Comparison of cardiovascular mortality between MAFLD and NAFLD: A cohort study

https://doi.org/10.1016/j.numecd.2023.01.013Get rights and content

Highlights

  • The evidence regarding the association between MAFLD and CVD mortality is limited.

  • MAFLD is associated with increased CVD mortality in a young Korean population.

  • However, the presence of NAFLD was not associated with CVD mortality.

  • Our results suggest MAFLD would be a stronger predictor of CVD mortality than NAFLD.

Abstract

Background and aims

A new diagnostic criterion of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. However, only few studies have shown that MAFLD predicts cardiovascular disease (CVD) mortality better than non-alcoholic fatty liver disease (NAFLD). Therefore, a cohort study was conducted to assess this relationship.

Methods and results

Health examination data from health care centers in South Korea were assessed after excluding participants with missing covariates and cancer history (n = 701,664). Liver ultrasonography reports, laboratory and anthropometric data were extracted. Diagnoses of NAFLD and MAFLD were performed according to standard definitions. Participants were categorized based on the presence of NAFLD and MAFLD. In addition, participants were classified into five categories: no fatty liver disease (no FLD), NAFLD-only, MAFLD-only, both FLDs, and alcoholic FLD (AFLD) and non-MAFLD. Multivariable regression modeling was performed.

The median follow-up duration was 8.77 years, and 52.56% of participants were men. After stratifying the cohort into no-MAFLD and MAFLD groups, MAFLD was associated with increased CVD mortality (adjusted HR 1.14, 95% CI 1.02–1.28). When participants were divided into no-NAFLD and NAFLD groups, there was a non-significant trend towards an increase in CVD mortality in NAFLD group (adjusted HR 1.07, 95% CI 0.95–1.21). When participants were divided into five categories, MAFLD-only group showed increased CVD mortality (adjusted HR 1.35, 95% CI 1.07–1.70) while NAFLD-only group showed no significant association with CVD mortality (adjusted HR 0.67, 95% CI 0.38–1.19).

Conclusions

In conclusion, MAFLD is associated with increased CVD mortality in a relatively young Korean population.

Introduction

The prevalence of fatty liver disease (FLD) is increasing worldwide owing to the widespread western lifestyle, increased prevalence of obesity and type 2 diabetes, and related metabolic derangements [[1], [2], [3], [4]]. Traditionally, two major categories existed in FLD: non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) [5,6]. Although this classification of FLD has been used for nearly 35 years, it has a blind spot because NAFLD does not include FLD with other coexisting liver diseases or moderate alcohol intake [7]. This problem led to the development of a new class of FLD, known as metabolic dysfunction-associated fatty liver disease (MAFLD) [7,8] to include these patient populations that were previously challenging to classify.

The newly proposed definition of MAFLD consists of hepatic fat and metabolic abnormalities regardless of alcohol consumption or secondary causes of liver diseases and steatosis [7,9]. This new definition is expected to facilitate the identification of patients with FLD with chronic liver diseases or alcoholism, which were previously excluded by the traditional NAFLD definition [9]. However, this change has also provoked new concerns. Younossi et al. suggested that this change is premature because the new terminology was created without evidence of the pathogenesis of MAFLD or the effect of MAFLD on long-term complications [10].

Many researchers have investigated the association between FLD and cardiovascular disease (CVD) mortality [[11], [12], [13], [14]]. Growing evidence suggests that patients with NAFLD are at increased risk of developing type 2 diabetes, coronary artery disease, cardiomyopathy, and cardiac arrhythmias, which may lead to increased CVD mortality [7,[15], [16], [17]]. These findings suggest that NAFLD is a predictor of CVD events, independent of traditional risk factors [14,18].

Considering the new definition of MAFLD, one could speculate that MAFLD is associated with higher CVD mortality, as it incorporates a wider range of patients with FLD with metabolic derangements [7]. However, data on CVD mortality in the MAFLD population are limited [7]. There is debate over whether the MAFLD definition predicts CVD mortality better than the NAFLD classification [7]. To clarify this ambiguity, we conducted a large-scale cohort study to assess the relationship between FLD and CVD mortality.

Section snippets

Study population

The Kanbguk Samsung Health Study (KSHS) data were used for our analysis. The cohort and methods have been described in a previous study by our team [19]. In brief, the KSHS cohort was created using data from regular comprehensive health examinations among employers in Korea's public or private sectors. All examinations were conducted at two health examination centers in South Korea. Extensive information was collected using a standardized questionnaire during the health examination, including

Baseline characteristics

The median follow-up duration was 8.77 years, and the mean follow-up duration was 9.24 ± 5.26 years. The mean age of the participants was 39.81 ± 10.92 years, and 52.56% (n = 368,824) were men (Supplemntary Table 1). Among the 701,664 study participants, participants were stratified into no-MAFLD (n = 523,933, 74.67%), and MAFLD (n = 177,731, 25.33%) group. The proportions of men (76.73%), smokers (30.64%), and individuals with high alcohol consumption (16.4%) were higher in the MAFLD group

Discussion

To our knowledge, this was one of the major studies to date that showed the association between MAFLD and the risk of CVD mortality in a cohort of individuals who underwent liver ultrasonography to define hepatic steatosis. In our study cohort, the presence of MAFLD was associated with an increased risk of CVD mortality, whereas the presence of NAFLD did not show any such significant association. When we divided the participants into 5 categories, the MAFLD-only group was associated with an

Conclusions

In conclusion, our study showed that the presence of MAFLD was associated with increased CVD mortality in a relatively young Korean population. However, the strength of this association was not strong. Therefore, careful application of MAFLD for CVD risk prediction is required.

Funding

None.

Author contributions

TKY: Conceptualization, methodology, writing – original draft, and writing – review and editing. MYL: Formal analysis and investigation. SHK: Writing – review and editing; M-HZ: writing – review and editing; GT: writing – review and editing; CDB: writing – review and editing; K-CS: conceptualization, methodology, writing – review and editing, supervision, and project administration.

Ethical statement

The Institutional Review Board of Kangbuk Samsung Hospital (IRB No.:2022- 05- 024) approved the current study. Informed consent was waived because we used only non-identifiable data obtained during the health-screening examinations.

Data sharing statement

The data that support the findings of this study are available on request from the corresponding author, Ki-Chul Sung, upon reasonable request.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

None.

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