Key result
Nonalcoholic fatty liver disease was associated with significantly lower flow-mediated dilation compared with controls (SMD -1.37; 95% CI -1.91 to -0.83; p<0.001), indicating endothelial dysfunction.
Why the study?
Individuals with NAFLD face increased cardiovascular risk, and endothelial dysfunction may constitute the missing link in this interaction.
Is nonalcoholic fatty liver disease associated with worse endothelial dysfunction (assessed by FMD) compared to controls?
Meta-Analysis (n=5,486)
Is nonalcoholic fatty liver disease associated with worse endothelial dysfunction (assessed by FMD) compared to controls?
Standardized Mean Difference: -1.37 (95% CI -1.91–-0.83)
p-value: p=<0.001
NAFLD is significantly associated with endothelial dysfunction as measured by reduced flow-mediated dilation, with more pronounced impairment in nonalcoholic steatohepatitis.
NAFLD may indicate elevated cardiovascular risk via endothelial impairment; confirms association with reduced FMD but leaves open causality and intervention effects.
Individuals with nonalcoholic fatty liver disease (NAFLD) are characterized by increased cardiovascular risk. Endothelial dysfunction, a mechanism implicated in those processes, may constitute the missing link in this interaction. Therefore, this systematic review and meta-analysis aims to evaluate the association of endothelial dysfunction, assessed by flow-mediated dilation (FMD) of the brachial artery, with NAFLD. We conducted a systematic literature search for studies assessing the difference in FMD between patients with NAFLD and controls. Exclusion criteria consisted of preclinical studies, studies in children/adolescents, no FMD assessment, and the absence of an NAFLD/control group. The database search identified 96 studies. Following the application of the exclusion criteria, 22 studies were included in the meta-analysis (NAFLD: 2164 subjects; control: 3322 subjects). Compared with controls, patients with NAFLD had significantly lower FMD% values (SMD: −1.37, 95% CI −1.91 to −0.83, p < 0.001, I2: 98%). Results remained unaffected after exclusion of any single study. Subgroup analysis revealed significantly decreased FMD in NAFLD subjects diagnosed with liver ultrasound or liver biopsy compared with method combination or other methods, while no differences were observed according to the chosen cuff inflation threshold, the presence of a significant difference in obesity measures between the groups, or the type of the control group (age- and sex-matched vs. other). Funnel plot asymmetry was not observed. Finally, compared with patients with pure steatosis, individuals with nonalcoholic steatohepatitis had significantly lower FMD (SMD: −0.81, 95% CI −1.51 to −0.31, p = 0.003, I2: 81%). In conclusion, FMD of the brachial artery, indicative of endothelial dysfunction, was significantly reduced in subjects with nonalcoholic fatty liver disease. Patients with nonalcoholic steatohepatitis might be facing a more pronounced endothelial impairment.
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Theofilis et al. (2022) conducted a meta-analysis in Nonalcoholic fatty liver disease (NAFLD) (n=5,486). Nonalcoholic fatty liver disease (NAFLD) vs. Controls without NAFLD was evaluated on Flow-mediated dilation (FMD) of the brachial artery (SMD -1.37, 95% CI -1.91 to -0.83, p=<0.001). Nonalcoholic fatty liver disease was associated with significantly lower flow-mediated dilation compared with controls (SMD -1.37; 95% CI -1.91 to -0.83; p<0.001), indicating endothelial dysfunction.
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