Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study)

Käräjämäki, Aki Juhani; Pätsi, Olli-Pekka; Savolainen, Markku J.; Kesäniemi, Y. Antero; Huikuri, Heikki V.; Ukkola, Olavi

doi:10.1371/journal.pone.0142937

Cited by 125 publications

(110 citation statements)

References 58 publications

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“…After excluding duplicates, based on the titles and abstracts of 89 citations (in accordance with the aforementioned exclusion criteria of the meta‐analysis), we initially identified 11 potentially relevant studies from PubMed, Web of Science and Scopus databases prior to December 14, 2018 (date last searched). After examining the full text of these 11 publications, we further excluded 2 studies, because of unsatisfactory inclusion criteria ( n = 1) or unsatisfactory outcome measures ( n = 1), as specified in the PRISMA flow diagram.…”

Section: Resultsmentioning

confidence: 99%

“…Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and is a major health problem worldwide, owing to its associated morbidity and increased mortality . As it will be discussed in greater detail below, a number of observational studies have recently examined the association between NAFLD and risk of both prevalent and incident AF in middle‐aged and elderly individuals, but these have produced conflicting results …”

Section: Introductionmentioning

confidence: 99%

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Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

Mantovani

Dauriz

Sandri

et al. 2019

Liver International

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Background & Aims Recent studies examined the association between non‐alcoholic fatty liver disease (NAFLD) and risk of atrial fibrillation (AF) in adults, but the findings have been inconsistent. We provided a quantitative estimate of the magnitude of the association between NAFLD and risk of AF. Methods We searched publication databases using predefined keywords to identify observational studies (published up to December 14, 2018), in which NAFLD was diagnosed by biopsy, imaging or biochemistry and AF was diagnosed by medical history and electrocardiograms. Data from selected studies were extracted and meta‐analysis was performed using random‐effects modelling. Results Nine cross‐sectional and longitudinal studies were included in the final analysis (n = 364 919 individuals). Meta‐analysis of data from 5 cross‐sectional studies showed that NAFLD was associated with an increased risk of prevalent AF (random‐effects odds ratio 2.07, 95% CI 1.38‐3.10; I2 = 54.7%), independent of age, sex, body mass index, hypertension and other common AF risk factors. This risk was particularly high among patients with established diabetes (n = 1 study; random‐effects odds ratio 5.17, 95% CI 2.05‐13.02). Meta‐analysis of data from 4 longitudinal studies showed that NAFLD was independently associated with a 10‐year increased risk of incident AF only in type 2 diabetic patients (n = 1 study; random‐effects hazard ratio 4.96, 95% CI 1.42‐17.28). Sensitivity analyses did not modify these findings. Funnel plots did not reveal significant publication bias. Conclusions NAFLD is associated with an increased risk of AF in middle‐aged and elderly individuals (especially in those with type 2 diabetes). However, the observational design of the eligible studies does not allow for proving causality.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

Mantovani

Dauriz

Sandri

et al. 2019

Liver International

View full text Add to dashboard Cite

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“…NAFLD has been shown to be associated with an increased risk of AF, independently of gender, age, hypertension, LV hypertrophy and PR interval[12,67,68]. Additionally, a prospective study of nearly 1000 subjects has reported that NAFLD is an independent risk factor of AF[69]. …”

Section: Clinical and Subclinical Cvd And Nafld Markersmentioning

confidence: 99%

Nonalcoholic fatty liver disease - A multisystem disease?

Mikolašević

Milić

Wensveen

et al. 2016

WJG

160

155

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Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians.

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“…The association between non-alcoholic fatty liver disease (NAFLD) and AF has recently been presented [7, 8]. The mechanisms that link these two entities are not completely understood, but it is reasonable to assume that this association is causal [7] and two-way.…”

Section: Introductionmentioning

confidence: 99%

Presence of atrial fibrillation is associated with liver stiffness in an elderly Finnish population

et al. 2017

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BackgroundChronic liver injury from different etiologies drives liver fibrosis. However, little is known about the associated factors, systemic factors in particular. Recently, non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation have been shown to be associated with each other. Thereby, we aimed to study the association between atrial fibrillation and liver stiffness.StudyExtensive clinical measurements including echocardiography of the heart, transient elastography (TE) of the liver and the presence of atrial fibrillation were determined in elderly Finnish study subjects (n = 76, mean age 73 years) from OPERA (Oulu Project Elucidating the Risk of Atherosclerosis) study cohort. Half of the study subjects had non-alcoholic fatty liver disease, whereas others did not have any known hepatic morbidity. The present study was cross-sectional by nature.ResultsThe subjects with atrial fibrillation had higher TE values (with atrial fibrillation TE = 9.3kPa, without atrial fibrillation TE = 6.3kPa, p = 0.018). When the cohort was divided to four subgroups (those without NAFLD or atrial fibrillation, with NAFLD but without atrial fibrillation, with both conditions, and with atrial fibrillation but without NAFLD), the TE value was the highest in the subjects with both conditions (5.3kPa, 7.4kPa, 10.8kPa and 7.8kPa, respectively, p = 0.019). Moreover, the higher the TE value, the more prevalent atrial fibrillation was (the atrial fibrillation prevalence by tertiles of TE 27% / 36% / 77%, p = 0.001). Likewise, the greater the TE value, the greater the left atrial diameter, a collateral of atrial fibrillation (left atrial diameters by tertiles of TE 39mm / 45mm / 48mm, p<0.001) was. All these p-values for continuous variables remained statistically significant even after adjustment for common clinically relevant risk factors.ConclusionsThere is an association between atrial fibrillation and liver stiffness. This novel association may have multiple explanations and mechanistic links, which are discussed here and need further studies, prospective studies in particular.

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Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study)

Cited by 125 publications

References 58 publications

Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

Association between non‐alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta‐analysis

Nonalcoholic fatty liver disease - A multisystem disease?

Presence of atrial fibrillation is associated with liver stiffness in an elderly Finnish population

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