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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 1  |  Page : 10-13

Study of serum uric acid and homocysteine levels in acute ischemic stroke


Department of General Medicine, MR Medical College, Kalaburagi, Karnataka, India

Date of Submission03-Mar-2020
Date of Decision27-Mar-2020
Date of Acceptance09-May-2020
Date of Web Publication03-Feb-2021

Correspondence Address:
Dr. Srinith B Patil
H. No. 17A, Shri Sadan, 1st Cross, Near, Basava PU College, Jayanagar, Sedam Road, Kalaburagi - 585 105, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_13_20

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  Abstract 


Introduction: Worldwide, stroke is the third most common cause of death after coronary heart disease and all cancer deaths. All the physicians have a role to play in the prevention of stroke by encouraging the reduction in risk factors. Ischemic stroke accounts for >80% of total stroke events. There is growing evidence that high serum uric acid and homocysteine levels contribute to the pathogenesis of ischemic stroke, and early identification of individuals at risk could be of help in primary prevention strategies. Aims: The aim was to study the association between levels of serum uric acid and homocysteine and acute ischemic stroke and to compare them with control subjects. Materials and Methods: A case–control study was carried out among 100 subjects, which included 50 cases of first-time ischemic stroke and 50 healthy controls attending the outpatient department and casualty, in whom serum uric acid levels, serum homcysteine, and other associated risk factors were evaluated. Results: The overall mean age of the case population was 55.84 ± 15.57 years and control was 59.92 ± 11.62 years. Among the 50 cases of first-time ischemic stroke and 50 controls, males constituted 32 (64%) and 30 (60%), respectively. The mean uric acid level in case population was 5.32 ± 1.09 mg/dl and in controls was 3.21 ± 1.01 (P = 0.001). The mean homocysteine level in case population was 20.85 ± 10.85 μmol/l and in controls was 8.10 ± 3.54 (P = 0.001). Among the case population, 28 (56%) were found to have hypertension, followed by smoking 19 (38%), diabetes mellitus 18 (36%), and alcoholism 13 (26%). Conclusion: Significant elevation of both uric acid and homocysteine in a cohort of stroke patients when compared to the control group was found. Thus, it is concluded from the present study that an elevated uric acid and homocysteine level appears to be an important risk factor for stroke. Hypertension was found to be the most common modifiable risk factor.

Keywords: Homocysteine, stroke, uric acid


How to cite this article:
Patil SB, Belli B, Biradar S, Patil A. Study of serum uric acid and homocysteine levels in acute ischemic stroke. APIK J Int Med 2021;9:10-3

How to cite this URL:
Patil SB, Belli B, Biradar S, Patil A. Study of serum uric acid and homocysteine levels in acute ischemic stroke. APIK J Int Med [serial online] 2021 [cited 2021 May 14];9:10-3. Available from: https://www.ajim.in/text.asp?2021/9/1/10/308645




  Introduction Top


Stroke is a global health problem, defined as rapidly developing clinical symptoms and/or signs of focal or at times a global loss of cerebral function with symptoms lasting more than 24 h or leading to death with no other apparent reason other than that of vascular origin, namely lesion of the vessel wall, occlusion of vessels by thrombus or embolus, and ruptured or altered permeability of the vessel wall.[1] The prevalence of stroke in the Indian population is 90–222/lakh population, with 28–30 day case fatality ranging from 18% to 41%.[[2]] In spite of advances made in the diagnosis and management of stroke patients, there remains a substantial number of stroke events that cannot be explained on the basis of conventional risk factors, leading to look for newer risk factors. There is growing evidence that high serum uric acid and homocysteine levels contribute to the pathogenesis of ischemic stroke. Although there are studies that show no increase in risk, still there is debate regarding the strength and validity of the association. This disparity may be partly explained by methodological differences between the different studies, such as use of fasting and nonfasting samples, differing timing of sampling poststroke, and different subtypes of strokes studied.[3] The absence of any such data in the region was one of the motivating factors for the present study.

Aims and objectives

The aim was to study the association between levels of serum uric acid and homocysteine and acute ischemic stroke and to compare them with the control population.


  Materials and Methods Top


It is a case–control study conducted over 19 months from November 2016 to June 2018. The number of subjects was 100, with 50 cases and 50 controls. The study subjects were selected after applying inclusion–exclusion criteria.

Inclusion criteria for cases

Inclusion criteria for cases included patients admitted to the hospital with first-ever-in lifetime acute ischemic stroke with computed tomography (CT) scan evidence of infarction within 72 h of the onset of stroke.

Exclusion criteria for cases

  1. Patients with a previous history of transient ischaemic attack/cerebrovascular accident
  2. Patients who are on thiazide diuretics
  3. Patients who are known cases of gout or show clinical evidences of gout
  4. Patients with chronic renal failure
  5. Patients whose CT scan show hemorrhage or other space-occupying lesions other than infarct
  6. Patients who were of known cardiac diseases which could be sources of emboli or whose echocardiogram shown sources of emboli
  7. Patients with hemotological abnormalities such as leukemia or other myeloproliferative disorders
  8. Patients on antitubercular treatment containing pyrazinamide.


Inclusion criteria for controls

Inclusion criteria for controls included persons without any risk factors (described in exclusion criteria for cases) which may cause raised uric acid and homocysteine levels.

Patient recruitment

Patients attending the outpatient department and casualty of the hospital and satisfying the inclusion–exclusion criteria were taken as cases and controls after obtaining written informed consent from the patient or relatives. Detailed history; physical examination; relevant laboratory investigations such as complete blood count, serum uric acid, serum homocysteine, and serum creatinine; and radiological investigations such as noncontrast CT of the brain or magnetic resonance imaging of the brain were carried out.

Data entry and analysis

Descriptive and inferential statistical analysis was carried out in the study. The results were analyzed using computer software packages (SPSS, version 18; IBM, India). The results on continuous variables were presented as mean ± standard deviation (minimum–maximum) and categorical variables as absolute numbers (n) and relative frequency (%). Significance was assessed at a 5% level of significance. Chi-square test with Yates' correction was used to find the significance difference of study parameters between the groups.


  Results Top


The overall mean age of the case population was 55.84 ± 15.57 years and control was 59.92 ± 11.62 years [Table 1]. Twenty-seven (54%) individuals of the case population were between 51 and 70 years of age, followed by 11 (22%) who were between 31 and 50 years and cases between 11–20 and 71–90 were 6 each (12%). Twenty-seven (54%) individuals of the control population were between 51 and 70 years [Table 2].
Table 1: Baseline characteristics of case and control groups

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Table 2: Age distribution of study population

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Among the case and control population, males constituted 32 (64%) and 30 (60%), respectively, and females constituted 18 (36%) and 20 (40%), respectively [Table 3].
Table 3: Gender distribution of the study population

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Most of the case population, 32 (64%), had uric acid between 2.1 and 6 mg/dl and 18 (36%) had uric acid =6.1 mg/dl. Among the control population, 49 (98%) had uric acid levels between 2.1 and 6 mg/dl. The mean uric acid level in case population was 5.32 ± 1.09 mg/dl and in controls was 3.21 ± 1.01 [Table 4]. The difference between the groups was statistically significant (P = 0.001).
Table 4: Distribution of uric acid in the study population

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Nearly three-fourth, 36 (72%), of the case population had high homocysteine =15.1 μmol/l, followed by 13 (26%) had between 4.1 and 15 μmol/l. Most of the control population, 43 (86%), had homocysteine between 4.1 and 15 μmol/l. The mean homocysteine level in case population was 20.85 ± 10.85 μmol/l and in controls was 8.10 ± 3.54 μmol/l [Table 5]. The difference between the groups was significant (P = 0.001).
Table 5: Distribution of homocysteine in the study population

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Among the case population, 28 (56%) were found to have hypertension, followed by smoking 19 (38%), diabetes mellitus 18 (36%), and alcoholism 13 (26%) [Graph 1].



Abnormalities in the anterior circulation were found in 47 (94%) cases and 3 (6%) had abnormalities in the posterior circulation [Graph 2].



The association between serum uric acid levels and factors such as hypertension (P = 0.217), diabetes mellitus (P = 0.364), smoking (P = 0.923), and alcohol intake (P = 0.830) was found to be statistically not significant

The association between serum homocysteine levels and factors such as hypertension (P = 0.327), diabetes mellitus (P = 0.381), smoking (P = 0.290), and alcohol intake (P = 0.791) was found to be statistically not significant.


  Discussion Top


The most important risk factors for stroke are increasing age and hypertension. Male gender is said to be at more risk of stroke than female. Other risk factors for stroke include diabetes mellitus, dyslipidemias, cardiac disease, transient ischemic attacks, smoking, family history of stroke, sedentary life style, peripheral vascular disease, use of oral contraceptive pills, infections, migraine, and alcohol consumption. In spite of advances made in the diagnosis and management of stroke patients, there remains a substantial number of stroke events that cannot be explained on the basis of conventional risk factors leading to search for uncommon risk factors such as hyperuricemia and hyperhomocysteinemia which have shown to play a role in causation of ischemic stroke.

Uric acid is a product of metabolism of purine nucleotides that are the principal constituents of cellular energy stores, such as adenosine triphosphate (ATP) and components of deoxyribonucleic acid (DNA) and ribonucleic acid.[4] Direct exposure of endothelial cells to uric acid slightly reduces basal or vascular endothelial growth factor stimulated nitric oxide production. Thus, uric acid can dose dependently reduce nitric oxide bioavailability.[5] In experimental studies, uric acid has been shown to stimulate the release of interleukin-I b (IL-I b), IL-6, and tumor necrosis factor-alpha synthesis,[6] thus contributing to the development of human vascular disease and atherosclerosis through a pro-inflammatory pathway. We have found from the present study that stroke patients had a significantly elevated level of serum uric acid than the control population. The findings of our study are similar to the study by Deepak et al.,[7] Kaur et al.,[8] and Behera et al.[9] where the mean serum uric acid level was 6.07 ± 2.68 mg/dl, 6.0 ± 2.30 mg/dl, and 5.52 ± 1.40 mg/dl, respectively.

Homocysteine is a sulfur containing amino acid formed from the thiol group during the metabolism of methionine. Homocysteine stimulates vascular smooth muscle proliferation and increases DNA synthesis, cyclin A.[10] It increases platelet adhesion and aggregation and inhibition of Na + K + ATPase activity and hemolysis of erythrocytes. Homocysteine may enhance the binding of lipoprotein (a) to fibrin.[11] In high concentration, it activates factor V, reduces protein C activation, inactivates the cofactor activity of thrombomodulin, and suppresses thrombomodulin;[12] thus, homocysteine affects the endothelial surface, vascular smooth muscle cells, plasma lipoproteins, connective tissues, platelets, coagulation factors, blood lipids, and nitric oxide leading to thromboembolism and atherosclerosis and vascular endothelial damage causing ischemic stroke. We have found from the present study that stroke patients had a significantly elevated level of serum homocysteine than the control population. The findings of our study are similar to the study by Coull BM,[13] Delser et al.,[14] Rahman et al.,[15] and Gajbhare and Juvale[16] study where serum homocysteine levels were 15.78 ± 5.40, 26.2 pmol/l, 21.89 ± 9.38, and 30.10 ± 14.8, respectively.

Hypertension (56%) was the most common risk factor, followed by smoking (52.08%) and then diabetes (36%). The present study demonstrated the substantial role of modifiable risk factors such as hypertension, diabetes mellitus, cigarette smoking, and alcohol consumption in stroke.

The sample size is small and limits the generalization of the observations. The present study could not measure Vitamin B12 and folate levels, which are cofactors in homocysteine metabolism and documented to be strong correlates of homocysteine levels. Further, prospective studies with a higher sample size to look for the association or causation of both serum uric acid and homocysteine in stroke patients are required.


  Conclusion Top


The present study found a significant elevation of both uric acid and homocysteine in a cohort of stroke patients when compared to the control group; thus, it is prudent to use serum homocysteine and uric acid level as an important tool to investigate all cases of ischemic stroke and also in those who are at risk of developing it; hence, it is concluded from the present study that an elevated serum homocysteine and uric acid level appears to be an important risk factor for stroke, and primary and secondary prevention strategies targeting the traditional modifiable risk factors and interventions reducing serum homocysteine and uric acid levels among the Indian population would benefit them.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Smith WS, Claiborne Johnston S, Claude Hemphill J. Cerebrovascular Diseases, Harrison's Principles of Internal Medicine. 19th ed, McGraw-Hill, New York; 2015. p. 2559.  Back to cited text no. 1
    
2.
Taylor FC, Suresh Kumar K. Stroke in India Factsheet (updated 2012), South Asia Network for Chronic Disease, IIPH Hyderabad, Public Health Foundation of India; 2012.  Back to cited text no. 2
    
3.
Eikelboom JW, Hankey GJ, Anand SS, Lofthouse E, Staples N, Baker RI. Association between high homocysteine and ischemic stroke due to large and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 2000;31:1069-75.  Back to cited text no. 3
    
4.
Ruggiero C, Cherubini A, Ble A, Bos AJ, Maggio M, Dixit VD, et al. Uric acid and inflammatory markers. Eur Heart J 2006;27:1174-81.  Back to cited text no. 4
    
5.
Gersch C, Palii SP, Kim KM, Angerhofer A, Johnson RJ, Henderson GN. Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids 2008;27:967-78.  Back to cited text no. 5
    
6.
Johnson RJ, Rodriguez-Iturb?e B, Kang DH, Feig DI, Herrera-Acosta J. A unifying pathway for essential hypertension. Am J Hypertens 2005;18:431-40.  Back to cited text no. 6
    
7.
Tripathi VD, Hussain Z. A study to find out relationship in between serum uric acid level and stroke, Int J Adv Med 2017;4:1255-9.  Back to cited text no. 7
    
8.
Kaur L, Khurana A, Sachdev JK, Mohan G. Evaluation of serum uric acid in acute ischaemic stroke. Int J Adv Med 2017;4:60-5.  Back to cited text no. 8
    
9.
Behera BK, Hui PK, Simethy R. Serum uric acid level in acute I schemic stroke in eastern India. Int J Res Med Sci 2017;5:2353-7.  Back to cited text no. 9
    
10.
Prasad K. Homocysteine, a risk factor for cardiovascular disease. Int J Angiol 1999;8:76-86.  Back to cited text no. 10
    
11.
Neki NS. Hyperhomocysteinemia-An independent risk factor for cardiovascular diseases JIACM 2003;4:55-60.  Back to cited text no. 11
    
12.
Den Heijer M, Blom HJ, Gerrits WB. Is hyperhomocysteinemia a risk factor for recurrent venous thrombosis. Lancet 1995;345:882-5.  Back to cited text no. 12
    
13.
Coull BM, Malinow MR. Elevated plasma homocysteine concentration as a possible independent risk factor for stroke. Stroke 1990;21:576.  Back to cited text no. 13
    
14.
Del Ser T, Barba R, Herranz AS. Hyperhomocysteinemia is a risk factor for secondary vascular events in stroke patients. Cerebrovascular Dis. 2001;12:91-8.  Back to cited text no. 14
    
15.
Rahman A, Gupta R, Quraishi F, Saha U, Miah M N, Ali Z. Relationship between Homocysteine and ischemic stroke. Bangladesh J Med 2015;25:8-12.  Back to cited text no. 15
    
16.
Gajbhare PT, Juvale NI. The study of plasma homocysteine level as a risk factor for ischemic strokes in young patients. Int J Adv Med 2017;4:1019-25.  Back to cited text no. 16
    



 
 
    Tables

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



 

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