Stress-related risk profiles and low-grade inflammation in a real-world clinical cohort

Background Chronic diseases impose a substantial burden on health systems. Psychological stress is an adaptive response but, when prolonged, may contribute to dysregulation and is associated with increased risk of chronic diseases, including cardiovascular disease. Inflammation represents a key biological pathway linking stress and chronic disease and can be assessed using routine biomarkers. Purpose We quantified perceived chronic stress in a hospital-based cohort to identify subgroups at increased chronic disease risk. We further examined associations between stress and systemic inflammation using C-reactive protein (CRP) and a composite inflammation score, with sensitivity analyses to limit acute inflammatory outliers. Methods A 58-item questionnaire was administered to patients and visitors in a tertiary hospital. Perceived stress was assessed using four items adapted from the Perceived Stress Scale (PSS-10) and was divided into three groups. The cutpoints were distribution-informed and the analysis was considered exploratory. In participants with laboratory data, low-grade inflammation was summarized by a composite score based on CRP, platelet count, and neutrophil-to-lymphocyte ratio (NLR), excluding CRP ≥50 mg/L. Log(CRP), platelets, and NLR were z-standardized, equally weighted, summed, and rescaled from 0 through 1. Sensitivity analyses included CRP winsorization (p99) and alternative restrictions. Multivariable linear regression identified independent correlates of stress; the inflammation score was added in the laboratory subset. Results Among 1104 participants with stress data, 267 (24.2%) had low, 646 (58.5%) intermediate, and 191 (17.3%) high stress levels. Age was similar across groups, whereas female sex was more frequent in the high-stress group (23.2% vs 45.3%; p<0.001). Higher stress was accompanied by higher depressive symptoms and sleep problems (both p<0.001), higher medication use and chronic disease burden (both p<0.001), and lower socioeconomic indicators (education p=0.001; net household income p<0.001). Leisure-time physical activity decreased with increasing stress (p<0.001). In 415 participants with laboratory data, stress correlated with the low-grade inflammation score (Spearman’s ρ=0.20; p<0.001). In multivariable regression, higher stress was independently associated with female sex, greater depressive symptoms, and lower physical activity, while older age and private health insurance were associated with lower stress. In the laboratory subset, the inflammation score remained independently associated with stress (β=0.20; p=0.001). Conclusion Higher perceived stress levels were strongly associated with chronic disease burden and low-grade systemic inflammation. Assessment of chronic stress through targeted screening including preventive counselling may help identify highly vulnerable patients and address this modifiable risk domain.Table 1Figure 1