Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Users Online: 158
Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Advertise | Login 
     

Table of Contents
ORIGINAL ARTICLE
Year : 2012  |  Volume : 6  |  Issue : 2  |  Page : 75-79

Serum uric acid and acute stroke outcome in Nigerian Africans


1 Department of Medicine, Neurology Unit, University of Benin Teaching Hospital, Benin City, Nigeria
2 Department of Chemical Pathology, University of Benin Teaching Hospital, Benin City, Nigeria

Date of Web Publication7-Mar-2013

Correspondence Address:
Frank Aiwansoba Imarhiagbe
Neurology Unit, Department of Medicine, University of Benin Teaching Hospital, Benin City
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0331-3131.108125

Rights and Permissions
   Abstract 

Background : Serum uric acid (SUA) has long been recognized as a potent antioxidant in plasma and increasingly its prognostic value and therapeutic role in acute stroke has been proven in different population groups.
Aim: To assess the role of admission SUA in acute stroke outcome in a Nigerian population.
Setting: A tertiary neurologic care center in Nigeria.
Design: Prospective observational study.
Materials and Methods: Total 240 acute stroke patients aged 30-91 years with first-ever stroke had their blood samples taken consecutively for SUA and blood sugar within 48 hours of onset of stroke symptoms. All were followed-up for outcome within 42 days from the date of admission. Outcome was either discharged to follow-up and still in care or in-hospital death. Stroke subtypes were defined by cranial computed tomography (CT) scan; stroke severity was assessed by the admission Glasgow coma scale (GCS).
Statistics: Age, sex, SUA, blood sugar and GCS were compared between the stroke outcome groups. SUA and stroke outcome was tested on simple logistic regression after adjustment for age above 60 years and elevated blood sugar above 200 mg/dl. The contribution of SUA, blood sugar, age, stroke subtype and GCS to time of all cause in-hospital mortality was tested on Cox regression.
Results: 1) Mean SUA, age and blood sugar were higher and mean GCS was lower in the deceased group (P < 0.001, 0.001, 0.001 and 0.001). 2) SUA predicted poorer outcome of acute stroke after adjustment for age above 60 years and blood glucose level above 200 mg/dl (P = 0.045, n = 96). 3) SUA, blood glucose and age predicted time to in-hospital mortality (P < 0.001, 0.047, <0.001).
Conclusion: SUA predicts poorer outcome and time to all cause in-hospital mortality in acute stroke and may also become a reliable surrogate of acute stroke outcome in Africans as shown in other populations.

Keywords: Uric acid, acute, stroke, outcome, Africa


How to cite this article:
Imarhiagbe FA, Idemudia JO. Serum uric acid and acute stroke outcome in Nigerian Africans. Ann Nigerian Med 2012;6:75-9

How to cite this URL:
Imarhiagbe FA, Idemudia JO. Serum uric acid and acute stroke outcome in Nigerian Africans. Ann Nigerian Med [serial online] 2012 [cited 2020 Aug 10];6:75-9. Available from: http://www.anmjournal.com/text.asp?2012/6/2/75/108125


   Introduction Top


Interest in SUA in acute stroke is generated among other reasons by its role as an antioxidant and also because it offers a potential therapeutic option, but the prognostic significance of SUA in acute strokes can best be described as controversial at present. [1],[2],[3] Acute stroke outcome is generally influenced by stroke severity, age of the patient and quality of care received, and presence of co-morbid conditions. [4]

The oxidative stress that follows acute strokes has more recently been implicated in the neuronal injury, which to a large extent influences the severity and outcome. [5],[6],[7] Oxidative stress is caused by reactive intermediate oxygen and nitrogen species called free radicals, which have largely deleterious effects in biologic tissues and antioxidants, are known to counteract, or in the least, mitigate their deleterious effects. [8],[9],[10]

Once thought to be a metabolically inert product of purine metabolism, uric acid is now being recognized as a potent antioxidant of which concentration in plasma is nearly 10 times higher than other antioxidants, including vitamins C and E and so it accounts for a substantial part of the antioxidant property of plasma. [11] Other endogenous antioxidants include glutathione, L-carnithine, coenzyme Q, melatonin, alpha lipoic acid and bilirubin. [12] Uric acid is described as a strong endogenous antioxidant that is consumed early in acute stroke and presently its combination with recombinant tissue plasminogen activator is believed to be synergistic in experimental models of acute ischemic strokes. [13],[14] SUA could therefore serve potentially as a surrogate marker of oxidative stress and an add-on therapy in acute stroke. [14]

The other mechanisms in which SUA causes injury to the cardiovascular system includes its effects on the endovascular endothelium, increases in platelet aggregation, alteration in hemorrheology and inhibition of the synthesis of nitric oxide. [15]

The relationship between hypertension, diabetes mellitus and elevated SUA is not causal and when elevated SUA is present, it has been associated with poorer cardiovascular end points and renal outcomes in the 2 conditions. [15] In a landmark study, improved cardiovascular end points were attributed to the hypouricemic effect of Losartan ahead of its hypotensive effect, a finding that somewhat divested elevated SUA from blood pressure in cardiovascular outcomes including strokes. [16]

SUA is generally increased in gout, poor renal function and by certain drugs like thiazide diuretics. [17] While some have associated elevated SUA with poorer outcomes in acute strokes, others have found different results. In this study, the relationship between admission SUA and the outcome of first-ever acute stroke was investigated in a stroke unit in a tertiary care facility in sub-Saharan Africa.


   Materials and Methods Top


Total 240 acute stroke patients aged 30-91 years (median 60 years), who were admitted into the stroke unit of the University of Benin Teaching Hospital for first-ever acute stroke had their blood samples taken for SUA and blood sugar within 48 hours of onset of stroke symptoms. All patients were consecutively enrolled in the unit protocols for acute stroke care and followed-up for outcome within 6 weeks (42 days) from the date of admission. Outcome was either discharged to follow-up and still in care or in-hospital death. Stroke pathologic subtypes were defined by cranial CT as acute infarct or intracerebral hemorrhage for all study subjects and stroke severity was assessed by the admission GCS.

Biochemical assays were done in the hospital's main laboratory. SUA level was estimated by the uricase method and study was approved by the Ethics Committee of the hospital.

Exclusion

History of gout, thiazide diuretics or allopurinol, or serum creatinine above 2 mg/dl, patients admitted after 48 hours of onset of stroke symptoms or discharged against medical advice.

Statistics

Basic data of age, sex, SUA, blood sugar, blood pressure, stroke subtypes and GCS were expressed as mean ± standard deviation (SD) or percentages and continuous variables were compared between the stroke outcome groups using the independent t-test.

The relationship between SUA and GCS was tested on Pearson's correlation and the predictive relationship between SUA and stroke outcome was tested on logistic regression after adjustment for age above 60 years and elevated blood sugar above 200 mg/dl. The relationship between elevated SUA above or equal to 8 mg/dl and stroke outcome was also tested on logistic regression. The contribution of serum uric acid, blood sugar, age, stroke subtype and GCS to time of all cause in-hospital mortality was tested on Cox proportional hazard regression. Analysis was done with SPSS® version 17 and P < 0.05 was taken as significant for all tests.


   Results Top


A total of 240 participants were studied with a mean age of 59.65 ± 12.73 years (range, 30-91 and a median of 60 years) comprising 120 females and 120 males. There were a total of 102 (42.5%) cases of acute intracerebral hemorrhage and 138 (57.5%) cases of acute infarct. They were divided into 2 groups 3-4 discharged or still in care (n = 168) and those that died from all cause in-hospital mortality (n = 72) [Table 1].
Table 1: Basic data of study participants


Click here to view


The group that was discharged or still in care had a mean age of 56.00 ± 11.24 years and the in-hospital mortality group had a mean age of 68.16 ± 11.96 years. The percentage distribution of females and males in the 2 outcome groups were 30% and 40% (discharged or still in-care) and 20% and 10% (in-hospital mortality), respectively. There were more cases of hemorrhage than infarct (37.5% versus 32.5% of the total) in the group that was discharged or still in-care compared to (5% versus 25% of the total) the in-hospital mortality group as shown in [Table 1].

The group with in-hospital mortality had significantly higher mean age (P < 0.001), mean blood sugar (P < 0.001) and mean serum uric acid levels (P < 0.001) and a lower mean GCS score (P < 0.001) respectively, compared to the group that was discharged or still in-care [Table 1].

There was however no significant differences in the mean systolic and diastolic blood pressures of both groups (P = 0.433 and P = 0.121, respectively) [Table 1].

When stroke subtypes were stratified by SUA levels, there was no significant difference, but stratification by GCS level showed a significant difference (P = 0.664 and 0.027), respectively as shown in [Table 2].
Table 2: Stroke subtype stratification by serum uric acid and glasgow coma scale


Click here to view


SUA correlated significantly with GCS (r = −0.189, P = 0.008) as shown in [Table 3].
Table 3: Correlation of serum uric acid and glasgow coma scale


Click here to view


SUA was significantly associated with poorer acute stroke outcome after adjusting for advancing age above 60 years and elevated blood sugar above 200 mg/dl OR = 1.496 (1.008-2.219), P = 0.045, n = 96). Elevated SUA above or equal to 8 mg/dl was also significantly associated with poorer outcome (in-hospital mortality), OR = 1.757, (1.251-2.470) P = 0.001, n = 84 as shown in [Table 4].
Table 4: SUA and acute stroke outcome after adjustment for age above 60 years and random blood sugar above 200 mg/dl and SUA above or equal to 8 mg/dl


Click here to view


The significant contribution of serum uric acid (P = 0.024) and the other covariates of blood sugar (P < 0.001) and age (P < 0.001) to time of all cause in-hospital mortality on Cox proportional hazard regression is shown in [Table 5]. However, stroke subtype and GCS did not significantly predict time of in-hospital mortality (P = 0.173, P = 0.256).
Table 5: Serum uric acid, random blood sugar, stroke subtype, age, GCS and time to all cause in-hospital mortality


Click here to view



   Discussion Top


Elevated SUA is linked with poorer acute stroke outcomes and an increased risk of repeat vascular events as well as a higher incidence of first-ever acute stroke independent of other biochemical derangements. [3] Recent evidence has also suggested favorable associations of cardiovascular event prevention and better outcome with the hypouricemic drug allopurinol. [1],[18] However, some studies have, in contrast, associated elevated SUA with better outcomes in acute strokes. [5],[19] The relationship between SUA and acute stroke outcome was found to be dependent on the level of uric acid in another related study, in which low and elevated levels were both associated with poorer outcome compared to normal levels. [20]

In this study, both acute hemorrhagic and ischemic strokes were considered. We note the significant difference between the mean ages of the 2 outcome groups, with a higher mean age associated with in-hospital mortality. This is in agreement with advancing age as a predictive factor in poorer acute stroke outcome. [18],[21] We also note the significant difference in the mean blood sugar levels between the outcome groups. Higher mean blood sugar was associated with in-hospital mortality. Elevated blood sugar is also known to influence stroke outcomes negatively. [19],[22] The mean SUA was also higher in the deceased group, suggesting the association of elevated SUA with poorer acute stroke outcome. GCS, a reflection of stroke severity was significantly lower in the in-hospital mortality group. [23],[24] GCS correlates reliably with well known stroke severity scales like the National Institutes of Health Stroke Scale (NIHSS) and Canadian Neurological Scale (CNS). [25],[26]

The absence of any significant differences between the mean blood pressures of both groups is noteworthy, as it somewhat divests blood pressure from SUA and speaks against any possible confounding effect of high blood pressure in the relationship between acute stroke outcome and SUA in this study. This last point is also corroborated in the Losartan Introduction in Favorable Endpoint (LIFE) study where improved cardiovascular end points or outcomes were attributed to the hypouricemic effect of Losartan independent of the reduction in blood pressure. [16]

The significant difference between the GCS and of the stroke subtypes may have accounted for the higher in-hospital mortality of the cases with intracerebral infarct compared with those with intracerebral hemorrhage.

More remarkably, SUA correlated with GCS significantly and this suggests a tendency of SUA to indirectly reflect stroke severity. SUA also showed a significant predictive relationship to poorer acute stroke outcome independent of advancing age above 60 years and elevated blood sugar above 200 mg/dl as shown in an earlier study. [3] Elevated SUA up to 8 mg/dl and above was also significantly predictive of poorer acute stroke outcome. SUA is normally between 2 and 7 mg/dl in health with slightly higher values in men compared to women and levels up to 8 mg/dl and above are clearly in the elevated range. [5] SUA levels may also be influenced by diet, age, diabetes mellitus, drugs and poor renal function. [8],[27],[28]

The contribution of SUA to the time of all cause in-hospital mortality is also noted. It is in consonance with the predictive effect of SUA on poorer acute stroke outcomes mentioned earlier in this study. SUA together with random blood sugar and age significantly predicted time to all cause in-hospital mortality. GCS however did not significantly predict the time to all cause in-hospital mortality in comparison to its very significant effect on the 42-day outcome probably as a result of the wide variability of GCS in the deceased patients in relation to time of death. GCS is undoubtedly one of the most reliable indices of prognosis in strokes, whether it equally predicts the time to outcome cannot be said emphatically from currently available literature on the subject. [23],[29] Stroke subtype also did not significantly predict time of all cause mortality. Hemorrhagic strokes have been more associated with poorer outcomes in strokes, compared to infarcts; this however may not translate to prediction of time to acute stroke outcome. [30]

The recognition of elevated SUA as a predictor variable in the outcome of acute stroke independent of advancing age and elevated blood sugar in this study as in some earlier ones and the correlation of SUA with GCS, adds to the growing line of evidence on the relationship between SUA and acute stroke outcome. SUA may become a reliable biochemical surrogate marker or proxy of acute stroke outcome and by extension, a potential therapeutic target in Africans as shown previously in other populations. [14] Larger prospective studies would probably better clarify the issues raised.


   Acknowledgment Top


We acknowledge the contributions of doctors and support staff of the neurology/stroke unit and the research laboratory in the University of Benin Teaching Hospital.

 
   References Top

1.Muir SW, Harrow C, Dawson J, Lees KR, Weir CJ. Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke. Stroke 2008;39:3303-7.  Back to cited text no. 1
    
2.Karagiannis A, Mikhailidis DP, Tziomalos K, Sileli M, Savvatianos S, Kakafika A, et al. Serum uric acid as an independent predictor of early death after acute stroke. Circ J 2007;71:1120-7.  Back to cited text no. 2
[PUBMED]    
3.Weir CJ, Muir SW, Walters MR, Lees KR. Serum urate as an independent predictor of poor outcome and future vascular events after acute stroke. Stroke 2003;34:1951-6.  Back to cited text no. 3
[PUBMED]    
4.Kazmierski R. Predictors of early mortality in patients with ischaemic stroke. Expert Rev Neurother 2006;6:1349-62.  Back to cited text no. 4
[PUBMED]    
5.Chamorro A, Obach V, Cervera A, Revilla M, Deulofeu R, Aponte JH. Prognostic significance of uric acid serum concentration in patients with acute ischemic stroke. Stroke 2002;33:1048-52.  Back to cited text no. 5
[PUBMED]    
6.Cherubini A, Polidori MC, Bregnocchi M, Pezzuto S, Cecchetti R, Ingegni T, et al. Antioxidant profile and early outcome in stroke patients. Stroke 2000;31:2295-300.  Back to cited text no. 6
[PUBMED]    
7.Bowman GL, Shannon J, Frei B, Kaye JA, Quinn JF. Uric acid as a CNS antioxidant. J Alzheimers Dis 2010;19:1331-6.  Back to cited text no. 7
[PUBMED]    
8.Benzie IF. Evolution of antioxidant defence mechanisms. Eur J Nutr 2000;39:53-61.  Back to cited text no. 8
[PUBMED]    
9.Sahnoun Z, Jamoussi K, Zeghai KM. Free radicals and antioxidants: Human physiology, pathology and therapeutic aspects. Therapie 1997;52:251-70.  Back to cited text no. 9
    
10.Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.  Back to cited text no. 10
[PUBMED]    
11.Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 1993;84:407-12.  Back to cited text no. 11
[PUBMED]    
12.Rizzo AM, Berselli P, Zava S, Montorfano G, Negroni M, Corsetto P, et al. Endogenous antioxidants and radical scavengers. Adv Exp Med Biol 2011;698:52-67.  Back to cited text no. 12
    
13.Amaro S, Soy D, Obach V, Cervera A, Planas A, Chamorro A. A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischaemic stroke. Stroke 2007;38:2173-5.  Back to cited text no. 13
    
14.Amaro S, Chamorro Ã. Translational stroke research of the combination of thrombolysis and antioxidant therapy. Stroke 2011;42:1495-9.  Back to cited text no. 14
    
15.Alderman M, Aiyer KJ. Uric acid: Rolle in cardiovascular disease and effects of losartan. Curr Med Res Opin 2004;20:369-79.  Back to cited text no. 15
[PUBMED]    
16.Devereux RB, Dahlof B. Potential mechanisms of stroke benefit favoring Losartan Intervention For Endpoint reduction (LIFE) study. Curr Med Res Opin 2007;23:443-57.  Back to cited text no. 16
    
17.Charles BA, Shriner D, Doumatey A, Cheng G, Zhou J, Huang H, et al. A genome-wide association study of serum uric acid in African Americans. BMC Med Genomics 2011;4:17.  Back to cited text no. 17
    
18.Strazzullo P, Puig JG. Uric acid and oxidative stress: Relative impact on cardiovascular risk. Nutr Metab Cardiovasc Dis 2007;17:409-14.  Back to cited text no. 18
[PUBMED]    
19.Zhang B, Gao C, Yang N, Zhang W, Song X, Yin J, et al. Is elevated SUA associated with a worse outcome in young Chinese patients with acute cerebral ischemic stroke? BMC Neurol 2010;10:82.  Back to cited text no. 19
[PUBMED]    
20.Seet RC, Kasiman K, Gruber J, Tang SY, Wong MC, Chang YH, et al. Is uric acid protective or deleterious in acute ischemic stroke? A prospective cohort study. Atherosclerosis 2010;209:215-9.  Back to cited text no. 20
    
21.Longo-Mbenza B, Lelo Tshinkwela M, Mbulu Pukuta J. Rates and predictors of stroke associated case fatality in black central African patients. Cardiovasc J Afr 2008;19:72-6.  Back to cited text no. 21
    
22.Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in non-diabetic and diabetic patients: A systematic overview. Stroke 2001;32:2426-32.  Back to cited text no. 22
[PUBMED]    
23.Cheung RT, Zou LY. Use of the original, modified, or new intracerebral haemorrhage score to predict mortality and morbidity after intracerebral haemorrhage. Stroke 2003;34:1717-22.  Back to cited text no. 23
[PUBMED]    
24.Weingarten S, Bolus R, Riedinger MS, Maldonado L, Stein S, Ellrodt AG. The principle of parsimony: Glasgow Coma Score predicts mortality as well as the APACHE 2 score for stroke patients. Stroke 1990;21:1280-2.  Back to cited text no. 24
[PUBMED]    
25.Sun TK, Chiu SC, Yeh SH, Chang KC. Assessing reliability and validity of the Chinese version of the stroke scale: Scale development. Int J Nurs Stud 2006;43:457-63.  Back to cited text no. 25
[PUBMED]    
26.Nilanont Y, Komoltri C, Saposnik G, Cote R, Di Legge S, Jin Y. The Canadian Neurological Scale and the NIHSS: Development and validation of a simple conversion model. Cerebrovasc Dis 2010;30:120-6.  Back to cited text no. 26
    
27.Newman EJ, Rahman FS, Lees KR, Weir CJ, Walters MR. Elevated serum urate concentration independently predicts poor outcome following stroke in patients with diabetes. Diabetes Metab Res Rev 2006;22:79-82.  Back to cited text no. 27
[PUBMED]    
28.Satirapoj B, Supasyndh O, Nata N, Phulsuksombuti D, Utenam D, Kajanaku I, et al. High levels of uric acid correlate with decline of filtration rate in chronic kidney disease. J Med Assoc Thai 2010;93 suppl 6:s65-70.  Back to cited text no. 28
    
29.Flemming KD, Wijdicks EF, Li H. Can we predict poor outcome at presentation in patients with lobar haemorrhage? Cerebrovasc Dis 2001;11:183-9.  Back to cited text no. 29
[PUBMED]    
30.Obiako OR, Oparah SK, Ogunniyi A. Prognosis and outcome of acute stroke in the University College Hospital Ibadan, Nigeria. Niger J Clin Pract 2011;14:359-62.  Back to cited text no. 30
[PUBMED]  Medknow Journal  



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Acknowledgment
    References
    Article Tables

 Article Access Statistics
    Viewed2616    
    Printed134    
    Emailed0    
    PDF Downloaded478    
    Comments [Add]    

Recommend this journal