Long-term Cardiovascular Health Research Articles

Vascular Placental Pathology and Cardiac Structure in Stillborn Fetuses.

Adverse pregnancy outcomes, including preterm birth and preeclampsia, are associated with worse cardiovascular outcomes for offspring. Examination of the placenta is important for understanding how the prenatal period shapes long-term cardiovascular health. We sought to investigate the association between placental vascular malperfusion and fetal cardiac structure. Data obtained from the Stillbirth Collaborative Research Network included stillbirths with placental pathology and autopsy. Stillbirths were classified in two ways: based on severity of placental maternal vascular malperfusion (MVM) and based on cause of death (MVM, fetal vascular malperfusion (FVM), or acute infection/controls). Organ weight and heart measures were standardized by gestational age (GA) and compared across groups. We included 329 stillbirths in the analysis by MVM severity and 76 in the analysis by cause of death (COD). While z-scores for most organ weights/heart measures were smaller when COD was attributed to MVM as compared with FVM or controls, heart weight and brain weight z-score did not differ by COD (p>0.05). In analyses accounting for body size, the difference between heart and body weight z-score was -0.05 (SD: 0.53) among those with MVM as a COD and -0.20 (SD: 0.95) among those with severe MVM. Right and left ventricle thicknesses and tricuspid, pulmonary, mitral, and aortic valve circumferences were consistently as expected or larger than expected for GA and body weight. In analysis investigating severity of MVM, those with the most severe MVM had heart measures that were as expected or larger than expected for body weight while those with only mild to moderate MVM had heart measures that were generally small relative to body weight. When assessed as COD or based on severity, MVM was associated with heart measures that were as expected or larger than expected for GA and body weight, indicating that possible heart sparing.

Pre-existing maternal cardiovascular disease and the risk of offspring cardiovascular disease from infancy to early adulthood.

A variety of maternal heart conditions are associated with abnormal placentation and reduced foetal growth. However, their impact on offspring's long-term cardiovascular health is poorly studied. This study aims to investigate the association between intrauterine exposure to pre-existing maternal cardiovascular disease (CVD) and offspring CVD occurring from infancy to early adulthood, using paternal CVD as a negative control. This nationwide cohort study used register data of live singletons without major malformations or congenital heart disease born between 1992 and 2019 in Sweden. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for essential maternal characteristics. Paternal CVD served as a negative control for assessment of unmeasured genetic and environmental confounding. Of the 2 597 786 offspring analysed (49.1% female), 26 471 (1.0%) were born to mothers with pre-existing CVD. During a median follow-up of 14 years (range 1-29 years), 17 382 offspring were diagnosed with CVD. Offspring of mothers with CVD had 2.09 times higher adjusted HR of CVD (95% CI 1.83, 2.39) compared with offspring of mothers without CVD. Compared with maternal CVD, paternal CVD showed an association of smaller magnitude (HR 1.49, 95% CI 1.32, 1.68). Increased hazards of offspring CVD were also found when stratifying maternal CVD into maternal arrhythmia (HR 2.94, 95% CI 2.41, 3.58), vascular (HR 1.59, 95% CI 1.21, 2.10), and structural heart diseases (HR 1.48, 95% CI 1.08, 2.02). Maternal CVD was associated with an increased risk of CVD in offspring during childhood and young adulthood. Paternal comparison suggests that genetic or shared familial factors may not fully explain this association.

The MuCAYAplus study- Influence of physical activity and metabolic parameters on structure and function of the cardiovascular system in young athletes

Exercise has a significant impact on the cardiovascular health of children and adolescents, with alterations in cardiovascular structure and function evident even at an early age. Engagement in regular moderate physical activity (PA) is associated with long-term cardiovascular health benefits and reduced risk of cardiovascular disease and mortality later in life. However, competitive sports often involve training intensities beyond recommended levels for young athletes, potentially leading to adverse cardiovascular outcomes. This emphasizes the importance of early monitoring of the cardiovascular status to prevent detrimental adaptations to intense physical exercise. The MuCAYAplus study (NCT06259617) aims to investigate the yet unclear adaptations to intense exercise in young athletes, focusing on various factors, including cardiovascular health, physical activity, cardiopulmonary performance, body composition, eating habits and biochemical markers.In this longitudinal prospective study, a sample of 250 young competitive athletes (age 10-17) will undergo yearly examinations at the Institute of Preventive Pediatrics at the Technical University of Munich (TUM) over the span of three years. The testing protocol includes anthropometric measurements, basic medical examinations, electrocardiography together with blood pressure and pulse wave analysis, echocardiography, sonography of the carotid artery, blood sampling for laboratory analysis, cardiopulmonary exercise testing on a bicycle ergometer and completion of questionnaires regarding physical activity (MoMo-PAQ) and nutrition.It is not yet fully understood how exercise influences cardiac and vascular remodeling during long-term exercise and how different biochemical and metabolic parameters, body composition and nutrition impact such adaptations. The MuCAYAplus study seeks to address these gaps in knowledge and provide comprehensive evidence on the longitudinal effects of exercise on the cardiovascular system of young athletes.

Deep Inspiration Breath Hold in Left-Sided Breast Radiotherapy: A Balance Between Side Effects and Costs

BackgroundDeep inspiration breath hold (DIBH) is an effective technique for reducing heart exposure during radiotherapy for left-sided breast cancer. Despite its benefits, cost considerations and its impact on workflow remain significant barriers to widespread adoption. ObjectivesThis study aimed to assess the cost-effectiveness of DIBH and compare its operational, financial, and clinical outcomes with free breathing (FB) in breast cancer treatment. MethodsTreatment plans for 100 patients with left-sided breast cancer were generated using both DIBH and FB techniques. Dosimetric data, including the average mean heart dose, were calculated for each technique and used to estimate the cardiotoxicity of radiotherapy. A state-transition microsimulation model based on SCORE2 (Systematic Coronary Risk Evaluation) algorithms projected the effects of DIBH on cardiovascular outcomes and quality-adjusted life-years (QALYs). Costs were calculated from a provider perspective using time-driven activity-based costing, applying a willingness-to-pay threshold of €40,000 for cost-effectiveness assessment. A discrete event simulation model assessed the impacts of DIBH vs FB on throughput and waiting times in the radiotherapy workflow. ResultsIn the base case scenario, DIBH was associated with an absolute risk reduction of 1.72% (95% CI: 1.67%-1.76%) in total cardiovascular events and 0.69% (95% CI: 0.67%-0.72%) in fatal cardiovascular events over 20 years. Additionally, DIBH was estimated to provide an incremental 0.04 QALYs (95% CI: 0.05-0.05) per left-sided breast cancer patient over the same time period. However, DIBH increased treatment times, reducing maximum achievable throughput by 12.48% (95% CI: 12.36%-12.75%) and increasing costs by €617 per left-sided breast cancer patient (95% CI: €615-€619). The incremental cost-effectiveness ratio was €14,023 per QALY. ConclusionsDespite time investments, DIBH is cost-effective in the Belgian population. The growing adoption of DIBH may benefit long-term cardiovascular health in breast cancer survivors.

Pediatric Blood Pressure and Cardiovascular Health in Adulthood.

This review summarizes current knowledge on blood pressure in children and adolescents (youth), with a focus on primary hypertension-the most common form of elevated blood pressure in this demographic. We examine its etiology, progression, and long-term cardiovascular implications. The review covers definitions and recommendations of blood pressure classifications, recent developments in measurement, epidemiological trends, findings from observational and clinical studies, and prevention and treatment, while identifying gaps in understanding and suggesting future research directions. Youth hypertension is an escalating global issue, with regional and national variations in prevalence. While the principles of blood pressure measurement have remained largely consistent, challenges in this age group include a scarcity of automated devices that have passed independent validation for accuracy and a generally limited tolerance for ambulatory blood pressure monitoring. A multifaceted interplay of factors contributes to youth hypertension, impacting long-term cardiovascular health. Recent studies, including meta-analysis and sophisticated life-course modelling, reveal an adverse link between youth and life-course blood pressure and subclinical cardiovascular outcomes later in life. New evidence now provides the strongest evidence yet linking youth blood pressure with clinical cardiovascular events in adulthood. Some clinical trials have expanded our understanding of the safety and efficacy of antihypertensive medications in youth, but this remains an area that requires additional attention, particularly regarding varied screening approaches. This review outlines the potential role of preventing and managing blood pressure in youth to reduce future cardiovascular risk. A global perspective is necessary in formulating blood pressure definitions and strategies, considering the specific needs and circumstances in low- and middle-income countries compared to high-income countries.

Diet quality and cardiometabolic risk factors among breast cancer survivors in the Pathways Study.

11039 Background: Women with breast cancer (BC) have higher risk of developing cardiometabolic conditions compared to women without BC. However, the relationship between healthy eating and onset of cardiometabolic conditions in BC survivors remains unknown. We set out to determine if diet quality at BC diagnosis was related to subsequent development of hypertension, diabetes, and dyslipidemia. Methods: This analysis included 3,415 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive BC (stages I-IV) at Kaiser Permanente Northern California (KPNC) between 2005 and 2013. Food frequency questionnaires were administered at or around the time of BC diagnosis and five diet quality indices (DQI) aligned with healthy eating were evaluated: Dietary Approaches to Stop Hypertension (DASH), a healthy plant-based dietary index (hPDI), 2020 Healthy Eating Index (HEI), American Cancer Society nutrition guidelines (ACS), and the alternate Mediterranean Diet (aMED). Incident hypertension, diabetes, and dyslipidemia were ascertained through electronic health records and participants were followed through first indication of these conditions, disenrollment from KPNC, death, or December 31, 2021. Scores were categorized into ascending quartiles of concordance for each DQI, and multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated. Results: There were 554 (16.2%) incident cases of hypertension, 362 (10.6%) of diabetes, and 652 (19.1%) of dyslipidemia over 39,263 person-years of follow-up. Participants in the highest compared to lowest HEI quartile had lower risks of hypertension (HR=0.70, 95% CI 0.53-0.92, Ptrend<0.01), diabetes (HR=0.56, 95% CI 0.40-0.77, Ptrend<0.001), and dyslipidemia (HR=0.76, 95% CI 0.59-0.99, Ptrend=0.03). Participants in the highest vs lowest hPDI quartile had lower risks of hypertension (HR=0.74, 95% CI 0.55-0.98, Ptrend<0.05) and diabetes (HR=0.65, 95% CI 0.46-0.93, Ptrend=0.02), but not dyslipidemia. Women in the highest vs lowest DASH and ACS quartiles had lower risks of diabetes (DASH:HR=0.56, 95% CI 0.39-0.79, Ptrend<0.001; ACS:HR=0.57, 95% CI 0.40-0.79, Ptrend<0.001), but not hypertension or dyslipidemia. No statistically significant differences for aMED were observed between those in the highest vs lowest quartiles. Overall, HRs were similar across DQIs for hypertension and diabetes, except for aMED, which slightly attenuated for diabetes. Conclusions: Diets concordant with HEI may provide the most overall benefit for preventing cardiometabolic conditions after a BC diagnosis. The benefit of diets aligned with hPDI, DASH, ACS, and aMED appear to vary by cardiometabolic condition. Future analyses will examine how these benefits may be modified by BC treatments. Consuming a healthful diet should be recommended to BC survivors for long-term cardiovascular health.

Invited Commentary: Raising a High-Pressure Alarm About Pediatric Hypertension.

Hypertension is a common "silent killer" in adult medicine, but epidemiologic estimates of elevated blood pressure in children and adolescents are challenged by under-diagnosis and resultant low utilization of relevant administrative or billing codes. In the article by Horgan et al (Am J Epidemiol 2024), children and adolescents with hypertension and elevated blood pressure were identified using direct assessment of blood pressure measurements available in the electronic health record from both inpatient and outpatient visits ("clinical cohort") in comparison to diagnosis codes ("claims-based cohort"). The study population included 3.75 million pediatric healthcare visits available in the US Food and Drug Administration's Sentinel System. While the study applied a relatively novel methodology to interrogate available clinical data within the EHR to better understand the prevalence of pediatric hypertension and raised concern for a higher occurrence of hypertension among children and adolescents than previously realized using claims codes, the utility of the prevalence estimates may be limited by the potential for misclassification bias inherent in EHR data. However, these data raise important concerns about relaying solely on ICD-9-CM/ICD-10-CM codes to quantify the epidemiology of pediatric hypertension and highlight opportunities to address elevated blood pressure in children that could improve long-term cardiovascular health.

Vegetarianism and Cardiovascular Health

The impact of dietary choices on cardiovascular health has garnered significant attention, and vegetarianism has emerged as a dietary pattern of particular interest in this research field. A recent body of research suggests that adopting a vegetarian diet may potentially reduce the risk of cardiovascular diseases, however, this relationship still needs to be clarified. The present study aimed to identify the differences in 10-year cardiovascular risk (CVR) and its associated factors between Vegetarians (VG) and Omnivores (OM). This cross-sectional design analysis involved 110 participants (both sexes, mean age of 49 yo) including 55 OM and 55 VG. Metabolic markers were measured from capillary blood sampling (LINX DUO, Menarini), and 10-year CVR was calculated through SCORE2. No statistically significant differences between the two dietary patterns analyzed were found for 10-year CVR. However, a slight tendency towards a higher CVR in OM was observed (OM: 3.16% versus VG: 2.60%; t = 0.970; p = 0.334). The OM population also showed statistically higher values of total cholesterol (OM: 199.00 mg/dL versus VG: 172.00 mg/dL), c-LDL (OM: 117.87 mg/dL versus VG: 99.85 mg/dL), and non-HDL cholesterol (OM: 138.00 mg/dL versus VG: 116.00 mg/dL), compared to VG. These factors are all related to the increased risk of developing cardiovascular events (both fatal and non-fatal) at 10 years. The consumption of sweets, sugar-sweetened beverages (SSB), and fast food proved to be a risk factor for a high-risk SCORE2 for cardiovascular events at 10 years in 1.6%, 2.6%, and 2.1%, respectively. On the other hand, the consumption of vegetables (1%) and fruit (0.3%), as well as high adherence to the Mediterranean diet (MedDiet) in OM (41%) and a high quality diet in VG (13.9%) proved to be protective factors against a high-risk SCORE2 for cardiovascular events at 10 years. In conclusion, this study revealed intriguing insights into the complex relationship between dietary patterns, metabolic markers, and 10-year CVR. These results suggest that 10-year CVR is influenced by the quality of the diet (as no differences were observed for lifestyle variables such as smoking status and physical activity), and not by the dietary pattern alone. It is important to note that the intake of sweets, SSB, fast food, and an unhealthy diet appear to increase the risk of cardiovascular diseases rather than the dietary pattern followed (Mediterranean or Vegetarian). These findings underscore the significance of individual dietary components in shaping long-term cardiovascular health and emphasize the need for further research to refine dietary recommendations and enhance cardiovascular outcomes. This research was funded by national funds through FCT - Foundation for Science and Technology, I.P. (Portugal), under the [UIDB/04567/2020] and [UIDP/ 04567/2020] projects, and by COFAC/ILIND—Cooperativa De Formação e Animação Cultural CRL/Instituto Lusófono de Investigação e Desenvolvimento (grant COFAC/ILIND/CBIOS/2/2021). R.M. is funded by the FCT - Foundation for Science and Technology, I.P. (Portugal) Scientific Employment Stimulus contract [reference number CEEC/04567/CBIOS/2020]. C.F-P. is funded by the FCT - Foundation for Science and Technology, I.P. (Portugal) Scientific Employment Stimulus contract [reference number CEEC/CBIOS/NUT/2018]. 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.

Impact of hypertensive disorders of pregnancy and gestational diabetes mellitus on offspring cardiovascular health in early adolescence

Adverse pregnancy outcomes, including hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), influence maternal cardiovascular heath (CVH) long after pregnancy, but their relationship to offspring CVH following in utero exposure remains uncertain. To examine associations of HDP or GDM with offspring CVH in early adolescence. This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study from 2000 to 2006 and the HAPO Follow-Up Study from 2013 to 2016. This analysis included 3,317 mother-child dyads from 10 field centers, comprising 70.8% of HAPO Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures were having any HDP or GDM compared with not having HDP or GDM, respectively (reference). The outcome was offspring CVH at ages 10 to 14 years, based on four metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The outcome was primarily defined as having at least one CVH metric that was non-ideal versus all ideal (reference), and secondarily as the number of non-ideal CVH metrics: at least one intermediate metric, one poor metric, or at least two poor metrics versus all ideal (reference). Modified Poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. Among 3,317 maternal-child dyads, the median (IQR) ages were 30.4 (25.6, 33.9) years for pregnant individuals and 11.6 (10.9, 12.3) years for children. During pregnancy, 10.4% of individuals developed HDP and 14.6% developed GDM. At follow-up, 55.5% of offspring had at least one non-ideal CVH metric. In adjusted models, having HDP (aRR 1.14; 95% CI 1.04, 1.25) or having GDM (aRR 1.10; 95% CI 1.02, 1.19) was associated with greater risk that offspring developed less-than-ideal CVH at ages 10 to 14 years. The above associations strengthened in magnitude as the severity of adverse CVH metrics increased (i.e., with the outcome measured as >1 intermediate, 1 poor, and >2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. In this multi-national prospective cohort, pregnant individuals who experienced either HDP and GDM were at significantly increased risk of having offspring with worse CVH in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Lipid-Lowering Therapy after Acute Coronary Syndrome.

Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like "lower is better" and "strike early and strong" should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence.

Blood pressure and lipid profiles in children born after ART with frozen embryo transfer.

Are blood pressure (BP) and lipid profiles different between children conceived after ART with frozen embryo transfer (FET), fresh embryo transfer (fresh-ET), and natural conception (NC)? Girls conceived after FET had significantly higher systolic BP and heart rate compared with girls born after fresh-ET; boys conceived after FET had a slightly more favourable lipid profile compared with boys born after fresh-ET and NC. Children conceived after ART with FET are more often born large for gestational age (LGA). LGA in general increases the risk of obesity, diabetes, and cardiovascular disease later in life. Studies on mice and humans on the whole ART population have raised concerns about premature vascular ageing and higher BP. The cardiovascular health of children born after FET is scarcely explored and the results are diverging. This study was part of the cohort study 'Health in Childhood following Assisted Reproductive Technology' (HiCART), which included 606 singletons (292 boys) born between December 2009 and December 2013: 200 children were conceived after FET; 203 children were conceived after fresh-ET; and 203 children were conceived naturally and matched for birth year and sex. The study period lasted from January 2019 to September 2021. The included children were 7-10 years of age at examination and underwent a clinical examination with anthropometric measurements, pubertal staging, and BP measurement. Additionally, a fasting blood sample was collected and analysed for cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides. Systolic and diastolic BP were converted to standard deviation scores (SDS) using an appropriate reference and accounting for height (SDS) of the child. The three study groups were compared pairwise using a univariate linear regression model. Mean differences were adjusted for confounders using multiple linear regression analyses. Girls and boys conceived after FET had significantly higher birthweight (SDS) compared with naturally conceived peers (mean difference: girls: 0.35, 95% CI (0.06-0.64), boys: 0.35, 95% CI (0.03-0.68)). Girls conceived after FET had significantly higher systolic BP (SDS) and heart rate compared with girls conceived after fresh-ET (adjusted mean difference: systolic BP (SDS): 0.25 SDS, 95% CI (0.03-0.47), heart rate: 4.53, 95% CI (0.94-8.13)). Regarding lipid profile, no significant differences were found between the three groups of girls. For the boys, no significant differences were found for BP and heart rate. Lipid profiles were more favourable in boys born after FET compared with both boys conceived after fresh-ET and NC. All outcomes were adjusted for parity, maternal BMI at early pregnancy, smoking during pregnancy, educational level, birthweight, breastfeeding, child age at examination, and onset of puberty. The participation rate varied from 18 to 42% in the three groups, and therefore selection bias cannot be excluded. However, extensive non-participant analyses were performed that showed almost no differences in background characteristics between participants and non-participants in the three groups, making selection bias less likely. The higher birthweight in children conceived after FET was associated with increased systolic BP (SDS) and heart rate in girls conceived after FET compared with fresh-ET. This may be an early indicator of compromised long-term cardiovascular health in this group. The study was not powered to investigate these outcomes and further studies are therefore warranted to confirm the findings. The study was funded by the Novo Nordisk Foundation (grant number: NNF18OC0034092, NFF19OC0054340) and Rigshospitalets Forskningsfond. The authors have no conflicts of interest to declare. ClinicalTrials.gov identifier: NCT03719703.

Evidence for hypoxia-induced dysregulated cholesterol homeostasis in preeclampsia: Insights into the mechanisms from human placental cells and tissues.

Preeclampsia (PE) poses a considerable risk to the long-term cardiovascular health of both mothers and their offspring due to a hypoxic environment in the placenta leading to reduced fetal oxygen supply. Cholesterol is vital for fetal development by influencing placental function. Recent findings suggest an association between hypoxia, disturbed cholesterol homeostasis, and PE. This study investigates the influence of hypoxia on placental cholesterol homeostasis. Using primary human trophoblast cells and placentae from women with PE, various aspects of cholesterol homeostasis were examined under hypoxic and hypoxia/reoxygenation (H/R) conditions. Under hypoxia and H/R, intracellular total and non-esterified cholesterol levels were significantly increased. This coincided with an upregulation of HMG-CoA-reductase and HMG-CoA-synthase (key genes regulating cholesterol biosynthesis), and a decrease in acetyl-CoA-acetyltransferase-1 (ACAT1), which mediates cholesterol esterification. Hypoxia and H/R also increased the intracellular levels of reactive oxygen species and elevated the expression of hypoxia-inducible factor (HIF)-2α and sterol-regulatory-element-binding-protein (SREBP) transcription factors. Additionally, exposure of trophoblasts to hypoxia and H/R resulted in enhanced cholesterol efflux to maternal and fetal serum. This was accompanied by an increased expression of proteins involved in cholesterol transport such as the scavenger receptor class B type I (SR-BI) and the ATP-binding cassette transporter G1 (ABCG1). Despite these metabolic alterations, mitogen-activated-protein-kinase (MAPK) signaling, a key regulator of cholesterol homeostasis, was largely unaffected. Our findings indicate dysregulation of cholesterol homeostasis at multiple metabolic points in both the trophoblast hypoxia model and placentae from women with PE. The increased cholesterol efflux and intracellular accumulation of non-esterified cholesterol may have critical implications for both the mother and the fetus during pregnancy, potentially contributing to an elevated cardiovascular risk later in life.

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

Body mass index and weight gain in pregnancy and cardiovascular health in middle age: A cohort study.

To examine associations between body mass index (BMI) in early pregnancy and gestational weight gain (GWG) with cardiovascular health in middle age using the 'Life's Essential 8' (LE8) concept of the American Heart Association (AHA). Population-based cohort study. Swedish CardioPulmonary bioImage Study (SCAPIS). A total of 8871 women from SCAPIS were included. Information on cardiovascular health in middle age was collected from SCAPIS and linked to pregnancy weight data obtained from the Swedish Medical Birth Register, with an average follow-up time of 24.5 years. An LE8 score between 0 and 100 was determined, where a score under 60 points was defined as poor cardiovascular health. Binary logistic regression and restricted cubic splines were used. Cardiovascular health according to LE8 in middle age. The odds of having poor cardiovascular health in middle age were significantly higher in women who had overweight (adjusted odds ratio, aOR 3.30, 95% CI 2.82-3.88) or obesity (aOR 7.63, 95% CI 5.86-9.94), compared with women classified as being of normal weight in pregnancy. Higher odds were also found for excessive GWG (aOR 1.31, 95% CI 1.09-1.57), compared with women who gained weight within the recommendations. A high BMI in early pregnancy and excessive GWG were associated with greater odds of poor cardiovascular health in middle age. Although further studies are needed, our results highlight pregnancy as an important period to support long-term cardiovascular health.

Rationale and design of the Children's Oncology Group study AAML1831 integrated cardiac substudies in pediatric acute myeloid leukemia therapy.

Pediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline exposure. Early left ventricular systolic dysfunction (LVSD) compromises anthracycline delivery and is associated with inferior event-free and overall survival in de novo pediatric AML. Thus, effective cardioprotective strategies and cardiotoxicity risk predictors are critical to optimize cancer therapy delivery and enable early interventions to prevent progressive LVSD. While dexrazoxane-based cardioprotection reduces short-term cardiotoxicity without compromising cancer survival, liposomal anthracycline formulations have the potential to mitigate cardiotoxicity while improving antitumor efficacy. This overview summarizes the rationale and methodology of cardiac substudies within AAML1831, a randomized Children's Oncology Group Phase 3 study of CPX-351, a liposomal formulation of daunorubicin and cytarabine, in comparison with standard daunorubicin/cytarabine with dexrazoxane in the treatment of de novo pediatric AML. Children (age <22 years) with newly diagnosed AML were enrolled and randomized to CPX-351-containing induction 1 and 2 (Arm A) or standard daunorubicin and dexrazoxane-containing induction (Arm B). Embedded cardiac correlative studies aim to compare the efficacy of this liposomal anthracycline formulation to dexrazoxane for primary prevention of cardiotoxicity by detailed core lab analysis of standardized echocardiograms and serial cardiac biomarkers throughout AML therapy and in follow-up. In addition, AAML1831 will assess the ability of early changes in sensitive echo indices (e.g., global longitudinal strain) and cardiac biomarkers (e.g., troponin and natriuretic peptides) to predict subsequent LVSD. Finally, AAML1831 establishes expert consensus-based strategies in cardiac monitoring and anthracycline dose modification to balance the potentially competing priorities of cardiotoxicity reduction with optimal leukemia therapy. This study will inform diagnostic, prognostic, preventative, and treatment strategies regarding cardiotoxicity during pediatric AML therapy. Together, these measures have the potential to improve leukemia-free and overall survival and long-term cardiovascular health in children with AML. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04293562.

Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance

Nephron endowment at birth impacts long-term renal and cardiovascular health, and it is contingent on the nephron progenitor cell (NPC) pool. Glycolysis modulation is essential for determining NPC fate, but the underlying mechanism is unclear. Combining RNA sequencing and quantitative proteomics we identify 267 genes commonly targeted by Wnt activation or glycolysis inhibition in NPCs. Several of the impacted pathways converge at Acetyl-CoA, a co-product of glucose metabolism. Notably, glycolysis inhibition downregulates key genes of the Mevalonate/cholesterol pathway and stimulates NPC differentiation. Sodium acetate supplementation rescues glycolysis inhibition effects and favors NPC maintenance without hindering nephrogenesis. Six2Cre-mediated removal of ATP-citrate lyase (Acly), an enzyme that converts citrate to acetyl-CoA, leads to NPC pool depletion, glomeruli count reduction, and increases Wnt4 expression at birth. Sodium acetate supplementation counters the effects of Acly deletion on cap-mesenchyme. Our findings show a pivotal role of acetyl-CoA metabolism in kidney development and uncover new avenues for manipulating nephrogenesis and preventing adult kidney disease.

Abstract 17170: Association of Plasma Homocysteine Levels in Cancer Survivors - Data From Framingham Heart Study Offspring Cohort

Introduction: Cancer survivors experience a high prevalence of vascular remodeling from their anti-cancer therapies, which can lead to arterial stiffness. High plasma homocysteine (Hcy) is associated with increased cardiovascular disease risk via its role in decreasing nitric oxide bioavailability and impairing vascular function. However, there is limited work on its role in cancer survivorship. We, therefore, hypothesized that survivors of breast, gastrointestinal, and prostate cancer with elevated plasma Hcy values have higher arterial stiffness and lower endothelial function compared to those with low plasma Hcy. Methods: We evaluated cardiovascular disease-free cancer survivors in the Framingham Heart Study Offspring Cohort (n=196, 66±8 years old, 55.1% women, 26.4±1.2 years from cancer diagnosis, Range: [23.8 - 29.6 years]) with plasma Hcy measurements. The cohort median plasma Hcy was used to define low (&lt;8.16 μmol/L) and high Hcy (≥8.16 μmol/L) groups. Arterial stiffness was assessed via carotid-femoral pulse wave velocity (cfPWV). Peripheral vascular endothelial function was assessed via endothelium-dependent brachial artery flow-mediated dilation (FMD). Differences in cfPWV, FMD, and cardiovascular risk factors were assessed via independent sample t-test or chi-square test. Differences in cfPWV and FMD were further assessed via one-way ANCOVA with age, sex, and cardiovascular medications included as covariates. Results: cfPWV was significantly higher in the high Hcy (9.9±1.5m/s) vs. low Hcy group (8.5±1.9m/s, p=0.005); however, there were no differences in FMD between groups (2.4±1.7 vs. 2.7±2.0%, p=0.42). After controlling for our covariates, cfPWV was still significantly higher in the high Hcy group (Mean[95% CI]): (9.8[9.0-10.61]) compared to the low Hcy group (8.5[8-9.1]) (p=0.015). Conclusions: Our findings suggest an association between elevated Hcy and an increase in arterial stiffness in cancer survivors. This supports the potential adverse consequences of vascular stiffening following cancer diagnosis and treatment which could have long-term cardiovascular health implications.

Improving the screening process for obstructive sleep apnea in the primary care setting.

There is a high prevalence of obstructive sleep apnea (OSA) in the primary care setting that is underdiagnosed and underreported in 75-80% of the population. If untreated, OSA has implications for long-term cardiovascular, cerebrovascular, and metabolic health. At a primary care clinic in New Jersey, patients at high risk for OSA were not being routinely screened for the condition. This project intended to address the administration of the STOP-Bang Questionnaire among asymptomatic high-risk patient populations with hypertension and/or obesity. In addition to determining each participant's level of risk for OSA, and in turn, facilitating referrals and diagnostic testing per a provider's discretion. The STOP-Bang Questionnaire, a validated screening tool for OSA, was implemented in a primary care practice to measure levels of risk for OSA among eligible participants. A total of 32 out of the 100 patients assessed were identified as high risk for OSA. After screening, 36 participants were referred for confirmatory testing. The STOP-Bang Questionnaire, a validated screening tool for OSA, is recommended for all asymptomatic high-risk patients, specifically for those with obesity and/or hypertension, at least annually. The use of a screening tool evaluates a level of risk, promotes detection of disease in the primary stages, delays disease progression, and improves treatment initiatives.

Early Childhood Education and Midlife Ideal Cardiovascular Health in a Prospective Urban Cohort

This cohort study assesses whether preschool is associated with long-term cardiovascular health as measured by the American Heart Association’s Ideal Cardiovascular Health Index.

Non-Invasive Approaches in Interventional Cardiology for Addressing Cardiovascular Disease Burden in Low-Income Countries.

Interventional cardiology has traditionally been associated with invasive procedures such as angioplasty and stenting. However, there is a growing recognition of the importance of non-invasive strategies in the field of interventional cardiology. This scientific article explores the role of non-invasive interventions, including lifestyle modifications, patient education, and comprehensive management approaches, in preventing and managing cardiovascular disease. By empowering patients and focusing on holistic care, these non-invasive strategies have the potential to significantly improve patient outcomes and reduce the burden of cardiovascular disease. This article highlights the various non-invasive interventions, their mechanisms of action, and their impact on patient well-being and long-term cardiovascular health. Additionally, it discusses the challenges and opportunities associated with implementing these strategies in clinical practice, emphasizing the importance of a multidisciplinary approach and patient-centered care. Through a comprehensive understanding of non-invasive strategies, interventional cardiologists can optimize patient care and contribute to the prevention and management of cardiovascular disease.