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CLINICAL RESEARCH: AORTIC ATHEROSCLEROSIS AND STROKE

Aortic Atherosclerosis, Hypercoagulability, and Stroke

The APRIS (Aortic Plaque and Risk of Ischemic Stroke) Study

Marco R. Di Tullio, MD^_*,_*, Shunichi Homma, MD, FACC^_*, Zhezhen Jin, PhD and Ralph L. Sacco, MD

^_* Department of Medicine, Columbia University Medical Center, New York, New York
Department of Biostatistics, Columbia University Medical Center, New York, New York
Departments of Neurology, Epidemiology, and Human Genetics, University of Miami, Miami, Florida

Manuscript received January 15, 2008; revised manuscript received March 14, 2008, accepted April 16, 2008.

^_* Reprint requests and correspondence: Dr. Marco R. Di Tullio, Columbia University Medical Center, PH3-342, 622 West 168th Street, New York, New York 10032 (Email: md42{at}columbia.edu).

Objectives: Our goal was to assess the effect of hypercoagulability on the risk of stroke in patients with aortic plaques.

Background: Atherosclerotic plaques in the aortic arch are a risk factor for ischemic stroke. Their relationship with blood hypercoagulability, which might enhance their embolic potential and affect treatment and prevention, is not known.

Methods: We performed transesophageal echocardiography in 255 patients with first acute ischemic stroke and in 209 control subjects matched by age, gender, and race/ethnicity. The association between arch plaques and hypercoagulability, and its effect on the stroke risk, was assessed with a case-control design. Stroke patients were then followed prospectively to assess recurrent stroke and death.

Results: Large (4 mm) arch plaques were associated with increased stroke risk (adjusted odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.3 to 4.6), especially when ulcerations or superimposed thrombus were present (adjusted OR: 3.3, 95% CI: 1.4 to 8.2). Prothrombin fragment F 1.2, an indicator of thrombin generation, was associated with large plaques in stroke patients (p = 0.02), but not in control subjects. Over a mean follow-up of 55.1 ± 37.2 months, stroke patients with large plaques and F 1.2 over the median value had a significantly higher risk of recurrent stroke and death than those with large plaques but lower F 1.2 levels (230 events per 1,000 person-years vs. 85 events per 1,000 person-years; p = 0.05).

Conclusions: In patients presenting with acute ischemic stroke, large aortic plaques are associated with blood hypercoagulability, suggesting a role for coagulation activation in the stroke mechanism. Coexistence of large aortic plaques and blood hypercoagulability is associated with an increased risk of recurrent stroke and death.

Key Words: stroke • atherosclerosis • aorta • coagulation

Abbreviations and Acronyms   AF = atrial fibrillation   CI = confidence interval   OR = odds ratio   TEE = transesophageal echocardiography

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