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

Circulation, Volume 146, Issue Suppl_1, Page A12063-A12063, November 8, 2022. Introduction:Antidepressants, namely selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are efficacious in reducing posttraumatic stress disorder (PTSD) symptoms, but their implications for cardiovascular health are unclear. Although SSRI/SNRI treatment could improve PTSD—thus decreasing cardiovascular risk, antidepressant use has also predicted cardiovascular events. This study examined if antidepressant use was associated with developing ischemic heart disease (IHD) in women veterans with PTSD.Methods:The Veterans Affairs (VA) electronic health record (EHR) database was used to identify women veterans with PTSD who engaged with VA healthcare from 2000-2019. Antidepressant use (documented in the EHR) was categorized as SSRIs, SNRIs, both SSRIs/SNRIs, other, or none (ref). We used Cox regression with time-varying exposure and covariates to estimate effects of antidepressants on risk of incident IHD (angina, MI, CAD). Once a woman was exposed to antidepressants, she was considered exposed until IHD onset or censoring. Age, race, ethnicity, and a range of time-varying risk factors [traditional risk factors (e.g., hypertension), other medical risk factors (e.g., obesity), women-specific risk factors (e.g., preeclampsia), psychiatric risk factors (e.g., depression)], were covariates.Results:The analytic sample comprised 143,324 women without IHD at start of follow-up; mean age was 36.1 years (SD=11.0). Over a median follow-up of 8.6 years, there were 6,633 incident IHD cases. When adjusting for demographics and traditional IHD risk factors, exposure to SNRIs was associated with a 33% greater rate of IHD (95% CI: 1.24-1.43), SSRIs with a 27% greater rate (95% CI: 1.20-1.34), both SSRIs/SNRIs with a 59% greater rate (95% CI: 1.01-2.49), and other antidepressants with a 24% greater rate (95% CI: 1.17-1.31). Associations with SNRIs (HR=1.21, 95% CI: 1.12-1.30), SSRIs (HR=1.15, 95% CI: 1.09-1.22), and other antidepressants (HR=1.19, 95% CI: 1.13-1.26) remained significant in fully adjusted models.Conclusions:Antidepressant use in women veterans with PTSD may exacerbate risk of IHD. Mechanism-focused research and further work in women veterans without PTSD is also needed.

Circulation, Volume 146, Issue Suppl_1, Page A12676-A12676, November 8, 2022. Backgrounds:Psychological stress increases leukocyte accumulation within atherosclerotic lesions and exacerbates plaque vulnerability. However, the stress-induced real-time behavior of immune cells in the atheroma has been poorly definedin vivo. Here, we aim to investigate whether stress stimulates the inflammatory leukocyte dynamics in the atherosclerotic plaques and destabilizes the lesions using customizedin vivocell tracking strategies.Methods and Results:We developed a system and motion reconstruction algorithm that can probe and compensate for respiratory and pulsatile movements. Individual leukocytes near the atherosclerotic plaques were imaged in real-time by adapting a custom-built high-speed intravital microscopy system with multiple fluorescence channels. Stress was achieved by immobilization procedures and/or stereotaxic application of stress stimulus onto the brain amygdala. The high spatial and temporal resolution of our real-time cell tracking system allowed clear identification of rhodamine 6G-positive leukocytesin vivo. In the common femoral artery bifurcation of apolipoprotein E knockout mice, white blood cells firmly adhered to the inner layer of the vessel walls while some slowly flowed along the endothelium (Figure). We further demonstrate that the stress increased the rolling and adhesion of inflammatory leukocyte subsets near the atherosclerotic lesions, and enhanced the plaque macrophage activity as assessed byin vivoimaging. Confocal laser scanning microscopy and immunostaining analyses corroborated thein vivofindings that the stress induced the destabilization of the atherosclerotic plaques.Conclusion:Our data show that stress stimulated the dynamics of inflammatory leukocyte subsets in atherosclerotic environments and increased the plaque vulnerability as assessed by the customized high-resolution motion-compensatedin vivoimaging strategy.

Circulation, Volume 146, Issue Suppl_1, Page A14078-A14078, November 8, 2022. Objectives:In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of right ventricular: pulmonary arterial (RV:PA) uncoupling can be leveraged for sub-phenotyping and targeted therapies. In this study, we aim to distinguish mechanisms of RV:PA uncoupling in PH-HFpEF due to high RV afterload (afterload-sensitive; AS) and impaired left ventricular-interventricular septal contributions to RV function (ventricular interdependence; VI).Methods:Subjects (n=13) with early-stage PH (per echo) and NYHA II-III dyspnea were prospectively enrolled. Exclusion criteria: advanced disease with NYHA IV, LVEF

Circulation, Volume 146, Issue Suppl_1, Page A10461-A10461, November 8, 2022. Introduction:The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. Single-Cell RNA sequencing (scRNA seq) was employed to characterize transcriptional differences in various cell types between aged and young mice which may contribute to aged-related vulnerability to ischemic insult. Pyruvate Dehydrogenase Kinase 4 (Pdk4) has been shown to impact capacity for fatty-acid oxidation (FAO) and consequently adaption to metabolic alterations of ischemic insult.Hypothesis:Alteration of Pdk4 expression levels is an adaptive response transcriptionally under pathological stress to maintain metabolic homeostasis during ischemia and reperfusion (I/R).Methods:Young (3-5 months) and aged (24-26 months) C57BL/6J mice were subjected toin vivoregional 45 min of ischemia and 24 hr of reperfusion (I/R) or sham operations. Bioinformatic analysis was done using Seurat integration vignettes allowing for cell type identification and differential expression testing. Observing genetic expression profiles by cell types. Substrate metabolism was determined with working heart system and Seahorse XF Analyzer.Results:Pdk4 was profoundly found in cardiomyocytes versus fibroblasts, endothelial cells and macrophages of both young and aged hearts. Interestingly, I/R stress triggered Pdk4 mRNA expression of young but not aged cardiomyocytes. Moreover, there is a relative higher Pdk4 level in aged versus young cardiomyocytes under sham operations, indicating Pdk4 mRNA respond to pathological stress. Theex vivoworking heart perfusion data showed that young versus aged hearts exhibited higher FAO in response to I/R. Moreover, Seahorse XF Analyzer showed a higher glycolysis rate in young versus aged cardiomyocytes during I/R. It suggests that an impaired cardiomyocyte Pdk4 mRNA response occurred in aging under I/R stress conditions, this could result in cardiac maladaptive metabolic alterations in aging during pathological stress.Conclusions:Alterations in Pdk4 levels of cardiomyocytes regulates cardiac adaptive metabolism in response to pathological stress. This adaptive regulation of cardiomyocyte Pdk4 is impaired in aging that leads to more vulnerability of aged versus young hearts to ischemic insult.

Circulation, Volume 146, Issue Suppl_1, Page A14263-A14263, November 8, 2022. Introduction:The presence of pulmonary vascular disease (PVD) may be under-recognized during standard hemodynamic evaluation in patients with Fontan physiology. Assessment of pulmonary vascular reserve (VR) (Δ pulmonary artery pressure/Δ cardiac index) utilizing pharmacologic stress testing could be a better way of identifying PVD in pediatric patients. The objective of this study is to diagnose Fontan patients with PVD utilizing pharmacologic stress testing.Hypothesis:Pharmacologic stress testing will unmask Fontan patients as having PVD.Methods:Single center record review of cardiac catheterizations with dobutamine administration in Fontan patients from January 2021 to June 2022. Following acquisition of baseline data on room air, a dobutamine infusion was started at 5 mcg/kg/min with dose escalation as needed until an appropriate heart rate response was achieved. Hemodynamics were reassessed at each dose interval, but data are reported at the highest cardiac index (CI). Abnormal VR was defined as > 3 mmHg/l.Results:Eighteen Fontan patients (87% male) were included. Median age at the time of catheterization was 14 (IQR 11, 16) years with mean duration of Fontan circulation of 9.9 ± 3.9 years. The primary indication for catheterization was exercise intolerance (65%). Dobutamine administration did not result in a significant change in indexed pulmonary vascular resistance (PVRi) (2.1 ± 0.8 v 2.4 ± 1.31 iWU, p = 0.21) or Fontan pressure (12 [IQR 11, 14] v 14 (IQR 12, 15), p=1.0]. Eight patients had a PVRi ≥ 2.0 iWu at baseline; while 4 (22% of the cohort) had a PVRi < 2.0 iWU at baseline but had an abnormal VR.Conclusions:PVD is common in Fontan patients but may be missed in some patients without pharmacologic stress testing. Accurate diagnosis of PVD will allow for optimization of Fontan circulation with pulmonary vasodilators.

Circulation, Volume 146, Issue Suppl_1, Page A13635-A13635, November 8, 2022. Introduction:Among females in the United States, Black females suffer from the highest rates of hypertension, coronary artery disease, and total cardiovascular disease (CVD) mortality. Vascular endothelial dysfunction precedes overt CVD and predicts CVD risk and has been reported in this population, but this is not always a consistent finding. Although psychosocial stress from numerous sources likely contributes to this disparity, the precise pathways and mechanisms remain incompletely understood. A growing literature suggests that internalization and coping may be more important than exposure to stressors alone. Therefore, we examined the relationship between endothelial function (brachial artery flow-mediated dilation, FMD) and psychosocial stress exposure (adverse childhood experiences, ACEs; past week discrimination, PWD) versus internalization/coping (John Henryism Active Coping Scale, JHAC12; Giscombe Superwoman Schema Questionnaire, G-SWS-Q). We hypothesized that 1) FMD would be blunted in Black relative to White females and 2) among Black females, internalization and maladaptive coping would exhibit a stronger negative relationship with FMD than exposure to stressful experiences alone.Methods:Twelve Black (21 ± 3 yr) and 8 White (25 ± 6 yr) healthy females underwent standard FMD testing. Black participants completed the ACEs, PWD, JHAC12, and G-SWS-Q inventories. Higher scores indicated greater stressor exposure or endorsement of the internalization/coping constructs.Results:Brachial artery FMD was lower in Black relative to White females (4.93 ± 3.10 vs 8.58 ± 1.62%;p< .01). Neither ACEs (r= -.10,p= .75) nor PWD (r= -.24,p= .45) were associated with FMD. JHAC12 scores were (r= -.61,p= .02) and SWS scores tended to be (r= -.39,p= .11) negatively associated with FMD. Among the SWS subscales, SWS-Resistance to Being Vulnerable (r= -.51,p= .04) and SWS-Intense Motivation to Succeed (r= -.54,p= .04) were negatively associated with FMD.Conclusion:These preliminary data indicate that 1) brachial artery endothelial function is blunted in young Black females and 2) reduced vascular function in Black females may be due more to internalization and maladaptive coping than exposure to stressful experiences alone.

Circulation, Volume 146, Issue Suppl_1, Page A11029-A11029, November 8, 2022. Mitochondrial diseases are some of the most common genetically inherited disorders, yet the prognosis for affected patients has not drastically improved in recent years. Most therapies are supportive as the underlying biochemical derangements in these diseases are incompletely understood. Mitochondrial functions rely on the import of nuclear-encoded proteins, and it has recently been appreciated that defective import of mitochondrial proteins can result in the cytosolic accumulation of these preproteins. The accumulation of these preproteins results in cellular toxicity independently of any changes to the mitochondrial bioenergetic function, raising the possibility that mitochondrial protein import stress may be a yet uncharacterized pathway that links mitochondrial dysfunction with pathology. Here, we model this cytosolic mitochondrial precursor overaccumulation stress (mPOS) in mice through overexpression of the inner mitochondrial membrane protein Adenine Nucleotide Translocase 1 (ANT1). The goal of this study is to determine whether ANT1 can induce mPOS and tissue remodeling prior to the onset of cardiac bioenergetic defects. Using isolated cardiac mitochondria from these mice, we detected a moderate decrease in the levels of Complex I, II ,and IV. By measuring oxygen consumption in these mitochondria from 2-month-old animals, we found only a mild reduction in complex II based state 3 and 4 respirations. No change in complex I-based state 3 and 4 respirations was observed. Using RNAseq and western blot analysis, we find the robust activation of the integrated stress response (ISR). Transcriptomic data further demonstrates a strong upregulation of transcripts involved with 1-carbon metabolism, the amino acid starvation response, and proteolysis. Using echocardiographic evaluation of heart function on anesthetized mice at 6 months old, we find no significant alteration in systolic function. Together these data support the idea that mPOS may be a potent trigger of the ISR in a bioenergetics-independent manner. Whether activation of the ISR can alter cardiac function later in life is being evaluated.

Circulation, Volume 146, Issue Suppl_1, Page A15616-A15616, November 8, 2022. Introduction:Peripheral artery disease (PAD) affects >8 million people nationwide and is disabling. PAD-associated myopathy causes weakness yet is understudied. Unbiased transcriptomic profiling of muscle satellite cells (MuSC) which drive recovery may elucidate the etiology of ischemic myopathic change.Hypothesis:MuSC in PAD differentially express injury associated pathways that may be novel targets for intervention to reduce ischemic myopathy.Methods:Muscle tissue biopsies were obtained during lower extremity amputation or bypass in PAD/ischemic (N=4; ABI

Circulation, Volume 146, Issue Suppl_1, Page A13610-A13610, November 8, 2022. Nearly half of adult population has hypertension which is a main risk factor for cardiovascular disease. Mitochondrial dysfunction contributes to hypertension and targeting mitochondria can potentially improve treatment of hypertension. We found hyperacetylation of mitochondrial Cyclophilin D (CypD) in essential hypertension and proposed that CypD acetylation can promote endothelial dysfunction and hypertension. CypD acetylation is mediated by general control of amino acid synthesis 5 like 1 (GCN5L1) protein which is counteracted by deacetylase Sirt3. We tested potential role GCN5L1 and Sirt3 in endothelial dysfunction and hypertension. Western blot of aortic mitochondria showed an increased GCN5L1 level in hypertensive mice coupled with the reduction of Sirt3 deacetylase resulting in 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. We reported pathogenic role of lipid oxidation products isolevuglandins (isoLGs) and scavenging isoLGs by mitochondria-targeted mito2HOBA reduces mitochondrial acetylation. We tested if mitochondrial isoLGs contributes to acetylase/deacetylase imbalance driving CypD acetylation. Treatment with mito2HOBA improves Sirt3 expression and reduces GCN5L1 level resulting in normalization of GCN5L1/Sirt3 ratio and reduced CypD acetylation. To define the pathophysiological role of GCN5L1 in endothelial cells we tested if GCN5L1 depletion prevents cytokine-induced of mitochondrial oxidative stress. Indeed, treatment of human aortic endothelial cells with AngII+TNFα induces mitochondrial O2.-, however, GCN5L1 depletion using siRNA completely abrogated the cytokine-induced mitochondrial oxidative stress. To define the role GNC5L1 in pathogenesis of endothelial dysfunction we developed new tamoxifen-inducible endothelial specific GNC5L1 knockout mice (EcGNC5L1KO). Depletion of endothelial GCN5L1 reduces vascular mitochondrial O2.-, prevents inactivation of endothelial nitric oxide and preserves endothelial dependent relaxation in angiotensin II-infused EcGNC5L1KOmice compared with wild-type littermates. These data support the pathogenic role of GNC5L1 in CypD acetylation and endothelial dysfunction and targeting GNC5L1 can be beneficial in cardiovascular disease.

Circulation, Volume 146, Issue Suppl_1, Page A10720-A10720, November 8, 2022. Background:Parents of infants with congenital heart disease (CHD) have described substantial stress over infant growth. Poor growth trajectory (GT) during early infancy may be a source of traumatic stress. The purpose of this study was to determine if differences exist in parent posttraumatic stress (PTS) between parents of infants with healthy versus poor GTs from hospital discharge to 4 months post discharge.Methods:This secondary analysis of a previously reported RCT (REACH telehealth trial NCT01941667) included parents of infants with CHD with stress measures at discharge and study end (n=136). Posttraumatic Diagnostic Scale was used to measure PTS. Weights were converted to weight for age Z scores (WAZ) using World Health Organization standards. WAZ-GT classes were identified using latent class growth modeling. We used multivariate logistic regression modeling to examine associations between WAZ-GT and parental PTS over the study period, adjusting for covariates.RESULTSOne-quarter of parents (n=37, 28%) demonstrated at least moderate PTS symptom severity at discharge and one-third at study end (n=40, 31%). We identified four distinct classes of infant WAZ-GT (Figure). Among the identified GTs, two were considered healthy growth patterns: “stable around WAZ=0” (n=51, 37.5%) and “maintaining WAZ > 0” (n=12, 8.8%). Therefore, these two patterns were collapsed to serve as one reference group for the analysis. Two additional WAZ-GT classes were identified that reflected poor growth: “partially-recovered” (n=44, 32.4%) and “never-recovered” (n=29, 21.3%). Parents of infants in the “never recovered” GT were at greater risk (OR=4.58; CI=1.54-13.64) for experiencing at least moderate PTS symptom severity at end of study as well as over time from discharge to end of study (OR=3.91; CI=1.60-9.86).CONCLUSIONResults offer new insights that parents of infants with poor GT are at increased risk for persistent PTS and may need additional screening and intervention.

Circulation, Volume 146, Issue Suppl_1, Page A11202-A11202, November 8, 2022. Introduction:Caregivers of patients with heart failure (HF) are at high risk of low quality of life due to stress-related to caregiving. Self-reported measures are commonly used to assess relatively long-term stress related to caregiving. Still, biological markers of stress, a short-term stress measure, are rarely used. There is limited knowledge on whether both can predict the quality of life in caregivers of patients with HF.Hypothesis:The stress biomarker (serum cortisol) and subjective distress related to caregiving (Caregiver Burden Inventory) predict the quality of life in caregivers of patients with HF.Methods:In this cross-sectional study, Taiwanese caregivers of patients with HF completed surveys including stress-related caregiving and quality of life measured by the Caregiving Burden Inventory and the Short Form-36, respectively. A blood sample for serum cortisol was collected between 9 and 12 AM. Independent t-test and multivariable linear regression analysis were conducted adjusting for age, gender, education, marital status, relationship with care-recipient and depressive symptoms (Patient Health Questionnaire).Results:Of the 113 caregivers (mean age 54.5 years, 70.8% female, 78% married/cohabitated), 59% cared for patients with NYHA class III/V. Single caregivers had higher serum cortisol levels than married caregivers (11.4 vs. 8.5, p =.002). Males had a significantly higher serum cortisol level than females (10.7 vs. 8.5, p =.010), but males reported a lower caregiver burden than females (1.3 vs. 1.6, p =.049). Both serum cortisol (β =-.36, P=.012) and caregiver burden (β = -.29, P= .018) were significant predictors of physical well-being. Serum cortisol (β= -.28, p=.026) and caregiver burden (β =-.25, p =.027) also significantly predicted mental well-being.Conclusions:Although stress levels are different by caregivers’ characteristics, both cortisol level and self-report caregiver burden have similar predictability of quality of life in caregivers of patients with HF. Reducing stress and caregiver burden is necessary to improve the quality of life in this population.

Circulation, Volume 146, Issue Suppl_1, Page A14359-A14359, November 8, 2022. Background:Psychosocial stress is associated with worse cardiac outcomes, but little is known about the prognostic impact of marital stress in young adults (≤55 years) with acute myocardial infarction (AMI). We investigated the association between marital stress and 1-year health outcomes in young AMI survivors.Methods:We used data from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled people aged 18-55 years with AMI (2008-2012). Marital stress was assessed among married/partnered participants at 1 month post-AMI using the Stockholm Marital Stress Scale, categorized as absent/mild, moderate, and severe. Main outcomes were physical/mental health status, generic/disease-specific quality of life, angina, depressive symptoms, and all-cause readmission at 1 year post-AMI. Linear and logistic regression models were sequentially adjusted for baseline health status, demographics, and socioeconomic factors (including education level, income level, employment status, and insurance status).Results:Among the 1593 married/partnered participants in our study, more women reported severe marital stress than men (39.4% vs 30.4%, p=0.001). Having severe marital stress was associated with worse physical and mental health, lower generic and cardiovascular-specific quality of life, more angina and depressive symptoms, and 1.48 times higher all-cause readmission at 1 year post-AMI. These associations remained significant after adjusting for baseline health score and patient demographics (Table Model 1), but they attenuated and became non-significant when further adjusting for socioeconomic factors (Model 2).Conclusion:Marital stress was associated with worse health outcomes in young AMI patients, which can be partially mediated by socioeconomic factors. Further research is needed to understand this complex relationship and potential causal pathway associated with these findings.

Circulation, Volume 146, Issue Suppl_1, Page A14139-A14139, November 8, 2022. Introduction:AHA guidelines recommend non-invasive cardiac testing (NIT) within 72 hours after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS), after acute myocardial infarction (AMI) has been excluded. However, the effectiveness of this strategy to reduce the risk of future AMI or death, in low-risk patients is contested.Hypothesis:We hypothesized that in patients with low risk based on history, electrocardiogram, age, risk factors and troponin (HEART) based scoring, early NIT may not be beneficial compared to higher risk.Methods:We compared the effectiveness of early NIT vs. no early testing, in a retrospective cohort of adult (age ≥18) members of the Kaiser Permanente Southern California health system from 05/2016-12/2020. We included all adults presenting at EDs with suspected ACS and who had data to compute HEART score. We stratified the cohort into low risk (score 0-3); intermediate risk (score 4-6) and high-risk (score ≥7) based on HEART score. Within each group, confounder adjusted instrumental variables models were used to evaluate the marginal effect of early NIT, and the number needed to treat (NNT) was calculated as the inverse of the absolute composite risk reduction in death/AMI within 30 days of ED discharge.Results:The cohort included 174,936 patients [61% Low risk (mean age 53; female 58%; early NIT 5%), 36% intermediate risk (mean age 71; female 72%; early NIT 18%), and 3% high risk (mean age 74, female 45%; early NIT 23%)]. The risk reduction in 30-day death/AMI due to early NIT increased progressively through the intermediate-risk (NNT = 59) and high-risk groups (NNT = 24) (Table 1). Risk reduction in the low-risk group was not statistically significant.Conclusions:HEART score based high risk patients may benefit the most from early NIT. However, the majority of the suspected ACS cohort was classified as low risk and the benefit of early NIT on 30-day death/AMI was uncertain in this low-risk group.

Circulation, Volume 146, Issue Suppl_1, Page A11938-A11938, November 8, 2022. Background:BP risk class assessment has been relying on resting BP (rBP) measurements by healthcare providers. Often, this measurement does not correlate with 24-hour ambulatory BP monitoring nor with at-home measurements.Purpose:To assess whether abnormal rise in BP post-mild exercise protocol (PMEP), which resembles most of the activities subjects are under all day, will be more physiologic and informative for risk stratification, beyond the rBP measurements.Methods:We screened 2,924 subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System, also known as the Rasmussen Risk Score, which consists of 10 tests: 7 vascular and 3 cardiac (published previously). The vascular tests include rBP, BP PMEP (2.4 mi/hr and 7% elevation for 3 minutes), small (C2) artery stiffness, and CIMT. Out of the total subjects, 1094 (37%) were asymptomatic and on no medications. These were divided into four BP classes according to the current ACC/AHA guidelines.Results:In the table, normotension with an abnormal rise in BP PMEP has significant cardiovascular structural and functional abnormalities (CVSFA) than those without. Also noted, the higher the BP class, the higher the CVSFA with and without an abnormal rise in BP PMEP.Conclusions:Abnormal rise in BP PMEP in normotensive subjects is associated with significant CVSFA. This may represent a “masked hypertension” cohort. These findings mandate early diagnosis, follow-up, and optimal treatment. Additionally, an abnormal rise in BP PMEP in other classes is more pronounced with stepwise increases in BP class. Hence, we advocate for PMEP for BP classification and treatment. Early detect to protect.

Circulation, Volume 146, Issue Suppl_1, Page A14065-A14065, November 8, 2022. Introduction:While a link between chronic stress and cardiovascular disease (CVD) is well established, the neurocircuit alterations underlying this association remain unclear. We leveraged advanced multimodal imaging to gain insights into neurocircuit alterations that associate with atherosclerosis.Methods:Individuals with posttraumatic stress disorder (PTSD), trauma-exposed controls without PTSD (TC), and healthy controls (HC) were prospectively enrolled. Participants underwent whole-body18F-fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG-PET/MR) imaging. Stress-related neural network activity (SNNA) was assessed on PET as amygdala metabolic activity relative to regulatory (ventromedial prefrontal cortex [vmPFC]) activity. The structural integrity of the uncinate fasciculus, the major white matter tract connecting the amygdala to vmPFC, was assessed using diffusion tensor imaging (DTI). Atherosclerotic burden was assessed on MR as vessel normalized wall index and standard deviation (SD) of vessel wall thickness.Results:Of 91 participants (24 PTSD, 42 TC, 24 HC), 57% were female, and the median age was 37 years. Compared to controls, individuals with PTSD had higher SNNA (Fig 1A) and lower uncinate fasciculus integrity (Fig 1B). SNNA and uncinate fasciculus integrity were negatively correlated (r = – 0.30, p=0.008). Those with PTSD had higher ascending aorta normalized wall indices (p=0.018, adjusted for Framingham risk score). Notably, the SD of carotid wall thickness correlated positively with SNNA and negatively with uncinate fasciculus integrity (Fig 1C & D).Conclusion:These findings suggest that increases in the amygdala relative to vmPFC metabolic activity or disruptions of their structural interconnections may potentiate atherosclerosis. Interventions targeting this stress-related neural network may reduce adverse brain-heart interactions and related cardiovascular disease burden.

Circulation, Volume 146, Issue Suppl_1, Page A9764-A9764, November 8, 2022. Introduction:Hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) is able to yield important information regarding molecular and functional imaging in a one-stop examination. The aim of this study was to investigate the relationship between coronary flow reserve (CFR) and left ventricular longitudinal strain (LVLS) using simultaneous acquisitions on hybrid13N-ammonia PET/MRI.Methods:Thirty-eight patients with suspected coronary artery disease (CAD) who underwent13N-ammonia PET/MRI were enrolled. Vasodilator stress was induced by intravenous injection of adenosine. CFR was calculated from dynamic acquisition of13N-ammonia PET. LVLS was evaluated by feature-tracked MRI. Myocardial flow reserve (MFR) and LVLS values were based on a 17-segment model and three coronary territories, left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA).Results:We analyzed 577 myocardial segments in the left ventricle. LVLS under vasodilator stress was significantly increased compared with LVLS at rest in myocardial segments with MFR ≥2.0 (P