• cardiovascular outcomes
• carotid endarterectomy
• carotid plaques
• high-sensitivity C-reactive protein
• stroke
• uric acid

Introduction - We aimed to determine whether baseline Uric Acid (UA) and high sensitivity C-Reactive Protein (hs-CRP) are predictive of plaque stability, acute ischemic cerebrovascular events (CVA) and cardiovascular events and death in patients undergoing carotid endarterectomy (CEA). Serum uric acid is a risk factor for atherosclerosis, a marker of oxidative stress, and may serve as a marker of cardiovascular outcomes. Hs-CRP is a risk factor for atherosclerosis and plaque rupture, a marker of inflammation and a novel biomarker that may predict cardiovascular risk. Its role in patients undergoing CEA is not established.
Methods - We enrolled 327 patients for the UA study and a total of 251 for the hs-CRP study. They all underwent CEA between 2/2002 and 6/2017 and completed comprehensive baseline laboratory testing prior to CEA including testing for novel biomarkers as hs-CRP were analyzed. Through the electronic chart as well as via regular nursing follow-up for a median of 10.9 years (IQR 7.3, 13.4), patients were followed for the development of CVA (including stroke and transient ischemic attack) and for cardiovascular events. Patients were stratified according to plaque stability as unstable (those who presented with a history of >1 CVA) and stable (those with no history of CVA).
Results - Uric acid predicts carotid plaque stability, cerebrovascular events, cardiovascular events and death in patients undergoing carotid endarterectomy. Baseline uric acid was significantly higher in patients presenting with unstable plaque vs. stable plaque (6.5(IQR 5.6, 7.9) vs. 5.8(IQR 4.8,6.6);p<0.001). Baseline uric acid was higher among patients who developed CVA vs those without CVA [(6.9 + 2.1) mg/dL vs.(6.4+ 1.7) mg/dL; p=0.037].After adjusting for diabetes, cholesterol, systolic blood pressure, smoking, age, aspirin, and creatinine, uric acid and cholesterol were both independent predictors of CVA in this population [uric acid:(LR 4.84, p=0.03);cholesterol:(L-R 11.8,p=0.0006)]. Baseline serum uric acid levels were significantly higher in patients who developed cardiovascular events vs. those that did not[6.87+2.29 vs. 6.39 +1.61);p=0.047).Baseline serum uric acid was independently associated with cardiovascular events when adjusting for age, creatinine, diabetes mellitus, and hyperlipidemia (L-R 4.0,p=0.04).
High-sensitive C-Reactive Protein predicts cerebrovascular and cardiovascular events in patients undergoing carotid endarterectomy.In univariate analysis, baseline hs-CRP was significantly higher in patients who developed CVA during follow-up vs. those that did not (8.1 (IQR 2.2, 46.3) mg/L vs.3.85 (0.9, 11.75) mg/L; p=0.0054). After adjusting for confounders including age, diabetes mellitus, cholesterol, systolic blood pressure, history of smoking, aspirin use and duration of follow-up, log hs-CRP was an independent predictor of CVA during follow-up after CEA (L-R 9.9;p=0.0016). In univariate analysis, baseline log hs-CRP levels were higher among patients who developed cardiac events when compared to those who did not (1.79+1.74 mg/L vs. 1.22 +1.81 mg/L;p=0.03). After adjustment for age, diabetes, cholesterol, smoking, and hypertension, log hs-CRP was independently predictive of cardiovascular events during follow-up (LR 4.58,p=0.03).
Conclusions - Our findings suggest that uric acid and hs-CRP may be a novel predictor for ischemic cerebrovascular and cardiovascular events during follow-up after CEA. Further investigation is necessary to determine the role of uric acid and hs-CRP as a modifiable risk factor and the therapeutic potential of reducing uric acid and hs-CRP levels in these patients.