in non-alcoholic fatty liver disease as a predictor of carotid plaque development: a retrospective cohort study based on regular health check-up data in China

“…Epidemiological studies and meta-analysis have found a close association between NAFLD and subclinical atherosclerosis and CVD [ 9 , 12 , 23 , 24 ]. NAFLD is considered as hepatic manifestation of the MetS, and increasing evidence suggested that NAFLD may be both a cause and a consequence of MetS and its components, with insulin resistance (IR) as a common pathophysiological mechanism [ 25 , 26 ].…”

“…A cross-sectional study including 400 individuals in Italy found that individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis as compared with individuals at low probability of fibrosis [ 5 ]. A longitudinal cohort study on 1120 T2DM showed that hepatic steatosis with fibrosis is independently associated with the progression of carotid atherosclerosis [ 12 ].A retrospective cohort study on 3,185 adult men without carotid atherosclerosis at baseline showed that NAFLD patients with a high NFS and fibrosis-4 scores at baseline had higher risk of subclinical carotid atherosclerosis development [ 9 ], however, this finding is only generalisable to male population. A cross-sectional study with 251 subjects in Malaysian showed that NAFLD and advanced liver fibrosis assessed using FibroScan appeared to be not associated with increased CIMT [ 14 ]; however, given the small sample size, the result may be affected by insufficient statistical power.…”

“…According to a long-term, clinical study with 20.4-year follow-up, patients with simple hepatic steatosis were more likely to follow a relatively benign course and have a good prognosis, with mortality similar to the general population [ 27 ].A narrative review and clinical perspective of prospective data have suggested that NAFLD uncomplicated by steatohepatitis or fibrosis is insufficient to be considered as high risk for CVD [ 28 ]. A longitudinal cohort also found that hepatic steatosis without fibrosis was not statistically significantly associated with CP progression in T2DM [ 12 ].…”

Association Between the Triglyceride–Glucose Index and Outcomes of Nonalcoholic Fatty Liver Disease: A Large-Scale Health Management Cohort Study

“… 2 NAFLD is inextricably linked with type 2 diabetes (T2DM), metabolic syndrome, cardiovascular events, and chronic kidney disease and increases the risk of obstructive sleep apnoea, osteoporosis, and hypothyroidism. 3–7 Therefore, the high incidence and concealed health dangers of NAFLD have become a public health issue that should not be ignored.…”