Adult Cardiovascular Disease Research Articles

Mendelian randomization provides evidence for a causal effect of serum insulin-like growth factor family concentration on risk of atrial fibrillation.

Atrial fibrillation (AF) is one of the most common persistent arrhythmias among adult cardiovascular diseases. It is important to identify potential risk factors for AF. Members of the insulin-like growth factor (IGF) family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases, and previous population-based studies indicate associations between IGF family members and AF. However, the causal effects of IGF family members in AF have not been evaluated. In the current study two-sample Mendelian Randomization (MR) was used to assess genetic relationships between IGF family members and AF. MR was performed based on genome-wide association study (GWAS) datasets, and concentration levels of 14 IGF family members were retrieved. An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations. A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects. Two-sample MR packages were used to perform MR analysis in R. MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods were used. In two-sample MR assessments there were lower levels of circulating IGF binding protein 3 in both WM [odds ratio (OR) 0.964, 95% confidence interval (CI) 0.940-0.960, P = 0.006] and IVW (OR 0.968, 95%CI: 0.947-0.987, P = 0.001) analyses. Higher serum levels of IGF2 receptor were associated with AF (OR 1.045, 95%CI: 1.016-1.076, P = 0.039). In reverse MR analysis conducted to investigate casual effects, elevated levels of circulating CYR61 were associated with AF (OR 1.060, 95%CI: 1.005-1.119, P = 0.031). The results of the present study provide novel insights into the pathogenesis of AF, and the implications of serum IGF family member concentrations when assessing the risk of AF. The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF. Further observational and experimental studies are critically needed.

Association between Tonsillectomy and Cardiovascular Diseases in Adults.

This study aimed to evaluate the association between tonsillectomy and cardiovascular diseases (CVDs) in the Korean adult population. Using data from the 2002-2015 Korean National Health Insurance Service-Health Screening Cohort, a total of 1082 participants aged 40 years or older who had undergone tonsillectomy were matched with 4328 control individuals for age, sex, income, and region of residence. We evaluated the incidence of CVDs in both the tonsillectomy and control groups and calculated the hazard ratios (HRs) of stroke, ischemic heart disease (IHD), and heart failure (HF) for participants who underwent tonsillectomy using a stratified Cox proportional hazard model. The incidence rates of stroke (81.3 vs. 46.6 per 10,000 person-years) and IHD (112.3 vs. 64.9 per 10,000 person-years) were significantly higher in patients who had undergone tonsillectomy than in the control group. After adjustment, the tonsillectomy group exhibited a 1.78-fold and 1.60-fold higher occurrence of stroke (CI = 1.32-2.42, p < 0.001) and IHD (CI = 1.24-2.08, p < 0.001), respectively, compared to the control group. However, there was no significant difference in the incidence rate of tonsillectomy and control groups (11.1 vs. 6.1 per 10,000 person-years). The HR of HF did not differ significantly between the tonsillectomy and control groups in the adjusted model (p = 0.513). We identified a significant relationship between a history of tonsillectomy and occurrence of stroke/IHD in the Korean adult population.

Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort

BackgroundIn 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort.ResultsWe found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism.ConclusionsOur study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.

Child-to-adult body size change and risk of type 2 diabetes and cardiovascular disease.

Childhood overweight increases the risk of type 2 diabetes and cardiovascular disease in adulthood. However, the impact of childhood leanness on adult obesity and disease risk has been overlooked. We examined the independent and combined influences of child and adult body size on the risk of type 2 diabetes and cardiovascular disease. Data from the UK Biobank on 364,695 individuals of European ancestry and free of type 2 diabetes and cardiovascular disease were divided into nine categories based on their self-reported body size at age 10 and measured BMI in adulthood. After a median follow-up of 12.8 years, 33,460 individuals had developed type 2 diabetes and/or cardiovascular disease. We used Cox regression models to assess the associations of body size categories with disease incidence. Individuals with low body size in childhood and high body size in adulthood had the highest risk of type 2 diabetes (HR 4.73; 95% CI 4.50, 4.99), compared to those with average body size in both childhood and adulthood. This was significantly higher than the risk in those with high body size in both childhood and adulthood (HR 4.05; 95% CI 3.84, 4.26). By contrast, cardiovascular disease risk was determined by adult body size, irrespective of childhood body size. Low body size in childhood exacerbates the risk of type 2 diabetes associated with adult obesity but not the risk of cardiovascular disease. Thus, promoting healthy weight management from childhood to adulthood, among lean children, is crucial.

Protective Effects of Perinatal Resveratrol on Bisphenol A Exposure-Induced Cardiovascular Alterations and Hepatic Steatosis in Adult Offspring Mice: A Histopathological Study

Perinatal bisphenol A (BPA) exposure promotes the risk of cardiovascular diseases in adulthood. Currently, there is a dire need to develop new therapeutic strategies and options to treat the adverse fetal programming consequences of this exposure. The present study explored the protective effects of perinatal resveratrol (Rsv) administration on BPA exposure-induced adverse cardiovascular changes and hepatic steatosis in adult offspring mice. Pregnant apolipoprotein E-deficient mice were exposed to BPA in drinking water (1 μg/mL) or to both BPA (1 μg/mL) and Rsv (oral; 20 mg kg−1 day−1) during the gestation and lactation periods. Tissues from the heart, liver, left kidney, and brachiocephalic artery from adult offspring (20 weeks old) were processed for staining with H and E, Masson’s trichrome, and Verhoeff–van Gieson and subsequent histology analysis. In both female and male mice who received Rsv supplementation, the following changes were observed in the brachiocephalic arterial wall: (a) a reduction in the BPA exposure-induced increased thickness ratio of the tunica intima to tunica media from 1.3 ± 1.1 µm to 0.5 ± 0.37 µm (p = 0.027) and 0.72 ± 0.58 µm to 0.29 ± 0.25 µm (p = 0.038), respectively, (b) a reduction in the number of elastic lamina breaks (p &lt; 0.05), and (c) the prevention of the BPA exposure-induced progression of atherosclerotic lesions. Further, it also reduced the BPA exposure-induced increased left ventricular thickness by 135 µm and 131 µm in female and male offspring, respectively. The BPA exposure-induced hepatic steatosis score was also significantly reduced with Rsv treatment in female offspring mice (p = 0.02). Renal cortical cytoplasmic vacuolation was identified in both BPA and/or Rsv-treated groups. Our findings suggest that Rsv could be a potential protective candidate against perinatal BPA exposure-induced cardiovascular changes and hepatic steatosis.

Predicting adverse outcomes in adults with a community-acquired lower respiratory tract infection: a protocol for the development and validation of two prediction models for (i) all-cause hospitalisation and mortality and (ii) cardiovascular outcomes

BackgroundCommunity-acquired lower respiratory tract infections (LRTI) are common in primary care and patients at particular risk of adverse outcomes, e.g., hospitalisation and mortality, are challenging to identify. LRTIs are also linked to an increased incidence of cardiovascular diseases (CVD) following the initial infection, whereas concurrent CVD might negatively impact overall prognosis in LRTI patients. Accurate risk prediction of adverse outcomes in LRTI patients, while considering the interplay with CVD, can aid general practitioners (GP) in the clinical decision-making process, and may allow for early detection of deterioration. This paper therefore presents the design of the development and external validation of two models for predicting individual risk of all-cause hospitalisation or mortality (model 1) and short-term incidence of CVD (model 2) in adults presenting to primary care with LRTI.MethodsBoth models will be developed using linked routine electronic health records (EHR) data from Dutch primary and secondary care, and the mortality registry. Adults aged ≥ 40 years with a GP-diagnosis of LRTI between 2016 and 2019 are eligible for inclusion. Relevant patient demographics, medical history, medication use, presenting signs and symptoms, and vital and laboratory measurements will be considered as candidate predictors. Outcomes of interest include 30-day all-cause hospitalisation or mortality (model 1) and 90-day CVD (model 2). Multivariable elastic net regression techniques will be used for model development. During the modelling process, the incremental predictive value of CVD for hospitalisation or all-cause mortality (model 1) will also be assessed. The models will be validated through internal-external cross-validation and external validation in an equivalent cohort of primary care LRTI patients.DiscussionImplementation of currently available prediction models for primary care LRTI patients is hampered by limited assessment of model performance. While considering the role of CVD in LRTI prognosis, we aim to develop and externally validate two models that predict clinically relevant outcomes to aid GPs in clinical decision-making. Challenges that we anticipate include the possibility of low event rates and common problems related to the use of EHR data, such as candidate predictor measurement and missingness, how best to retrieve information from free text fields, and potential misclassification of outcome events.

Saturated Fat Intake and the Prevention and Management of Cardiovascular Disease in Adults: An Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guideline.

Cardiovascular disease (CVD) is the leading cause of death in the United States and globally and is largely attributable to atherosclerosis. Evidence indicates that multiple dietary components contribute to the complex causes of CVD and associated events and mortality. Public health authorities and scientific organizations have recommended reduced saturated fatty acid (SFA) intake for decades to promote cardiovascular health, which is linked to favorable impacts on established and emerging atherosclerotic CVD risk factors. Recently, a debate has emerged about whether SFA intake should be reduced for CVD prevention, which has contributed to confusion among health care professionals, including registered dietitian nutritionists (RDNs), and the general public, and necessitates the critical evaluation of the evidence. The objective of this evidence-based nutrition practice guideline is to provide health care and public health professionals, particularly RDNs, with evidence-based recommendations on how to address SFA intake in adults within an individualized healthy dietary pattern. Moderate evidence supports the reduction of SFA intake for CVD event reduction, low- to moderate-certainty evidence supports prioritization of replacement of SFAs with polyunsaturated fatty acids, and low-certainty evidence supports focusing on reducing the total amount of SFA rather than specific food sources of SFA. Guideline implementation should include consideration of individual preferences; principles of inclusion, diversity, equity, and access; and potential nutritional deficiencies that may occur with reduced SFA intake. Future research is needed to address gaps that were identified and provide high-quality evidence to support stronger future recommendations based on the relationship between SFA and CVD.

Development and Validation of a Risk Prediction Model for Atherosclerotic Cardiovascular Disease in Japanese Adults: The Hisayama Study.

Development and Validation of a Risk Prediction Model for Atherosclerotic Cardiovascular Disease in Japanese Adults: The Hisayama Study.

Unseating the Sedentary Threat: A Vital Strategy for Curbing Cardiovascular Disease in Young Adults.

Unseating the Sedentary Threat: A Vital Strategy for Curbing Cardiovascular Disease in Young Adults.

Prevalence of Acetylsalicylic Acid Use for Primary Prevention of Cardiovascular Disease Amongst Older Adults From 2017-2021: a Retrospective Cross-Sectional Study.

Three landmark trials on the use of acetylsalicylic acid (ASA) for primary prevention of cardiovascular disease (CVD) were published in 2018. Since then, major clinical practice guidelines have been updated with recommendations against the routine use of ASA for primary CVD prevention, particularly in older adults. However, little is known about the uptake of this evidence into real world practice. The purpose of this study was to assess the change in ASA usage for primary prevention of CVD in older adults between 2017 and 2021. A retrospective cross-sectional study of ASA use for primary prevention in ambulatory older adults without known CVD in an urban Canadian city was conducted. Seven hundred and fifty-six participants were included. The mean age was 78.9 years (standard deviation 7.9) and 64.8% were female. One hundred and thirty (17.2%) participants used ASA for primary prevention, including 20.3% in 2017, 17.0% in 2018, 21.8% in 2019, 16.3% in 2020, and 11.0% in 2021 (p = .061). Female sex was associated with lower ASA use (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.68) and hypertension was associated with higher ASA use (OR 2.72, 95% CI 1.73-4.29). Use of ASA for primary CVD prevention in older Canadians decreased between 2017 and 2021, suggesting an uptake of clinical trial data and practice guideline recommendations. Focusing on deprescribing of ASA for primary CVD prevention continues to be warranted, given the risks associated with ASA in this population.

Association Between the Triglyceride-Glucose Index and The Risk of Cardiovascular Disease in Kurdish Adult: Result from RANCD Cohort Study

Background: The triglyceride-glucose (TyG) index, a consistent content for insulin resistance, has been related to cardiovascular disease (CVD). We aimed to perused the relationship between the TyG index and development of CVD in Kurdish adults. Materials and Methods: In this cross-sectional study, data was used from the Ravansar Noncommunicable Diseases (RaNCD) Cohort Study. Subjects with a history of stroke, myocardial infarction, or coronary artery disease, or who were currently receiving medications for these conditions, were classified as CVD patients. Results: The research comprised 9723 individuals overall (51.76% of whom were female, mean age 47.3 ±8.26 year). We found that the TyG index in CVD patients (8.82±0.81) was substantially higher than that in non-CVD patients (P=0.001), and the top quartile of the TyG had significantly more BMI (28.73±4.20), TG (239.45±103.30), and FBS (117.85±50.36) values than the lowest quartiles (P=0.001). The TyG and CVD showed a positive association according to the cohort data. The chances of CVD were 2.54 (95% CI: 2.16-2.98) times higher in the fourth tertile of the TYG index than in the first tertile. After controlling for confounding factors, their association was still significant (OR: 1.58, 95%Ci: 1.35-1.95). The predictive value of the TYG score was 63% for females and 57% for males, according to ROC curve research. Conclusion: According to the findings, risk of cardiovascular disease was linearly correlated with the triglyceride glucose index. Moreover, the TyG may be more accurate predictor of CVD in female.

Impact of Hypomethylating Agents on Cardiovascular Disease Risk Among Patients with Myelodysplastic Syndromes

Introduction: The association between clonal hematopoiesis (CH) and cardiovascular disease (CVD) risk has drawn attention to cardiovascular outcomes in myelodysplastic syndromes (MDS). CVD accounts for 25% of deaths in MDS, potentially via CH-mediated accelerated atherosclerosis from inflammatory vascular responses. We previously demonstrated that MDS was independently associated with increased risk of CVD in older adults from SEER-Medicare. We subsequently hypothesized that treatment with hypomethylating agents (HMA) could reduce CVD risk by ameliorating CH clones and reducing the inflammation. In this study, we aimed to define the impact of HMA on incident cardiovascular events among older adults with MDS. Methods: We identified subjects ≥66 years diagnosed with MDS from 2007 to 2017 in SEER-Medicare. Exclusion criteria including lacking continuous Medicare parts A, B, and D, enrolled in HMO, or incomplete follow-up. Demographics included age, sex, race, rurality, socioeconomic quintile, marital status, and geographic region. Baseline CVD risk factors, defined from ICD-9/10 codes, included hypertension, hyperlipidemia, diabetes, atrial fibrillation, pre-existing cardiac disease, obesity, and smoking. MDS factors, defined using HCPCS codes, ICD-O-3 codes and prescription records, included MDS subtype and histologic risk stratification, transfusion dependence and treatment with hypomethylating agents (HMA), lenalidomide, or erythropoietin-stimulating agents (ESA) as time-varying variables. Incident CVD was defined as new myocardial infarction (MI) and/or ischemic stroke occurring after MDS diagnosis, using published ICD-9/10 algorithms. We controlled for confounding using 2 complementary analytic approaches. First, we assessed the association between HMA use and CVD using propensity score adjusted cause-specific competing risk Cox hazard models with death as competing risk, Second, we used a case-crossover design with conditional logistic regression, in which subjects with CVD served as their own controls, using a 3-month HMA treatment window and a control period 6 months prior to the incident event. Results: We identified a cohort of 15,227 eligible patients with MDS. Of these, 1,125 patients had an MI and/or ischemic stroke within 1 year before MDS diagnoses and were excluded. We analyzed 14,102 MDS patients, with median age 82 years (IQR 77 - 86), who were predominantly male (53.8%), non-Hispanic white (88.6%), and from urban/suburban areas (86.2%). MDS was of low, intermediate, and high histologic risk in 14.7%, 72.8%, and 12.5%, respectively, and 28.6% were transfusion dependent. Pre-existing CVD risk factors at time of MDS diagnosis were present in 12,538 patients, with baseline cardiovascular risk defined as low, intermediate, and high in 11.1%, 32.3%, and 56.6% of the cohort. The cumulative incidences of MI, ischemic stroke and composite CVD events were 11.3%, 10.6% and 20.4%, respectively. The propensity score (PS) conditional probability for being treated with HMA included demographic variables, CVD risk factors, MDS histology and transfusion dependence. Our PS model adequately predicted HMA treatment propensity (AUC 0.76). Cause-specific regression with death as competing risk, adjusted for PS and other MDS-specific treatments (ESA and lenalidomide), showed no significant effect of HMA on the risk of composite CVD events, MI, or ischemic stroke (Table 1). Conditional logistic regression in the case-crossover analysis of 1,907 patients with composite CVD events showed no significant effect of HMA. Results were similar for analysis of patients with MI and ischemic stroke (Table 2). Conclusions: No study has previously investigated the effect of HMA therapy on cardiovascular outcomes in patients with MDS. We demonstrate that HMA therapy is not associated with a significant risk reduction in cardiovascular events among patients with MDS patients from the SEER-Medicare database. These results show that HMA therapy is unlikely to reduce cardiovascular mortality and underscore the need for alternative therapeutic strategies targeting cardiovascular health patients with MDS.

Risk of hypertension in adult patients on antiretroviral therapy: a propensity score matching analysis

Background: Hypertension is a major risk factor that contributes to cardiovascular diseases in adults with HIV infection. Although a relationship exists between antiretroviral therapy (ART) and components of the metabolic syndrome, it is unclear whether HIV or anti retrovirals are explanatory risk factors for hypertension in Persons Living with HIV (PLWH). The present study used propensity-scored-matching (PSM) analysis to estimate ART's average treatment effect (ATT) on blood pressure and hypertension in PLWH. Objective: The present study used PSM analysis to estimate the average treatment effect of ART on blood pressure and hypertension in patients attending the HIV clinic at the Korle-Bu Teaching Hospital (KBTH) in Accra. Methods: A hospital-based comparative cross-sectional study was conducted at the HIV Clinic of the Korle-Bu Teaching Hospital in Accra, Ghana. A simple random sampling technique was used to recruit 59 ART-exposed and 59 ART-naïve study participants. The ATT was estimated using the kernel matching or weighting strategy with a bandwidth of 0.06,and standard errors were bootstrapped with 150 replications. Results: The prevalence of hypertension in the ART-exposed and ART-naive study participants in the final propensity score-matching sample was 42.4% (95% CI, 36.2-48.8) and 17.0% (95% CI, 9.3-28.9) respectively and the estimated ATT was 26.2% (p&lt;0.001) indicating a statistically significant difference between the ART-exposed group and the ART-naive group. The estimated ATT on systolic blood pressure was 12.0 mmHg (95% CI, 5.7-18.3; p&lt;0.001) and that on diastolic blood pressure was 6.1 mmHg (95% CI, 1.3-10.8; p=0.012) Conclusion: A plausible causal link is reported between ART and hypertension. Significant ATT of ART suggests increases in blood pressure values represent a transition from association to causation. This transition could be a significant step in policy formulation in taking preventive action against hypertension and its complications among PLWH.

Outdoor artificial light at night and cardiovascular disease in adults: a Chinese nationwide cohort study

Abstract Background Although the electric light is a significant promotion in the human progress and civilization, its adverse effects of outdoor artificial light at night (ALAN) are being extensively studied. However, the association of outdoor ALAN and cardiovascular disease (CVD) has never been confirmed in large nationwide studies, especially in urban areas with high exposure levels and in rural areas with low exposure levels, respectively. Purpose To explore the association between outdoor ALAN and CVD. Methods This national study enrolled 12,686 adults ≥ 40 years across China. The outdoor ALAN exposure (nW/cm2/sr) with the resolution of the 500 meters around each participant's location was obtained from satellite image data via Visible Infrared Imaging Radiometer Suite day-night band on board the Joint Polarorbiting Satellite System. CVD was defined by a doctor's record of diagnoses, including heart disease and stroke. Poisson regression model and restricted cubic spline models were used to estimate the relationship between outdoor ALAN and CVD in urban and rural areas, respectively. Subgroup analysis was also conducted using Poisson models for each subgroup. Results At a median follow-up of 7 years, 1,732 cases of CVD were identified. The mean age of the participants was 58 years and 49% were males. In urban areas, outdoor ALAN exposure at the highest quartile (Q4) increased the incidence of CVD among participants by 34% compared to those exposure at the lowest quartile (Q1) (incident rate ratio, IRR: 1.34,95% CI: 1.07—1.69, p = 0.01), adjusting for age, sex, BMI, education, smoke ever, alcohol consumption, physical activity and household consumption. In rural areas, compared with those at the Q1 of outdoor ALAN exposure, exposure at the Q4 reduced the incidence of CVD by 17% (IRR: 0.83, 95% CI: 0.70—0.98, p = 0.028) after full adjustment. Dose-response relationship indicated that outdoor ALAN levels were linearly associated with decreased CVD in rural area (p for non-linearity = 0.370), while the association between outdoor ALAN levels and CVD was shown as an inverse "U" shape in urban area (p for non-linearity ≤ 0.001). Subgroup analysis shown that the CVD risk of middle-aged people, people with history of alcohol consumption, or people with low levels of physical activity were susceptible to outdoor ALAN exposure. Conclusions Outdoor ALAN exposure was associated with the risk of CVD, which was heterogeneous with different levels of exposure range. In rural areas with low outdoor ALAN exposure settings, outdoor ALAN exposure was negatively correlated with the risk of developed CVD, while the association was reverse in urban areas with high outdoor ALAN exposure settings. We call for a reduction in the use of high-intensity ALAN and to pay attention to the effects of emotional, psychological, and biological changes associated with outdoor ALAN exposure on cardiovascular health.Figure 1

Influence of birth weight on later life cardiovascular structure, function and disease: unpacking influences from direct genetic effects versus intrauterine programming

Abstract Aims The cardinal risk factors for cardiovascular disease in adulthood are well-recognised. In addition to these, observational studies have suggested that intrauterine and early developmental factors might play a role. However, observational associations are liable to influence by residual confounding and bias. Additionally, observational and genetic studies to date have not been able to isolate the fetal versus maternal influences. Purpose We aim to explore the causal relevance of birth weight on cardiovascular disease and cardiac structure and function using Mendelian randomization (MR), and specifically investigate the role of fetal genetic effects (reflecting the direct causal influence of birth weight) versus maternal genetic effects (reflecting the influence of the intrauterine environment). Methods Uncorrelated (r2&amp;lt;0.001), genome-wide significant (p&amp;lt;5x10-8) SNPs were extracted from genome-wide association study summary statistics for gestational age-adjusted birth weight overall, and after isolating the indirect maternal versus direct fetal genetic effects. Inverse-variance weighted Mendelian randomisation (MR) was utilised for primary analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 15 measures of cardiac structure and function indexed to body surface area. Multivariable MR was utilised to explore potential mediation of effects observed on cardiovascular outcomes by cardiometabolic risk factors. P-values were FDR-adjusted to account for multiple testing. Results Higher genetically-predicted birth weight was associated with higher risk of atrial fibrillation (OR 1.26 [1.15-1.39], p&amp;lt;0.001), but lower risk of coronary artery disease (OR 0/78 [0.71-0.86] p&amp;lt;0.001). These associations were driven predominantly by direct fetal genetic effects. For the association with atrial fibrillation, there was no evidence of mediation through body mass index or height. For the association with coronary artery disease, there was at least partial mediation through systolic blood pressure (Figure 1). Higher genetically-predicted birth weight was associated with a greater chamber volumes, but lower ejection fraction (Figure 2), driven by direct fetal genetic effects. Conclusion The results of this study suggest that lower birthweight is associated with higher risk of coronary artery disease, partly mediated by a higher systolic blood pressure. Conversely, a greater birth weight was associated with higher risk of atrial fibrillation, and this was not mediated by body mass index or height. Higher birth weight was also associated with greater chamber volumes and lower ejection fraction. The associations were in all cases predominantly driven by direct fetal effects, suggesting a causal relevance of birth weight itself, and not of the intrauterine environment, on later life cardiovascular disease.Figure 1Figure 2

Aspirin overuse in primary prevention: nationwide temporal trends in low-dose aspirin therapy for primary prevention of cardiovascular disease in adults with and without diabetes

Abstract Background Aspirin therapy for primary prevention of cardiovascular disease (CVD) is controversial. European Society of Cardiology guideline recommendations have changed in the last decades, and aspirin is currently not recommended in individuals with low/moderate cardiovascular (CV) risk but may be considered in high-risk individuals with diabetes. Purpose We report temporal trends in primary prevention aspirin prescription among individuals with and without diabetes and describe characteristics of incident aspirin users. Methods Using Danish nationwide registries, we identified incident and prevalent aspirin users in a population ≥40 years without CVD, eligible for primary preventive aspirin therapy from 2000 through 2020. Temporal trends in aspirin use with and without diabetes were assessed, as were CV risk factors among incident users. Individuals in Denmark are primarily seen by general practitioners who have a gate-keeper function for secondary hospital-based care. Results A total of 522,680 individuals started aspirin therapy during the study period. The number of incident users peaked in 2002 (39,803 individuals, 1.78% of the eligible population) and was lowest in 2019 (11,898 individuals, 0.49%), with similar trends for subjects with and without diabetes (Figure 1). A large proportion of incident users had no CV risk factors (diabetes, hypertension, hypercholesterolemia, or chronic obstructive pulmonary disease [a proxy for smoking]); however, this proportion decreased from 53.9% in 2000 to 30.9% in 2020 (Figure 2). The number of prevalent aspirin users peaked at 7.7% in 2008 and was 3.3% in 2020. For subjects with diabetes, the peak was observed in 2009 at 38.5% and decreased to 17.1% in 2020. Conclusion Prescription of aspirin for primary prevention of CVD has decreased over the last two decades in individuals both with and without diabetes. However, aspirin appears to be inappropriately prescribed in many primary prevention adults as a large proportion of incident users had no CV risk factors. Efforts to inform appropriate prescription of aspirin are needed, e.g., by improved guidance for general practitioners.Figure 1Figure 2

Associations of built environment characteristic using NEWS questionnaires with major cardiovascular diseases and all-cause mortality

Abstract Background The WHO of 2016 reports that cardiovascular diseases (CVDs) represent the leading cause of death in most countries and China has one of the highest prevalence of CVDs[1-2]. In order to reduce the burden of CVD risk factors, environmental interventions have become increasingly recognized as necessary approaches to health promotion and diseases prevention[3]. Pervious evidence mainly from the western countries, examined the effects of built environment on health (i.e. physical activity, mental health, self-reported health scale and CVD risk factors) , while the potential impact on CVDs has not been fully explored[4]. Thus, the aim of this study is to evaluate the longitudinal relationships between perceived built environment attributes using neighborhood environment walkability scale (NEWS) questionnaire and the CVDs in Chinese adults, to explore the different between urban and rural areas, and to provide a logical foundation for both research and policy making. Methods PURE-China is a prospective cohort study, recruiting participants aged 35–70 years from 115 urban and rural communities in 12 provinces of China between 2005 and 2009[5]. Baseline including NEWS information was collected using standardized questionnaires. Participants without any NEWS data and with baseline CVDs were excluded. The primary outcome is the composite of major CVD events and all-cause mortality. The main exposure variables including land use mix-diversity, land use-access, streets connectivity, infrastructure for walking and cycling, aesthetics, safety from traffic, safety from crime, and community satisfaction. Cox frailty model with random intercepts to account for cluster were used to assess the association between total built environment score/ subscales score and the time to occurrence of events. Based and fully-adjusted model were estimated and presented as HR and 95%CI. Interactions and stratified subgroup analysis were also tested. Results A total of 32,534 PURE participants were included with averaged 51 years old and 59.9% females. During a median follow-up period of 11.7 years (IQR 9.4 – 12.2), we documented 3298 (10.2%) new CVD events and 1639 (5.1%) all cause deaths. Table 1 summarizes based models and adjusted models results. For composite outcomes, higher level of land use access (HR, 1.06; 95%CI, 1.01-1.11), aesthetics (HR, 1.07; 95%CI, 1.02-1.12), safety from crime (HR, 1.06; 95%CI, 1.01-1.10), community satisfaction (HR, 1.04; 95%CI, 1.00-1.09), combined BE metrics (HR, 1.05; 95%CI, 1.01-1.10) were associated with a lower risk of composite outcome in adjusted model. For major CVD events more statistically significant differences were observed. Conclusions and Relevance High level of specific BE characteristics were associated with lower risk of all-cause mortality and CVD in China. Our findings may guide policy makers on how to implement BE measures to easing the burden of CVDs and premature deaths.Table 1

Abstract 12832: Risk of Extreme Wet Climate Conditions and Racial/Ethnic-Specific Cardiovascular Mortality in Southwest United States

Introduction: Coastal regions are highly vulnerable to extreme climate conditions, which are known to have effects on adult cardiovascular disease mortality (CVDM). Racial/ethnic (R/E) minority populations (ie Non-Hispanic (NH) Black) are known to have a greater incidence of CVDM compared to their NH White counterparts. Consequently, there is a need to document associations between climate extremes and R/E-specific CVDM. Hypothesis: Extreme wet conditions associated with CVDM should vary by R/E, where strongest increased risk is expected for minority populations. Methods: Population-based study using sex, age (45-84 years), and R/E-specific (NH White, Black, Asian, &amp; Hispanic/Latino) CVD deaths [ICD-10 (I00-99)] from CDC for Southwest US (California, Arizona, New Mexico) from Jan 1999 to Dec 2020. Climate exposure categories (mild, moderate, extreme dry/wet) were based on Palmer Drought Severity Index (PDSI), which integrates temperature and precipitation. With population estimates, CVDM rates were associated with PSDI categories using negative binomial regression upon adjusting for diabetes, smoking prevalence, sex, trend, month, state, unemployment rate, and air pollution (PM 2.5 ). Results: From 1999-2020, 1,307,418 (67.6% NH White, 16.1% Hispanic, 7.4% NH Asian, 8.9% NH Black) CVD deaths were recorded. CVDM was associated with a significant increased risk during extreme wet events (compared to extreme drought) only among NH Asian (adjusted rate ratio [RR] 1.08; 95% CI 1.06-1.09) and NH White (RR 1.02; 95% CI 1.01-1.025) in Southwest US (Figure). Insignificant interactions were observed between extreme wet and PM2.5 on CVDM by R/E. Conclusions: Extreme wet climate conditions were associated with an increased risk of CVDM among NH Asian and White adults. Both climate extreme events and R/E should be considered as predisposing risk factors for CVDM. Further studies are needed to assess such CVDM risk factors for other susceptible areas in the US.

Abstract 12288: Sex Differences in Cardiac Adaptation to Obesity During Adolescence: A Role of Cardiopulmonary Exercise Testing

Introduction: Heart size is known to increase in obese individuals as a physiological adaptation. Cardiac hypertrophy is also regarded as a risk factor for future adult cardiovascular disease. Sex differences of cardiac adaptation to obesity during adolescence are poorly understood. Hypothesis: Physiological cardiac responses to obesity are different between male and female adolescents. Methods: Anthropometric measurements, left ventricular mass index (LVMI; g/m 2.7 ), and cardiopulmonary exercise testing parameters were analyzed. Peak oxygen consumption (VO2), ventilatory anaerobic threshold (VAT), and submaximal sloop parameters including ΔVO2/Δheart rate (HR) and ΔHR/Δwork rate (WR) were obtained. Data are shown as mean ± standard deviation. * denotes weight-indexed value. Results: Table 1 showed enrolled obese adolescents (19 males and 40 females). ΔVO2/ΔHR and ΔHR/ΔWR are surrogates of stroke volume and HR-dependency, respectively. Males showed significantly higher pVO2, pVO2*, VAT*, ΔVO2/ΔHR, and ΔVO2*/ΔHR but lower ΔHR/ΔWR and ΔHR/ΔWR* than females, suggesting males had higher peak exercise performance, higher stroke volume, and lower HR-dependency than females. Significant correlation was noted between LVMI and VAT* only in males (p = 0.045) and between LVMI and body mass index (BMI) only in females (p = 0.006), suggesting cardiac hypertrophy may not effectively contribute to exercise performance in females (Figure 1). Cardiac hypertrophy assessed by LVMI presented different physiological significance between obese males and females. Conclusions: Cardiac adaptation to obesity occurs differently between males and females during adolescence.

Long-term glucocorticoids in relation to the metabolic syndrome and cardiovascular disease: A systematic review and meta-analysis.

The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. We also performed a meta-analysis on the cross-sectional difference in HairF levels between individuals with versus without CVD. Seven studies were included regarding MetS, sixteen regarding CVD, and one regarding both. Most articles indicated a strong, consistent cross-sectional association of higher HairF and HairE levels with CVD, which was confirmed by our meta-analysis for HairF (eight studies, SMD=0.48, 95% confidence intervals [CIs]: 0.16-0.79, p=0.0095). Moreover, these relationships appear largely independent of standard risk factors. Age seems relevant as the effect seems stronger in younger individuals. Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration.