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.
Guo et al. (Tue,) studied this question.