Inflammatory Genotype Moderates the Association Between Anxiety and Systemic Inflammation in Adults at Risk for Cardiovascular Disease

Background Cardiovascular disease is a significant health problem in the United States, attributed to more than 30% of all deaths annually. Anxiety has been associated with cardiovascular disease risk and is thought to be associated with cardiovascular disease risk through inflammatory pathways. Objective The purposes of this study were to examine the relationship between anxiety and systemic inflammation in individuals at risk for cardiovascular disease and to determine if single-nucleotide polymorphisms (SNPs) associated with inflammation moderate this relationship. Methods A secondary analysis was conducted using baseline data from a study investigating the impact of genetics on response to a cardiovascular disease risk reduction intervention. Anxiety was measured using the Brief Symptom Inventory. Protein levels for C-reactive protein and interleukin-6 (IL-6) were measured in serum, and genomic DNA was assayed for SNPs in the C-reactive protein, IL-6, and IL-6R genes. Multiple linear regressions were performed to examine if anxiety predicted inflammation and if SNPs moderated associations. Results Participants (N = 398) were white, aged 51 +/- 13 years, and 73% women. There was a significant interaction between rs4129267 genotype and anxiety (P = .010), with the association significant only for individuals with the CC genotype (b = 0.243, SE = 0.04, P < .001). No moderation effect existed for rs1205 or rs1800797. Conclusion Anxiety was positively associated with IL-6 protein levels, but moderation analysis indicated that this was significant only for individuals with the rs4129267 CC genotype. This suggests that genotypic differences may exist in anxiety response, placing certain individuals at higher risk for inflammation and, subsequently, cardiovascular disease.