Motivation
In the black population of South Africa, cardiovascular disease (CVD) is rapidly increasing due to
urbanisation. Stroke is usually accompanied by a prothrombotic haemostatic profile. Changing
lifestyle factors that accompany the urbanisation process could have a negative impact on the
haemostatic profile of black South Africans. Elevated levels of pro-coagulant factors, von
Willebrand factor (vWF), fibrinogen and fibrin D-dimer have been reported in the black population,
which could increase the black population’s susceptibility to CVD. However, low levels of
plasminogen activator inhibitor-1 (PAI-1) previously reported in the black population could
contribute towards a pro-fibrinolytic state, which may counteract the hypercoagulant state. This
may have a beneficial effect on the haemostatic profile of the black population. More investigation
into the haemostatic profile of black South Africans is therefore needed to determine if an altered
haemostatic profile exists in this group, and if so, to what extent these alterations may relate to
cardiovascular dysfunction. This study included markers of both the coagulation (vWF, fibrinogen,
fibrin D-dimer) and fibrinolytic (PAI-1, fibrin D-dimer and fibrinolytic potential) systems in an
attempt to investigate the haemostatic profile of the black population of South Africa, and for
comparison purposes that of the white population as well. The relationship of these markers’ with
selected markers of cardiovascular function was also examined to determine if they could possibly
contribute to an increase in cardiovascular risk, especially in the black population.
Aims
The aims of this study were to first compare coagulation and fibrinolysis markers in the black and
white populations of South Africa. Furthermore, to determine if associations exist between the
selected components of the haemostatic system and markers of cardiovascular function,
especially in the black population of South Africa, who tends to be at a higher cardiovascular risk
due to altered metabolic and haemostatic profiles.
Methodology
The Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study was a
prospective cohort study that consisted of 409 participants at baseline (2008-2009) that were
equally distributed according to both ethnicity (200 black; 209 white) and gender (black, 101 men,
99 women; white, 101 men, 108 women). At follow-up (2011/2012) the cohort totalled 359
participants (170 black, 88 men and 82 women; 189 white, 93 men and 96 women). Data from
baseline measurements were used for the first two manuscripts (chapters 2 and 3), while followup
data was used for the third manuscript (chapter 4). vWF, fibrinogen, PAI-1, fibrin D-dimer, CLT,
serum peroxides, glutathione, glutathione peroxidase and reductase activity were determined,
and ambulatory blood pressure and the retinal vessel calibres were measured. The groups were
stratified by ethnicity as specified by statistical interaction terms. T-tests and chi-square tests were
used to compare means and proportions, respectively. Pearson and partial regression analyses
were used to determine correlations between the components of the haemostatic system and
cardiovascular function markers. This was followed by multiple linear regression analyses to
investigate whether independent associations exist between the variables in both ethnic groups.
P-values ≤0.050 were deemed significant.
Results and conclusion of each manuscript
The first manuscript (chapter 2) compares the haemostatic profiles of the black and white
population to determine whether ambulatory blood pressure is related to components of the
haemostatic system. The black participants displayed a prothrombotic profile with significantly
higher vWF, fibrinogen, PAI-1, fibrin D-dimer and a longer CLT than their white counterparts.
Furthermore, partial and multiple linear regression analyses showed a positive association of
systolic and diastolic blood pressure with fibrin D-dimer in the black population, while a negative
association existed between ambulatory blood pressure and CLT in the white population. These
associations suggest that fibrin D-dimer may contribute, at least in part, to the high prevalence of
hypertension in the black population.
The second manuscript (chapter 3) determined associations between markers of the haemostatic
and oxidant-antioxidant systems in the black and white populations. In addition to the
prothrombotic profile that exists in the black population, this group also had significantly higher
serum peroxides (oxidative stress) and lower glutathione peroxidase activity (antioxidant) levels.
Multiple linear regression analyses indicated positive associations between fibrinogen and serum
peroxides in both populations. In the white population, an additional positive association was
found between serum peroxide and CLT. In the black population, vWF and CLT were negatively
associated with GPx activity. The results suggest that there are ethnic-specific relationships
between the haemostatic and oxidant-antioxidant systems.
The third manuscript (chapter 4) investigated the relationships between the retinal vessel calibres
and components of the haemostatic system in the black and white population. The investigation
focussed specifically on arteriolar diameters in the lower median, since a narrow arteriolar
diameter is known to be associated with elevated blood pressure. In both ethnic groups, a
narrower arteriolar calibre was accompanied by narrower venular calibres. Independent positive
associations were found between the central retinal vein equivalent (CRVE) and fibrinogen in the
black population, as well as vWF and CLT in the white population. In addition, independent
negative associations were found between the central retinal artery equivalent and CLT in the
black population and with vWF in the white population. The results suggest that haemostatic
alterations are linked to early vascular changes that may differ between ethnicities.
General conclusion
Ethnic-specific relationships between the components of the haemostatic system and measures
of cardiovascular function are evident. The prothrombotic profile that is observed in the black
population, together with the adverse associations of the haemostatic components with blood
pressure, a compromised oxidant-antioxidant profile, and retinal vessel calibres may contribute,
at least in part, to the high cardiovascular and cerebrovascular risk evident in this population
group. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/15353 |
| Date | January 2015 |
| Creators | Lammertyn, Leandi |
| Source Sets | North-West University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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