Nonalcoholic Fatty Liver Disease Is Associated With Increased Risk of Atrial Fibrillation

Xiaoyan Cai; Sulin Zheng; Ying Liu; Yan Zhang; Jianhua Lu; Yuli Huang


Liver International. 2020;40(7):1594-1600. 

In This Article


Studies Retrieved and Characteristics

The initial search returned 267 articles. After screening the abstracts, 27 qualified for a full-text review (Figure 1). Finally, 6 studies involving 614 673 participants (women 56.1%) were included in the analysis.[22–27] The key characteristics of the included studies were presented in Table 1. The median follow-up duration was 10.0 years (range 3.7–16.3 years) and 7271 cases of incident AF were recorded. The median proportion of NAFLD in the studies was 28.5%. Two studies used ultrasonography,[26,27] two studies used fatty liver index[22,25] and 1 study[24] used computed tomography to diagnose NAFLD respectively. One study included patients with an initial diagnosis of NAFLD (ICD-10: K75.8, K76.0) based on database record.[23] The minimally and maximally adjusted confounders in estimated risk model were presented in the Supplementary File S2, and the details of the quality assessment were presented in the Supplementary File S3. Based on maximally adjusted confounders, 5 studies met our criteria for adequate adjustment. Two studies were graded as having fair quality, and four studies were graded as having good quality according to the Newcastle-Ottawa quality assessment.

Figure 1.

Flow of papers through review. CIs, confidence intervals; NAFLD, nonalcoholic fatty liver disease

Association Between NAFLD and Risk of AF

Random-effects model was used for analysis as significant heterogeneity was detected among studies (I2 = 54%, P = .05). After multivariable adjustment, NAFLD was associated with an increased risk of incident AF (RR 1.19, 95% CI 1.07–1.31, P = .001) (Figure 2). No publication bias was identified based on inspection of the funnel plot (Supplementary File S4). In 4 studies, the risk of AF associated with NAFLD was also reported in minimally adjusted RRs (unadjusted or age and gender adjusted). Pooled data showed that before adjusted for other cardiovascular risk factors, there was a 65% increased risk of AF in patients with NAFLD (RR 1.65, 95% CI 1.23–2.20, P < .001) (Figure 3). There was significant heterogeneity for the risk of AF between minimally and maximally adjusted models (I2 = 77.1%, P for heterogeneity = 0.04).

Figure 2.

Forest plot of multivariable adjusted risk of atrial fibrillation associated with NAFLD. CIs, confidence intervals; NAFLD, nonalcoholic fatty liver disease; RR, relative risk

Figure 3.

Forest plot for risk of atrial fibrillation associated with NAFLD in minimally adjusted model. CIs, confidence intervals; NAFLD, nonalcoholic fatty liver disease; RR, relative risk

The absolute risks of AF in non-NAFLD and NAFLD across studies were presented in Supplementary File S5. Compared with non-NAFLD, the absolute risk increase in NAFLD for AF was 1.3 (95% CI 0.5–2.1) per 1000 person-years. Based on the pooled adjusted RR and median prevalence of NAFLD, the PARs of AF associated with NAFLD were 5.1% (95% CI 2.0%–8.1%).

Pooled data from each subgroup were combined using the random-effects model. There was no significant heterogeneity in all subgroup analyses, except for enrolment based on general population or diabetes (general population: RR 1.16, 95% CI 1.09–1.23; diabetes: RR 4.37, 95% CI 1.38–13.84; I2 = 80.2%, P for subgroup heterogeneity = 0.02) (Table 2). The sensitivity analyses confirmed that the association between AF and NAFLD did not change with the use of random-effects models or fixed-effects models for the meta-analysis or with recalculation of the RRs by omitting one study at a time.