Psychosocial and behavioural exposome dysregulation triggers immunometabolic distress- related subclinical atherosclerosis
S Morini, F R Jimenez Trinidad, A D'Aiello, L Genuardi, D Pedicino, D Tarquini, A De Ciutiis, G Iannaccone, M Brecciaroli, A Buffon, S Filomia, A De Prisco, A Santoliquido, G Liuzzo, A SeverinoAbstract
Background
Beyond traditional cardiovascular risk factors, the exposome, encompassing psychosocial and behavioural component such as diet, physical activity, stress, sleep quality or smoking, may contribute to immunometabolic imbalance and the development of atherosclerosis.
Purpose
To investigate the effect of the psychosocial and behavioural exposome on immunometabolic distress mediating subclinical atherosclerosis.
Methods
We analysed data from the CV-PREVITAL study, a multicentre, prospective, randomized, controlled, open-label trial of primary cardiovascular prevention enrolling 30,000 Italian individuals. Sociodemographic, anthropometric, and clinical data were systematically collected. Psychosocial and behavioural exposome components were evaluated using standardized questionnaires. The present analysis includes 1,000 consecutive participants (53% male; mean age 57±7 years) from our centre, in which inflammatory biomarkers and subclinical atherosclerosis were assessed. Subclinical atherosclerosis was assessed by carotid and femoral echo-Doppler-measured Intima-to-Media Thickness (IMT) and categorized as absent (IMT ≤0.9 mm), early (IMT 0.9–1.5 mm) or mild (IMT>1.5 mm).
Results
Participants displayed a broad range of cardiovascular risk profiles. Classical risk factors (dyslipidaemia, hypertension, overweight, and HbA1c) were strongly associated with subclinical atherosclerosis. Psychosocial and behavioural exposome components were directly associated with cardiovascular risk factors and with estimated cardiovascular risk (SCORE2), particularly among individuals with atherosclerosis, but not independently with atherosclerotic burden. Mediation analysis demonstrated a significant indirect contribution of exposome features to atherosclerosis through inflammatory activation (IL-6 pathway) and metabolic modulation, notably via HDL cholesterol and HbA1c.
Conclusions
Psychosocial and behavioural exposome dysregulation contributes to subclinical atherosclerosis by triggering immunometabolic distress, highlighting the exposome as a relevant upstream determinant of cardiovascular risk.