NAFLD Is Associated With Increased Risk of Atrial Fibrillation

In This Article

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%, P for 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.

Conclusions: NAFLD is associated with increased risk of incident AF. The strength of the association between NAFLD and AF is partially attributed to the co-existing cardiometabolic risk factors.

Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a lifetime risk of up to 25%.^[1] It is associated with a four- to five-fold increased risk of ischaemic stroke.^[2] Detection and proper management of the risk factors of AF can reduce the incidence and morbidity of AF.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a prevalence ranging from 25% to 45%.^[3] NAFLD is characterized by excessive hepatic lipid accumulation associated with metabolic abnormalities in the absence of excessive alcohol consumption and other known liver disease.^[4] Accumulating evidence showed that NAFLD is associated with extrahepatic morbidity, including malignancies and cardiovascular disease.^[5,6] NAFLD is also associated with the prevalence of cardiac arrhythmias, especially AF.^[7,8] However, meta-analyses of observational studies showed inconsistent results for the associations among NAFLD and the risk of incident AF, which may be caused by differences in study characteristics and inclusion criteria.^[9,10] Furthermore, NAFLD and AF share multiple common risk factors, including obesity and diabetes.^[3,11] It remains unclear whether NAFLD is an independent risk factor of AF, or whether NAFLD is an epiphenomenon of other cardiometabolic factors causally related to AF.

Therefore, we performed an updated meta-analysis of cohort studies to examine the association of NAFLD with the risks of AF. Two key questions were explored: 1) Is NAFLD associated with an increased risk of AF? 2) What is the strength of confounders on the estimated risk of AF associated with NAFLD?

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.