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Comparative association of MAFLD/MASLD and Subtypes with Cardiovascular Diseases Outcomes

Huizhen Jin¹, Zhuoshuai Liang¹, Xinmeng Hu¹

¹Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun, 130021, China.

Nutrition, Metabolism, and Cardiovascular Diseases : NMCD

|April 6, 2025

Abstract

Background And Aims:

Metabolic dysfunction-associated steatotic liver disease (MASLD) acts as an alternative for demarcating metabolic dysfunction-associated fatty liver disease (MAFLD). This study aimed to investigate the factors that significantly influence the relationship between MAFLD and MASLD in relation to the incidence of major cardiovascular outcomes.

Methods And Results:

A total of 340,998 participants in the UK Biobank study were included. Multivariable Cox proportional hazards models were used to estimate the effect of MAFLD and MASLD on the outcomes of cardiovascular diseases (CVDs) (coronary artery disease, stroke, heart failure, and CVD-related death) with hazard ratios (HRs) and 95 % confidence intervals (CIs). A total of 126,077 (36.97 %) participants had MAFLD and 97,418 (28.57 %) had MASLD. Over a median follow-up of 13.5 years (interquartile range 12.6-14.2), there were 41,548 new events of CVDs recorded. MAFLD (HR = 1.52; 95 % CI: 1.49-1.55) and MASLD (HR = 1.42; 95 % CI: 1.39-1.45) were associated with high risks of CVDs. Among the subtypes of MAFLD and steatotic liver disease (SLD), MAFLD diabetes subtype (HR = 2.26; 95 % CI: 2.17-2.35) and alcohol-associated liver disease (ALD) (HR = 1.65; 95 % CI: 1.55-1.76) exhibited the highest risk of CVDs. MAFLD overweight without MD subtype were not associated with CVDs. The effect of MAFLD on the CVD outcomes was consistent regardless of the presence of MASLD.

Conclusion:

The metabolic health status and alcohol consumption function as more critical factors than obesity in assessing CVD outcomes in participants with MAFLD or MASLD.

Insights

Metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) increase cardiovascular disease (CVD) risk. Metabolic health and alcohol consumption are key factors, more so than obesity, in assessing these risks.

Area of Science:

Hepatology
Cardiology
Metabolic Diseases

Background:

Metabolic dysfunction-associated steatotic liver disease (MASLD) is proposed as an alternative to metabolic dysfunction-associated fatty liver disease (MAFLD).
Understanding the relationship between these liver conditions and cardiovascular outcomes is crucial for patient management.

Purpose of the Study:

To investigate factors influencing the association between MAFLD and MASLD with major cardiovascular outcomes.
To determine the relative importance of metabolic health, obesity, and alcohol consumption in predicting cardiovascular disease (CVD) risk in individuals with these liver conditions.

Main Methods:

Analysis of UK Biobank data from 340,998 participants.
Utilized multivariable Cox proportional hazards models to assess the impact of MAFLD and MASLD on CVD incidence.
Followed participants for a median of 13.5 years, recording major cardiovascular events.

Main Results:

Both MAFLD (HR=1.52) and MASLD (HR=1.42) were significantly associated with increased CVD risk.
MAFLD with diabetes (HR=2.26) and alcohol-associated liver disease (ALD) (HR=1.65) showed the highest CVD risks.
MAFLD without metabolic dysfunction in overweight individuals was not linked to increased CVD risk.

Conclusions:

Metabolic health status and alcohol consumption are more critical predictors of CVD outcomes in MAFLD/MASLD patients than obesity.
These findings highlight the importance of metabolic and lifestyle factors in stratifying cardiovascular risk in individuals with fatty liver disease.

Read full analysis

Keywords:

Cardiovascular diseases Metabolic dysfunction-associated fatty liver disease Metabolic dysfunction-associated steatotic liver disease Steatotic liver disease UK Biobank

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