Coronary artery calcification as a predictor of mortality and major cardiovascular events in patients with chronic kidney disease: a systematic review and meta-analysis
N Vythoulkas-Biotis, N Madouros, T Theodoropoulou, A Apostolos, N Ktenopoulos, D D ChlorogiannisAbstract
Background
Patients with chronic kidney disease (CKD) are at an increased risk for cardiovascular disease due to accelerated ectopic calcification, especially when involving the coronary arteries.
Purpose
This systematic review and meta-analysis aims to identify the pooled risk of major adverse cardiovascular events (MACE) and all-cause mortality in patients with CKD and CAC.
Methods
A systematic search using PubMed, Scopus, and Cochrane databases was conducted to identify studies reporting high and/or low CAC scores and their association with all-cause mortality and MACE in patients with CKD. Hazard ratios (HR) for each study were pooled using random-effects models and heterogeneity was assessed using the I² statistic. Subgroup analyses were performed according to CAC categories, and univariate and multivariate meta-regression analyses explored potential moderators including publication year, age, and male sex.
Results
A total of 21 studies, comprising of 42,859 patients, were included in the meta-analysis. CAC was identified as a significant prognostic factor for both all-cause mortality (HR: 1.89; 95%CI: 1.55 - 2.30; p < 0.001) and MACE (HR: 2.16; 95%CI: 1.61 – 2.88; p < 0.001). Test for subgroup differences revealed that higher CAC scores were associated with increased risk of all-cause mortality (CAC 1-100: HR: 1.39, 95%CI: 1.17 – 1.65, I2 = 0%; CAC 100-400: HR: 2.12, 95%CI: 1.68 – 2.68, I2 = 0%; CAC >400: HR: 2.63, 95%CI: 2.02 – 3.43, I2 = 0%; p<0.01). Regarding MACE, although the risk increased progressively with higher CAC scores (CAC 1-100: HR: 2.07, 95%CI: 1.33 – 3.22, I2 = 66.6%; CAC 100-400: HR: 2.91, 95%CI: 1.46 – 5.80, I2 = 78.2%; CAC >400: HR: 5.07, 95%CI: 1.96 – 13.13, I2 = 64.1%), the between-subgroup differences were not significant (p=0.22). Meta-regression demonstrated a significant moderating effect of publication year on all-cause mortality in both univariate and multivariate models.
Conclusions
This meta-analysis highlights that patients with CKD and CAC are at a significant risk for MACE and all-cause mortality, with this relationship being linear. These findings underscore the prognostic value of CAC, although prospective research is needed to evaluate these associations.