A lthough there are a variety of established risk factors for ischemic stroke and its common pathophysiologies are well known, a specific cause remains undefined in 25%-40% of instances. That rate is influenced in part by the thoroughness of the poststroke evaluation.1 A cause, however, can remain undetermined in up to 12% of patients having an acute event, even with a full diagnostic assessment.
2At least part of the diagnostic uncertainty can be related to the impact of relatively unrecognized risk factors. For example, the most widely used stroke risk assessment tool, the Framingham stroke risk profile, includes the following wellrecognized stroke risk factors: age, systolic blood pressure, use of antihypertensive medications, diabetes mellitus, smoking, having cardiovascular disease, atrial fibrillation and left ventricular hypertrophy on electrocardiography.3 Although this tool is useful, many people have strokes despite a low Framingham stroke risk profile score, which does not incorporate a variety of less established risk factors. In this week's CMAJ, Bouzas-Mosquera and colleagues 4 describe an independent, graded association between left atrial size on electrocardiography and stroke risk in women but not in men. Prior studies reported a similar relation between left atrial size and ischemic stroke risk in men, but not in women. 5,6 The reason for the discrepancy among these studies is uncertain, and the findings need to be validated through replication in other patient populations. Bouzas-Mosquera and coauthors posit that the variability among reports might be a result of differences in study populations. Another possibility is that left atrial enlargement is a risk marker that only indirectly reflects one or a combination of risk factors. For example, left atrial enlargement is associated with an increased risk of atrial fibrillation, 7 which is a major stroke risk factor that may become apparent only with prolonged and repeated cardiac monitoring.Left atrial enlargement also might be a marker for other conditions that could increase stroke risk. For example, left atrial dysfunction can occur in patients with a patent foramen ovale. Patent foramen ovale (not assessed in the study by Bouzas-Mosquera and colleagues) is found more commonly in patients with cryptogenic stroke than in those with no history of stroke or in those who have stroke of determined cause.
9Paradoxical embolism through a patent foramen ovale may be important in the pathophysiology of acute stroke in patients with deep vein thrombosis, a relatively rare event.The role of patent foramen ovale in patients without a source of embolism is less certain. There is no difference in the rate of recurrent stroke between groups of patients with otherwise cryptogenic stroke who do or do not have a patent foramen ovale, regardless of the type of medical treatment (antiplatelet medication v. anticoagulation). One randomized trial with results reported in abstract form (CLOSURE-1, 2011 International Stroke Conference) found no difference in the ...