Background: Silent brain infarction (SBI) is a marker of stroke risk in asymptomatic carotid stenosis. Increased SBI burden downstream of stenosis has not been consistently shown, emphasizing that mechanisms of SBI formation in carotid stenosis remain unclear. Coated-platelets are a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, and elevated levels are associated with TIA/stroke in asymptomatic carotid stenosis. We now examine if coated-platelet levels are associated with SBI in asymptomatic carotid stenosis.
Methods: Consecutive asymptomatic ≥50% carotid stenosis patients were enrolled and coated-platelets assayed. Brain MRI or CT scans within 12 months of enrollment were reviewed by a blinded neurologist for SBI, defined as a focal, ≥ 3mm, cavitary lesion with T1 hypointensity and T2 hyperintensity features on MRI or hypodense on CT. Demographics, medications and comorbidities were recorded. The optimal coated-platelet cutoff was determined by ROC analysis. Logistic regression analysis included variables having significant (p<.05) bivariate correlations with SBI as potential predictors. Variables with p<0.05 were retained in the final model.
Results: Brain imaging was available for 64 subjects. The optimal coated-platelet cutoff for predicting SBI was 52.7% (p=0.0002) by ROC analysis. Both elevated coated-platelets (OR=10.4, p=0.043) and SSRI use (OR=3.8, p=0.027) were associated with increased odds of SBI (p=0.005). Stenosis ≥70% was associated with presence (p=0.0005) and number (p<0.0001) of downstream SBI on bivariate analysis, but was no longer significant in the multivariate model (p=0.14).
Conclusions: Elevated coated-platelets and SSRI use were associated with SBI in this asymptomatic carotid stenosis cohort. Interestingly, presence of ≥70% stenosis was no longer significantly associated with SBI after accounting for coated-platelet levels and SSRI use by multivariate analysis. SSRI use has been linked to recurrent stroke previously, although results have varied. Our findings are the first showing a strong association between platelet procoagulant potential and SBI and warrant further study to confirm our results and explore mechanisms involved.