Cardiovascular Risk In Later Life Research Articles

Prevalence of metabolic sy ndrome and its risk factors among medical undergraduates at Northern Border University, Arar, Saudi Arabia

Purpose: To determine the prevalence of metabolic syndrome (MetS) and its associated factors among medical undergraduates of Northern Border University. Methods: This cross-sectional study was performed on 200 medical undergraduates of Northern Border University, Arar, Saudi Arabia from August 2023 to October 2023. Data on demographic details and anthropometric measurements were collected. Complete lipid profile and blood glucose levels were measured after at least 8-h fast. The International Diabetes Federation (IDF) recommendations were utilized for diagnosing MetS. The data obtained were analyzed using Statistical Package for Social Sciences (SPSS), version 20.0. Group differences were analyzed using Chi-square test and Post hoc analysis. Results: The estimated overall prevalence of MetS was 21.5 %. Metabolic syndrome (MetS) was more prevalent among older students (37.36 %) and obese students (45.28 %) than among younger and non-obese students. Female students had a higher prevalence of MetS (29 %) than their male counterparts (14 %). The most frequent risk factors for MetS were elevated waist circumference (36 %) and low HDL levels (33 %). The majority of students (76.7 %) with high waist circumference had 2 or more risk factors for MetS. Students with a positive family history of hypertension and obesity showed greater prevalence of MetS. Conclusion: The study has demonstrated a high prevalence of MetS among young adults in Arar, Saudi Arabia. High prevalence of obesity and elevated waist circumference suggests that early and targeted interventions are required to prevent the development of MetS and cardiovascular risk in later life.

Abstract P203: Microvascular Imaging As Early Predictor For Cardiac Dysfunction After Preeclampsia

Preeclampsia (PE), the most common pregnancy disease, is the main cause for maternal and fetal mortality and morbidity worldwide. The disease is characterized by a sudden increase in blood pressure in combination with signs of end organ damage, e.g. proteinuria and the underlying mechanisms are poorly understood. Immune dysregulation and endothelial dysfunction are important pathomechanisms leading to PE, we hypothesize that anti-angiogenesis and dysregulation of microvascular perfusion postpartum lead to the increased cardiovascular risk in later life. In addition, we will test if the examination of retinal vessels can be used as a diagnostic window for early risk prediction of cardiovascular alterations. In a well-established transgenic rat model for PE, we performed speckle tracking echocardiography, immunostaining, RNA sequencing and small vessel imaging by micro-computed tomography of the heart and the eyes in former preeclamptic rats (PEpp) and healthy controls (WTpp). A reduction of cardiac vessels (AUC 0-200 μm: WTpp 77.19±4.64 vs. PEpp 62.59±2.72) in combination with an increase of small vessels in the retina (AUC 0-50 μm: WTpp 52.89±1.47 vs. PEpp 59.54±1.09) is shown postpartum. Data from echocardiography (Global longitudinal strain: WTpp -22.03±2.47 % vs. PEpp -14.50±1.80 %) and histological staining (CD31: WTpp 292.7±30.9 per fov vs. PEpp 219.0±10.5 per fov) support the hypothesis of persistent cardiovascular alterations after PE. Performing RNAseq, 65 genes were found to be permanently altered in the left ventricle of the heart of preeclamptic rats compared to 4 genes in controls. In the retinal tissue, 39 genes in PEpp and no genes in WTpp were identified postpartum compared to never pregnant animals (adjusted p-value < 0.05,

Associations of blood pressure trajectories in early life with target organ damage in midlife : a 30-year cohort study.

Hypertension is a pivotal factor in cardiovascular risk. However, the association of longitudinal blood pressure (BP) trajectories in the early life and cardiovascular risk assessed by target organ damage (TOD) in adulthood is poorly reported. The objective of this study was to identify the association between systolic BP, diastolic BP, and mean atrial pressure (MAP) trajectories early in life with a single or multiple TOD in later life. We identified BP trajectories from 6 to 45 year-old using group-based trajectory models among 2430 individuals in the Hanzhong Adolescent Hypertension Study and examined the relationship between BP trajectories and cardiovascular risk in later life. Four discrete long-term systolic BP, diastolic BP, and MAP trajectories were identified, namely, low stable, moderate stable, high stable (low increasing), and moderate increasing groups, based on the BP levels at baseline and in the 30-year follow-up. The carotid intima-media thickness were higher in persistently high or increasing trajectories in comparison to the low stable group. Individuals with deteriorative trajectories during early life were at an increased risk of suffering from a single TOD, including left ventricular hypertrophy (LVH) and carotid atherosclerosis (CA) in middle age (36-49 years old). Moreover, higher BP trajectories were correlated with the presence of combined TODs load stage which were assessed by CA, LVH, arteriosclerosis and subclinical renal damage (SRD). Higher longitudinal BP trajectories early in life were associated with increased cardiovascular risk in midlife, and identifying BP trajectories in early life can help screen individuals with TOD later. LVH, left Ventricular Hypertrophy; CA, carotid atherosclerosis; SRD, subclinical renal damage; TOD, target organ damage.

TYPE 2 DIABETES IN YOUNG ADULTS: PREVALENCE AND RISK FACTOR CONTROL IN A TERTIARY DIABETES CENTRE

Objective: The prevalence of type 2 diabetes (T2DM) is increasing in younger adults. Diagnosis at young age translates into increased lifetime complications risk and number of years of life lost. Despite this, clinical guidelines advocate risk-factor management based on 10-year rather than lifetime risk, and there are no specific treatment targets for young adults as this group is under-represented in outcome studies. We reviewed prescribing; risk-factor management; glycaemic control; and follow-up arrangements in people with T2DM aged 18-30 living in North-East Glasgow. Design and method: We used the Scottish Care Information – Diabetes Collaboration (Sci-Diabetes) registry to identify all individuals with T2DM aged 18-30 years and collected data from online medical records. Results: We identified a cohort of 74 (70% female) individuals. Mean age at diagnosis was 23 years. Social deprivation was high (mean SIMD 1.7). Mean HbA1c was 60.4 (range 32 – 119) mmol/mol with 35 (47%) requiring more than 1 glucose-lowering medication and 7 were (9%) insulin-treated. Mean BMI was 35kg/m2 and 55 (74%) individuals were clinically obese. Dietetic review was documented in 30 (45%), GLP-1 analogues were prescribed to 18 (24%). Blood pressure (mean 125/82; range 100-168/60-101) mmHg was above target in 16 (22%) individuals. Only 8 (10%) and 4 (5%) people were on anti-hypertensive and lipid-lowering drugs respectively. Pregnancy advice had been given in 39 (75%) of female patients. Seventeen (22%) individuals were lost to follow-up. Conclusions: Follow-up and risk-factor control are inconsistent in this high-risk group. Service innovation is urgently required to ensure young adults with T2DM are offered appropriate and accessible follow-up in order to minimise cardiovascular risk in later life.

The association between urinary cotinine level and metabolic syndrome profiles among adolescents: findings from the Ewha Birth and growth study

Background:Secondhand smoke (SHS) exposure among adolescents who are still developing can negatively affect their physical and psychological health, including metabolic syndrome (MetS), which is a risk factor for cardiovascular disease. However, the relationship between exposure to SHS and MetS in adolescence has not been evaluated.Methods:A total of 240 subjects aged 13–15 years who were followed up in the Ewha Birth and Growth Study were included in this study. Using the urinary cotinine level, the participants’ exposure to SHS was divided into tertiles, and the continuous MetS score (cMetS) and its components were compared among the three groups using a generalized linear model and trend analysis. Univariate and multivariate linear regression analyses were performed. We adjusted for several confounding variables including sex, father’s education level, father’s current alcohol consumption status, moderate physical activity, and overweight status.Results:The association between cMetS and the urinary cotinine level was not significant. However, the higher the urinary cotinine level, the lower the high-density lipoprotein cholesterol (HDL-C) level. In particular, the significance of the HDL-C level was maintained after adjusting for covariates.Conclusions:This study supports an association between SHS exposure and the components of MetS in adolescents aged 13–15 years, and it suggests the need to address SHS exposure in adolescents to reduce the cardiovascular risk in later life.

OR14-1 Preimplantation embryo development is associated with both birth size and post-natal growth and can predict adult cardiovascular risk

Abstract Background The link between birth-size, early childhood growth and later life cardiovascular (CV) risk is well recognised. The contribution to CV risk of growth and cell differentiation during pre-implantation embryo development is unknown. Aims Develop a transcriptomic model of developmental trajectory in the pre-implantation embryo and link this model to birthweight, child growth and CV risk in later life. Methods Single cell RNA velocity1 and pseudotime analyses were used to infer developmental trajectory in the preimplantation human embryo2. Time series clustering was used to identify genes with similar activity patterns. These data were compared with independent genomic data from four further data sets. I) Birthweight genome wide association study (GWAS)3. II) Genes correlated with gestation4. III) A previously identified set of 55 genes that classify pre-hypertensive young adults using their blood methylome at age 0, 7 and 17 years5. IV) A set of genes with differential methylation associated with linear childhood growth6. Data sets III) and IV) were derived from the Avon Longitudinal Study of Parents and Children (n=6487). Enrichment was assessed using the hypergeometric test and confirmed via random permutation (1×105-fold) and z-score analysis. Random Forest was used to determine the predictive value presented as the area under the curve (AUC) of the receiver operating characteristic. Results 8256 genes contributed to the velocity of mRNA change in the preimplantation embryo and a temporal wave pattern was revealed with peaks of velocity at 3, 4, and 5-days post-fertilisation. Genes associated with the velocity of the developmental trajectory formed 6 clusters, in which metabolic pathways were over-represented (adj. p<0.02). We found that 16/60 birthweight GWAS (I) and 3096/10521 gestation correlated genes (II) were associated with embryonic developmental trajectory (both 2-fold enrichment, p<5×10-3). Furthermore, 11/55 pre-hypertensive associated genes (III) were linked with embryonic developmental trajectory (>10-fold enrichment, p<1×10-8), these 11 genes predicted adult pre-hypertension in small for gestational age catch-up growth (cuSGA) with an AUC=0.98. Of the 8256 developmental trajectory genes, 307 were differentially methylated in linear childhood growth (IV) (2.3-fold over-enrichment, p<1×10-8). Conclusion Waves of gene expression velocity occur in preimplantation human embryos. These waves mark major developmental transitions and form a transcriptomic developmental trajectory which is associated with both birthweight and gestation. The transcriptomic developmental trajectory genes are over-enriched for genes associated with the linear phase of childhood growth and for genes associated with and predictive for the development of adult pre-hypertension in cuSGA. Pre-implantation gene expression can therefore be linked to the origins of adult disease. 1. LaManno, et al. (2018). Nature. 560(7719): 494-8. 2. Petropoulos, et al. (2016). Cell. 165(4): 1012-26. 3. Horikoshi, et al. (2016). Nature 538(7624): 248-252. 4. Rasmussen, et al. (2022). Nature. https://doi.org/10.1038/s41586-021-04249-w 5. Garner, et al (2021). JES. 5: A654–A655. 6. Garner, et al (2019) ESPE Abstracts 92FC12.6 Presentation: Sunday, June 12, 2022 11:00 a.m. - 11:15 a.m.

Effect of Folate and/or Vitamin B12 Supplementation between 6 to 30 Months of Age on Markers of Cardiovascular Illness at School Age: A Secondary Analysis

ObjectivesDeficiencies of vitamin B12 and folate in childhood are associated with cardiovascular risk in later life. The main objective of this analysis is to measure the effect of vitamin B12 and/or folic acid supplementation in children between 6 to 30 months of age on biochemical markers of cardiovascular risk at school age.MethodsThis is a follow-up study of a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial which assessed the effect of 2 recommended daily allowances of vitamin B12 and/or folic acid supplementation for 6 months on the risk of common infections in children aged between 6 to 30 months. The follow-up study was done 6 years later. The outcomes of the current analyses were plasma concentrations of total homocysteine, leptin, high molecular weight (HMW) adiponectin, and total adiponectin. We used multivariable linear regression to measure the effect of vitamin B12, folic acid, or both during early childhood on these outcomes. We included interaction terms in the statistical models to measure whether the two vitamins modified the effect of each other.ResultsCompared to the placebo, giving both B12 and folate supplementation resulted in 1.19 μmol/L (95% confidence interval: 0.09, 2.30) lower total homocysteine concentration at 7 years of age. There was no effect of B12 and folate supplementation on any of the other biomarkers. The effect of folic acid or vitamin B12 alone did not reach statistical significance for any of the outcomes.ConclusionsVitamin B12 and folic acid supplementation in early life resulted in lower plasma homocysteine at school age. Elevated homocysteine is a risk factor for many illnesses and our findings support improving the status of these vitamins in early life.Funding SourcesThe main study and follow-up study were funded by Thrasher Research Fund and Research Council of Norway.

Blood Pressure Levels and Maternal Outcome in Women with Preeclampsia - a Retrospective Study from a Large Tertiary Obstetric Centre.

Introduction Patients with high blood pressure levels are at high risk for acute complications as well as serious long-term consequences. Women with preeclampsia often experience very high blood pressure levels during pregnancy and postpartum and are also known to have a higher cardiovascular risk in later life. Material and Methods In our single-centre retrospective cohort study, we analysed 158 pregnancies complicated by preeclampsia in regard to maternal outcome. We divided the patient cohort into three subgroups according to the blood pressure levels during hospital stay. Results Pre-existing arterial hypertension was significantly more common in patients with a hypertensive crisis (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 120 mmHg) during pregnancy than in patients with moderate or severe hypertension (p = 0.001). Women with a hypertensive crisis had an unfavourable outcome compared to women with lower blood pressure levels. These women developed a HELLP-syndrome significantly more often (p = 0.013). Moreover, most of the women with a hypertensive crisis during pregnancy were still hypertensive at hospital discharge (p = 0.004), even though they were administrated antihypertensive agents more often (p < 0.001) compared to women with lower blood pressure values. Conclusion Preeclamptic women with hypertensive crises should be identified quickly and monitored closely to avoid further complications. Standardized follow-up programs are lacking, but especially these patients seem to be at high risk for persistent hypertension and increased cardiovascular morbidity and therefore should receive specialist follow-up, including hypertensiologists, cardiologists and gynaecologists. Large prospective trials are required for a better understanding of these interrelations and to develop a specific follow-up program.

Kinetics of Postpartum Mesenteric Artery Structure and Function Relative to Pregnancy and Lactation in Mice

Epidemiological evidence suggests that normal pregnancy in women is associated with decreased cardiovascular risk in later life. Clinical studies have provided evidence that alterations in vascular function and structure are detectable long after delivery. To understand these findings, we examined mesenteric artery reactivity at both early (3 days and 2–4 weeks) and late (12 weeks) postpartum (PP) time points in relation to late pregnancy (LP) and lactation. Vessels from virgin controls, LP, PP, and nursing and non-nursing mothers were tested for responses to phenylephrine (PE), high potassium solutions (high K+), and acetylcholine (ACh). Passive arterial distensibility, vessel dimensions, and collagen and elastin content were evaluated for the studied groups. We observed that (1) there was a significant inhibition of vascular reactivity to PE in LP, 3 days and 2 weeks PP vessels that returned to pre-pregnancy levels at 4 and 12 weeks PP; (2) inhibition of NO production in PP vessels restored PE-induced constriction to pre-pregnancy levels; (3) vasodilator responses to ACh were similar at all PP periods; (4) LP and early PP was associated with a persistent increase in arterial distensibility that correlates with a PP-induced reduction in wall collagen, and regressed to pre-conception levels at 12 weeks PP; (5) vessels from non-nursing PP mice demonstrated an increased PE reactivity, diminished responses to ACh, and reduced distensibility compared to breastfeeding mice. These studies provide a timeframe for mesenteric artery adaptations that occur during pregnancy and extend to the PP period, but which may be modified by PP events.

Variations in Cardiovascular Structure, Function, and Geometry in Midlife Associated With a History of Hypertensive Pregnancy.

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m2; P=0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; P=0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; P=0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m2; P=0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; P=0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; P=0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm2; P=0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure (P<0.01, P=0.01, and P=0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.

Biochemical predictors for metabolic syndrome in preterm infants according to weight ratio.

Prematurity and low birth weight predispose preterm infants to cardiovascular disease in later life. Is the metabolic profile of these children impacted by the relation between birth weight and gestational age (GA)? This study aimed to evaluate whether the relationship between birth weight and GA of preterm infants has a positive correlation with the metabolic profile from birth to the sixth month of corrected age. This is a longitudinal, prospective study with a cohort of 70 preterm and 54 term infants, who were enrolled in the study and shared into two groups: Appropriate for GA (AGA) and Small for GA (SGA), both classified at birth by Fenton and Kim curves. Longitudinal evaluation of anthropometry measures and blood samples of total cholesterol, glucose, triglycerides, and insulin were collected at birth, NICU discharge, and the sixth month of corrected age. Data were analyzed using descriptive and inferential statistical analysis (ANOVA, Fisher test, Shapiro-Wilk, and Cochran test). The effect size was 0.15, power was 0.92, and confidence interval 95%. No significant statistical differences were observed in relation to biochemical tests between AGA and SGA groups. However, a significant increase in triglyceride results above the reference values for age in the SGA group was observed throughout the follow-up. Changes observed in the preterm infant metabolic profile show no correlation with adequacy of birth weight. Preterm lipid profile requires continuous evaluation at follow-up, due to the increased cardiovascular risk in later life.

Statins Reverse Postpartum Cardiovascular Dysfunction in a Rat Model of Preeclampsia.

Preeclampsia is associated with increased cardiovascular long-term risk; however, the underlying functional and structural mechanisms are unknown. We investigated maternal cardiac alterations after preeclampsia. Female rats harboring the human angiotensinogen gene [TGR(hAogen)L1623] develop a preeclamptic phenotype with hypertension and albuminuria during pregnancy when mated with male rats bearing the human renin gene [TGR(hRen)L10J] but behave physiologically normal before and after pregnancy. Furthermore, rats were treated with pravastatin. We tested the hypothesis that statins are a potential therapeutic intervention to reduce cardiovascular alterations due to simulated preeclamptic pregnancy. Although hypertension persists for only 8 days in pregnancy, former preeclampsia rats exhibit significant cardiac hypertrophy 28 days after pregnancy observed in both speckle tracking echocardiography and histological staining. In addition, fibrosis and capillary rarefaction was evident. Pravastatin treatment ameliorated the remodeling and improved cardiac output postpartum. Preeclamptic pregnancy induces irreversible structural changes of cardiac hypertrophy and fibrosis, which can be moderated by pravastatin treatment. This pathological cardiac remodeling might be involved in increased cardiovascular risk in later life.

Early Assessed Total Cholesterol Significantly Improves The Prediction Of Cardiovascular Risk In Later Life

Background and Aims: Longtime follow-up (FU) data for coronary risk patients exceeding a 10-year FU and cholesterol measurements being unbiased by statin treatment are scarce. The aim of this study was to investigate the impact of total cholesterol (TC), determined in the course of an early life general health check, compared to TC, measured at advanced age, on the cardiovascular risk.

The Perinatal Condition Around Birth and Cardiovascular Risk Factors in the Japanese General Population: The Suita Study.

Aim: To investigate the relationship between perinatal condition around birth and cardiovascular risk in later life.Methods: Retrospective data were examined from 1241 city dwellers (521 men, 720 women; age 41–69 years) who had undergone medical examination at a single institution including blood tests and physical measurements from 2007 to 2008. The questionnaire was conducted to determine how perinatal factors affect their lives later. We also selected and studied a total of 28 individuals (12 men and 16 women) specifically about the conformity rate of the breastfeeding method between participants' memories and what was written in the maternal and child health handbooks.Results: The conformity rate of the breastfeeding method between a self-questionnaire and his/her maternal and child health handbook was well correlated (r = 0.73; p < 0.025). Among the data in women who were born at home, HbA1C levels (5.36 ± 0.03 vs. 5.25 ± 0.05 mg/dL, p = 0.03) and low-density lipoprotein cholesterol (136.0 ± 1.4 vs. 129.3 ± 2.5 mg/dL, p = 0.04) were higher than women who were born at the hospital. Women raised by formula showed higher low-density lipoprotein cholesterol levels than women fed breast milk or a mixture of breast milk and formula (150.2 ± 4.8 vs. 138.7 ± 3.7, 142.5 ± 2.6 mg/dL, p = 0.04). Fasting blood glucose levels at an adult time in men and women born through breech presentation were higher than those by the cephalic presentation (123.2 ± 7.8 vs. 106.8 ± 1.2 mg/dL, p = 0.03).Conclusion: The study proposed that some perinatal conditions around birth such as delivery place, presenting part, and lactation affected especially Japanese women's cardiovascular risks between ages 41 and 69 years.

Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages

Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults. To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages. In this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had received pseudocontinuous arterial spin labeling magnetic resonance imaging. Cardiovascular risk was measured at 5-year intervals across 5 phases from September 1991 to October 2013. Arterial spin labeling scans were acquired between April 2014 and December 2014. Data analysis was performed from June 2016 to September 2018. Framingham Risk Score (FRS) for cardiovascular disease, comprising age, sex, high-density lipoprotein cholesterol level, total cholesterol level, systolic blood pressure, use of antihypertensive medications, cigarette smoking, and diabetes, was assessed at 5 visits. Cerebral blood flow (CBF; in milliliters per 100 g of tissue per minute) was quantified with pseudocontinuous arterial spin labeling magnetic resonance imaging. Of 116 adult participants, 99 (85.3%) were men. At the first examination, mean (SD) age was 47.1 (5.0) years; at the last examination, mean (SD) age was 67.4 (4.9) years. Mean (SD) age at MRI scan was 69.3 (5.0) years. Log-FRS increased with time (B = 0.058; 95% CI, 0.044 to 0.072; P < .001). Higher cumulative FRS over the 20-year period (measured as the integral of the rate of change of log-FRS) was associated with lower gray matter CBF (B = -0.513; 95% CI -0.802 to -0.224; P < .001) after adjustment for age, sex, education, socioeconomic status, cognitive status, arterial transit time, use of statins, and weekly alcohol consumption. Voxelwise analyses revealed that this association was significant in 39.6% of gray matter regions, including the posterior cingulate, precuneus, lateral parietal cortex, occipital cortex, hippocampi, and parahippocampal gyrus. The strength of the association of higher log-FRS with lower CBF decreased progressively from the first examination (R2 = 0.253; B = -10.816; 99% CI -18.375 to -3.257; P < .001) to the last (R2 = 0.188; B = -7.139; 99% CI -14.861 to 0.582; P = .02), such that the most recent FRS measurement at mean (SD) age 67.4 (4.9) years was not significantly associated with CBF with a Bonferroni-corrected P < .01 . Cardiovascular risk in midlife was significantly associated with lower gray matter perfusion at older ages, but this association was not significant for cardiovascular risk in later life. This finding could inform the timing of cardiovascular interventions so as to be optimally effective.

146. Regulatory (auto-) antibodies against G-coupled receptors in women ten years after early-onset preeclampsia: Results from the PREVFEM study

Introduction Preeclampsia (PE) is associated with an increased cardiovascular risk in later life, especially in women after early-onset PE. We and others have shown that activating antibodies against angiotensin II receptor type 1 (AT1-) are present in women with PE, even after pregnancy. Further, regulatory (auto-) antibodies against G-coupled receptors (GPCR) have been shown to contribute to cardiovascular disease. Hypothesis We tested the hypothesis that regulatory autoantibodies’ titers are elevated in women with a history of early-onset PE and correlate to physiological parameters and clinical outcomes. Methods We investigated data from PREVFEM (Preeclampsia Risk EValuation in FEMales) retrospective matched case-control study, which was performed in Zwolle, The Netherlands, from 2008 until 2010. All women registered in the early PE database as well as an equal number of age-matched females without PE from the regular obstetric database in the same time period (1991–2007) were invited to participate in the PREVFEM study. Autoantibodies against AT1-, β1-adrenergic receptors, endothelin I receptor A (ETAR), protease-activated receptor 1 (PAR1) and C-X-C3 chemokine binding receptors (CXC3R) were determined in 609 samples (306 cases and 303 controls) by using commercially available ELISA (Celltrend, Luckenwalde, Germany). Results The titer levels of AT1-, β1-, ETAR-, PAR1- and CXC3R-autoantibodies were not significantly different between control and former PE groups 10 years after index pregnancy. Former PE women showed a significantly higher prevalence of hypertension (43% vs. 17%, p Discussion Regulatory autoantibodies against GPCR do not identify women at higher risk for cardiovascular disease 10 years after early-onset PE. The need to search for biomarkers identifying women at risk before cardiovascular symptoms is continuing.

Reevaluation of Protein Intake for Preterm Infants.

Growth failure caused by undernutrition is considered one of the major causes for psychomotor delay in extremely preterm infants, and the concept for "aggressive nutritional approach" is widely accepted worldwide. Based on this, postnatal early catch-up growth due to sufficient supply of nutrients including sufficient amounts of amino acids is believed to be essential for a better outcome; however, there is no definitive evidence of aggressive nutrition on better outcomes in mortality, growth, and neurodevelopment. On the contrary, epidemiological evidence suggests that low birth weight and a rapid catch-up growth after birth are major risk factors for insulin resistance and diabetes in later life; higher protein intake during postnatal period relates to higher cardiovascular risk in later life. Considering these, optimal nutrition, especially protein administration, should be reevaluated. In this review, current opinions on the nutrition for the preterm infants are surveyed. In addition, I propose a new concept for optimized protein amount for the preterm infants based on the difference of amino acid metabolism between fetuses and preterm infants.

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia

Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10–20%), but ABCA1-mediated efflux was decreased (by 20–35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples (P< 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia (P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia (P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis.

Impaired functional capacity of fetal endothelial cells in preeclampsia.

ObjectivesPreeclampsia is one of the main contributers to maternal and fetal morbidity and mortality during pregnancy. A history of preeclampsia puts mother and offspring at an increased cardiovascular risk in later life. We hypothesized that at the time of birth functional impairments of fetal endothelial cells can be detected in pregnancies complicated by preeclampsia and that a therapeutic intervention using 1,25 (OH)2 vitamin D3 can reverse the adverse effects of preeclampsia on cell function.MethodsHuman umbilical vein endothelial cells (HUVEC) were isolated from umbilical cords obtained from preeclamptic (N = 12) and uncomplicated pregnancies (N = 13, control). Placental villous tissue fragments from uncomplicated term pregnancies were incubated in explant culture for 48 h at 2% (hypoxia), 8% or 21% O2. Explant conditioned media (CM) was collected and pooled according to oxygen level. We compared the ability of preeclampsia vs. control HUVEC to migrate, proliferate, and form tubule-like networks in a Matrigel assay, in the presence/absence of CM and 1,25(OH)2 vitamin D3.ResultsHUVEC from preeclamptic pregnancies showed reduced migration (P = 0.04) and tubule formation (P = 0.04), but no change in proliferation (P = 0.16) compared to healthy pregnancies. Placental villous explant CM derived from 2% O2 incubations significantly reduced HUVEC migration, when compared to non-CM (P = 0.04). Vitamin D3 improved HUVEC function in neither of the groups. There was no significant difference in VEGF gene expression between healthy and preeclamptic pregnancies and no effect of Vitamin D3 on VEGF expression.ConclusionsReduced functional abilities of fetal endothelial cells from preeclamptic pregnancies suggests that disease pathways, possibly originating from the dysfunctional placenta, negatively impact fetal endothelium. The neutral effect of 1,25(OH)2 vitamin D3 contrasts with previous findings that vitamin D rescues the poor migration, proliferation and tubule formation exhibited by cord blood fetal endothelial progenitor cells from preeclamptic pregnancies. Further investigations to distinguish pathways by which offspring exposed to preeclampsia are at risk for cardiovascular disease are needed.

Is Sex Good for Your Health? A National Study on Partnered Sexuality and Cardiovascular Risk among Older Men and Women.

Working from a social relationship and life course perspective, we provide generalizable population-based evidence on partnered sexuality linked to cardiovascular risk in later life using national longitudinal data from the National Social Life, Health and Aging Project (NSHAP) (N = 2,204). We consider characteristics of partnered sexuality of older men and women, particularly sexual activity and sexual quality, as they affect cardiovascular risk. Cardiovascular risk is defined as hypertension, rapid heart rate, elevated C-reactive protein (CRP), and general cardiovascular events. We find that older men are more likely to report being sexually active, having sex more often, and more enjoyably than are older women. Results from cross-lagged models suggest that high frequency of sex is positively related to later risk of cardiovascular events for men but not women, whereas good sexual quality seems to protect women but not men from cardiovascular risk in later life. We find no evidence that poor cardiovascular health interferes with later sexuality for either gender.