Mitral annular calcium (MAC) has been shown to be an independent predictor of stroke, but the basis for this association remains incompletely defined. We investigated the extent to which aortogenic embolism may mediate the MAC-stroke relationship. In a cross-sectional study of patients referred for transesophageal echocardiography at our institution for evaluation of cerebral ischemia, we assessed the relationship between MAC and proximal and distal complex aortic atheroma (CAA). Among 419 patients composing the study cohort, MAC was associated with atherosclerosis risk factors, prior cardiovascular disease, atrial fibrillation, ipsilateral large-artery stenosis, left-heart abnormalities and aortic valve calcium. MAC was associated with CAA of the proximal and distal thoracic aorta in unadjusted analyses, and these associations became stronger with increasing MAC severity. After adjustment for clinical and echocardiographic covariates, MAC exhibited a significant association with proximal and distal CAA in the entire cohort. In patients without an alternative potential mechanism for cerebral ischemia, however, the relationship with proximal CAA became more pronounced (adjusted odds ratio=2.74, 95% confidence interval=1.22-6.16), but that for distal CAA changed little and became non-significant (adjusted odds ratio=1.97, 95% confidence interval=0. 87-4.45). In this cohort with cerebral ischemia, MAC was significantly associated with proximal and distal CAA independent of clinical and echocardiographic covariates, but among individuals without identifiable alternative mechanisms, the magnitude of the relation increased only for proximal CAA. These findings support the role of proximal CAA as a direct mediator of the increased stroke risk associated with MAC.Mitral annular calcium (MAC) 1 is an independent predictor of stroke, 2-4 but the mechanisms underlying the MAC-stroke relationship are not well delineated. 4 Protruding, ulcerated or mobile atheromatous plaques of the thoracic aorta also exhibit a strong association with stroke; 5-7 the presence of complex plaque of the ascending aorta and aortic arch quadruples the risk
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