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. 2025 May 21;22(1):46.
doi: 10.1186/s12986-025-00942-z.

Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD): data from the NHANES III (1988-1994)

Ying Zhang  1 , Peng-Yu Luo  1 , Yu-Na Tang  1 , Jing Wang  1 , Shuai Gao  1 , Yu-Chen Fan  1 , Kai Wang  2   3
Affiliations

Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD): data from the NHANES III (1988-1994)

Ying Zhang et al. Nutr Metab (Lond). .

Abstract

Background: The prognostic value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study aimed to evaluate the associations between the NHHR and all-cause and cause-specific mortality in patients with MASLD.

Methods: Data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES III and the National Death Index (NDI). The NHHR was calculated according to the formula. The results of mortality associated with the NDI were recorded as of December 31, 2019. We used a multivariate Cox proportional hazard model and restricted cubic spline (RCS) regression to assess the associations between the NHHR and all-cause and cause-specific mortality. In addition, subgroup analyses were performed to explore the relationships between the NHHR and all-cause and cause-specific mortality.

Results: This study included 3155 patients with a definite diagnosis of MASLD. A total of 1,381 (43.8%) patients with MASLD died, and 1,774 (56.2%) survived. Multivariate Cox proportional hazards model analysis showed that NHHR was not significantly associated with all-cause mortality in MASLD patients. The RCS curve showed a significant nonlinear trend between the NHHR and all-cause mortality in patients with MASLD. Subgroup analysis revealed that the NHHR was better suited to predict cardiovascular mortality in patients without advanced fibrosis.

Conclusions: Our study revealed the clinical value of the NHHR in the prediction of mortality in the MASLD population. The NHHR can be used as a biomarker for follow-up in people without advanced fibrosis.

Keywords: MASLD; Mortality; NHANES III; NHHR.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All survey protocols were approved by the National Center for Health Statistics Ethics Review Board in USA. All participants provided written informed consent before participation. Consent for publication: All authors have reviewed and approved the final version of the manuscript. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Nonlinear relationships between the NHHR and mortality according to the three models. The solid lines in the figure represent the HRs, and the shaded regions represent the 95% CIs. Model 1 was not adjusted. Model 2 was adjusted for age, sex, race, education level, marital status, and income; Model 3 was further adjusted for smoking status, sedentary lifestyle status, diabetes status, and hypertension status on the basis of Model 2. (A) Model 1 and all-cause mortality (B) Model 2 and all-cause mortality (C) Model 3 and all-cause mortality (D) Model 1 and cardiovascular mortality (E) Model 2 and cardiovascular mortality (F) Model 3 and cardiovascular mortality (G) Model 1 and diabetes mortality (H) Model 2 and diabetes mortality (I) Model 3 and diabetes mortality
Fig. 2
Fig. 2
Subgroup analysis of the association between the NHHR and MASLD mortality. Red dots indicate the HR, and the bars on both sides of the dots indicate the 95% CI of the HR. (A) NHHR and all-cause mortality. (B) NHHR and cardiovascular mortality. (C) NHHR and diabetes mortality
See this image and copyright information in PMC

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