Alcohol and Steatotic Liver Disease Exhibit Divergent Associations with High Plasma Small Dense LDL-C Concentration
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ID: 317825
2026
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Abstract
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 two 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, whereas alcohol-related associations remained robust, as the PD was lower for SLD(+) than for SLD(-) within each alcohol category. 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.
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| Authors | Yasuhiro Matsubayashi, Kiminori Kato, Mao Watanabe, Yasuki Ito, Noriyuki Satoh, Takaaki Sato, Masaru Kitazawa, Takaho Yamada, Hirohito Sone |
| Journal | the journal of clinical endocrinology & metabolism |
| Year | 2026 |
| DOI |
10.1210/clinem/dgag234
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| URL | |
| Keywords | Keywords not found |
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