THE EFFECT OF DIET ON THE PATTERN OF GASTROOESOPHAGEAL REFLUX IN THE RURAL SETTING OF THE EASTERN CAPE
- Authors: NDEBIA EUGENE JAMOT
- Date: 2015
- Language: English
- Type: PhD Manuscript
- Identifier: http://hdl.handle.net/11260/2051 , vital:40807
- Description: Gastro-oesophageal reflux is the return of stomach contents back up into the oesophagus. Excessive reflux of acid content into the oesophagus can cause oesophageal disorders such as heartburn, gastro-oesophageal reflux disease and oesophagitis. The prevalence of oesophageal disorders appears to be high in North America, Europe, japan and China while epidemiology data from Africa, South America and Middle East are unknown. More data is required in Africa because population diversity in reflux symptoms may exist and it is important that standard reference ranges of reflux profiles are established for African countries. The aims of this study was to establish a data base of gastro-oesophageal reflux pattern in the Eastern Cape rural area, to compare our findings with similar western studies and to establish the effect diet, H. pylori infection, gender, weight and age on the observed reflux pattern. The reflux pattern was evaluated in healthy subjects for 24h using the newer technique involving the recording of eosophageal intraluminal impedance and pH simultaneously. The technique gives quantitative data on the frequency, nature, type, and duration, and correlates them to the pH of the reflux. The diet survey was done using the usual pattern diet questionnaire, the body mass index (BMI) was calculated and the quantification of H. pylori antibodies IgG was determined in the serum of each participant using an ELISA kit. In total, 77 participants including 48 females and 29 males were included in the study. The mean age was 35 (range 18 - 60) years for females and 37 (range 18 - 54) for males. The mean BMI was 29 (range 19 - 42) for females and 23 (range 18- ii 30) for males. The total number of refluxes recorded in 24h in this population was presented as median, 25th, 75th and 95th percentile corresponding to 49, 29, 65 and 97, respectively. Of these, 37 % were acidic, 43 % were weakly acidic and 20 % were non-acidic. In term of reflux composition 12 % were liquid, 24 % were gas (belches) and 64 % were mixed (gas and liquid). The oesophageal bolus clearance time was 18 s while the acidity of the reflux was completely neutralised 30 s after a reflux. The oesophageal bolus exposure time was 14 min/day and while acid exposure time was 15 min/day. More refluxes were found in upright position compared to supine position. They were a higher number of refluxes and a predominance of non-acid reflux in the present study compared to western countries. We found that most refluxes were postprandial and some parameters of the pattern of gastro-oesophageal reflux were significantly influenced by the traditional diet. Higher carbohydrate, protein and fat in the meal were associated with a high frequency of refluxes most of which were acidic and weakly acidic while higher fruit and vegetable consumption was associated with fewer refluxes. An increased number of non-acid refluxes were observed in high carbohydrate maize based diet. Nearly all participants of the present study were positive for H. pylori and those with a higher concentration of H. pylori IgG in the serum had less oesophageal acid exposure. Females, older and overweight participants presented with an increased frequency of reflux. This study provides normal references values for the pattern of Gastrooesophageal reflux in the rural population of South Africa. The observed pattern of reflux is positively influenced by the traditional diet which is mainly carbohydrate maize based and also by BMI, weight and gender
- Full Text:
- Authors: NDEBIA EUGENE JAMOT
- Date: 2015
- Language: English
- Type: PhD Manuscript
- Identifier: http://hdl.handle.net/11260/2051 , vital:40807
- Description: Gastro-oesophageal reflux is the return of stomach contents back up into the oesophagus. Excessive reflux of acid content into the oesophagus can cause oesophageal disorders such as heartburn, gastro-oesophageal reflux disease and oesophagitis. The prevalence of oesophageal disorders appears to be high in North America, Europe, japan and China while epidemiology data from Africa, South America and Middle East are unknown. More data is required in Africa because population diversity in reflux symptoms may exist and it is important that standard reference ranges of reflux profiles are established for African countries. The aims of this study was to establish a data base of gastro-oesophageal reflux pattern in the Eastern Cape rural area, to compare our findings with similar western studies and to establish the effect diet, H. pylori infection, gender, weight and age on the observed reflux pattern. The reflux pattern was evaluated in healthy subjects for 24h using the newer technique involving the recording of eosophageal intraluminal impedance and pH simultaneously. The technique gives quantitative data on the frequency, nature, type, and duration, and correlates them to the pH of the reflux. The diet survey was done using the usual pattern diet questionnaire, the body mass index (BMI) was calculated and the quantification of H. pylori antibodies IgG was determined in the serum of each participant using an ELISA kit. In total, 77 participants including 48 females and 29 males were included in the study. The mean age was 35 (range 18 - 60) years for females and 37 (range 18 - 54) for males. The mean BMI was 29 (range 19 - 42) for females and 23 (range 18- ii 30) for males. The total number of refluxes recorded in 24h in this population was presented as median, 25th, 75th and 95th percentile corresponding to 49, 29, 65 and 97, respectively. Of these, 37 % were acidic, 43 % were weakly acidic and 20 % were non-acidic. In term of reflux composition 12 % were liquid, 24 % were gas (belches) and 64 % were mixed (gas and liquid). The oesophageal bolus clearance time was 18 s while the acidity of the reflux was completely neutralised 30 s after a reflux. The oesophageal bolus exposure time was 14 min/day and while acid exposure time was 15 min/day. More refluxes were found in upright position compared to supine position. They were a higher number of refluxes and a predominance of non-acid reflux in the present study compared to western countries. We found that most refluxes were postprandial and some parameters of the pattern of gastro-oesophageal reflux were significantly influenced by the traditional diet. Higher carbohydrate, protein and fat in the meal were associated with a high frequency of refluxes most of which were acidic and weakly acidic while higher fruit and vegetable consumption was associated with fewer refluxes. An increased number of non-acid refluxes were observed in high carbohydrate maize based diet. Nearly all participants of the present study were positive for H. pylori and those with a higher concentration of H. pylori IgG in the serum had less oesophageal acid exposure. Females, older and overweight participants presented with an increased frequency of reflux. This study provides normal references values for the pattern of Gastrooesophageal reflux in the rural population of South Africa. The observed pattern of reflux is positively influenced by the traditional diet which is mainly carbohydrate maize based and also by BMI, weight and gender
- Full Text:
ARTERIAL TONE IN BLACK WOMEN WITH PREECLAMPSIA FROM TRANSKEI REGION OF SOUTH AFRICA
- Authors: AMBROSE VINCENT NAMUGOWA
- Date: 2014
- Language: English
- Type: PhD Manuscript
- Identifier: http://hdl.handle.net/11260/2016 , vital:40802 , DOCTOR OF PHILOSOPHY (Ph.D) (In Health Sciences, Physiology)
- Description: Women with pre-eclampsia have an increased risk of cardiovascular disease later in life. The mechanisms which mediate this heightened risk are poorly understood; it was long believed that pre-eclampsia was cured by delivery of the foetus. But it is now apparent that the risks of complications persist for some time after delivery. The aim of the study was to establish the presence and pattern of endothelial dysfunction during gestation and postpartum among women who develop preeclampsia in the Transkei region of South Africa. This was a two parts study: part one was a cross-sectional experimental study, which involved 85 women with established pre-eclampsia (PE) and 112 pregnant controls (PC); part two was a prospective longitudinal study which involved 36 previously pre-eclamptic women and 86 non-pregnant controls (NPC). Maternal wave reflection (augmentation index) and carotid-femoral pulse wave velocity were assessed noninvasively, using applanation tonometry with the SphygmoCor device. Endothelial function was assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index fingers; induced flow-mediated reactive hyperaemia; the ratio of the readings before and after occlusion was then used to calculate the score, the reactive hyperaemia index (RHI) as a measure of endothelial function. In part one, the measurements were adjusted for maternal age, heart rate, mean arterial pressure, and aortic time to wave reflection and expressed as multiples of the median (MoM) of the pregnant control group.PE group compared with pregnant controls, PE had higher median pulse wave velocity [1.2 inter-quartile range (IQR) 1.08-1.35 MoM vs. 0.97, IQR 8.6-1.09 MoM; p=0.0000].In contrast, there were no ii significant differences between the two groups median of central augmentation index (1.0, IQR -0.4 -1.7 MoM vs. 0.9, IQR 0.69-1.36 MoM; p=0.765). RHI was higher in PE than controls (1.16, IQR 1-1.33 MoM vs. 1, IQR 0.9- 1.18 MoM; p=0.0000). Early-onset pre-eclampsia had higher median brachial blood pressure (87.5, IQR 79-101 vs. 82, IQR 65-88 mmHg; p=0.02), higher mean arterial pressure (110, IQR97-120 vs.101 IQR 88-110 mmHg; p=0.04) and higher central diastolic blood pressure (90, IQR 80-103 vs.84, IQR 67-90 mmHg; p=0.017) than the lateonset pre-eclampsia. Pulse wave velocity (carotid-femoral) was increased in pregnant women with preeclampsia during the third trimester. Reactive hyperaemia index, a measure of endothelial function, was higher in pregnant women with pre-eclampsia than pregnant controls. This suggests that regional (aortic) arterial stiffness is increased, but endothelial function, as assessed by ENDOPAT 2000 device, was not compromised in rural African women with pre-eclampsia. Pulse wave reflection, as assessed by augmentation index adjusted to heart rate of 75 beats/min, was increased in women who had early-onset pre-eclampsia more than those with late-onset pre-eclampsia. Brachial diastolic blood pressure was higher in early-onset pre-eclampsia which resulted in lower brachial pulse pressure than in the late-onset pre-eclampsia. Furthermore, the mean arterial pressure was higher in early-onset than late onset pre-eclampsia. This suggests that early onset pre-eclampsia is more severe condition than the late-onset pre-eclampsia. In part two, pulse wave velocity remained significantly higher in previously preeclamptic women than non-pregnant controls up to three months after delivery iii (p<0.05).Then it reduced to non significant values. Regional (aortic) arterial stiffness, though it persists for some time after delivery, it is transitory in previously pre-eclamptic women from the rural Africa setting. All blood pressure indices (central and brachial pressures), were increased in women who previously had pre-eclampsia as compared to non pregnant controls up to one year postpartum. Although pulse wave velocity and augmentation decrease to low values with time after delivery increased blood pressure is an indication of compromised arterial compliance in women with previously pre-eclampsia.
- Full Text:
- Authors: AMBROSE VINCENT NAMUGOWA
- Date: 2014
- Language: English
- Type: PhD Manuscript
- Identifier: http://hdl.handle.net/11260/2016 , vital:40802 , DOCTOR OF PHILOSOPHY (Ph.D) (In Health Sciences, Physiology)
- Description: Women with pre-eclampsia have an increased risk of cardiovascular disease later in life. The mechanisms which mediate this heightened risk are poorly understood; it was long believed that pre-eclampsia was cured by delivery of the foetus. But it is now apparent that the risks of complications persist for some time after delivery. The aim of the study was to establish the presence and pattern of endothelial dysfunction during gestation and postpartum among women who develop preeclampsia in the Transkei region of South Africa. This was a two parts study: part one was a cross-sectional experimental study, which involved 85 women with established pre-eclampsia (PE) and 112 pregnant controls (PC); part two was a prospective longitudinal study which involved 36 previously pre-eclamptic women and 86 non-pregnant controls (NPC). Maternal wave reflection (augmentation index) and carotid-femoral pulse wave velocity were assessed noninvasively, using applanation tonometry with the SphygmoCor device. Endothelial function was assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index fingers; induced flow-mediated reactive hyperaemia; the ratio of the readings before and after occlusion was then used to calculate the score, the reactive hyperaemia index (RHI) as a measure of endothelial function. In part one, the measurements were adjusted for maternal age, heart rate, mean arterial pressure, and aortic time to wave reflection and expressed as multiples of the median (MoM) of the pregnant control group.PE group compared with pregnant controls, PE had higher median pulse wave velocity [1.2 inter-quartile range (IQR) 1.08-1.35 MoM vs. 0.97, IQR 8.6-1.09 MoM; p=0.0000].In contrast, there were no ii significant differences between the two groups median of central augmentation index (1.0, IQR -0.4 -1.7 MoM vs. 0.9, IQR 0.69-1.36 MoM; p=0.765). RHI was higher in PE than controls (1.16, IQR 1-1.33 MoM vs. 1, IQR 0.9- 1.18 MoM; p=0.0000). Early-onset pre-eclampsia had higher median brachial blood pressure (87.5, IQR 79-101 vs. 82, IQR 65-88 mmHg; p=0.02), higher mean arterial pressure (110, IQR97-120 vs.101 IQR 88-110 mmHg; p=0.04) and higher central diastolic blood pressure (90, IQR 80-103 vs.84, IQR 67-90 mmHg; p=0.017) than the lateonset pre-eclampsia. Pulse wave velocity (carotid-femoral) was increased in pregnant women with preeclampsia during the third trimester. Reactive hyperaemia index, a measure of endothelial function, was higher in pregnant women with pre-eclampsia than pregnant controls. This suggests that regional (aortic) arterial stiffness is increased, but endothelial function, as assessed by ENDOPAT 2000 device, was not compromised in rural African women with pre-eclampsia. Pulse wave reflection, as assessed by augmentation index adjusted to heart rate of 75 beats/min, was increased in women who had early-onset pre-eclampsia more than those with late-onset pre-eclampsia. Brachial diastolic blood pressure was higher in early-onset pre-eclampsia which resulted in lower brachial pulse pressure than in the late-onset pre-eclampsia. Furthermore, the mean arterial pressure was higher in early-onset than late onset pre-eclampsia. This suggests that early onset pre-eclampsia is more severe condition than the late-onset pre-eclampsia. In part two, pulse wave velocity remained significantly higher in previously preeclamptic women than non-pregnant controls up to three months after delivery iii (p<0.05).Then it reduced to non significant values. Regional (aortic) arterial stiffness, though it persists for some time after delivery, it is transitory in previously pre-eclamptic women from the rural Africa setting. All blood pressure indices (central and brachial pressures), were increased in women who previously had pre-eclampsia as compared to non pregnant controls up to one year postpartum. Although pulse wave velocity and augmentation decrease to low values with time after delivery increased blood pressure is an indication of compromised arterial compliance in women with previously pre-eclampsia.
- Full Text:
ARTERIAL TONE IN BLACK WOMEN WITH PREECLAMPSIA FROM TRANSKEI REGION OF SOUTH AFRICA
- Authors: AMBROSE VINCENT NAMUGOWA
- Date: 2014
- Language: English
- Type: PhD Manuscript
- Identifier: http://hdl.handle.net/11260/2023 , vital:40803 , DOCTOR OF PHILOSOPHY (Ph.D) (In Health Sciences, Physiology)
- Description: Women with pre-eclampsia have an increased risk of cardiovascular disease later in life. The mechanisms which mediate this heightened risk are poorly understood; it was long believed that pre-eclampsia was cured by delivery of the foetus. But it is now apparent that the risks of complications persist for some time after delivery. The aim of the study was to establish the presence and pattern of endothelial dysfunction during gestation and postpartum among women who develop preeclampsia in the Transkei region of South Africa. This was a two parts study: part one was a cross-sectional experimental study, which involved 85 women with established pre-eclampsia (PE) and 112 pregnant controls (PC); part two was a prospective longitudinal study which involved 36 previously pre-eclamptic women and 86 non-pregnant controls (NPC). Maternal wave reflection (augmentation index) and carotid-femoral pulse wave velocity were assessed noninvasively, using applanation tonometry with the SphygmoCor device. Endothelial function was assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index fingers; induced flow-mediated reactive hyperaemia; the ratio of the readings before and after occlusion was then used to calculate the score, the reactive hyperaemia index (RHI) as a measure of endothelial function. In part one, the measurements were adjusted for maternal age, heart rate, mean arterial pressure, and aortic time to wave reflection and expressed as multiples of the median (MoM) of the pregnant control group.PE group compared with pregnant controls, PE had higher median pulse wave velocity [1.2 inter-quartile range (IQR) 1.08-1.35 MoM vs. 0.97, IQR 8.6-1.09 MoM; p=0.0000].In contrast, there were no ii significant differences between the two groups median of central augmentation index (1.0, IQR -0.4 -1.7 MoM vs. 0.9, IQR 0.69-1.36 MoM; p=0.765). RHI was higher in PE than controls (1.16, IQR 1-1.33 MoM vs. 1, IQR 0.9- 1.18 MoM; p=0.0000). Early-onset pre-eclampsia had higher median brachial blood pressure (87.5, IQR 79-101 vs. 82, IQR 65-88 mmHg; p=0.02), higher mean arterial pressure (110, IQR97-120 vs.101 IQR 88-110 mmHg; p=0.04) and higher central diastolic blood pressure (90, IQR 80-103 vs.84, IQR 67-90 mmHg; p=0.017) than the lateonset pre-eclampsia. Pulse wave velocity (carotid-femoral) was increased in pregnant women with preeclampsia during the third trimester. Reactive hyperaemia index, a measure of endothelial function, was higher in pregnant women with pre-eclampsia than pregnant controls. This suggests that regional (aortic) arterial stiffness is increased, but endothelial function, as assessed by ENDOPAT 2000 device, was not compromised in rural African women with pre-eclampsia. Pulse wave reflection, as assessed by augmentation index adjusted to heart rate of 75 beats/min, was increased in women who had early-onset pre-eclampsia more than those with late-onset pre-eclampsia. Brachial diastolic blood pressure was higher in early-onset pre-eclampsia which resulted in lower brachial pulse pressure than in the late-onset pre-eclampsia. Furthermore, the mean arterial pressure was higher in early-onset than late onset pre-eclampsia. This suggests that early onset pre-eclampsia is more severe condition than the late-onset pre-eclampsia. In part two, pulse wave velocity remained significantly higher in previously preeclamptic women than non-pregnant controls up to three months after delivery iii (p<0.05).Then it reduced to non significant values. Regional (aortic) arterial stiffness, though it persists for some time after delivery, it is transitory in previously pre-eclamptic women from the rural Africa setting. All blood pressure indices (central and brachial pressures), were increased in women who previously had pre-eclampsia as compared to non pregnant controls up to one year postpartum. Although pulse wave velocity and augmentation decrease to low values with time after delivery increased blood pressure is an indication of compromised arterial compliance in women with previously pre-eclampsia.
- Full Text:
- Authors: AMBROSE VINCENT NAMUGOWA
- Date: 2014
- Language: English
- Type: PhD Manuscript
- Identifier: http://hdl.handle.net/11260/2023 , vital:40803 , DOCTOR OF PHILOSOPHY (Ph.D) (In Health Sciences, Physiology)
- Description: Women with pre-eclampsia have an increased risk of cardiovascular disease later in life. The mechanisms which mediate this heightened risk are poorly understood; it was long believed that pre-eclampsia was cured by delivery of the foetus. But it is now apparent that the risks of complications persist for some time after delivery. The aim of the study was to establish the presence and pattern of endothelial dysfunction during gestation and postpartum among women who develop preeclampsia in the Transkei region of South Africa. This was a two parts study: part one was a cross-sectional experimental study, which involved 85 women with established pre-eclampsia (PE) and 112 pregnant controls (PC); part two was a prospective longitudinal study which involved 36 previously pre-eclamptic women and 86 non-pregnant controls (NPC). Maternal wave reflection (augmentation index) and carotid-femoral pulse wave velocity were assessed noninvasively, using applanation tonometry with the SphygmoCor device. Endothelial function was assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index fingers; induced flow-mediated reactive hyperaemia; the ratio of the readings before and after occlusion was then used to calculate the score, the reactive hyperaemia index (RHI) as a measure of endothelial function. In part one, the measurements were adjusted for maternal age, heart rate, mean arterial pressure, and aortic time to wave reflection and expressed as multiples of the median (MoM) of the pregnant control group.PE group compared with pregnant controls, PE had higher median pulse wave velocity [1.2 inter-quartile range (IQR) 1.08-1.35 MoM vs. 0.97, IQR 8.6-1.09 MoM; p=0.0000].In contrast, there were no ii significant differences between the two groups median of central augmentation index (1.0, IQR -0.4 -1.7 MoM vs. 0.9, IQR 0.69-1.36 MoM; p=0.765). RHI was higher in PE than controls (1.16, IQR 1-1.33 MoM vs. 1, IQR 0.9- 1.18 MoM; p=0.0000). Early-onset pre-eclampsia had higher median brachial blood pressure (87.5, IQR 79-101 vs. 82, IQR 65-88 mmHg; p=0.02), higher mean arterial pressure (110, IQR97-120 vs.101 IQR 88-110 mmHg; p=0.04) and higher central diastolic blood pressure (90, IQR 80-103 vs.84, IQR 67-90 mmHg; p=0.017) than the lateonset pre-eclampsia. Pulse wave velocity (carotid-femoral) was increased in pregnant women with preeclampsia during the third trimester. Reactive hyperaemia index, a measure of endothelial function, was higher in pregnant women with pre-eclampsia than pregnant controls. This suggests that regional (aortic) arterial stiffness is increased, but endothelial function, as assessed by ENDOPAT 2000 device, was not compromised in rural African women with pre-eclampsia. Pulse wave reflection, as assessed by augmentation index adjusted to heart rate of 75 beats/min, was increased in women who had early-onset pre-eclampsia more than those with late-onset pre-eclampsia. Brachial diastolic blood pressure was higher in early-onset pre-eclampsia which resulted in lower brachial pulse pressure than in the late-onset pre-eclampsia. Furthermore, the mean arterial pressure was higher in early-onset than late onset pre-eclampsia. This suggests that early onset pre-eclampsia is more severe condition than the late-onset pre-eclampsia. In part two, pulse wave velocity remained significantly higher in previously preeclamptic women than non-pregnant controls up to three months after delivery iii (p<0.05).Then it reduced to non significant values. Regional (aortic) arterial stiffness, though it persists for some time after delivery, it is transitory in previously pre-eclamptic women from the rural Africa setting. All blood pressure indices (central and brachial pressures), were increased in women who previously had pre-eclampsia as compared to non pregnant controls up to one year postpartum. Although pulse wave velocity and augmentation decrease to low values with time after delivery increased blood pressure is an indication of compromised arterial compliance in women with previously pre-eclampsia.
- Full Text:
Pulse amplitude tonometry and angiogenic factors in preeclampsia in rural African women
- Authors: Meeme, Allen
- Date: 2014
- Language: English
- Type: Doctor of Philosophy (Ph.D) (Health Sciences, Physiology)
- Identifier: http://hdl.handle.net/11260/2009 , vital:40800
- 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.
- Full Text:
- Authors: Meeme, Allen
- Date: 2014
- Language: English
- Type: Doctor of Philosophy (Ph.D) (Health Sciences, Physiology)
- Identifier: http://hdl.handle.net/11260/2009 , vital:40800
- 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.
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