http://hyper.ahajournals.org/ Downloaded from Watanabe et al S(P)RR During Pregnancy 1251invasion and migration. 16,17 Clinically during pregnancy, it is well-known that even women with no complication exhibit BP changes with gestational age; the BP is typically at its lowest between 24 and 26 gestational weeks, increasing thereafter until the end of the pregnancy. 18 In addition, the circulating RAS is involved in the development of hypertensive disorders, including preeclampsia, during pregnancy. 1,16,19 However, no evidence suggests that the tissue RAS contributes to BP changes during pregnancy.On the basis of these background findings, the present study was conducted to examine whether the tissue RAS contributed to BP changes during pregnancy and the incidence of preeclampsia. To this end, we assessed the relationship between plasma s(P)RR concentrations and BP levels during pregnancy in a prospective cohort study. Methods Study ParticipantsIn this prospective cohort study, Japanese pregnant women whose first visit to the National Center for Child Health and Development hospital was at <16 weeks and 0 days of gestation were enrolled between January and December 2010. At recruitment, written informed consent was obtained from all participants. The study protocol was approved by the ethics committee of the National Center for Child Health and Development (Tokyo, Japan).The expected due date was confirmed by ultrasound in all participants. Inclusion criteria were systolic BP <140 mm Hg and diastolic BP <90 mm Hg at the time of enrollment (<16 weeks of gestation) and the absence of preexisting hypertensive disorders and renal disease. The study initially enrolled 477 pregnant women who met the criteria; however, 40 pregnant women were excluded because of early abortion (n=8) or the inability to follow-up because of relocation (n=32), resulting in a total of 437 study participants.Plasma samples were obtained at 3 prenatal visits throughout the pregnancy and at time of delivery. The first sample was obtained before 16 weeks 0 days gestation (early pregnancy), the second between 16 weeks 0 days and 27 weeks 6 days gestation (mid-pregnancy), and the third after 28 weeks 0 days gestation (late pregnancy) at routine blood testing during prenatal visits. The fourth blood sample was obtained at time of delivery. We determined s(P)RR concentrations for first, second, and third trimester using the blood samples obtained in early, middle, and late pregnancy, respectively. We then analyzed s(P) RR concentrations in early pregnancy in association with BP values measured at 16 to 20, 20 to 24, 24 to 28, 28 to 32, 32 to 36, and 36 to 40 weeks of gestation (6 periods). Similarly, s(P)RR concentrations in mid-pregnancy were analyzed in association with BP levels measured at 28 to 32, 32 to 36, and 36 to 40 weeks gestation (3 periods) and s(P)RR concentrations in late pregnancy with BP levels measured at 36 to 40 weeks gestation (1 period). Finally, s(P)RR at delivery was used for analysis of the association between s(P)RR conce...
Hypertensive disorders of pregnancy are known to be a risk factor for future cardiovascular diseases. In contrast, there is a paucity of data on the not so distant future prognosis of hypertensive disorders of pregnancy. In the present study, we evaluated the incidence of the diseases causing cardiovascular problems (hypertension, diabetes mellitus, dyslipidemia and metabolic syndrome) 5 years after delivery in Japanese women with hypertensive disorders of pregnancy. We performed a double-cohort study and compared medical conditions between women with and without a history of hypertensive disorders of pregnancy. A total of 1513 women who participated in the cohort study were invited to undergo a medical checkup 5 years after the index delivery, of whom 829 responded. After excluding pregnant and lactating women at the time of examination, 25 women with hypertensive disorders of pregnancy and 746 control subjects were analyzed. The incidence of hypertension was significantly higher among women with hypertensive disorders of pregnancy than women who were normotensive during pregnancy (24.0 vs. 2.5%, P<0.001). They were also at an increased risk of subsequent hypertension 5 years after the index delivery, after adjusting for confounding factors such as age, body mass index, family history of hypertension and salt intake (odds ratio 7.1, 95% CI, 2.0-25.6, P<0.003). These is no significant difference in the incidence of diabetes mellitus, dyslipidemia and metabolic syndrome. In conclusion, hypertensive disorders of pregnancy are strong risk factors for subsequent hypertension only 5 years after delivery.
Angiotensin receptor blockers (ARBs) are known to reduce the cardiovascular risk in hypertensive patients. This study was designed to examine the effect of an ARB candesartan on subclinical atherosclerosis assessed by cardio-ankle vascular index (CAVI) in comparison with calcium channel blockers (CCBs) alone in hypertensive patients with metabolic syndrome (MetS). A total of 53 consecutive hypertensive patients with MetS were randomly assigned to the candesartan group, in which candesartan was added on, or the CCBs group, in which CCBs were added on. Clinical and biological parameters were obtained before and after the 12-month treatment period. The primary measure of efficacy was the %change in CAVI. When treated with candesartan, but not CCBs, CAVI significantly decreased from 8.7 to 7.7 by 11%. Blood pressure (BP) significantly decreased with both treatments, but the differences between groups were not significant. The changes in other parameters remained unchanged in both the groups. Analysis of covariance found that both the BP reduction and the therapy difference contributed to the decrease in CAVI, but the BP reduction was not involved in the decrease in CAVI caused by the difference in the therapy. Candesartan may be a better antihypertensive drug than CCBs to improve subclinical atherosclerosis of patients with MetS.
Background Although low birth weight in Japan has slightly increased over the past several decades, the association between maternal birth weight and pregnancy outcomes remains poorly understood. Methods In this hospital-based, prospective cohort study conducted at the National Center for Child Health and Development, we obtained information on pregnant women’s birth weight via their maternal and child health handbook. We analyzed 944 women born at term after dividing them into five categories according to their birth weight: <2500 g, 2500–2999 g, 3000–3499 g, 3500–3999 g, and ≥4000 g. Multivariate logistic regression analysis and trend analysis were used to elucidate the extent to which maternal birth weight was associated with small-for-gestational-age and low birth weight in offspring, as well as with hypertensive disorders of pregnancy. Results Compared with women with a birth weight of 3000–3499 g, those born with a birth weight <2500 g had a significantly higher risk of low birth weight (adjusted odds ratio: 5.39, 95% confidence interval: 2.06–14.1) and small-for-gestational-age (adjusted odds ratio: 9.11, 95% confidence interval: 3.14–26.4) infants. No significant association was found between the incidence of hypertensive disorders of pregnancy and preterm birth. A linear relationship was observed between the lower birth weight categories and a higher risk of low birth weight and small-for-gestational-age (p-values for trends: 0.009 and <0.001, respectively), but no linear relationship was observed for the risk of preterm birth and hypertensive disorders of pregnancy (p-value for trends: 0.317 and 0.157, respectively). Conclusions Our findings suggest that lower maternal birth weight is associated with small-for-gestational-age and low birth weight in offspring of women born at term.
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