Metabolic dysfunction-associated steatotic liver disease increases the risk of incident cardiovascular disease: a nationwide cohort study

Abstract

Background: The various subcategories under the overarching term of steatotic liver disease (SLD) have been recently proposed by the nomenclature consensus group and endorsed by international academic liver societies. Our aim was to investigate the association between each subtype of SLD and incident cardiovascular disease (CVD) in a nationwide Korean cohort.

Methods: From a nationwide health screening database from Korea, 351,068 individuals aged 47-86 years between January 1, 2009 and December 31, 2010 were included and followed until December 31, 2019 for a median of 9.0 years. Individuals were categorised into no SLD, metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-related liver disease (ALD). Hepatic steatosis was defined as fatty liver index ≥60. The primary outcome was a composite CVD, which includes non-fatal and fatal myocardial infarction and stroke. The subdistribution hazard ratio (SHR) was calculated using the Fine-Gray model with treating non-CVD-related death as a competing risk.

Findings: There were 199,817 male (56.9%) and 151,251 female (43.1%) with a median age of 55 years (interquartile range, 50-61). The prevalence of no SLD, MASLD, MetALD, and ALD was 44.3%, 47.2%, 6.4%, and 2.1%, respectively; and the incidence rate of CVD in each subcategory was 6.2, 8.5, 8.5, and 9.6 per 1000 person-years, respectively. MASLD (SHR, 1.19; 95% confidence interval [CI], 1.15-1.24), MetALD (SHR, 1.28; 95% CI, 1.20-1.36), and ALD (SHR, 1.29; 95% CI, 1.18-1.41) increased the risk of CVD compared to no SLD, which increment was in consecutive order (P_trend < 0.001).

Interpretation: Individuals with MASLD, MetALD, or ALD are at an increased risk of developing incident CVD. Higher risk of CVD observed in MetALD compared to MASLD suggests the additive impact of alcohol consumption in conjunction with cardiometabolic risk factors on CVD development. These findings support and validate the utility of the new consensus criteria for SLD in predicting CVD.

Funding: The National Research Foundation of Korea and the Korea Centers for Disease Control and Prevention.

Keywords: Cardiovascular disease; Cardiovascular risk factors; Metabolic dysfunction-associated steatotic liver disease; Nonalcoholic fatty liver disease.

Fig. 1

Flow diagram for inclusion of study participants. Study participants were derived from the National Health Insurance Service Health Screening Cohort after excluding participants with death, history of cardiovascular disease, missing information for alcohol consumption or other covariates, chronic viral hepatitis, and cryptogenic steatotic liver disease.

Fig. 2

Association of steatotic liver disease subtypes with the risk of incident cardiovascular disease. Subdistribution hazard ratios (95% CIs) were calculated using the Fine and Gray’s model after adjustments for age, sex, body mass index, household income, hypertension, diabetes, dyslipidaemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, aspirin, and non-steroidal anti-inflammatory drugs. Acronyms: PY, person-year; SHR, subdistribution hazard ratio; CI, confidence interval; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction-associated steatotic liver disease with increased alcohol intake; ALD, alcohol-related liver disease.

Fig. 3

Restricted cubic splines for the association of alcohol consumption with the risk of incident cardiovascular disease among individuals with metabolic dysfunction-associated steatotic liver disease. Subdistribution hazard ratios (95% CIs) were calculated using the Fine and Gray’s model after adjustments for age, sex, body mass index, household income, hypertension, diabetes, dyslipidaemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, aspirin, and non-steroidal anti-inflammatory drugs. (A) Association of alcohol consumption with cardiovascular disease, (B) Association of alcohol consumption with coronary heart disease, and (C) Association of alcohol consumption with stroke.

Fig. 4

Restricted cubic splines for the association of cardiometabolic risk factors with the risk of incident cardiovascular disease among individuals with metabolic dysfunction-associated steatotic liver disease. Subdistribution hazard ratios (95% CIs) were calculated using the Fine and Gray’s model after adjustments for age, sex, body mass index, household income, hypertension, diabetes, dyslipidaemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, aspirin, and non-steroidal anti-inflammatory drugs. (A) Association of waist circumference with cardiovascular disease, (B) Association of fasting serum glucose with cardiovascular disease, (C) Association of systolic blood pressure with cardiovascular disease, (D) Association of triglycerides with cardiovascular disease, and (E) Association of HDL-cholesterol with cardiovascular disease.