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. 2025 Jul 1;23(1):32.
doi: 10.1186/s12963-025-00396-8.

Non-linear correlation between the ratio of high-density lipoprotein cholesterol to C-reactive protein and all-cause mortality in adults: an extensive study based on nationwide data

Shujuan Qiu  1 , Jinhua Zhu  2 , Mengxue Yuan  1 , Zhentao Guo  3
Affiliations

Non-linear correlation between the ratio of high-density lipoprotein cholesterol to C-reactive protein and all-cause mortality in adults: an extensive study based on nationwide data

Shujuan Qiu et al. Popul Health Metr. .

Abstract

Background: Previous research has explored the association between the ratio of high-density lipoprotein cholesterol to C-reactive protein (HDL-C/CRP) and the mortality risk in individuals with heart failure. This study aims to investigate the correlation between HDL-C/CRP ratio and all-cause mortality through the analysis of extensive data derived from the general public.

Methods: This study analyzed NHANES data and surveyed 28,544 adults from America. Survival outcomes were evaluated using Kaplan-Meier curves, while a survey-weighted multivariable Cox proportional hazards model was employed. Restricted cubic splines (RCS) and hierarchical analysis were used to investigate associations and interactions, respectively. Additionally, the ability of lnHDL-C/CRP to predict all-cause death was assessed using receiver operating characteristic curves.

Results: During a mean follow-up period of 156.5 months, 5965 (20.9%) died from any cause. Weighted RCS analysis revealed an L-shaped association between HDL-C/CRP ratio and all-cause mortality. Below a lnHDL-C/CRP of 6.65 (HDL-C/CRP ratio of 773), the likelihood of all-cause death decreased by 14% with every 1-point rise in lnHDL-C/CRP [HR (95% CI) 0.86 (0.81, 0.90)]. Including lnHDL-C/CRP in the baseline risk model significantly enhanced its predictive power for mortality. Consistent findings were observed in subgroups, with individuals under 60 years or with a BMI over 30 showing a stronger correlation between HDL-C/CRP ratio and overall mortality risk.

Conclusions: The association between HDL-C/CRP ratio and overall mortality in the general US adult population is non-linear, particularly significant in adults under 60 years old and obese individuals. HDL-C/CRP ratio could be regarded as a potential marker for assessing mortality risk.

Keywords: All-cause mortality; General population; HDL-C/CRP ratio; Non-linear association.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The NCHS conducted the survey and received approval from the NCHS Institutional Review Board (IRB). Prior to data collection and NHANES health examinations, all eligible subjects provided informed consent. It is verified by all authors that the methods were carried out following the appropriate NHANES Analytic Guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Survey weighted Kaplan–Meier survival analysis curves for all-cause mortality by HDL-C/CRP ratio. lnHDL-C/CRP Tertiles(T): T1: < 4.87; T2: 4.87–6.06; T3: ≥ 6.06
Fig. 2
Fig. 2
Association between HDL-C/CRP ratio and all-cause mortality in US adults. Each hazard ratio was computed with a lnHDL-C/CRP level of 5.47 as the reference. Adjusted for gender, age, race/ethnicity, smoking status, BMI, physical activity, albumin, uric acid, HbA1c, eGFR, diabetes, hypertension, and cardiovascular disease. HDL-C, High density lipoprotein cholesterol; CRP, C-reactive protein. BMI, body mass index; HbA1c, glycosylated hemoglobin; eGFR, glomerular filtration rate; HR Hazard Ratio.CI, confidence interval
Fig. 3
Fig. 3
Receiver operating characteristic curves assessing the predictive ability of lnHDL-C/CRP for all-cause mortality. Baseline risk model vs + HbA1c. Baseline risk model includes age, smoking status, BMI, eGFR, albumin, diabetes, and CVD. HDL-C, High density lipoprotein cholesterol; CRP, C-reactive protein. BMI, body mass index; eGFR, glomerular filtration rate; CVD, cardiovascular disease
Fig. 4
Fig. 4
Survey weighted subgroup analysis of the association between HDL-C/CRP ratio and all-cause mortality. Adjusted for gender, age, race/ethnicity, smoking status, BMI, physical activity, albumin, uric acid, HbA1c, eGFR, diabetes, hypertension, and cardiovascular disease, except the subgroup factors themselves. HDL-C, High density lipoprotein cholesterol; CRP, C-reactive protein. BMI, body mass index; HbA1c, glycosylated hemoglobin; eGFR, glomerular filtration rate; CI, confidence interval
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