Abstract

Introduction: Several lines of evidence indicate that some cases of cryptogenic stroke may be due to an atrial cardiopathy that forms a nidus for thrombus formation and embolization even in the absence of atrial fibrillation (AF). Hypothesis: We hypothesized that evidence of atrial cardiopathy other than AF is independently associated with stroke. Methods: We examined the association between several markers of atrial cardiopathy and the risk of ischemic stroke among participants in the Cardiovascular Health Study, which prospectively enrolled community-dwelling adults ≥65 years of age. The exposures of interest were P-wave terminal force in electrocardiogram lead V 1 (PTFV 1 ), left atrial dimension on echocardiogram, amino terminal pro-B-type natriuretic peptide (NT-proBNP), and incident AF. The primary outcome was adjudicated ischemic stroke. We used Cox proportional hazards analysis to examine associations with stroke for all four markers together along with adjustment for traditional vascular risk factors. Results: Among 3,723 participants who were free of stroke and AF at baseline and who had data on all atrial cardiopathy markers, 585 patients (15.7%) experienced an incident ischemic stroke during a median 12.9 years of follow-up. When the four atrial cardiopathy markers were combined in one model along with traditional vascular risk factors, we found significant associations with stroke for PTFV 1 (hazard ratio [HR] per 1,000 μV*ms, 1.04; 95% confidence interval [CI], 1.0006-1.08), NT-proBNP (HR per doubling of NT-proBNP, 1.09; 95% CI, 1.03-1.16), and incident AF (HR, 2.04; 95% CI, 1.67-2.48), but not left atrial dimension (HR per cm, 0.96; 95% CI, 0.84-1.10). Conclusions: In a large, prospective, longitudinal study, we found that evidence of abnormal atrial substrate, defined more broadly than just AF, was associated with subsequent ischemic stroke. These findings support the hypothesis that left atrial thromboembolism can occur in the absence of AF.

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