History Of Gestational Hypertension Research Articles

165. Improved prediction of gestational hypertension by inclusion of placental growth factor and Pregnancy Associated Plasma Protein-A in a sample of Ghanaian women

Introduction This study was nested in a prospective cohort of 1010 pregnant women attending antenatal clinics in two public hospitals in Accra, Ghana. Objectives We assessed whether adding the biomarkers Pregnancy Associated Plasma Protein-A (PAPP-A) and Placental Growth Factor (PlGF) to maternal clinical characteristics improved the prediction of a previously developed model for gestational hypertension in a cohort of Ghanaian pregnant women. Methods Pregnant women who were normotensive, at a gestational age at recruitment of between 8 and 13 weeks and provided a blood sample for biomarker analysis were eligible for inclusion. From serum, biomarkers PAPP-A and PlGF concentrations were measured by the AutoDELFIA immunoassay method and multiple of the median (MoM) values corrected for gestational age (PAPP-A and PlGF) and maternal weight (PAPP-A) were calculated. To obtain prediction models, these biomarkers were included with clinical predictors maternal weight,height, diastolic blood pressure, a previous history of gestational hypertension, history of hypertension in parents and parity in a logistic regression to obtain prediction models. The Area Under the Receiver Operating Characteristic Curve (AUC) was used to assess the predictive ability of the models. Results Three hundred and seventy-three women participated in this study. The area under the curve (AUC) of the model with only maternal clinical characteristics was 0.75 (0.64–0.86) and 0.89(0.73–1.00) for multiparous and primigravid women respectively. The AUCs after inclusion of both PAPP-A and PlGF were 0.82 (0.74–0.89) and 0.95 (0.87–1.00) for multiparous and primigravid women respectively. Discussion Adding the biomarkers PAPP-A and PlGF to maternal characteristics in a prediction model for gestational hypertension in a cohort of Ghanaian pregnant women improved predictive ability. Further research using larger sample sizes in similar settings to validate these findings is recommended.

Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: High BMI is key

ObjectiveHypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder. Study designPlasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients. ResultsPlasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002). ConclusionOur results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.

Improved prediction of gestational hypertension by inclusion of placental growth factor and pregnancy associated plasma protein-a in a sample of Ghanaian women

BackgroundWe assessed whether adding the biomarkers Pregnancy Associated Plasma Protein-A (PAPP-A) and Placental Growth Factor (PlGF) to maternal clinical characteristics improved the prediction of a previously developed model for gestational hypertension in a cohort of Ghanaian pregnant women.MethodsThis study was nested in a prospective cohort of 1010 pregnant women attending antenatal clinics in two public hospitals in Accra, Ghana. Pregnant women who were normotensive, at a gestational age at recruitment of between 8 and 13 weeks and provided a blood sample for biomarker analysis were eligible for inclusion. From serum, biomarkers PAPP-A and PlGF concentrations were measured by the AutoDELFIA immunoassay method and multiple of the median (MoM) values corrected for gestational age (PAPP-A and PlGF) and maternal weight (PAPP-A) were calculated. To obtain prediction models, these biomarkers were included with clinical predictors maternal weight, height, diastolic blood pressure, a previous history of gestational hypertension, history of hypertension in parents and parity in a logistic regression to obtain prediction models. The Area Under the Receiver Operating Characteristic Curve (AUC) was used to assess the predictive ability of the models.ResultsThree hundred and seventy three women participated in this study. The area under the curve (AUC) of the model with only maternal clinical characteristics was 0.75 (0.64–0.86) and 0.89(0.73–1.00) for multiparous and primigravid women respectively. The AUCs after inclusion of both PAPP-A and PlGF were 0.82 (0.74–0.89) and 0.95 (0.87–1.00) for multiparous and primigravid women respectively.ConclusionAdding the biomarkers PAPP-A and PlGF to maternal characteristics to a prediction model for gestational hypertension in a cohort of Ghanaian pregnant women improved predictive ability. Further research using larger sample sizes in similar settings to validate these findings is recommended.

Low Calcium Intake in Midpregnancy Is Associated with Hypertension Development within 10 Years after Pregnancy: The Norwegian Mother and Child Cohort Study

Background: Low dietary calcium intake may be a risk factor for hypertension, but studies conflict.Objective: We evaluated the ability to predict hypertension within 10 y after delivery based on calcium intake during midpregnancy.Methods: The Norwegian Mother and Child Cohort Study of women delivering in 2004-2009 was linked to the Norwegian Prescription Database (2004-2013) to ascertain antihypertensive medication usage >90 d after delivery. Women with hypertension before pregnancy were excluded, leaving 60,027 mothers for analyses. Age and energy-adjusted cubic splines evaluated dose-response curves, and Cox proportional hazard analyses evaluated HR and 95% CIs by calcium quartiles adjusting for 7 covariates. Analyses were stratified by gestational hypertension and by sodium-to-potassium intake ratio (<0.76 compared with ≥0.76).Results: Participants had a mean ± SD age of 30.5 ± 4.6 y, a body mass index (in kg/m2) of 24.0 ± 4.3 before pregnancy, and a mean follow-up duration of 7.1 ± 1.6 y. Cubic spline graphs identified a threshold effect of low calcium intake only within the range of dietary inadequacy related to increased risk. The lowest calcium quartile (≤738 mg/d; median: 588 mg/d), relative to the highest quartile (≥1254 mg/d), had an HR for hypertension of 1.34 (95% CI: 1.05, 1.70) among women who were normotensive during pregnancy, and an HR of 1.62 (95% CI: 1.14, 2.35) among women who had gestational hypertension, after adjusting for covariates. Women with gestational hypertension, who were in the lowest quartile of calcium intake, and who had a high sodium-to-potassium intake ratio had a risk of hypertension more than double that of their counterparts with a calcium intake in the highest quartile. Results were attenuated by adjusting for covariates (HR: 1.92; 95% CI: 1.09, 3.39).Conclusions: The results suggest that low dietary calcium intake may be a risk factor or risk marker for the development of hypertension, particularly for women with a history of gestational hypertension.

Pregnancy outcomes in women with previous gestational hypertension: A cohort study to guide counselling and management.

In pregnant women with previous gestational hypertension: to compare the prevalence of preeclampsia as defined by the 2001 versus the 2014 International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria, to determine the rates of fetal growth restriction (FGR) as defined, not only by birthweight centile, but in combination with fetal ultrasound studies and, finally, to determine rates of other related outcomes such as gestational diabetes (GDM) and obstetric cholestasis (OC). This was a retrospective observational study based at the Antenatal Hypertension Clinic, Kings College Hospital, London. Routinely collected data of 773 women booked between 2011 and 2016 with a history of gestational hypertension was analysed. All women were normotensive at booking and those with chronic hypertension were excluded. Hypertensive disorders of pregnancy (ISSHP-2014), FGR, GDM. Forty-nine percent developed one or more pregnancy complications, of which 72% were hypertensive disorders of pregnancy, 25.8% preeclampsia, 25% GDM and 19% FGR. Overall recurrence rate of preeclampsia was 12.5% (ISSHP-2014). Higher blood pressure and body mass index at booking were associated with higher risk of preeclampsia and GDM. Earlier gestation of previous hypertension was associated with higher risk of preeclampsia and FGR. The ISSHP-2014 compared to the 2001 guidelines classified 56% more women as having preeclampsia. Pregnant women with a history of gestational hypertension have a 49% chance of developing a complication related to a hypertensive disorder, GDM and OC. The rate of preeclampsia was more than doubled if the updated ISSHP-2014 definition was used.

P 33 Does the performance of mean arterial pressure for the screening of preeclampsia differ between women with chronic hypertension and women with a history of gestational hypertension?

Question Recent studies have demonstrated that different parameters of blood pressure may hold valuable information not only in the diagnosis of preeclampsia (PE) but also in identifying women in their first and second trimester at risk of developing PE later in the pregnancy. One such promising component is mean arterial blood pressure (MAP). This study aims to examine the prediction of MAP for PE, renal dysfunction, liver dysfunction and fetal growth restriction (FGR) in two groups of high-risk pregnant women: with chronic hypertension or a history of gestational hypertension. Methods A retrospective study was conducted on women with chronic hypertension ( N = 478) and normotensive women with a history of gestational hypertension ( N = 511) who booked with the Antenatal Hypertension Clinic, Kings College Hospital, London, between 2009–2016. Blood pressure was measured repeatedly antenatally using an automated device validated for use in pregnancy and PE. The updated International Society for the Study of Hypertension in Pregnancy (ISSHP)-2014 definition of PE was used. We constructed probit models to determine the predictive capacity of MAP by comparing the Receiver Operating Characteristic Curves (ROC) in the two groups. Wald tests of the null hypothesis that the two ROC curves are equal at different false-positive rates were performed. Age and medication use were taken into account in the comparisons. STATA 14.0 was used for the analysis. Results The area under the curves (AUC) for the prediction of PE ( p = p = 0.079) was 0.66 (95% CI: 0.62–0.71) and 0.79 (95% CI: 0.74–0.85) for women with chronic hypertension and history of gestational hypertension, respectively (Fig. 1). There were no differences found between the AUC for the prediction of FGR and liver dysfunction. Estimates were adjusted for age and medication use, with the latter being strongly associated with hypertension status. Conclusion The ability of MAP to predict PE and renal dysfunction is significantly affected by the woman’s hypertensive status, with improved performance in women with a history of gestational hypertension.

P 34 Does performance of mean arterial blood pressure for the screening of preeclampsia improve after controlling for the use of anti-hypertensive medication?

Question Mean arterial pressure (MAP) is a useful biomarker for the screening of preeclampsia (PE). However, MAP, a function of cardiac output and peripheral resistance, is dependent on other maternal characteristics and, for its effective use in screening, these need to be taken into account. One such characteristic is the use of anti-hypertensive medication. The aim of our study was to evaluate the impact of the use of anti-hypertensive medication on the performance of MAP as a screening tool for PE in pregnant women with chronic hypertension or a history of gestational hypertension. Methods A retrospective study was conducted on women with chronic hypertension (N = 478) and normotensive women with a history of gestational hypertension (N = 511) who booked with the Antenatal Hypertension Clinic, Kings College Hospital, London, between 2009–2016. Blood pressure was measured repeatedly antenatally using an automated device validated for use in pregnancy and PE. The more updated International Society for the Study of Hypertension in Pregnancy (ISSHP)-2014 definition of PE was used. We constructed probit Receiver Operating Characteristic Curves (ROC) models to determine the predictive capacity of MAP in women taking anti-hypertensive medication and in those who were not. Wald tests of the null hypothesis that the two ROC curves are equal at different false-positive rates were performed. Age and medication use were taken into account in the comparisons. Results The area under the curves (AUC) for the prediction of PE (p = Conclusion The ability of MAP to predict PE and renal dysfunction is significantly improved by controlling for the use of anti-hypertensive medication in a high-risk pregnant population.

Development and validation of a prediction model for gestational hypertension in a Ghanaian cohort

ObjectiveTo develop and validate a prediction model for identifying women at increased risk of developing gestational hypertension (GH) in Ghana.DesignA prospective study. We used frequencies for descriptive analysis, χ2 test...

32 Gestational hypertensive disorders and retinal microcirculation: The Generation R Study

Introduction Gestational hypertensive disorders (GHD), such as gestational hypertension (GH) and pre-eclampsia (PE), are risk factors for cardiovascular disease (CVD) in later life. Although the exact underlying mechanisms are not clear, changes in the microcirculation have also been proposed as a potential pathway in the development of CVD. Objective We examined whether a history of GHD is related to the maternal status of the microcirculation after pregnancy, as visualized by retinal imaging. Methods This study was embedded in the Generation R Study, a population-based prospective cohort study. Data on pregnancy, including GHD, and retinal vessel calibers six years after pregnancy were available for 3391 women. Retinal arteriolar and venular calibers were measured unilaterally from digitalized retinal photographs. Results Women with a history of PE had smaller retinal arteriolar calibers than women with a normotensive pregnancy (age-adjusted difference: −0.49SDS; 95% confidence interval (CI) −0.74, −0.25)). Additional adjustment for retinal venular caliber, ethnicity, educational level, smoking and pre-pregnancy BMI did not alter these results. After including mean arterial blood pressure at the time of retinal imaging, the association attenuated (−0.22SDS; 95% CI −0.43, −0.01), but remained significant. For women with a history of GH similar trends were observed, which disappeared after including mean arterial blood pressure at the time of retinal imaging in the model (−0.001SDS; 95% CI −0.14, 0.14). With respect to retinal venular calibers, we did not observe consistent trends for women with a history of PE. However, in women with a history of GH we observed larger venular calibers (multi-variable adjusted 0.16SDS; 95% CI 0.01, 0.31) than in women with a previous normotensive pregnancy. Conclusions Women with a history of GHD show an altered state of the microcirculation as reflected by smaller retinal arteriolar vessel calibers and larger retinal venular calibers six years after index pregnancy. These microvascular changes may contribute to the development of CVD in later life.

Gestational hypertension and chronic hypertension on the risk of diabetes among gestational diabetes women

AimsWe aimed to examine the association of gestational hypertension and chronic hypertension at the inter-conception examination with type 2 diabetes risk among women with a history of gestational diabetes. MethodsWe conducted a population-based study among 1261 women who had a history of gestational diabetes at 1–5years after delivery in Tianjin, China. Logistic regression or Cox regression was used to assess the associations of gestational hypertension and chronic hypertension at the inter-conception examination with pre-diabetes and type 2 diabetes risks. ResultsGestational diabetic women who had a history of gestational hypertension but did not use antihypertensive drugs during pregnancy had a 3.94-fold higher risk (95% CI: 1.94–8.02) of developing type 2 diabetes compared with those who were normotensive in index pregnancy. Compared with gestational diabetic women who had normal blood pressure at the inter-conception examination, hypertensive women at the inter-conception examination were 3.38 times (95% CI: 1.66–6.87) and 2.97 times (95% CI: 1.75–5.05) more likely to develop diabetes and prediabetes, respectively. The odds ratios of type 2 diabetes and prediabetes associated with each 5mmHg increase in systolic blood pressure were 1.25 (95% CI: 1.03–1.51) and 1.20 (95% CI: 1.06–1.35). Each 5mmHg increase in diastolic blood pressure contributed to a 1.49-fold higher risk (95% CI: 1.18–1.88) for type 2 diabetes and a 1.42-fold higher risk (95% CI: 1.22–1.65) for prediabetes. ConclusionsFor women with prior gestational diabetes, gestational hypertension and chronic hypertension at the inter-conception examination were risk factors for type 2 diabetes.

Abstract P165: Effects of Lactation on Postpartum Blood Pressure among Women with Gestational Hypertension and Preeclampsia

Introduction: Lactation is associated with improved maternal blood pressure (BP) in later life and in the postpartum period among normotensive women. However, little is known about whether lactation is also cardio-protective in women with pregnancy-related hypertensive disorders. This study aimed to characterize the relationship between lactation and postpartum BP in women who remained normotensive during pregnancy compared to those who developed preeclampsia or gestational hypertension. Hypothesis: Lactation will be associated with lower postpartum BP, particularly in women with hypertensive disorders of pregnancy. Methods: Data were obtained from a cohort of normotensive women who participated in the Prenatal Exposures &amp; Preeclampsia Prevention study (n=651; 65% African American; 83% overweight or obese prior to pregnancy). Women were enrolled during pregnancy and attended a postpartum visit where data on lactation and BP were collected following a standardized protocol. Analysis of variance (ANOVA) was used to assess the relationship between lactation and postpartum BP in women who remained normotensive during pregnancy, developed gestational hypertension (2 or more BP measurements &gt;140/90), or developed preeclampsia (gestational hypertension plus proteinuria). Further analyses adjusted for age, race, smoking, prepregnancy weight, and time since delivery. Results: A total of 439 women attended the postpartum study visit (mean time since birth 8.5 months); 50 (11%) developed gestational hypertension, and 38 (9%) preeclampsia. Lactation was reported by 246 (56%) with 84 (19%) reporting lactation for ≥ 6 months. Women who lactated were older, wealthier, and more likely to plan to lactate compared to those who did not lactate. There was no association between lactation duration and postpartum systolic BP for women who remained normotensive during pregnancy (never lactated: 111.0 mmHg vs. lactated ≥ 6 months: 112.9 mmHg, p=0.83) nor among women who developed preeclampsia (never lactated: 121.3 mmHg vs. lactated ≥ 6 months: 128.3 mmHg, p=0.35). However, greater lactation duration was associated with lower systolic BP among women who developed gestational hypertension (never lactated: 127.8 mmHg vs. lactated ≥ 6 months: 109.4 mmHg, p=0.04). This relationship remained significant after adjusting for covariates. Similarly, lactation was associated with lower postpartum diastolic BP only for women with a history of gestational hypertension. Conclusions: Lactation appears to lower postpartum BP among women who develop gestational hypertension, but do not develop preeclampsia. Future work should investigate the mechanisms driving the relationship between lactation and postpartum BP in gestational hypertension.

Cost-effectiveness analysis of cardiovascular risk factor screening in women who experienced hypertensive pregnancy disorders at term

To assess the cost-effectiveness of post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term. Two separate Markov models evaluated the cost-effectiveness analysis of hypertension (HT) screening and screening on metabolic syndrome (MetS), respectively, as compared to current practice in women with a history of term hypertensive pregnancy disorders. Analyses were performed from the Dutch health care perspective, using a lifetime horizon. One-way sensitivity analyses and Monte Carlo simulation evaluated the robustness of the results. Both screening on HT and MetS in women with a history of gestational hypertension or pre-eclampsia resulted in increase in life expectancy (HT screening 0.23year (95% CI -0.06 to 0.54); MetS screening 0.14years (95% CI -0.16 to 0.45)). The gain in QALYs was limited, with HT screening and MetS screening generating 0.04 QALYs (95% CI -0.12 to 0.20) and 0.03 QALYs (95% CI -0.14 to 0.19), resulting in costs to gain one QALY of €4228 and €28,148, respectively. Analyses for uncertainty showed a chance of 74% and 75%, respectively, that post-partum screening is cost-effective at a threshold of €60,000/QALY. According to the available knowledge post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term is likely to be cost-effective.

Association of hypertension and abdominal obesity with some features of gynecologic history

Aim. To study the association of some gynecologic history data in hypertensive women with abdominal obesity. Methods. A cohort of 315 women aged 21-59 years, including 53 healthy volunteers with normal blood pressure, 63 female patients with prehypertension and 197 hypertensive women, was examined. The mean age of hypertensive women was 47.0±7.0 years. Patients with symptomatic hypertension were excluded from the study. The patients were questioned about gynecologic history data (the number of pregnancies, abortions, miscarriages, history of gestational hypertension) and anthropometry. Patients were divided to 2 groups according to presence (137 female patients, mean age 47.8±6.3 years) or absence (178 female patients, mean age 44.4±7.3 years) of abdominal obesity. Results. There was a significantly higher number of women who had had pregnancies (97.3 versus 83.0%), deliveries (94.7 versus 76.5%), including two and more deliveries (69.9 versus 38.2%), and two and more abortions (64.6 versus 34.0%) among hypertensive women with abdominal obesity compared to non-obese women with normal blood pressure; higher mean rates of pregnancies, deliveries and abortions, more frequent history of gestational hypertension (51.3 versus 14.9%) were revealed as well. Conclusion. The combination of abdominal obesity and hypertension in women aged 21-59 years is associated with higher number of previous pregnancies, abortions, miscarriages and pregnancies, abortions, miscarriages, and history of gestational hypertension.

Cardiovascular risk estimation in women with a history of hypertensive pregnancy disorders at term: a longitudinal follow-up study

BackgroundCardiovascular disease is associated with major morbidity and mortality in women in the Western world. Prediction of an individual cardiovascular disease risk in young women is difficult. It is known that women with hypertensive pregnancy complications have an increased risk for developing cardiovascular disease in later life and pregnancy might be used as a cardiovascular stress test to identify women who are at high risk for cardiovascular disease. In this study we assess the possibility of long term cardiovascular risk prediction in women with a history of hypertensive pregnancy disorders at term.MethodsIn a longitudinal follow-up study, between June 2008 and November 2010, 300 women with a history of hypertensive pregnancy disorders at term (HTP cohort) and 94 women with a history of normotensive pregnancies at term (NTP cohort) were included. From the cardiovascular risk status that was known two years after index pregnancy we calculated individual (extrapolated) 10-and 30-year cardiovascular event risks using four different risk prediction models including the Framingham risk score, the SCORE score and the Reynolds risk score. Continuous data were analyzed using the Student’s T test and Mann–Whitney U test and categorical data by the Chi-squared test. A poisson regression analysis was performed to calculate the incidence risk ratios and corresponding 95% confidence intervals for the different cardiovascular risk estimation categories.ResultsAfter a mean follow-up of 2.5 years, HTP women had significantly higher mean (SD) extrapolated 10-year cardiovascular event risks (HTP 7.2% (3.7); NTP 4.4% (1.9) (p<.001, IRR 5.8, 95% CI 1.9 to 19)) and 30-year cardiovascular event risks (HTP 11% (7.6); NTP 7.3% (3.5) (p<.001, IRR 2.7, 95% CI 1.6 to 4.5)) as compared to NTP women calculated by the Framingham risk scores. The SCORE score and the Reynolds risk score showed similar significant results.ConclusionsWomen with a history of gestational hypertension or preeclampsia at term have higher predicted (extrapolated) 10-year and 30-year cardiovascular event risks as compared to women with a history of uncomplicated pregnancies. Further large prospective studies have to evaluate whether hypertensive pregnancy disorders have to be included as an independent variable in cardiovascular risk prediction models for women.

Gestational hypertension: a neglected cardiovascular disease risk marker

The purpose of this study is to examine hypertension and cholesterol screening, knowledge of heart attack symptoms, and cardiovascular disease (CVD) risk factors among women with a history of gestational hypertension. We used weighted 2008 National Health Interview Survey data to examine health indicators and modifiable CVD risk factors and to estimate prevalence and adjusted odds ratios for recommended CVD screening and knowledge of heart attack symptoms by hypertension history among 11,970 adult women. Among women with gestational hypertension only (n = 301), 93% received the recommended screening for hypertension; 75% received screening for dyslipidemia, and 40% correctly identified 5 of 5 heart attack symptoms. The odds of CVD screenings and knowledge did not differ between women with a history of gestational hypertension and those with no hypertension. However, women with gestational hypertension had higher rates of obesity (43%), CVD (18%), and diabetes mellitus (13%), compared with women without a history of hypertension (21%, 8%, and 3%, respectively). A history of gestational hypertension is a neglected CVD risk marker.

Abstract P3-11-16: First Pregnancy Events Determine Future Breast Density Independent of Systemic Sex Steroid Levels

Abstract Introduction: Pregnancy outcomes (e.g., preterm birth, preeclampsia, and birthweight) have been associated with altered breast cancer risk. Hypotheses linking pregnancy outcomes and subsequent breast cancer risk include persistent changes in endogenous hormones and/or imprinted changes in mammary gland differentiation and morphology. Limited information exists on the relationship between pregnancy characteristics and mammographic density. The Marin Women's Study (MWS) was initiated in 2006 to examine breast cancer in a mammography population in an area with high breast cancer incidence (Marin County). MWS enrollment occurs at mammography sites in Marin County that participate in the San Francisco Mammography Registry, one of seven registries included in the National Cancer Institute Breast Cancer Surveillance Consortium. The MWS includes ∼14,000 participants, covering ∼80% of the County's mammography screening population. An analysis was undertaken using MWS data to examine the relationship between first pregnancy outcomes and later life mammographic density, controlling for standard breast cancer risk factors. Methods: Reproductive characteristics were self-reported on the MWS questionnaire at the time of mammogram. Volumetric compositional breast density (BDsxa) using single X-ray absorptiometry techniques (SXA) was measured on screening digital mammography examinations measured by the San Francisco Mammography Registry. Systemic sex steroid hormone levels were measured on a single early morning saliva sample. Women were excluded if they reported a history of breast cancer, if their first birth was a multi-fetal gestation, if they reported using antiestrogens within the five years preceding the questionnaire, or if they were missing data on any of the model variables. Robust regression models were controlled for current age, body mass index (BMI), race, education, physical activity, alcohol consumption, smoking, family history of breast cancer, hysterectomy, menopausal status, and hormone use at the time of mammography. Results: The study population included 2162 parous women. Using multivariable regression we found that a history of gestational hypertension during first pregnancy was associated with a statistically significant decrease in BDsxa (b=-0.29, p=0.01), while each month of breastfeeding after first birth was associated with a statistically significant increase in BDsxa (b=0.01, p=0.01). Menopausal status (pre-and peri-vs. postmenopausal) and age at first birth (&amp;lt;30 vs. 30+ y) modified these associations. Reproductive factors explained a greater proportion of the variability in BDsxa in premenopausal than in postmenopausal women (40% vs 31%), and a greater proportion of variability in those with a later age at first birth (45% of age 30+ y vs. 36% of age &amp;lt;30y). Salivary hormone levels (E2, P, T, DHEA) were not consistently associated with breast density. Conclusions: This analysis demonstrates that a woman's first pregnancy outcomes may determine future breast density, and that this association varies by age at first birth and menopausal status at the time of breast density measurement. These findings suggest that pregnancy may exert its influence on future breast cancer risk via changes in breast morphology and density. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-16.

Effects of Current Size, Postnatal Growth, and Birth Size on Blood Pressure in Early Childhood

In a prospective study, we investigated the impact of early growth on blood pressure at 3 years of age. We measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) for 590 children 3 years of age and related measurements to current size and size at birth, 6 months, 1 year, and 2 years of age. SBP was related positively to weight at 3 and 2 years and, after adjustment for current size, negatively to weight at birth and 6 months but not at 1 or 2 years. No effect was observed for DBP. A family history of hypertension was associated with higher maternal blood pressure, greater weight, and gestational hypertension (P = .05). Mothers with a history of gestational hypertension had higher SBP and DBP values (P < .001). In multivariate linear regression analyses, SBP was influenced positively by weight at 3 years and family history of hypertension and negatively by weight at 6 months. None of the factors was associated with DBP. For 3-year-old children, current weight was a determinant of SBP and postnatal growth to 6 months of age was more predictive than birth weight. A family history of hypertension is important in determining maternal blood pressure. These observations suggest a window in which postnatal growth might be modified.

History of Gestational Hypertension Is Associated With the Metabolic Syndrome and Masked Hypertension But Not Arterial Stiffness in Women With Essential Hypertension

The underlying mechanisms of subsequent increased risk of cardiovascular disease with a history of gestational hypertension (GH) are not known. Untreated hypertensive women (n=155, age 43+/-1 years) underwent ambulatory blood pressure (BP) monitoring and assessment of aortic pulse wave velocity (PWV) and augmentation index (AIx). Despite identical clinic BP readings, the group of women with GH (n=54) had higher (P=.002) ambulatory daytime systolic BP levels and a greater number of extreme nocturnal dippers (P=.005) than the group without GH. Women with GH had higher body mass index (P=.003), greater waist circumference (P=.02), higher levels of triglycerides (P=.002), lower levels of high-density lipoprotein cholesterol (P=.004), a higher prevalence of the metabolic syndrome (P<.05) and microalbuminuria (P=.004), higher plasma renin activity (P=.03), and higher aldosterone levels (P=.01). There was no significant difference in PWV and AIx between the 2 groups. The higher prevalence of the metabolic syndrome, microalbuminuria, masked hypertension, and activation of the renin-angiotensin-aldosterone system but not arterial stiffness may explain the subsequent propensity to high BP and cardiovascular disease in women with GH.

Cardiovascular Risk Factors in Healthy Women With Previous Gestational Hypertension

There is evidence from epidemiologic studies that gestational hypertension (GH) carries an increased risk of cardiovascular disease later in life. This study was an attempt to determine whether GH in a previous pregnancy, defined as newly developed hypertension after 20 weeks gestation, is associated with endothelial dysfunction or carbohydrate and lipid metabolic changes typical of insulin resistance in currently healthy women. Endothelium-dependent brachial artery flow-mediated dilatation (FMD) and endothelium-independent nitroglycerin-induced dilatation were estimated ultrasonically in 15 women with a history of GH and 15 others who had had normal pregnancies. The interval between delivery and evaluation was at least 12 months and averaged 20 months. Women with gestational diabetes were not included. Apart from blood pressure, there were no significant demographic or pregnancy differences between the 2 groups of women. Fasting insulin levels were 60% higher in women with previous GH, and insulin resistance, expressed as homeostasis model assessment (HOMA), was 80% greater. Fasting glucose levels were comparable in the 2 groups and all women had normal lipid profiles. Nevertheless, previous GH was associated with 20% lower levels of high-density lipoprotein (HDL) cholesterol and 60% higher levels of free fatty acids. Women with past GH had higher total and free testosterone levels, which, however, remained within the normal range. Although all women were normotensive, both systolic and diastolic pressures were significantly higher in those with previous GH. FMD in the previous GH group was nearly 55% that of control women, but there was no difference in nitroglycerin-induced dilatation. Linear regression analysis showed that total testosterone correlated strongly and negatively with FMD; correlation with free testosterone was somewhat less. FMD also correlated negatively and closely with HOMA and fasting insulin, and it correlated positively with HDL cholesterol and body mass index. Total testosterone accounted for 34% of the variance in FMD, and HOMA contributed 22% more. Endothelial dysfunction is characteristic in healthy women having GH diagnosed in a previous pregnancy. There also are early signs of disordered carbohydrate, lipid, and hormone metabolism. These findings might help to explain reports of increased cardiovascular disease in these women.

The Risk of Maternal Ischemic Heart Disease After Gestational Hypertensive Disease

Previous studies have found that a history of preeclampsia is a risk factor for cardiovascular disorders later in life. Because preeclampsia most often complicates first pregnancies, its development during later pregnancies may be even more closely associated with the later development of ischemic heart disease (IHD). This cross-sectional population-based study aimed at determining whether IHD later in life is more likely after more severe or recurrent gestational hypertensive disease. The study cohort numbered 403,550 women who gave birth for the first time in Sweden in the years 1973-1982. Of these, 207,054 women had a second child during the same period. Participants were followed for 15 years starting 4 to 14 months after the index pregnancy. Hypertensive disease developed in 20,469 women during their first pregnancy, and 1.3% of these women were later hospitalized for IHD or died of this cause during follow up compared with only 0.6% of women in the total cohort. After adjusting for maternal age, socioeconomic status, and the hospital where each woman gave birth, the risk of being hospitalized for or dying of IHD was 1.6 (95% confidence interval [CI], 1.3-2.0) for women who had gestational hypertension in their first pregnancy, 1.9 (95% CI, 1.6-2.2) for women who had mild preeclampsia, and 2.8 (95% CI, 2.2-3.7) for women who had severe preeclampsia, compared with women who did not develop hypertension during the first pregnancy. Interestingly, women who had a preterm delivery were also at increased risk of developing IHD in later life (IRR, 1.3; 95% CI, 1.1-1.5) as were those who had an SGA infant (IRR, 1.8; 95% CI, 1.6-2.3). Women who had all 3 complications-namely, preterm birth, small-for-gestational-age infant, and any kind of hypertensive disease-were at highest risk (IRR, 2.6; 95% CI, 1.8-4.7). Of the 207,054 women who had 2 pregnancies during the study period, 0.6% developed IHD. After adjusting for maternal age, socioeconomic status, and the hospital where each woman gave birth, the risk of developing IHD was 1.9 (95% CI, 1.5-2.4) in women who were hypertensive only in their first pregnancy, and 2.4 (95% CI, 1.8-3.2) in women who were hypertensive only in their second pregnancy, compared with women with 2 normal pregnancies. The risk of developing IHD was highest (2.8 [95% CI, 2.0-3.9]) in women who were hypertensive in both pregnancies. This study shows that the risk of IHD in women who have given birth is increased if they had gestational hypertensive disease. The degree of risk increases along with the severity of the hypertension, and the risk is highest if hypertension recurs during a second pregnancy. Nevertheless, the absolute risk is small, and nearly 90% of women with IHD have no history of gestational hypertension. The investigators therefore recommend that information about the increased risk of IHD should not be given to all women who have gestational hypertensive disease.