Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANES

Abstract Background Several studies have suggested a potential link between cardiovascular health, inflammation, and cardiorenal syndrome (CRS). However, the exact mechanism by which inflammation affects the relationship between cardiovascular health and CRS remains unclear. CRS refers to a syndrome...

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Main Authors: Zhe Fang, Jiawen Zhao, Hongyang Gong
Format: Article
Language:English
Published: BMC 2025-08-01
Series:BMC Cardiovascular Disorders
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Online Access:https://doi.org/10.1186/s12872-025-05094-9
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author Zhe Fang
Jiawen Zhao
Hongyang Gong
author_facet Zhe Fang
Jiawen Zhao
Hongyang Gong
author_sort Zhe Fang
collection DOAJ
description Abstract Background Several studies have suggested a potential link between cardiovascular health, inflammation, and cardiorenal syndrome (CRS). However, the exact mechanism by which inflammation affects the relationship between cardiovascular health and CRS remains unclear. CRS refers to a syndrome in which dysfunction in either the heart or kidneys leads to acute or chronic dysfunction in the other organ. Life’s Crucial 9 (LC9) is a recently proposed cardiovascular health assessment tool. The neutrophil-to-albumin ratio (NPAR) is a novel inflammatory-nutritional composite biomarker that integrates neutrophil-mediated immune activation with the nutritional status reflected by albumin levels. This study aimed to explore the relationship between LC9 and CRS and assess whether NPAR modulates this association. Methods This study employed subgroup analysis, restricted cubic splines (RCS), threshold effect analysis, and multivariable logistic regression to investigate the relationships between LC9 and CRS, and NPAR and CRS. Additionally, mediation analysis was conducted to evaluate the potential role of NPAR in the relationship between LC9 and CRS. Results A total of 25,610 participants were included in the study, of whom 1,240 experienced CRS events. Multivariable logistic regression analysis revealed that for every 10-unit increase in LC9 score, the risk of CRS decreased by 36% (OR = 0.64, 95% CI: 0.55, 0.76). For each 1-unit increase in NPAR, the risk of CRS increased by 12% (OR = 1.12, 95% CI: 1.07, 1.17). After grouping LC9 and NPAR by tertiles, the highest LC9 tertile (T3) showed a 52% reduction in CRS risk compared to the lowest tertile (T1) (OR = 0.48, 95% CI: 0.26, 0.88), while the highest NPAR tertile (T3) had a 2.07-fold increase in CRS risk compared to the lowest tertile (T1) (OR = 2.07, 95% CI: 1.54–2.78). RCS analysis demonstrated a linear negative correlation between LC9 and CRS risk, whereas NPAR was non-linearly associated with CRS risk, with an inflection point at 13.66. Mediation analysis indicated that NPAR mediated 8.14% (P < 0.001) of the association between LC9 and CRS. Conclusion LC9 is significantly negatively associated with CRS risk, and this relationship is partially mediated by NPAR. Given the limitations of this cross-sectional study, further prospective studies are needed to confirm the causal relationship and explore the potential mechanisms.
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spelling doaj-art-cc969edcc6b24613bd6879c98f00a91f2025-08-24T11:06:55ZengBMCBMC Cardiovascular Disorders1471-22612025-08-0125111210.1186/s12872-025-05094-9Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANESZhe Fang0Jiawen Zhao1Hongyang Gong2Healthcare management center, The Second Hospital of Shandong UniversityJiangxi Province Environmental Monitoring CentreDepartment of Physiology, College of Medicine, Chosun UniversityAbstract Background Several studies have suggested a potential link between cardiovascular health, inflammation, and cardiorenal syndrome (CRS). However, the exact mechanism by which inflammation affects the relationship between cardiovascular health and CRS remains unclear. CRS refers to a syndrome in which dysfunction in either the heart or kidneys leads to acute or chronic dysfunction in the other organ. Life’s Crucial 9 (LC9) is a recently proposed cardiovascular health assessment tool. The neutrophil-to-albumin ratio (NPAR) is a novel inflammatory-nutritional composite biomarker that integrates neutrophil-mediated immune activation with the nutritional status reflected by albumin levels. This study aimed to explore the relationship between LC9 and CRS and assess whether NPAR modulates this association. Methods This study employed subgroup analysis, restricted cubic splines (RCS), threshold effect analysis, and multivariable logistic regression to investigate the relationships between LC9 and CRS, and NPAR and CRS. Additionally, mediation analysis was conducted to evaluate the potential role of NPAR in the relationship between LC9 and CRS. Results A total of 25,610 participants were included in the study, of whom 1,240 experienced CRS events. Multivariable logistic regression analysis revealed that for every 10-unit increase in LC9 score, the risk of CRS decreased by 36% (OR = 0.64, 95% CI: 0.55, 0.76). For each 1-unit increase in NPAR, the risk of CRS increased by 12% (OR = 1.12, 95% CI: 1.07, 1.17). After grouping LC9 and NPAR by tertiles, the highest LC9 tertile (T3) showed a 52% reduction in CRS risk compared to the lowest tertile (T1) (OR = 0.48, 95% CI: 0.26, 0.88), while the highest NPAR tertile (T3) had a 2.07-fold increase in CRS risk compared to the lowest tertile (T1) (OR = 2.07, 95% CI: 1.54–2.78). RCS analysis demonstrated a linear negative correlation between LC9 and CRS risk, whereas NPAR was non-linearly associated with CRS risk, with an inflection point at 13.66. Mediation analysis indicated that NPAR mediated 8.14% (P < 0.001) of the association between LC9 and CRS. Conclusion LC9 is significantly negatively associated with CRS risk, and this relationship is partially mediated by NPAR. Given the limitations of this cross-sectional study, further prospective studies are needed to confirm the causal relationship and explore the potential mechanisms.https://doi.org/10.1186/s12872-025-05094-9Life's crucial 9Neutrophil percentage-to-albumin ratioCardiorenal syndromeNHANESMediation analysis
spellingShingle Zhe Fang
Jiawen Zhao
Hongyang Gong
Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANES
BMC Cardiovascular Disorders
Life's crucial 9
Neutrophil percentage-to-albumin ratio
Cardiorenal syndrome
NHANES
Mediation analysis
title Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANES
title_full Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANES
title_fullStr Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANES
title_full_unstemmed Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANES
title_short Neutrophil percentage-to-albumin ratio mediates the association between life’s crucial 9 with cardiorenal syndrome: a secondary data analysis from NHANES
title_sort neutrophil percentage to albumin ratio mediates the association between life s crucial 9 with cardiorenal syndrome a secondary data analysis from nhanes
topic Life's crucial 9
Neutrophil percentage-to-albumin ratio
Cardiorenal syndrome
NHANES
Mediation analysis
url https://doi.org/10.1186/s12872-025-05094-9
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