Reviews in Cardiovascular Medicine (Jul 2025)
Vitamin D as a Key Mediator Between C-reactive Protein to Albumin Ratio and Congestive Heart Failure in an Elderly Population: An Innovative Exploration Using the NHANES Database
Abstract
Background: The C-reactive protein-to-albumin ratio (CAR), a marker of inflammation and nutritional status (calculated as C-reactive protein [CRP]/albumin [ALB]), is associated with increased mortality in congestive heart failure (CHF). However, whether vitamin D modulates the CAR-CHF relationship remains unclear. Using data from the National Health and Nutrition Examination Survey (NHANES), this study aimed to investigate the mediating role of vitamin D in the association between CAR and CHF among older adults, with implications for cardiovascular disease prevention. Methods: Data from NHANES 2001–2010 were analyzed, including adults aged ≥65 years. Multivariate logistic regression was used to assess the independent association of CAR and 25-hydroxyvitamin D [25(OH)D] with CHF. Pearson correlation evaluated bivariate relationships between continuous variables (vitamin D, CAR), while Spearman correlation assessed associations between the dichotomous CHF status and continuous variables (vitamin D, CAR). Mediation analysis (Hayes’ PROCESS Model 4, 5000 bootstrap samples) tested whether 25(OH)D mediated the CAR-CHF link. Subgroup analyses explored effect modification by age, sex, and comorbidities. Results: A total of 4128 participants (mean age: 70.0 years; 55.81% male) were included, with 247 (5.98%) diagnosed with CHF. Vitamin D deficiency (25(OH)D <20 ng/mL) and insufficiency (20–30 ng/mL) were prevalent (71.2%). Key findings included: Bivariate associations: Lower 25(OH)D correlated with higher CAR (r = –0.12, p = 0.004) and increased CHF risk (Spearman ρ = –0.061, p < 0.01), while CAR was positively correlated with CHF (Spearman ρ = 0.080, p < 0.01). Multivariate analysis: CAR was an independent risk factor for CHF (adjusted OR for highest vs. lowest quartile: 1.96, 95% confidence interval (CI): 1.31–2.95, p < 0.001; p-trend < 0.001. Vitamin D sufficiency (25(OH)D ≥30 ng/mL) was associated with a lower CHF risk compared to deficiency (25(OH)D <20 ng/mL, OR: 0.56, 95% CI: 0.38–0.83, p = 0.003), indicating that deficiency was indirectly linked to higher risk. Mediation effect: 25(OH)D partially mediated the CAR-CHF association, explaining 3.00% of the total effect (indirect effect: 0.002, 95% CI: 0.001–0.005, p = 0.039). Predictive value: CAR had modest accuracy for CHF (area under the curve (AUC) = 0.597, 95% CI: 0.560–0.634), with an optimal cut-off of 0.149 (sensitivity: 59.1%, specificity: 56.4%). Conclusion: Elevated CAR and vitamin D deficiency are independently associated with increased CHF risk in older adults. Vitamin D partially mediated the association between CAR and CHF, underscoring its role in linking inflammation/nutrition status to cardiovascular risk. Clinicians should monitor both biomarkers in CHF prevention, prioritizing inflammation control and vitamin D repletion in high-risk populations.
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