ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Translational and Clinical Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1585811
Associations between High-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, and Their Ratio with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Cohort Study
Provisionally accepted
- 1Second Affiliated Hospital of Dalian Medical University, Dalian, China
- 2Health Management Center of the Second Affiliated Hospital of Dalian Medical University, Dalian, China
- 3Department of General Medicine of the Second Affiliated Hospital of Dalian Medical University, Dalian, China
- 4Department of Gastroenterology of the Second Affiliated Hospital of Dalian Medical University, Dalian, China
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Objective: High-density lipoprotein cholesterol (HDL-C), non-HDL-C, and the ratio of non-HDL-C to HDL-C (NHHR) are closely correlated with multiple metabolic diseases. This study aims to dissect their associations and differences in relation to new-onset MASLD.: Data were collected from research subjects at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Participants were stratified by quartiles of HDL-C, non-HDL-C, and NHHR. Kaplan-Meier analysis, Cox proportional hazards models, restricted cubic splines (RCS), sensitivity analyses, and receiver operating characteristic (ROC) curves were employed to evaluate associations between NHHR, non-HDL-C, HDL-C, and new-onset MASLD and compare predictive performance across lipid parameters.Results: A total of 36,897 participants (mean age 42.1 years; 56.5% female) were followed for a mean of 3.19 years, with 20.3% developing new-onset MASLD. Cox regression showed that compared to the Q1 group, the Q4 group of NHHR and non-HDL-C had a 134% (HR=2.34, 95% CI: 2.13-2.56) and 22% (HR=1.22, 95% CI: 1.13-1.31) higher risk of MASLD, respectively, while HDL-C was associated with a 45% lower risk (HR=0.55, 95% CI: 0.50-0.60). RCS analysis demonstrated nonlinear relationships for NHHR (threshold = 2.54) and HDL-C (threshold = 1.31 mmol/L), whereas non-HDL-C displayed a linear, positive association with MASLD risk. Stratified analyses revealed that elevated non-HDL-C levels conferred higher MASLD risk in men, whereas females, younger adults, and individuals with lower cardiometabolic burden (BMI <24 kg/m², nonhypertensive, and nonhyperuricemic status) showed steeper increases in MASLD risk with rising NHHR quartiles. ROC analysis indicated NHHR was superior to other lipid parameters in predicting MASLD risk.Decreases in HDL-C levels and increases in non-HDL-C and NHHR levels may increase the risk of MASLD. The NHHR can be used as a new index that is stronger than other lipoproteins for the prediction of MASLD.
Keywords: Non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio, Non-high-density lipoprotein cholesterol, High-density lipoprotein cholesterol, Metabolic dysfunction-associated steatotic liver disease, Retrospective study
Received: 01 Mar 2025; Accepted: 28 May 2025.
Copyright: © 2025 Leng, Chen, Miao, Hu, Song, He and Deng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Song Leng, Second Affiliated Hospital of Dalian Medical University, Dalian, China
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