Chronic emotional stress and mediating role of Interleukin-6 in the association with cardiometabolic disorders in a multiethnic middle-aged and older US population

Introduction Chronic emotional stress is a well-recognized risk factor for psychiatric and cardiometabolic disorders. The mediating role of low-grade inflammation in older, ethnically diverse populations has never been studied. Methods The multiethnic ≥ 50-year-old study population is a subset of the Health and Aging Brain Study: Health Disparities (HABS-HD) study. Adjusted logistic and linear regression were used to assess associations. Statistical mediation analysis with non-parametric bootstrapping of confidence intervals was used to determine the intermediate role of Interleukin-6 (IL-6). Results The study included 2,173 participants (50-92 years). Black participants disclosed higher chronic stress levels than White and Hispanic participants. Having a chronic stress total score ≥ six points is associated with 53% higher odds of disclosing concomitant cardiovascular disease (CVD) (adj.OR=1.53 [1.10-2.53]), 31% of Type-2 diabetes (T 2 DM) (adj.OR=1.31[1.06-1.62]), 23% of hypertension (adj.OR=1.23 [1.02-1.49]), and 30% obesity (adj.OR=1.3[1.09-1.55]). These associations were statistically mediated by IL-6 (12% ( p-value FDR =0.012) of the association with CVD, 17% T 2 DM ( p-value FDR <0.001), 18% hypertension ( p-value FDR <0.001), and 29% obesity ( p-value FDR =0.005)). Conclusions The study highlights a further aspect of the pathophysiological mechanisms involved in the brain-body communication. While IL-6 partially explains statistical associations between chronic emotional stress and major cardiometabolic disorders, no causal effects can be inferred from this study owing to the cross-sectional design. Larger longitudinal studies are needed to better clarify the temporal relationship between the events and to build upon our findings.