NAFLD Is Associated With Increased Risk of Atrial Fibrillation

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.

Abstract and Introduction

Abstract

Background & Aims: Whether nonalcoholic fatty liver disease (NAFLD) is associated with risk of incident atrial fibrillation (AF) independent of established cardiovascular risk factors remains controversial. We aimed to provide a quantitative estimate of the association between NAFLD and risk of AF after adjustment for cardiometabolic risk factors.

Methods: In this study, we searched PubMed and Embase for studies published from database inception until January 31, 2020. Cohort studies reported adjusted relative risks (RRs) and 95% confidence intervals (CIs) for AF of NAFLD compared with non-NAFLD were included for analysis.

Results: A total of 6 cohort studies were included, comprising 614 673 individuals for analysis. The median follow-up duration was 10.0 years with 7271 cases of incident AF. Compared with non-NAFLD, minimally adjusted models without adjustment for cardiometabolic risk factors showed that NAFLD was associated with increased risk of AF (RR 1.65, 95% CI 1.23–2.20, I² = 63.0%). After adjustment for multiple cardiometabolic risk factors, the association between NAFLD and risk of AF was still higher than that in non-NAFLD (RR 1.19, 95% CI 1.04–1.31, I² = 54.0%). There was significant heterogeneity for the risk of AF between minimally and maximally adjusted models (I² = 77.1%, Pfor heterogeneity = 0.04). 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.

Table 1. Characteristics of included studies in the meta-analysis
Study	Participants	Study design	Region	NAFLD definition and prevalence (%)	Sample size (% women)	Incident AF (N)	Age (y), average	Follow-up (y)	Baseline CVD excluded
Roh 2020²²	General population	Prospective cohort study	Korea	Fatty liver index ≥30 (25.9%)	334 180 (51.7)	1415	41.8	5.3	Yes
Labenz 2019²³	General population	Retrospective cohort study	Germany	Database record (50%)	44 096 (49.8)	3307	55.6	10.0	Yes
Long 2017²⁴	General population	Prospective cohort study	US	Computed Tomography (20%)	2060 (53.0)	153	59.0	12.0	No
You 2016²⁵	General population	Prospective cohort study	Korea	Fatty liver index ≥30 (31.0%)	232 979 (63.7)	2261	49.0	3.7	Yes
Käräjämäki 2015²⁶	Hypertensive patients with matched control	Prospective cohort study	Italy	Ultrasonography (26.0%)	958 (53.4)	93	51.1	16.3	No
Targher 2013²⁷	Type 2 diabetes	Prospective cohort study	Italy	Ultrasonography (39.5%)	400 (70.3)	42	64.0	10.0	Yes

Abbreviations: AF, atrial fibrillation; CVD, cardiovascular disease; NAFLD, nonalcoholic fatty liver disease.

Table 2. Subgroup analyses of the association between NAFLD and risk of atrial fibrillation
Subgroup	No of studies	RR (95% CI)	I²/P value for heterogeneity within the subgroup	I²/P value for heterogeneity among subgroups
Ethnicity
Asians	2	1.18 [1.07, 1.32]	55.0%/0.13	0%/0.53
Non-Asians	4	1.34 [0.93, 1.92]	64.0%/0.04	0%/0.53
Gender
Male	3	1.16 [1.00, 1.35]	59.0%/0.09	0%/0.55
Female	3	1.24 [1.06, 1.45]	56.0%/0.10	0%/0.55
Study design
Prospective cohort	5	1.22 [1.04, 1.44]	61.0%/0.03	0%/0.46
Retrospective cohort	1	1.14 [1.04, 1.25]	NA	0%/0.46
Participant's average age
<55 years	3	1.21 [1.07, 1.37]	66.0%/0.05	0%/0.97
≥55 years	3	1.23 [0.82, 1.86]	55.0%/0.11	0%/0.97
Methods for defining NAFLD
Ultrasonography	2	1.18 [1.07, 1.32]	55.0%/0.13	31.7%/0.22
Fatty Liver Index	2	2.44 [1.09, 5.43]	43.0%/0.19
Computed Tomography	1	0.96 [0.64, 1.45]	NA
Databases record	1	1.14 [1.04, 1.25]	NA
Enrolment
General population	3	1.16 [1.09, 1.23]	12.0%/0.33	80.2%/0.02
Diabetes	1	4.37 [1.38, 13.84]	NA	80.2%/0.02
Sample
<10 000	3	1.69 [0.82, 3.52]	74.0%/0.02	0%/0.32
≥10 000	3	1.17 [1.10, 1.24]	23.0%/0.27	0%/0.32
Follow-up duration
<10 years	2	1.18 [1.07, 1.32]	55.0%/0.13	0%/0.53
≥10 years	4	1.34 [0.93, 1.92]	64.0%/0.04	0%/0.53
Adjustment of confounders
Adequate^a	5	1.23 [1.05, 1.43]	59.0%/0.04	0%/0.36
Not adequate	1	1.13 [1.03, 1.24]	NA	0%/0.36

Abbreviations: NA, not available; NAFLD, nonalcoholic fatty liver disease.
^aAdequate adjustment denoted adjustment of at least five of six confounders including gender, age, hypertension or blood pressure or antihypertensive treatment, body mass index or other measure of overweight/obesity, cholesterol and smoking.