Abstract
BACKGROUND: This meta-analysis aimed to evaluate the association between serum C-reactive protein (CRP) levels and delirium risk, encompassing postoperative delirium (POD) and delirium secondary to other medical conditions. METHODS: A systematic search was conducted across PubMed, Web of Science, and the Chinese National Knowledge Infrastructure database. The odds ratio (OR) with their 95% confidence intervals (CI) from each study were extracted and used to estimate the effects. Meta-regression analysis was utilized to identify potential sources of heterogeneity. Subgroup analyses were applied to explore the association under different disease types (POD vs. non-POD), and age groups (>70 years or ≤70 years) among delirium patients. RESULTS: A total of 9,002 patients from 32 included studies were analyzed in this meta-analysis. Of these, 21 studies comprising 5,006 patients examined the association of CRP with delirium using continuous data, while 11 studies involving 3,996 patients employed categorical data by dividing patients into high and low groups based on the CRP value. The pooled data from continuous data showed that CRP levels were significantly associated with delirium (OR: 1.10, 95% CI: 1.01-1.20, p = 0.030); and the pooled data from categorical data revealed that high CRP levels increased the risk of delirium (OR: 2.66, 95% CI: 2.00-3.53, p < 0.001). Significant heterogeneity was found across the studies; however, meta-regression analysis did not demonstrate that variables such as age, study location, study design, disease type, and diagnostic criteria were primary sources of heterogeneity. Subgroup analysis indicated that CRP levels were associated with an increased risk of delirium regardless of disease type and age group. CONCLUSION: Elevated serum CRP levels are significantly but modestly associated with delirium risk in diverse clinical populations. Given the observational nature of the included studies and high heterogeneity, these findings support CRP as a correlate, rather than a causal mediator, of delirium-related inflammation.