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Post-traumatic stress disorder (PTSD) has been associated with cardiovascular disease (CVD), but the mechanisms remain unclear. Autonomic dysfunction, associated with higher CVD risk, may be triggered by acute PTSD symptoms. We hypothesized that a laboratory-based trauma reminder challenge, which induces acute PTSD symptoms, provokes autonomic dysfunction in a cohort of veteran twins. We investigated PTSD-associated real-time physiologic changes with a simulation of traumatic experiences in which the twins listened to audio recordings of a one-minute neutral script followed by a one-minute trauma script. We examined two heart rate variability metrics: deceleration capacity (DC) and logarithmic low frequency (log-LF) power from beat-to-beat intervals extracted from ambulatory electrocardiograms. We assessed longitudinal PTSD status with a structured clinical interview and the severity with the PTSD Symptoms Scale. We used linear mixed-effects models to examine twin dyads and account for cardiovascular and behavioral risk factors. We examined 238 male Veteran twins (age 68 ± 3 years old, 4% black). PTSD status and acute PTSD symptom severity were not associated with DC or log-LF measured during the neutral session, but were significantly associated with lower DC and log-LF during the traumatic script listening session. Long-standing PTSD was associated with a 0.38 (95% confidence interval, −0.83,− 0.08) and 0.79 (−1.30, −0 .29) standardized unit lower DC and log-LF, respectively, compared to no history of PTSD. Traumatic reminders in patients with PTSD lead to real-time autonomic dysregulation and suggest a potential causal mechanism for increased CVD risk, based on the well-known relationships between autonomic dysfunction and CVD mortality.

Objective Posttraumatic stress disorder (PTSD) has been related to accelerated biological aging processes, but objective evidence for this association is limited. DNA methylation (DNAm) age acceleration is a novel measure of biological aging which may help clarify if PTSD is related to biological aging processes. We aim to examine whether PTSD is associated with biological aging using a comprehensive set of DNAm age acceleration markers, and to what extent the unshared environment contributes to the association. Methods Using a cross-sectional co-twin control study design, we investigated the association of the clinical diagnosis and symptom severity of posttraumatic stress disorder with six measurements of DNAm age acceleration based on epigenome-wide data derived from peripheral blood lymphocytes of 296 male twins from the Vietnam Era Twin Registry. Results Twins with current PTSD had significantly advanced DNAm age acceleration compared with twins without PTSD for five out of six measures of DNAm age acceleration. Across almost all measures of DNAm age acceleration, twins with current PTSD were "epigenetically older" than their twin brothers without PTSD: estimated differences ranged between 1.6 (95% confidence interval 0.0 to 3.1) to 2.7 (95% confidence interval 0.5 to 4.8) biological age year-equivalents. A higher CAPS score was also associated with a higher within-pair DNAm age acceleration. Results remained consistent after adjustment for behavioral and cardiovascular risk factors. Conclusions PTSD is associated with epigenetic age acceleration, primarily through unshared environmental mechanisms as opposed to genetic or familial factors. These results suggest that PTSD is related to systemic processes relevant to biological aging.

Introduction: Poor nutritional status worsens clinical outcomes in multiple disease states. Protein-Energy Malnutrition (PEM) worsens outcomes for patients with systolic heart failure (SysHF). Similarly, Atrial Fibrillation (AF) worsens outcomes of SysHF. The impact of PEM on patients with SysHF & AF is not known. Therefore, our study sought to measure the effect of PEM on clinical outcomes in patients with SysHF & AF. Methods: We queried the National Inpatient Sample (NIS) between 2016 & 2017. NIS was searched for adult patients hospitalized with SysHF with a history of AF as a principal diagnosis with & without PEM as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality, while secondary outcomes were the length of stay (LOS), total hospital charge, cardiac arrest, cardiogenic shock, & respiratory failure. A multivariable logistic & linear regression analysis was applied to estimate the odds for the clinical outcome. A p-value Results: There were 270,580 SysHF with history of AF admissions, approximately 5.4% (14,611) had PEM. PEM vs No PEM cohorts include; (Mean Age of 77 vs 75 years], Males [57.8% vs 60.9%], Whites [76.5% vs 76.4%], Black [11.8% vs 13%]. PEM resulted in increased LOS (10 days vs 5.4 days, Adjusted LOS 3.6 days [3.1-4.3, P = Conclusion: In conclusion, PEM raised the risk of adverse clinical outcomes & increased hospital expense in patients hospitalized with SysHF & AF. Assessing nutritional status will aid in risk assessment & help guide cardiovascular treatment. Whether treating protein malnutrition will improve cardiovascular outcomes is unknown.

Background: Atrial fibrillation with rapid ventricular response (AFib with RVR) is an arrhythmia caused by the atria of the heart beating chaotically and irregularly and is frequently associated with worse outcomes in chronic kidney disease (CKD). We sought to investigate the length of stay (LOS) in patients presenting at the emergency department with Afib with RVR and a history of CKD. Methods: Comorbidity, clinical outcomes and length of stay (LOS) were analyzed retrospectively in a cohort of 1638 patients presenting with new-onset of Afib with RVR at the emergency department from 2013 to 2018. Patients with a history of CKD vs. no history of CKD were compared using descriptive statistics, chi-square and Mann-Whitney tests. Results: The 343 patients admitted with a history of CKD had a median [IQR] glomerular filtration rate of 42 [29.4-51], were older 76(10.4) vs. 70.4(14) years of age, p2 DS 2 -VASc score of 5[4-6] vs. 4[2-5] (P Conclusion: CKD patients admitted with new-onset of Afib with RVR required additional care and longer LOS. Prevalence of other comorbidities is higher in this population, including heart failure and hypertension (most common), and thyroid disorder and COPD (least common).

Background Black patients tend to develop coronary artery disease at a younger age than other groups. Previous data on racial disparities in outcomes of myocardial infarction (MI) have been inconsistent and limited to older populations. Our objective was to investigate racial differences in the outcome of MI among young and middle‐aged patients and the role played by socioeconomic, psychosocial, and clinical differences. Methods and Results We studied 313 participants (65% non‐Hispanic Black) Conclusions Among young and middle‐aged adult survivors of an MI, Black patients have a 2‐fold higher risk of adverse outcomes, which is largely driven by upstream socioeconomic factors rather than downstream psychological and clinical risk factors.

Background Posttraumatic Stress Disorder (PTSD) is prevalent among patients who survived an acute coronary syndrome, and is associated with adverse outcomes, but the mechanisms underlying these associations are unclear. Individuals with PTSD have enhanced sensitivity of the noradrenergic system to stress which may lead to immune activation. We hypothesized that survivors of a myocardial infarction (MI) who have PTSD would show an enhanced inflammatory response to acute psychological stress compared to those without PTSD. Methods Individuals with a verified history of MI within 8 months and a clinical diagnosis of current PTSD underwent a mental stress speech task. Inflammatory biomarkers including interleukin-6 (IL-6), high-sensitivity C reactive protein (HsCRP), matrix metallopeptidase 9 (MMP-9), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and monocyte chemoattractant protein (MCP)-1 were measured at rest and 90 min after mental stress. Results Among 271 patients in the study (mean age 51 ± 7 years, 50% female, 60% African-American), the prevalence of PTSD was 12%. Mental stress resulted in a significant increase in IL-6, but the increase was more marked in patients with PTSD (126% increase) than those without (63% increase) (p = 0.001). MCP-1 showed a modest increase with stress which was similar in patients with PTSD (9% increase) and without PTSD (6% increase) (p = 0.35). CRP did not increase with stress in either group. Conclusion MI patients with current PTSD exhibit enhanced IL-6 response to psychosocial stress, suggesting a mechanistic link between PTSD and adverse cardiovascular outcomes as well as other diseases associated with inflammation.

Background: Atrial fibrillation with rapid ventricular response (AFib with RVR) is frequently associated with worse outcomes in diabetes mellitus (DM) and chronic kidney disease (CKD). We sought to investigate the heart failure (HF) risk among patients hospitalized with Afib with RVR and history of DM with and without CKD. Methods: Clinical variables were collected from 1635 patients presenting to the hospital with Afib with RVR 2013 to 2018. Patients were stratified based on DM and CKD status and compared using descriptive statistics, chi-square, Friedman and Mann-Whitney tests. Results: There were 162 patients admitted with a history of DM and CKD, they had a median [IQR] glomerular filtration rate of 39.8 [30-51], with median age of 74[66-80]. Median BNP levels were higher in the DM and CKD groups (Fig1). There was incremental HF risk based on DM and CKD status with the highest risk in patients with DM and CKD (DM OR 1.366 [1.067-1.749], CKD OR 2.021 [1.441-2.835], DM+CKD OR 3.307[2.226-4.912]. Conclusion: In patients hospitalized with Afib with RVR, higher BNP levels and clinical HF were more common among patients with DM with or without CKD. Patients with diabetes and CKD had the highest odds for HF and warrant consideration for specific diabetes treatments that can lower the risk of HF hospitalization. Disclosure V. Namdarizandi: None. V. Sharma: None. D. M. Brandt: None. K. Shemisa: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc. A. Zain elabidin: None. A. Alkhayru: None. B. Tappuni: None. B. Kaseer: None. H. Elabd: None. L. Pereira: None. S. Kasan: None. M. Fatuyi: None.

Background: Patients with diabetes mellitus (DM) are at increased risk for complications when hospitalized for COVID-19. We sought to investigate with the risk factors and clinical outcomes in diabetic patients hospitalized with COVID-19. Methods: Clinical variables were analyzed retrospectively in a cohort of patients admitted with COVID-19 from 01/ 2020 to 06/2020. Patients were stratified by history of DM and compared using descriptive statistics, χ2, and Mann-Whitney tests. Results: Among the 321 patients, 35% (114) had a history of DM with median age of 66.5[55-76]. Diabetic patients had a higher BMI 32[27-40] vs. 29 [24-34] (P 100 pg/ml was found in 90% (10) of DM patients with CA vs. 43.8% (48) in DM patient without CA (No CA) Fig1. Conclusion: Hospitalized DM patients with COVID-19 with a BNP>100 pg/ml were at higher risk of CA. Identifying subclinical HF using BNP may be helpful in predicting and implementing strategies to lower adverse cardiovascular outcomes in DM patients hospitalized with COVID-19. Screening DM patients hospitalized with COVID-19 using BNP may be beneficial. Disclosure A. Zain elabidin: None. K. Shemisa: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc. L. Pereira: None. V. Namdarizandi: None. M. Fatuyi: None. S. Kasan: None. V. Sharma: None. B. Tappuni: None. B. Kaseer: None. D. M. Brandt: None.

Risk factors such as obesity, hypertension, diabetes and hyperlipidemia are associated with higher rates of COVID-19 morbidity and mortality. Little is known about clinical outcomes in patients with metabolic syndrome (MetS) hospitalized with COVID-19. We sought to investigate the clinical predictors and hospital outcomes. Data were collected from 321 patients hospitalized with COVID-19 at two affiliate hospitals between Jan 1 and July 31, 2020. Patients were identified as having MetS by meeting three of the five standard criteria on hospital admission. Among 321 patients (median age 67 years), 50.3% were female, and 48% had MetS. MetS patients had a higher prevalence of diabetes (64 vs. 9%), hypertension (64 vs. 30%), hyperlipidemia (57 vs. 22%), CAD (26 vs. 13%) and CKD (32 vs. 16%), P

Introduction The prevalence of both metabolic syndrome (MetS) and atrial fibrillation (AF) are on the rise. Studies investigating the association between MetS and AF on clinical outcomes remains limited. Methods We queried the 2017-2018 National Inpatient Sample (NIS) for adult patients with MetS as primary diagnosis with and without AF as a secondary diagnosis. The primary outcome was inpatient mortality, while secondary outcomes were length of stay (LOS), total hospital cost (THC), cardiac arrest (CA), NSTEMI, cardiogenic shock (CS), respiratory failure (RF), need for invasive mechanical ventilation (IMV) and congestive heart failure (CHF). A multivariable logistic regression analysis was applied to estimate the clinical outcome. A p-value of Results A total of 97,420 patients with MetS were admitted, of which 15.38% had AF. AF vs No AF cohorts included a mean age of 69.7 years [CI 69.2-70.1] vs 55.6 years [CI 55.0-56.1]), males (59.8% vs 44.8%); white (83.1% vs 69.4%), black (8.2% vs 13.7%), and Hispanic (5.1% vs 11.6%). AF was significantly associated with multiple adverse clinical outcomes (Table 1) including mortality, CA, NSTEMI, HF, RF, CS, need for IMV, and greater LOS (p Conclusion We observed that MetS patients with AF had worse clinical outcomes. Possible reasons for these differences include a greater burden of atherosclerosis, adverse cardiac remodeling and chronic kidney disease. Further research into biomarkers of risk may help predict adverse clinical outcomes.

Introduction: Atrial fibrillation is associated with increased risk of heart failure and mortality. The association of QRS duration (QRSd) with morbidity and mortality is understudied in patient with atrial fibrillation (AF) Hypothesis: We sought to investigate the association of prolonged QRSd (≥120 ms) and risk of heart failure and in-hospital death in patients admitted for AF with rapid ventricular response (RVR) Methods: A retrospective study in a community hospital using EPIC database analyzed 1637 patients from 2013-2018 with admission codes of AF with RVR. The cohort was then stratified based on QRSd ≥120ms vs Results: Among the 1637 patients who were admitted with AF with RVR, 233 (14%) had QRS ≥120ms. Patient’s characteristics with QRSd≥120 compared to those with QRSd Conclusions: In patients who were admitted with AF with RVR, QRSd≥120ms was associated with a higher burden of cardiovascular disease, CHA2DS2Vasc score and an increased risk of heart failure resulting in worse clinical outcomes. Higher median BNP values suggest that worsening heart failure contributed to higher in-hospital mortality. Heart failure associated mortality could be alleviated with medical management or cardiac resynchronization therapy.

Background: Cardiovascular (CV) disease is a major cause of morbidity in patients with type 2 diabetes mellitus (DM2). DM2 patients often experience Atrial Fibrillation (AF) with aggravated CV morbidity and mortality. We investigated the clinical risk factors in patients with DM2 hospitalized with AF with rapid ventricular response (RVR). Methods: A retrospective study was conducted using a community hospital EMR database from 2013-2018. Adults with admission codes for AF with RVR were included in the study, and were stratified based on the presence or absence of DM2. Patient characteristics, and clinical outcomes were compared. Results: Among 1643 patients with AF with RVR, 501 (30.5%) had DM2. Median (IQR) age for DM2 patients compared to controls was 72(64, 79) vs. 73(62, 83), P=0.12, 54.5% vs. 54.6% were female P=0.98, had coronary artery disease [39.5% vs. 25.3% (P Conclusion: Among patients hospitalized for AF with RVR, DM2 patients had a higher prevalence of cardiovascular disease and longer LOS. A higher prevalence of HF may be a contributing factor to longer LOS. Understanding the risk of HF in patients with DM2 and AF is needed to address clinical outcomes in the future. Disclosure A. Alkhayru: None. B. Tappuni: None. B. Kaseer: None. D.M. Brandt: None. F. Ghazi: Speaker’s Bureau; Self; AstraZeneca K.K., Boston Scientific, Janssen Pharmaceuticals, Inc. M.W. Winner: None. K. Shemisa: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc.

Objective This study aimed to investigate the relationship between waist circumference as a measure of abdominal obesity and brain responses to stress among patients with coronary artery disease (CAD). Methods Patients with CAD (N = 151) underwent acute mental stress tasks in conjunction with high-resolution positron emission tomography and radiolabeled water imaging of the brain. Brain responses to mental stress were correlated with waist circumference. Results Waist circumference was positively correlated with increased activation in the right and left frontal lobes (β values ranging from 2.81 to 3.75 in the paracentral, medial, and superior gyri), left temporal lobe, left hippocampal, left amygdala, left uncus, and left anterior and posterior cingulate gyri (β values ranging from 2.93 to 3.55). Waist circumference was also negatively associated with the left and right parietal lobes, right superior temporal gyrus, and right insula and precuneus (β values ranging from 2.82 to 5.20). Conclusion Increased brain activation in the brain regions involved in the stress response and autonomic regulation of the cardiovascular system during psychological stress may underlie stress-induced overeating and abdominal obesity in patients with CAD.

BACKGROUND: Circulating progenitor cells (CPC) have been associated with memory function and cognitive impairment in healthy adults. However, it is unclear whether such associations also exist in patients with coronary artery disease (CAD). OBJECTIVE: To assess the association between CPCs and memory performance among individuals with CAD. METHODS: We assessed cognitive function in 509 patients with CAD using the verbal and visual Memory subtests of the Wechsler memory scale-IV and the Trail Making Test parts A and B. CPCs were enumerated with flow cytometry as CD45(med)/CD34+ blood mononuclear cells, those co-expressing other epitopes representing populations enriched for hematopoietic and endothelial progenitors. RESULTS: After adjusting for demographic and cardiovascular risk factors, lower number of endothelial progenitor cell counts were independently associated with lower visual and verbal memory scores (p for all < 0.05). There was a significant interaction in the magnitude of this association with race (p < 0.01), such that the association of verbal memory scores with endothelial progenitor subsets was present in Black but not in non-Black participants. No associations were present with the hematopoietic progenitor-enriched cells or with the Trail Making Tests. CONCLUSION: Lower numbers of circulating endothelial progenitor cells are associated with cognitive impairment in patients with CAD, suggesting a protective effect of repair/regeneration processes in the maintenance of cognitive status. Impairment of verbal memory function was more strongly associated with lower CPC counts in Black compared to non-Black participants with CAD. Whether strategies designed to improve regenerative capacity will improve cognition needs further study.

Rationale: Blacks compared with whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes; however, little is known about racial differences in CPCs. Objective: To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction and the predictive value of CPC counts in blacks compared with whites. Methods and Results: CPCs were enumerated by flow cytometry as CD45med + blood mononuclear cells expressing CD34+, CD133+, VEGF2R+, and CXCR4+ epitopes in 1747 subjects, mean age 58.4±13, 55% male, and 26% self-reported black. Patients presenting with acute myocardial infarction (n=91) were analyzed separately. Models were adjusted for relevant clinical variables. SDF-1α (stromal cell-derived factor-1α), VEGF (vascular endothelial growth factor), and MMP-9 (matrix metallopeptidase-9) levels were measured (n=561), and 623 patients were followed for median of 2.2 years for survival analysis. Blacks were younger, more often female, with a higher burden of cardiovascular risk, and lower CPC counts. Blacks had fewer CD34+ cells (−17.6%; [95% confidence interval (CI), −23.5% to −11.3%]; P P P P =0.04) compared with whites. The association between lower CPC counts and black race was not affected by risk factors or cardiovascular disease. Results were validated in a separate cohort of 411 patients. Blacks with acute myocardial infarction had significantly fewer CPCs compared with whites ( P =0.02). Blacks had significantly lower plasma MMP-9 levels ( P P =0.03) and whites (hazard ratio, 1.79; [95% CI, 1.09–2.94]; P =0.02) without significant interaction. Conclusions: Black subjects have lower levels of CPCs compared with whites which is partially dependent on lower circulating MMP-9 levels. Impaired regenerative capacity is predictive of adverse outcomes in blacks and may partly account for their increased risk of cardiovascular events.

Rationale: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). Objective: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. Methods and Results: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31–2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18–5.13) increase in all-cause mortality, P =0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. Conclusions: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.

OBJECTIVES: Research suggests that following a myocardial infarction (MI), women under the age of 60 have more elevated depressive symptoms and adverse outcomes than similarly aged men. Identifying risk factors that contribute to gender differences in depressive symptoms among this group may be critical to the development of psychosocial interventions. Experiences of discrimination may be an important correlate of depressive symptoms in this group; however, studies of this relationship have largely been cross-sectional and focused on healthy populations. This study examines longitudinal associations among gender, discrimination, and depressive symptoms in a young post-MI cohort. METHODS: Participants were 313 adults from the Myocardial Infarction and Mental Stress Ischemia Study 2 of young (≤60 yrs) post-MI patients. At baseline and 6 month follow-up, depressive symptoms were measured with the Beck Depression Inventory-II and discrimination was assessed with the 10-item version Everyday Discrimination scale. Linear regression models were used to assess the longitudinal association between reports of discrimination and depressive symptoms adjusted for sociodemographic characteristics, psychosocial factors and health status indicators and tested for gender differences. RESULTS: The mean age was 51.2, 49.6% were women, and 69.5% were African-American. Although the discrimination-by-gender interaction was marginally significant (p=.09) in the fully adjusted model, findings suggest that the association between changes in reports of discrimination and depressive symptoms over time may be more pronounced for women (β=.61, standard error=.15, p

Background Higher symptom levels of a variety of measures of emotional distress have been associated with cardiovascular disease ( CVD ), especially among women. Here, our goal was to investigate the association between a composite measure of psychological distress and incident cardiovascular events. Methods and Results In a prospective cohort study, we assessed 662 individuals (28% women; 30% blacks) with stable coronary artery disease. We used a composite score of psychological distress derived through summation of Z‐transformed psychological distress symptom scales (depression, posttraumatic stress, anxiety, anger, hostility, and perceived stress) as a predictor of an adjudicated composite end point of adverse events (cardiovascular death, myocardial infarction, stroke, heart failure, or unstable angina). During a mean follow‐up of 2.8 years, 120 (18%) subjects developed CVD events. In the overall population, there was no association between the psychological distress measure and CVD events, but there was a sex‐based interaction ( P =0.004). In women, higher psychological distress was associated with a higher incidence of CVD events; each SD increase in the composite score of psychological distress was associated with 1.44 times adjusted hazard of CVD events (95% CI, 1.09–1.92). No such association was found in men. Conclusions Among patients with coronary artery disease, higher psychological distress is associated with future cardiovascular events in women only.

African Americans tend to develop coronary artery disease (CAD) at a younger age than other groups. Previous data on racial disparities in outcomes of myocardial infarction (MI) have not been consistent and have mostly been limited to older populations. Young African American MI patients may

Atrial fibrillation (AF) is associated with increased risk of heart failure (HF) and mortality. There is a paucity of evidence for HF patients hospitalized with AF. We sought to investigate the short-term clinical outcomes in patients hospitalized for AF with rapid ventricular response (RVR). A

Background Young women with coronary artery disease ( CAD ), a group with high psychosocial burden, were previously shown to have higher levels of interleukin‐6 ( IL ‐6) compared with men of similar age. We sought to examine IL ‐6 response to acute stress in CAD patients across sex and age, and contrast results to healthy controls and other biomarkers known to increase with mental stress (monocyte chemoattractant protein‐1 and matrix metallopeptidase‐9) and known limited stress‐reactivity (high‐sensitivity C‐reactive protein). Methods and Results Inflammatory biomarkers were measured at rest and 90 minutes after mental stress (speech task) among 819 patients with CAD and 89 healthy controls. Repeated‐measures models were used to investigate age (continuous) and sex differences across time, before and after adjusting for demographics, CAD risk factors, depressive symptoms, medication use, and CAD severity. Among patients with CAD , the mean age was 60 years (range, 25–79) and 31% were women. Younger women with CAD had significantly higher concentrations of IL ‐6 at rest, 90 minutes after mental stress, as well as a higher response to stress, compared with similarly aged men ( P IL ‐6 increased with age, and there were no sex differences in IL ‐6 levels or response to stress among controls. Inflammatory responses to stress for high‐sensitivity C‐reactive protein, monocyte chemoattractant protein‐1, and matrix metallopeptidase‐9 among CAD patients were similar in women and men. Conclusions IL ‐6 response to mental stress are higher in young women with CAD than men of similar age.

Living in neighborhoods characterized by poverty may act as a chronic stressor that results in physiological dysregulation of the sympathetic nervous system. No previous study has assessed neighborhood poverty with hemodynamic, neuroendocrine, and immune reactivity to stress. We used data from 632 patients with coronary artery disease. Patients’ residential addresses were geocoded and merged with poverty data from the 2010 American Community Survey at the census-tract level. A z-transformation was calculated to classify census tracts (neighborhoods) as either having ‘high’ or ‘low’ poverty. Systolic blood pressure, diastolic blood pressure, heart rate, rate-pressure product, epinephrine, interleukin-6, and high-sensitivity C-reactive protein were measured before and after a public speaking stress task. Multilevel models were used for repeated measures and accounting for individuals nested within census tracts. Adjusted models included demographics, lifestyle and medical risk factors, and medication use. Another set of models included propensity scores weighted by the inverse probability of neighborhood status for sex, age, race, and individual-level income. The mean age was 63 years and 173 were women. After adjusting for potential confounders, participants living in high (vs. low) poverty neighborhoods had similar hemodynamic values at rest and lower values during mental stress for systolic blood pressure (157 mmHg vs. 161 mmHg; p = 0.07), heart rate (75 beats/min vs. 78 beats/min; p = 0.02) and rate-pressure product (11839 mmHg x beat/min vs 12579 mmHg x beat/min; p = 0.01). P-values for neighborhood poverty-by-time interactions were < 0.05. Results were similar in the propensity weighted models. There were no significant differences in inflammatory and epinephrine responses to mental stress based on neighborhood poverty status. A blunted hemodynamic response to mental stress was observed among participants living in high poverty neighborhoods. Future studies should explore whether neighborhood poverty and blunted hemodynamic response to stress translate into differences in long-term cardiovascular outcomes.

Background: Exposure to psychological stress has been associated with the development of sustained arrhythmias. Acute changes in atrial electrophysiology may serve as intermediate phenotypes for stress-induced arrhythmia. The relationship between atrial electrical changes and stress related changes in heart rate and myocardial ischemia is unknown. We sought to study the effect of altered atrial electrophysiology and stress related rise in HR and myocardial ischemia in females and males. Methods: We examined if acute mental stress was associated with abnormal P-wave axis development in 359 patients (mean age=56 ± 9.9 years; 62% men; 43% white) with stable coronary heart disease and normal baseline P-wave axis (between 0° and 75°) who underwent mental stress testing (speech task). We computed the percentage of patients who had abnormal P-wave axis during stress and recovery. Sex-stratified analyses were performed. A multivariable logistic regression model was used to determine if mental stress ischemia independent predictors of abnormal P-wave axis development. Results: A total of 46 (13%) patients developed abnormal P-wave axis during either stress or recovery (stress: n=43, 12%; recovery: n=12, 3%). A rise in heart rate during mental stress was associated with an increased risk of abnormal P-wave axis development (per 5-unit increase: OR=1.37, 95%CI=1.03, 1.30). Mental stress-induced myocardial ischemia was associated with increased risk of abnormal P-wave axis in women (OR=5.2, 95%CI=1.7, 15.6) and not in men (OR=0.1, 95%CI=0.01, 1.01), p-interaction=0.004). Interactions were not detected for other characteristics. Conclusion: Acute mental stress results in the development of abnormal P-wave axis, and this phenomenon is related to increases in heart rate and, among women, mental stress-induced ischemia. Our data suggest that acute psychological stress can promote adverse transient electrical changes in the atria.

Introduction: Reduced functional capacity, assessed by self-reported Duke Activity Status Index (DASI) is associated with adverse outcomes. Peripheral microvascular dysfunction, measured as reduced digital reactive hyperemia index (RHI) is also associated with adverse events. Whether microvascular dysfunction is related to functional capacity is unknown. Hypothesis: We hypothesized that peripheral microvascular dysfunction is associated with diminished functional capacity. Methods: In 531 patients with stable CAD (age 62±9, 75% male, 30% Black, EF 55±13%) enrolled in the Mental Ischemia Prognosis Study, self-reported functional capacity was assessed with the DASI questionnaire with a score of >25 as the cutoff for normal. Pulsatile arterial tonometry (EndoPat, Itamar Inc.) was used to measure digital RHI during 5 minutes of upper arm occlusion with blood pressure cuff followed by reperfusion. Logistic regression was used to model reduced RHI (25 vs ≤ 25). Results: Median RHI was 2.01 [IQR 1.67, 2.49] while median DASI score was 45 [29,53], equivalent to 8.3 METs. Compared to those with normal DASI score (>25; N=425), subjects with low DASI score (≤25; N=106) had lower RHI (1.88 [1.64, 2.24] vs 2.06 [1.69, 2.54], P=0.048), higher BMI (32±7 kg/m 2 vs 29±5 kg/m 2 , P Conclusion: Poor functional capacity is independently associated with microvascular dysfunction in patients with stable CAD, and illustrates a potential mechanism by which reduced functional capacity increases cardiovascular risk. Whether improvement in functional capacity by exercise/rehabilitation programs improves microvascular function requires further investigation.

Introduction: Peripheral arterial vasoconstriction during mental stress (MS) has been associated with mental stress-induced myocardial ischemia, which in turn has been linked with worse cardiovascular outcomes. It is unknown whether the magnitude of peripheral vasoconstriction with MS is predictive of long term outcomes. Hypothesis: We hypothesized that greater peripheral arterial vasoconstriction during MS would be associated with adverse events among patients with coronary artery disease (CAD). Methods: Four hundred sixty-three patients with stable CAD and normal left ventricular function, (age 63±9, 75% male, 27% Black, EF 60±8 %) underwent MS testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured at baseline and during MS using peripheral arterial tonometry (PAT), and the PAT ratio of pulse wave amplitude (during mental stress/ baseline) was calculated. Cox proportional hazard models were calculated to examine the association between the PAT ratio and outcomes. Results: Median PAT ratio during MS was 0.68, indicating 32% average constriction with MS compared to rest. Subjects with greater peripheral constriction [low ( Conclusion: Greater peripheral arterial vasoconstriction with MS is associated with a higher risk of adverse cardiovascular outcomes in patients with CAD.

Pregnancy related heart disease is prevalent & exhibits significant morbidity. Peripartum Cardiomyopathy (PPCM) & Preeclampsia (PE) are 2 conditions with significant overlap. We sought to determine clinical risk factors of PPCM versus PE. A retrospective case control study was undertaken using our

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice and so is depression with a prevalence of 16% in the United States. Whether depressive symptoms are associated with AF remains unclear, with previous studies yielding inconsistent results. Our objective was to

The patient presented with fatigue, cough, light-headedness, and a heart rate of 30 beats per minute.

Endothelial cells are involved in regulating coronary blood flow (CBF) and coronary vascular resistance (CVR). However, the role of endothelial function in regulating CBF responses during mental stress (MS) remains understudied In 38 patients (Age 61±11 years) with stable CAD, endothelium