Ischemic stroke leads to increase of intracranial free radicals and peroxynitrite, which causes brain cell death [16]. SUA is a natural antioxidant that exists in body, and concentration is approximately 10 times higher than other endogenous antioxidants [17]. SUA can scavenge oxygen free radicals and prevent lipid peroxidation effects [18]. However, until now, one is still not sure whether hyperuricemia is a protective factor or risk factor in AIS patients.
Some studies [5, 6] found the association between high SUA level and mortality of myocardial infarction, stroke, and cardiovascular disease, although it is unclear whether SUA elevation was a cause or a result [7]. Karagiannis A et al [8] showed that elevated SUA level was an independent predictor of early death after acute stroke. Kim SY et al [9] demonstrated that hyperuricemia might slightly increase mortality and the incidence of stroke.
On the contrary, some studies showed high SUA level might have neuroprotective effects in patients with AIS [11, 12], and both exogenous and endogenous UA are presented as neuroprotective roles [19, 20]. Some researchers [21] attribute it to the strong antioxidant capacity of urate. More and more studies [2–4] demonstrate that high SUA level usually predict a better outcome. A meta-analysis included 8131 AIS patients for less than a 1-year follow up found that high SUA level had a protective effect on neurological prognosis after ischemic stroke [22]. Besides, in 2014, a phase 2b/3 clinical trial (URICO-ICTUS) with 420 AIS patients completed a 90-day follow up period showed that patients with UA therapy had a better prognosis than the placebo group [23]. All these studies have demonstrated the protective effects of high UA level on AIS patients. Furthermore, our study concluded that hyperuricemia was still a protective factor for AIS in a long-term follow up. The powerful antioxidant capacity of UA may be the reason for the benefit of patients with ischemic stroke.
Aspirin is the most common antiplatelet agent recommended in guidelines. However, more and more clinical physicians observed resistance in antiplatelet therapy [24, 25]. Our study found that the incidence of AR was high in Chinese populations(19.33%), which was significantly associated with ischemic events recurrence even during the 3-year follow up. Another study has also demonstrated that AR is associated with an increased risk of severe stroke and large infarct volume in patients [25]. Only one study explored the effects of hyperuricemia on AR [15], it demonstrated that high SUA levels could be used as independent predictors of AR. But our study did not find any relationship between AR and hyperuricemia. Meanwhile, we also found that patients with stroke history were more likely to experience recurrent ischemic events, which were mostly due to more risk factors and poor cerebrovascular conditions. We did not find more recurrence occurred in diabetes patients and need to enlarge the sample size.
The use of daily low-dose aspirin (100 mg/day) reduces UA excretion in urine and increases the SUA level [13, 14]. However, there are no guidelines to suggest whether to discontinue aspirin in AIS patients with hyperuricemia. Some studies have shown that [14] usage of lowering-uric-acid drugs instead of discontinuing aspirin will be more beneficial for patients with ischemic stroke. Our study investigated the relationship among hyperuricemia, recurrent ischemic events, and AR. Hyperuricemia can reduce the incidence of ischemic events with increased risk of AR. Therefore, we believe that AIS patients who had hyperuricemia may not need to discontinue aspirin.