Non-alcoholic fatty liver disease and cardiovascular risk

Table 2 Studies evaluating coronary artery disease and carotid disease in non-alcoholic fatty liver disease

Ref.	Study characteristics	Modality to assess CV risk	Diagnosis of NAFLD Ultrasound	Main findings
Sinn et al[16] (2016)	Retrospective cohort study - 8020 men (average age, 49.2 yr) without carotid atherosclerosis at baseline and with proven NAFLD	CIMT on carotid ultrasound		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
Pais et al[35] (2016)	Longitudinal cohort study - 1871 subjects (mean age 53 yr; 65% males). Half of cohort had steatosis while half did not	CIMT on carotid ultrasound	Fatty Liver Index	Steatosis occurred in 12% and CP in 23% of patients. C-IMT increased in patients with steatosis occurrence whereas it did not change in those that stayed free of steatosis. Steatosis at baseline predicted CP occurrence independent of age, sex, type-2 diabetes, tobacco use, hsCRP, hypertension and C-IMT
Park et al[36] (2016)	Longitudinal cohort study - 1732 subjects underwent serial CAC evaluation. Half the cohort had NAFLD and half did not	Calcium scoring CT to assess CAC	Ultrasound	More subjects with NAFLD than without showed CAC development or progression. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification after adjusting for traditional metabolic risk factors. The severity of NAFLD was dose-dependently associated with the development of CAC
Kim et al[15] (2012)	Retrospective chart review- 4 023 subjects (mean age, 56.9 ± 9.4 yr; 60.7% males) without known liver disease or a history of ischemic heart disease	Calcium scoring CT to assess CAC	Ultrasound	Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease
Fracanzani et al[20] (2016)	Longitudinal cohort study - 125 NAFLD patients and 250 age and gender matched Controls at baseline and 10 yr later were followed. Incidence of cardiovascular and cerebral events was recorded	CIMT on carotid ultrasound	Ultrasound	Major cardiovascular events were observed in 19% of NAFLD patients, with an estimated cumulative risk significantly higher in NAFLD than in Controls. Presence of plaques and of steatosis were the strongest predictors for cardiovascular events. Grade of steatosis, ALT and GGT levels were higher in NAFLD patients who developed cardiovascular events. CIMT value after 10 years was significantly higher in NAFLD than in Controls. NAFLD should be included among risk factors for cardiovascular damage and underline the utility to evaluate, once it is diagnosed, the presence of atherosclerotic lesions
Nahandi et al[17] (2014)	Case control study - 151 patients in three groups: group I including 49 patients with NAFLD and DM; group II including 50 non-diabetic NAFLD patients; and the control including 52 normal subjects as group III	CIMT on carotid ultrasound	Ultrasound	There is a significant association between the presence of NAFLD and atherosclerosis, but this association was independent of DM. The grade of NAFLD and elevated liver function tests had no effect on severity of atherosclerosis

NAFLD: Non-alcoholic fatty liver disease; CT: Computed tomography; CAC: Coronary artery calcification; CIMT: Carotid intima-media thickness; CP: Carotid plaque; DM: Diabetes mellitus.