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.