Association of C-reactive protein to albumin ratio with all-cause and cardiovascular mortality in patients with chronic kidney disease stages 3-5

Abstract

Background: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5.

Methods: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients.

Results: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels.

Conclusions: A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.

Keywords: C-reactive protein to albumin ratio; Cardiovascular disease; Chronic kidney disease; Mortality; NHANES.

Fig. 1

Participant selection process flowchart. Abbreviation: NHANES, National Health and Nutritional Examination Survey; CAR, C-reactive protein to albumin ratio; eGFR, estimated glomerular filtration rate.

Fig. 2

Kaplan-Meier curves of the survival rate between low and high CAR groups. (A) all-cause mortality in all participants; (B) CVD mortality in all participants; (C) all-cause mortality in the population aged ≤65; (D) CVD mortality in the population aged ≤65; (E) all-cause mortality in the population aged >65; (F) CVD mortality in the population aged >65. CAR, C-reactive protein to albumin ratio.

Fig. 3

Subgroup analysis forest plot illustrating the association between high CAR group and mortality. (A) all-cause mortality; (B) CVD mortality. HRs were calculated using multivariable Cox regression models, adjusting for variables listed in the fully adjusted model (excluding stratified variables). Abbreviation: CAR, C-reactive protein to albumin ratio; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval; PIR, poverty income ratio; BMI, body mass index; eGFR, estimated glomerular filtration rate.