Pre-pregnancy blood pressure and pregnancy outcomes: a nationwide population-based study.

BACKGROUND: Hypertension has been known to increase the risk of obstetric complications. Recently, the American College of Cardiology endorsed lower thresholds for hypertension as systolic blood pressure of 130-139 mmHg or diastolic blood pressure 80-89 mmHg. However, there is a paucity of information regarding the impact of pre-pregnancy blood pressure on pregnancy outcomes. We aimed to evaluate the effect of pre-pregnancy blood pressure on maternal and neonatal complications. METHODS: In this nationwide, population based study, pregnant women without history of hypertension and pre-pregnancy blood pressure < 140/90 mmHg were enrolled. The primary outcome of composite morbidity was defined as any of the followings: preeclampsia, placental abruption, stillbirth, preterm birth, or low birth weight. RESULTS: A total of 375,305 pregnant women were included. After adjusting for covariates, the risk of composite morbidity was greater in those with stage I hypertension in comparison with the normotensive group (systolic blood pressure, odds ratio = 1.68, 95% CI: 1.59 - 1.78; diastolic blood pressure, odds ratio = 1.56, 95% CI: 1.42 - 1.72). There was a linear association between pre-pregnancy blood pressure and the primary outcome, with risk maximizing at newly defined stage I hypertension and with risk decreasing at lower blood pressure ranges. CONCLUSIONS: 'The lower, the better' phenomenon was still valid for both maternal and neonatal outcomes. Our results suggest that the recent changes in diagnostic thresholds for hypertension may also apply to pregnant women. Therefore, women with stage I hypertension prior to pregnancy should be carefully observed for adverse outcomes.

Human-induced pluripotent stem cells for modelling metabolic perturbations and impaired bioenergetics underlying cardiomyopathies.

Normal cardiac contractile and relaxation functions are critically dependent on a continuous energy supply. Accordingly, metabolic perturbations and impaired mitochondrial bioenergetics with subsequent disruption of ATP production underpin a wide variety of cardiac diseases, including diabetic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, anthracycline cardiomyopathy, peripartum cardiomyopathy, and mitochondrial cardiomyopathies. Crucially, there are no specific treatments for preventing the onset or progression of these cardiomyopathies to heart failure, one of the leading causes of death and disability worldwide. Therefore, new treatments are needed to target the metabolic disturbances and impaired mitochondrial bioenergetics underlying these cardiomyopathies in order to improve health outcomes in these patients. However, investigation of the underlying mechanisms and the identification of novel therapeutic targets have been hampered by the lack of appropriate animal disease models. Furthermore, interspecies variation precludes the use of animal models for studying certain disorders, whereas patient-derived primary cell lines have limited lifespan and availability. Fortunately, the discovery of human-induced pluripotent stem cells has provided a promising tool for modelling cardiomyopathies via human heart tissue in a dish. In this review article, we highlight the use of patient-derived iPSCs for studying the pathogenesis underlying cardiomyopathies associated with metabolic perturbations and impaired mitochondrial bioenergetics, as the ability of iPSCs for self-renewal and differentiation makes them an ideal platform for investigating disease pathogenesis in a controlled in vitro environment. Continuing progress will help elucidate novel mechanistic pathways, and discover novel therapies for preventing the onset and progression of heart failure, thereby advancing a new era of personalized therapeutics for improving health outcomes in patients with cardiomyopathy.

Pregnancy alters lateral parabrachial nucleus but not hypothalamic Fos expression following hypotensive hemorrhage.

The goal of these experiments was to determine if hemorrhage-induced Fos expression in the hypothalamus and lateral parabrachial nucleus (LPBN) is altered by reproductive cycle phase or pregnancy. Conscious unrestrained female Sprague-Dawley rats were subjected to a 16 ml/kg hemorrhage on the morning of the metestrus or proestrus phases of the estrous cycle, or on day 12-14 of pregnancy (mid-gestation). Hemorrhage induced a significant increase (p < 0.01) in the number of Fos-immunoreactive cell nuclei in the supraoptic nucleus, and in both the magnocellular and parvicellular components of the paraventricular hypothalamic nucleus, that did not differ between groups. In virgin females, hemorrhage also induced a significant increase in LPBN Fos expression that did not differ between metestrus and proestrus. In pregnant animals, there was an increase in basal LPBN Fos expression, but hemorrhage induced no further increase in the number of Fos-immunoreactive neurons in the LPBN. Mean arterial pressure decreased (p < 0.001) and plasma renin activity increased (p < 0.01) to a similar extent in all three groups after 16 ml/kg blood loss. In summary, the number of paraventricular and supraoptic nucleus neurons activated by hemorrhage is unaffected by estrous cycle phase or pregnancy. In contrast, pregnancy significantly attenuates the LPBN response to hemorrhage.

Hypertension in pregnancy.

Hypertension in pregnancy is still a leading cause of morbidity and mortality in mother and fetus. This review of the literature from 1991 to 1992 focuses on research relating to the causes of preeclampsia and the pathogenesis of the marked vasoconstriction so characteristic of this disease. Reports hypothesizing primary roles for endothelial cell dysfunction, aberrations in prostaglandin synthesis, fatty acid and antioxidant metabolism, as well as for dietary calcium deficiency and the renin-angiotensin system are analyzed; articles regarding clinical trials whose origins derive from some of these hypotheses, such as low-dose aspirin and calcium supplementation to prevent preeclampsia, are appraised. The review concludes by examining several controversies regarding management of pregnant women with chronic hypertension, including the proper way to measure blood pressure in pregnancy, the diastolic level at which treatment with antihypertensive medications should commence, and the choice of drugs that are safe and preferable for use during gestation.

Magnesium supplement in pregnancy-induced hypertension. A clinicopathological study.

The placenta and the umbilical cord obtained from 18 women with pregnancy-induced hypertension were investigated by light microscopy. The umbilical artery was studied by electron microscopy. 10 placentae and umbilical cords from normal pregnancies served as controls. The study was performed as a double-blind randomized controlled study in which 11 women were allocated to magnesium and 7 to placebo treatment. The treatment comprised a 48-hour intravenous magnesium/placebo infusion followed by daily oral magnesium/placebo intake until one day after delivery. Magnesium supplement increased birth weight and placental weight significantly. Light microscopic study of the placentae and the umbilical cord arteries showed no difference between the three groups concerning the occurrence of infarctions, cytotrophoblastic hyperplasia, vasculo-syncytial membranes, basement membrane thickening, stromal fibrosis or intervillous fibrin. Ultrastructurally, the endothelial cells of the umbilical arteries from women with pregnancy-induced hypertension showed a significant increase in the amount of dilated endoplasmic reticulum and basal laminae thickness when all 18 cases were compared with the controls. There was no significant difference when the magnesium group, the placebo group and the control group were compared separately. The present study suggests that magnesium supplement has a beneficial effect on fetal growth in pregnancy-induced hypertension. With regard to the light and electron microscopic changes we were unable to demonstrate any significant difference between the magnesium, placebo and control groups.