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 2173 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 (T₂DM) (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 % T₂DM (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.