Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults

Abstract

Observational studies suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased carotid intimal medial thickness (C-IMT) and carotid plaques in both children and adults. We carried out a meta-analysis to evaluate the relationship between NAFLD and carotid atherosclerosis measured as C-IMT and carotid plaque prevalence. Medline (Ovid), PubMed, Web of Science, and CINAHL databases were searched from 1946 to September 2014, complemented with a manual review of references of the published articles for studies that compared C-IMT or carotid plaque prevalence in adults and children. Results were pooled using both fixed and random effects models. Of the studies identified, 20 were suitable for testing the effect of NAFLD on C-IMT in adults, 13 for testing the effect of NAFLD on carotid plaque prevalence in adults, and five for testing the effect of NAFLD on C-IMT in the pediatric population. The pooled data from 20 studies (19,274 adult participants: NAFLD=8652, controls=10,622) showed significantly increased C-IMT in patients with NAFLD, compared with controls without NAFLD, according to both fixed [standardized mean difference (SMD)=0.251, 95% confidence interval (CI): 0.220-0.282, P<0.001] and random effects models (SMD=0.944, 95% CI: 0.728-1.160, P<0.001). NAFLD was also found to be associated with a higher carotid artery plaque prevalence when compared with controls, according to both fixed (OR=1.273, 95% CI=1.162-1.394, P<0.001) and random effects models (OR=1.769, 95% CI: 1.213-2.581, P=0.003), on pooling of 13 studies (14,445 adult participants: NAFLD=5399 and controls=9046). Analysis of pooled data from five studies in the pediatric population (1121 pediatric participants: NAFLD=312 and controls=809) also found NAFLD to be associated with significantly increased C-IMT according to fixed (SMD=0.995, 95% CI: 0.840-1.150, P<0.001) and random effects models (1.083, 95% CI: 0.457-1.709, P=0.001). NAFLD is associated with increased C-IMT in both children and adults, and with increased carotid plaque prevalence in adults. Individuals identified with carotid disease should be evaluated for NAFLD and vice versa.

Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications

“…Arterial stiffness is a well-accepted marker of CVD preceding arterial hypertension [29] and NAFLD is independently associated with increased vascular stiffness [28]. The carotid intimal media thickness (cIMT), a marker for generalised atherosclerotic burden, or the effective carotid plaque burden is also associated with NAFLD [30]. Finally, significant associations are observed of NAFLD with left ventricular (LV) diastolic dysfunction and LV mass [31,32].…”

“…Increased cIMT [30] Elevated serum elastase [43] elevated TGF-β [44] Arterial stiffening [28] Endothelium Endothelial dysfunction [27,28] Increased levels of ADMA [50,52] lower levels of HMGB1 [53] Endothelium disruption and repair [55] Reduced circulation EPCs [55] Redox status FGF21 ↑/FGF-resistance [124,125] CAD and NAFLD positively associated with FGF21 [126] SeP ↑ [127] Correlated with hsCRP and arterial stiffness [127] or cIMT [128] ANGPTL's ↑ [135] Associated with subclinical CVD [132][133][134] Paracrine cell signaling…”

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

“…Non-alcoholic steatohepatitis (NASH), one of several categories of NAFLD which is characterized by lobular in ammation and hepatocyte ballooning, produces more signi cant liver injury like brosis or cirrhosis compared to simple NAFLD [8], and patients with NASH were reported to have much higher incidence of coronary artery disease-related mortality [9][10][11]. In this aspect, there had been numerous previous studies investigating the causal relationship between NAFLD/NASH and carotid atherosclerosis [12][13][14][15], regarding carotid atherosclerosis as a surrogate marker of coronary atherosclerosis. Therefore, it might be important to assess hepatic steatosis and brosis to identify those at high risk of cardiovascular disease, and to optimally commence medical interventions [16,17].…”

Parameters of Carbohydrate Metabolism and Expression of Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease and Hypertensive Depending on Lipid Parameters

“…В настоящее время доказано, что ИР и эндотелиальная дисфункция являются звеньями одной цени и играют важную роль в формировании метаболических нарушений и, как следствие, ССЗ. Именно эндотелиальная дисфункция приводит к формированию атеросклероза и обусловливает развитие атеротромбоза [14].…”