Risk of cardiovascular events in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis

Aims: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease and has been repeatedly associated with an increased risk of cardiovascular disease. However, the extent of such association is unclear. We conducted a systematic review and meta-analysis of the literature to evaluate the risk of myocardial infarction (MI), ischaemic stroke (IS), atrial fibrillation (AF), and heart failure (HF) in NAFLD patients. Methods and results : According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed and EMBASE, from inception to 6 March 2021, and included all studies reporting the incidence of MI, IS, AF, and HF in patients with and without NAFLD. Random-effect fmodels were used to estimate pooled odds ratio (OR), 95% confidence intervals (CI), and 95% prediction intervals (PI); subgroup analyses, meta-regressions, and sensitivity analyses were additionally performed. Among 3254 records retrieved from literature, 20 studies were included. Non-alcoholic fatty liver disease was associated with an increased risk of MI (OR: 1.66, 95% CI: 1.39-1.99, 95% PI: 0.84-3.30), IS (OR: 1.41, 95% CI: 1.29-1.55, 95% PI 1.03-1.93), AF (OR: 1.27, 95% CI: 1.18-1.37, 95% PI: 1.07-1.52), and HF (OR: 1.62, 95% CI: 1.43-1.84, 95% CI: 1.04-2.51). We identified significant subgroup differences according to geographical location, study design, NAFLD definition, and risk of bias; meta-regressions identified mean age, male sex, and study-level characteristics as potential moderators of the risk of MI and IS. Conclusions : Non-alcoholic fatty liver disease was associated with increased risk of MI, IS, AF, and HF. Age, sex, and study characteristics may moderate the strength of this association. Further studies are required to evaluate specific cardiovascular prevention strategies in patients with NAFLD.