Publications by authors named "Viola Vaccarino"

363 Publications

Association of Depressive Symptoms with Sleep Disturbance: A Co-twin Control Study.

Ann Behav Med 2021 May 15. Epub 2021 May 15.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Background: Few studies have comprehensively evaluated the association of depression with sleep disturbance using a controlled twin study design.

Purpose: To cross-sectionally evaluate the association of depression with both objective and subjective sleep disturbance.

Methods: We studied 246 members of the Vietnam Era Twin Registry. We measured depressive symptoms using the Beck Depression Inventory-II (BDI) and assessed major depression using structured clinical interviews. Twins underwent one-night polysomnography and 7-day actigraphy to derive measures of objective sleep and completed the Pittsburgh Sleep Quality Index for subjective sleep. Multivariable mixed-effects models were used to examine the association.

Results: Twins were all male, mostly white (97%), with a mean (SD) age of 68 (2). The mean (SD) BDI was 5.9 (6.3), and 49 (20%) met the criteria for major depression. For polysomnography, each 5-unit higher BDI, within-pair, was significantly associated with 19.7 min longer rapid eye movement (REM) sleep latency, and 1.1% shorter REM sleep after multivariable adjustment. BDI was not associated with sleep architecture or sleep-disordered breathing. For actigraphy, a higher BDI, within-pair, was significantly associated with lower sleep efficiency, more fragmentation and higher variability in sleep duration. BDI was associated with almost all dimensions of self-reported sleep disturbance. Results did not differ by zygosity, and remained consistent using major depression instead of BDI and were independent of the presence of comorbid posttraumatic stress disorder and antidepressant use.

Conclusions: Depression is associated with REM sleep disruption in lab and sleep fragmentation and sleep variability at home, but not with sleep architecture or sleep-disordered breathing.
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http://dx.doi.org/10.1093/abm/kaab040DOI Listing
May 2021

Neurobiological Pathways Linking Acute Mental Stress to Impairments in Executive Function in Individuals with Coronary Artery Disease.

J Alzheimers Dis Rep 2021 Feb 2;5(1):99-109. Epub 2021 Feb 2.

Emory Clinical Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.

Background: Individuals with coronary artery disease (CAD) have worse executive function compared to the general population but the mechanisms are unknown.

Objective: To investigate the role of acute mental stress (MS) on the executive function of patients with CAD.

Methods: Participants with stable CAD underwent acute MS testing with simultaneous peripheral vascular function measurements and brain imaging using high resolution-positron emission tomography. Digital pulse wave amplitude was continuously measured using peripheral artery tonometry (PAT, Itamar Inc). Stress/rest PAT ratio (sPAT) of pulse wave amplitude during MS/baseline was calculated as a measure of microvascular constriction during MS. Plasma levels of catecholamine and interleukin-6 were assessed at baseline and after MS. Executive function was assessed both at baseline and at 2 years follow-up using the Trail Making Test parts A and B.

Results: We studied 389 individuals with brain data available for 148 participants. Of this population follow-up cognitive assessments were performed in 226 individuals (121 with brain imaging). After multivariable adjustment for baseline demographics, risk factors, and medication use, a lower sPAT, indicating greater vasoconstriction, a higher inferior frontal lobe activation with MS, and increases in norepinephrine and IL-6 levels with MS were all independently associated with greater time to complete Trail B test.-38.4pt.

Conclusion: In response to acute MS, greater peripheral vasoconstriction, higher inferior frontal lobe brain activation, and increases in the levels of norepinephrine and IL-6 are associated with worse executive function.
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http://dx.doi.org/10.3233/ADR-200287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990469PMC
February 2021

Transfer learning from ECG to PPG for improved sleep staging from wrist-worn wearables.

Physiol Meas 2021 Mar 24. Epub 2021 Mar 24.

Department of Biomedical Informatics, Emory University, Atlanta, Georgia, UNITED STATES.

Objective: To develop a sleep staging method from wrist-worn accelerometry and the photoplethysmogram (PPG) by leveraging transfer learning from a large electrocardiogram (ECG) database.

Approach: In previous work, we developed a deep convolutional neural network for sleep staging from ECG using the cross-spectrogram of ECG-derived respiration and instantaneous beat intervals, heart rate variability metrics, spectral characteristics, and signal quality measures derived from 5,793 subjects in Sleep Heart Health Study (SHHS). We updated the weights of this model by transfer learning using PPG data derived from the Empatica E4 wristwatch worn by 105 subjects in the `Emory Twin Study Follow-up' (ETSF) database, for whom overnight polysomnographic (PSG) scoring was available. The relative performance of PPG, and actigraphy (Act), plus combinations of these two signals, with and without transfer learning was assessed.

Main Results: The performance of our model with transfer learning showed higher accuracy (1-9 percentage points) and Cohen's Kappa (0.01-0.13) than those without transfer learning for every classification category. Statistically significant, though relatively small, incremental differences in accuracy occurred for every classification category as tested with the McNemar test. The out-of-sample classification performance using features from PPG and actigraphy for four-class classification was Accuracy (Acc)=68.62% and Kappa=0.44. For two-class classification, the performance was Acc=81.49% and Kappa=0.58.

Significance: We proposed a combined PPG and actigraphy-based sleep stage classification approach using transfer learning from a large ECG sleep database. Results demonstrate that the transfer learning approach improves estimates of sleep state. The use of automated beat detectors and quality metrics means human over-reading is not required, and the approach can be scaled for large cross-sectional or longitudinal studies using wrist-worn devices for sleep-staging.
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http://dx.doi.org/10.1088/1361-6579/abf1b0DOI Listing
March 2021

Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

Arterioscler Thromb Vasc Biol 2021 May 18;41(5):1801-1809. Epub 2021 Mar 18.

Department of Epidemiology (A.Y., MG., S.M.S., C.L., K.M., A.J.S., B.P., I.U., V.V.), Rollins School of Public Health, Emory University, Atlanta, GA.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.316083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062308PMC
May 2021

Cardiovascular pathophysiology from the cardioneural perspective and its clinical applications.

Trends Cardiovasc Med 2021 Mar 9. Epub 2021 Mar 9.

Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, CNR 3053, Atlanta, GA 30322, United States; Department of Medicine, Division of Cardiology, Emory University School of Medicine, United States.

Coronary heart disease and psychological stress factors such as depression are prevalent and associated with high morbidity/mortality; they are also challenging to manage, especially when treated in isolation of each other. Recent advances support an integrated approach to their management that is built on a foundation of an extensive, multi-component network of neurological structures. In this review, we describe this extensive cardioneural network that encompasses the heart, brain, spinal cord, and ganglia throughout the body, and then discuss ambulatory and laboratory-based non-invasive measures of this network that both measure psychological stress and heart disease severity. Lastly, we discuss their potential transformative clinical and public health applications, and also possible cardioneural interventions such as exercise and biofeedback.
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http://dx.doi.org/10.1016/j.tcm.2021.03.001DOI Listing
March 2021

Association of Psychosocial Factors With Short-Term Resting Heart Rate Variability: The Atherosclerosis Risk in Communities Study.

J Am Heart Assoc 2021 Feb 26;10(5):e017172. Epub 2021 Feb 26.

Department of Medicine School of Medicine Emory University Atlanta GA.

Background Psychosocial factors predict heart disease risk, but our understanding of underlying mechanisms is limited. We sought to evaluate the physiologic correlates of psychosocial factors by measuring their relationships with heart rate variability (HRV), a measure of autonomic health, in the ARIC (Atherosclerosis Risk in Communities) study. We hypothesize that increased psychosocial stress associates with lower HRV. Methods and Results We studied 9331 participants in ARIC with short-term HRV data at visits 2 and 4. The mean (SD) age was 54.4 (5.7) years, 55% were women, and 25% were Black. Psychosocial factors included: (1) vital exhaustion (VE), (2) anger proneness, a personality trait, and (3) perceived social support. Linear models adjusted for sociodemographic and cardiovascular risk factors. Low frequency HRV (ln ms) was significantly lower in the highest versus lowest quartiles of VE (B=-0.14, 95% CI, -0.24 to -0.05). When comparing this effect to age (B=-0.04, 95% CI, -0.05 to -0.04), the difference was equivalent to 3.8 years of accelerated aging. Perceived social support associated with lower time-domain HRV. High VE (versus low VE) also associated with greater decreases in low frequency over time, and both anger and VE associated with greater increases in resting heart rate over time. Survival analyses were performed with Cox models, and no evidence was found that HRV explains the excess risk found with high VE and low perceived social support. Conclusions Vital exhaustion, and to a lesser extent anger and social support, were associated with worse autonomic function and greater adverse changes over time.
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http://dx.doi.org/10.1161/JAHA.120.017172DOI Listing
February 2021

Epigenetic Age Acceleration and Cognitive Decline: A Twin Study.

J Gerontol A Biol Sci Med Sci 2021 Feb 19. Epub 2021 Feb 19.

Department of Epidemiology, Emory University Rollins School of Public Health, NE, Atlanta, GA.

Background: Little is known about the role of DNA methylation (DNAm) epigenetic age acceleration in cognitive decline. Using a twin study design, we examined whether DNAm age acceleration is related to cognitive decline measured longitudinally in persons without a clinical diagnosis of dementia.

Methods: We studied 266 paired male twins (133 pairs) with a mean age of 56 years at baseline. Of these, 114 paired twins returned for a follow-up after an average of 11.5 years. We obtained six indices of DNAm age acceleration based on epigenome-wide data from peripheral blood lymphocytes. At both baseline and follow-up, we administered a battery of cognitive measures and constructed two composite scores, one for executive function and one for memory function. We fitted multivariable mixed regression models to examine the association of DNAm age acceleration markers with cognitive function within pairs.

Results: In cross sectional analyses at baseline, there was no association between DNAm age acceleration and cognitive function scores. In longitudinal analyses, however, comparing twins within pairs, each additional year of age acceleration using the Horvath's method was associated with a 3% decline (95% CI, 1% to 5%) in the composite executive function score and a 2.5% decline (95% CI, 0.01% to 4.9%) in the memory function score. These results did not attenuate after adjusting for education and other risk factors.

Conclusions: Middle-aged men who had older DNAm age relative to their brothers of the same demographic age, showed a faster rate of cognitive decline in the subsequent 11.5 years. These results point to the role of epigenetic modifications in cognitive aging.
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http://dx.doi.org/10.1093/gerona/glab047DOI Listing
February 2021

Mental stress-induced myocardial ischemia and cognitive impairment in coronary atherosclerosis.

J Psychosom Res 2021 02 25;141:110342. Epub 2020 Dec 25.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States of America; Emory Clinical Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States of America. Electronic address:

Objective: To understand if presence of mental stress-induced myocardial ischemia (MSIMI) is associated with higher prevalence of cognitive impairment at baseline and its decline over time.

Methods: A cohort of participants with stable coronary atherosclerosis underwent acute mental stress testing using a series of standardized speech/arithmetic stressors. The stress/rest digital vasomotor response to mental stress (sPAT) was assessed to measure microvascular constriction during mental stress. Patients received 99mTc-sestamibi myocardial perfusion imaging at rest, with mental stress and with conventional (exercise/pharmacological) stress. Cognitive function was assessed both at baseline and at a 2 year follow-up using the Trail Making Test parts A and B and the verbal and visual memory subtests of the Wechsler Memory Scale.

Results: We studied 486 individuals (72% male, 32.1% Black, 62 ± 9 (mean ± SD) years old). After multivariable adjustment for baseline demographics, risk factors, and medication use, presence of MSIMI was associated with 21% and 20% slower completion of Trail-A and Trail-B, respectively (p for all <0.01). After a 2-year follow-up period, presence of MSIMI was associated with a 33% slower completion of Trail-B, denoting cognitive decline (B = 0.33, 95% CI, 0.04, 0.62). A lower sPAT, indicating greater vasoconstriction, mediated the association between MSIMI and worsening Trail-B performance by 18.2%. Ischemia with a conventional stress test was not associated with any of the cognitive tests over time.

Conclusion: MSIMI is associated with slower visuomotor processing and worse executive function at baseline and with greater decline in these abilities over time.
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http://dx.doi.org/10.1016/j.jpsychores.2020.110342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857648PMC
February 2021

Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial.

Neurobiol Stress 2020 Nov 20;13:100264. Epub 2020 Oct 20.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.

Objective: Exacerbated autonomic responses to acute stress are prevalent in posttraumatic stress disorder (PTSD). The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to acute stress in patients with PTSD. The authors hypothesized tcVNS would reduce the sympathetic response to stress compared to a sham device.

Methods: Using a randomized double-blind approach, we studied the effects of tcVNS on physiological responses to stress in patients with PTSD (n = 25) using noninvasive sensing modalities. Participants received either sham (n = 12) or active tcVNS (n = 13) after exposure to acute personalized traumatic script stress and mental stress (public speech, mental arithmetic) over a three-day protocol. Physiological parameters related to sympathetic responses to stress were investigated.

Results: Relative to sham, tcVNS paired to traumatic script stress decreased sympathetic function as measured by: decreased heart rate (adjusted β = -5.7%; 95% CI: ±3.6%, effect size d = 0.43, p < 0.01), increased photoplethysmogram amplitude (peripheral vasodilation) (30.8%; ±28%, 0.29, p < 0.05), and increased pulse arrival time (vascular function) (6.3%; ±1.9%, 0.57, p < 0.0001). Similar (p < 0.05) autonomic, cardiovascular, and vascular effects were observed when tcVNS was applied after mental stress or without acute stress.

Conclusion: tcVNS attenuates sympathetic arousal associated with stress related to traumatic memories as well as mental stress in patients with PTSD, with effects persisting throughout multiple traumatic stress and stimulation testing days. These findings show that tcVNS has beneficial effects on the underlying neurophysiology of PTSD. Such autonomic metrics may also be evaluated in daily life settings in tandem with tcVNS therapy to provide closed-loop delivery and measure efficacy.ClinicalTrials.gov Registration # NCT02992899.
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http://dx.doi.org/10.1016/j.ynstr.2020.100264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739181PMC
November 2020

Sexual Differences in Genetic Predisposition of Coronary Artery Disease.

Circ Genom Precis Med 2021 Feb 17;14(1):e003147. Epub 2020 Dec 17.

Department of Epidemiology (Y.H., Q.H., M.G., V.V., Y.V.S.), School of Medicine, Emory University, Atlanta, GA.

Background: The genomic structure that contributes to the risk of coronary artery disease (CAD) can be evaluated as a risk score of multiple variants. However, sex differences have not been fully examined in applications of genetic risk score (GRS) of CAD.

Methods: Using data from the UK Biobank, we constructed a CAD-GRS based on all known loci, 3 mediating trait-based (blood pressure, lipids, and body mass index) subscores, and a genome-wide polygenic risk score based on 1.1 million variants. The differences in genetic associations with prevalent and incident CAD between men and women were investigated among 317 509 unrelated individuals of the European ancestry. We also assessed interactions with sex for 161 individual loci included in the comprehensive GRS.

Results: For both prevalent and incident CAD, the associations of comprehensive and genome-wide GRSs were stronger among men than women. Using a score of 161 loci, we observed a 2.4× higher risk for incident CAD comparing men with high genetic risk to men with low genetic risk but an 80% greater risk comparing women with high genetic risk to women with low genetic risk (interaction =0.002). Of the 3 subscores, the blood pressure-associated subscore exhibited sex differences (interaction =0.0004 per SD increase in subscore). Analysis of individual variants identified a novel gene-sex interaction at locus .

Conclusions: Sexual differences in genetic predisposition should be considered in future studies of CAD, and GRSs should not be assumed to perform equally well in men and women.
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http://dx.doi.org/10.1161/CIRCGEN.120.003147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887043PMC
February 2021

Association between symptoms of psychological distress and cognitive functioning among adults with coronary artery disease.

Stress Health 2020 Dec 14. Epub 2020 Dec 14.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Greater psychological distress is associated with cognitive impairment in healthy adults. Whether such associations also exist in patients with coronary artery disease (CAD) is uncertain. We assessed cognitive function in 496 individuals with CAD using the verbal and visual memory subtests of the Wechsler Memory Scale and executive functioning measured by the Trail Making Test Parts A and B. 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) and scores for each individual psychological scale. Multivariable linear regression models were used to determine the association between memory scores (as outcomes) and the psychological distress scores (both composite score and individual scales). After adjusting for demographic and cardiovascular risk factors, a higher psychological distress score was independently associated with worse memory and executive functioning. Each standard deviation increase in psychological distress score was associated with 3% (95% confidence interval [CI], 1%-5%) to 5% (95% CI, 3-7%) worse cognitive performance (higher Trail A and Trail B, and lower verbal and visual memory scores). Among individuals with CAD, a higher level of psychological distress is independently associated with worse cognitive performance. These findings suggest that psychological risk factors play a role in cognitive trajectories of persons with CAD.
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http://dx.doi.org/10.1002/smi.3018DOI Listing
December 2020

Neighborhood characteristics and ideal cardiovascular health among Black adults: results from the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity.

Ann Epidemiol 2020 Dec 5. Epub 2020 Dec 5.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. Electronic address:

Purpose: Neighborhood environment is increasingly recognized as an important determinant of cardiovascular health (CVH) among Black adults. Most research to date has focused on negative aspects of the neighborhood environment, with little attention being paid to the specific positive features, in particular the social environment, that promote cardiovascular resilience among Black adults.We examined whether better neighborhood physical and social characteristics are associated with ideal CVH among Black adults, as measured by Life's Simple 7 (LS7) scores.

Methods: We recruited 392 Black adults (age 53 ± 10 years, 39% men) without known CV disease living in Atlanta, GA. Seven neighborhood domains were assessed via questionnaire: asthetic quality, walking environment, safety, food access, social cohesion, activity with neighbors, and violence. CVH was determined by LS7 scores calculated from measured blood pressure; glucose; cholesterol; body mass index (BMI); and self-reported exercise, diet, and smoking, and categorized into poor (0-8), intermediate (9-10), and ideal (11-14). Multinomial logistic regression was used to examine the association between neighborhood characteristics and the odds of intermediate/ideal CVH categories compared with poor CVH after adjustment for age, gender, household income, education, marital status, and employment status.

Results: Better scores in the neighborhood domains of social cohesion and activity with neighbors were significantly associated with higher adjusted odds of ideal LS7 scores (OR 2.02, 95% CI [1.36-3.01] and 1.71 [1.20-2.45] per 1 standard deviation [SD] increase in respective scores). These associations were stronger for both social cohesion (OR 2.61, 95% CI [1.48-4.61] vs. 1.40 [0.82-2.40]) and activity with neighbors (OR 1.82, 95% CI [1.15-2.86] vs. 1.53 [0.84-2.78]) in Black women than men. Specifically, better scores in social cohesion were associated with higher odds of ideal CVH in exercise (OR 1.73 [1.16-2.59]), diet (OR 1.90 [1.11-3.26]), and BMI (OR 1.52 [1.09-2.09]); better scores in activity with neighbors were also similarly associated with higher odds of ideal CVH in exercise (OR 1.48 [1.00-2.19]), diet (OR 2.15 [1.23-3.77]), and BMI (OR 1.45 [1.07-1.98]; per 1 SD in respective scores).

Conclusions: More desirable neighborhood characteristics, particularly social cohesion and activity with neighbors, were associated with better CVH among Black adults.
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http://dx.doi.org/10.1016/j.annepidem.2020.11.009DOI Listing
December 2020

Association of Early-Life Trauma and Risk of Adverse Cardiovascular Outcomes in Young and Middle-aged Individuals With a History of Myocardial Infarction.

JAMA Cardiol 2020 Nov 13. Epub 2020 Nov 13.

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

Importance: Compared with older patients, young adults with a history of myocardial infarction (MI) tend to have a higher burden of psychosocial adversity. Exposure to early-life stressors may contribute to the risk of adverse outcomes in this patient population, potentially through inflammatory pathways.

Objective: To investigate the association of early-life trauma with adverse events and examine whether inflammation plays a role.

Design, Setting, And Participants: This cohort study included patients aged 18 to 60 years with a verified history of MI in the past 8 months from a university-affiliated hospital network. Baseline data were collected from June 2011 to March 2016, and follow-up data were obtained through July 2019. Analysis began September 2019.

Exposures: Early-life trauma was assessed using the Early Trauma Inventory-Self Report short form (ETI-SR-SF), both as a continuous and as a binary variable at the threshold of a score of 7 or higher. Inflammatory biomarkers, interleukin 6, and C-reactive protein were obtained at baseline.

Main Outcomes And Measures: A composite end point of recurrent MI, stroke, heart failure hospitalization, and cardiovascular death over a median 3-year follow-up.

Results: Of 300 patients, the mean (SD) age was 51 (7) years, 198 (66%) were African American, and 150 (50%) were women. Compared with participants with MI with an ETI-SR-SF score less than 7, those with a score of 7 or higher had higher levels of interleukin 6 and C-reactive protein at baseline. Compared with participants with an ETI-SR-SF score less than 7, those with a score of 7 or higher were at a greater risk for adverse outcomes, with a hazards ratio of 2.3 (95% CI, 1.3-3.9). Results remained consistent in multivariable analysis. Further adjustment for C-reactive protein rendered the results no longer statistically significant. Early-life trauma displayed a dose-dependent response when analyzed as a continuous variable and by quartiles.

Conclusions And Relevance: Early-life trauma is an independent risk factor for adverse outcomes in young and middle-aged individuals with a history of MI. Neurobiological mechanisms leading to lifetime activation of systemic inflammatory cascades may be implicated.
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http://dx.doi.org/10.1001/jamacardio.2020.5749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666433PMC
November 2020

The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD).

J Psychiatr Res 2021 May 31;137:579-588. Epub 2020 Oct 31.

Emory University School of Medicine, Atlanta GA; Atlanta VAMC, Decatur, GA, USA; The Vietnam Era Twin Registry, Seattle Veterans Administration Epidemiology Research, USA.

Background: Studies using structural magnetic resonance imaging (MRI) volumetrics showed smaller hippocampal volume in patients with post-traumatic stress disorder (PTSD). These studies were cross-sectional and did not address whether smaller volume is secondary to stress-induced damage, or whether pre-existing factors account for the findings. The purpose of this study was to use a co-twin case control design to assess the relative contribution of genetic and environmental factors to hippocampal volume in PTSD.

Methods: Monozygotic (N = 13 pairs) and dizygotic (N = 21 pairs) twins with a history of Vietnam Era military service, where one brother went to Vietnam and developed PTSD, while his brother did not go to Vietnam or develop PTSD, underwent MR imaging of the brain. Structural MRI scans were used to manually outline the left and right hippocampus on multiple coronal slices, add the areas and adjust for slice thickness to determine hippocampal volume.

Results: Twins with Vietnam combat-related PTSD had a mean 11% smaller right hippocampal volume in comparison to their twin brothers without combat exposure or PTSD (p < .05). There was no significant interaction by zygosity, suggesting that this was not a predisposing risk factor or genetic effect.

Conclusions: These findings are consistent with smaller hippocampal volume in PTSD, and suggest that the effects are primarily due to environmental effects such as the stress of combat.
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http://dx.doi.org/10.1016/j.jpsychires.2020.10.042DOI Listing
May 2021

Individual Psychosocial Resilience, Neighborhood Context, and Cardiovascular Health in Black Adults: A Multilevel Investigation From the Morehouse-Emory Cardiovascular Center for Health Equity Study.

Circ Cardiovasc Qual Outcomes 2020 10 7;13(10):e006638. Epub 2020 Oct 7.

Department of Epidemiology, Rollins School of Public Health (V.V., T.T.L.), Emory University, Atlanta, GA.

Background: Despite well-documented cardiovascular disparities between racial groups, within-race determinants of cardiovascular health among Black adults remain understudied. Factors promoting cardiovascular resilience among Black adults in particular warrant further investigation. Our objective was to examine whether individual psychosocial resilience and neighborhood-level cardiovascular resilience were associated with better cardiovascular health in Black adults, measured utilizing Life's Simple 7 (LS7) scores.

Methods: We assessed LS7 scores in 389 Black adults (mean age, 53±10 years; 39% men) living in Atlanta, Georgia. A composite score of individual psychosocial resilience was created by assessing environmental mastery, purpose in life, optimism, resilient coping, and depressive symptoms. Neighborhood-level cardiovascular resilience was separately determined by the census tract-level rates of cardiovascular mortality/morbidity events. Generalized linear mixed regression models were used to examine the association between individual psychosocial resilience, neighborhood cardiovascular resilience, and LS7 scores.

Results: Higher individual psychosocial resilience was significantly associated with higher LS7 (β=0.38 [0.16-0.59] per 1 SD) after adjustment for sociodemographic factors. Similarly, higher neighborhood-level cardiovascular resilience was significantly associated with higher LS7 (β=0.23 [0.02-0.45] per 1 SD). When jointly examined, high individual psychosocial resilience (>median) was independently associated with higher LS7 (β=0.73 [0.31-1.17]), whereas living in high-resilience neighborhoods (>median) was not. The largest difference in LS7 score was between those with high and low psychosocial resilience living in low-resilience neighborhoods (8.38 [7.90-8.86] versus 7.42 [7.04-7.79]).

Conclusions: Individual psychosocial resilience in Black adults is associated with better cardiovascular health.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059442PMC
October 2020

Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation.

JMIR Mhealth Uhealth 2020 09 22;8(9):e20488. Epub 2020 Sep 22.

School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, United States.

Background: Transcutaneous cervical vagus nerve stimulation (tcVNS) is a promising alternative to implantable stimulation of the vagus nerve. With demonstrated potential in myriad applications, ranging from systemic inflammation reduction to traumatic stress attenuation, closed-loop tcVNS during periods of risk could improve treatment efficacy and reduce ineffective delivery. However, achieving this requires a deeper understanding of biomarker changes over time.

Objective: The aim of the present study was to reveal the dynamics of relevant cardiovascular biomarkers, extracted from wearable sensing modalities, in response to tcVNS.

Methods: Twenty-four human subjects were recruited for a randomized double-blind clinical trial, for whom electrocardiography and photoplethysmography were used to measure heart rate and photoplethysmogram amplitude responses to tcVNS, respectively. Modeling these responses in state-space, we (1) compared the biomarkers in terms of their predictability and active vs sham differentiation, (2) studied the latency between stimulation onset and measurable effects, and (3) visualized the true and model-simulated biomarker responses to tcVNS.

Results: The models accurately predicted future heart rate and photoplethysmogram amplitude values with root mean square errors of approximately one-fifth the standard deviations of the data. Moreover, (1) the photoplethysmogram amplitude showed superior predictability (P=.03) and active vs sham separation compared to heart rate; (2) a consistent delay of greater than 5 seconds was found between tcVNS onset and cardiovascular effects; and (3) dynamic characteristics differentiated responses to tcVNS from the sham stimulation.

Conclusions: This work furthers the state of the art by modeling pertinent biomarker responses to tcVNS. Through subsequent analysis, we discovered three key findings with implications related to (1) wearable sensing devices for bioelectronic medicine, (2) the dominant mechanism of action for tcVNS-induced effects on cardiovascular physiology, and (3) the existence of dynamic biomarker signatures that can be leveraged when titrating therapy in closed loop.

Trial Registration: ClinicalTrials.gov NCT02992899; https://clinicaltrials.gov/ct2/show/NCT02992899.

International Registered Report Identifier (irrid): RR2-10.1016/j.brs.2019.08.002.
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http://dx.doi.org/10.2196/20488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539162PMC
September 2020

Relation of High-sensitivity Cardiac Troponin I Elevation With Exercise to Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

Am J Cardiol 2020 12 15;136:1-8. Epub 2020 Sep 15.

Emory Clinical Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

High sensitive cardiac troponin I (hs-cTnI) increases with inducible myocardial ischemia in patients with coronary artery disease (CAD). We aimed to assess if the change in hs-cTnI levels with exercise stress testing is associated with major adverse cardiac events (MACE). A cohort of 365 (age 62 ± 9 years, 77% men) patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging with treadmill testing. Plasma hs-cTnI level was measured at rest and at 45 min after stress. Multivariable Fine & Gray's subdistribution hazards models were used to determine the association between the change in hs-cTnI and MACE, a composite end point of cardiovascular death, myocardial infarction, and unstable angina requiring revascularization. During a median follow-up of 3 years, 39 (11%) patients experienced MACE. After adjustment, for each two-fold increment in hs-cTnI with stress, there was a 2.2 (95% confidence interval 1.3-3.6)-fold increase in the hazard for MACE. Presence of both a high resting hs-cTnI level (>median) and ≥ 20% stress-induced hs-cTnI elevation was associated with the highest incidence of MACE (subdistribution hazards models 4.6, 95% confidence interval 1.6 to 13.0) compared with low levels of both. Risk discrimination statistics significantly improved after addition of resting and change in hs-cTnI levels to a model including traditional risk factors and inducible ischemia (0.67 to 0.71). Conversely, adding inducible ischemia by SPECT did not significantly improve the C-statistic from a model including traditional risk factors, baseline and change in hs-cTnI (0.70 to 0.71). In stable CAD patients, higher resting levels and elevation of hs-cTnI with exercise are predictors of adverse cardiovascular outcomes beyond traditional cardiovascular risk factors and presence of inducible ischemia.
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http://dx.doi.org/10.1016/j.amjcard.2020.09.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057114PMC
December 2020

Application of Noninvasive Vagal Nerve Stimulation to Stress-Related Psychiatric Disorders.

J Pers Med 2020 Sep 9;10(3). Epub 2020 Sep 9.

School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Background: Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation.

Methods: New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders.

Results: This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders.

Conclusions: nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.
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http://dx.doi.org/10.3390/jpm10030119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563188PMC
September 2020

Sex differences in the inflammatory response to stress and risk of adverse cardiovascular outcomes among patients with coronary heart disease.

Brain Behav Immun 2020 11 8;90:294-302. Epub 2020 Sep 8.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States; Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States.

Stress may contribute to progression of coronary heart disease (CHD) through inflammation, especially among women. Thus, we sought to examine whether increased inflammatory response to stress among patients with CHD is associated with a greater risk of cardiovascular events and whether this risk is higher in women. We examined inflammatory biomarkers known to increase with mental stress (speech task), including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and matrix metallopeptidase-9 (MMP-9) among 562 patients with stable CHD. Inflammatory response, the difference between post-stress and resting values, was examined as a predictor of major adverse cardiovascular events (MACE) using subdistribution hazards models for competing risks adjusting for demographics, cardiovascular risk factors, and medications. MACE was defined as a composite endpoint of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure. All biomarkers were standardized. The mean age was 63 years (range 34-79) and 24% were women. During a median follow-up of 3 years, 71 patients experienced MACE. Overall, there was no significant association between inflammatory response to stress and risk of MACE, but there were sex-based interactions for IL-6 (p = 0.001) and MCP-1 (p = 0.01). The risk of MACE increased 56% (HR: 1.56; 95% CI: 1.21, 2.01; p = 0.001) and 30% (HR: 1.30; 95% 1.09, 1.55; p = 0.004) for each standard deviation increase in IL-6 and MCP-1 response to mental stress for women, respectively, while there was no association among men. Increased inflammation in response to stress is associated with future adverse cardiovascular outcomes among women with CHD.
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http://dx.doi.org/10.1016/j.bbi.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872132PMC
November 2020

Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

Catheter Cardiovasc Interv 2020 Sep 9. Epub 2020 Sep 9.

Division of Cardiology, Department of Internal Medicine, Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, USA.

Background: Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy.

Methods: 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10 M, 81 mcg over 3 minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140 ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBF ).

Results: Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBF ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBF change ≤50%. CFR modestly correlated with HMR (r = -0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p = .02), higher FFR (p = .03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina.

Conclusion: In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.
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http://dx.doi.org/10.1002/ccd.29237DOI Listing
September 2020

Diet, Stress and Mental Health.

Nutrients 2020 Aug 13;12(8). Epub 2020 Aug 13.

Department of Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA 30332, USA.

Introduction: There has long been an interest in the effects of diet on mental health, and the interaction of the two with stress; however, the nature of these relationships is not well understood. Although associations between diet, obesity and the related metabolic syndrome (MetS), stress, and mental disorders exist, causal pathways have not been established.

Methods: We reviewed the literature on the relationship between diet, stress, obesity and psychiatric disorders related to stress.

Results: Diet and obesity can affect mood through direct effects, or stress-related mental disorders could lead to changes in diet habits that affect weight. Alternatively, common factors such as stress or predisposition could lead to both obesity and stress-related mental disorders, such as depression and posttraumatic stress disorder (PTSD). Specific aspects of diet can lead to acute changes in mood as well as stimulate inflammation, which has led to efforts to assess polyunsaturated fats (PUFA) as a treatment for depression. Bidirectional relationships between these different factors are also likely. Finally, there has been increased attention recently on the relationship between the gut and the brain, with the realization that the gut microbiome has an influence on brain function and probably also mood and behavior, introducing another way diet can influence mental health and disorders. Brain areas and neurotransmitters and neuropeptides that are involved in both mood and appetite likely play a role in mediating this relationship.

Conclusions: Understanding the relationship between diet, stress and mood and behavior could have important implications for the treatment of both stress-related mental disorders and obesity.
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http://dx.doi.org/10.3390/nu12082428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468813PMC
August 2020

Racial disparities in sleep disturbances among patients with and without coronary artery disease: The role of clinical and socioeconomic factors.

Sleep Health 2020 10 18;6(5):570-577. Epub 2020 Aug 18.

Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, Georgia, USA; Emory Clinical Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA. Electronic address:

Objective: To investigate differences in sleep quality by race in participants with and without a prior myocardial infarction (MI).

Design: Case-control study.

Setting: Emory-affiliated hospitals in Atlanta, Georgia.

Participants: Two hundred seventy-three individuals (190 Black) ≤60 years of age with a verified MI in the previous 8 months, and 100 community controls (44 Black) without a history of MI.

Measurements: Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Psychological factors were assessed using standardized questionnaires and clinical risk factors through medical history and chart review.

Results: A significant interaction existed between race and MI status on sleep quality (P= .01), such that Black individuals with a history of MI, but not controls, reported worse sleep quality than their non-Black counterparts. Among MI cases, being Black was independently associated with higher PSQI scores after adjusting for baseline demographics (B = 2.17, 95% confidence interval 1.17, 3.17, P = .006). Clinical risk factors, psychological factors and socioeconomic status (household income and years of education) all contributed equally to explain race-related disparities in sleep among MI cases. After further adjustment for these factors, the association was attenuated and no longer significant (B = 0.70, 95% confidence interval = -0.10, 1.21, P = .26).

Conclusion: Black post-MI patients, but not healthy controls, have significantly poorer sleep quality than non-Blacks. This difference is driven by a combination of factors, including clinical risk factors, psychological factors as well as adverse socioeconomic conditions among Black individuals with MI.
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http://dx.doi.org/10.1016/j.sleh.2020.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704917PMC
October 2020

Association Between Mental Stress-Induced Inferior Frontal Cortex Activation and Angina in Coronary Artery Disease.

Circ Cardiovasc Imaging 2020 08 10;13(8):e010710. Epub 2020 Aug 10.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (K.M., B.B.L., V.V., A.J.S.).

Background: The inferior frontal lobe is an important area of the brain involved in the stress response, and higher activation with acute mental stress may indicate a more severe stress reaction. However, it is unclear if activation of this region with stress correlates with angina in individuals with coronary artery disease.

Methods: Individuals with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors in conjunction with high resolution positron emission tomography imaging of the brain. Blood flow to the inferior frontal lobe was evaluated as a ratio compared with whole brain flow for each scan. Angina was assessed with the Seattle Angina Questionnaire's angina frequency subscale at baseline and 2 years follow-up.

Results: We analyzed 148 individuals with coronary artery disease (mean age [SD] 62 [8] years; 69% male, and 35.8% Black). For every doubling in the inferior frontal lobe activation, angina frequency was increased by 13.7 units at baseline ([Formula: see text], 13.7 [95% CI, 6.3-21.7]; =0.008) and 11.6 units during follow-up ([Formula: see text], 11.6 [95% CI, 4.1-19.2]; =0.01) in a model adjusted for baseline demographics. Mental stress-induced ischemia and activation of other brain pain processing regions (thalamus, insula, and amygdala) accounted for 40.0% and 13.1% of the total effect of inferior frontal lobe activation on angina severity, respectively.

Conclusions: Inferior frontal lobe activation with mental stress is independently associated with angina at baseline and during follow-up. Mental stress-induced ischemia and other pain processing brain regions may play a contributory role.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.010710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422935PMC
August 2020

Non-invasive vagal nerve stimulation decreases brain activity during trauma scripts.

Brain Stimul 2020 Sep - Oct;13(5):1333-1348. Epub 2020 Jul 10.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA; Atlanta VA Medical Center, Decatur, GA, USA.

Background: Traumatic stress can have lasting effects on neurobiology and result in psychiatric conditions such as posttraumatic stress disorder (PTSD). We hypothesize that non-invasive cervical vagal nerve stimulation (nVNS) may alleviate trauma symptoms by reducing stress sympathetic reactivity. This study examined how nVNS alters neural responses to personalized traumatic scripts.

Methods: Nineteen participants who had experienced trauma but did not have the diagnosis of PTSD completed this double-blind sham-controlled study. In three sequential time blocks, personalized traumatic scripts were presented to participants immediately followed by either sham stimulation (n = 8; 0-14 V, 0.2 Hz, pulse width = 5s) or active nVNS (n = 11; 0-30 V, 25 Hz, pulse width = 40 ms). Brain activity during traumatic scripts was assessed using High Resolution Positron Emission Tomography (HR-PET) with radiolabeled water to measure brain blood flow.

Results: Traumatic scripts resulted in significant activations within the bilateral medial and orbital prefrontal cortex, premotor cortex, anterior cingulate, thalamus, insula, hippocampus, right amygdala, and right putamen. Greater activation was observed during sham stimulation compared to nVNS within the bilateral prefrontal and orbitofrontal cortex, premotor cortex, temporal lobe, parahippocampal gyrus, insula, and left anterior cingulate. During the first exposure to the trauma scripts, greater activations were found in the motor cortices and ventral visual stream whereas prefrontal cortex and anterior cingulate activations were more predominant with later script presentations for those subjects receiving sham stimulation.

Conclusion: nVNS decreases neural reactivity to an emotional stressor in limbic and other brain areas involved in stress, with changes over repeated exposures suggesting a shift from scene appraisal to cognitively processing the emotional event.
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http://dx.doi.org/10.1016/j.brs.2020.07.002DOI Listing
March 2021

High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients.

Ann Intern Med 2020 07;173(1):76-77

Emory University School of Medicine, Atlanta, Georgia (J.H.K., M.H., A.A.Q.).

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http://dx.doi.org/10.7326/L20-0260DOI Listing
July 2020

Young Women's Perceptions of Heart Disease Risk.

J Adolesc Health 2020 11 2;67(5):708-713. Epub 2020 Jul 2.

Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.

Purpose: Heart disease is the number one cause of death in women. Little is known about how adolescent and young adult women perceive their risk of heart disease.

Methods: We conducted eight online, semistructured focus groups with 35 young women aged 15-24 years recruited from two primary care practices in Boston, MA. Focus group discussion topics built upon data from a larger sample of women who completed the American Heart Association Women's Health Study survey. Topics included health concerns salient to young women, perceived susceptibility to heart disease, and barriers to heart-healthy behaviors. We used qualitative coding and thematic analyses to synthesize data.

Results: Participants were surprised to learn that heart disease is the leading cause of death in women. Young women discussed age ("I feel like those are things I associate with older people like 40"), gender ("I usually hear more about men suffering from heart problems than women"), and social norms ("we're so pressured just to grow up and [be] more focused on pregnancies or depression or our weight") as reasons for their low perceived risk for heart disease. Participants noted several barriers to adopting heart-healthy behaviors including stress, lack of time, and low perceived risk. "We just don't have time to worry about hearts. Especially if our hearts aren't bothering us to begin with and we can't see it."

Conclusions: Perceptions of age, gender, and social norms contribute to low heart disease awareness among young women, which in turn may limit heart-healthy behaviors.
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http://dx.doi.org/10.1016/j.jadohealth.2020.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606261PMC
November 2020

Higher Activation of the Rostromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Individuals With Coronary Artery Disease.

Circulation 2020 Aug 11;142(5):455-465. Epub 2020 Jun 11.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (K.M., B.B.L., B.D.P., Z.A., Y.V.S., M.G., V.V., A.J.S.).

Background: Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in individuals with coronary artery disease. Certain brain regions that control both emotional states and cardiac physiology may be involved in this relationship. The rostromedial prefrontal cortex (rmPFC) is an important brain region that processes stress and regulates immune and autonomic functions. Changes in rmPFC activity with emotional stress (reactivity) may be informative of future risk for MACE.

Methods: Participants with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors and simultaneous brain imaging with high-resolution positron emission tomography brain imaging. We defined high rmPFC activation as a difference between stress and control scans greater than the median value for the entire cohort. Interleukin-6 levels 90 minutes after stress, and high-frequency heart rate variability during stress were also assessed. We defined MACE as a composite of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure hospitalization.

Results: We studied 148 subjects (69% male) with mean±SD age of 62±8 years. After adjustment for baseline demographics, risk factors, and baseline levels of interleukin-6 and high-frequency heart rate variability, higher rmPFC stress reactivity was independently associated with higher interleukin-6 and lower high-frequency heart rate variability with stress. During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. Each increase of 1 SD in rmPFC activation with mental stress was associated with a 21% increase risk of MACE (hazard ratio, 1.21 [95% CI, 1.08-1.37]). Stress-induced interleukin-6 and high-frequency heart rate variability explained 15.5% and 32.5% of the relationship between rmPFC reactivity and MACE, respectively. Addition of rmPFC reactivity to conventional risk factors improved risk reclassification for MACE prediction, and C-statistic improved from 0.71 to 0.76 (=0.03).

Conclusions: Greater rmPFC stress reactivity is associated with incident MACE. Immune and autonomic responses to mental stress may play a contributory role.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677173PMC
August 2020

Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure.

Hypertension 2020 07 10;76(1):195-205. Epub 2020 Jun 10.

Department of Endocrinology (B.H.R.W., J.V.v.V.-O.), University Medical Center Groningen, University of Groningen, The Netherlands.

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with <1×10. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (<1×10) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with <0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 () and cg00716257 () determined by environmental effects acting on both systolic BP and methylation levels.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295009PMC
July 2020

Impact of Social Vulnerability on COVID-19 Incidence and Outcomes in the United States.

medRxiv 2020 Apr 14. Epub 2020 Apr 14.

Importance Prior pandemics have disparately affected socially vulnerable communities. Whether regional variations in social vulnerability to disasters influence COVID-19 outcomes and incidence in the U.S. is unknown. Objective To examine the association of Social Vulnerability Index (SVI), a percentile-based measure of county-level social vulnerability to disasters, and its sub-components (socioeconomic status, household composition, minority status, and housing type/transportation accessibility) with the case fatality rate (CFR) and incidence of COVID-19. Design Ecological study of counties with at least 50 confirmed COVID-19 cases as of April 4th, 2020. Generalized linear mixed-effects models with state-level clustering were applied to estimate county-level associations of overall SVI and its sub-component scores with COVID-19 CFR (deaths/100 cases) and incidence (cases/1000 population), adjusting for population percentage aged >65 years, and for comorbidities using the average Hierarchical Condition Category (HCC) score. Counties with high SVI (≥median) and high CFR (≥median) were identified. Setting Population-based study of U.S. county-level data. Participants U.S. counties with at least 50 confirmed COVID-19 cases. Main outcomes and measures COVID-19 CFR and incidence. Results Data from 433 counties including 283,256 cases and 6,644 deaths were analyzed. Median SVI was 0.46 [Range: 0.01-1.00], and median CFR and incidence were 1.9% [Range: 0-13.3] and 1.2 per 1000 people [Range: 0.6-38.8], respectively. Higher SVI, indicative of greater social vulnerability, was associated with higher CFR (RR: 1.19 [1.05, 1.34], p=0.005, per-1 unit increase), an association that strengthened after adjustment for age>65 years and comorbidities (RR: 1.63 [1.38, 1.91], p<0.001), and was further confirmed in a sensitivity analysis limited to six states with the highest testing levels. Although the association between overall SVI and COVID-19 incidence was not significant, the SVI sub-components of socioeconomic status and minority status were both predictors of higher incidence and CFR. A combination of high SVI (≥0.46) and high adjusted CFR (≥2.3%) was observed in 28.9% of counties. Conclusions and Relevance Social vulnerability is associated with higher COVID-19 case fatality. High social vulnerability and CFR coexist in more than 1 in 4 U.S. counties. These counties should be targeted by public policy interventions to help alleviate the pandemic burden on the most vulnerable population.
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http://dx.doi.org/10.1101/2020.04.10.20060962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217093PMC
April 2020

Summary of Updated Recommendations for Primary Prevention of Cardiovascular Disease in Women: JACC State-of-the-Art Review.

J Am Coll Cardiol 2020 05;75(20):2602-2618

Rush Medical College, Rush University, Chicago, Illinois.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for women in the United States and worldwide. There has been no American College of Cardiology (ACC)/American Heart Association guideline update specifically for the prevention of CVD in women since 2011. Since then, the body of sex-specific data has grown, in addition to updated hypertension, cholesterol, diabetes, atrial fibrillation, and primary prevention guidelines. The ACC CVD in Women Committee undertook a review of the recent guidelines and major studies to summarize recommendations pertinent to women. In this update, the authors address special topics, particularly the risk factors and treatments that have led to some controversies and confusion. Specifically, sex-related risk factors, hypertension, diabetes, hyperlipidemia, anticoagulation for atrial fibrillation, use of aspirin, perimenopausal hormone therapy, and psychosocial issues are highlighted.
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http://dx.doi.org/10.1016/j.jacc.2020.03.060DOI Listing
May 2020