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INTRODUCTION: Visualisation of the microcirculation through retinal imaging can provide information on the health of systemic vasculature. Characterisation of the retinal vasculature throughout pregnancy using retinal imaging is a novel approach to examine physiological changes to the cardiovascular system, and may be useful to predict early pathophysiological signs of adverse maternal outcomes. OBJECTIVES: To characterise the retinal vascular and blood pressure (BP) changes that occur throughout a healthy pregnancy. METHODS: Data was collected from women recruited at 13±2 weeks of gestation from Royal Prince Alfred Hospital, a major tertiary referral hospital in Sydney, Australia. Retinal images centred on the optic disc and BP readings were collected throughout pregnancy. Postnatal data was collected from medical records, and women with hypertensive disorders of pregnancy and gestational diabetes mellitus were excluded. This left a final group of 19 women. Retinal images from 13±2, 19±2, 29±2 and 38±2 weeks gestation were graded using semi-automated retinal vascular calibre measurement (IVAN) software and the central retinal arteriolar equivalent (CRAE), and central retinal venular equivalent (CRVE). BP data was collected at the same time points as the retinal images. Analysis of data was performed using paired t-tests and repeated measures analysis of variance (ANOVA). Women with missing data points were excluded from the analysis at the relevant time points. RESULTS: Over the course of pregnancy, there was a significant dilatation of retinal arterioles between 13±2 and 19±2weeks (from 166.4 to 172.7µm, SE: 3.7µm, n=19, p=0.01), corresponding to a significant fall in diastolic BP during this time (from 64.6 to 60.2mmHg, SE: 1.5mmHg, p=0.01). No significant changes in venular diameter or systolic BP were noted. Between 19±2 and 29±2weeks (n=4), no significant changes to retinal arteriolar or venular diameter were seen although there were significant increases in both systolic and diastolic BP (SBP: from 100.3 to 109.9mmHg, SE: 1.9mmHg, p=0.01; DBP: from 59.3 to 64.6mmHg, SE: 6.9mmHg, p=0.01). Between 29±2 and 38±2weeks (n=3), no significant changes in retinal arteriolar, and venular diameter or BP were observed. CONCLUSION: An increase in retinal arteriolar diameter between 13±2 and 19±2 weeks gestation was observed, which corresponded to a decrease in both systolic and diastolic BP. However, between 19±2 and 29±2 weeks there was no change in vasculature, even though there was a significant increase in BP. By characterising the changes to retinal vessels that occur throughout a healthy pregnancy, we can further our understanding of the response of the systemic vasculature to pregnancy, which may provide clues to early vascular disease of pregnancies.
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INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are characterised by vascular dysfunction. Retinal vascular imaging is a novel, non-invasive way to characterise early microvascular changes in pregnancy, and as a result has the potential to be used to predict the onset of HDP. OBJECTIVES: To characterise retinal vascular changes that occur in HDP, and compare these changes to those in healthy pregnancies. METHODS: Women were recruited at 13±2 weeks of gestation from Royal Prince Alfred Hospital, a major metropolitan tertiary referral hospital in Sydney, Australia. Retinal images centred on the optic disc and blood pressure (BP) readings were collected at 13±2, 19±2, 29±2 and 38±2 weeks gestation. Retinal images were graded using semi-automated retinal vascular calibre measurement software (IVAN) and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were calculated. Within and between subject repeat measures analysis was performed on images from each trimester, using paired t-tests and repeated measures analysis of variance (ANOVA). Multiple linear regressions were used to model the average arteriole diameter adjusted for age, tobacco consumption and body mass index (BMI). All tests were two-sided using a 5% level of significance. A clinical diagnosis of HDP was obtained from postnatal medical record data. Women with missing data points were excluded from the analysis at that time point. RESULTS: Of the 39 women included in the study, 6 (15%) were diagnosed with HDP. In the HDP cohort, repeated measures ANOVA revealed no significant changes in arteriolar or venular diameter measurements throughout pregnancy. Paired t-tests indicated no significant differences in any of the outcome measures between HDP and healthy pregnancies at 13±2 (n=36) and 19±2 (n=39)weeks. At 29±2weeks (n=39), there was a significantly smaller venular diameter in HDP pregnancies (220.4±6.9µm vs 239.1± 5.4µm in healthy pregnancies, p=0.03). At 38±2weeks (n=39), arteriolar diameter was significantly smaller in HDP pregnancies (148.6±6.0µm vs 164.1±4.6µm in healthy pregnancies, p=0.04). Similar results persisted following adjustments for cardiovascular risk factors (age, tobacco use and BMI). CONCLUSION: Significant differences in the retinal vasculature develop in HDP as compared to healthy pregnancies. These differences appear at29±2weeks gestation and persist throughout the rest of the pregnancy. Retinal vascular imaging is a promising tool for the detection of the early microvascular changes in HDP, prior to diagnosis.
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INTRODUCTION: Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal and perinatal morbidity and mortality worldwide. In Australia approximately 10% of all pregnancies are affected by HDP. There is growing evidence that endothelial damage caused by HDP remains after pregnancy and has long term consequences on maternal health. OBJECTIVES: The aim of our research was to determine the association between HDP and risk of having high blood pressure in later life. METHODS: Self-reported data regarding a physician's diagnosis of HDP and of high blood pressure later in life were obtained from women recruited from the 45 and Up Study, Australia. Relative risks (converted from odds ratios) and 99% confidence intervals were estimated using logistic regression, adjusting for demographic and lifestyle characteristics. RESULTS: A total of 82,164 women were included in the study, of which 9,845 reported having HDP. Women who had HDP had a significantly increased risk of having high blood pressure later in life compared to women who did not have HDP (adjusted relative risk of 2.05, 99% CI 1.99-2.11, p<0.001). The results showed that women who had HDP develop high blood pressure 6.3 years (99% CI 5.85-6.66, p<0.001) earlier compared to women without HDP. CONCLUSION: Women who have HDP are at a greater risk of future onset of high blood pressure compared to women who have a healthy pregnancy. Women with HDP should be monitored closely in the years following pregnancy for early identification and intervention of high blood pressure.
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INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of mortality worldwide in women aged >54years. There is a strong association between HDP and the development of hypertension in later life. OBJECTIVES: To ascertain the current health profile of some of the women who were diagnosed with a HDP and participated in a trial during the time period of 1980-1989 and to examine the association between the two. METHODS: Women who delivered at a major teaching hospital during the designated time period and who were enrolled at that time in trials examining HDP treatments and outcomes were invited to participate in a health status evaluation. Their medical histories, time sequenced blood pressure readings, urinalysis, BMI and pulse wave analysis were compared using standard statistical techniques of Chi-square analysis and Student's t-tests obtained from IBM SPSS v.19™. RESULTS: Thirty-nine women from the trials were available for follow-up. Of these women, 85% had current CVD, of which 88% had hypertension, 59% hypercholesterolaemia and 3% had experienced a CVA. Compared to the general female population of 22% for CVD this equates to a RR of 7.2 (CI 95% 3.042-15.13). CONCLUSION: HDP is associated with an increased risk of CVD compared to the general female population. Women who experience HDP in their pregnancy should be monitored regularly due to an increased risk of CVD and potentially early onset of the disease.
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INTRODUCTION: Hypertensive Disorders of Pregnancy (HDP) remain a leading cause of maternal morbidity and mortality worldwide affecting up to 10% of all pregnancies. Previous works inform that long term morbidity includes cardiovascular disease, including ischaemic heart disease, stroke and hypertension. The extent of long term mortality amongst women distant from the primary pregnancy event is not known. OBJECTIVES: To determine mortality rates and cause of death for women who had hypertension during pregnancy between the years 1980-86. METHODS: Women who had hypertension during pregnancy were identified via by ICD-9 coding. From record examination, there was an existing cohort of women who participated in clinical trials at Royal Prince Alfred Hospital in the 1980's. These trials included placebo controlled for blood pressure in pregnancy. The deaths among this cohort were identified by the NSW Registry of Birth Deaths and Marriages. The causes of death were verified from the International Classification of Diseases versions depending upon the year of death. RESULTS: There were a total of 332 women identified as participating in the various trials between the years 1980-86. Of these, there were 17 deaths reported by 2011. This gives an overall mortality rate of 5.1%. Five of these deaths were due to CVD. This equates to an RR of 44.6 (CI 95% 17.43-112.56). CONCLUSION: Women with hypertensive disorders in pregnancy have a higher mortality rate compared to the general female population. Further research is required to determine the relationship between HDP and future hypertension and whether the type of treatment and management women receive with HDP effects their risk of future long term health outcomes.
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1. Increases in soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) contribute to the pathogenesis of pre-eclampsia. Soluble Flt-1 binds to circulating free vascular endothelial growth factor and placenta growth factor and this is associated with endothelial dysfunction. Soluble endoglin, a transforming growth factor (TGF)-beta coreceptor, was reported to synergize with sFlt-1 to amplify endothelial dysfunction by inhibiting TGF-beta1-mediated vasorelaxation. 2. The aim of the present study was to examine whether the antihypertensive drugs clonidine (0.08-1.3 microg/mL), diazoxide (25-300 microg/mL), frusemide (60-1000 microg/mL) and hydralazine (6.3-100 microg/mL) have any effect on placental production of sFlt-1 and sEng in placentas from normal and pre-eclamptic pregnancies. 3. Explants were taken from non-laboured term placentas of normal pregnancy (n = 5) and women with pre-eclampsia (n = 5). Villous explants were cultured with increasing doses of antihypertensive drugs. Placental sFlt-1 and sEng production was examined using ELISA. 4. Baseline sFlt-1 production was higher in placentas from women with pre-eclampsia than from normal pregnancy (4.5 +/- 1.4 vs 3.2 +/- 0.6 ng/mg of total protein, respectively; P < 0.001), as was sEng production (9.0 +/- 2.3 vs 4.1 +/- 0.6 ng/mg of total protein, respectively; P < 0.001). With the exception of frusemide, none of the antihypertensive drugs tested had any effect on sFlt-1 and sEng production from placental explants of normal pregnancy and women with pre-eclampsia. Increasing frusemide concentrations were correlated with increased sEng production in normal pregnancy (P < 0.005). 5. In conclusion, placental sFlt-1 and sEng production was higher in pre-eclampsia and antihypertensive drugs had no effect on placental production of sFlt-1 and sEng in vitro.
