The prognostic value of serum uric acid in the acute phase of hemorrhagic stroke patients in black Africans

Introduction Very few studies have been conducted to evaluate the prevalence of hyperuricemia and its impact on the prognosis amongst acute hemorrhagic stroke (AHS) patients. The objectives was to determine the prevalence of hyperuricemia in AHS patients and examined the association between hyperuricemia and stroke outcomes in the Douala General Hospital (DGH). Methods This was a hospital based prospective cohort which included AHS patients with baseline SUA levels and 3 months post stroke follow-up data. SUA values were divided into quintiles. Associations between hyperuricemia and stroke outcomes were analyzed using multiple logistic regression and survival analysis (cox regression and Kaplan Meier). Results A total of 221 AHS patients were reviewed with a mean age of 55.8±11.8 years. The prevalence of hyperuricemia among AHS patients was 34.4% with mean SUA level of 376.8±131.9 μmol/l. On multivariate analysis, hyperuricemia was not independently associated with early death [(OR = 1.072 (CI: 0.370-3.056; p = 0.897)] and poor functional outcome [(OR=2.487 (CI: 0.771-8.699; p = 0.154)] after hemorrhagic stroke. No significant increase in stroke deaths was observed across higher SUA quintiles amongst hemorrhagic stroke patients (p = 0.326). No statistically significant correlation was observed between SUA level and NIHSS (r = 0.063, p = 0.353) and between SUA level and mRS (r = 0.030, p = 0.662) in hemorrhagic stroke. Conclusion About one third of patients present with hyperuricemia in the acute phase of hemorrhagic stroke. Hyperuricemia can act as risk factor for stroke because of its relationship with CVRFs but hyperuricemia has no impact on the severity and short-term outcome amongst black African hemorrhagic stroke patients.


Introduction
Stroke is the second leading cause of death and the leading cause of adult disability worldwide [1,2]. Stroke ranks 6 th out of the top ten causes of death and accounts for one of the top frequent neurological disease consulting at the neurology units [3]. The burden of stroke seems to be shifting to the developing world and currently two-thirds of stroke mortality cases occur in sub-Saharan Africa [4,5]. In Africa, stroke case fatality ranges from 31.9% to as high as 69.7% when due to hemorrhagic stroke [6][7][8]. Uric acid is a powerful anti-oxidant that exerts neuroprotective effects by acting as a free radical scavenger in plasma [9][10][11]. It has been reported that increased levels of uric acid are associated with established cardiovascular risk factor such as elevated serum triglyceride and cholesterol concentration, hypertension, obesity, insulin resistance and metabolic syndrome [9,12]. The role of SUA in acute stroke is poorly understood since some studies demonstrate that SUA is associated with adverse outcomes and mortality [13][14][15][16][17][18] while other studies are suggesting that SUA may be beneficial and protect against poor outcomes [19,20]. Despite these controversies as to whether there is a relation between SUA levels and outcome after acute stroke, the role of SUA in the acute phase of hemorrhagic stroke only has received scant attention in world literature.
Therefore, in this study we estimated the prevalence of hyperuricemia in hemorrhagic stroke and determined its relationship with CVRFs and stroke outcome within 3 months post stroke onset. Patients with incomplete files, acute ischemic stroke and cerebral venous thrombosis were excluded. Data collection and patient management: Demographic data, including age, sex and relevant medical history such as hypertension (HTN), diabetes mellitus (DM), smoking history, alcohol abuse, use of diuretics, history of diseases like chronic kidney disease (CKD), gout and other cardiovascular events such as atrial fibrillation, congestive heart failure (CHF), coronary artery disease (CAD) and ischemic heart disease (IHD) were recorded. Baseline vital and anthropometric parameters such as blood pressure, pulse, respiratory rate, oxygen saturation weight, height and an abdominal circumference values were recorded using standard operating procedures.  HDLc considered as HDLc levels < 1.0 mmol/l in males or < 1.3 mmol/l in females and high TG considered as TG levels > 1.7 mmol/l. Independent Samples t-test was used to assess differences in continuous variables since the normality assumption was not violated following Kolmogorov-Smirnov and Shapiro-Wilk test for normality. Cramer's V, Chi Square test and Fisher's Exact Test were used for categorical variables. Univariate analysis was first performed with demographic characteristics and the risk factors of stroke by cross-tabulations with X 2 or Fisher's exact tests for the unadjusted odds ratios (ORs) and then multiple logistic regression was done to adjust the confounding effects of the dependent predictors of death during admission. All predictor variables with p values < 0.2 that were gotten from the univariate analysis were included in our multivariate analysis. Survival analysis was performed using Kaplan Meier and Cox regression analysis. Level of significance was considered 0.05 (two-sided).

Results
Basic characteristics of the study population: Table 1 shows the basic characteristics of the study population: A total of 221 patients with hemorrhagic stroke were included amongst which 134 were males (60.6%). The mean age was 55.8±11.8 years with most patients aged 46-60 years (49.8%). Table 1  Among stroke survivors (n=104), 60.6% and 39.4% had good and bad functional outcomes. Overall, the 3 months post stroke mortality was 46.9% (92/196). The mean SUA concentration ± SD (standard deviation) of stroke survivors of 354.9 ± 91.7 µmol/l was significantly lower than that of those who died 388.8 ± 118.0 µmol/l, p-value=0.025. The mean ± SD duration of hospital stay and of follow up was 9.7 ± 7.0 days and 49.9 ± 40.7 days respectively.

Correlation
between SUA and clinical data on admission: Table 2 shows the correlation between SUA and clinical data on admission; there was a weak negative significant correlation between age and SUA concentration (r = -0.158*, p=0.019, n=221) and there was also a weak negative significant correlation between Comparison of SUA levels with CVRFs amongst hemorrhagic stroke patients:    [14]. This difference can be accounted for by differences in the methodology and the sample size in the Ghanaian study was small (147). Therefore, it is possible to conclude that this high prevalence of hyperuricemia may simply reflect its association or correlation with CVRFs present amongst hemorrhagic stroke patients.
In our study, we found no statistically significant correlation between SUA level and NIHSS and between SUA level and mRS in hemorrhagic stroke. We also noted a weak negative significant correlation between Glasgow coma score and SUA concentration. syndrome. Regardless of these findings, it is therefore possible to imply that hyperuricemia is a possible risk factor for stroke and primary prevention of stroke will be crucial in the reduction of mortality and morbidity related to hemorrhagic stroke amongst Cameroonians. The strength of this study was the fact that we prospectively explored different aspects of stroke outcomes in relation to uric acid amongst a cohort of patients with ICH but as a limitation, we were not able to explore certain variables that could have been more appropriate such the glycated hemoglobin (HbA1c).
We used blood glucose levels in the study instead of the HbA1c hence overestimating the proportion of patients with diabetes mellitus as stress hyperglycemia could occur in acute conditions such as stroke. Despite these limitations, we have been able to assess the relationship between uric acid and stroke outcome.

Conclusion
Our findings suggest that one third of patients present with hyperuricemia in the acute phase of hemorrhagic stroke.
Hyperuricemia can act as a risk factor for stroke because of its relationship with CVRFs but it is not an independent predictor of the mortality and adverse outcome amongst black African hemorrhagic stroke patients.
What is known about this topic

Competing interests
The author declare no competing interests.  Table 1: Shows the general characteristics of the study population included in the study