We found that uric acid is independently associated with the presence of CMBs in patients with acute ischemic stroke. The association sustained in patients with deep or infratentorial CMBs but not among those with strictly lobar CMBs. Furthermore, this association was strengthened in patients with hypertension. In patients without hypertension, however, uric acid was not related to the presence of CMBs.
CMBs are divided into two subtypes according to its main pathology, hypertensive microangiopathy and cerebral amyloid angiopathy 
. CMBs related with hypertensive predominantly located at deep brain structure, basal ganglia, thalamus, and brain stem. In contrast, CMBs related with cerebral amyloid angiopathy are commonly found in subcortical area. For hypertensive CMBs, chronic hypertension is the most consistent and important risk factor 
. Moreover, hypertensive CMBs have been associated with hypertensive organ damage, including left ventricular mass index 
, hypertensive retinopathy 
, and chronic kidney disease 
. Several pathophysiological mechanisms linking uric acid to hypertensive organ damage at the cellular and tissue levels have been proposed, including a proliferation of vascular smooth muscle cells 
, stimulation of the inflammatory pathway 
, and possible prothrombotic effects mediated by platelet activation 
. Furthermore, uric acid has proven to be an excellent marker for tissue ischemia and endothelial dysfunction 
, and it has been shown to play a role in the evolution of atherosclerotic lesions 
. Analyses based on the Framingham Heart Study have shown that serum uric acid was an independent predictor of the presence and progression of hypertension 
. Taken together, our results that uric acid is associated with deep or infratentorial CMBs but not with lobar CMBs and that the relationship between uric acid and CMBs was found in patients with hypertension but not in those without hypertension suggest that CMBs may be the brain phenotype of hypertensive organ damage and uric acid may in part mediate the injury process.
Ample evidence has indicated that CMBs are closely related to ICH 
. Earlier studies have suggested that CMBs could be a representative marker of ICH based on reports that the risk factors for CMBs are similar to those for ICH and on the common histopathologic findings for both types of lesions 
. Furthermore, recent reports have strongly corroborated the association between CMBs and ICH: (1) Regional association between CBMs and ICH 
; (2) Association between CMBs and volume, occurrence, and recurrence of ICH 
; (3) Relationship of CMBs with warfarin-related hemorrhage 
; and (4) Association between CMBs and the hemorrhagic transformation after thrombolysis 
. Hence, it seems plausible to assume that increased levels of uric acid might increase a risk of ICH.
In the present study, we found no significant association between uric acid and WMLs. This is supposedly caused by a crude white matter lesion grading system. In a previous study demonstrating a positive association between uric acid and WMLs, the WMLs were calculated in a quantitative manner 
. However, we graded WMLs according to the system described by Fazekas 
Several limitations of our study deserve comment. First, it is well known that patients with acute stroke, even without a history of previous hypertension, often have a high blood pressure 
. Previous studies have shown that blood pressure gradually declines and reaches baseline level at 7 days after symptom onset 
. Although only 4.1% patients in our study had a blood pressure measurement within 7 days after symptom onset and the association between uric acid and CMBs sustained after excluding these patients, we could not completely rule out the possibility that a blood pressure variation caused by acute stroke has influenced out results. Second, our study included patients with acute ischemic stroke. The presence of CMBs could therefore be affected by acute ischemic stroke 
. However, a previous report have revealed that a rapid appearance of CMBs after ischemic stroke was related with only the presence of baseline CMBs and white matter lesion volumes. Thus, we believe that this bias had little impact on our results 
. Third, there is a possibility of selection bias. To minimize the likelihood of bias, we studied all consecutive patients, and uric acid was measured as a part of the routine work-up. Fourth, we were unable to obtain the information as to whether the patients had used uric acid-lowering agents. After a meticulous search in the medical records, we found some patients who were taking uric acid-lowering agents. However, this investigation raised a possibility of an additional bias because we were unable to inspect the entire sample due to the retrospective nature of our study. Finally, our hypothesis-generating cross-sectional study was unable to provide a direct causal relationship between uric acid and CMBs.
Although it is indeterminate whether hyperuricemia is an independent risk factor requiring treatment, or if it is an innocent bystander in proximity to vascular accidents that merely reflects an adverse risk factor pattern, recent evidence suggests that uric acid may be deleterious to the brain rather than protective 
. Given that the presence of CMBs portends an increased risk of ICH our study suggests another detrimental role of uric acid as a potential ICH risk factor.