Circulating Interleukin-6 Levels Are Associated with Abdominal Aortic Aneurysm Presence: A Meta-analysis and Meta-regression of Case-Control Studies

Background: In a number of relatively small-size studies, investigators have measured and compared circulating interleukin-6 (IL-6) levels in cases with abdominal aortic aneurysm (AAA) and controls without AAA to assess its possible role in the pathogenesis or progression of AAA. To summarize the present evidence for an association between circulating IL-6 levels and AAA presence, we performed a meta-analysis of case-control studies that compared circulating IL-6 levels between patients with AAA and subjects without AAA. Methods: MEDLINE and EMBASE were searched through December 2013 using Web-based search engines (PubMed and OVID). Eligible studies were case-control studies of patients with AAA and subjects without AAA reporting circulating IL-6 levels. For each study, data regarding plasma or serum IL-6 levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Mixed-effects (unrestricted maximum likelihood) meta-regression analyses were performed to determine whether the differences in circulating IL-6 levels were modulated by the prespecified factors. Results: Our search identified 13 eligible studies enrolling a total of 1,029 cases with AAA and 924 controls without AAA. Pooled analysis of the 13 studies demonstrated significantly greater circulating IL-6 levels in the AAA group than those in the control group (random-effects SMD 0.59; 95% CI 0.37-0.80; P for effect <0.00001; P for heterogeneity <0.0000). The meta-regression coefficient for the mean age (P = 0.10196) and the proportion of current smokers (P = 0.29893) was not statistically significant. That for the mean AAA diameter, however, was significantly positive (coefficient 0.02789; 95% CI 0.00778-0.04800; P = 0.00657), and that for the proportion of men was significantly negative (coefficient -0.01823; 95% CI -0.03202 to -0.00445; P = 0.00952). Conclusions: Circulating IL-6 levels are greater in patients with AAA than those in subjects without AAA, which suggest that greater circulating IL-6 levels are associated with AAA presence. As the mean AAA diameter and the proportion of men increase, circulating IL-6 levels in patients with AAA are respectively more and less greater than those in controls without AAA.