Publications by authors named "Arshed A Quyyumi"

308 Publications

Defining Patient-Oriented Natural Language Processing: A New Paradigm for Research and Development to Facilitate Adoption and Use by Medical Experts.

JMIR Med Inform 2021 Sep 28;9(9):e18471. Epub 2021 Sep 28.

Predictive Health Institute and Center for Health Discovery and Well Being, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.

The capabilities of natural language processing (NLP) methods have expanded significantly in recent years, and progress has been particularly driven by advances in data science and machine learning. However, NLP is still largely underused in patient-oriented clinical research and care (POCRC). A key reason behind this is that clinical NLP methods are typically developed, optimized, and evaluated with narrowly focused data sets and tasks (eg, those for the detection of specific symptoms in free texts). Such research and development (R&D) approaches may be described as problem oriented, and the developed systems perform specialized tasks well. As standalone systems, however, they generally do not comprehensively meet the needs of POCRC. Thus, there is often a gap between the capabilities of clinical NLP methods and the needs of patient-facing medical experts. We believe that to increase the practical use of biomedical NLP, future R&D efforts need to be broadened to a new research paradigm-one that explicitly incorporates characteristics that are crucial for POCRC. We present our viewpoint about 4 such interrelated characteristics that can increase NLP systems' suitability for POCRC (3 that represent NLP system properties and 1 associated with the R&D process)-(1) interpretability (the ability to explain system decisions), (2) patient centeredness (the capability to characterize diverse patients), (3) customizability (the flexibility for adapting to distinct settings, problems, and cohorts), and (4) multitask evaluation (the validation of system performance based on multiple tasks involving heterogeneous data sets). By using the NLP task of clinical concept detection as an example, we detail these characteristics and discuss how they may result in the increased uptake of NLP systems for POCRC.
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http://dx.doi.org/10.2196/18471DOI Listing
September 2021

Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study.

Arterioscler Thromb Vasc Biol 2021 Sep 23:ATVBAHA121316574. Epub 2021 Sep 23.

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA. (Z.A., J.H.K., M.G., K.M., B.L., A.M., A.J.S., M.S.H., V.V., A.A.Q.).

Objective: Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes. Approach and Results: Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34-expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3±2.4 pg/mL and 0.1±1.0 mg/L; =0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, -0.17; <0.001). Using linear regression, IL-6 and high-sensitivity CRP levels declined by -0.59 (95% CI, -0.90 to -0.20) pg/mL and -0.13 (-0.28 to 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables, as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95% CI, 9-13) greater risk of death/myocardial infarction. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts.

Conclusions: Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes.
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http://dx.doi.org/10.1161/ATVBAHA.121.316574DOI Listing
September 2021

Association of physical activity with arterial stiffness among Black adults.

Vasc Med 2021 Sep 22:1358863X211032725. Epub 2021 Sep 22.

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Arterial stiffness is a precursor for the development of hypertension and premature cardiovascular disease (CVD). Physical activity has been associated with lower arterial stiffness among largely White populations, but the types of activity required and whether these findings apply to Black adults remain unknown. We examined whether physical activity levels were associated with arterial stiffness among Black adults in two independent cohorts. In the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity, 378 Black adults (age 52.8 ± 10.3, 39.7% male) without known CVD living in Atlanta, GA were recruited. Arterial stiffness was measured as pulse wave velocity (PWV). Total and domain-specific physical activity were assessed by self-report. Multiple linear regression models were used to investigate differences across physical activity levels after adjusting for age, sex, CVD risk factors, and socioeconomic status. Findings were validated in an independent cohort of Black adults ( = 55, age 50.4 ± 9.2, 23.6% male). After adjustment for covariates, lower arterial stiffness was associated with higher self-reported levels of sport/exercise (6.92 ± 1.13 vs 7.75 ± 1.14, < 0.001, highest vs lowest quartile) and home/life activities (7.34 ± 1.24 vs 7.73 ± 1.07, = 0.04, highest vs lowest quartile), but not work, active living, or the overall physical activity scores. These findings were replicated in the independent cohort where higher levels of sport/exercise remained associated with lower arterial stiffness (6.66 ± 0.57 vs 8.21 ± 0.66, < 0.001, highest vs lowest quartile). Higher levels of sport/exercise and home/life-related physical activities (in comparison to occupational physical activity) are associated with lower arterial stiffness in Black adults.
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http://dx.doi.org/10.1177/1358863X211032725DOI Listing
September 2021

Racial Disparities in Adverse Cardiovascular Outcomes After a Myocardial Infarction in Young or Middle-Aged Patients.

J Am Heart Assoc 2021 Sep 25;10(17):e020828. Epub 2021 Aug 25.

Division of Cardiology Department of Medicine Emory University School of Medicine Atlanta GA.

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) <61 years old hospitalized for confirmed type 1 MI at Emory-affiliated hospitals and followed them for 5 years. We used Cox proportional-hazard models to estimate the association of race with a composite end point of recurrent MI, stroke, heart failure, or cardiovascular death after adjusting for demographic, socioeceonomic status, psychological, and clinical risk factors. The mean age was 50 years, and 50% were women. Compared with non-Black patients, Black patients had lower socioeconomic status and more clinical and psychosocial risk factors but less angiographic coronary artery disease. The 5-year incidence of cardiovascular events was higher in Black (35%) compared to non-Black patients (19%): hazard ratio (HR) 2.1, 95% CI, 1.3 to 3.6. Adjustment for socioeconomic status weakened the association (HR 1.3, 95% CI, 0.8-2.4) more than adjustment for clinical and psychological risk factors. A lower income explained 46% of the race-related disparity in outcome. 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.
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http://dx.doi.org/10.1161/JAHA.121.020828DOI Listing
September 2021

Association between race and maladaptive concentric left ventricular hypertrophy in American-style football athletes.

Br J Sports Med 2021 Aug 13. Epub 2021 Aug 13.

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

Objectives: American-style football (ASF) athletes are at risk for the development of concentric left ventricular hypertrophy (C-LVH), an established cardiovascular risk factor in the general population. We sought to address whether black race is associated with acquired C-LVH in collegiate ASF athletes.

Methods: Collegiate ASF athletes from two National Collegiate Athletic Association Division-I programmes were recruited as freshmen between 2014 and 2019 and analysed over 3 years. Demographics (neighbourhood family income) and repeated clinical characteristics and echocardiography were recorded longitudinally at multiple timepoints. A mixed-modelling approach was performed to evaluate acquired C-LVH in black versus white athletes controlling for playing position (linemen (LM) and non-linemen (NLM)), family income, body weight and blood pressure.

Results: At baseline, black athletes (N=124) were more often NLM (72% vs 54%, p=0.005) and had lower median neighbourhood family income ($54 119 vs $63 146, p=0.006) compared with white athletes (N=125). While both black and white LM demonstrated similar increases in C-LVH over time, among NLM acquired C-LVH was more common in black versus white athletes (postseason year-1: N=14/89 (16%) vs N=2/68 (3%); postseason year-2: N=9/50 (18%) vs N=2/32 (6%); postseason year-3: N=8/33 (24%) vs N=1/13 (8%), p=0.005 change over time). In stratified models, black race was associated with acquired C-LVH in NLM (OR: 3.70, 95% CI 1.12 to 12.21, p=0.03) and LM was associated with acquired C-LVH in white athletes (OR: 3.40, 95% CI 1.03 to 11.27, p=0.048).

Conclusions: Independent of family income and changes in weight and blood pressure, black race was associated with acquired C-LVH among collegiate ASF NLM and LM was associated with acquired C-LVH in white athletes.
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http://dx.doi.org/10.1136/bjsports-2021-104333DOI Listing
August 2021

Association Between Early Trauma and Ideal Cardiovascular Health Among Black Americans: Results From the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity.

Circ Cardiovasc Qual Outcomes 2021 09 12;14(9):e007904. Epub 2021 Aug 12.

Department of Epidemiology (V.V., T.T.L.), Emory University, Atlanta, GA.

Background: Early trauma (general, emotional, physical, and sexual abuse before age 18 years) has been associated with both cardiovascular disease risk and lifestyle-related risk factors for cardiovascular disease, including smoking, obesity, and physical inactivity. Despite higher prevalence, the association between early trauma and cardiovascular health (CVH) has been understudied in Black Americans, especially those from low-income backgrounds, who may be doubly vulnerable. Therefore, we investigated the association between early trauma and CVH, particularly among low-income Black Americans.

Methods: We recruited 457 Black adults (age 53±10, 38% male) without known cardiovascular disease from the Atlanta, GA, metropolitan area using personalized, community-based recruitment methods. The Early Trauma Inventory was administered to assess overall early traumatic life experiences which include physical, sexual, emotional abuse, and general trauma. Our primary outcome was the American Heart Association Life's Simple 7, which is a set of 7 CVH metrics, including 4 lifestyle-related factors (smoking, body mass index, physical activity, and diet) and three physiologically measured health factors (blood pressure, total blood cholesterol, and blood glucose). We used linear regression models adjusting for age, sex, socioeconomic status, and depression to test the association between early trauma and CVH and tested the early trauma by household income (<$50 000) interaction.

Results: Higher levels of early trauma were associated with lower Life's Simple 7 scores (β, -0.05 [95% CI, -0.09 to -0.01], =0.02, per 1 unit increase in the Early Trauma Inventory score) among lower, but not higher, income Black participants ( value for interaction=0.04). Subtypes of early trauma linked to Life's Simple 7 were general trauma, emotional abuse, and sexual abuse. Exploratory analyses demonstrated that early trauma was only associated with the body mass index and smoking components of Life's Simple 7.

Conclusions: Early trauma, including general trauma, emotional abuse, and sexual abuse, may be associated with worse CVH among low-, but not higher-income Black adults.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.121.007904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455434PMC
September 2021

A Multi-center Genome-wide Association Study of Cervical Dystonia.

Mov Disord 2021 Jul 28. Epub 2021 Jul 28.

Department of Neurology, University of Lübeck, Lübeck, Germany.

Background: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility.

Objective: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach.

Methods: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal.

Results: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823).

Conclusion: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28732DOI Listing
July 2021

Temporal trends in the association of social vulnerability and race/ethnicity with county-level COVID-19 incidence and outcomes in the USA: an ecological analysis.

BMJ Open 2021 07 22;11(7):e048086. Epub 2021 Jul 22.

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

Background: The COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the USA initially, but the temporal trends during the year-long pandemic remain unknown.

Objective: We examined the temporal association of county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the USA in the year starting in March 2020.

Methods: Counties (n=3091) with ≥50 COVID-19 cases by 6 March 2021 were included in the study. Associations between SVI (and its subcomponents) and county-level racial composition with incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time-varying associations between weekly number of cases/deaths and SVI or racial composition. Data were adjusted for percentage of population aged ≥65 years, state-level testing rate, comorbidities using the average Hierarchical Condition Category score, and environmental factors including average fine particulate matter of diameter ≥2.5 μm, temperature and precipitation.

Results: Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio per 10 percentile increase: 1.02, 95% CI 1.02 to 1.03, p<0.001) and death per capita (1.04, 95% CI 1.04 to 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by the winter, a period that coincided with a sharp increase in infection rates and mortality, and when counties with higher proportion of white residents were disproportionately represented ('third wave'). By spring of 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of black residents also observed similar temporal trends in COVID-19-related adverse outcomes. Counties with greater proportion of Hispanic residents had worse outcomes throughout the duration of the analysis.

Conclusion: Except for the winter 'third wave', when majority of the white communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations experienced worse COVID-19 outcomes.
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http://dx.doi.org/10.1136/bmjopen-2020-048086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300549PMC
July 2021

Cardiovascular disease risk and pathophysiology in South Asians: can longitudinal multi-omics shed light?

Wellcome Open Res 2020 20;5:255. Epub 2021 May 20.

Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, New Delhi, India.

Cardiovascular disease (CVD) is the leading cause of mortality in South Asia, with rapidly increasing prevalence of hypertension, type 2 diabetes (T2DM) and hyperlipidemia over the last two decades. Atherosclerotic CVD (ASCVD) affects South Asians earlier in life and at lower body weights, which is not fully explained by differential burden of conventional risk factors. Heart failure (HF) is a complex clinical syndrome of heterogeneous structural phenotypes including two major clinical subtypes, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). The prevalence of HF in South Asians is also rising with other metabolic diseases, and HFpEF develops at younger age and leaner body mass index in South Asians than in Whites. Recent genome-wide association studies, epigenome-wide association studies and metabolomic studies of ASCVD and HF have identified genes, metabolites and pathways associated with CVD traits. However, these findings were mostly driven by samples of European ancestry, which may not accurately represent the CVD risk at the molecular level, and the unique risk profile of CVD in South Asians. Such bias, while formulating hypothesis-driven research studies, risks missing important causal or predictive factors unique to South Asians. Importantly, a longitudinal design of multi-omic markers can capture the life-course risk and natural history related to CVD, and partially disentangle putative causal relationship between risk factors, multi-omic markers and subclinical and clinical ASCVD and HF. In conclusion, combining high-resolution untargeted metabolomics with epigenomics of rigorous, longitudinal design will provide comprehensive unbiased molecular characterization of subclinical and clinical CVD among South Asians. A thorough understanding of CVD-associated metabolomic profiles, together with advances in epigenomics and genomics, will lead to more accurate estimates of CVD progression and stimulate new strategies for improving cardiovascular health.
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http://dx.doi.org/10.12688/wellcomeopenres.16336.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176264PMC
May 2021

Ecological Analysis of the Temporal Trends in the Association of Social Vulnerability and Race/Ethnicity with County-Level COVID-19 Incidence and Outcomes in the United States.

medRxiv 2021 Jun 7. Epub 2021 Jun 7.

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

Background: The COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the U.S. initially, but the temporal trends during the year-long pandemic remain unknown.

Objective: We examined the temporal association between the county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the U.S. in the year starting in March 2020.

Methods: Counties (n=3091) with ≥ 50 COVID-19 cases by March 6 , 2021 were included in the study. Associations between SVI (and its subcomponents) and county level racial composition with the incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time varying associations between weekly number of cases/deaths and SVI or racial composition. Data was adjusted for percentage of population aged ≥65 years, state level testing rate, comorbidities using the average Hierarchical Condition Category (HCC) score, and environmental factors including average fine particulate matter (PM ), temperature and precipitation.

Results: Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio [IRR] per-10 percentile increase:1.02, (95% CI 1.02, 1.03, p<0.001), and death per capita (1.04, (95% CI 1.04, 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by the winter, a period that coincided with a sharp increase in infection rates and mortality, and when counties with higher proportion of White residents were disproportionately represented ("third wave"). By Spring of 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of Black residents also observed similar temporal trends COVID-19-related adverse outcomes. Counties with greater proportion of Hispanic residents had worse outcomes throughout the duration of the analysis.

Conclusion: Except for the winter "third wave" when majority White communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations, experienced worse COVID-19 outcomes.

Article Summary/strengths & Limitations: Examined full 12 months of county-level data in the US delineating the temporal trends in the association between social vulnerability index and COVID-19 outcomesInvestigated COVID-19 outcomes in predominantly Black and Hispanic communities in comparison to White communities in the USAnalysis is ecological, descriptive, and on the county-level rather than on an individual levelAnalysis adjusted for confounders including county level age ≥ 65, comorbidities, and environmental factorsAnalysis limited to the US.
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http://dx.doi.org/10.1101/2021.06.04.21258355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202439PMC
June 2021

Brain-heart connections in stress and cardiovascular disease: Implications for the cardiac patient.

Atherosclerosis 2021 07 30;328:74-82. Epub 2021 May 30.

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

The influence of psychological stress on the physiology of the cardiovascular system, and on the etiology and outcomes of cardiovascular disease (CVD) has been the object of intense investigation. As a whole, current knowledge points to a "brain-heart axis" that is especially important in individuals with pre-existing CVD. The use of acute psychological stress provocation in the laboratory has been useful to clarify the effects of psychological stress on cardiovascular physiology, immune function, vascular reactivity, myocardial ischemia, neurobiology and cardiovascular outcomes. An emerging paradigm is that dynamic perturbations of physiological and molecular pathways during stress or negative emotions are important in influencing cardiovascular outcomes, and that some patient subgroups, such as women, patients with an early-onset myocardial infarction, and patients with adverse psychosocial exposures, may be at especially high risk for these effects. This review summarizes recent knowledge on mind-body connections in CVD among cardiac patients and highlights important pathways of risk which could become the object of future intervention efforts. As a whole, this research suggests that an integrated study of mind and body is necessary to fully understand the determinants and consequences of CVD.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254768PMC
July 2021

The black box of coronary microcirculation: Is it at the tip of the finger?

Int J Cardiol 2021 08 1;336:29-31. Epub 2021 Jun 1.

Emory Women's Heart Center and Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States of America.

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http://dx.doi.org/10.1016/j.ijcard.2021.05.049DOI Listing
August 2021

Everyday Discrimination and Mental Stress-Induced Myocardial Ischemia.

Psychosom Med 2021 06;83(5):432-439

From the Department of Epidemiology (McKinnon, Shah, Moazzami, Sullivan, Elon, Vaccarino, Lewis), Rollins School of Public Health, Emory University; Division of Cardiology, Department of Medicine (Shah, Lima, Moazzami, Young, Almuwaqqat, Quyyumi, Vaccarino), Emory University School of Medicine, Atlanta; Atlanta VA Medical Center (Shah, Bremner), Decatur; Department of Radiology (Garcia), Emory University School of Medicine; Department of Psychiatry and Behavioral Sciences (Bremner, Raggi), Emory University School of Medicine, Atlanta, Georgia; and Mazankowski Alberta Heart Institute (Raggi), University of Alberta, Edmonton, Canada.

Objective: Mental stress-induced myocardial ischemia (MSIMI), a transient myocardial ischemic response to mental stress, is associated with poorer outcomes among patients with coronary heart disease and is more likely to occur among women. However, predictors of MSIMI are not well explored. The current study investigated the association between experiences of everyday discrimination and MSIMI among patients with recent myocardial ischemia and contrasted the results with conventional stress-induced myocardial ischemia (CSIMI). We examined sex differences in associations.

Methods: We studied 295 post-MI patients (145 women, 150 men). Provocation of myocardial ischemia with mental stress (speech task) and conventional stress (exercise or pharmacologic) was assessed by myocardial perfusion imaging. Frequency of exposure to everyday discrimination was assessed via questionnaire using the Everyday Discrimination Scale (EDS).

Results: The mean age was 51 years in both women and men, and the EDS score ranged from 10 to 38 (mean [standard deviation] = 17 [6] years). After multivariable analysis, each standard deviation increase in the EDS score (more frequent exposure) was associated with an increased odds of MSIMI (odds ratio [OR] = 1.57 [1.10-2.23]). The EDS score was not associated with CSIMI (OR = 0.86 [0.64-1.17]). Women demonstrated a twofold increase (OR = 1.96 [1.13-3.38], p = .02) in the adjusted odds of MSIMI, with each standard deviation increase in the EDS score compared with a 1.4-fold increase (OR = 1.40 [0.80-2.44], p = .24) among men; however, interaction was not statistically significant.

Conclusions: Among post-MI patients, everyday discrimination was positively associated with occurrence of MSIMI, but not with CSIMI; associations were more pronounced among women.
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http://dx.doi.org/10.1097/PSY.0000000000000941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225242PMC
June 2021

Food Access and Cardiovascular Outcomes in Metropolitan Atlanta Census Tracts With Residents at Low Risk and High Risk of Cardiovascular Disease: The Morehouse-Emory Cardiovascular Center for Health Equity Study.

Prev Chronic Dis 2021 05 6;18:E42. Epub 2021 May 6.

Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, Georgia.

Introduction: Perceived and actual access to healthy foods may differ in urban areas, particularly among Black people. We assessed the effect of objective and perceived neighborhood food access on self-reported cardiovascular disease (CVD) among Black people living in areas of high risk and low risk for the disease in Atlanta, Georgia. We hypothesized that perceived and objective food access would independently predict self-reported CVD.

Methods: We used survey data from the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity Study. Study participants consisted of 1,402 Black adults, aged 35 to 64, residing in urban Atlanta census tracts with high rates or low rates of CVD. We assessed perceived neighborhood healthy food access by self-reported selection and quality of produce and low-fat food options. We assessed objective food access by the 2015 US Department of Agriculture Food Access Research Atlas. Low access was defined as census tracts with at least 500 people living more than 1 mile from a large food retailer. Self-reported CVD included related conditions and/or procedures. We used multilevel logistic models adjusted for demographic characteristics to examine the association between objective and perceived food access and self-reported CVD.

Results: Overall, self-reported CVD was not significant for perceived (odds ratio = 0.87; 95% CI, 0.59-1.29) or objective (odds ratio = 0.74; 95% CI, 0.48-1.12) healthy food access. Similar results were obtained among adults living in areas with higher-than-expected rates of CVD.

Conclusion: Results of this study suggest the odds for self-reported CVD events were not significantly affected by perceived or objective access to healthy foods.
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http://dx.doi.org/10.5888/pcd18.200316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139486PMC
May 2021

Vascular Regenerative Capacity and the Obesity Paradox in Coronary Artery Disease.

Arterioscler Thromb Vasc Biol 2021 06 15;41(6):2097-2108. Epub 2021 Apr 15.

Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute (A. Mehta, S.J.I., D.S.D., Z.A., A.N., A.A.A., A.H., A.V., S.F.A., A. Mokhtari, I.H., L.S.S., Y.-A.K., A.A.Q.), Emory University School of Medicine, Atlanta, GA.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147702PMC
June 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

Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.

Eur Heart J 2021 05;42(18):1742-1756

Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, 1462 Clifton Road NE, Atlanta, GA 30322, USA.

Aims: Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.

Methods And Results: We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.

Conclusion: The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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http://dx.doi.org/10.1093/eurheartj/ehab107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244638PMC
May 2021

Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.

Eur Heart J 2021 03;42(9):919-933

Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.

Aims: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.

Methods And Results: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro.

Conclusions: A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.
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http://dx.doi.org/10.1093/eurheartj/ehaa1040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936531PMC
March 2021

Highly elevated polygenic risk scores are better predictors of myocardial infarction risk early in life than later.

Genome Med 2021 01 28;13(1):13. Epub 2021 Jan 28.

School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, EBB1 Suite 2115, Georgia Tech, Atlanta, GA, 30332, USA.

Background: Several polygenic risk scores (PRS) have been developed for cardiovascular risk prediction, but the additive value of including PRS together with conventional risk factors for risk prediction is questionable. This study assesses the clinical utility of including four PRS generated from 194, 46K, 1.5M, and 6M SNPs, along with conventional risk factors, to predict risk of ischemic heart disease (IHD), myocardial infarction (MI), and first MI event on or before age 50 (early MI).

Methods: A cross-validated logistic regression (LR) algorithm was trained either on ~ 440K European ancestry individuals from the UK Biobank (UKB), or the full UKB population, including as features different combinations of conventional established-at-birth risk factors (ancestry, sex) and risk factors that are non-fixed over an individual's lifespan (age, BMI, hypertension, hyperlipidemia, diabetes, smoking, family history), with and without also including PRS. The algorithm was trained separately with IHD, MI, and early MI as prediction labels.

Results: When LR was trained using risk factors established-at-birth, adding the four PRS significantly improved the area under the curve (AUC) for IHD (0.62 to 0.67) and MI (0.67 to 0.73), as well as for early MI (0.70 to 0.79). When LR was trained using all risk factors, adding the four PRS only resulted in a significantly higher disease prevalence in the 98th and 99th percentiles of both the IHD and MI scores.

Conclusions: PRS improve cardiovascular risk stratification early in life when knowledge of later-life risk factors is unavailable. However, by middle age, when many risk factors are known, the improvement attributed to PRS is marginal for the general population.
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http://dx.doi.org/10.1186/s13073-021-00828-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845089PMC
January 2021

Letter to the Editor in Response to Khazanchi et al.

J Gen Intern Med 2021 04 19;36(4):1113-1114. Epub 2021 Jan 19.

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.

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http://dx.doi.org/10.1007/s11606-021-06594-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815283PMC
April 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

Sexual Differences in Genetic Predisposition of Coronary Artery Disease.

Circ Genom Precis Med 2021 02 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 2021 Aug 26;37(3):538-546. Epub 2020 Dec 26.

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395370PMC
August 2021

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178422PMC
December 2020

Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial.

Circ Cardiovasc Interv 2020 12 4;13(12):e008204. Epub 2020 Dec 4.

Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (J.-S.K., O.Y.H., P.E., R.R., M.R., S.K., S.G., H.H., N.S., G.M.B., C.L., P.K.M., A.A.Q., H.S.).

Background: Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease.

Methods: In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed.

Results: No significant differences in ΔSAQ angina frequency scores (=0.53) or Duke Activity Status Index (=0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores (=0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 (=0.02).

Conclusions: Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008204DOI Listing
December 2020

Daytime sleepiness predicts inflammation and ambulatory blood pressure in sleep apnoea.

ERJ Open Res 2020 Oct 26;6(4). Epub 2020 Oct 26.

Emory Nell Hodgson Woodruff School of Nursing, Atlanta, GA, USA.

Introduction: Sleepiness in obstructive sleep apnoea is associated with cardiovascular risk; however, the biological mechanisms are not known. This study explored whether those with subjective sleepiness have increased plasma tumour necrosis factor-related protein 1 (C1qTNF1), a novel adipose-derived hormone (adipokine), and 24-h ambulatory blood pressure (ABP) compared to those without sleepiness in newly diagnosed, treatment-naïve participants with obstructive sleep apnoea.

Methods: Overall, 94 participants were included in the analysis. Participants completed the Epworth Sleepiness Scale (ESS), 24-h ABP was monitored, and plasma C1qTNF1 was measured. Sleepy participants were defined as ESS≥10 and nonsleepy as ESS<10. Multiple linear regression was used to explore differences in C1qTNF1, and 24-h mean arterial pressure (MAP) between sleepy and nonsleepy participants, adjusting for age, sex, body mass index, apnoea-hypopnoea index, and smoking status.

Results: C1qTNF1 was significantly higher in sleepy participants (n=57) compared to nonsleepy participants (n=37) (β=0.41 NPX, 95% CI 0.02, 0.80; p=0.04). The 24-h MAP was significantly higher in sleepy participants compared to nonsleepy participants (β=4.06 mmHg, 95% CI 0.36, 7.77; p=0.03).

Conclusions: Our findings show that sleepiness is associated with inflammation and higher 24-h MAP in sleep apnoea.
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http://dx.doi.org/10.1183/23120541.00310-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682673PMC
October 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

Inhibition of iNOS augments cutaneous endothelial NO-dependent vasodilation in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks.

Am J Physiol Heart Circ Physiol 2021 01 30;320(1):H190-H199. Epub 2020 Oct 30.

Department of Kinesiology and Health, Georgia State University, Atlanta, Georgia.

We tested the hypothesis that inducible nitric oxide synthase (iNOS) contributes to reduced nitric oxide (NO)-dependent vasodilation in non-Hispanic Blacks and prehypertensive non-Hispanic Whites. Twenty Black and twenty White participants (10 normotensive, 10 prehypertensive per group; = 40 total) participated in this study. Participants were instrumented with two microdialysis fibers, and each site was randomized as control (lactated Ringer) or iNOS inhibition (0.1 mM 1400W). Laser-Doppler flow probes and local heaters were used to measure skin blood flow and heat the skin to induce vasodilation, respectively. Each site was heated from 33°C to 39°C (rate: 0.1°C/s). Once a plateau was established, 20 mM nitro-l-arginine methyl ester (l-NAME), a nonspecific NOS inhibitor, was infused at each site to quantify NO-dependent vasodilation. At control sites, %NO-dependent vasodilation was reduced in prehypertensive Whites (47 ± 10%NO) and in both normotensive and prehypertensive Blacks (39 ± 9%NO and 28 ± 5%NO, respectively) relative to normotensive Whites (73 ± 8%NO; < 0.0001 for all comparisons). Compared with respective control sites, iNOS inhibition increased NO-dependent vasodilation in prehypertensive Whites (68 ± 8%NO) and in both normotensive and prehypertensive Blacks (78 ± 8%NO and 55 ± 6%NO, respectively; < 0.0001 for all comparisons). We failed to find an effect for normotensive Whites (77 ± 7%NO). After iNOS inhibition, %NO-dependent vasodilation was similar between normotensive Whites, prehypertensive Whites, and normotensive Blacks. Inhibition of iNOS increased NO-dependent vasodilation to a lesser extent in prehypertensive Blacks. These data suggest that iNOS contributes to reduced NO-dependent vasodilation in prehypertension and in Black participants. Inducible nitric oxide synthase (iNOS) is typically upregulated in conditions of increased oxidative stress and may have detrimental effects on the vasculature. Endothelial nitric oxide (NO), which is cardioprotective, is reduced in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks. We found that inhibition of iNOS can increase endothelial NO-dependent vasodilation in prehypertensive White participants and in both normotensive and prehypertensive Black participants.Inducible nitric oxide (NO) synthase (iNOS) can be upregulated under conditions of increased oxidative stress and may have detrimental effects on the vasculature. Endothelial NO, which is cardioprotective, is reduced in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks. We found that inhibition of iNOS can increase endothelial NO-dependent vasodilation in prehypertensive White participants and in both normotensive and prehypertensive Black participants.
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http://dx.doi.org/10.1152/ajpheart.00644.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847065PMC
January 2021

Nocturnal blood pressure is associated with sympathetic nerve activity in patients with chronic kidney disease.

Physiol Rep 2020 10;8(20):e14602

Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Elevated nocturnal blood pressure (BP) and nocturnal non-dipping are frequently observed in patients with chronic kidney disease (CKD) and are stronger predictors of cardiovascular complications and CKD progression than standard office BP. The sympathetic nervous system (SNS) is thought to modulate diurnal hemodynamic changes and the vascular endothelium plays a fundamental role in BP regulation. We hypothesized that SNS overactivity and endothelial dysfunction in CKD are linked to elevated nocturnal BP and non-dipping. In 32 CKD patients with hypertension (56 ± 7 years), office BP, 24-hr ambulatory BP, muscle sympathetic nerve activity (MSNA) and endothelial function via flow-mediated dilation (FMD) were measured. Participants were subsequently divided into dippers (nighttime average BP > 10% lower than the daytime average BP, n = 8) and non-dippers (n = 24). Non-dippers had higher nighttime BP (p < .05), but not office and daytime BP, compared to dippers. MSNA burst incidence (81 ± 13 versus 67 ± 13 bursts/100 HR, p = .019) was higher and brachial artery FMD (1.7 ± 1.5 versus 4.7 ± 1.9%, p < .001) was lower in non-dippers compared to dippers. MSNA and FMD each predicted nighttime systolic (β = 0.48,-0.46, p = .02, 0.07, respectively) and diastolic BP (β = 0.38,-0.47, p = .04, 0.03, respectively) in multivariate-adjusted analyses. Our novel findings demonstrate that unfavorable nocturnal BP profiles are associated with elevated SNS activity and endothelial dysfunction in CKD. Specifically, CKD patients with higher nighttime BP and the non-dipping pattern have higher MSNA and lower FMD. These support our hypothesis that SNS overactivation and endothelial dysfunction are linked to the dysregulation of nighttime BP as well as the magnitude of BP lowering at nighttime in CKD.
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http://dx.doi.org/10.14814/phy2.14602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592496PMC
October 2020

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
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