Alcohol and steatotic liver disease exhibit divergent associations with high plasma small dense LDL-C concentration
Yasuhiro Matsubayashi, Kiminori Kato, Mao Watanabe, Yasuki Ito, Noriyuki Satoh, Takaaki Sato, Masaru Kitazawa, Takaho Yamada, Hirohito SoneAbstract
Background
Within the metabolic dysfunction-associated steatotic liver disease (MASLD)/MASLD with increased alcohol intake (MetALD)/alcohol-associated liver disease (ALD) framework, cardiovascular risk varies by alcohol exposure. As small dense low-density lipoprotein cholesterol (sdLDL-C) is highly atherogenic, this study assessed the relative effects of steatotic liver disease (SLD) and alcohol consumption on sdLDL-C elevation and the effects of conventional fasting lipids (low-density lipoprotein cholesterol [LDL-C]/high-density lipoprotein cholesterol [HDL-C]/triglycerides [TGs]) on these associations.
Methods
This cross-sectional study enrolled 55 745 participants who underwent health screenings in Niigata, Japan between April 2024 and March 2025. Alcohol consumption was self-reported as low, moderate, or excessive. Participants were grouped by SLD status and alcohol consumption. sdLDL-C was directly measured, with high sdLDL-C defined as ≥35 mg/dL. Multivariable linear regression (sdLDL-C) and logistic regression (high sdLDL-C) analyses used 2 models: model 1 was adjusted for age, sex, body mass index, smoking, lipid-lowering medication, antihypertensive medication, and diabetes, and model 2 was further adjusted for LDL-C, HDL-C, and TGs. Marginal standardized prevalence and standardized prevalence differences (PDs) were estimated using g-computation with 2000 bootstrap iterations.
Results
The crude prevalence of high sdLDL-C was influenced by SLD and alcohol consumption, being highest in the SLD(+)/excessive alcohol consumption group (76.4%). In model 2, SLD-related associations were attenuated, as reflected by markedly reduced PDs between SLD(+) and SLD(−) within each alcohol category, whereas alcohol-related associations remained robust.
Conclusion
Alcohol exposure contributes to an atherogenic sdLDL-C phenotype beyond conventional fasting lipids within contemporary SLD categories, indicating potential relevance for risk profiling in MetALD/ALD.