Abstract Body: Introduction. Allostatic load (AL) is a composite measure of multisystem physiological dysregulation. Elevated AL has been identified as a precursor to cardiovascular and metabolic diseases in older adults, but its role in young adults remains unclear.

Methods. In this cross-sectional study, we examined the association between AL and three markers of subclinical atherosclerosis among 304 young adults (mean age=25.1 years) participating in the MetaAir2 study from 2018 to 2025. AL score was generated from 14 biomarkers representing four physiological domains: 1) HPA axis and sympathetic nervous system: cortisol, epinephrine, norepinephrine; 2) Inflammatory system: C-reactive protein, interleukin-6; 3) Metabolic system: BMI, total cholesterol, HDL, HbA1c, glucose, insulin; and 4) Cardiovascular system: systolic and diastolic blood pressure, heart rate. Each biomarker was dichotomized as 1 (high risk; exceeding clinical cut points) or 0 (low risk). System-specific scores were calculated as the mean of dichotomized biomarkers within each system. The four system-specific scores were then summed to generate a total AL score (range: 0–4), with higher values indicating greater physiological dysregulation. Subclinical atherosclerosis was assessed using 3 measures obtained from carotid artery ultrasonography: intima-media thickness (IMT), arterial stiffness (distensibility), and gray-scale median of the intima-media complex (IM-GSM). Associations between AL and subclinical atherosclerosis were evaluated using multivariable linear regression, adjusting for age, sex, race, ethnicity, physical activity, and parental education.

Results. Higher overall allostatic load (AL) scores were significantly associated with greater IMT (β=25.5, 95% CI: 8.7, 39.6), lower arterial distensibility (β=-3.9, 95% CI: -5.7, -2.1), and lower IM-GSM (β=-3.8, 95% CI: -7.4, -0.3), indicating that increased physiological wear and tear is linked to thicker arterial walls, reduced elasticity, and greater lipid deposition—characteristics of early atherosclerosis. Further, system-specific analysis indicated that the inflammatory system score was significantly associated with IMT and IM-GSM, the metabolic system was associated with all three markers, and the cardiovascular system was associated with arterial distensibility only.

Conclusion. Higher AL scores across multiple physiological systems are associated with greater risk of specific components of subclinical atherosclerosis in young adults.