Cardiovascular Disease In Later Life Research Articles

Altered retinal vasculature in childhood cancer survivors: Data from the German CVSS-study.

Childhood cancer is a risk factor for cardiovascular diseases in later life. Retinal examination allows to non-invasively observe the vasculature of an end-organ. We observe alterations in long-term childhood cancer survivors (CCS). In the Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer-Study, 1002 CCS (23-48 years) having neoplasia prior to 15 years of age were prospectively enrolled in a general and ophthalmologic examination including fundus photography. Central retinal vessel equivalents (arterial: CRAE; venous CRVE) were measured and linear regression analysis was computed to compare CCS to controls from the population-based Gutenberg Health Study (GHS) with adjustment for potential cardiovascular and ophthalmological confounders. Differences in cancer types and treatments were explored. For 837 CCS (45.3% female), CRAE and CRVE were conducted. Both were smaller in CCS previously having leukaemia, central nervous system tumour, neuroblastoma, renal tumour, malignant bone tumour, soft tissue sarcoma and germ cell tumour than in GHS controls. No difference was found for CCS with prior lymphoma. Previous radiotherapy of head or neck was associated with a smaller CRVE. Higher mean arterial blood pressure and intake of antihypertensive medication were associated with smaller CRAE. Retinal vasculature is altered in CCS leading to smaller retinal arteries and veins. Our finding indicates that childhood cancer and its treatment leads to systemic alterations of the microcirculation on both branches of the vasculature system. While the retinal venous vasculature is altered by radiotherapy, the lower vessel width of the arterial branch is associated with arterial hypertension.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts. Integrating childhood obesity GWAS summary statistics with our existing 3D genomic datasets for 57 human cell types, consisting of high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, and RNA-seq, we applied stratified LD score regression and calculated the proportion of genome-wide SNP heritability attributable to cell type-specific features, revealing pancreatic alpha cell enrichment as the most statistically significant. Subsequent chromatin contact-based fine-mapping was carried out for genome-wide significant childhood obesity loci and their linkage disequilibrium proxies to implicate effector genes, yielded the most abundant number of candidate variants and target genes at the BDNF, ADCY3, TMEM18, and FTO loci in skeletal muscle myotubes and the pancreatic beta-cell line, EndoC-BH1. One novel implicated effector gene, ALKAL2 - an inflammation-responsive gene in nerve nociceptors - was observed at the key TMEM18 locus across multiple immune cell types. Interestingly, this observation was also supported through colocalization analysis using expression quantitative trait loci (eQTL) derived from the Genotype-Tissue Expression (GTEx) dataset, supporting an inflammatory and neurologic component to the pathogenesis of childhood obesity. Our comprehensive appraisal of 3D genomic datasets generated in a myriad of different cell types provides genomic insights into pediatric obesity pathogenesis.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts. Integrating childhood obesity GWAS summary statistics with our existing 3D genomic datasets for 57 human cell types, consisting of high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, and RNA-seq, we applied stratified LD score regression and calculated the proportion of genome-wide SNP heritability attributable to cell type-specific features, revealing pancreatic alpha cell enrichment as the most statistically significant. Subsequent chromatin contact-based fine-mapping was carried out for genome-wide significant childhood obesity loci and their linkage disequilibrium proxies to implicate effector genes, yielded the most abundant number of candidate variants and target genes at the BDNF, ADCY3, TMEM18, and FTO loci in skeletal muscle myotubes and the pancreatic beta-cell line, EndoC-BH1. One novel implicated effector gene, ALKAL2 – an inflammation-responsive gene in nerve nociceptors – was observed at the key TMEM18 locus across multiple immune cell types. Interestingly, this observation was also supported through colocalization analysis using expression quantitative trait loci (eQTL) derived from the Genotype-Tissue Expression (GTEx) dataset, supporting an inflammatory and neurologic component to the pathogenesis of childhood obesity. Our comprehensive appraisal of 3D genomic datasets generated in a myriad of different cell types provides genomic insights into pediatric obesity pathogenesis.

Excessive hypercholesterolaemia during pregnancy as a risk factor for endothelial dysfunction in pre-eclampsia.

Pregnancy induces significant changes in the maternal cardiovascular system, and insufficient vascular endothelial adaptations to pregnancy contribute to the development of pregnancy complications such as pre-eclampsia. Pre-eclampsia is not only a major cause of maternal morbidity and mortality, but also a significant risk factor for the development of later-life cardiovascular disease. However, the specific mechanisms underlying the pathophysiology of pre-eclampsia, as well as the mechanisms for an increased susceptibility to cardiovascular disease later in life, are not fully characterized. In this review, we discuss the concept that excessive pregnancy-specific dyslipidaemia, particularly hypercholesterolaemia, is a significant risk factor for the development of pre-eclampsia. We further outline novel potential mechanisms (i.e. oxidized low-density lipoprotein receptor 1 and toll-like receptor 4) underlying endothelial dysfunction induced by excessively high cholesterol levels during pregnancy (in the context of pre-eclampsia), in addition to discussing the overall implications of having had a pregnancy complicated by pre-eclampsia on later-life maternal vascular health. Determining the mechanisms by which excessive, pregnancy-specific dyslipidaemia/hypercholesterolaemia impact maternal endothelial health in pregnancy, and later in life, will create a window of opportunity to diagnose and develop targeted therapy for a susceptible population of women, aiming to ultimately reduce the societal burden of cardiovascular disease.

Life course cumulative PM2.5 exposure since childhood and albuminuria in midlife: a 30-year prospective cohort study

Abstract Background Previous studies have confirmed the adverse effect of ambient fine particulate matter (PM2.5) on kidney and cardiovascular diseases. However, the effects of long-term cumulative PM2.5 exposure on albuminuria, particularly from childhood to middle age, remains uncertain. Purposes We aimed to investigate the association between cumulative PM2.5 exposure and albuminuria across three distinct time frames using data from the 30-year population-based cohort study. Methods Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 1643 children and adolescents were followed with 6 visits over 30 years. The annual mean PM2.5 concentration for the period 1987-2017, at the address of each participant, was obtained from the MERRA-2 and CHAP datasets in China. We assessed cumulative PM2.5 exposure as the area under the curve (AUC) and used the linear regression models to estimate the association between cumulative PM2.5 exposure and urinary albumin-to-creatinine ratio (uACR) in 2017. Results In full adjustment for potential confounders, childhood and life course cumulative PM2.5 exposure was positively associated with uACR in midlife [childhood: β=0.103 (95%CI: 0.003, 0.202); life course: β=0.078 (95%CI: 0.004, 0.153)]. However, the relationship between adulthood cumulative PM2.5 exposure and uACR in middle age was not statistically significant. In addition, the associations of adulthood and life course cumulative PM2.5 exposure with uACR in middle age were only observed in non-smokers [β=0.109 (95% CI: 0.002, 0.216)], but not in smokers. Conclusions Cumulative PM2.5 exposure during childhood and over the life course is associated with higher uACR in midlife, especially for children and non-smokers. Lowering PM2.5 pollution early in life could prevent the development of renal dysfunction and cardiovascular disease in later life.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts. Integrating childhood obesity GWAS summary statistics with our existing 3D genomic datasets for 57 human cell types, consisting of high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, and RNA-seq, we applied stratified LD score regression and calculated the proportion of genome-wide SNP heritability attributable to cell type-specific features, revealing pancreatic alpha cell enrichment as the most statistically significant. Subsequent chromatin contact-based fine-mapping was carried out for genome-wide significant childhood obesity loci and their linkage disequilibrium proxies to implicate effector genes, yielded the most abundant number of candidate variants and target genes at the BDNF, ADCY3, TMEM18 and FTO loci in skeletal muscle myotubes and the pancreatic beta-cell line, EndoC-BH1. One novel implicated effector gene, ALKAL2 - an inflammation-responsive gene in nerve nociceptors - was observed at the key TMEM18 locus across multiple immune cell types. Interestingly, this observation was also supported through colocalization analysis using expression quantitative trait loci (eQTL) derived from the Genotype-Tissue Expression (GTEx) dataset, supporting an inflammatory and neurologic component to the pathogenesis of childhood obesity. Our comprehensive appraisal of 3D genomic datasets generated in a myriad of different cell types provides genomic insights into pediatric obesity pathogenesis.

Elevated Cardiovascular Biomarkers Following Hypertensive Disorder of Pregnancy.

Hypertensive disorder of pregnancy (HDP) is associated with an increased risk for later-life cardiovascular disease (CVD). Whether the HDP pregnancy itself confers risk towards CVD later in life is suggested in several epidemiologic studies. Given this connection and that the HDP exposure itself may play a role, understanding whether markers associated with cardiovascular risk vary based on HDP history in the years following pregnancy may assist with risk stratification and development of targeted interventions. We measured 77 proteins (CVD-associated and inflammatory markers) in n=22 individuals with a history of HDP and n=43 matched controls with no HDP history at a median of 4 years after pregnancy. Several CVD-associated proteins (fibrinogen, fetuin-A, L-selectin, and alpha-1-acid glycoprotein) were significantly elevated, by orders of magnitude, in individuals with a history of HDP compared to normotensive pregnancies (all p<0.0001). In multivariable linear regression models controlling for age, body mass index, chronic hypertension, and diabetes, a history of HDP remained associated with higher levels of CVD-associated proteins (all p<0.0001). We clustered samples based on global patterns of CVD protein expression and found a significant difference in CVD protein expression patterns between post-Normal and post-HDP samples. Conversely, differences in circulating inflammatory markers were largely insignificant or more subtle than that observed with the CVD-associated proteins. Identification of biomarkers associated with CVD in the intervening years after HDP but before evident CVD is critical to understanding post-HDP cardiovascular risk to provide insight for the development of therapeutic interventions that mitigate CVD event risk in this high-risk population.

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.

Postpartum haemorrhage and risk of cardiovascular disease in later life: A population-based record linkage cohort study.

To investigate the association between postpartum haemorrhage (PPH) and subsequent cardiovascular disease. Population-based retrospective cohort study, using record linkage between Aberdeen Maternity and Neonatal Databank (AMND) and Scottish healthcare data sets. Grampian region, Scotland. A cohort of 70 904 women who gave birth after 24 weeks of gestation in the period 1986-2016. We used extended Cox regression models to investigate the association between having had one or more occurrences of PPH in any (first or subsequent) births (exposure) and subsequent cardiovascular disease, adjusted for sociodemographic, medical, and pregnancy and birth-related factors. Cardiovascular disease identified from the prescription of selected cardiovascular medications, hospital discharge records or death from cardiovascular disease. In our cohort of 70 904 women (with 124 795 birth records), 25 177 women (36%) had at least one PPH. Compared with not having a PPH, having at least one PPH was associated with an increased risk of developing cardiovascular disease, as defined above, in the first year after birth (adjusted hazard ratio, aHR 1.96; 95% confidence interval, 95% CI 1.51-2.53; p < 0.001). The association was attenuated over time, but strong evidence of increased risk remained at 2-5 years (aHR 1.19, 95% CI 1.11-1.30, P < 0.001) and at 6-15 years after giving birth (aHR 1.17, 95% CI 1.05-1.30, p = 0.005). Compared with women who have never had a PPH, women who have had at least one episode of PPH are twice as likely to develop cardiovascular disease in the first year after birth, and some increased risk persists for up to 15 years.

The association of female reproductive factors with history of cardiovascular disease: a large cross-sectional study

BackgroundThis study aimed to explore the association of female reproductive factors (age at first birth (AFB), age at last birth (ALB), number of pregnancies, and live births) with history of cardiovascular disease (CVD).MethodsA total of 15,715 women aged 20 years or over from the National Health and Nutrition Examination Surveys from 1999 to 2018 were included in our analysis. Weighted multivariable logistic regression analysis and restricted cubic spline (RCS) model were used to evaluate the association of AFB and ALB with history of CVD in women. Additionally, the relationship between the number of pregnancies, and live births and history of CVD was also explored.ResultsAfter adjusting for potential confounding factors, the RCS plot showed a U-curve relationship between AFB, ALB and history of CVD. Among them, AFB was associated with congestive heart failure (CHF), heart attack, and stroke in a U-shaped curve. Additionally, this U-shaped correlation also exists between ALB and CHF and stroke. However, the number of pregnancies and live births was liner positive associated with history of CVD, including coronary heart disease, CHF, angina pectoris, heart attack, and stroke.ConclusionsWomen with younger or later AFB and ALB have higher odds of CVD in later life. Further study is warranted to verify the underlying mechanisms of this association.

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&lt;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&lt;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&lt;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.