Risultati per: Nelle donne lo stress danneggia la salute dell’intestino

Circulation, Volume 150, Issue Suppl_1, Page A4143303-A4143303, November 12, 2024. Introduction:Preeclampsia is a hypertensive disorder of pregnancy associated with cardiovascular disease. Systemic peripartum microvascular alternations have been implicated in pregnancies complicated by preeclampsia. Whether coronary microvascular dysfunction is a potential mediator of preeclampsia-associated cardiovascular risk is unknown. We aimed to determine whether individuals with a history of preeclampsia have coronary microvascular dysfunction measured by cardiac magnetic resonance imaging (CMR) at least 5 years postpartum.Methods:Women with singleton pregnancies complicated by preeclampsia and a comparator group with uncomplicated, normotensive deliveries were identified and prospectively enrolled to undergo regadenoson stress perfusion CMR (1.5T Signa Artist GE HealthCare) at least 5 years postpartum. Using the dual sequence technique, fully quantitative perfusion values were determined using Fermi deconvolution. Myocardial perfusion reserve (MPR) was calculated as the ratio of stress to rest myocardial blood flow (MBF).Results:Twenty-three subjects (41.0 ± 6 years, 12.7 ± 5 years post-partum) were included. Women with a history of preeclampsia (n=11) were compared to a control group of women with prior normotensive pregnancy (n=12) (Figure 1A). Obesity and diabetes were more common with preeclampsia, but there was no significant difference in the presence of hypertension between the groups (Table 1A). There was no difference in stress MBF. However, preeclampsia was associated with higher rest MBF (1.47 ± 0.54 mL/g/min vs. 1.19 ± 0.29 mL/g/min; p=0.07) and MPR (1.96 ± 0.46 vs 2.66 ± 1.0; p=0.02) compared to normotensive pregnancy (Figure 1). Similarly, corrected MPR remained significantly lower with prior preeclampsia versus uncomplicated pregnancy (2.36 ± 1.0 vs 3.36 ± 1.46; p=0.03).Conclusions:In this study, we observed significantly reduced coronary microvascular function following a pregnancy complicated by preeclampsia at least 5 years postpartum. Heightened cardiovascular risk factors may attenuate this association; however, these observations indicate that systemic microvascular dysfunction in preeclampsia also involves the coronary microcirculation. Further research is needed to better understand the timing and association of these microvascular changes concerning preeclampsia and later heart disease.

Circulation, Volume 150, Issue Suppl_1, Page A4147667-A4147667, November 12, 2024. The co-chaperone BAG3 is critical for protein quality control at the cardiac sarcomere. BAG3 binds to Hsp70 and coordinates the assembly of the CASA (chaperone-assisted selective autophagy) complex, thus supporting proteostasis and cardiomyocyte contractility. BAG3 mutations and/or decreased BAG3 levels are associated with cardiomyopathies, whereas BAG3 overexpression rescues ventricular function after myocardial infarction in mice. Despite BAG3’s promise as a therapeutic target, the mechanisms underlying BAG3 regulation are largely unresolved. Here, we investigate the mechanisms of BAG3 downregulation after stress. We found that BAG3 protein is reduced in human dilated cardiomyopathy hearts compared to non-failing hearts, yet there is an increase inbag3mRNA transcript, suggesting BAG3’s downregulation in heart disease may be controlled post-transcriptionally. To identify these post-transcriptional pathways, we subjected neonatal rat ventricular myocytes (NRVMs) to prolonged hypoxia-reoxygenation (H/R) stress, which recapitulated the decrease in BAG3 levels observed in human heart disease. Notably, disrupting Hsp70 binding to BAG3 in NRVMs via the drug JG-98 decreases BAG3’s half-life by ~90%, suggesting that Hsp70 protects BAG3 from degradation. Loss of Hsp70-mediated protection could contribute to declining BAG3 levels, so we quantified Hsp70 abundance after H/R stress in NRVMs, finding no significant change. We also found that overexpressing inducible Hsp70 did not rescue BAG3 levels. To examine BAG3 regulationin vivo,we subjected wildtype mice to ischemia-reperfusion injury. After 24 hours, male mice had no change in Hsp70 abundance in the left ventricle, whereas Hsp70 was significantly upregulated in female mice. Despite this difference in Hsp70, BAG3 levels were decreased by ~20% in both sexes. Thus, ourin vivoandin vitrodata both suggest that BAG3 downregulation is not caused by loss of Hsp70 binding/protection. Interestingly, the decline in full-length BAG3 (85 kDa) was accompanied by an increase in a BAG3 cleavage product at 74 kDa. We analyzed this product via mass spectrometry, discovering that it lacks a third of the WW domain, which is involved in autophagy. In future experiments, BAG3 cleavage will be explored as a potential mechanism of BAG3 loss. Such mechanisms will provide insight into how to maintain BAG3 levels, and thus cardiac function, during stress.

Circulation, Volume 150, Issue Suppl_1, Page A4141710-A4141710, November 12, 2024. Background:Stress perfusion CMR has excellent diagnostic and prognostic values in assessing chest pain syndromes. AI-guided methods may overcome complex scanning and increase clinical adaptation of stress CMR.Aim:To assess the benefits of AI-guided stress perfusion CMR.Methods:Consecutive patients with stable chest pain underwent stress CMR using either a standard scanning method (SOC) or an AI-assist (AIA) machine learning protocol to automate scan planning, plane prescription, sequence tuning, and image reconstruction. Scan duration, the ratio of scan preparation time over the entire scan duration, and scan quality using a 5-point scale were compared between AIA and SOC. Cox regression models were constructed to associate evidence of ischemia on stress CMR, by either scanning method, with composite endpoints including cardiovascular death, non-fatal MI, unstable angina hospitalization, and late CABG. A second composite endpoint included the performance of additional cardiac imaging tests (stress imaging and CCTA) and invasive coronary procedures after CMR.Results:Among 594 patients (62.8 ± 14 years), 29% underwent stress CMR with AIA. 26% had stress-perfusion ischemia, and 39% had LGE present. AIA stress CMR had lower scan duration (median 44.0 [IQR 40-47] vs. 52.5 min [IQR 46-60]; p

Circulation, Volume 150, Issue Suppl_1, Page A4145955-A4145955, November 12, 2024. Introduction:Cardiovascular problems are the primary cause of morbidity and death in people with diabetes mellitus.The whole nature of diabetic cardiomyopathy(DCM) is yet unknown.In order to investigate the pathogenesis of DCM and find possible treatment targets,animal models have proven invaluable.It has been common practice to create experimental models of type 2 diabetes(T2DM) using streptozotocin (STZ).Finerenone(F) is a selective mineralocorticoid receptor antagonist and reduces cardiovascular and adverse renal outcomes in diabetes.Exenatide(E) has been approved by the FDA to improve glycemic control in T2DM.Aim:The aim of this study is to investigate the possible cardiorenal protective effects of potential heart failure and chronic kidney injury associated with T2DM and to assess the potential therapeutic roles of Finerenone and Exenatide.To understand the interactions on cardiorenal outcomes of heart failure and diabetes and to effectively manage these two conditions.Methodology:Wistarmale rats with streptozotocin-induced T2DM were used.Five different groups were established as 1)Control,2)STZ,3)STZ+F,4)STZ+E,5)STZ+F+E groups.During the 21-day experiment, blood glucose concentrations were measured in all animal experimental groups.The kidney, heart tissues, and blood serum were collected. Serum urea and creatinine were exanimated.Total antioxidant status(TAS) and total oxidant status(TOS) were examined from blood serum,kidney,heart tissues by spectrophotometric assays. Kidney, heart tissues and blood IL-6, IL-1β, TNF-α gene expressions were examined by qPCR. Cardiac troponin T(cTnT) and troponin I(cTnI) gene expressions were examined by qPCR.p-STAT3 and p-NRF2 protein expressions in heart tissue were assessed by western blotting.Results:Serum urea and creatinine were significantly lower in STZ+E+F group than control group. TAS were significantly higher in STZ+E+F group than control group in serum,heart and kidney tissues.TOS, IL-1β, IL-6, and TNF-α gene expressions were lower in STZ+E+F groups than control group significantly in serum, heart and kidney tissues.cTnT and cTnI gene expressions and p-STAT3 and p-NRF2 protein expressions were lower in STZ+E+F groups than control group significantly in heart tissues.Conclusion:This study demonstrates the potential beneficial effects of Finerenone and Exenatide on cardiorenal complications in T2DM. Evaluation of these drugs in treatment strategies and further clinical trials are recommended.

Circulation, Volume 150, Issue Suppl_1, Page A4146754-A4146754, November 12, 2024. Background:Dobutamine stress echocardiography (DSE) is a frequently used tool in cardiovascular (CV) risk assessment of liver transplantation (LT) candidates. Its prognostic value compared to traditional cardiac risk stratification remains unclear.Research Question:How does the prognostic value of pre-transplant DSE in LT candidates compare to the revised cardiac risk index (RCRI)?Aim:Compare DSE’s prognostic value to RCRI in LT patients and analyze post-transplant CV outcomes.Methods:This single-center study included adult patients undergoing pre-transplant DSE as part of LT evaluation from 2008-2021. DSE were categorized as positive, negative, or inadequate. Primary outcomes were post-operative ischemic cardiac events and mortality, with secondary outcome of transplant delays from inadequate DSE. Mann-Whitney U and Fischer’s exact tests compared variables; logistic regression assessed RCRI and DSE for 30-day mortality and cardiac events.Results:Of 981 LT candidates, 644 (66%) had pre-transplant DSE with minimum 2-year follow-up. Average age was 57 ± 7 years, with 33% women. Four and eleven patients experienced cardiac events and mortality 1 (p-value 0.50), 0.51 for DSE (p-value 0.82), and 0.52 for RCRI >1 and DSE combined (p-value 0.80) in predicting 30-day mortality and cardiac events.Conclusion:Our study demonstrates limited prognostic value of DSE above RCRI score alone for predicting post-transplant mortality. Inadequate DSE was frequent and extended LT wait times. Further research is necessary to define clinically relevant subgroups and refine CV risk assessment in LT candidates.

Circulation, Volume 150, Issue Suppl_1, Page A4131424-A4131424, November 12, 2024. Introduction:Anomalous aortic origin of a coronary artery (AAOCA) can result in sudden cardiac death in the young and risk stratification is challenging. Though dobutamine stress cardiac MRI (DS-CMR) is feasible in pediatric patients, exercise stress CMR (ES-CMR) has lower rates of adverse events, higher diagnostic accuracy, and the ability to better reflect the physiologic changes occurring with exercise. No studies have evaluated ES-CMR in the pediatric population. We aim to describe our institution’s experience with ES-CMR using supine bicycle ergometry in patients with AAOCA.Methods:We retrospectively reviewed the medical records of AAOCA patients who underwent ES-CMR at our institution between 2011 and 2024 for demographic, clinical presentation, cardiopulmonary exercise test (CPET) and ES-CMR data. The exercise-based portion of the CMR consisted of supine cycle ergometry utilizing a ramp protocol, immediately after which perfusion imaging was performed. We used descriptive statistics for data analysis.Results:Of 38 patients who underwent ES-CMR, the median age was 16 years (range 13-24) and 68% were male. Diagnoses included anomalous right coronary artery (N=28), anomalous left coronary artery (N=8), and single coronary artery (N=1 single right, N=1 single left). Median maximal heart rate (HR) during ES-CMR was 160 bpm (range 130-190, median 80% predicted) with a median maximal HR during patients’ most recent CPET of 187 bpm (range 160-203, median 97% predicted). No patients had perfusion defects at rest or with exercise stress, or evidence of myocardial scarring. There were no adverse events.Discussion:We demonstrate for the first time the use of ES-CMR in a cohort of pediatric and young adult patients with AAOCA. ES-CMR can provide a unique modality to assess for ischemia at rest and stress as a means of risk stratification and simulate physiologic changes occurring with exercise stress in a single study. Although maximum heart rates during supine cycle ergometry are lower than those reached during CPET, they are similar to those reached during DS-CMR. ES-CMR can be a helpful and safe diagnostic tool in patients with AAOCA.

Circulation, Volume 150, Issue Suppl_1, Page A4134792-A4134792, November 12, 2024. Background:The cardiac Na+channel NaV1.5 (encoded bySCN5A) governs cardiac inward Na+current (INa) and the fast upstroke and plateau phases of the cardiac action potential. Mutations in NaV1.5 can cause acquired or inherited arrhythmias and conduction diseases, including ~20% of cases of Brugada Syndrome (BrS). Changes in INacan impact Ca2+handling and cardiac excitation-contraction coupling. We have previously shown that SIRT1-mediated deacetylation of NaV1.5 increased INa. Recently, potential mutations (including P114T) in SIRT5, another NAD+-dependent deACYLase in the Sirtuin family localized to mitochondria, were identified in small families with BrS.Hypothesis:Sirt5 dysfunction evokes arrhythmias via Na+and Ca2+mishandling in an oxidative stress-dependent manner in mouse hearts.Aims:To explore the potential role of SIRT5 in BrS using heterologous expression systems and homozygous P114T-Sirt5 knock-in (P114T-KI) mice.Methods:Protein expression and physical interactions were detected by immunoprecipitation and immunoblot. The effects of SIRT5 on Na+current was measured using patch clamp in HEK cells and mouse cardiac myocytes. Confocal microscopy was used to measure reactive oxygen species (ROS) and for Ca2+imaging.Results:Both WT and P114T-SIRT5 co-immunoprecipitate with NaV1.5, but WT increased peak INain HEK cells while P114T did not (Fig A,B). Live-cell staining using DCFDA or mitoSOX showed that P114T-KI hearts had increased basal ROS and were more sensitive to oxidative stress induced by H2O2than WT littermates. P114T-KI hearts had increased Na+/Ca2+exchange protein 1 (NCX1) expression, and Langendorff-perfused hearts displayed abnormal Ca2+handling and arrhythmias (Fig C). Notably, treatment with the mitochondrial ROS scavenger mitotempo mitigated the aberrant Ca2+handling and arrhythmias.Conclusion:These findings suggest that the P114T-SIRT5 causes abnormal Na+and Ca2+handling and arrhythmias in a ROS-dependent manner, highlighting potential mechanisms underlying BrS. This finding may pave the way for the use of SIRT5 or its activators as novel anti-arrhythmic therapies in the future.

Circulation, Volume 150, Issue Suppl_1, Page A4140555-A4140555, November 12, 2024. Background:Psychological stress and poor sleep quality are interrelated and disproportionately affect adults who have multiple risk factors of cardiovascular disease (CVD). Sleep hygiene practices, such as maintaining an optimal household environment and engaging in healthy bedtime behaviors, are essential to sleep health. These practices may also impact psychological stress; however, their relationships remain under-studied. This study aimed to examine the associations among sleep hygiene practices, sleep quality, and psychological stress in adults with multiple CVD risk factors.Methods:Adults diagnosed with hypertension and type 2 diabetes completed an online survey (N = 300). Psychological stress and sleep quality were assessed using the Perceived Stress Scale 4 and the Pittsburgh Sleep Quality Index, respectively. A sleep hygiene instrument was used to examine 8 individual factors focusing on negative household environment (safety, physical comfort, temperature, and light) and poor in-bed behaviors (watching TV, playing video games, using screens, and eating). Multiple regression was employed to examine the association of each sleep hygiene factor with sleep quality and psychological stress. Subsequently, mediation analyses were conducted to examine the mediating role of sleep in the association between the composite sleep hygiene score and psychological stress.Results:Of the sample, 78% reported poor sleep quality and 44% reported high psychological stress. Individual sleep hygiene factors (e.g., unsafe household and eating at bedtime), as well as the composite sleep hygiene score, were significantly associated with poorer sleep quality and higher psychological stress. Sleep quality partially mediated the association between the composite sleep hygiene score and psychological stress (Indirect effect: 0.183; 95% bootstrap confidence interval: 0.057-0.339).Conclusions:The findings showed strong links between sleep hygiene practices, sleep quality, and psychological stress. Although causality cannot be inferred, current evidence suggests that promoting sleep hygiene education and implementing strategies to enhance sleep quality may alleviate psychological burdens in adults with multiple CVD risk factors.

Circulation, Volume 150, Issue Suppl_1, Page A4141274-A4141274, November 12, 2024. Background:Atherosclerosis is the most common cause of cardiovascular death. Oxidative stress is related to the initiation and progression of atherosclerosis. However, how oxidative stress affects the progression of atherosclerosis in vivo has not yet been fully investigated. Non-obstructive general angioscopy (NOGA) can meticulously visualize directly aortic atherosclerosis in vivo. The purpose of this study was to evaluate the relationships between oxidative stress and NOGA-derived aortic plaques.Methods:We investigated 120 consecutive cases with coronary artery disease evaluated for the aorta by NOGA between July 2021 and February 2024. Atherosclerotic lesions of the aorta were screened using NOGA immediately after coronary arteriography. NOGA examination evaluated the counts of ruptured plaques, chandelier signs, intense yellow plaques, and red thrombi in the aorta. Regarding the number of each plaque, we assessed the proportion of aortic findings detected by NOGA at each vertebral level. Derivatives of reactive oxygen metabolites (d-ROMs) levels as indices of reactive oxygen species production were evaluated.Results:The mean age was 66 years, and the median d-ROM value was 289 U.CARR [interquartile range: 251-339]. The d-ROM value was significantly correlated with the proportion of ruptured plaques (r=0.28, p=0.015), but not correlated with the other plaque characteristics. In a multiple linear regression analysis for the proportion of ruptured plaques in the aorta, d-ROMs were one of the independent factors adjusted for age, sex, hypertension, dyslipidemia, and diabetes mellitus (β=0.14, p=0.004).Conclusion:The value of d-ROMs was related to the proportion of ruptured plaques in the aorta, but not to the proportion of the other plaque characteristics. Oxidative stress may help to elucidate the mechanism for the progression of aortic atherosclerosis.

Circulation, Volume 150, Issue Suppl_1, Page A4146930-A4146930, November 12, 2024. Background:Young adulthood (19–39 years) is the life stage of greatest declines in cardiovascular health (CVH). It is hypothesized that this decline may be related to competing demands (e.g., stressors) of this period of the lifecourse such as work and child-rearing. The AHA’s Life’s Essential 8 CVH framework identifies the scored domains (behavioral and clinical factors), as needing to be contextualized by the important construct of psychological health (including stress). However, scarce data are available to assess the relationship between CVH and reported stress – especially among YA.Purpose:The current study aims to be the first to use Cosmos electronic health record (EHR) data to assess the relationship between YA CVH and reported stress in a nationally representative, very large sample of YAs.Methods:Cosmos is a platform hosting de-identified Epic EHR data on >250 million patients. We assessed Cosmos data from May 2022 through April 2024 to identify all YAs with reported stress data (5-point scale from “not at all” to “very much”). We then compared trends of each CVH metric across stress categories.Results:1,397,375 individuals 19 – 39 years of age had reported stress data available. The sample was 62% White, 17% Black, 4% Asian, 12% Hispanic, and 63% female. Generally, stress levels were stable across YA age groups (Figure 1). For lifestyle behavior related domains (physical activity (PA), smoking, and BMI), the prevalence of “poor” CVH scores (worst categorization) increased in YA as reported stress amount increased (Figure 2). Prevalence of “poor” scores in clinical metrics (BP, HbA1c, nonHDL-C) were not associated with stress.Conclusion:In a very large sample of YA, greater reported stress was associated worse CVH for the behavioral domains of PA, smoking and BMI. Interventions aimed at reducing stress in YA may have the added benefit of improving CVH.

Circulation, Volume 150, Issue Suppl_1, Page A4146699-A4146699, November 12, 2024. Background:Growing evidence suggests that blunted blood pressure and heart rate responses to acute psychological stress independently associate with an increased risk of adverse outcomes in individuals with CHD, but assessment of mental stress reactivity in clinical settings is resource intensive. An alternative approach is to passively measure stress physiology at home with wearables, which is easier to translate into clinical practice. We tested the hypothesis that blunted mental-stress hemodynamic reactivity in the lab is associated with digital biomarkers of autonomic inflexibility at home.Methods:We conducted a mental stress test in 239 participants (age < 60 years) with an MI within 8 months. Participants underwent a speech stressor task in front of an audience to induce mental stress, during which blood pressure and heart rate were measured repeatedly during a baseline 15-minute rest period and 5-minute stress challenge. Participants went home with a 7-day Holter monitor to measure autonomic function. We examined vagal autonomic inflexibility with deceleration capacity (DC), a digital biomarker calculated via phase rectified signal averaging of heart rate intervals. We also examined low frequency (LF) heart rate variability (HRV), an indirect measure of baroreceptor sensitivity. We measured mean values from 5-minute windows during sedentary periods only to avoid confounding due to physical activity. We used multivariable linear regression models to adjust for potential confounding due to age, beta-blockers, and sex.Results:The mean age was 52 years, 51% were black, and 36% were women. Lower DC most strongly associated with a blunted change in heart rate during acute mental stress challenge (adjusted p

Circulation, Volume 150, Issue Suppl_1, Page A4143092-A4143092, November 12, 2024. Background:Very high level, lifelong aerobic exercise results in lower ventricular stiffness and left ventricular wall stress (LVWS) LVWS is an important predictor of future heart failure risk. To what degree LVWS changes with various doses of lifelong aerobic exercise is unknown.Objective:The purpose of this study was to determine the impact of lifelong exercise on LVWS.Methods:Seniors (n = 58) who consistently participated in lifelong patterns of exercise training were recruited and categorized into 3 groups: “sedentary” (

Circulation, Volume 150, Issue Suppl_1, Page A4140852-A4140852, November 12, 2024. Introduction:Posttraumatic stress disorder (PTSD) is an independent cardiovascular disease (CVD) risk factor with high prevalence in women, particularly women veterans (WV). While the impact of PTSD on ischemic heart disease (IHD) and stroke has been well established, its impact on a comprehensive set of CVD outcomes has not been studied in WV, a growing population at high risk for CVD in the U.S. The goal of this project was to investigate the impact of PTSD on a comprehensive set of CVD conditions in WV.Methods:National Veterans Health Affairs (VHA) electronic health records were used to identify all women who visited any VAs from 1/1/2000 to 12/31/2019. PTSD and CVD were identified based on International Classification of Disease versions 9 and 10 diagnoses ( 1 inpatient or 2 outpatient encounter documentations). Incident CVD outcomes included first onset of IHD, stroke, cardiomyopathy/heart failure (HF), pulmonary arterial hypertension/pulmonary hypertension (PH), atrial flutter/fibrillation (AF), peripheral arterial disease (PAD), venous thromboembolism (VTE), and aortic stenosis (AS). Propensity score matching and Cox survival analyses were performed to assess associations of PTSD with incident CVD outcomes.Results:We identified 622,312 WV, with 140,210 (22.53%) with PTSD. After 1:1 matching, 202,896 patients were included in the final analysis. WV had a mean age of 39.1 years, and the mean [MOU1] follow-up was 5.72 years. Table 1 reveals the association of PTSD with an incident CVD composite and the different component outcomes individually.Conclusion:In a large sample of WV, we demonstrate significant and clinically relevant associations of PTSD with a comprehensive set of incident CVD outcomes. The potential association with some of the specific outcomes warrant further investigation. Maybe more of a call to action for PTSD screening and treatment to potentially offset CVD risk instead?

Circulation, Volume 150, Issue Suppl_1, Page A4137913-A4137913, November 12, 2024. Background:Cardiac sarcoidosis (CS) was characterized by formation of granulomas in the heart. Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of major cardiovascular adverse events (MACE). Although immunosuppressive therapy is recommended for active CS, there is no established markers for treatment and prognosis.Hypothesis:We hypothesized that the inflammation and oxidative stress in heart were associated with MACE after steroid therapy.Aims:We identified prognostic markers for MACE in patients with CS after steroid therapy.Methods:This study was a prospective observational cohort study. Patients with CS diagnosed according to Japanese criteria were enrolled in this study. Patients with abnormal accumulation of18F-FDG in heart were treated with steroids with standard guideline-recommended protocol.18F-FDG PET were performed after more than 6 months of induction. Urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, and indices of cardiac and renal function were measured. The major outcome was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and radiological relapse with exacerbation of clinical manifestation.Results:Fifty consecutive patients with CS underwent steroid therapy and followed up (median follow-up period of 58 months). 39 of 50 patients underwent 18F-FDG PET/CT more than 6 months after steroid therapy. During the follow-up period, 17 of 39 patients showed MACE, consisting of sVT/SCD (N= 11), hospitalization (N= 2) and radiological relapse (N= 4). A Cox proportional-hazard model showed that the U-8-OHdG and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis revealed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 11.6 ng/mg Cr (AUC 0.913, sensitivity 86.7%, specificity 90.0%) and 4.64 (AUC 0.878, sensitivity 76.5%, specificity 91.0%), respectively (Fig.1). Patients with a U-8-OHdG ≧11.6 ng/mg Cr or SUV max ≧4.64 had a significantly higher MACE risk (P values for U-8-OHdG and SUV max were both 0.001 by Log Rank analysis) (Fig.2). It is noted that U-8-OHdG

Circulation, Volume 150, Issue Suppl_1, Page A4125025-A4125025, November 12, 2024. Background:Chronic stress is associated with cardiovascular disease (CVD) in part through neural mechanisms that potentiate inflammation. Disrupted social connections are associated with higher chronic stress. As such, we hypothesized that: 1) previously married (divorced, separated) individuals have higher major adverse cardiovascular event (MACE) risk compared to married individuals and 2) that greater activation of stress-related neural-immune mechanisms contributes to this relationship.Methods:Participants (N=75,638) enrolled in the Mass General Brigham Biobank were studied. Marital status and MACE were identified using survey data and ICD-10 codes, respectively. A subset (N=1,121) underwent clinical18F-FDG-PET imaging, enabling assessment of stress-related neural activity as the ratio of the amygdala to prefrontal cortex activity (AmygAc). Clinical high-sensitivity C-reactive protein (hs-CRP) levels were assessed in another subset of the cohort (N=10,358). Linear and Cox regression and mediation analyses were used.Results:Among participants (median age 62 years; 53% female), 2,978 subjects developed MACE after Biobank enrollment. Previously married (vs. currently married) individuals had greater MACE risk (HR 1.33 [95% CI: 1.20,1.57], p=

Circulation, Volume 150, Issue Suppl_1, Page A4139600-A4139600, November 12, 2024. Background:Cardiac injury after subarachnoid hemorrhage (SAH) is a well-recognized phenomenon with electrocardiogram (ECG) changes, arrhythmias and myocardial dysfunction. Neurocardiac injury has been commonly reported with increased severity of SAH, however much of the evidence has focused on high grade SAH requiring hemodynamic support or mechanical ventilation. In this study we focused on neurocardiac injury with high grade World Federation of Neurological Surgeons (WFNS) grade 3-5 SAH requiring intensive care management.Methods:Patients admitted to our intensive care unit from 2009-2019 with an WFNS 3-5 aneurysmal SAH with an echocardiogram within 7 days of admission were included in our study. Electrocardiogram, cardiac biomarkers and data regarding mortality and neurological complications were collected retrospectively.Results:A total of 242 patients were included in our study analysis with 11 (5%), 89 (37%), and 142 (59%) had WFNS grade 3, 4 or 5 SAH, respectively. Of the 95 patients that underwent echocardiography in the first week, 38 (40%) had a reduced ejection fraction, which was mild (LVEF 40-52%) in 13 (14%), moderate (LVEF 30-39%) in 14 (15%), and severe (LVEF < 30%) in 11 (12%). Independent predictors of reduced ejection fraction included a lower presenting GCS score (OR 1.2 per one point reduction in (Glasgow Coma Score) GCS, 95% CI 1.0-1.5, p = 0.03), elevated troponin T concentration (OR 6.1, 95% CI 1.2-31.3, p = 0.03) and T wave inversion on ECG (OR 9.1, 95% CI 1.6-52.3, p = 0.01). In patients with reduced ejection fraction, classical apical wall motion abnormality was more prevalent in older populations (median age 64 years (apical) vs 50 years (basal wall motion abnormality) and 52 years (other) p = 0.03). In all wall motion abnormality groups, there was a female predominance. Classic Takotsubo wall motion was associated with an anterior SAH aneurysm location (p = 0.03) and highest proportion of moderate to severe LV dysfunction (p = 0.04). ICU mortality did not differ based on the pattern of wall motion abnormalities.Conclusion:Predictors of neurocardiac injury in high grade SAH include troponin elevation, T wave abnormalities and lower presenting GCS. Aneurysm location was associated with wall motion abnormalities and degree of LV dysfunction. Patients with WFNS 3-5 SAH are at increased risk of neurocardiac injury. ECG changes, cardiac biomarker elevation and aneurysm location can help identify patients who warrant echocardiography.