Circulation, Volume 146, Issue Suppl_1, Page A12932-A12932, November 8, 2022. Introduction:Exercise Stress Echocardiography (ESE) is recommended as a screening tool for the evaluation of Coronary Artery Disease (CAD) in patients with suspected Radiation-Induced Heart Disease (RIHD). Up to now, studies have only evaluated its association with the extent of CAD.HypothesisCancer survivors treated with chest Radiotherapy (RT) that undergo an ESE and have a +ESE develop more MACE than those who have -ESE.Methods:A retrospective, descriptive, cohort study was conducted. Patients who had chest RT and underwent ESE with Treadmill Bruce Stress Protocol, from 2000 to 2012, at Mayo Clinic Rochester and Mayo Clinic Health System were included. A univariate analysis was performed to characterize the population. An analysis including Kruskal Wallis and Pearson Chi-Squared tests was completed to identify variables associated with + SE (Table 1). Multivariable Cox Model for MACE was conducted and is shown in Table 2. A time-to-event curve using Kaplan-Meier estimates is shown in Figure 1.Results:We identified 113 patients, with a mean age of 67 years and a median follow-up of 15.1 years. Of those, 99% were female, 98% were breast cancer survivors, 59% had HTN, 14% DM, 11% AFib, 2% COPD, and 12% had a history of MI. All the patients received >3000cGy of Photon RT, and 57% were treated with systemic cancer therapies. A +ESE was seen in 20.3% of the patients with no significant difference in METS achieved compared with patients who had a -ESE. COPD, RT dose, and systemic therapies, specifically doxorubicin, were associated with a +ESE. The cumulative incidence of MACE was higher in the group of +ESE (p=0.029). After adjustment for HTN, DM, smoking history, hyperlipidemia, and prior MI, the HR for MACE associated with a +ESE was 1.97 (1.09-3.59).Conclusion:MACE was more frequent in patients with a +ESE who received chest RT and doxorubicin versus -ESE. These results support the usefulness of ESE in cancer survivors after RT as a cardiovascular screening tool.
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Abstract 14447: Multi-Center Evaluation of Stress Myocardial Blood Flow by Cardiac Magnetic Resonance in Known and Suspected Ischemic Heart Disease: Preliminary Findings From the AQUA-MBF Initiative
Circulation, Volume 146, Issue Suppl_1, Page A14447-A14447, November 8, 2022. Introduction:Quantitative myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) in several mostly small, single-center studies. The AQUA-MBF (Assessment ofQUAntitativeMBF) study is a multicenter initiative involving 16 centers.Hypothesis:The goal of this sub-study is to determine if MBF can differentiate CAD, CMD, and normal volunteers in this multicenter setting.Methods:We present data from 53 subjects (15 with CAD, 20 at risk for CMD and 18 controls) who underwent vasodilator stress CMR (Figure) using 1.5T and 3.0T MR scanners (General Electric). At risk for CMD was defined as having diabetes and 2 other risk factors in absence of ≥50% stenosis based on coronary CT. CAD was defined as the presence of stenosis ≥70% based on invasive coronary angiography. Stress perfusion images were acquired using the dual sequence technique. Stress MBF was measured in each of the 16 AHA segments using Fermi deconvolution (Circle Cvi42). In the CAD group, each segment was further classified as having late gadolinium enhancement (LGE), supplied by CAD, or a normal remote territory. The means of the 5 groups were compared using one-way analysis of variance.Results:The segmental stress MBF (ml/g/min) for the 5 groups are shown in figure. Compared to the normal group, segmental stress MBF in 4 disease groups were significantly lower (p
Abstract 15067: Stress Hyperglycemia on Hospital Admission Drives the Risk of Re-Hospitalization for Chest Pain in INOCA Patients
Circulation, Volume 146, Issue Suppl_1, Page A15067-A15067, November 8, 2022. Introduction:Ischemia with non-obstructive coronary arteries (INOCA) is a relatively new condition, often observed in patients with angina. However, the exact pathophysiology of INOCA is not fully understood, and its management remains very debated.Hypothesis:We hypothesized that admission hyperglycemia in INOCA patients could be associated with the risk of being re-hospitalized for chest pain.Methods:We evaluated INOCA patients referred to our Institution between 2016 and 2021 for percutaneous coronary intervention (PCI). We divided our population in quintiles according to the values of the stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose (expressed as mmol/L) and HB1Ac (%). We calculated Kaplan-Meier product limits for cumulative ratio of reaching the endpoint and we applied the log-rank test. To further confirm our results, we performed a multivariable analysis in order to adjust for potential confounders.Results:2874 INOCA patients were enrolled in our study. At 1-year follow-up, the risk of hospitalization for chest pain was progressively higher in patients with higher SHR values (p
Abstract 10098: Assessment of a Rate Pressure Product Target During Stress Echocardiograms in Patients With Advanced Cirrhosis
Circulation, Volume 146, Issue Suppl_1, Page A10098-A10098, November 8, 2022. Introduction:Dobutamine and exercise stress echo are routinely performed on patients with advanced cirrhosis though have low sensitivity in this patient population, even when target heart rate is achieved. This is in part due to their unique cardiovascular physiology which is frequently marked by reduced peripheral vascular resistance with low blood pressure, impaired chronotropic response to stress, hyperdynamic left ventricular systolic function and elevated cardiac output. In the general population, achieving a rate pressure product (RPP), defined as peak systolic blood pressure multiplied by peak heart rate, > 25,000 is typically considered a high level of stress and is an adequate workload to detect ischemia, however this has not been validated in patients with advanced cirrhosis. We aimed to assess the impact of achieving a RPP > 25,000 on the ability of stress echo to detect obstructive coronary artery disease (CAD) in patients with advanced cirrhosis.Methods:We performed a case-control study on patients with advanced cirrhosis where 88 had and 97 did not have CAD based on invasive coronary angiography. A total of 159 patients (85.9%, 77 with CAD and 82 without) had dobutamine and 26 (14.1%, 11 with CAD and 15 without) had exercise as their stress modality. Continuous variables were compared by means of Wilcoxon Rank Sum test. Categorical variables were expressed as numbers and percentages and compared by means of chi-square and Fisher exact tests.Results:The average maximum RPP was 19,999 ± 4,969.4 with 32 patients (17.3%) achieving a RPP > 25,000 (14 with and 18 without CAD, P = 0.63). The average percent of maximum predicted HR (MPHR) achieved was 86.7 ± 9.2% with 136 patients (73.5%) achieving > 85% of MPHR. Achieving a maximum RPP > 25,000 (OR 0.83, 95% CI 0.39 – 1.79, P = 0.63) or a MPHR > 85% (OR 1.04, 95% CI 0.54 – 1.99, P = 0.92) did not improve the ability of stress echo to detect obstructive CAD.Conclusions:Achieving a maximum RPP > 25,000 did not improve the ability of stress echo to detect obstructive CAD in patients with advanced cirrhosis.
Abstract 11330: Association of Left Ventricular Wall Stress and Incident Heart Failure in Elderly Community Dwelling Individuals
Circulation, Volume 146, Issue Suppl_1, Page A11330-A11330, November 8, 2022. Introduction:Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and risk of incident HF in community dwelling individuals.Methods:Using data from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center, we studied 4,601 participants of the Atherosclerosis Risk in Communities study without prevalent HF who underwent echocardiography at visit 5 (2011-2013). LV end systolic and diastolic wall stress (LVESWS, LVEDWS) were calculated from chamber and wall thickness measures, E/e’ as a surrogate for LV end diastolic pressure, and systemic blood pressure. Incident HF was assessed by cohort surveillance for hospitalized HF through December 31, 2016. The relationship between LVESWS and LVEDWS was examined by Spearman rank correlation. The association between wall stress and risk of incident HF was tested in Cox regression adjusted for demographics, traditional CV risk factors, prevalent CAD and atrial fibrillation, as well as creatinine, NT-proBNP, troponin, triglycerides, C-reactive protein, LV ejection fraction, and LV mass.Results:The cohort was elderly (median age 75 years), predominantly female (58%), with 18% of individuals identifying as black. Median LVESWS and LVEDWS were 48.8 (IQR: 39.3, 60.1) and 18.9 (IQR: 15.8, 22.5) kdynes/cm2, respectively. LVESWS and LVEDWS were modestly correlated (rho = 0.30, p
Abstract 15081: The Viscoelastic Yield Stress of Blood is Negatively Associated With Pulmonary Blood Flow in the Fontan Circulation
Circulation, Volume 146, Issue Suppl_1, Page A15081-A15081, November 8, 2022. Introduction:In the Fontan (FN) circulation pulmonary blood flow (Qp) is passive, resulting in severely decreased shear rate and velocity in pulmonary arteries to the point of stasis. Yield stress (YS) is the shear stress required for blood to transition from stasis to a moving fluid. Therefore, YS may be a determinant of Qp in FN. We evaluated YS in patients with FN and Glenn (GLN) circulations and whether increased YS is associated with decreased Qp.Methods:We enrolled 20 patients with biventricular (2V) congenital heart disease (CHD) and 41 patients with single ventricle CHD (19 FN and 22 GLN) who were undergoing a clinically indicated cardiac catheterization. Two patients were excluded due to pulmonary vascular disease. We obtained blood samples at the time of catheterization and measured blood viscosity across shear rates 1 s-1to 1000 s-1using a Rheolog viscometer We calculated YS by curve-fitting of the viscosity measurements to a Casson fluid model.Hypothesis:We hypothesize that higher yield stress will be associated with lower pulmonary blood flow in Fontan circulation.Results:The FN group was the oldest and had the largest BSA (FN >2V >GLN; pFN >2V; p
Abstract 12063: Antidepressant Use and Incident Ischemic Heart Disease in Women Veterans With Posttraumatic Stress Disorder
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.
Abstract 13379: Perceived Stress and Cardiovascular Risk Among Older Persons With HIV
Circulation, Volume 146, Issue Suppl_1, Page A13379-A13379, November 8, 2022. Background:Cardiovascular disease (CVD) is highly prevalent among older persons with HIV (OPWH) occurring on average a decade earlier than non-infected individuals largely due to chronic inflammation, vascular pathology, and psychosocial stressors. Effective cardiovascular risk reduction strategies such as exercise have been shown to lower both physiological and psychosocial stressors but have not been widely reported in the HIV population.Objective:To evaluate the effect of a one-year, moderate intensity aerobic exercise intervention on perceived stress among OPWH with ≥ 2 CVD risk factors.Methods:A secondary analysis was performed utilizing data from Project FiTBRAiN, a 2-arm RCT that included Let’s Move (moderate intensity aerobic exercise intervention) or Let’s Flex (flexibility/stretching attention control) groups. The 14-item Perceived Stress Scale (PSS) was utilized to measure participants’ perceived stress. Data analysis included an analysis of variance with pairwise and between-group differences reported.Results:Participants (n=115) reported a mean age of 55±5.2, and the majority were African American (n=100, 87.0%) and male (n=66, 57.4%). The most common cardiovascular comorbidities were elevated: total cholesterol (n=114, 99.1%), systolic blood pressure (n=108, 93.9%), diastolic blood pressure (n=98, 85.2%), and participants had a mean BMI of 28.29. Baseline 14-item PSS scores for the Let’s Move Program and Let’s Flex Program were 19.49 (SD=7.94) and 21.13 (SD=8.64), respectively, indicating moderate stress levels. Over all time points, the control group (Let’s Flex) had higher perceived stress than the intervention group (Let’s Move), but were not significant.Conclusions:Our findings suggest that moderate levels of psychological stress were present in this population and may be a risk factor for CVD among OPWH. The consistent finding that perceived stress remained lower over time indicates that aerobic exercise may be beneficial for stress reduction. Additional research is needed to determine the optimal dose and mode of exercise that is most beneficial for stress reduction in this population.
Abstract 10218: Differences in Treadmill Exercise Stress Testing Parameters Among Electronic Cigarette Vapers, Combustible Cigarette Smokers, and Controls: The Clues Study
Circulation, Volume 146, Issue Suppl_1, Page A10218-A10218, November 8, 2022. Background:Use of electronic nicotine delivery devices is increasing but their effects on exercise function are not well-characterized. We hypothesized that treadmill stress test outcomes would differ between chronic electronic cigarette users (“vapers”), combustible cigarette users (“smokers”), and non-smoking/non-vaping controls.Methods:CLUES (HL1393301) was a cross-sectional study of 395 individuals: 164 exclusive vapers (exhaled carbon monoxide [CO] 5 ppm, positive urine NicCheck I), and 114 non-vaping/non-smoking controls (CO
Abstract 12929: Association of Posttraumatic Stress Disorder With Stroke in Women Veterans
Circulation, Volume 146, Issue Suppl_1, Page A12929-A12929, November 8, 2022. Introduction:Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans. To date, the evidence for the potential association of PTSD with other cardiovascular disorders remains limited. Furthermore, the overwhelming majority of the research in this area has been conducted predominately in men. The goal of this investigation was to evaluate the association of PTSD with incident stroke in a large cohort of women veterans.Methods:Veterans Affairs (VA) electronic health records were used to identify women veterans aged ≥18 years who visited any VAs nationwide from 1/1/2000-12/31/2017. Diagnosis of each risk factor and disorder was based on administrative billing codes (International Classification of Disease versions 9 and 10). The final study cohorts included 1:2 matched group of patients with and without PTSD respectively. The cohorts were matched for age, traditional risk factors such as diabetes, hypertension, hyperlipidemia and smoking, as well as obesity, chronic kidney disease, psychiatric disorders (depression, anxiety), female specific risk factors (e.g., pre-eclampsia), drug and alcohol dependence, neuroendocrine disorders (e.g., hypo or hyperthyroidism), and number of visits. Cox regression was used to model incident stroke as a function of PTSD.Results:The study population included 398,769 patients, including 132,293 with PTSD and 265,846 matched patients without PTSD. The cox regression analysis revealed that PTSD was significantly associated with greater rates of incident stroke (hazard ratio [HR]=1.64, 95% confidence interval: 1.43-1.86, p
Abstract 10199: Increased Aortic Wall Shear Stress in Marfan Patients Long-Term After Proximal Grafting Assessed by 4D Flow Cardiac Magnetic Resonance
Circulation, Volume 146, Issue Suppl_1, Page A10199-A10199, November 8, 2022. Introduction:For Marfan syndrome patients (MFS) with thoracic aortic aneurysms (TAA), prosthetic graft surgery provides lifesaving benefits, but adverse event risk persists in the native aorta for which mechanism is unclear. Sustained impact of proximal grafts on biomechanics within and distal to grafts is unknown.Methods:MFS patients with chronic ( > 6 month) proximal grafts were compared to non-surgical MFS (nsMFS) and age/sex matched controls: Wall shear stress (WSS) on 4D flow cardiac MRI and size (diameter) were quantified at aortic landmarks (ascending, arch, descending, thoracoabdominal).Results:34 subjects were studied including MFS late (7.3±6.7 years) after graft implantation (n=12). Post-surgical MFS were of similar age (p=0.93) and sex (p=0.64) to controls but older than non-surgical MFS (45±10 vs 33±11 yo, p=0.01): In the ascending aorta (grafted territory), post-surgical MFS had higher WSS (1.17±0.55 Pa) than nsMFS (0.74±0.17 Pa) and controls (0.60±0.17 Pa; p=0.002 for trend). Similarly, in the (native) descending aorta, WSS was higher in post-surgical (1.06±0.24 Pa) than nsMFS (0.97±0.11) and controls (0.83±0.16; p=0.02) (Figure) paralleling results in the arch (p=0.06) and a similar trend in the thoracoabdominal aorta (p=0.12). Among the overall MFS cohort (n=23), proximal graft implantation associated with increased WSS in the ascending and descending aorta (both p
Abstract 13105: The Effect of Mechanical Stress on Cardiac Fibroblasts in Pulmonary Arterial Hypertension
Circulation, Volume 146, Issue Suppl_1, Page A13105-A13105, November 8, 2022. Introduction:Pulmonary arterial hypertension (PAH) is a rare fatal disease with vascular remodeling leading to increased right ventricular pressure followed by fibrosis. To study PAH-induced cardiac fibrosis we develop anin vitromodel of the failing right ventricle, for which cardiac fibroblasts (cFBs) were generated from healthy subjects’ and PAH patients’ induced pluripotent stem cells (iPSC).Methods:Confluent iPSC were induced to differentiate by adding 12 μM CHIR99021 for 24h to RPMI supplemented with B27 without insulin. Next, cells recovered for 24 h in RPMI supplemented with B27 without insulin, followed by stimulation with 75 ng/ml FGF2 up to day 20. Finally, the differentiated cells were reseeded and submitted to 10% cyclic stretch at 1 Hz for 4 days using the Flexcell FX-6000 system. Control and PAH cFBs were characterized at gene and protein levels.Results:The differentiated cells had a spindle morphology typical of FBs. Furthermore, the presence of cardiac (GATA4, TCF21) and fibroblast (VIM, PDGFRα, COL1A1) markers at gene and protein levels confirmed the cFB identity. Comparable expression of fibroblast related genes was observed in PAH cFBs as well as controls. Over 4 weeks of culture, iPSC-cFBs increasingly expressed markers of activated FBs (ACTA2andPOSTN)over time, similar to in vitro adult cFBs. When exposed to mechanical stretch, cell aligned to the stretch direction. Surprisingly, no increase in gene expression of extracellular matrix (COL1A1, COL3A1) or activated fibroblasts (ACTA2, POSTN) markers was observed.Interestingly, under static and stretch conditions expression of these genes was increased in PAH cFBs compared to healthy cells.Conclusion:The cellular morphology after differentiation as well as the gene and protein analyses indicate that cFBs were successfully generated. Furthermore, cyclic stretch induced alignment of the cells but was not sufficient to stimulate fibroblast activation in either PAH or healthy cFBs.
Abstract 10270: High Shear Stress Decreases ERG Causing Endothelial to Mesenchymal Transition and Pulmonary Arterial Hypertension
Circulation, Volume 146, Issue Suppl_1, Page A10270-A10270, November 8, 2022. Introduction:Computational modeling studies indicated that pathological high shear stress (HSS) of 100 dynes/cm2is generated in pulmonary arteries (PA) (100-500μM) in patients with a ventricular septal defect or idiopathic pulmonary arterial hypertension (PAH) and occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH.Hypothesis:Pathological HSS induces EndMT, which contributes to the initiation and progression of PAH.Methods:We applythe Ibidi perfusion system to human PA endothelial cells (EC), to determine whether HSS (100 dynes/cm2) induces EndMT, when compared to normal laminar shear stress (LSS) (15 dynes/cm2). We assessed the mechanism and targeted it to prevent PAH in a mouse with HSS resulting from an aortocaval (AV) shunt.Results:HSS induced EndMT, as assessed by an increase in transcription factors, SNAI1 and SNAI2, reduced BMPR2 (previously shown to inhibit EndMT), decreased EC markers PECAM1 and CDH5, and increased mesenchymal markers, ACTA2 and FSP-1. While the flow-induced transcription factors, KLF2 and KLF4 were similar in LSS and HSS, the co-transcription factor ERG was reduced with HSS. IndeedERGsiRNA under LSS caused EndMT whereas under HSS, transfection ofERGprevented EndMT. To address the significance of our observations in an animal model we created an AV shunt in mice and compared PAH in those sham operated vs transfected with an adeno-associated viral (AAV2- ESGHGYF) vector selectively targeting PAEC with aluciferase(control) or anERGexpressing construct (N=10 per group). Eight weeks after AV shunt, right ventricular systolic pressures was 21.9 ±0.6 mmHg in sham, 37.2±1.0 mmHg in AV shunt with luciferase vector (p
Abstract 14606: Accurate Detection of Acute Psychological Stress Events Using Single Lead ECG Data
Circulation, Volume 146, Issue Suppl_1, Page A14606-A14606, November 8, 2022. Introduction:Stress has been linked to numerous health conditions, including heart disease, diabetes, and mental health issues. By monitoring changes in physiological signals, such as heart rate (HR) and heart rate variability (HRV), wearable biosensing technology allows acute stress to be non-invasively tracked over long periods, providing valuable insights for preventative healthcare.Methods:This two-phase study comprised several protocols designed to induce varying levels of psychological stress in participants (N=39). HR and HRV metrics, derived from electrocardiogram (ECG) data collected throughout the protocol on the single lead HeartKey®Chest Module, were used by the HeartKey Stress algorithm to generate a relative stress score (0-100), which was validated against two clinically recognized methodologies for assessing patient stress: i) state-trait anxiety index (STAI), a questionnaire that subjectively measured the individual’s perceptual stress after each stage of the protocol, and ii) electrodermal activity (EDA), which continuously monitored conductive changes at the skin’s surface with an Empatica®E4 wrist wearable.Results:Over both phases, participant STAI scores increased significantly during stress protocols (49.9 ± 23.3) relative to the baseline (30.0 ± 10.0). Mean HR showed a similar significant increase (p< 0.001), and HRV gradually decreased throughout the testing protocol. HeartKey Stress scores derived from HR and HRV data showed a strong correlation to STAI scores. Furthermore, the HeartKey Stress trend closely replicated that of the EDA data.Conclusions:HeartKey Stress algorithm consistently generated accurate and reliable stress scores in response to events of induced, acute psychological stress. The results suggest that the algorithm has potential utility for continuous clinical monitoring of patients with stress-related illnesses.
Abstract 10014: Work-Related Stress and Ideal Cardiovascular Health: The Multi-Ethnic Study of Atherosclerosis
Circulation, Volume 146, Issue Suppl_1, Page A10014-A10014, November 8, 2022. Background:Work-related stress is a psychosocial risk factor linked to a higher risk of adverse health outcomes, especially cardiovascular disease (CVD). However, the association between work-related stress and ideal cardiovascular health (CVH) is not well established. We examined whether work-related stress was negatively associated with favorable CVH in a multi-ethnic population of adults free of CVD at baseline.Methods:We analyzed cross-sectional data of 6,486 men and women aged 45-84 years. Work-related stress was assessed by the presence or absence of ongoing job difficulty and ongoing job difficulty for >6 months. CVH was measured by a scoring system that assigned points to 7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure and blood glucose). Each metric had 3 categories: poor (0 points), intermediate (1 point) and ideal (2 points). The total score attainable was 14 points, categorized as inadequate (0-8 points), average (9-10 points) and optimal (11-14 points). We used polytomous logistic regression to examine the association of work-related stress with the CVH score and number of ideal metrics, adjusted for sociodemographic factors.Results:The mean age (SD) was 62 (10) years and 53% were women. Ongoing job difficulty was reported by 14% of participants while 13% reported ongoing job difficulty for >6 months. Participants who reported ongoing job difficulty had 21% and 24% lower odds of having average and optimal CVH scores, respectively(Table).Additionally, the presence of ongoing job difficulty for >6 months was associated with 23% and 24% lower odds of having average and optimal CVH scores, respectively. A similar trend was observed for the association of work-related stress with the number of ideal metrics.Conclusion:Work-related stress was negatively associated with favorable CVH. Stress reduction and CVH promotion programs in the workplace may decrease the incidence of CVD.
Abstract 10461: Single-Cell Transcriptional Analysis of Altered Cardiomyocyte Pdk4 as Indicator of Ischemic Stress Vulnerability in Aging
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.