Lam, Josephine

Background: Uric acid (UA) concentration within carotid plaque and its association with cerebrovascular events have not been detected or quantified. Systemically, serum UA is a marker of inflammation and risk factor for atherosclerosis. However, its association with carotid plaque instability and stroke pathogenesis remains unclear. In patients undergoing carotid endarterectomy, we aimed to determine whether UA is present differentially in symptomatic versus asymptomatic carotid plaques and whether serum UA is associated with cerebrovascular symptoms (stroke, transient ischemic attack, or amaurosis fugax). Methods: Carotid atherosclerotic plaques were collected during carotid endarterectomy. The presence of UA was assessed using Gomori methenamine silver staining as well as anti-UA immunohistochemical staining and its quantity measured using an enzymatic colorimetric assay. Clinical information was obtained through a retrospective review of data. Results: UA was more commonly detected in symptomatic (n=23) compared with asymptomatic (n=9) carotid plaques by Gomori methenamine silver (20 [86.9%] versus 2 [22.2%]; P =0.001) and anti-UA immunohistochemistry (16 [69.5%] versus 1 [11.1%]; P =0.004). UA concentration was higher in symptomatic rather than asymptomatic plaques (25.1 [9.5] versus 17.9 [3.8] µg/g; P =0.021). Before carotid endarterectomy, serum UA levels were higher in symptomatic (n=341) compared with asymptomatic (n=146) patients (5.9 [interquartile range, 4.6–6.9] mg/dL versus 5.2 [interquartile range, 4.6–6.2] mg/dL; P =0.009). Conclusions: The current study supports a potential role of UA as a potential tissue participant and a systemic biomarker in the pathogenesis of carotid atherosclerosis. UA may provide a mechanistic explanation for plaque instability and subsequent ischemic cerebrovascular events.

Introduction: Uric acid (UA) level within carotid plaque specimens and its association with cerebrovascular events has not been detected or quantified. Systemically, serum uric acid (SUA) is a marker of inflammation and risk factor for atherosclerosis. However, its association with carotid plaque instability and subsequent cerebrovascular events remains unclear. Hypothesis: We hypothesized that UA may play a role in carotid artery atherosclerosis and stroke pathogenesis. In patients undergoing carotid endarterectomy (CEA), we aimed to determine whether UA is present differentially in carotid plaques of symptomatic versus asymptomatic patients and whether SUA is associated with cerebrovascular symptoms before surgery and major adverse cardiovascular events (MACE) in the follow-up to CEA. Methods: We prospectively collected 32 carotid plaques during CEA. We qualitatively assessed the presence of UA by using Gomori methenamine silver (GMS) staining and immunohistochemistry with anti-UA antibodies. We extracted and measured the quantity of UA in carotid plaques by using an enzymatic colorimetric assay. A retrospective analysis of a clinical database of 534 consecutive patients who underwent CEA was performed. We defined as symptomatic those patients with history of stroke, TIA and amaurosis fugax. Results: UA positive staining was detected in higher number of carotid plaques from symptomatic compared to asymptomatic patients on both staining, GMS [20 (86.9%) vs 2 (22.2%); p=0.001] and immunohistochemistry anti-UA [16 (69.5%) vs 1 (11.1%); p=0.004]. Moreover, we found a significantly higher concentration of UA in carotid plaque from symptomatic compared to asymptomatic patients [25.1 (9.5) μg/g vs 17.9 (3.8) μg/g; p=0.021]. SUA level in patients prior to CEA was significantly higher in the symptomatic compared to the asymptomatic group [6.0 (4.8-7.1) mg/dL vs 5.2 (4.4-6.3) mg/dL; p<0.001] and it was significantly higher in patients who developed MACE after CEA versus those that did not [6.0 (4.8-7.1) mg/dL vs 5.4 (4.5-6.6) mg/dL; p=0.021]. Conclusions: UA may provide a mechanistic explanation as systemic biomarker and potential tissue contributor for carotid plaque instability and subsequent cerebrovascular and cardiovascular symptoms.