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Introduction: Aortic (Ao) and carotid (Ca) atherosclerosis (Athero) and cerebrovascular disease (CVD) are common and associated with high morbidity and mortality in systemic lupus erythematosus (SLE). However, it is unknown whether Ao and Ca Athero are parallel or divergently associated with CVD.Methods: 77 SLE patients (age 37±12 years, 70 women) and 26 age-and-sex matched healthy controls (age 34±11 years, 22 women) underwent 1) transesophageal echocardiography and carotid ultrasonography for detection of Athero defined as intima-media thickening (≥2SD of the mean intima-media thickness in controls) or plaques (focal and protruding intima-media thickening that exceeds 50% of the surrounding vessel wall); 2) assessment of prevalent CVD defined as acute stroke/TIA, neurocognitive dysfunction, or focal brain injury on MRI; and 3) assessment of incident stroke/TIA, cognitive disability, or death during a median follow-up of 52 months.Results: Ao but not Ca Athero was more frequent in patients than in controls (42% versus 8%, p=0.006, and 17% versus 12%, p=0.75). Acute stroke/TIA occurred in 31% of patients, focal brain injury in 54%, neurocognitive dysfunction in 44%, or any CVD in 70% of patients. During follow-up, 26% of patients developed stroke/TIA, cognitive disability, or died. Ao but not Ca Athero was associated with prevalent focal brain injury (p=0.06), cognitive dysfunction (p=0.04), or any CVD (p=0.03) (Table 1). Ca Athero was associated with acute stroke/TIA (p=0.02), but Ao Athero detected more patients with these conditions (50% versus 33%). Although Ao and Ca Athero were associated with incident stroke/TIA, cognitive disability, or death (both p≤0.01), Ao Athero identified more patients with these events (65% versus 45%).Conclusion: In patients with SLE Ao as compared to Ca Athero is associated with higher prevalence and incidence of CVD and mortality. Therefore, Ao Athero may be a stronger pathogenic factor or marker for CVD in SLE than Ca Athero.