Cardiovascular Disease In Later Life Research Articles

The Value of First Trimesteric 3D Ultrasound Placental Volume in Prediction of Pre-Eclampsia in High-Risk Pregnant Women

Abstract Background Hypertension with pregnancy remains a major health issue for women and neonates worldwide. Pre-eclampsia (PE) complicates 2–5% of all pregnancies and is a leading cause of maternal and neonatal mortality and morbidity. PE and eclampsia are responsible for approximately 14% of maternal mortality. PE is also associated with later-life cardiovascular disease among women and their offspring. Aim of the Work To determine the value of first trimesteric placental volume in predicting pre-eclampsia in high-risk pregnant women. Patients and Methods This Prospective observational study was conducted at tertiary care hospital at Ain Shams University hospitals from September 2019 till November 2021 and performed on a total of 125 pregnant women with high risk of PE at 12 to 12 + 6 week of gestation attending Fetal care unit, Ain Shams University Maternity Hospital. Results DBP statistically had significant moderate diagnostic performance with DBP cut-off value of ≥ 79.0 mmHg in predicting preterm delivery and SGA with significant low diagnostic performance in predicting NICU admission with DBP sensitivity of 83.3%, 67.9%, 64.5% and specificity of 74.8%, 76.3% and 76.6% in predicting preterm delivery, SGA and NICU admission respectively. Conclusion Placental volume and diastolic blood pressure (DBP) were significantly lower in cases with preeclampsia and predictive of maternal complications of HELLP syndrome, Renal impairment, ICU admission and predictive of preterm labor, SGA and NICU admission.

The RhoA guanine exchange factor ABR: a glucose-sensitive mediator of actin reorganization in feto-placental arterial endothelial cells altered by gestational diabetes mellitus.

In utero exposure to gestational diabetes mellitus (GDM) programs the fetus, increasing offspring risk for endothelial dysfunction and cardiovascular disease later in life. Hyperglycaemia is widely recognized as the driving force of diabetes-induced programming. We have previously shown that GDM exposure alters DNA methylation and gene expression associated with actin remodelling in primary feto-placental arterial endothelial cells (fpEC). Thus, we hypothesized that hyperglycaemic insults underlie programmed changes in fpEC morphology and actin organization by GDM. Therefore, arterial fpECs isolated after normal and GDM pregnancy, as well as normal fpECs that were exposed to hyperglycaemia in vitro, were analysed for the effect of GDM and hyperglycaemia on actin organization and network formation. Integration of gene expression and DNA methylation data identified the RhoA activator active BCR-related (ABR) as programmed by GDM and altered by in vitro hyperglycaemia. ABR silencing in GDM-exposed cells reduced RhoA activity by 34±26% (P=0.033) and restored normal fpEC phenotype. In fact, in vitro hyperglycaemia induced a similar fpEC phenotype as intrauterine exposure to GDM, i.e. round morphology and increased network formation on Matrigel by 34±33% (P=0.022) vs. 22±20% for GDM (P=0.004). Thus, we identified ABR as a novel glucose sensitive regulator of actin organization and cell shape, programmed by GDM and upregulated by hyperglycaemia. Identification of mechanisms induced by hyperglycaemia and affecting endothelial function in the long term will contribute to understanding GDM-induced programming of offspring endothelial dysfunction and cardiovascular disease. Future studies could focus on investigating the prevention or reversal of such malprogramming. KEY POINTS: In utero exposure to gestational diabetes mellitus (GDM) affects future health of the offspring, with an increased risk for endothelial dysfunction and cardiovascular disease in later life. GDM alters DNA methylation and expression of ABR in feto-placental arterial endothelial cells (fpEC), a model for endothelial cells exposed to the intrauterine environment of the fetus. GDM phenotype of fpECs is also induced by hyperglycaemia in vitro, and is characterized by altered actin organization and cell shape, which can be restored by ABR silencing. Revealing the cellular mechanisms induced by GDM and hyperglycaemia is important for understanding the mechanisms of how these conditions disturb endothelial function in the offspring.

ASSOCIATION OF BLOOD PRESSURE TRAJECTORIES SINCE YOUNG ADULTHOOD WITH CARDIOVASCULAR DISEASES IN LATER LIFE

Objective: To identify blood pressure (BP) trajectories since young adulthood and to determine their association with risk of cardiovascular diseases (CVD) in later life. Design and method: This cohort study used data of young adults aged 18 to 39 years from the Kailuan Cohort, a prospective longitudinal study of Chinese men and women. Using group-based trajectory modeling, distinct BP trajectories from 2006 to 2010 were identified for 5 BP traits (mid-BP, SBP, DBP, MAP, and PP). Main outcomes were incident CVD (coronary revascularization, myocardial infarction, heart failure, or stroke), which were collected until 31 December 2020. Cox proportional hazards regression models were used to estimate the associations between BP trajectories and the risk of incident CVD. Results: Of the 11 535 adults included in the study (mean [SD] age, 32.6 [5.1] years), 8708 (75.5%) were men. We identified 3 trajectories for all BP traits (except for PP, which was 2). Among them, the mid-BP trajectory distribution was 4566 individuals (39.6%) with low-increasing, 5996 (52.0%) with moderate-increasing, and 973 (8.4%) with high-stable. Compared with the mid-BP low-increasing trajectory group, individuals in the moderate-increasing and high-stable groups had higher risk of CVD (moderate: HR, 2.44; 95% CI, 1.47 to 4.06; high: HR, 3.82; 95% CI, 1.98 to 7.39) after adjusting for socio-demographics and cardiovascular risk factors, as well as the baseline mid-BP level. Results were consistent after additionally adjusting for cumulative mid-BP exposure during 2006 to 2010 (moderate: HR, 2.31; 95% CI, 1.41 to 3.79; high: HR, 3.18; 95% CI, 1.72 to 5.90). Besides, the increased CVD risk associated with higher trajectories were also significant for SBP, DBP, MAP, and PP, and remained robust through several sensitivity analyses, which included excluding those who ever used antihypertensive drugs during 2006 to 2010, excluding events within the first year of follow-up, and considering death as competing risk. Conclusions: Higher BP trajectories since early adulthood were associated with an increased risk of CVD in later life. Early detection of BP trajectories may assist in more accurate identification of individuals with high risk of future CVD.

Excessive Hypercholesterolemia in Pregnancy Impairs Later-life Maternal Vascular Function in Rats

Background: Preeclampsia is a significant risk factor for the development of later-life cardiovascular disease; however, the underlying molecular mechanisms are not fully understood. Studies have shown that excessive hypercholesteremia occurring during pregnancy increases the risk of vascular pregnancy complications, such as preeclampsia. Bioavailability of nitric oxide (NO), a critical endothelium-derived vasodilator in pregnancy, is reduced in both hypercholesteremia and preeclampsia. However, the later-life vascular impact of excessive pregnancy-specific hypercholesteremia is not known. Hypothesis: Excessive hypercholesteremia in pregnancy impairs later-life maternal vascular function by reducing NO availability. Methods: Sprague-Dawley rats were fed a control diet (CD) or high cholesterol diet (HCD; 2% cholesterol + 0.5% cholic acid) from gestational day 6 to 20 (term=22 days; n=10-12). After pregnancy, all dams received a CD. Three months after pregnancy (equal to ~10 years in humans), mesenteric (systemic resistance arteries) and carotid (vascular bed that supplies blood to the cerebral vasculature) arteries were isolated, and endothelium-dependent (to methacholine, MCh) and -independent (to sodium nitroprusside, SNP) vasodilation, plus vasoconstriction responses (to phenylephrine, PE) were assessed using wire myography. NO contribution was assessed using a pan-NO synthase inhibitor (L-NAME; 100 μmol). Data were summarized as maximum responses (Emax), sensitivity (pEC50), or delta Emax (control vs. L-NAME). The statistical tests applied were a Student’s t-test or two-way ANOVA with Sidak’s post-hoc test (significance: p<0.05). Results: In mesenteric arteries, vasodilation to MCh or SNP was not different between the CD and HCD groups three months after the insult. However, L-NAME reduced maximum vasodilation to MCh in the HCD group (p=0.0433) but not in CD animals. Similarly, vasoconstriction to PE was not different between groups, but L-NAME increased the PE sensitivity in the HCD group (p=0.0423), without effects in the CD animals. In carotid arteries, a HCD during pregnancy reduced vasodilation to MCh (p=0.0345), and while L-NAME prevented vasodilation to MCh in both groups (p<0.0001), this effect was more pronounced in the HCD compared to CD group (delta Emax, p=0.0422). Vasodilation to SNP was similar between groups. Vasoconstriction responses to PE were increased in carotid arteries of HCD compared to CD animals (p=0.0357). L-NAME increased PE-mediated vasoconstriction in both groups (CD: 4.32-fold and HCD: 2.71-fold), but this NO modulation was significantly less in the HCD group compared to CD (delta Emax, p=0.0337). Conclusion: Exposure to a HCD, during pregnancy only, impaired later-life maternal vascular function in carotid, but not mesenteric arteries, suggesting vascular-bed specific effects in animals with a history of preeclampsia. Moreover, a HCD during pregnancy altered the NO pathway in both vascular beds, indicating that long-term alterations in NO were established during pregnancy. In summary, excessive pregnancy-specific hypercholesterolemia contributes to later-life maternal vascular dysfunction via modulation of the NO pathway, which may help explain the increased cardiovascular risk after preeclampsia. This work was supported by a foundation grant from the Canadian Institutes of Health Research (CIHR FS154313) and by the Women and Children’s Health Research Institute (WCHRI) through the generosity of the Stollery Children’s Hospital Foundation and the Alberta Women’s Health Foundation. A.A.O. is supported by a WCHRI postdoctoral fellowship through the generosity of the Stollery Children’s Hospital Foundation and the Alberta Women’s Health Foundation. E.E. was supported by a summer research studentship from Alberta Innovates. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 62: Association of Cardiovascular Health Trajectories Through Young Adulthood With Later-Life Incident Cardiovascular Disease and Mortality: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Associations of mid-life cardiovascular health (CVH) and incident cardiovascular disease (CVD) are well-studied. Less is known about patterns of young adulthood (YA) CVH, including its changes, and associations with later-life CVD outcomes. Methods: CVH was defined by Life’s Essential 8 (LE8) score. First, we used latent class modeling (SAS Proc Traj) to determine trajectories of continuous CVH scores (0-100) for CARDIA participants with ≥3 CVH measurements in YA (from year [Y]0, mean age 25, to Y20, mean age 45). Second, we examined direction and magnitude of change in CVH status (low, moderate, or high) between 2 CVH measurements (at Y0 and Y20), comparing participants with increased, decreased, or stable CVH status. Outcomes included incident CVD (MI, heart failure, stroke, CVD death) after Y20. Cox proportional hazards regression was used to estimate HRs for associations of YA CVH patterns with incident CVD. Results: There were 4,257 participants in YA (44% female, 48% Black) included. In the trajectory analysis, we identified four distinct CVH trajectory groups ( Figure 1A ): compared to the Persistently-High CVH group, the Moderate-Low-Declining and Moderate-Declining CVH trajectory groups had substantially higher hazards for incident CVD ( Figure 1B ). In the CVH status change analysis (N=2,884; Figure 1B ), compared to Stable High CVH in YA, Stable Low CVH had a 19-fold higher risk for incident CVD, and both increasing and decreasing CVH status in YA had greater risk for incident CVD as well. Conclusions: Trajectories of declining moderate and low CVH in YA had substantially higher risk for later-life incident CVD events. Those with decreasing CVH and those who started with lower CVH and improved it through YA, were also at higher risk. These data suggest that early life CVH and maintaining high CVH through YA are both important for prevention of later-life CVD.

Abnormal Lipid Profile Level in Neonates and Possible Development of Atherosclerosis in Adulthood: Mini Review

The lipid profile during the neonatal period plays a pivotal role in determining the future risk of atherosclerosis and cardiovascular diseases in adulthood. Abnormal lipid levels in neonates have been associated with an increased propensity for the development of atherosclerosis later in life. This review aims to explore the significance of abnormal lipid profiles in neonates and their potential implications for the development of atherosclerosis in adulthood. The discussion encompasses the mechanisms underlying lipid metabolism in early life, the impact of various factors on lipid levels in neonates, and the long-term consequences of abnormal lipid profiles. Understanding the relationship between neonatal lipid profiles and the risk of atherosclerosis in adulthood is crucial for developing preventive strategies and interventions aimed at reducing the burden of cardiovascular diseases in later life. This review synthesizes idea from existing literature to provide insights into the importance of early lipid assessment and its implications for long-term cardiovascular health. Keywords: Abnormal Lipid Profile, Neonates, Atherosclerosis, Cardiovascular Risk, Lipid Metabolism, Early Life, Long-term Health, Preventive Strategies, Cardiovascular Disease

Genomic variation associated with cardiovascular disease progression following preeclampsia: a systematic review.

Women with a history of preeclampsia (PE) have been shown to have up to five times the risk of developing later-life cardiovascular disease (CVD). While PE and CVD are known to share clinical and molecular characteristics, there are limited studies investigating their shared genomics (genetics, epigenetics or transcriptomics) variation over time. Therefore, we sought to systematically review the literature to identify longitudinal studies focused on the genomic progression to CVD following PE. A literature search of primary sources through PubMed, Scopus, Web of Science and Embase via OVID was performed. Studies published from January 1, 1980, to July 28, 2023, that investigated genomics in PE and CVD were eligible for inclusion. Included studies were screened based on Cochrane systematic review guidelines in conjunction with the PRISMA 2020 checklist. Eligible articles were further assessed for quality using the Newcastle-Ottawa scale. A total of 9,231 articles were screened, with 14 studies subjected to quality assessment. Following further evaluation, six studies were included for the final review. All six of these studies were heterogeneous in regard to CVD/risk factor as outcome, gene mapping approach, and in different targeted genes. The associated genes were RGS2, LPA, and AQP3, alongside microRNAs miR-122-5p, miR-126-3p, miR-146a-5p, and miR-206. Additionally, 12 differentially methylated regions potentially linked to later-life CVD following PE were identified. The only common variable across all six studies was the use of a case-control study design. Our results provide critical insight into the heterogeneous nature of genomic studies investigating CVD following PE and highlight the urgent need for longitudinal studies to further investigate the genetic variation underlying the progression to CVD following PE.

Long-Term Impacts of Preeclampsia on the Cardiovascular System of Mother and Offspring.

Preeclampsia is a pregnancy-specific complication that is associated with an increased postpartum risk of cardiovascular disease (CVD) in both women and their offspring, although the underlying mechanisms have yet to be fully elucidated. Nevertheless, differential methylation of cytosine-phosphate-guanosine islands and alterations in the expression of microRNA, associated with an elevated risk of CVD, have been observed in women and their children following preeclampsia. Among this specific population, genetic and epigenetic factors play crucial roles in the development of CVD in later life. A series of biomolecules involved in inflammation, oxidative stress, and angiogenesis may link pregnancy vascular bed disorders in preeclampsia to the pathogenesis of future CVD and thus could be valuable for the prediction and intervention of long-term CVD in women with a history of preeclampsia and their offspring. Here, we present insights into the cardiovascular structure and functional changes of women with a history of preeclampsia and their offspring. With a focus on various underlying mechanisms, the conclusions from this review are expected to provide more potential diagnostics and treatment strategies for clinical practice.

ASSOCIATIONS OF LONG-TERM VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY WITH SUBCLINICAL KIDNEY DAMAGE AND ALBUMINURIA IN ADULTHOOD: A 30-YEAR PROSPECTIVE COHORT STUDY

Objective: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with the risk of cardiovascular disease. We therefore aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. Design and method: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BP variability by standard deviation (SD) and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/ 1.73 m2 or elevated urinary albumin-to creatinine ratio (uACR) at least 30 mg/g. Albuminuria was defined as uACR greater than 30 mg/g. Results: During a follow-up of 30 years, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics and mean BP during 30 years, higher SDSBP, ARVSBP, SDDBP, ARVDBP, SDMAP, ARVMAP and ARVPP were significantly associated with higher risk of SKD [ORs (95% CIs) were 1.14(1.06 - 1.23), 1.15(1.08 - 1.21), 1.12(1.06 - 1.17), 1.16(1.08 - 1.25), 1.12(1.07 - 1.17), 1.18(1.10 - 1.27) and 1.11(1.03 - 1.21), respectively]. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria [ORs (95% CIs) were 1.07(1.03 - 1.10) for SDSBP, 1.13(1.06 - 1.20) for ARVSBP, 1.11(1.06 - 1.17) for SDDBP, 1.14(1.06 - 1.23) for ARVDBP, 1.18(1.09 - 1.27) for ARVMAP and 1.08(1.01 - 1.17) for ARVPP]. Long-term BP variability for 30 years from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. Conclusions: Identifying long-term BP variability from early age may assist in predicting kidney disease and cardiovascular disease in later life.

The Impact of Bisphenol A Exposure during Pregnancy on the Heart of Mother and Fetal Rats

In utero bisphenol A (BPA) exposure has been reported to increase the risk of cardiovascular disease (CVD) in adult life. Thus, this study aimed to investigate the impact of in utero BPA exposure on proteins expression related to cardiac function in heart of rat foetuses (Rattus norvegicus). In here, pregnant rats were divided into tween-80 (vehicle control), 0.05 mg/mL and 0.2 mg/mL BPA via drinking water for 19 days: from pregnancy day 2 till 21. Caesarean section was conducted on pregnancy day 21 to collect plasma and heart of both mother and foetuses. BPA-exposed pregnant rats showed significant increase in blood pressure (BP) and reduction in glycogen content (p<0.05) in comparison to control pregnant rats. Remarkably, reduced expression of cardiac troponin I (cTnI) and redistribution of alpha fetoprotein (AFP) expression were in foetus of BPA-exposed mother in comparison with foetus of control mother. Hypoxia induced factor-1 alpha (HIF-1α) expression was elevated in BPA-exposed foetal heart compared to the control. The findings in here suggest the risk of in utero BPA exposure on both foetus and mother, which may increase the risk of CVD in later life by altering the expression of protein crucial for heart development and function.

Risk factors for arterial hypertension in women with abdominal obesity and hypertensive disorders of pregnancy in the history

The article provides data from epidemiological studies on the correlation between hypertensive disorders in pregnant women and the risk of cardiovascular diseases in later life, describes possible pathophysiological determinants for the occurrence of arterial hypertension after complicated pregnancy. The most informative predictors of the development of arterial hypertension in women with abdominal obesity are described, which were indicators of waist circumference, uterine artery resistance index, N-terminal fragment of the brain natriuretic peptide and highly sensitive C-reactive protein; a mathematical model was calculated to predict the probability of developing arterial hypertension in women with abdominal obesity and hypertensive disorders of pregnancy one year after delivery.

Abstract 18: Impact of Preeclampsia on Cardiovascular Risk Factors in Mothers and Newborns

Introduction: Preeclampsia is a multifactorial disease and a cause of maternal and neonatal morbidity and mortality. Women with preeclampsia have increased risk of cardiovascular diseases in later life. The impact on the offspring is, however, still uncertain. Lipid traits in newborns are considered to reflect the child’s own production. Hypothesis: We assessed the hypothesis that preeclampsia increases risk of future cardiovascular disease in both mother and offspring. Methods: For this purpose, we used the Copenhagen General Population Study comprising 59,571 women of which 1,365 had a diagnosis of preeclampsia to investigate the association between preeclampsia and risk of cardiovascular diseases. Further, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and assessed the impact of preeclampsia on atherogenic lipid traits in cord blood. Results: Age adjusted hazard ratios for preeclampsia versus no preeclampsia (95% CI) were 1.48 (1.13-1.94) for ischemic heart disease, 1.50 (1.07-2.12) for ischemic cerebrovascular disease, and 1.53 (1.22-1.91) for composite vascular disease. Corresponding multivariable adjusted hazard ratios (95% CI) were 1.31 (1.00-1.72), 1.44 (1.02-2.02), and 1.39 (1.11-1.74). Concentrations of non-HDL cholesterol, total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides in cord blood increased stepwise from no preeclampsia (n=11,221) to mild/moderate preeclampsia (n=253) to severe preeclampsia (n=104) (p for trends <0.0001 for non-HDL cholesterol, total cholesterol and LDL cholesterol; p for trend=0.0002 for apolipoprotein B; p for trend=0.003 for triglycerides). Multivariable adjusted odds ratios (95% CI) for preeclampsia versus no preeclampsia (reference) for cord blood concentrations above the 80 th percentile were 2.09 (1.67-2.61) for non-HDL cholesterol, 1.58 (1.25-2.01) for total cholesterol, 1.72 (1.37-2.16) for LDL cholesterol, 1.38 (1.07-1.78) for apolipoprotein B, and 2.64 (2.07-3.35) for triglycerides. Conclusion: Women with preeclampsia had increased risk of future cardiovascular disease and lipid traits in umbilical cord blood of their offspring were elevated. This indicates that preeclampsia affects lipid metabolism during fetal life and potentially contributes to an increased risk of future cardiovascular disease in offspring of mothers with preeclampsia.

Preeclampsia and Obesity-The Preventive Role of Exercise.

Obesity is now recognized as a worldwide epidemic. An inadequate diet and reduced physical activity are acknowledged as the leading causes of excess body weight. Despite growing evidence that obesity is a risk factor for unsuccessful pregnancies, almost half of all women who become pregnant today are overweight or obese. Common complications of pregnancy in this group of women are preeclampsia and gestational hypertension. These conditions are also observed more frequently in women with excessive weight gain during pregnancy. Preeclampsia is one of the most serious pregnancy complications with an unpredictable course, which in its most severe forms, threatens the life and health of the mother and her baby. The early identification of the risk factors for preeclampsia development, including obesity, allows for the implementation of prophylaxis and a reduction in maternal and fetal complications risk. Additionally, preeclampsia and obesity are the recognized risk factors for developing cardiovascular disease in later life, so prophylaxis and treating obesity are paramount for their prevention. Thus, a proper diet and physical activity might play an essential role in the prophylaxis of preeclampsia in this group of women. Limiting weight gain during pregnancy and modifying the metabolic risk factors with regular physical exercise creates favorable metabolic conditions for pregnancy development and benefits the elements of the pathogenetic sequence for preeclampsia development. In addition, it is inexpensive, readily available and, in the absence of contraindications to its performance, safe for the mother and fetus. However, for this form of prevention to be effective, it should be applied early in pregnancy and, for overweight and obese women, proposed as an essential part of planning pregnancy. This paper aims to present the mechanisms of the development of hypertension in pregnancy in obese women and the importance of exercise in its prevention.

JS-HR-4: PREECLAMPSIA UP TO DATE; WHAT WE SHOULD KNOW FOR MOTHER AND CHILD.

Preeclampsia (PE) is a systemic hypertensive disorder of pregnancy thought to arise from placental maladaptation and subsequent systemic inflammatory processes. PE is associated with significant maternal and fetal mortality with hypertensive disorder of pregnancy accounting for -14% of maternal deaths globally and also with increased maternal risks for chronic diseases in later life. In 2017, the American College of Cardiology/American Heart Association hypertension treatment guidelines identified hypertension as blood pressure (BP) 130/80 mmHg. The reference BP for hypertension during pregnancy as specified in international guidelines is still > 140/90 mmHg. Also, recommended target BP level differs between these guidelines. A large number of studies have been examining the incidence of PE and fetal outcomes according to BP levels to figure out the optimal level for pregnant women. Given only termination of pregnancy has been proved to initiate the resolution of PE once it has developed, prevention of PE is a health care priority. However, the predictive value of BP and other clinical characteristics for PE is relatively low, and therefore, improved method for the prediction of PE and associated adverse outcomes is required. Past history of PE is now widely known to link with major chronic diseases such as hypertension, type 2 diabetes mellitus, dyslipidemia, cardiovascular disease in later life. Since many cardiovascular risk factors are modifiable and related to lifestyle, all women with prior PE should be followed-up by physician even after resolution of PE (eg. hypertension, proteinuria). However, no long-term follow-up strategy for former-PE patient has yet been established. The 2019 Maternal Mortality update from the WHO report indicated the major contribution of PE and eclampsia to worldwide maternal deaths. Further investigation is needed to decrease PE related maternal and fetal deaths and also to reduce maternal risks for chronic diseases in later life. Participation of physicians is necessary to offer appropriate medical care to women with prior PE.

Clusters of lifestyle behaviors associated with atherosclerosis risk factors in children and adolescents with congenital heart disease: Floripa CHild Study.

Secondary cardiovascular disease is the main cause of mortality in congenital heart disease (CHD) patients. The cardiovascular risk could be widely prevented with adherence to a healthy lifestyle, however, clusters of lifestyle behaviors related to atherosclerosis risk factors in children and adolescents with CHD remain unclear. We aimed to describe the clusters of lifestyle behaviors of children and adolescents with CHD and to evaluate their association with atherosclerosis risk factors. Cross-sectional study on 227 children and adolescents with CHD (median age: 10.02 [IQR:7.08-13.02] years). Dietary intake, physical activity (PA), and sedentary behavior (SB) were evaluated. Clusters of lifestyle behaviors were determined using two-step cluster analysis. Atherosclerosis risk factors evaluated include body fat mass, central obesity, blood pressure, lipid parameters, glucose, C-reactive protein, and carotid intima-media thickness (cIMT). Multiple logistic regressions were used. The "unhealthy:high SB+low PA" cluster was associated with elevated body fat mass, central obesity, and elevated cIMT. Furthermore, the "unhealthy:low PA+unhealthy eating habits" cluster was associated with elevated body fat mass, central obesity, and elevated glucose. The unhealthier lifestyle behavior clusters were associated with atherosclerosis risk factors in children and adolescents with CHD. Multidisciplinary strategies to promote healthy behaviors are needed to prevent cardiovascular disease in later life.

Differential affinity chromatography reveals a link between Porphyromonas gingivalis-induced changes in vascular smooth muscle cell differentiation and the type 9 secretion system.

Porphyromonas gingivalis is implicated in adverse pregnancy outcome. We previously demonstrated that intrauterine infection with various strains of P. gingivalis impairs the physiologic remodeling of the uterine spiral arteries (IRSA) during pregnancy, which underlies the major obstetrical syndromes. Women diagnosed with IRSA also have a greater risk for premature cardiovascular disease in later life. The dysregulated plasticity of vascular smooth muscle cells (VSMCs) is present in both IRSA and premature cardiovascular events. We hypothesized that VSMCs could serve as a bait to identify P. gingivalis proteins associated with dysregulated VSMC plasticity as seen in IRSA. We first confirmed that dams with P. gingivalis A7UF-induced IRSA also show perturbed aortic smooth muscle cell (AoSMC) plasticity along with the P. gingivalis colonization of the tissue. The in vitro infection of AoSMCs with IRSA-inducing strain A7UF also perturbed AoSMC plasticity that did not occur with infection by non-IRSA-inducing strain W83. Far-Western blotting with strain W83 and strain A7UF showed a differential binding pattern to the rat aorta and primary rat AoSMCs. The affinity chromatography/pull-down assay combined with mass spectrometry was used to identify P. gingivalis/AoSMC protein interactions specific to IRSA. Membrane proteins with a high binding affinity to AoSMCs were identified in the A7UF pull-down but not in the W83 pull-down, most of which were the outer membrane components of the Type 9 secretion system (T9SS) and T9SS cargo proteins. Additional T9SS cargo proteins were detected in greater abundance in the A7UF pull-down eluate compared to W83. None of the proteins enriched in the W83 eluate were T9SS components nor T9SS cargo proteins despite their presence in the prey preparations used in the pull-down assay. In summary, differential affinity chromatography established that the components of IRSA-inducing P. gingivalis T9SS as well as its cargo directly interact with AoSMCs, which may play a role in the infection-induced dysregulation of VSMC plasticity. The possibility that the T9SS is involved in the microbial manipulation of host cell events important for cell differentiation and tissue remodeling would constitute a new virulence function for this system.

Preterm birth and metabolic implications on later life: A narrative review focused on body composition.

Preterm newborn infants are characterized by low body weight and lower fat mass at birth compared with full-term newborn neonates. Conversely, at term corrected age, body fat mass is more represented in preterm newborn infants, causing a predisposition to developing metabolic syndrome and cardiovascular diseases in later life with a different risk profile in men as compared with women. Postnatal growth is a complex change in anthropometric parameters and body composition. Both quantity and quality of growth are regulated by several factors such as fetal programming, early nutrition, and gut microbiota. Weight gain alone is not an optimal indicator of nutritional status as it does not accurately describe weight quality. The analysis of body composition represents a potentially useful tool to predict later metabolic and cardiovascular risk as it detects the quality of growth by differentiating between fat and lean mass. Longitudinal follow-up of preterm newborn infants could take advantage of body composition analysis in order to identify high-risk patients who apply early preventive strategies. This narrative review aimed to examine the state-of-the-art body composition among born preterm children, with a focus on those in the pre-school age group.

Cardiometabolic Risks in Gestational Diabetes Mellitus: A Mini-Review

Diabetes is one of the most common medical problems encountered in about 3.8% - 41% of pregnancies across the various parts of India. It contributes to maternal morbidity and mortality, especially in developing countries. Insulin resistance and β – cell dysfunction are the characteristics of GDM. Women with GDM had many immediate adverse fetomaternal and neonatal outcomes. In addition to the immediate adverse outcomes, women with GDM also had long-term complications such as dyslipidemia, metabolic syndrome, hypertension, type 2 diabetes, cardiovascular disease in later life. Current evidence suggests that GDM is highly associated with cardiometabolic risks (CMR) during gestation and in post-gestational period. Though the mechanism behind the pathogenesis of CMR in GDM is multifactorial, placental hormones, inflammation, endothelial dysfunction and oxidative stress play a significant role in the pathophysiology of cardiovascular risks in pregnant women with GDM.

Chronic developmental hypoxia alters mitochondrial oxidative capacity and reactive oxygen species production in the fetal rat heart in a sex-dependent manner.

Insufficient oxygen supply (hypoxia) during fetal development leads to cardiac remodeling and a predisposition to cardiovascular disease in later life. Previous work has shown hypoxia causes oxidative stress in the fetal heart and alters the activity and expression of mitochondrial proteins in a sex‐dependent manner. However, the functional effects of these modifications on mitochondrial respiration remain unknown. Furthermore, while maternal antioxidant treatments are emerging as a promising new strategy to protect the hypoxic fetus, whether these treatments convey similar protection to cardiac mitochondria in the male or female fetus has not been investigated. Therefore, using an established rat model, we measured the sex‐dependent effects of gestational hypoxia and maternal melatonin treatment on fetal cardiac mitochondrial respiration, reactive oxygen species (ROS) production, and lipid peroxidation. Pregnant Wistar rats were subjected to normoxia or hypoxia (13% oxygen) during gestational days (GDs) 6–20 (term ~22 days) with or without melatonin treatment (5 µg/ml in maternal drinking water). On GD 20, mitochondrial aerobic respiration and H2O2 production were measured in fetal heart tissue, together with lipid peroxidation and citrate synthase (CS) activity. Gestational hypoxia reduced maternal body weight gain (p < .01) and increased placental weight (p < .05) but had no effect on fetal weight or litter size. Cardiac mitochondria from male but not female fetuses of hypoxic pregnancy had reduced respiratory capacity at Complex II (CII) (p < .05), and an increase in H2O2 production/O2 consumption (p < .05) without any changes in lipid peroxidation. CS activity was also unchanged in both sexes. Despite maternal melatonin treatment increasing maternal and fetal plasma melatonin concentration (p < .001), melatonin treatment had no effect on any of the mitochondrial parameters investigated. To conclude, we show that gestational hypoxia leads to ROS generation from the mitochondrial electron transport chain and affects fetal cardiac mitochondrial respiration in a sex‐dependent manner. We also show that maternal melatonin treatment had no effect on these relationships, which has implications for the development of future therapies for hypoxic pregnancies.

Early life exposure to the Chinese Famine of 1959-1961 is an independent risk factor of adulthood elevated homocysteine, hyperuricemia, high LDL, and hypertension.

Famine exposure in early life was associated with cardiovascular diseases in later life. Whether biochemical surrogates of cardiovascular diseases, such as homocysteine and uric acid, are also associated with famine exposure is unknown so far. Data were derived from a population-based cross-sectional study in the Hunan Province of China, which was heavily affected by the Famine in 1959-1961. A total of 1,150 adults born between 1952and1964 were selected, and 5 cohorts were defined: no exposure, fetal, early childhood, mid-childhood, and late childhood exposure. Compared with the no-famine exposure group, participants exposed to famine in their fetal period had a higher risk of high homocysteine in adulthood with OR of 2.21 (95% CI: 1.01-4.83), whereas famine exposures in early, mid, or late childhood were not significantly associated with high homocysteine in adulthood. Similarly, participants in the fetal famine exposure group had a 1.59-fold higher risk of hyperuricemia (OR = 2.59, 95% CI: 1.07-5.30) and a 2.03-fold higher risk of high low-density lipoprotein cholesterol (LDL) (OR = 0.03, 95% CI: 1.35-6.78) in adulthood compared to those without famine exposure, respectively. We furthermore conducted a meta-analysis including 16 studies regarding the association between fetal famine exposure and adulthood hypertension, including our study. The meta-analysis, including 34,804, subjects showed that fetal famine exposure is associated with a higher risk of adulthood hypertension (OR=1.22, 95% CI: 1.07-1.40). Taken together, fetal famine exposure is related to higher odds of cardio-metabolic risk factors, such as high homocysteine, hyperuricemia, and LDL as well as hypertension, suggesting that undernutrition during fetal life may affect metabolism of homocysteine, uric acid, and LDL in adulthood.