| Objective:Uric acid(UA)may be both beneficial and detrimental.On one hand,UA can acquire pro-oxidant properties,which may play a critical role in the development of atherosclerosis.However,there is uncertainty about the relationship between UA and atherosclerosis in acute ischemic stroke patients.On the other hand,UA can be a protective antioxidant.However,there is uncertainty about the prognostic significance of UA and its change in ischemic stroke patients with reperfusion therapy.In the current study,we aimed to(1)explore the association between UA and atherosclerotic lesions and polyvascular disease in large-artery atherosclerosis ischemic stroke patients,and to(2)investigate the association between UA and its change and outcome in patients with reperfusion therapy.Materials and Methods:1.Acute ischemic stroke patients were consecutively enrolled between January 1st,2015 and July 31st,2020.According to TOAST classification,large-artery atherosclerosis ischemic stroke patients were screened out for analysis.UA was measured within 24 h from stroke onset.Computed tomography angiography was performed to evaluate intracranial and extracranial atherosclerosis.Atherosclerotic lesions were defined as the extent of stenosis≥50%.Atherosclerotic lesions were divided into intracranial atherosclerosis,extracranial atherosclerosis,and coexistence of intracranial and extracranial atherosclerosis.The number of cerebral arteries with atherosclerotic lesions was recorded as well.We included cerebrovascular disease,coronary vascular disease,and lower extremity artery disease as atrisk vascular beds.During hospitalization,atherosclerotic lesions in coronary artery and lower extremity artery were examined based on previous history and relevant examinations,including coronary computed tomography and lower extremity arterial ultrasound.Patient baseline characteristics,vascular risk factors,and laboratory test results were documented as well.Univariate analysis was performed to determine potential confounding factors.Multivariate logistic regression analysis was conducted to explore the relationship between UA and intracranial,extracranial atherosclerosis and polyvascular disease.2.Acute ischemic stroke patients with reperfusion therapy were consecutively enrolled between January 1st,2015 and July 31 st,2020.UA was measured upon admission.During hospitalization,follow-up measurements of UA were conducted.The interval between admission and measurement of UA was documented.The change in UA levels(ΔUA)was determined by calculating the difference between admission UA and the lowest UA among all follow-up measurements,with a positive ΔUA suggesting a decrease in UA levels.Patients’ baseline characteristics,vascular risk factors,laboratory test results,and treatment during hospitalization were documented as well.We evaluated patient 3-month outcome by modified Rankin Scale(m RS).Poor outcome was defined as m RS >2.Univariate analysis was performed to determine potential confounding factors.Multivariate logistic regression analysis was conducted to explore the relationship between admission UA and outcome,as well as the relationship between ΔUA and outcome.Results:1.A total of 1034 large-artery atherosclerosis ischemic stroke patients were included(mean age 65.4±13.6 years,67.7% males).The mean UA on admission was 5.88±1.67mg/d L.A total of 640(61.9%)patients had intracranial atherosclerosis,230(22.2%)patients had extracranial atherosclerosis,and 164(15.9%)patients had coexistence of intracranial and extracranial atherosclerosis.A total of 368(35.6%)patients had at least two cerebral arteries with atherosclerotic lesions.A total of 169(16.3%)patients had polyvascular disease,with 160(15.4%)patients had atherosclerotic lesions in 2 vascular territories(118 with cerebrovascular and coronary vascular disease and 42 with cerebrovascular and lower extremity artery disease)and 9(0.9%)patients had atherosclerotic lesions in 3 vascular territories.After adjustment for age,gender,hypertension,diabetes,smoking,alcohol consumption,and low-density lipoprotein,UA was associated with intracranial atherosclerosis(OR 1.27,95% CI 1.14-1.41,P<0.001),at least two cerebral arteries with atherosclerotic lesions(OR 1.51,95% CI 1.35-1.69,P<0.001),and polyvascular disease(OR 1.15,95% CI 1.03-1.29,P=0.018),while the association between UA and extracranial atherosclerosis was insignificant(OR 0.98,95% CI 0.90-1.06,P=0.592).2.A total of 499 patients with reperfusion therapy were included(mean age 67.9±14.0,54.9% males).The mean UA on admission was5.99±1.62mg/d L.The median ΔUA was 1.95mg/d L(IQR 0.88-3.23mg/d L).A total of 471 patients(94.4%)had decreased UA levels during hospitalization,while 28 patients(5.6%)had increased UA levels during hospitalization.The median interval between admission and the lowest follow-up measurement of UA was 91.2h(IQR 24.9-151h).A total of 226(45.3%)patients had a good 3-month outcome,while 273(54.7%)patients had a poor 3-month outcome(m RS>2).Compared to patients with good 3-month outcome,patients with poor 3-month outcome were older and showed higher frequency of diabetes,atrial fibrillation,and diuretics usage during hospitalization,lower rate of male,smoking,and alcohol consumption,higher admission NIHSS score and glucose,lower e GFR,low-density lipoprotein,and total cholesterol.After adjustment for above confounders as well as hypertension,white blood cell count,reperfusion therapy method,TOAST classification,UA on admission was negatively associated with poor outcome(P for trend=0.016).Compared to patients with admission UA<5.33mg/d L,patients with admission UA≥5.33mg/d L had lower risk of poor 3-month outcome(OR 0.45,95% CI0.27-0.74,P=0.002).ΔUA was independently associated with 3-month outcome(OR 1.21,95% CI 1.03-1.42,P=0.020),with the risk of poor outcome increased stepwise with ΔUA(P for trend=0.011).Conclusion:1.In large-artery atherosclerosis ischemic stroke patients,UA was independently associated with intracranial atherosclerosis.Moreover,UA was independently associated with polyvascular disease.2.In ischemic stroke patients with reperfusion therapy,UA on admission was negatively associated with poor 3-month outcome.Moreover,for most patients,UA decreased during hospitalization and ΔUA was independently associated with 3-month outcome.A high decrease in UA was associated with poor outcomes.However,these associations were insignificant among largeartery atherosclerosis ischemic stroke patients.3.UA may play different roles in formation of atherosclerosis and outcome of acute ischemic stroke patients.The pro-oxidant property of UA might be associated with atherosclerosis in ischemic stroke patients,while the antioxidant property of UA might be associated with ischemic stroke patient outcome.Clinicians should pay attention to patients with high UA levels and evaluate their atherosclerotic lesions thoroughly.For acute ischemic stroke patients with reperfusion therapy,monitoring UA levels may help clinicians to identify patients with high risk of poor outcome.Further studies are needed to verify our results. |
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