Cardiovascular Disease In Later Life Research Articles

Paternal programming of offspring cardiometabolic diseases in later life.

Early – intrauterine – environmental factors are linked to the development of cardiovascular disease in later life. Traditionally, these factors are considered to be maternal factors such as maternal under and overnutrition, exposure to toxins, lack of micronutrients, and stress during pregnancy. However, in the recent years, it became obvious that also paternal environmental factors before conception and during sperm development determine the health of the offspring in later life. We will first describe clinical observational studies providing evidence for paternal programming of adulthood diseases in progeny. Next, we describe key animal studies proving this relationship, followed by a detailed analysis of our current understanding of the underlying molecular mechanisms of paternal programming. Alterations of noncoding sperm micro-RNAs, histone acetylation, and targeted as well as global DNA methylation seem to be in particular involved in paternal programming of offspring's diseases in later life.

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.

Prenatal methyl-donor supplemented diet increases endoplasmic reticulum stress and inflammation in adipose tissue CD11b+ cells in F1 mice

Abstract The risk for development of metabolic and cardiovascular diseases in later life is increasing, as the population is becoming overweight and obese at earlier ages. Early-life nutritional programming influences late-life disease susceptibility across generations, in part through epigenetic mechanisms including DNA methylation. Using mouse models, it has been shown that prenatal diet rich in methyl donors (L-methionine, vitamin B-12, folic acid, choline, betaine, zinc) can increase airway reactivity but improves cardiovascular disease outcomes in F1 mice. Here, we used a prenatal diet enriched with methyl-donors to study the impact of the prenatal diet in the context of diet-induced obese F1 C57Bl/6 mice fed a 40% high-fat diet (HFD) for 16 weeks. F1 mice exposed to the prenatal methyl donor supplemented diet have increased number of adipose tissue ‘crown-like structures’ consisting of primarily CD11b+ cells. The prenatal diet was found to increase the expression of adipose tissue endoplasmic reticulum (ER) stress response genes Chop, Bip, and Atf4 in HFD F1 mice. Obesity-induced ER stress has been linked to adipose tissue chronic inflammation. We have previously established that ER stress contributes to aging adipose tissue macrophage inflammation. Interestingly, Mcp-1 and Tnfα gene expression were found to be increased in the CD11b+ cells of F1 mice adipose tissue. The results strongly support an important role of prenatal methyl-donors exposure in modulating diet-induced obesity ER stress response and inflammation in offspring.

Association of downregulated HDAC 2 with the impaired mitochondrial function and cytokine secretion in the monocytes/macrophages from gestational diabetes mellitus patients.

Gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular diseases in later life, yet with underlying mechanisms unclear. The present study was to explore the association of upregulated histone deacetylase 2 (HDAC 2) with the impaired mitochondrial function and the cytokine secretion in the monocytes/macrophages from GDM patients. In this study, we examined the mitochondrial function, proinflamatory cytokine secretion and the HDAC 2 level in the serum or in the monocytes/macrophages from GDM patients, investigated the influence by HDAC 2 inhibitor, AR-42 (N-hydroxy-4-[[(2S)-3-methyl-2-phenylbutanoyl]amino]benzamide), on the mitochondrial function and cytokine secretion in the isolated GDM monocytes/macrophages. Results demonstrated an increased mitochondria size, mitochondrial superoxide and reactive oxygen species (ROS) production, and an undermined mitochondria membrane potential (MMP) in the GDM monocytes/macrophages. And the serum levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 were also markedly higher in the GDM pregnancies, while the expression and activity of HDAC 2 was downregulated. Moreover, AR-42-mediated HDAC 2 inhibition in vitro contributed to the impaired mitochondrial function and the proinflamatory cytokine secretion. In conclusion, this study suggests an association of the impaired mitochondrial function and the promoted proinflamatory cytokine secretion with the reduced HDAC 2 activity in GDM. These findings may present HDAC 2 as a target for GDM treatment.

Peptidome profiling of umbilical cord plasma associated with gestational diabetes-induced fetal macrosomia

Fetal macrosomia, defined as a birth weight ≥4000g, may affect 15–45% of newborns of women with gestational diabetes mellitus (GDM). The associations between endogenous peptides and gestational diabetes-induced macrosomia have not been investigated extensively by peptidome analysis. Here, we analyzed the umbilical cord plasma by combining ultrafiltration using molecular weight cut-off filters and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to investigate potential associations of GDM with macrosomia. As macrosomic babies have increased susceptibility to obesity, diabetes and cardiovascular diseases in later life, we also aimed to identify specific biomarkers to detect these future diseases. Thirty pairs of GDM mothers and controls were randomly divided into three subgroups. We identified 235 peptides of around 1000–3000Da, originating from 115 proteins. Analyzing the cleavage sites revealed that these peptides were cleaved in regulation, which may reflect the protease activity and distribution in umbilical cord plasma. Four identified peptides, of 2471.7, 1077.2, 1446.5 and 2372.7Da, were significantly differentially expressed in the GDM macrosomia groups compared with controls, whose precursors may play a critical role in developing GDM macrosomia. We provide for the first time a validated GDM macrosomia peptidome profile and identify potential biomarkers linking the effects of macrosomia to later-life diseases. Biological significanceFetal macrosomia is the predominant adverse outcome of gestational diabetes mellitus (GDM), which is a frequent medical condition during pregnancy. Till now, the detailed molecular mechanisms underlying gestational diabetes-induced macrosomia are still not elucidated. With high detection sensitivity and high throughput of peptidome technology, it is now possible to systemically identify peptides possibly involved in the umbilical cord plasma of GDM induced macrosomia cases. With LC–MS/MS based quantification, totally, we identified 235 peptides originated from 115 precursor proteins. And four peptides of 2471.7, 1077.2, 1446.5 and 2372.7Da differentially expressed between GDM cases and compared controls. A precursor protein of 1077.2Da was fibrinogen alpha chain (FGA), which was also identified in the Ai et al. [29] study with a downregulated manner in the serum samples of GDM cases. And further analysis the cleavage pattern of the identified peptides revealed that the enzymes in tissues cleaved the protein according to their rules. Thus, this quantitative peptidome approach can identify related peptides that may play a role in the gestational diabetes-induced macrosomia, and give candidate biomarkers contributing to the development of later-life diseases in macrosomic babies.

Effects of lactation on postpartum blood pressure among women with gestational hypertension and preeclampsia

Women with a history of hypertensive disorders of pregnancy are at an increased risk of hypertension and cardiovascular disease in later life. Lactation has been associated with a reduced risk of maternal hypertension, both in the postpartum period and later life. However, little is known about whether lactation is also cardioprotective in women with hypertensive disorders of pregnancy such as preeclampsia or gestational hypertension. This study aimed to characterize the relationship between lactation and postpartum blood pressure among women with preeclampsia and gestational hypertension. Data were obtained from women who participated in the Prenatal Exposures and Preeclampsia Prevention study (n= 379; 66% African American; 85% overweight or obese). Women enrolled during pregnancy and attended a postpartum visit (on average, 9.1 months after delivery) during which data on lactation duration and blood pressure were collected. The significance of the associations between postpartum blood pressure and lactation among women who remained normotensive during pregnancy, developed gestational hypertension, or developed preeclampsia were assessed with an analysis of variance. Linear regression models were used to adjust for maternal age, race, education, prepregnancy weight, and time since delivery. Gestational hypertension affected 42 subjects (11%) and preeclampsia affected 33 (9%). Lactation was reported by 217 (57%) with 78 (21%) reporting ≥ 6 months of lactation. Women who lactated were somewhat older, more educated, and had higher socioeconomic status. Among women who had gestational hypertension, lactation was associated with lower systolic blood pressure (P= .02) and diastolic blood pressure (P= .02). This association persisted after adjustment for age, race, education, prepregnancy weight, and time since delivery. However, for women who had preeclampsia and women who remained normotensive during pregnancy, lactation was not associated with postpartum blood pressure in either bivariate or multivariate analyses. This study found that lactation is associated with lower postpartum blood pressure among overweight women who develop gestational hypertension but not among women who develop preeclampsia. Future studies are needed to explore the association of lactation and blood pressure in later life for women with hypertensive disorders of pregnancy.

Abstract 131: Effect of Fetal Alcohol Exposure on Stroke Severity and Blood Flow in Adult Mice

Background and Purpose: Metabolic and cardiovascular disease in later life may have developmental origins. The present study specifically tested the hypothesis that fetal alcohol exposure (FAE) will persistently influence blood flow in adulthood and result in greater impairment following ischemic stroke. Methods: Timed-pregnant C57Bl/6 female mice (GD12) were intragastrically gavaged with ethanol (3g/kg/bwt) or water twice per day from GD12 through 15. At 3 months of age, FAE and control males and females were subject to high-resolution ultrasound pulsed-wave Doppler imaging to record blood flow in carotid, abdominal, renal and femoral arteries. Blood flow was quantified. Thereafter, mice were subjected to middle cerebral artery occlusion (MCAo) using an intraluminal filament and sacrificed at 24 h post-stroke. Stroke induced brain damage was assessed by behavioral assays (adhesive tape test), neurological score and infarct volume. Results: Blood flow measurements indicated that fetal alcohol exposure increased acceleration in renal lobar arteries of ethanol exposed females (P<0.003), indicating that alcohol exposure may lead to impairment vascular tone and early signs of hypertension in end organs like kidney. In animals subject to MCAo, FAE adults exhibited greater neurological deficits at 24h post-stroke, as determined by their higher scores on a combination of different parameters of motor impairment and behavioral measures (neurologic score) compared to controls (P<0.0004). Sensorimotor deficits assessed by sticky tape test also showed that fetal alcohol exposed animals were severely affected (p<0.05) indicating that developmental alcohol exposure can impair adaptation in adult brain to an acute neural damage. There is also a significant correlation between the neurological scores and infarct volume in FAE females (p<0.05) but not FAE males, suggesting sex differences in response to FAE modify the relationship between stroke and outcomes. Conclusions: Our findings support a hypothesis that fetal alcohol exposure has long lasting and sexually dimorphic effects on adult health, resulting in impaired renal blood flow and poor stroke outcomes.

Gender differences in developmental programming of cardiovascular diseases.

Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increased blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood, in addition to exposure to adverse influences during fetal life, contributes to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life and later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex has an impact on the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low-birth weight men and women. Fewer still assess the impact of ageing on sex differences in programmed cardiovascular risk. Thus, the aim of the present review is to highlight current data about sex differences in the developmental programming of blood pressure and cardiovascular disease.

Adipokine, adropin and endothelin-1 levels in intrauterine growth restricted neonates and their mothers.

Intrauterine growth retardation/restriction (IUGR) is associated with fetal malnutrition. It has consequences for later life including increased incidence of obesity, diabetes mellitus, cardiovascular disease (CVD), and metabolic syndrome. Adipokines (adiponectin and leptin), adropin, and endothelin-1 are associated with obesity and metabolic syndrome regulation. Intrauterine changes in these mediators could affect programming of later adult obesity and metabolic syndrome. Our objectives were to compare the levels of these mediators in both cord and maternal blood between IUGR pregnancies and control, healthy pregnancies, and to study the correlation of adipokines with adropin and endothelin-1 in maternal and cord blood in IUGR pregnancies as well as in healthy control pregnancies. Maternal and cord blood samples were taken from 16 women with IUGR pregnancies and 16 women with healthy pregnancies. Serum levels of leptin, adiponectin, adropin, and endothelin-1 were measured by ELISA. Maternal blood adropin levels were significantly lower in the IUGR group than in the control group; the other mediators did not differ significantly. There was a positive correlation between maternal blood adropin and endothelin levels. (r=0.731, P=0.001) in the control but not the IUGR group. Cord blood adropin and adiponectin levels were significantly lower in the IUGR group compared with the control group, while leptin or endothelin-1 did not differ significantly. There was a negative correlation between adropin and leptin (r=-0.704, P=0.001) in the IUGR but not the control group cord blood. There were also positive correlations between endothelin and adropin for both groups (r=0.594, P=0.006; r=0.560, P=0.010, respectively); to the best of our knowledge, this is the first report of such a correlation. Differences in fetal expression of adropin and adiponectin in IUGR could influence programming of obesity, metabolic syndrome, diabetes, and CVD in later life.

Heart rate variability in neonates of type 1 diabetic pregnancy

BackgroundCardiomyopathy is a common finding in offspring of pre-gestational type 1 diabetic pregnancy. Echocardiographic and biochemical evidence of fetal cardiac dysfunction have also been reported. Studies suggest that offspring of diabetic mothers (ODM) undergo a fetal programming effect due to the hyperglycaemic intrauterine milieu which increases their risk of cardiovascular morbidity in adult life. Decreased neonatal heart rate variability (HRV) has been described in association with in-utero growth restriction, prematurity, sudden infant death syndrome and congenital heart disease. The effect of in-utero exposure to hyperglycaemia in diabetic pregnancy on neonatal HRV is unknown. AimsOur aim was to determine if neonatal HRV differs between normal and diabetic pregnancy. Study design and subjectsThis was a prospective observational study of 38 patients with pregestational type 1 diabetes and 26 controls. HRV assessment was performed using Powerlab (ADI Instruments Ltd). Outcome measuresHeart rate variability assessment and cord blood sampling for pH and glucose were performed for all neonates. Maternal glycaemic control was assessed via measurement of glycosylated haemoglobin in each trimester in the diabetic cohort. ResultsNeonates of diabetic mothers had evidence of altered heart rate variability, with increased low frequency to high frequency ratio (LF: HF), suggestive of a shift towards sympathetic predominance (p<0.05). This altered HRV was significantly related to fetal acidaemia, cord blood glucose values and maternal glycaemic control during pregnancy (p<0.05). ConclusionNeonates of pregestational diabetic pregnancy have altered HRV which is related to maternal hyperglycaemia, fetal acidaemia and fetal glycaemia. Exposure of the developing heart to fluctuations in maternal glycaemia with subsequent alterations in HRV may explain why infants of diabetic mothers are at greater risk of cardiovascular disease in later life.

Leukocyte Telomere Length in Young Adults Born Preterm: Support for Accelerated Biological Ageing.

BackgroundSubjects born preterm have an increased risk for age-associated diseases, such as cardiovascular disease in later life, but the underlying causes are largely unknown. Shorter leukocyte telomere length (LTL), a marker of biological age, is associated with increased risk of cardiovascular disease.ObjectivesTo compare LTL between subjects born preterm and at term and to assess if LTL is associated with other putative cardiovascular risk factors at young adult age.MethodsWe measured mean LTL in 470 young adults. LTL was measured using a quantitative PCR assay and expressed as T/S ratio. We analyzed the influence of gestational age on LTL and compared LTL between subjects born preterm (n = 186) and at term (n = 284). Additionally, we analyzed the correlation between LTL and potential risk factors of cardiovascular disease.ResultsGestational age was positively associated with LTL (r = 0.11, p = 0.02). Subjects born preterm had shorter LTL (mean (SD) T/S ratio = 3.12 (0.44)) than subjects born at term (mean (SD) T/S ratio = 3.25 (0.46)), p = 0.003). The difference remained significant after adjustment for gender and size at birth (p = 0.001). There was no association of LTL with any one of the putative risk factors analyzed.ConclusionsYoung adults born preterm have shorter LTL than young adults born at term. Although we found no correlation between LTL and risk for CVD at this young adult age, this biological ageing indicator may contribute to CVD and other adult onset diseases at a later age in those born preterm.

Proteomic Analysis of One-carbon Metabolism-related Marker in Liver of Rat Offspring

Maternal food intake has a significant effect on the fetal environment, and an inadequate maternal diet may result in intrauterine growth restriction. Intrauterine growth restriction newborn rat pups nursed by normal diet-fed dams exhibited rapid catch-up growth, which plays a critical role in the risk for metabolic and cardiovascular disease in later life. Specifically, one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. Data are available via ProteomeXchange with identifier PXD002578. We determined that betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p < 0.05). Moreover, the expression levels of betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial were negatively correlated with serum homocysteine concentration in male offspring exposed to maternal food restriction during gestation and normal diet during lactation. However, in female offspring only expression levels of methylenetetrahydrofolate dehydrogenase 1 were negatively correlated with homocysteine concentration. This study shows that maternal food restriction during late gestation and normal diet during lactation lead to increased homocysteine concentration through disturbance of one-carbon metabolism in the livers of male offspring. This suggests that male offspring have an increased gender-specific susceptibility to disease in later life through fetal programming.

Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon.

Intrauterine growth restriction increases the risk of perinatal complications and predisposes the infant to diabetes and cardiovascular disease in later life. Mechanisms by which maternal nutrient restriction (MNR) reduces fetal growth are poorly understood. We hypothesized that MNR decreases placental amino acid (AA) transporter activity, leading to reduced transplacental transfer of AAs. Pregnant baboons were fed either a control (ad libitum, n = 7), or MNR diet (70% of control diet, n = 7) from gestational day (GD) 30. At GD 165 (0.9 gestation), placentas (n = 7 in each group) were collected, and microvillous plasma membrane vesicles (MVM) isolated. MVM system A and system L AA transport was determined in vitro using radiolabeled substrates and rapid filtration techniques. In vivo transplacental AA transport was assessed by infusing nine (13)C- or (2)H-labeled essential AA as a bolus into the maternal circulation (n = 5 control, n = 4 MNR) at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each essential AA was calculated. Fetal and placental weights were significantly reduced in the MNR group compared with controls (P < 0.01). The activity of system A and system L was markedly reduced by 73 and 84%, respectively, in MVM isolated from baboon placentas at GD 165 following MNR (P < 0.01). In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly reduced for leucine, isoleucine, methionine, phenylalanine, threonine, and tryptophan in MNR baboons (P < 0.05). This is the first study to investigate placental AA transport in a nonhuman primate model of MNR. We demonstrate that the downregulation of system A and system L activity in syncytiotrophoblast MVM in MNR leads to decreased transplacental AA transport and, consequently, reduced circulating fetal AA concentrations, a potential mechanism linking maternal undernutrition to reduced fetal growth.

Peripheral Endothelial (Dys)Function, Arterial Stiffness and Carotid Intima-Media Thickness in Patients after Kawasaki Disease: A Systematic Review and Meta-Analyses.

BackgroundKawasaki disease (KD) is a systemic pediatric vasculitis. Its main complication is the development of coronary arterial aneurysms (CAA), causing an increased risk for ischemia and myocardial infarction. It is unclear whether KD patients, apart from the presence of CAA, have an increased cardiovascular disease (CVD) risk due to the previous systemic vasculitis. The aim of this study was to systematically review and meta-analyse the literature regarding surrogate markers for CVD risk in KD patients.MethodsMedline and Embase were searched for articles comparing endothelial dysfunction (flow-mediated dilation, nitroglycerin-mediated dilation and peripheral arterial tonometry), vascular stiffness (stiffness index, pulse wave velocity) and carotid intima-media thickness (cIMT) between patients and controls. Two investigators assessed the articles for eligibility and evaluated quality.ResultsThirty studies were included. For all outcomes, moderate to high heterogeneity between studies was found. Most studies reported a decreased flow-mediated dilation in the whole KD- and CAA-positive group compared to controls, while data on CAA-negative patients were conflicting. The stiffness index was increased in the majority of studies evaluating the whole KD- and CAA-positive group, but not in most studies on CAA-negative patients. Mean cIMT was neither significantly increased in the whole KD-group nor in the CAA-positive group nor in most studies studying CAA-negative patients. Studies measuring maximum cIMT were conflicting.ConclusionLiterature suggests that surrogate markers for CVD risk in KD patients are increased in CAA-positive but not in CAA-negative patients. This may indicate that CAA-positive patients should be monitored for CVD in later life. The results of this review have to be interpreted with care due to substantial heterogeneity between studies and methodological limitations, as well as the lack of long-term follow-up studies.

O122. The role of framing in modifying behavior to reduce cardiovascular risk after preeclampsia, a vignette study

Introduction Observational studies have consistently described that women with a history of hypertension in pregnancy have a markedly increased risk of cardiovascular disease (CVD) later in life. Pregnancy is suggested as a “stress test” that identifies women who are at risk for developing clinical cardiovascular disease in later life. This opens up the opportunity for preventive measures at a relatively young age. Helping women to address their cardiovascular risk by modifying lifestyle has proven difficult. Motivation to change behaviour is crucial for effective interventions. Research on promoting healthy lifestyle has demonstrated that even subtle differences in message framing can affect (intentions to improve) health-related behavior. So, framing risk information could be effective in motivating these women too. Perceived probability of developing a disease appears to be another important factor influencing people’s motivation to modify behavior. Objectives Investigating the impact of framing information as a health score versus a risk score and the impact of high versus low probability of developing CVD on the willingness to modify behavior after preeclampsia. Methods Obstetric nurses (n = 165) were invited to participate in a questionnaire containing two hypothetical scenarios, a case with mild preeclampsia and a case with severe preeclampsia. Scores of their willingness to modify behaviour were analysed on a Likert scale by ANOVA. Results We found no significant effect of framing F(3,287) = 1.932, p 0.166. A significant main effect was found of the severity of the case (F(3,287) = 11.12, p 0.001) and a non-significant interaction between severity and framing on the willingness to modify behavior (F(3,287) = 0.592, p 0.442). Conclusions Framing information in health or risk score and its interaction with probability is not of influence in motivating women to modify their lifestyle to decrease cardiovascular risk after preeclampsia. Framing in health or risk score does not seem to be contributing in clinical practice. Those who are presented with a higher risk are more motivated to change their lifestyle.

Impact of birth parameters and early life growth patterns on retinal microvascular structure in children: The Generation R Study.

The aim of the study was to examine the associations of birth outcomes and longitudinally measured fetal and infant growth patterns with retinal vessel calibers in childhood. In a population-based prospective cohort study among 4122 children, we measured growth characteristics in second and third trimester of pregnancy, at birth, and at 6, 12, 24, 36, 48, and 72 months. At the age of 6 years, we measured retinal arteriolar and venular calibers from digitized retinal photographs. We observed that compared with term-born children, those born preterm had narrower retinal arteriolar caliber [differences -0.46 standard deviation score (95% confidence interval -0.77 to -0.15) and -0.24 standard deviation score (95% confidence interval -0.42 to -0.05) for children born <34 and 34-37 weeks of gestation, respectively]. Children born with a low birth weight (<2500 g) had narrower retinal arteriolar caliber than children with a normal birth weight, but this association was fully explained by gestational age at birth. Accelerated infant growth until 24 months was associated with narrow retinal arteriolar caliber, especially among preterm-born children (P < 0.05). Early growth measures were not associated with retinal venular caliber. Preterm birth and accelerated infant growth are associated with narrower retinal arteriolar caliber in childhood. Whether these microvascular adaptations explain the well known associations of fetal and infant characteristics with cardiovascular disease in later life should be further studied.

The sequence of prenatal growth restraint and post-natal catch-up growth leads to a thicker intima-media and more pre-peritoneal and hepatic fat by age 3-6 years.

Infants born small-for-gestational-age (SGA) who develop post-natal weight catch-up are at risk for insulin resistance, central adiposity and cardiovascular disease in later life, even in the absence of overweight. In young (age 3-6 years) non-obese SGA children, we assessed arterial health (as judged by intima-media thickness [IMT]) and abdominal fat distribution (subcutaneous, visceral, preperitoneal and hepatic components by magnetic resonance imaging [MRI] and/or ultrasound [US]) besides a selection of endocrine markers. Comparisons of measures in SGA (n = 27) vs. appropriate-for-GA (AGA) children (n = 19) of similar height, weight and body mass index. Longitudinal outcomes (age 3-6 years) were carotid IMT (cIMT); fasting glucose, circulating insulin, IGF-I and high-molecular-weight (HMW) adiponectin; abdominal fat partitioning by US. Cross-sectional outcomes (age 6 years) were aortic IMT (aIMT) and abdominal fat partitioning by MRI. At 3 and 6 years, cIMT and IGF-I results were higher and HMW adiponectin lower in SGA than AGA children; at 6 years, SGA subjects had also a thicker aIMT and more pre-peritoneal and hepatic fat, and were less insulin sensitive (all P values between <0.05 and <0.0001). cIMT correlated positively with pre-peritoneal fat, particularly at 6 years. Post-SGA status and weight gain in early childhood (between 3 and 6 years) were independent predictors of cIMT at 6 years, explaining 48 % of its variance. SGA children aged 3-6 years were found to have a thicker intima- media and more pre-peritoneal and hepatic fat than AGA children of comparable size.

Pregnancy-induced hypertension is associated with an increase in the prevalence of cardiovascular disease risk factors in Japanese women

This study assessed whether pregnancy-induced hypertension (PIH) affects the prevalence of cardiovascular disease (CVD) risk factors in later life among Japanese women. Study participants were 1,185 women (mean [SD] age, 46.5 [5.6] y; range, 38-73 y) aged 40 years or older who underwent a health checkup at a periodic health examination facility between January 2012 and December 2013 and had experienced giving birth. Questionnaires were sent to potential participants, and they were encouraged to provide their Maternal and Child Health Handbook (handbook). We recruited 101 women with a history of PIH (PIH group) and 1,084 women with uncomplicated pregnancy at delivery (control group). Groupings were based on information from the handbook. We assessed the association between PIH and CVD in later life among Japanese women by focusing on hypertension, diabetes mellitus, and dyslipidemia as risk factors for CVD. Odds ratios (ORs) for the use of antihypertensive, diabetes mellitus, and dyslipidemic medications in the PIH group were determined. Women with PIH had increased risk of antihypertensive medication use compared with women without PIH (2.9% vs 13.9%; OR, 4.28; 95% CI, 2.14-8.57). Triglycerides were significantly higher and high-density lipoprotein cholesterol was significantly lower in the PIH group than in the control group. The OR for dyslipidemic medication use in the PIH group relative to the control group was 3.20 (95% CI, 1.42-7.22). Our findings suggest that a history of PIH may be associated with an increased risk of hypertension (a risk factor for CVD) in later life among Japanese women.

Relationship between maternal gestational hypertension and home blood pressure in 7-year-old children and their mothers: Tohoku Study of Child Development.

Women who had hypertensive disorders in pregnancy have an increased risk of cardiovascular diseases in later life. No studies, however, have investigated whether maternal hypertensive disorders in pregnancy affect self-measured blood pressure at home (HBP) in mothers and their children. We evaluated the association between maternal hypertension during pregnancy and HBP based on the prospective Tohoku Study of Child Development birth cohort study, which was performed in two areas in Japan. We included children in a singleton birth at term (36-42 weeks of gestation) with a birth weight of >2400 g. We collected prenatal care data from the medical charts. Because only two mothers experienced preeclampsia, we defined gestational hypertension (GH) as a hypertensive disorder in pregnancy. Seven years after birth, mothers and their children measured their HBP in the morning for 2 weeks. Of 813 eligible mothers, 28 (3.4%) experienced GH, and those were of a similar age compared with 785 non-GH mothers (37.3 vs. 38.0 years; P=0.41). Women with GH had higher body mass index (BMI) (23.8 vs. 21.4 kg m(-)(2); P=0.01) and elevated HBP (120.3/76.8 vs. 110.4/68.6 mm Hg; P<0.0002) 7 years after delivery. However, HBP was similar in children with and without GH mothers (93.5/55.9 vs. 94.1/56.1 mm Hg, P>0.38). These results were confirmatory in case-control (1:2) analyses with matching by maternal age, maternal BMI before pregnancy, survey area and parity. In conclusion, maternal GH did not affect HBP in offspring but strongly affected maternal HBP even 7 years after birth.

Impact of maternal obesity on fetal programming of cardiovascular disease.

The in utero environment is a key determinant of long-term health outcomes; poor maternal metabolic state and placental insufficiency are strongly associated with these long-term health risks. Human epidemiological studies link maternal obesity and offspring cardiovascular disease in later life, but mechanistic studies in animal models are limited. Here, we review the literature pertaining to maternal consequences of obesity during pregnancy and the subsequent impact on fetal cardiovascular development.