- Title
- Pulse amplitude tonometry and angiogenic factors in preeclampsia in rural African women
- Creator
- Meeme, Allen
- Description
- The pathogenesis of preeclampsia remains a puzzle despite extensive research that has been carried out over the years. Endothelial dysfunction and altered angiogenic balance have now been shown to play a significant role in the protean manifestations of this syndrome. There are several direct and indirect methods that have been used for assessing endothelial function during pregnancy. The most commonly used non-invasive method for assessing endothelial function in pregnancy has been the flow-mediated ultrasonic method. Because this method requires a skilled sonographer and a good quality ultrasound machine, it is not readily available for routine investigational use. Pulse amplitude tonometry using the EndoPAT 2000 is a novel non-invasive automated method that has been used rather extensively in recent years for assessing endothelial dysfunction in non-pregnant subjects, with only a few reports in pregnancy. This study set out to assess pulse amplitude tonometry using EndoPAT 2000 in normotensive and hypertensive pregnant women in rural African women to determine whether it can demonstrate endothelial dysfunction associated with preeclampsia. In addition, angiogenic factors known to be associated with preeclampsia were measured to assess whether there are any differences in their levels between normotensive and hypertensive pregnant women in the rural African setting. As HIV, a common condition in this population of antenatal mothers, is known to affect endothelial function, secondary evaluation was carried out based on the HIV status to assess if there are any differences in the tested parameters. This was a prospective case-control study conducted in Mthatha Hospital Complex, Eastern Cape, South Africa. A total of two hundred and fifteen (215) participants with known HIV status were recruited into the study; 105 women had preeclampsia (cases) and 110 were normotensive pregnant women (controls). Endothelial function was assessed using EndoPAT 2000 technique that measured pulse amplitude tonometry using the reactive hyperemia index (RHI, arbitrary units). Blood samples were also taken from the subjects and the serum was stored at -70°C until assayed for soluble fms-like tyrosine kinase (sFlt-1), placental growth factor (PlGF). Nitric oxide levels were measured indirectly using nitrite and nitrate levels in serum from blood samples taken from the test arm about 5 minutes after the end of the pulse amplitude tonometry, and these were measured using the Cayman colorimetric method. sFLt-1 and PIGF levels were quantified using specific enzyme linked immunosorbent assays (ELISA). Statistix 8.0 and Graphpad Prism 5 software were used for data analysis. Data were summarised as means ± standard error of the mean (SEM) for normally distributed data and medians (interquartile range, IQR) for non-normally distributed data. Two sample Student’s t-test was used to compare means while Mann-Whitney U test was used to compare medians. Spearman’s correlation and multiple regression analyses were used to determine correlations between variables. Secondary analysis was carried based on whether the cases were early onset or late onset and whether cases and controls were HIV-positive or negative. Kruskal-Wallis and one way ANOVA were used to compare means between cases and controls. Statistical significance was set at a p value of <0.05. Women with preeclampsia were found to have significantly lower RHI [1.70(1.04-3.61)au vs.1.81 (1.18-4.62) au; p˂0.05], lower PIGF levels (90.26 ± 8.99 pg/ml vs. 172.80 ± 20.24 pg/ml; p˂0.01) and higher sFlt1, (2087.3 ± 200.1 pg/ml vs. 1546.5 ± 91.9 pg/ml; p˂0.01) compared to normotensive controls. The sFlt1/PIGF ratio was also found to be higher among women with preeclampsia (66.77 ± 18.66 vs. 22.26 ± 2.95; p˂0.01) compared to the normotensive controls. Unlike the lower RHI, the nitrite and nitrate levels did not differ between preeclamptic and normotensive pregnant women (6.04 ± 0.52 µM vs 6.12 ± 0.49 µM; p>0.05). No significant relationship was observed between RHI and nitrite/nitrate levels (r=-0.08, p>0.05), RHI and pro-angiogenic factor PIGF (r=0.101, p>0.05) or RHI and anti-angiogenic factor sFlt1 (r= 0.002, p>0.05). There was also no significant relationship between RHI and the sFlt1/PlGF ratio (r=-0.047, p>0.05). HIV-positive status significantly affected sFlt1, baseline pulse wave amplitude and augmentation index compared to HIV-negative status in the different groups of women. RHI, PlGF and the sFlt1/PlGF ratio differences were not statistically significant. Pulse amplitude tonometry measured as reactive hyperemia index (RHI) using EndoPAT 2000 revealed the presence of endothelial dysfunction in rural African women with preeclampsia, thus suggesting that this technique can be used reliably to assess endothelial dysfunction in pregnant women. To our knowledge this is the first such report involving rural African women. The significant differences in the levels and ratios of angiogenic factors found in the preeclamptic women when compared with the normotensive controls in this study also confirm what has been reported in the literature. Although endothelial dysfunction was clearly demonstrable in the preeclamptic rural African women, this appears not to have been associated with either reduced or elevated levels of nitric oxide, as assessed using nitrite/ nitrate levels when compared with normotensive controls. This finding adds to the current conflicting reports on nitric oxide levels in preeclampsia reported in the literature. The RHI in both cases and control pregnant women was also not significantly correlated with the levels of nitrites/nitrates. Although this might raise some questions about the actual role of nitric oxide in endothelial dysfunction in rural African women with preeclampsia, the explanation for this finding might simply be the fact that NO has a very short half-life, and has to be measured indirectly using its more stable metabolites such as nitrites and nitrates. The absence of significant correlation between RHI and angiogenic factors demonstrated in this study could mean that the effect of sFlt1 may be more on the larger arteries than small resistance arteries from which RHI is obtained. It is recommended that prospective studies are carried out to determine whether the RHI becomes abnormal before the onset of clinical preeclampsia or not as the search for predictors of preeclampsia continues.
- Date
- 2014
- Type
- Doctor of Philosophy (Ph.D) (Health Sciences, Physiology)
- Identifier
- http://hdl.handle.net/11260/2009
- Identifier
- vital:40800
- Format
- Publisher
- Department of Physiology Faculty of Health Sciences
- Language
- English
- Rights
- Walter Sisulu University
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details | SOURCE1 | Allen's thesis pdf.pdf | 4 MB | Adobe Acrobat PDF | View Details |