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| ORIGINAL RESEARCH REPORT |
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| Year : 2018 | Volume
: 15
| Issue : 1 | Page : 22-26 |
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Pattern of von Willebrand factor in hypertensive patients in Lagos, Nigeria
Ann Abiola Ogbenna1, Chinwe Okpalanze2, Ademola Samson Adewoyin2, Eniola Enifeni3
1 Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
2 Division of Haematology, Pathcare Laboratories, Lagos, Nigeria
3 Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria
| Date of Web Publication | 23-Feb-2018 |
Correspondence Address:
Dr. Ann Abiola Ogbenna
Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Lagos
Nigeria
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jcls.jcls_92_17
Background and Objective: Hypertension alone accounts for 50% of death from stroke. Its ability to induce endothelial dysfunction leads to the release of von Willebrand factor (vWF), a prothrombotic glycoprotein. The increase secretion of vWF may account for increased risk of stroke in hypertensive disorders. This study aimed to determine the vWF:antigen (Ag) levels among hypertensives and assess its relationship with blood pressure and occurrence of stroke in hypertensives. Subjects and Methods: The study included 66 hypertensives, 33 with stroke (HS) and 33 without stroke (HWS), and 33 controls matched for age and sex. Structured questionnaires were used to obtain biodata and clinical information. Blood pressure was taken after 15 min rest. Four milliliters of blood was collected into 0.1 ml of 3.2% trisodium citrate for vWF:Ag assay and 4 ml into K-ethylenediaminetetraacetic acid anticoagulant bottles for blood grouping and erythrocyte sedimentation rate. Data were analyzed with SPSS version 21. Confidence interval was set at 95%. Results: Mean vWF:Ag levels were significantly higher in hypertensives compared with nonhypertensives (P = 0.005), but no statistically significant difference was observed between HS and HWS (P = 0.874). A positive correlation of vWF with systolic blood pressure was observed (r = 0.335, P = 0.001). Conclusion: Our study suggests that higher systolic blood pressure is associated with higher levels of endothelial activation and release of vWF.
Keywords: Blood pressure, endothelial dysfunction, hypertension, stroke, von Willebrand factor
How to cite this article:
Ogbenna AA, Okpalanze C, Adewoyin AS, Enifeni E. Pattern of von Willebrand factor in hypertensive patients in Lagos, Nigeria. J Clin Sci 2018;15:22-6 |
How to cite this URL:
Ogbenna AA, Okpalanze C, Adewoyin AS, Enifeni E. Pattern of von Willebrand factor in hypertensive patients in Lagos, Nigeria. J Clin Sci [serial online] 2018 [cited 2023 Mar 20];15:22-6. Available from: https://www.jcsjournal.org/text.asp?2018/15/1/22/226044 |
| Introduction | |  |
Hypertension is one of the most important causes of premature death globally with an increasing global prevalence. It is estimated that by 2025, 1.56 billion adults will be living with high blood pressure and a third of this population will be in the economically developing countries.[1] The overall prevalence in Nigeria ranges from 8% to 46%.[2] It remains the single most important risk factor in stroke. The risk of stroke increases with blood pressure. Evidence suggests that stroke risk is at least 4–6 folds higher in uncontrolled high blood pressure.[3]
Endothelial dysfunction is a risk factor for the development of clinical events and may represent a marker of atherothrombotic burden.[4] Endothelial dysfunction leads to the secretion and release of a glycoprotein called von Willebrand factor (vWF) which is a central protein in the regulation of blood coagulation. It serves as a major adhesive link between platelets and the blood vessel wall and also functions as a carrier in plasma for factor VIII.[5] It is also an important mediator of inflammation.[6] Because of its direct role in hemostasis and its indirect role as a marker of endothelial dysfunction, vWF is a potential risk indicator for cerebrovascular disease and may serve as a prognostic tool for disease progression.[7]
This study aimed to determine the vWF:Ag levels among hypertensives and assess its relationship with blood pressure and occurrence of stroke.
| Subjects and Methods | | |
This was a cross-sectional, analytical study, conducted at the Lagos University Teaching Hospital (LUTH), Nigeria. The study population comprised of adult hypertensives attending cardiology and neurology outpatient clinics of LUTH. The control population was recruited from apparently healthy staff of LUTH and from the donor clinic and was matched for age and sex. Patients with cancer, diabetics, nephrotic syndrome, sickle cell diseases, or elevated erythrocyte sedimentation rate (ESR) were excluded from the study. Pregnant women and those on warfarin or other anticoagulants were also excluded to limit bias.
Sample size was determined using a formula for comparing two independent means. For α = 0.05 (between each group) and a power of 80%, a sample size per group >26 participants was needed to detect an actual difference. Thirty-three hypertensives with stroke (HS), 33 without stroke (HWS), and 33 healthy controls were recruited. Hypertensives were defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg.[8] Informed consent was obtained from each participant after the purpose of research had been adequately explained to prospective participants in language they best understood.
Identification numbers were assigned to each participant. Structured interviewer-administered questionnaire was administered to each participant to obtain sociodemographic data and relevant clinical information; other medical data were obtained from the medical case notes. Systolic and diastolic pressure was taken twice and the average was recorded.
Eight milliliters of blood was collected from each participant after having rested for 15 min and 4 ml into an anticoagulated bottle with 0.1 ml of 3.25 trisodium citrate bottle. Another 4 ml was collected into a potassium ethylenediaminetetraacetic acid (EDTA) anticoagulated bottle for ESR and blood grouping. Samples were transported to laboratory immediately in cooler bags containing ice packs. Platelet-poor plasma was separated from sample in trisodium citrate bottle and stored at −70° C until they were ready for analysis. vWF:Ag was determined using von Willebrand enzyme-linked immunosorbent assay kit made by Helena in Beaumont, Texas, USA. Measurement of von Willebrand antigen for each sample was carried out in duplicates and the mean values recorded.
The EDTA samples were analyzed in not more than 1 h for full ESR using Dispette 2 citrate by Guest Scientific, Switzerland, according to package insert. Blood grouping (cell and serum) was done using monoclonal antisera from Biocheck Company, UK, and locally prepared known A and B cells, respectively. All assays were performed using appropriate daily control checks.
Data obtained were stored in an access file and analyzed using IBM SPSS Statistics Version 21, United States. The normality of the distribution was checked by stem and leaf plots and Kolmogorov–Smirnov test. vWF values across groups were compared with one-way analysis of variance followed by the post hoc Bonferroni test. Student t-test was used to compare two means. Pearson's correlation was used to determine relationship between vWF and systolic/diastolic blood pressure. Summary data for continuous variables are expressed as the mean ± standard deviation (SD). Confidence interval was set at 95%.
Ethical approval for this study was obtained from LUTH Research and Ethics Committee.
| Results | | |
This study included 99 participants in total. Thirty-three were hypertensives without stroke, 33 were hypertensives with stroke, and 33 were apparently healthy normotensive matched by age. The mean age of all the participants was 57 years ± 11 years; 47 were males and 52 were females. Thirty-nine patients were Igbo, 51 were Yoruba, and 9 were from other ethnic groups. None were Hausas [Table 1].
The overall mean plasma level of vWF:Ag in all participants was 1.39 ± 0.39 IU/ml. The mean plasma level of von Willebrand antigen was statistically significantly different between the three groups [Table 2]. Hypertensives with stroke had the highest mean (1.47 ± 0.38 IU/ml). Post hoc test, however, showed that the difference was mainly between the normotensive participants and hypertensives with stroke and without stroke (P = 0.031 and P = 0.046, respectively). There was no statistical difference in mean of vWF:Ag between hypertensives with stroke and those without strokes. | Table 2: Mean plasma levels of von Willebrand factor: antigen and blood pressure among study participants
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The overall mean systolic and diastolic blood pressure for all participants was 139.08/84.78 mmHg. The mean systolic and diastolic blood pressures for hypertensives without stroke, hypertensives with stroke, and apparently healthy normotensives were 135.73/82.53, 143.68/87.06, and 122.27/78.06 mmHg, respectively, and these were statistically different [Table 2]. Post hoc test showed that this difference in systolic blood pressure was mainly between normotensives and hypertensives (with and without stroke, P = 0.005 and P ≤ 0.001, respectively). Systolic blood pressure did not vary significantly among the two hypertensive subgroups (P = 0.337) while the diastolic blood pressure was only significantly different between normotensive participants and hypertensives (P = 0.016).
There was a moderate, positive correlation between systolic blood pressure and vWF:Ag (r = 0.335, n = 99, P = 0.001) [Figure 1]. No statistically significant linear correlation was observed between the diastolic blood pressure and vWF:Ag (r = 0.110, n = 99, P = 0.28) [Figure 2]. | Figure 1: Correlation between vWF:Ag level and systolic blood pressure (Original) (r = 0.335, n = 99, P = 0.001)
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 | Figure 2: Correlation between vWF:Ag level and diastolic blood pressure (Original) (r = 0.110, n = 99, P = 0.28)
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In all the study groups except the hypertensive with stroke, the mean vWF:Ag was higher in the non-O blood group compared with blood group O [Table 4].
| Discussion | | |
In this study, we assayed the plasma levels of vWF:Ag of hypertensives without stroke and hypertensives with stroke attending the cardiology and neurology clinics in LUTH, Lagos State, and apparently normal participants matched for age and sex. We also examined the relationship between vWF:Ag, blood pressure, history of stroke, and blood group of the participants.
This study showed that vWF:Ag levels were statistically significantly higher in hypertensives (mean ± SD; 1.46 ± 0.39 IU/ml) compared with nonhypertensives (1.23 ± 0.33 IU/ml; P = 0.005). This concurs with previous observations of high vWF levels in patients with hypertension.[9],[10],[11]
There was no statistically significant difference in the vWF:Ag of hypertensives with stroke (mean ± SD, 1.46 ± 0.41 IU/ml) compared with hypertensives without stroke (1.47 ± 0.38 IU/ml; P = 0.874). This could be due to the poststroke effect as samples were not collected at the acute phase. All the stroke participants were at the convalescence stage, and the effect of drugs and treatments could have obscured the vWF:Ag level. This is a limitation of this study and calls for further study evaluating the vWf antigen level at acute stage, monitoring it through the phases of convalescence.
A moderate, positive correlation was observed between systolic blood pressure and vWF:Ag (r = 0.335, n = 99, P = 0.001). Similar correlation has also been reported though with greater strengths of correlation.[12],[13]
vWF is a multimeric glycoprotein whose circulating plasma levels vary significantly within and between individuals. These variations have been associated with ABO blood type, estrogen levels, age, and stress.[14] The ABO blood group has been known to exert a major quantitative effect on circulating vWF levels. Studies have shown that 60% of the variation observed in plasma vWF levels is genetically determined while 30% of the total variation is explained by the effect of the ABO blood group.[15]
As expected, this study also demonstrated that vWF:Ag levels were significantly lower in individuals with blood group O (mean ± SD, 1.27 ± 0.38 IU/ml) compared with individuals with blood group non-O (1.57 ± 0.33 IU/ml; P < 0.001) [Table 4]. We also observed that blood group O showed the lowest level of vWF:Ag while blood group AB showed the highest level of vWF:Ag [Table 3]. This is also consistent with previous similar studies.[14],[16] | Table 3: Mean plasma levels of von Willebrand factor: antigen in the different blood groups of the participants
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The distribution vWF:Ag among group O and non-group O normotensives in index study is comparable with similar studies in Nigeria and beyond.[7],[9],[17],[18] However, we observed that among participants with a history of stroke, no statistical significant difference in vWF:Ag level was observed between the blood group O and nonblood group O participants [Table 4]. This may be attributed to the increased release of vWF secondary to endothelial dysfunction, thus obscuring the normally observed difference between blood group O and nonblood group O.
Patients already on antihypertensive may obscure the real magnitude of elevated blood pressure on the secretion of vWF, thus potentially weakening the study. However, the study excluded patients with diabetes mellitus, common comorbidity, and other systemic disorders to elucidate the specific levels of vWF attributable to hypertension only. Although excluding these disease conditions may limit generalization of findings to all hypertensives, it does not negate the thrombotic risk associated with high vWF, hence the clinical relevance of our results and inferences. | Table 4: Subgroup analysis of mean plasma levels of von Willebrand factor: antigen in individuals with blood group O versus non-O
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| Conclusion | | |
This study provides additional evidence that high blood pressure is associated with endothelial activation, with release of vWF. vWF is being proposed as a prognostic marker in hypertension-related stroke. There is a need for large-scale, multicenter study to confirm or disapprove its association with stroke occurrence in systemic hypertension.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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