Research, Volume: 14( 1) DOI: 10.37532/0974-7532.2019.14(1).147
Plasma Level of Homocysteine and Lipid Profile in Patients with Cerebrovascular Accident in Tertiary Health Centre in Ogbomoso Oyo State South-West Nigeria
- Joel Olufunminiyi Akande Department of Chemical Pathology, Bowen University Teaching Hospital, Ogbomoso Oyo State, Nigeria; Tel: +234-7066377491; E-mail: [email protected]
Received: November 6, 2019; Accepted: November 15, 2019; Published: November 25, 2019
Citation: Akande JO, Salawu AA, Akande RO, et al. Plasma Level of Homocysteine and Lipid Profile in Patients with Cardiovascular Event in Tertiary Health Centre in Ogbomoso Oyo State South-West Nigeria. Res Rev Biosci. 2019;14(1):147.
Apart from the traditional risk factors, there are newer risk factors such as high plasma level of Homocysteine, Folate deficiency and Vitamin B12 deficiency, associated with cardiovascular disease. Plasma Homocysteine level has been link to the level of LDL-C and functionality of HDL-C. This study is therefore designed to correlate plasma level of Homocysteine with Lipid profile in patient newly diagnosed of cerebrovascular accident. Seventy-Two newly diagnosed stroke patients were consecutively recruited into the study. Seventy-Two apparently healthy, age and sex matched volunteers were recruited from the community as controls. The data obtained were analyzed using SPSS version 20. Level of significance for the study was set at p<0.05. High plasma level of Homocysteine (12.72 ± 5.10 μmol/L), Total-Cholesterol (4.58 ± 1.40 mmol/L) and LDL (3.34 ± 1.41 mmol/L) were obtained from the study population when compared with Homocysteine (7.60 ± 1.80 μmol/L), Total-Cholesterol (3.93 ± 0.91) and LDL (2.23 ± 0.80 mmol/L) obtained from the controls and the difference was highly significant (p<0.01). The difference in the mean plasma level of HDL was statistically significant among study population (0.74 ± 0.32 mmol/L) when compared with Control (1.26 ± 0.38 mmol/L) p<0.001. Homocysteine had weak positive correlations with T-Cholesterol (r=0.172), LDL (r=0.213), Body Fat (r=178) and negative correlation with HDL (r=-0.178) but statistically significant p<0.05. We concluded that elevated plasma level of Homocysteine has significant correlat ion with abnormal lipid profile which is one of the major risk factors for cerebrovascular accident.
Cerebrovascular accident; Homocysteine; Lipid profile; HDL-C; LDL-C
The theme for World Stroke Day in 2008 was “Little stroke, big trouble” focusing on the importance of stroke as a critical warning sign of more debilitating vascular events or death. Presently, stroke constitutes a leading cause of mortality and long term physical and mental disability throughout the world [1,2].
The management is largely conservative, therefore primary prevention is the key to reducing the increasing burden of stroke worldwide especially in developing world like Nigeria [3,4]. A key component of the secondary prevention strategies for stroke advocated by the World Health Organization (WHO) is intensified reduction in exposure to major cardiovascular risk factors [5-7]. There are traditional risk factors associated with cardiovascular events, newer independent risk factors such as high plasma level of homocysteine, folate deficiency and vitamin B12 deficiency have come to limelight and have been focus of research lately. High plasma homocysteine level has been linked to the level of Low-Density Lipoprotein-Cholesterol (LDL-C) and functionality of High-Density Lipoprotein-Cholesterol (HDL-C) [4,8].
High plasma homocysteine concentrations have been associated with increased risk of Cardiovascular Diseases (CVD) [9,10]. However, several large randomized clinical trials have not been able to show a direct link between lowering homocysteine plasma levels with vitamin B therapy and reduction in the risk of CVD or mortality among subjects with known CVD . Endothelial dysfunction, increased oxidative stress, alterations of lipid metabolism, and induction of thrombosis have been suggested to be pathogenesis of CVD in Hyperhomocysteinemia [12,13]. However, the mechanism by which homocysteine could promote atherogenesis and thromboembolic disorders is far from clear and the role of Homocysteine in human CVD is largely unclear and subject of debate .
This study was, therefore, designed to see the relationship between plasma Homocysteine level and well established risk factor for CVD-abnormal lipid profile.
Materials and Methods
Bowen University Teaching Hospital (BUTH) and Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital (LTH) both located in Ogbomoso, Oyo State, Nigeria, were used as the sites of the study. The subjects were new clinically diagnosed with Cerebrovascular Accident (CVA) with CT scan confirmation. Patients with complications such as renal, liver pathology or other medical illnesses were excluded. Patients on lipid regulating drugs were also excluded from the study. History and physical examination were taken from the subjects and blood samples were collected for analysis It was a cross-sectional study with semi-structured questioner administered as a survey instrument. Seventy-Two newly diagnosed CVA patients presenting at Accident and Emergency units of both institutions were consecutively recruited into the study after obtaining their informed consent. Another seven-two apparently healthy normotensive, age, and sex-matched volunteers were recruited from Ogbomoso Community as controls after obtaining their informed consent.
Ethical clearances for the study were obtained from the Ethical Review Committee of Ladoke Akintola University of Technology Teaching Hospital and Bowen Teaching Hospital.
Blood sample collection, storage and laboratory analysis
A fasting venous blood was collected into 0.1% Na EDTA bottle from each subject and control using the standard technique of phlebotomy. Each sample was centrifuged at 3,000 xg for 5 minutes. The plasma obtained was stored frozen at -200°C before analysis. Plasma from both subjects and controls were analyzed in batches using standards and controls for all the biochemical parameters. The enzymatic endpoint was used for lipid profile parameters except LDL-Cholesterol, using kits from Randox Laboratories Limited, (Batch Number; CH 200 Lot 363904/97QX, TR 210 325799 87 D8, CH203 2344CH) Crumlin, UK. Low-density lipoprotein cholesterol was calculated using freidwald’s formula . Homocysteine was measured by Enzyme-Linked Immune-Sorbent Assay (ELISA) using commercial kits (Human) purchased from Span Biotech Limited (Batch Number; E201509198050), Hong Kong.
The data obtained were analyzed using Statistical Package for Social Sciences (SPSS) version 20. Frequency distribution tables were generated from variables like age, sex, religion, marital status, and ethnicity, while cross-tabulation and test statistics were done. The Chi-square test was used to compare proportion, while Student ‘t’ test was used to compare means of continuous variables. The Analysis of Variance (ANOVA) test was used to compare the means of more than two variables. Pearson's correlation analysis was used to test the strength and direction of relationship between continuous variables. The level of significance was set with p-value less than or equal to 0.05.
TABLE 1 shows the socio-demographic characteristics of the study population and controls. The study population included 72 patients with stroke and 72 apparently healthy people as controls. The age range for controls and subjects were between 30-95years. There was no significant difference in the mean age when compared to subjects with controls. The employment status in subjects compared with controls was significantly different (p<0.05) as shown above. All other socio-demographic characteristics were not statistically significant.
|Study population (n=72)||Control (n=72)||Total (N=144)|
|Age group (in years)||6.455||4||0.168|
|30-39||3 (4.2)||4 (5.6)||7 (4.9)|
|40-49||8 (11.1)||14 (19.4)||22 (15.3)|
|50-59||14 (19.4)||22 (30.6)||36 (25.0)|
|60-69||15 (20.8)||11 (15.3)||26 (18.0)|
|≥70||32 (44.4)||21 (29.2)||53 (36.8)|
|Male||31 (43.1)||22 (30.6)||53 (36.8)|
|Female||41 (56.9)||50 (69.4)||91 (63.2)|
|No formal education||30 (41.7)||35 (48.6)||65 (45.1)|
|Primary||16 (22.2)||18 (25.0)||34 (23.6)|
|Secondary||14 (19.4)||12 (16.7)||26 (18.1)|
|Tertiary||12 (16.7))||7 (9.7)||19 (13.2)|
|Christianity||57 (79.2)||57 (79.4)||114 (79.2)|
|Islam||15 (20.8)||15 (20.8)||30 (22.8)|
|Yes||35 (48.6)||47 (65.3)||82 (56.9)|
|No||37 (51.4)||25 (34.7)||62 (43.1)|
|Unskilled||15 (42.9)||28 (59.6)||43 (52.4)|
|Semiskilled||12 (34.3)||6 (12.8)||18 (22.0)|
|Skilled||8 (22.9)||13 (27.2)||21 (25.6)|
|Never married||0 (0.0)||2 (2.8)||2 (1.4)|
|Currently married||44 (61.1)||41 (56.9)||85 (59.0)|
|Separated||3 (4.2)||0 (0.0)||3 (2.1)|
|Divorced||0 (0.0)||3 (4.2)||3 (2.1)|
|Widowed||25 (34.7)||26 (36.1)||51 (35.4)|
TABLE 1. Demographic profile of the respondents.
TABLE 2 shows above statistically significant differences were observed in those who had hypertension, Family history of hypertension, involved in exercise, had DM and had a family history of DM (p<0.005) in study population compared to controls. More people had abnormal BMI in study population compared with controls and were statistically significant. Although, more people had abnormal waist/hip ratio among study population the differences were not statistically significant.
|Study population (n=72)||Control (n=7)||Total (n=144)|
|Yes frequently||8 (11.1)||2 (2.8)||10 (6.9)|
|Yes occasionally||6 (8.3)||2 (2.8)||8 (5.6)|
|No but in the past||6 (8.3)||6 (8.3)||12 (8.3)|
|No never before||52 (72.2)||62 (86.1)||114 (79.2)|
|Yes frequently||0 (0.0)||2 (2.8)||2 (1.4)|
|No but in the past||0 (0.0)||2 (2..8)||2 (1.4)|
|No never before||72 (100.0)||68 (94.4)||140 (97.2 )|
|Yes||54 (75.0)||0 (0.0)||54 (37.5)|
|No||18 (25.0)||72 (100.0)||90 (62.5)|
|Diabetic Mellitus (DM)||8.471||1||0.004**|
|Yes||8 (11.1)||0 (0.0)||8 (5.6)|
|No||64 (88.9)||72 (100.0)||136 (94.4)|
|Yes||6 (8.3)||32 (47.2)||38 (26.4)|
|No||66 (91.7)||38 (52.8)||104 (72.2)|
|Family history HNT||14.3954||2||0.001**|
|Yes||28 (38.9)||11 (15.3)||39 (27.1)|
|No||32 (44.4)||54 (75.0)||86 (59.7)|
|Don’t know||12 (16.7)||6 (8.3)||18 (12.5)|
|Family history DM||8.508||2||0.014*|
|Yes||14 (19.4)||3 (4.2)||17 (11.8)|
|No||38 (52.8)||49 (68.1.2)||87 (60.4)|
|Don’t know||20 (27.8)||20 (27.8)||40 (27.8)|
|Family history of stroke||2.165||2||0.339|
|Yes||6 (8.3)||6 (8.3)||12 (8.3)|
|No||55 (76.4)||48 (66.7)||103 (71.5)|
|Don’t know||11 (15.3)||18 (25.0)||29 (20.1)|
|Waist hip ratio||3.575||1||0.059|
|Normal||24 (33.3)||14 (19.4)||38 (26.4)|
|Elevated||48 (66.7)||57 (79.2)||105 (72.9)|
|Body mass index||16.784||3||0.001**|
|Underweight||0 (0.0)||6 (8.3)||6 (4.2)|
|Normal||27 (37.5)||43 (59.7)||70 (48.6)|
|Overweight||26 (36.1)||13 (18.4)||39 (27.1)|
|Obesity||19 (26.4)||10 (13.9)||29 (20.1)|
TABLE 2. Assessment of risk factors for stroke.
TABLE 3 shows high level of plasma Homocysteine (12.72 ± 5.10 μmol/L), Total Cholesterol (4.58 ± 1.40 mmol/L) and LDL-C (3.34 ± 1.41 mmol/L) in the study population when compared with Homocysteine (7.60 ± 1.80 μmol/L), Total Cholesterol (3.93 ± 0.91) and LDL-C (2.23 ± 0.80 mmol/L) than that of control and the difference was highly significant (p<0.01). The difference in the mean plasma level of HDL-C was statistically significant among study population (0.74 ± 0.32 mmol/L) when compared with Control (1.26 ± 0.38 mmol/L) p<0.001 The mean value of SBP (152.69 ± 29.80 mmHg) and DBP (89.38 ± 17.47 mmHg) for study population and SBP (117.23 ± 16.93 mmHg) and DBP (71.13 ± 11.59 mmHg) for controls and they were significantly elevated in study population (p<0.001). The Mean Body Fat (33.33 ± 6.49) in subjects compared with mean body fat (29.79 ± 7.97) in controls were significantly different (p<0.005).
|HCY(μmol/L)||12.72 ± 5.10||7.60 ± 1.80||8.073||**<0.001|
|Total- Chol (mmol/L)||4.58 ± 1.40||3.93 ± 0.91||3.136||**0.002|
|HDL-C (mmol/L)||0.74 ± 0.32||1.26 ± 0.38||8.89||**<0.001|
|LDL-C (mmol/L)||3.34 ± 1.41||2.23 ± 0.80||5.521||**<0.001|
|TRIG (mmol/L)||1.12 ± 0.68||0.98 ± 0.45||1.431||0.155|
|SBP (mmHg)||152.69 ± 29.80||117.23 ± 16.93||8.927||**<0.001|
|DBP (mmHg)||89.38 ± 17.47||71.13 ± 11.59||7.514||**<0.001|
|BODYFAT (%)||33.3 3± 6.49||29.79 ± 7.97||2.33||*0.021|
TABLE 3. Comparison of anthropometric measurements and biochemical parameters.
TABLE 4 shows that HCY had weak positive correlations with T-Chol (r=0.172), LDL-C (r=0.213), Body Fat (r=178) and negative correlation with HDL (r=˗0.178) but statistically significant p<0.05. T-Chol had a positive correlation with LDL-C (r=0.932 strong) and TRIG (r=0.309) both were highly significant, p<0.01. HDL-C showed a weak negative correlation with LDL-C (r=˗0.231), TRIG (r=˗0.170) and Waist/Hip ratio. The correlations were significant p<0.05. There was strong and highly significant correlation between percentage Body Fat and BMI (r=0.678), p<0.01. Also, a significant but weak positive correlation exists but percentage Body Fat and Waist/Hip ratio (r=0.215), p<0.5.
|Body fat (%)||r||0.178||0.025||-0.106||0.041||0.088||0.676||0.215||1|
TABLE 4. Correlation of plasma level of homocysteine, T-Chol, HDL-C, LDL-C, TRIG, BMI, WHR and % body fat in patients with stroke.
The aim of this study is to access the correlation between major risk factors of cerebrovascular accident for the purpose of primary prevention. The major risk factor for cerebrovascular accident in this study was hypertension. Seventy-five percent of the study population was hypertensive and was highly significant when compared with controls (p<0.001), this has been documented in studies [15,16]. Family history of hypertension, DM, and lack of regular exercise had been shown to play a significant role in development of the cardiovascular event, as well as abnormal anthropometric measurements such as BMI and Waist/Hip Ratio, are established risk factors for cardiovascular event and those were significantly high in the study population. Weight reduction and prescribed regular exercise have been found to be integral part of primary preventive measures [17,18].
Abnormal lipid profile was found to be high among the study population when compared with that of controls, that is, elevated plasma level of total cholesterol and LDL-Cholesterol while plasma level of HDL-Cholesterol was low. This abnormal pattern has been established and documented in many journals as primary risk factors for cardiovascular events. Primary and secondary preventive measures have been centered on the treatment of abnormal lipid profile [19,20].
A high significant plasma level of Homocysteine was observed in the study population when compared with that of controls. This is similar to a study done by Suleiman et al. in Northwest Nigeria . Elevated plasma level of Homocysteine has been implicated in pathogenesis of vascular events and now regards as isolated newer risk factor for stroke [13,22].
Pearsons correlation was done to see if there was any correlation between plasma level of Homocysteine and lipid parameters and various degrees of correlations were observed. We found that Total Cholesterol, LDL-Cholesterol, and Triglyceride have positive though weak correlation with plasma level of Homocysteine. This is similar to a report obtained from Brain Hospital, Affiliated Hospital of Xuzhou Medical University . Elevated plasma homocysteine levels have been linked with abnormal lipid profile. Homocysteine level was found to interfere with metabolism of lipids, especially Apo A1 in HDL-Cholesterol. Statistically significant, negative correlation between plasma level of Homocysteine and HDL-Cholesterol was observed in this study. This explained one of the pathophysiologies of elevated plasma Homocysteine levels as independent risk factor for cardiovascular disease [24,25]. Although, abnormal anthropometric measures have been linked with risk of cardiovascular event no significant correlation was found with plasma level of Homocysteine.
We concluded that elevated plasma level of Homocysteine has a significant correlation with abnormal lipid profile which is one of the major risk factors for cerebrovascular accident.
Conflicts of Interest
The authors declare that they have no conflicts of interest with the contents of this article.
- Shravani K, Parmar MY, Macharla R, et al. Risk factor assessment of stroke and its awareness among stroke survivors: A prospective study. Adv Biomed Res. 2015;4:187.
- Gedefa B, Menna T, Berhe T, et al. Assessment of risk factors and treatment outcome of stroke admissions at St. Paul’s teaching hospital, Addis Ababa, Ethiopia. J Neurol Neurophysiol. 2017;8:1-6.
- Gan Y, Wu J, Zhang S, et al. Prevalence and risk factors associated with stroke in middle-aged and older Chinese: A community-based cross-sectional study. Sci Rep. 2017;7:1-7.
- Okubadejo NU, Oladipo OO, Adeyomoye AA, et al. Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians. BMC Neurol. 2008;6:4-9.
- Kimando MW, Otieno FCF, Ogola EN, et al. Adequacy of control of cardiovascular risk factors in ambulatory patients with type 2 diabetes attending diabetes out-patients clinic at a county hospital, Kenya. BMC Endocr Disord. 2017;17:73-84.
- Owolabi MO, Arulogun O, Melikam S, et al. The burden of stroke in Africa: a glance at the present and a glimpse into the future. Cardiovasc J Afr. 2015;26:S27-38.
- Gould A, Asare H, Akpalu A, et al. Development of stroke care in Ghana. Int J Stroke. 2011;6:150-51.
- Obiako OR, Oparah SK, Ogunniyi A. Prognosis and outcome of acute stroke in the University College Hospital Ibadan, Nigeria. Niger J Cllinical Pract. 2011;14:359-62.
- Martí-Carvajal AJ, Solà I, Lathyris D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2015;1:CD006612.
- Kamath AF, Chauhan AK, Kisucka J, et al. Elevated levels of homocysteine compromise blood-brain barrier integrity in mice. Blood. 2006;107:591-3.
- Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6-15.
- Owolabi MO. Taming the burgeoning stroke epidemic in Africa: Stroke quadrangle to rescue. West Indian Med J. 2011;60:421-22.
- Della-Morte D, Beecham A, Rundek T, et al. Genetic linkage of serum homocysteine in dominican families the family study of stroke risk and carotid atherosclerosis. Stroke. 2010;41:1356-62.
- P. Krishnaveni, Vanitha MN Gowda. Assessing the validity of friedewald’s formula and anandraja’s formula for serum LDL-cholesterol calculation. J Clin Diagn Res. 2015;9:BCO1-4.
- Kim AS, Johnston SC. The current state and future of stroke temporal and geographic trends in the global stroke epidemic. Stroke. 2013;44:S123-25.
- Murray M, King C, Sorenson C, et al. Community awareness of stroke, hypertension and modifiable risk factors for cardiovascular disease in Nkonya-Wurupong, Ghana. J Public Health Africa. 2018;9:783.
- Boehme AK, Esenwa C, Elkind MSV. Stroke risk factors, genetics, and prevention. Circ Res. 2017;120:472-95.
- Salawu AA, Oloyede TW, Akande JO, et al. Analysis of obesity indices in predicting some traditional cardiovascular risk. J Med Dent Sci Res. 2016;3:126-33.
- Paciaroni M, Bogousslavsky J. Primary and secondary prevention of Ischemic Stroke. Eur Neurol. 2010;63:267-78.
- Jones P, Jones D. Stroke 2: Primary and secondary prevention strategies. Nurs Times. 2017;113:42-6.
- Suleiman H, Aliyu I, Abubakar S, et al. Assessment of homocysteine, Vitamin B 12, and Zinc levels among patients with acute ischemic stroke in Northwestern Nigeria. Niger J Basic Clin Sci. 2017;14:105.
- Ashjazadeh N, Fathi M, Shariat A. Evaluation of homocysteine level as a risk factor among patients with ischemic stroke and its subtypes. Iran J Med Sci. 2013;38:233-39.
- Pang H, Han B, Fu Q, et al. Association between homocysteine and conventional predisposing factors on risk of stroke in patients with hypertension. Sci Rep. 2018;8:3900-07.
- Momin M, Jia J, Fan F, et al. Relationship between plasma homocysteine level and lipid profiles in a community-based Chinese population. Lipids Health Dis. 2017;16:54-60.
- Ribas de Farias Costa P, Kinra S, D’Almeida V, et al. Serum homocysteine and cysteine levels and changes in the lipid profile of children and adolescents over a 12-month follow-up period. Clin Nutr ESPEN. 2017;21:13-29.