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. 2025 Mar 12;15(1):8538.
doi: 10.1038/s41598-025-93518-z.

There is a linear negative correlation between lipoprotein(a) and non-alcoholic fatty liver disease

Chunbo Li  1 , Mengchun Li  2 , Zhenwei Wang  3
Affiliations

There is a linear negative correlation between lipoprotein(a) and non-alcoholic fatty liver disease

Chunbo Li et al. Sci Rep. .

Abstract

This study aimed to investigate the relationship between lipoprotein(a) [Lp(a)] levels and non-alcoholic fatty liver disease (NAFLD), and to analyze its linear association and subgroup differences. This cross-sectional analysis was based on data from 2308 participants in the National Health and Nutrition Examination Survey (NHANES) III. Multivariate logistic regression models were used to assess the association between Lp(a) and NAFLD, adjusting for demographic factors, lifestyle behaviors, comorbidities, and biomarkers. Subgroup analyses were conducted based on age, sex, body mass index (BMI), diabetes, and hypertension. Restricted cubic spline (RCS) regression model was used to explore the nonlinear relationship between Lp(a) and NAFLD. Higher Lp(a) levels were significantly associated with a lower risk of NAFLD. In the fully adjusted model, compared to the lowest quartile group (Q1), the third and fourth quartiles (Q3 and Q4) had significantly reduced risks of NAFLD [Q3: OR = 0.701, 95% CI 0.511, 0.961; P = 0.027; Q4: OR = 0.605, 95% CI 0.438, 0.835; P = 0.002]. Subgroup analysis showed that the association between higher Lp(a) levels and reduced NAFLD risk was significant in individuals aged 50 years and older, those with BMI ≥ 30 kg/m2, non-diabetics, and those with hypertension. RCS analysis further confirmed a linear negative association between Log10Lp(a) and NAFLD risk (P = 0.029, P nonlinearity = 0.888). There is a significant linear negative association between Lp(a) levels and the risk of NAFLD, suggesting that Lp(a) may serve as a potential biomarker for assessing NAFLD risk.

Keywords: Lipoprotein(a); NHANES; Non-alcoholic fatty liver disease; Nonlinearity; Restricted cubic spline.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was conducted using publicly available data from the NHANES, which is collected and managed by the U.S. Centers for Disease Control and Prevention (CDC). NHANES data are de-identified and made publicly accessible, ensuring participant confidentiality. Therefore, this study did not require additional ethical approval or informed consent. The research followed the principles of the Declaration of Helsinki. Consent for publication: Not applicable.

Figures

Fig. 1
Fig. 1
Flowchart of study population enrollment. NHANES, National Health and Nutrition Examination Survey; Lp(a), lipoprotein(a).
Fig. 2
Fig. 2
Restricted cubic spline plot of the association between Lp(a) and NAFLD. Lp(a), lipoprotein(a); NAFLD, non-alcoholic fatty liver disease.
See this image and copyright information in PMC

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