Effect of stroke prevention medication on aortic atheroma progression assessed using new statistical paradigm

Abstract

Background: Progression of aortic arch atheroma (AA) is associated with vascular events in patients with stroke or transient ischemic attack (TIA). Studies investigating effect of stroke prevention medication on AA progression are limited to post-cerebral segments that may not be related to stroke pathophysiology and do not use information from the relevant segments adjacent to the origin of the cerebral blood vessels. Methods: AA atheroma was detected on baseline transesophageal echocardiogram (TEE) in 167 consecutive patients who had stroke or TIA. Of these, 125 consented to a follow-up TEE at12 months. Adequate paired AA images were obtained in 117 (78 with strokes, 39 with TIAs), which allowed detailed measurements of plaques. On admission for their index stroke or TIA, patients were assessed for stroke risk factors and stroke prevention medications (Statins, Antiplatelet therapy and oral anticoagulant). We assessed three segments of the AA adjacent to the origin of the cerebral blood vessels for plaque thickness by TEE and analyzed the effect of medication using joint modeling, with due consideration to confounding covariates. The statistical paradigm included a permutation testing procedure to determine the significance of medication effect on plaque progression in the three segments in combination. Results: Using the specified statistical paradigm, it is evident that statin therapy is effective in arresting the AA progression; however, there is no significant change induced by anticoagulant therapy. The cleaned data, after removal of influential observations, shows even more significance for the statin therapy. The constrained hypothesis tests in both cases show a smaller p-value suggesting that the statin therapy may be effective in arresting the AA progression. Conclusions: In this preliminary study of stroke/TIA patients with AA atheroma on transesophageal echocardiogram, AA atheroma progression was arrested by statin therapy, without any significant change induced by anticoagulant therapy. The statistical paradigm with due consideration of all segments implicated in stroke pathophysiology may be used to test the effect of other stroke prevention medications on AA progression.

Association of Dietary Factors with Progression of AA in Stroke/TIA Patients

“…Furthermore, few studies have suggested that elevated levels of inflammatory markers and hyperhomocysteinemia as isolated risk factors for the development and progression of AA [11,17,18]. Several studies have investigated the effect of medications, specifically statins in arresting AA progression [22]. This is a novel study in an effort to elicit the role of dietary factors in the development and progression of the aortic atheroma.…”

“…Studies have reported an association between hyperhomocysteinemia, [18,19] elevated cholesterol, [11] elevated WBC count [19], and fibrinogen level [20,21] with AA. Recently we reviewed the effect of medications –statins, antiplatelet agents and oral anticoagulants on aortic atheroma progression [22]. It is well known fact that there are several dietary risk factors influencing atherosclerosis and vascular events [23].…”