Amanda Green

Oxidative stress markers in hypertensive states of pregnancy: preterm and term disease

Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk.

OS102. Continuing pathology following a hypertensive pregnancy and the risk of future disease

INTRODUCTION New onset hypertension in pregnancy affects up to 6-8% of all pregnancies. For most women, hypertension and proteinuria settle following delivery. The National Institute for Health and Clinical Excellence (NICE) Hypertension in Pregnancy guideline recommends that this group of patients are reviewed by a medical professional postnatally [3]. However, studies have shown that blood pressure and urinalysis are often not checked in the postpartum period [4]. Women with a history of hypertension in pregnancy have a higher risk of future hypertension and cardiovascular disease (CVD) than women who have uncomplicated pregnancies [2]. Risk scores are available for assessing an individuals risk of CVD although they are not validated in women under 30. In UK, the most appropriate is QRISK2 score [1]. OBJECTIVES To determine the frequency of ongoing problems following a new onset hypertensive pregnancy and assess the risk of future cardiovascular disease. METHODS 351 women with new onset hypertension in pregnancy were reviewed 6 weeks postnatally. They were assessed for ongoing disease and cardiovascular risk. 10 year QRISK2 scores and heart age (the age at which a matched person has that score) were calculated. RESULTS 211 women with pre-eclampsia (PE) and 140 with gestational hypertension (GH) were reviewed. 9% and 11% of women with previous PE and GH respectively still required antihypertensive agents at follow-up. Only 1 woman required more than one antihypertensive medication (PE group). 19 women with PE (9%) had ongoing proteinuria (PCR>30). 5% had an estimated GFR <60ml/min. In addition to those with a strong family history of hypertension, 23 patients (6.5%) required investigation for ongoing problems. Risk factors for CVD were common 6 weeks after delivery: Although the overall risk of CVD was low (median 10 year QRISK2 score 0.3, median relative risk 1.0), with 41% of women having the lowest possible heart age, 22% of women had a significantly elevated risk of CVD (QRISK2 heart age ⩾age+10). CONCLUSION 16% of women had ongoing hypertension or proteinuria, evidence supporting the NICE guidance that all women with hypertension in pregnancy need follow-up after delivery. The overall risk of future CVD in women with previous hypertension in pregnancy is low but about one-fifth of women are at very high risk. A program of risk assessment is required to allow preventative measures to be implemented.

Postpartum evaluation of cardiovascular disease risk for women with pregnancies complicated by hypertension

OBJECTIVES Postpartum stratification of cardiovascular risk for women with pregnancies complicated by pre-eclampsia is challenging. Our aim was to identify potential clinical and biomarker predictors of future cardiovascular risk at six weeks postpartum in women with hypertensive pregnancies. STUDY DESIGN Prospective longitudinal cohort. MAIN OUTCOME MEASURES Ten year-Framingham cardiovascular risk scores were calculated for 477 women (94 with gestational hypertension, 288 with pre-eclampsia, 30 with superimposed pre-eclampsia, 51 with chronic hypertension, 14 women with uncomplicated pregnancies). B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and placental growth factor (PlGF) were quantified at six weeks postpartum. RESULTS Framingham cardiovascular risk scores were not higher in women with pregnancies complicated by pre-eclampsia than healthy controls, nor were scores higher in women with pre-existing chronic hypertension complicated with superimposed pre-eclampsia compared with those without superimposed pre-eclampsia. Women with gestational hypertension had higher risk scores than women with pre-eclampsia and healthy controls. Established risk factors of cardiovascular disease including diastolic blood pressure and previously diagnosed chronic hypertension were associated with higher scores, and African ethnicity, parity and estimated glomerular filtration rate also were independently associated with higher Framingham risk scores at six weeks postpartum. PlGF, BNP and NGAL concentrations were not associated with Framingham cardiovascular risk scores after adjustment for independent variables. CONCLUSIONS A history of pre-eclampsia or superimposed pre-eclampsia in most recent pregnancy was not associated with elevated Framingham risk score at six weeks postpartum. Established clinical predictors may enable risk stratification at six weeks postpartum, which are not enhanced by the biomarkers included in this study.

Adjustment for race in the estimation of glomerular filtration rate (GFR) is inappropriate in the British postnatal population.

We suppose that a few trophoblast cells might remain in the body after every pregnancy but they degenerate naturally. In rare instances, if this process is delayed, the transition of normal cells to malignant proliferation seems plausible. When a relatively large mass of trophoblastic tissue is retained for an extended period, the risk of neoplastic transformation is increased. The present case report raises the concern whether more intensive management is necessary to remove placental remnants even in asymptomatic women. Additionally, if unusual vaginal bleeding occurs after normal delivery, the possibility of gestational trophoblastic tumor should be ruled out.

PP074. Persistent proteinuria after a pre-eclamptic pregnancy.

INTRODUCTION There is increasing evidence to suggest that both preeclampsia and microalbuminuria are linked to long term cardiovascular and renal disease [1,2]. OBJECTIVES To identify the proportion and characteristics of women with persistent significant proteinuria at 6 weeks following delivery. METHOD We examined the blood pressure, serum electrolytes and urine protein creatinine ratio (PCR) in a cohort of 219 women who were seen following a pre-eclamptic pregnancy in a postnatal clinic at a minimum of 6 weeks following delivery. RESULTS A PCR>50mg/mmol (considered to be clinically significant) was seen in 4.1% women at 6 weeks after delivery. Women with a higher antenatal PCR were more likely to have a PCR>50mg/mmol at 6 weeks postnatal (p=0.003). Antenatal or postnatal blood pressure was not correlated with persistent significant proteinuria. Neither estimated nor calculated glomerular filtration rate (eGFR) at 6 weeks correlated with those having persistent proteinuria, however there was a trend towards lower eGFR and higher serum creatinine antenatally in this group (p=0.138 and p=0.088). CONCLUSION There are a small but worrying number of women who still have clinically significant proteinuria at 6 weeks after a pre-eclamptic pregnancy. This represents a group of women who may have a higher risk of cardiovascular and renal disease.

PP075. Poor renal function following hypertensive pregnancy: Older mothers and smaller babies

INTRODUCTION There is increasing evidence that hypertensive pregnancy is a risk factor for renal disease [1]. OBJECTIVES To examine the correlation between maternal and offspring characteristics and impaired glomerular filtration rate following a hypertensive pregnancy. METHOD We calculated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula corrected for body surface area in a cohort of 422 women at 6 weeks following a pregnancy complicated by all types of hypertension (pre-eclampsia, gestational hypertension, essential hypertension with and without superimposed pre-eclampsia). We performed statistical analysis using Spearmans rho to examine for correlations with maternal and fetal characteristics. RESULTS 2.1% women had poor renal function at 6 weeks after delivery with a GFR <60ml/min/1.73m(2). Older mothers were more likely to have a lower GFR (p=0.001). Women with poor renal function at 6 weeks were more likely to have had a low birth weight baby (p=0.002). The median birth weight for women with GFR<60ml/min/1.73m(2) was 2.85kg as opposed to 3.23kg for women with a GFR >60ml/min/1.73m(2). CONCLUSIONS Clinically significant renal impairment following a hypertensive pregnancy is a rare. Advancing maternal age represents an important risk factor for on-going renal disease in this population. Small babies are more likely in a hypertensive pregnancy [2] and may also represent a marker for poorer maternal health after birth in this population.