Carotid atherosclerosis and cerebral white matter lesions: sex-stratified mediation model

Background: White matter lesions (WML), associated with microvascular damage, have been linked to carotid atherosclerosis, although the evidence remains heterogeneous. objective: To evaluate whether metabolic pathways mediate the association between the number of carotid plaques and WML, considering sex moderation. Method: Secondary analysis of 1,904 adults with brain magnetic resonance imaging and carotid ultrasound. A sex-moderated mediation model with 5,000 bootstrap resamples was applied. LDL cholesterol, HDL cholesterol, triglycerides, glycated hemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure, and body mass index were evaluated as mediators, adjusting for age. results: A higher number of carotid plaques was associated with greater likelihood of WML in both women (B = 0.583; p < 0.001) and men (B = 0.491; p < 0.001). Significant indirect effects were identified mediated by HbA1c (women: 0.1206; men: 0.0328) and SBP (women: 0.0702; men: 0.0354). The plaque and sex interaction was significant for LDL and triglycerides. conclusions: The association between carotid plaques and WML may be partially mediated by HbA1c and SBP, with stronger effects in women. Longitudinal studies are required to confirm these mechanisms and their clinical relevance.