Aortic Atherosclerosis, Hypercoagulability, and Stroke: The APRIS (Aortic Plaque and Risk of Ischemic Stroke) Study

Abstract

Conclusion: In patients with acute ischemic stroke, large proximal aortic plaques are associated with hypercoagulability. The combination of large proximal aortic plaques and hypercoagulability results in an increased risk of recurrent stroke and death. Summary: Large plaques in the proximal portion of the aorta are associated with an increased risk of ischemic stroke. Plaque thickness is related to stroke risk, and a 4-mm thick plaque is considered clinically relevant for risk stratification. Ulcerations and mobile components of these plaques also contribute to embolic risk. It is suggested that superimposed thrombotic material on the aortic plaque may contribute to its thickness and the enhanced stroke potential of the plaque. The authors sought to determine whether a relationship existed between the aortic plaques and hypercoagulability that perhaps could predispose to thrombus formation and stroke risk. Transesophageal echocardiography was performed in 255 patients with a first ischemic stroke and in 209 control subjects matched by age, gender, and race/ethnicity. A case–control design was used to assess the association between arch plaques and hypercoagulability and its effect on stroke risk. Patients were followed up prospectively to assess for recurrent stroke and death. Arch plaques >4 mm were associated with increased stroke risk (adjusted odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3-4.6). This relationship was more pronounced when superimposed thrombus or ulcerations were present (adjusted OR, 3.3; 95% CI, 1.4-to 8.2). Prothrombin fragment F1.2 was associated with large plaques in patients with acute ischemic stroke but not in control subjects (P = .02). Mean follow-up was 55.1 ± 37.2 months. During follow-up, stroke patients with large plaques and F1.2 that exceeded the median value had an increased risk of recurrent stroke and death compared with those with large plaques but lower F1.2 levels (230 events/1000 patient-years vs 85 events/1000 patient-years; P = .05). Comments: This study draws an association between activation of coagulation parameters and risk of stroke in patients with aortic arch plaques. Prothrombin fragment F1.2 is a byproduct of the conversion of prothrombin to thrombin and is an excellent indicator of thrombin generation. The results of the study suggest an overall association between hypercoagulability, aortic plaque thickness, and ischemic stroke. The best treatment for emboli likely originating from an aortic plaque is unknown. Anticoagulation agents are usually prescribed for most thrombi, whereas antiplatelet agents are often used for plaques >4 mm in thickness but not without superimposed mobile thrombus. The results here suggest that prothrombin fragment F1.2 levels should be assessed in patients with large nonmobile aortic plaques and ischemic strokes, assessed at least for prognostic reasons. Future trials will be necessary to evaluate whether systemic anticoagulation may reduce the risk of subsequent stroke in patients with elevated fragment F1.2 levels and large proximal aortic plaques.