Prognostic significance of uric acid change in acute ischemic stroke patients with reperfusion therapy

Abstract

Background Uric acid (UA) is an important endogenous free radical scavenger that has been found to have a neuroprotective effect. However, there is uncertainty about the relationship between UA change and outcome in acute ischemic stroke (AIS) patients with reperfusion therapy. Methods We consecutively enrolled AIS patients with reperfusion therapy. UA was measured upon admission and during hospitalization. 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. Functional outcome was assessed by modified Rankin Scale (mRS) at 3 months. Poor outcome was defined as mRS >2. Results A total of 361 patients were included (mean age 68.7 ± 13.9 years, 54.3% males). The mean UA on admission was 355 ± 96.1 μmol/L. The median ΔUA was 121 μmol/L (IQR 50–192 μmol/L) and 18 (5%) patients had increased UA levels. UA on admission was positively associated with good outcome (p for trend = 0.017). When patients were classified into quartiles by ΔUA, patients with the largest decrease in UA (Q4: 199–434 μmol/L) had a higher risk of poor outcome at 3 months compared to patients with the least decrease in UA (Q1: 0–57 μmol/L) (OR 2.55, 95% CI 1.09–5.98, p = 0.031). The risk of poor outcome increased with ΔUA (p for trend = 0.048). Conclusions In patients with reperfusion therapy, high UA on admission was associated with a good 3‐month outcome, while a greater decrease in UA was associated with poor outcome.

J-Shaped Relationship of Serum Uric Acid with Unfavorable Short-Term Outcomes among Patients with Acute Ischemic Stroke

“…Contrary to the previously mentioned relationship between higher uric acid levels and poor outcomes, Tang et al found that lower uric acid levels are associated with poor outcomes [ 15 ]. However, higher uric acid levels have been associated with better stroke outcomes in some studies, and in patients with thrombolysis [ 5 , 16 , 17 , 18 , 19 ]. Furthermore, several studies have reported a U-shaped relationship between uric acid and poor stroke outcomes (including mortality) [ 20 , 21 , 22 , 23 ].…”

“…Uric acid has the useful ability to clear out peroxynitrite, nitric oxide, and hydroxyl radicals. It can therefore protect nerves from oxidative damage during an acute stroke and prevent worse outcomes [ 14 , 18 , 19 ]. However, elevated uric acid was also reported to promote atherosclerotic progression by increasing the production of free radicals and facilitating low-density lipoprotein cholesterol oxidation [ 35 ]; to increase the level of inflammatory cytokines; to increase platelet aggregation and thrombus formation [ 36 ]; and to be associated with carotid intima-media thickness [ 37 ], proximal extracranial artery stenosis [ 38 ], and intracranial arterial stenosis [ 39 ].…”

“…The neuroprotective antioxidant effect of uric acid has been documented by several studies in which patients with higher levels of uric acid during AIS exhibited a better outcome [ 5 , 6 , 14 , 18 , 19 ], particular in men [ 16 , 17 ], and patients with lower levels of uric acid had worse outcome [ 15 , 40 ]. Similar observation has been reported that patients with multiple sclerosis, neuromyelitis optica, and Parkinson’s disease showed lower uric acid levels when compared with healthy controls [ 41 , 42 ].…”

Uric Acid and Clinical Outcomes in Young Patients with Ischemic Stroke

“… 7–9 Several observational human studies demonstrated that increased serum UA levels were associated with better clinical outcome after AIS. 10–12 A randomized-controlled trial of intravenous UA administered during alteplase treatment for AIS also revealed that UA therapy had an excellent safety profile and ability to prevent early ischemic deterioration among thrombolysed patients. 13 …”

“…[7][8][9] Several observational human studies demonstrated that increased serum UA levels were associated with better clinical outcome after AIS. [10][11][12] A randomized-controlled trial of intravenous UA administered during alteplase treatment for AIS also revealed that UA therapy had an excellent safety profile and ability to prevent early ischemic deterioration among thrombolysed patients. 13 However, conflicting data have been reported regarding whether increased levels of serum UA are significantly associated with favorable outcomes in patients after ischemic stroke.…”