Chronic stress biology and psychosocial profiles in inherited cardiovascular conditions: hair cortisol, endocannabinoids, and interoception

Background Inherited cardiovascular conditions (ICCs) impose enduring demands related to prognosis uncertainty, symptom monitoring, genetic risk, lifestyle adjustment, and sudden cardiac death risk. Elevated psychological distress is documented in cardiovascular populations, but biological stress regulation and its correspondence with subjective distress remain poorly characterized in ICCs. Objectives To compare longer-term stress biomarkers and psychosocial profiles in ICC patients versus community controls, and to examine relationships between chronic stress biology and self-reported distress after adjustment for demographic and lifestyle covariates. Methods Adults with clinician-adjudicated ICCs (n = 57; confirmed and under evaluation) and matched controls (n = 57) completed validated measures of depression (PHQ-9), anxiety (GAD-7), perceived stress (PSS-14), psychopathology (SCL-90-R), and interoceptive sensibility (MAIA-2). Hair samples were analyzed to quantify hair cortisol concentration (HCC) and two endocannabinoids (AEA and 2-AG) using mass spectrometry and ELISA consistent with established guidance. Multivariate analyses of covariance were used to test group differences across biomarker, distress, and interoceptive outcome sets controlling for age, sex, education, smoking, and BMI. Partial Pearson correlations assessed associations between biomarkers and distress indices with the same covariate adjustments. Results Patients exhibited significantly higher HCC than controls (adjusted difference ≈15.7 pg/mg, p = .046), whereas %AEA and %2-AG did not differ by group. Multivariate distress profiles were elevated in patients, with significant group differences in depressive and anxiety symptoms (PHQ-9, GAD-7), and multiple SCL-90-R dimensions, but perceived stress (PSS-14) was comparable across groups. Interoceptive sensibility differed qualitatively, with patients reporting greater non-distracting and body listening tendencies and reduced trust in bodily sensations. After covariate adjustment, neither HCC nor endocannabinoid measures correlated significantly with depression, anxiety, or perceived stress; distress indices were strongly intercorrelated among themselves. Endocannabinoid markers were modestly interrelated, but uncorrelated with HCC. Conclusions ICC patients display modestly elevated longer-term HPA-axis activity and broadly elevated psychological symptom burden relative to controls, but chronic neuroendocrine load appears dissociated from self-reported distress. These findings highlight the value of integrated biomarker and psychometric assessment in cardiogenetic populations and suggest that embodied physiological stress and subjective distress may diverge under chronic disease conditions.