Mediating effect of pro-inflammatory cytokines in the association between depression, anxiety, and cardiometabolic disorders in an ethnically diverse middle-aged and older population

Abstract

Introduction: Neuroinflammation has been significantly associated with depression and anxiety, both of which are significantly associated with higher cardiometabolic risk. Systemic inflammation was also commonly described in patients with cardiometabolic disorders. It is thus unclear whether pro-inflammatory cytokines might mediate the effect between depression, anxiety, and cardiometabolic disorders, particularly in advanced ages. Methods: The multiethnic [&ge;] 50-year-old study population is a subset of the Health and Aging Brain Study: Health Disparities (HABS-HD). Logistic and linear regression adjusted for relevant covariables were used to assess associations. Non-linear models were evaluated using restricted cubic splines. Mediation analysis was used to determine the role of inflammation (Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukine-6 (IL-6)). Models were corrected for multiple testing using the False Discovery Rate (FDR)method. Results: In the 2093 included cases, depression and/or anxiety were significantly associated with 62% higher odds of CVD (OR=1.62 [95% CI: 1.22-2.15]), 54% of type 2 diabetes (OR=1.54 [95% CI: 1.29-1.85]), 26% of hypertension (OR=26% [95% CI: 1.07-1.48]), and 29% of obesity (OR=1.29 [95% CI: 1.11-1.51]). Only IL-6 showed a significant mediating role in the association of depression and/or anxiety with CVD (10%, p-valueFDR=0.016), type 2 diabetes (13%, p-valueFDR<0.001), hypertension (16%, p-valueFDR<0.001), and obesity (23%, p-valueFDR<0.001). Conclusions: Depression and anxiety are significantly associated with higher odds of major cardiometabolic disorders. IL-6 partly mediated most of these associations. It is, therefore, crucial to recognize the role of depression, anxiety, and neuroinflammation in the preventive and therapeutic management of cardiometabolic disorders.