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Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2 (2012) 240–339
Objectives: Therefore, we hypothesized that circulating VEGF-C and its circulating receptors (sVEGFR2 and sVEGFR3) may also be altered in preeclampsia and correlate with the severity of the phenotype. Methods: We analyzed plasma levels of VEGF-C, sVEGFR1, sVEGFR2 and sVEGFR3 in women with gestational hypertension (GHTN, n = 20), preeclampsia (PE, n = 20) and normotensive pregnancies (NP, n = 20) in the third trimester and values reported as mean ± SD in pg/ml. Results: As previously reported, sVEGFR1 levels were significantly higher in subjects with PE (19938 ± 12973) than in GHTN (7156 ± 5432), p < 0.01 or NP (7760 ± 6018), p < 0.01. VEGF-C levels were lower in subjects with GHTN (676 ± 323) than in PE (1335 ± 625), p < 0.01, but not statistically different than in NP (971 ± 556), p = 0.11. There was a trend towards lower sVEGFR-2 in PE as compared to GHTN or NP. Interestingly sVEGFR-3 was significantly lower in PE (54,371 ± 21,107) as compared to NP (83,709 ± 24,983), p < 0.01, but not different as compared to GHTN (54,642 ± 26,947). The ratio of sVEGFR-2 + sVEGFR-3/VEGFC was dramatically lower during PE (57 ± 38) as compared to GHTN (113 ± 72), p < 0.01 or NP (133 ± 91), p < 0.01. Conclusion: Preeclampsia is characterized by circulating pro-lymphangiogenic state as evidenced by decreased sVEGFR-3, slightly decreased VEGFR-2, increased VEGF-C and a dramatically lower ratio of sVEGFR2 + sVEGFR3/VEGFC. Our data suggests that the circulating pro-lymphoangiogenic state during preeclampsia may be a compensatory response to edema and hypertension. Additional studies are needed to evaluate the clinical relevance of the altered lymphangiogenic signalling pathway during preeclampsia. Disclosure of interest: T. Lely: None declared, S. Salahuddin: none declared, K. Holwerda: none declared, A. Karumanchi Consultant for: Roche and Beckman Coulter, Other: Co-inventor of multiple patents related to angiogenic proteins for the diagnosis and therapy of preeclampsia. These patents have been licensed to multiple companies. Financial interest in Aggamin LLC. , S. Rana: none declared. doi:10.1016/j.preghy.2012.04.127
PP017 Comparison of vascular function in preeclamptic and normotensive pregnant women in the rural eastern Cape province of South Africa A.V. Namugowa 1, A. Meeme 2,* (1 Physiology, Walter Sisulu University, Mthatha, South Africa, 2 Obstetrics and Gynecology, Walter Sisulu University, Mthatha, South Africa) Introduction: Preeclampsia is associated with arterial stiffness and endothelial dysfunction. Objectives: The aim of the study was to compare vascular function of pregnant women with preeclampsia and normotensives by non-invasive techniques. Methods: This was a comparative study where participants were recruited from Mthatha General Hospital complex Antenatal clinics. Fifty four (54) normotensive and 21 preeclamptic women were recruited into the study. Arterial stiffness was assessed using applanation tonometry with SphygmoCor device; central aortic pressures and peripheral and central augmentation index (Alx) and carotid-femoral pulse wave velocity was then calculated. Endothelial function was assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index fingers; after baseline recordings a blood pressure cuff was inflated on the nondominant arm then released after 5min to induce flow mediated reactive hyperemia; the ratio of the readings before and after occlusion was then used to calculate the score for endothelial function; the reactive hyperaemia index (RHI) Results: RHI was significantly higher; p < 0.001 among preeclamptic women compared to normotensives (1.76 ± 0.5 vs 1.45 ± 0.22) indicating good endothelial function. Pulse wave velocity was significantly higher; p < 0.001 in preeclamptic than normotensive women (6.7 ± 1.5 vs 5.1 ± 0.7) indicating arterial stiffness. Alx measured by the EndoPAT 2000 correlated with peripheral Alx (r = 0.623, p < 0.0001) and central Alx (r = 0.60, p < 0.0001) measured by the SphygmoCor. This means that either of these parameters can be used to assess arterial stiffness. Conclusion: In this interim analysis, we have demonstrated that women with preeclampsia have increased pulse wave velocity and peripheral augmentation index suggesting vascular stiffness. Low RHI values indicate endothelial
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2 (2012) 240–339
dysfunction in the general population; however our results showed a higher value in preeclampsia than in normal pregnancy. Could there be other factors responsible for RHI in pregnancy? Disclosure of interest: None declared. doi:10.1016/j.preghy.2012.04.128
PP018 Cardiac reflex responses measured by impedance cardiography are different between low and high cardiac output pre-eclampsia K. Tomsin 1,2,*, T. Mesens 1, J. Oben 1,2, G. Molenberghs 3, L. Peeters 4, W. Gyselaers 1,2 (1 Obstetrics and Gynaecology, Ziekenhuis Oost-Limburg, Genk, Belgium, 2 Faculty of Medicine, Hasselt University, Diepenbeek, Belgium 3 I-BioStat, Hasselt University, Diepenbeek, Belgium, 4 Obstetrics and Gynaecology (GROW), Maastricht University, Maastricht, The Netherlands) Introduction: Pre-eclampsia (PE) has been categorised into subtypes depending on low or high cardiac output (CO) states. Are cardiac reflex responses (CRR) different between these two subtypes? Objectives: Impedance cardiography (ICG) measurements of cardiac cycle time intervals (CCTI) before and after orthostatic challenge are evaluated in the clinical phase of PE with low and high CO (LPE and HPE, respectively). Methods: Examinations were performed in 25 LPE (CO 7 l/min) and 16 HPE (CO 9 l/min). A third generation ICG device using a four electrode arrangement (NICCOMO, Medis, Germany) was used to measure CCTI in supine position and after moving to upright position. The pre-ejection period (PEP) is the time-interval between ventricular depolarisation and start of aortic flow. The left ventricular ejection time (LVET) is the time-interval between opening and closing of the aortic valve. Systolic time ratio (STR) is PEP/LVET. Diastolic time (DT) is the heart period duration – (PEP + LVET). Time intervals were expressed as a percentage of the heart period duration, i.e. PEPi, LVETi and DTi. Orthostatic-induced changes from supine to upright position (cardiac reflex response or CRR) were evaluated using One-sample Wilcoxon Signed Rank Tests. All CRRs were compared between LPE and HPE using Mann–Whitney U tests. Data are presented as medians (interquartile ranges). Results: Maternal age was comparable between LPE and HPE [29 (26–34) vs 28 (26–33) years; p = 0.55]. This was also true for gestational age [34 (30–38) vs 36 (31–39) weeks; p = 0.50], and pre-gestational BMI [24 (22–30) vs 25 (24– 32); p = 0.21]. Birth weight percentiles were lower in LPE compared to HPE [18 (5–31) vs 44 (18–83); p < 0.01]. CRRs within each group are shown in Table 1. CRRs of PEP, PEPi and DT were different between LPE and HPE [p 0.04], whereas changes in LVET, LVETi, DTi and STR were not [p 0.09]. Reflex-induced changes of diastolic blood pressure and heart rate (HR) were not significantly different between LPE and HPE [p 0.41].
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Conclusion: Orthostasis does not change PEP in HPE, but induces a significant increase of PEP in LPE. PEP is dependent on HR, preload, afterload and sympathetic activity. There is no difference in the reflex-induced response of HR, DBP (afterload), and STR (sympathetic activity) between the two groups. This suggests that the orthostatic-induced change in the isovolumetric contraction time in LPE is preload-induced. Our observations suggest that hemodynamic background mechanisms behind LPE and HPE are different, and support the view that these subtypes are two different clinical entities. Disclosure of interest: None declared. doi:10.1016/j.preghy.2012.04.129
PP019 The role of renal markers in women with and without preeclampsia: Evaluation of urinary excretion of podocytes and proteins N. Sass 1,*, T.A. Facca 1, A.R.P.R. Pereira 2, E.A. Famá 3, S.K. Nishida 2, S.R. Moreira 2, V.P. Teixeira 2, G.M.M. Kirsztajn 2 (1 Obstetrics, Federal University of São Paulo, Brazil, 2 Nephrology, Federal University of São Paulo, Brazil, 3 Obstetrics, ABC Medical School, São Paulo, Brazil) Introduction: Preeclampsia (PE) is an important cause of glomerulopathy. Assessment of renal markers during pregnancy may have a predictive value for glomerular disease later in life. The early detection of PE may prevent the complications of this syndrome. Objectives: Assess the glomerular involvement in PE and in normal pregnancy by evaluating renal markers such as podocyturia and proteinuria. Methods: Case–control study with 39 pregnant women after 20 weeks of gestation (control group – CG with n = 25 and PE with n = 14), we assessed podocyturia (cytospin method) and proteinuria (albuminuria, urine protein:creatinine – PCR, urinary retinol protein – RBP and albumin/creatinine ratio – ACR). (Grant FAPESP 08/56338-1) Results: Mean ± standard deviation of age and mean gestational age of CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks and of PE, 26.4 ± 6.9 and 30.6 ± 5.6, respectively (p = 0.001). No statistical differences were found between podocyturia in CG and PE although it was more frequent in this last group (p = 0.258). Podocyte cells and parietal epithelial cells were detected in the slides. Mean ± standard deviation of urinary RBP (p = 0.017), albuminuria (p = 0.002) and UAC ratio (p = 0.006) of CG were 0.4 ± 0.7 mg/L, 7.3 ± 6.9 mg/L and 8.2 ± 6.7 mg/g and of PE, 2.0 ± 4.4 mg/L, 2267.4 ± 2130.8 mg/L (p = 0.002) and 3778.9 ± 4296.6 mg/g (p = 0.006), respectively. Mean value ± standard deviation of urine PCR in PE was 6.7 ± 6.1 g/g (p = < 0.001). Conclusion: Urinary RBP, PCR, albuminuria and UAC ratio were elevated in PE in comparison to CG indicating its glomerular involvement but there was no correlation between those renal parameters and podocyturia. RPC and UAC ratios were good predictors of PE, but not podocyturia. Either pod-
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2 (2012) 240–339
Objectives: Therefore, we hypothesized that circulating VEGF-C and its circulating receptors (sVEGFR2 and sVEGFR3) may also be altered in preeclampsia and correlate with the severity of the phenotype. Methods: We analyzed plasma levels of VEGF-C, sVEGFR1, sVEGFR2 and sVEGFR3 in women with gestational hypertension (GHTN, n = 20), preeclampsia (PE, n = 20) and normotensive pregnancies (NP, n = 20) in the third trimester and values reported as mean ± SD in pg/ml. Results: As previously reported, sVEGFR1 levels were significantly higher in subjects with PE (19938 ± 12973) than in GHTN (7156 ± 5432), p < 0.01 or NP (7760 ± 6018), p < 0.01. VEGF-C levels were lower in subjects with GHTN (676 ± 323) than in PE (1335 ± 625), p < 0.01, but not statistically different than in NP (971 ± 556), p = 0.11. There was a trend towards lower sVEGFR-2 in PE as compared to GHTN or NP. Interestingly sVEGFR-3 was significantly lower in PE (54,371 ± 21,107) as compared to NP (83,709 ± 24,983), p < 0.01, but not different as compared to GHTN (54,642 ± 26,947). The ratio of sVEGFR-2 + sVEGFR-3/VEGFC was dramatically lower during PE (57 ± 38) as compared to GHTN (113 ± 72), p < 0.01 or NP (133 ± 91), p < 0.01. Conclusion: Preeclampsia is characterized by circulating pro-lymphangiogenic state as evidenced by decreased sVEGFR-3, slightly decreased VEGFR-2, increased VEGF-C and a dramatically lower ratio of sVEGFR2 + sVEGFR3/VEGFC. Our data suggests that the circulating pro-lymphoangiogenic state during preeclampsia may be a compensatory response to edema and hypertension. Additional studies are needed to evaluate the clinical relevance of the altered lymphangiogenic signalling pathway during preeclampsia. Disclosure of interest: T. Lely: None declared, S. Salahuddin: none declared, K. Holwerda: none declared, A. Karumanchi Consultant for: Roche and Beckman Coulter, Other: Co-inventor of multiple patents related to angiogenic proteins for the diagnosis and therapy of preeclampsia. These patents have been licensed to multiple companies. Financial interest in Aggamin LLC. , S. Rana: none declared. doi:10.1016/j.preghy.2012.04.127
PP017 Comparison of vascular function in preeclamptic and normotensive pregnant women in the rural eastern Cape province of South Africa A.V. Namugowa 1, A. Meeme 2,* (1 Physiology, Walter Sisulu University, Mthatha, South Africa, 2 Obstetrics and Gynecology, Walter Sisulu University, Mthatha, South Africa) Introduction: Preeclampsia is associated with arterial stiffness and endothelial dysfunction. Objectives: The aim of the study was to compare vascular function of pregnant women with preeclampsia and normotensives by non-invasive techniques. Methods: This was a comparative study where participants were recruited from Mthatha General Hospital complex Antenatal clinics. Fifty four (54) normotensive and 21 preeclamptic women were recruited into the study. Arterial stiffness was assessed using applanation tonometry with SphygmoCor device; central aortic pressures and peripheral and central augmentation index (Alx) and carotid-femoral pulse wave velocity was then calculated. Endothelial function was assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index fingers; after baseline recordings a blood pressure cuff was inflated on the nondominant arm then released after 5min to induce flow mediated reactive hyperemia; the ratio of the readings before and after occlusion was then used to calculate the score for endothelial function; the reactive hyperaemia index (RHI) Results: RHI was significantly higher; p < 0.001 among preeclamptic women compared to normotensives (1.76 ± 0.5 vs 1.45 ± 0.22) indicating good endothelial function. Pulse wave velocity was significantly higher; p < 0.001 in preeclamptic than normotensive women (6.7 ± 1.5 vs 5.1 ± 0.7) indicating arterial stiffness. Alx measured by the EndoPAT 2000 correlated with peripheral Alx (r = 0.623, p < 0.0001) and central Alx (r = 0.60, p < 0.0001) measured by the SphygmoCor. This means that either of these parameters can be used to assess arterial stiffness. Conclusion: In this interim analysis, we have demonstrated that women with preeclampsia have increased pulse wave velocity and peripheral augmentation index suggesting vascular stiffness. Low RHI values indicate endothelial
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2 (2012) 240–339
dysfunction in the general population; however our results showed a higher value in preeclampsia than in normal pregnancy. Could there be other factors responsible for RHI in pregnancy? Disclosure of interest: None declared. doi:10.1016/j.preghy.2012.04.128
PP018 Cardiac reflex responses measured by impedance cardiography are different between low and high cardiac output pre-eclampsia K. Tomsin 1,2,*, T. Mesens 1, J. Oben 1,2, G. Molenberghs 3, L. Peeters 4, W. Gyselaers 1,2 (1 Obstetrics and Gynaecology, Ziekenhuis Oost-Limburg, Genk, Belgium, 2 Faculty of Medicine, Hasselt University, Diepenbeek, Belgium 3 I-BioStat, Hasselt University, Diepenbeek, Belgium, 4 Obstetrics and Gynaecology (GROW), Maastricht University, Maastricht, The Netherlands) Introduction: Pre-eclampsia (PE) has been categorised into subtypes depending on low or high cardiac output (CO) states. Are cardiac reflex responses (CRR) different between these two subtypes? Objectives: Impedance cardiography (ICG) measurements of cardiac cycle time intervals (CCTI) before and after orthostatic challenge are evaluated in the clinical phase of PE with low and high CO (LPE and HPE, respectively). Methods: Examinations were performed in 25 LPE (CO 7 l/min) and 16 HPE (CO 9 l/min). A third generation ICG device using a four electrode arrangement (NICCOMO, Medis, Germany) was used to measure CCTI in supine position and after moving to upright position. The pre-ejection period (PEP) is the time-interval between ventricular depolarisation and start of aortic flow. The left ventricular ejection time (LVET) is the time-interval between opening and closing of the aortic valve. Systolic time ratio (STR) is PEP/LVET. Diastolic time (DT) is the heart period duration – (PEP + LVET). Time intervals were expressed as a percentage of the heart period duration, i.e. PEPi, LVETi and DTi. Orthostatic-induced changes from supine to upright position (cardiac reflex response or CRR) were evaluated using One-sample Wilcoxon Signed Rank Tests. All CRRs were compared between LPE and HPE using Mann–Whitney U tests. Data are presented as medians (interquartile ranges). Results: Maternal age was comparable between LPE and HPE [29 (26–34) vs 28 (26–33) years; p = 0.55]. This was also true for gestational age [34 (30–38) vs 36 (31–39) weeks; p = 0.50], and pre-gestational BMI [24 (22–30) vs 25 (24– 32); p = 0.21]. Birth weight percentiles were lower in LPE compared to HPE [18 (5–31) vs 44 (18–83); p < 0.01]. CRRs within each group are shown in Table 1. CRRs of PEP, PEPi and DT were different between LPE and HPE [p 0.04], whereas changes in LVET, LVETi, DTi and STR were not [p 0.09]. Reflex-induced changes of diastolic blood pressure and heart rate (HR) were not significantly different between LPE and HPE [p 0.41].
251
Conclusion: Orthostasis does not change PEP in HPE, but induces a significant increase of PEP in LPE. PEP is dependent on HR, preload, afterload and sympathetic activity. There is no difference in the reflex-induced response of HR, DBP (afterload), and STR (sympathetic activity) between the two groups. This suggests that the orthostatic-induced change in the isovolumetric contraction time in LPE is preload-induced. Our observations suggest that hemodynamic background mechanisms behind LPE and HPE are different, and support the view that these subtypes are two different clinical entities. Disclosure of interest: None declared. doi:10.1016/j.preghy.2012.04.129
PP019 The role of renal markers in women with and without preeclampsia: Evaluation of urinary excretion of podocytes and proteins N. Sass 1,*, T.A. Facca 1, A.R.P.R. Pereira 2, E.A. Famá 3, S.K. Nishida 2, S.R. Moreira 2, V.P. Teixeira 2, G.M.M. Kirsztajn 2 (1 Obstetrics, Federal University of São Paulo, Brazil, 2 Nephrology, Federal University of São Paulo, Brazil, 3 Obstetrics, ABC Medical School, São Paulo, Brazil) Introduction: Preeclampsia (PE) is an important cause of glomerulopathy. Assessment of renal markers during pregnancy may have a predictive value for glomerular disease later in life. The early detection of PE may prevent the complications of this syndrome. Objectives: Assess the glomerular involvement in PE and in normal pregnancy by evaluating renal markers such as podocyturia and proteinuria. Methods: Case–control study with 39 pregnant women after 20 weeks of gestation (control group – CG with n = 25 and PE with n = 14), we assessed podocyturia (cytospin method) and proteinuria (albuminuria, urine protein:creatinine – PCR, urinary retinol protein – RBP and albumin/creatinine ratio – ACR). (Grant FAPESP 08/56338-1) Results: Mean ± standard deviation of age and mean gestational age of CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks and of PE, 26.4 ± 6.9 and 30.6 ± 5.6, respectively (p = 0.001). No statistical differences were found between podocyturia in CG and PE although it was more frequent in this last group (p = 0.258). Podocyte cells and parietal epithelial cells were detected in the slides. Mean ± standard deviation of urinary RBP (p = 0.017), albuminuria (p = 0.002) and UAC ratio (p = 0.006) of CG were 0.4 ± 0.7 mg/L, 7.3 ± 6.9 mg/L and 8.2 ± 6.7 mg/g and of PE, 2.0 ± 4.4 mg/L, 2267.4 ± 2130.8 mg/L (p = 0.002) and 3778.9 ± 4296.6 mg/g (p = 0.006), respectively. Mean value ± standard deviation of urine PCR in PE was 6.7 ± 6.1 g/g (p = < 0.001). Conclusion: Urinary RBP, PCR, albuminuria and UAC ratio were elevated in PE in comparison to CG indicating its glomerular involvement but there was no correlation between those renal parameters and podocyturia. RPC and UAC ratios were good predictors of PE, but not podocyturia. Either pod-
