93 results on '"Matthew J, Feinstein"'
Search Results
2. Immune cell subpopulations as risk factors for atrial fibrillation: The Cardiovascular Health Study and Multi-Ethnic Study of Atherosclerosis
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James S. Floyd, Colleen M. Sitlani, Margaret F. Doyle, Matthew J. Feinstein, Nels C. Olson, Susan R. Heckbert, Sally A. Huber, Russell P. Tracy, Bruce M. Psaty, and Joseph A.C. Delaney
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Published
- 2023
3. Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV
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Won Jun Lee, Haoxiang Cheng, Bridget M. Whitney, Robin M. Nance, Sierra R. Britton, Kristina Jordahl, Sara Lindstrom, Stephanie A. Ruderman, Mari M. Kitahata, Michael S. Saag, Amanda L. Willig, Greer Burkholder, Joseph J. Eron, Jason C. Kovacic, Johan L.M. Björkegren, W. Christopher Mathews, Edward Cachay, Matthew J. Feinstein, Mathew Budoff, Peter W. Hunt, Richard D. Moore, Jeanne Keruly, Mary E. McCaul, Geetanjali Chander, Allison Webel, Kenneth H. Mayer, Joseph A. Delaney, Paul K. Crane, Claudia Martinez, Heidi M. Crane, Ke Hao, and Inga Peter
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Cardiology and Cardiovascular Medicine - Published
- 2023
4. Association of Peripheral Lymphocyte Subsets with Cognitive Decline and Dementia: The Cardiovascular Health Study
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Alison E. Fohner, Colleen M. Sitlani, Petra Buzkova, Margaret F. Doyle, Xiaojuan Liu, Joshua C. Bis, Annette Fitzpatrick, Susan R. Heckbert, Sally A. Huber, Lewis Kuller, William T. Longstreth, Matthew J. Feinstein, Matthew Freiberg, Nels C. Olson, Sudha Seshadri, Oscar Lopez, Michelle C. Odden, Russell P. Tracy, Bruce M. Psaty, Joseph A. Delaney, and James S. Floyd
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Psychiatry and Mental health ,Clinical Psychology ,Risk Factors ,General Neuroscience ,Humans ,Cognitive Dysfunction ,Dementia ,General Medicine ,Geriatrics and Gerontology ,Cardiovascular System ,Lymphocyte Subsets - Published
- 2022
5. Brief Report: Insomnia and Risk of Myocardial Infarction Among People With HIV
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Brandon R. Luu, Robin M. Nance, Joseph A. C. Delaney, Stephanie A. Ruderman, Susan R. Heckbert, Matthew J. Budoff, William C. Mathews, Richard D. Moore, Matthew J. Feinstein, Greer A. Burkholder, Michael J. Mugavero, Joseph J. Eron, Michael S. Saag, Mari M. Kitahata, Heidi M. Crane, and Bridget M. Whitney
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Acquired Immunodeficiency Syndrome ,Prevention ,insomnia ,Clinical Sciences ,Myocardial Infarction ,HIV ,HIV Infections ,Cardiovascular ,type 2 myocardial infarction ,Heart Disease ,Good Health and Well Being ,Infectious Diseases ,Clinical Research ,Sleep Initiation and Maintenance Disorders ,Virology ,Public Health and Health Services ,Humans ,HIV/AIDS ,Pharmacology (medical) ,Longitudinal Studies ,type 1 myocardial infarction ,Heart Disease - Coronary Heart Disease - Abstract
BackgroundInsomnia is common among people with HIV (PWH) and may be associated with increased risk of myocardial infarction (MI). This study examines the association between insomnia and MI by MI type among PWH.SettingLongitudinal cohort study of PWH at 5 Centers for AIDS Research Network of Integrated Clinical Systems sites.MethodsClinical data and patient-reported measures and outcomes from PWH in care between 2005 and 2018 were used in this study. Insomnia, measured at baseline, was defined as having difficulty falling or staying asleep with bothersome symptoms. The Centers for AIDS Research Network of Integrated Clinical Systems centrally adjudicates MIs using expert reviewers, with distinction between type 1 MI (T1MI) and type 2 MI (T2MI). Associations between insomnia and first incident MI by MI type were measured using separate Cox proportional hazard models adjusted for age, sex, race/ethnicity, traditional cardiovascular disease risk factors (hypertension, dyslipidemia, poor kidney function, diabetes, and smoking), HIV markers (antiretroviral therapy, viral suppression, and CD4 cell count), and stimulant use (cocaine/crack and methamphetamine).ResultsAmong 12,448 PWH, 48% reported insomnia. Over a median of 4.4 years of follow-up, 158 T1MIs and 109 T2MIs were identified; approximately half of T2MIs were attributed to sepsis or stimulant use. After adjustment for potential confounders, we found no association between insomnia and T1MI (hazard ratio = 1.05, 95% confidence interval: 0.76 to 1.45) and a 65% increased risk of T2MI among PWH reporting insomnia compared with PWH without insomnia (hazard ratio = 1.65, 95% confidence interval: 1.11 to 2.45).ConclusionsPWH reporting insomnia are at an increased risk of T2MI, but not T1MI, compared with PWH without insomnia, highlighting the importance of distinguishing MI types among PWH.
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- 2022
6. Intersectionality-informed analysis of durable viral suppression disparities in people with HIV
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Adovich S. Rivera, Laura K. Rusie, Matthew J. Feinstein, Juned Siddique, Donald M. Lloyd-Jones, and Lauren B. Beach
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Infectious Diseases ,Immunology ,Immunology and Allergy - Published
- 2023
7. Associations between alcohol and cigarette use and type 1 and 2 myocardial infarction among people with <scp>HIV</scp>
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Lydia N. Drumright, Robin M. Nance, Stephanie A. Ruderman, Jimmy Ma, Bridget M. Whitney, Andrew Hahn, Rob J. Fredericksen, Brandon Luu, William B. Lober, Richard D. Moore, Matthew J. Budoff, Jeanne C. Keruly, Katerina Christopoulos, Sarah Puryear, Amanda Willig, Karen Cropsey, William C. Mathews, Edward Cachay, Laura Bamford, Joseph J. Eron, Sonia Napravnik, Kenneth H. Mayer, Conall O'Cleirigh, Mary E. Mccaul, Geetanjali Chander, Matthew J. Feinstein, Michael S. Saag, Mari M. Kitahata, Susan R. Heckbert, Heidi M. Crane, and Joseph A. C. Delaney
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Infectious Diseases ,Health Policy ,Pharmacology (medical) - Published
- 2023
8. Science and ART-Cardiovascular Disease Risk Assessment in HIV
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Matthew J. Feinstein
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Cardiology and Cardiovascular Medicine - Published
- 2022
9. Association of Cumulative Viral Load With the Incidence of Hypertension and Diabetes in People With HIV
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Adovich S. Rivera, Laura Rusie, Megan Plank, Juned Siddique, Lauren B. Beach, Donald M. Lloyd-Jones, and Matthew J. Feinstein
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Cardiovascular Diseases ,Incidence ,Hypertension ,Diabetes Mellitus ,Internal Medicine ,Humans ,HIV Infections ,Viremia ,Viral Load - Abstract
Background: HIV induces several metabolic derangements that contribute to cardiovascular disease, but it is unclear if HIV increases diabetes or hypertension risk. Refining longitudinal relationships between HIV-specific factors and cardiovascular disease risk factors across different care settings may help inform cardiovascular disease prevention among people with HIV (PWH). Methods: We tested the hypothesis that long-term higher cumulative viral load (viremia-copy-year) is associated with higher risk of diabetes and hypertension by analyzing electronic records of PWH from 2 distinct health systems in Chicago (Northwestern Medicine and Howard Brown Health Care) receiving care in 2004 to 2019. We used joint longitudinal-survival models to assess multivariable-adjusted associations. Subgroup analyses per site were also conducted. Results: We observed 230 (3.0%) incident diabetes cases in 7628 PWH without baseline diabetes and 496 (6.7%) hypertension cases in 7450 PWH without baseline hypertension. Pooled analysis showed a direct association of viremia-copy-year with incident hypertension (hazards ratio, 1.20 [95% CI, 1.14–1.26]) but not with diabetes (hazards ratio, 1.03 [95% CI, 0.96–1.10]). However, site-specific differences existed whereby the Northwestern-only analysis demonstrated a significant association of viremia-copy-year with hypertension (hazards ratio, 1.29 [95% CI, 1.08–1.32]). Additionally, higher social deprivation index (both sites) and diagnosis of mental health disorder (Howard Brown Health only) was associated with higher diabetes and hypertension risk. Conclusions: Cumulative viral load may be associated with incident hypertension among PWH. Associations of HIV control with cardiovascular disease risk factors among PWH may differ by health care system context.
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- 2022
10. Adverse Cardiac Effects of CAR T-Cell Therapy: Characteristics, Surveillance, Management, and Future Research Directions
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Prarthana J. Dalal, Nikita P. Patel, Matthew J. Feinstein, and Nausheen Akhter
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Cancer Research ,Mice ,Receptors, Chimeric Antigen ,Oncology ,Cardiovascular Diseases ,T-Lymphocytes ,Animals ,Humans ,Immunotherapy, Adoptive - Abstract
This review summarizes the current literature on the adverse cardiac effects of CAR T-cell therapy. Case reports and series suggest that major adverse cardiovascular events are not uncommon after CAR T-cell therapy; however, limited data exist regarding incidence, pathophysiology, and prevention strategies related to CAR T-associated cardiovascular events. As cellular therapy advances and the indications for its use continue to expand, it is essential to better understand its associated cardiovascular toxicities. Biomarkers, cardiac imaging, longitudinal data from larger populations, and translational research are all essential areas for further research. Interestingly, CAR T-cell therapy can also be used to reverse cardiac fibrosis in murine models. Altogether this underscores the need to broadly understand how T-cells, endogenous and engineered, may impact cardiovascular diseases.
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- 2022
11. Heart Failure in Chronic Infectious and Inflammatory Conditions: Mechanistic Insights from Clinical Heterogeneity
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Nour, Beydoun and Matthew J, Feinstein
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Heart Failure ,Inflammation ,Chronic Disease ,Humans ,Prognosis - Abstract
The balance between inflammation and its resolution plays an important and increasingly appreciated role in heart failure (HF) pathogenesis. In humans, different chronic inflammatory conditions and immune-inflammatory responses to infection can lead to diverse HF manifestations. Reviewing the phenotypic and mechanistic diversity of these HF presentations offers useful clinical and scientific insights.HF risk is increased in patients with chronic inflammatory and autoimmune disorders and relates to disease severity. Inflammatory condition-specific HF manifestations exist and underlying pathophysiologic causes may differ across conditions. Although inflammatory disease-specific presentations of HF differ, chronic excess in inflammation and auto-inflammation relative to resolution of this inflammation is a common underlying contributor to HF. Further studies are needed to phenotypically refine inflammatory condition-specific HF pathophysiologies and prognoses, as well as potential targets for intervention.
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- 2022
12. Assessing widening disparities in HbA1c and systolic blood pressure retesting during the COVID-19 pandemic in an LGBTQ+-focused federally qualified health center in Chicago: a retrospective cohort study using electronic health records
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Adovich S Rivera, Megan Plank, Ash Davis, Matthew J Feinstein, Laura K Rusie, and Lauren B Beach
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Endocrinology, Diabetes and Metabolism - Abstract
IntroductionTo assess disparities in retesting for glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) among people with diabetes mellitus (DM) and hypertension (HTN), respectively, we analyzed medical records from a lesbian, gay, bisexual, transgender, queer-specialized federally qualified health center with multiple sites in Chicago.Research design and methodsWe identified people with DM seen in 2018 and 2019 then assessed if individuals had HbA1c retested the following year (2019 and 2020). We repeated this using SBP for people with HTN. Rates of retesting were compared across gender, sexual orientation, and race and ethnicity and across the 2 years for each categorization with adjustment for socioeconomic indicators.ResultsRetesting rates declined from 2019 to 2020 for both HbA1c and SBP overall and across all groups. Cisgender women and transgender men with DM (vs cisgender men) and straight people (vs gay men) had significantly lower odds of HbA1c retesting for both years. There was evidence of widening of HbA1c retesting disparities in 2020 between gay men and other orientations. Cisgender women, straight people, and black people (vs white) with HTN had significantly lower odds of SBP retesting for both years. There was evidence of narrowing in the retesting gap between black and white people with HTN, but this was due to disproportionate increase in no retesting in white people rather than a decline in no retesting among black people with HTN.ConclusionsDisparities in DM and HTN care according to gender, race, ethnicity, and sexual orientation persisted during the pandemic with significant widening according to sexual orientation.
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- 2022
13. Circulating T Cells and Cardiovascular Risk in People With and Without HIV Infection
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Suman Kundu, Matthew S. Freiberg, Russell P. Tracy, Kaku A. So-Armah, John R. Koethe, Meredith S. Duncan, Hilary A. Tindle, Joshua A. Beckman, Matthew J. Feinstein, Wyatt J. McDonnell, Amy Justice, and Margaret F. Doyle
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Male ,T-Lymphocytes ,Incidence ,HIV Infections ,Middle Aged ,Cohort Studies ,CD28 Antigens ,Cardiovascular Diseases ,Risk Factors ,Heart Disease Risk Factors ,Humans ,Female ,Prospective Studies ,Cardiology and Cardiovascular Medicine - Abstract
Lower CD4The aim of this study was to explore the association between peripherally circulating CD4Data from 1,860 participants (1,270 PWH) without prevalent CVD from the VACS (Veterans Aging Cohort Study), a prospective, observational cohort of veterans with and without HIV infection, were analyzed. T cell subsets were quantified in baseline samples using flow cytometry. Incident CVD events were identified using International Classification of Diseases-9th Revision and International Classification of Diseases-10th Revision diagnosis and procedure codes. Participants were followed from baseline date (2005-2006) to the first of CVD incidence, death, or September 30, 2016. Cox proportional hazards regression was used to model associations between these T cell subsets and the risk for incident CVD while adjusting for demographics and other CVD risk factors.The median participant age at baseline was 51.6 years. Most were male (94%) and of Black race (69.1%). There were 344 incident CVD events (219 in PWH) during follow-up (median 9.8 years). In PWH, higher proportions (per SD increment) of T helper type 17 cells (adjusted HR: 1.19; 95% CI: 1.08-1.31), T effector memory cells re-expressing CD45RA (adjusted HR: 1.19; 95% CI: 1.07-1.34), and CD28Among PWH, T helper type 17 cells, senescent cells, and CD4
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- 2022
14. Brief Report: Differences in Types of Myocardial Infarctions Among People Aging With HIV
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William C. Mathews, Matthew J. Budoff, Heidi M. Crane, Bridget M. Whitney, Joseph A.C. Delaney, Robin M. Nance, Alan L. Landay, Katerina A. Christopoulos, Susan R. Heckbert, Amanda L. Willig, Kevin P. High, Joseph J. Eron, Richard D. Moore, Mari M. Kitahata, Michael S. Saag, and Matthew J. Feinstein
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Adult ,Male ,Aging ,Plaque instability ,Centers for AIDS Research Network of Clinical Information Systems ,Clinical Sciences ,Population ,Myocardial Infarction ,Human immunodeficiency virus (HIV) ,HIV Infections ,030312 virology ,Cardiovascular ,medicine.disease_cause ,Article ,Cohort Studies ,Sepsis ,03 medical and health sciences ,Virology ,type 2 MI ,medicine ,Humans ,Pharmacology (medical) ,Longitudinal Studies ,Young adult ,education ,Plaque ,Atherosclerotic ,Aged ,0303 health sciences ,education.field_of_study ,business.industry ,Incidence ,HIV ,Vasospasm ,Middle Aged ,medicine.disease ,Laboratory results ,Plaque, Atherosclerotic ,Good Health and Well Being ,Infectious Diseases ,Public Health and Health Services ,HIV/AIDS ,type 1 MI ,Female ,business ,Demography - Abstract
Background Type 1 myocardial infarctions (T1MIs) result from atherosclerotic plaque instability, rupture, and/or erosion. Type 2 MIs (T2MIs) are secondary to causes such as sepsis and cocaine-induced vasospasm resulting in an oxygen demand-supply mismatch and are associated with higher mortality than T1MIs. T2MIs account for a higher proportion of MIs among people living with HIV (PLWH) compared with the general population. We compared MI rates by type among aging PLWH. We hypothesized that increases in MI rates with older age would differ by MI types, and T2MIs would be more common than T1MIs in younger individuals. Methods Potential MIs from 6 sites were centrally adjudicated using physician notes, electrocardiograms, procedure results, and laboratory results. Reviewers categorized MIs by type and identified causes of T2MIs. We calculated T1MI and T2MI incidence rates. Incidence rate ratios were calculated for T2MI vs. T1MI rates per decade of age. Results We included 462 T1MIs (52%) and 413 T2MIs (48%). T1MI rates increased with older age, although T1MIs occurred in all age decades including young adults. T2MI rates were significantly higher than T1MI rates for PLWH younger than 40 years. T1MI rates were similar or higher than T2MI rates among those older than 40 years (significantly higher for those aged 50-59 and 60-69 years). Conclusions Rates of T2MIs were higher than T1MIs until age 40 years among PLWH, differing from the general population, but rates of both were high among older PLWH. Given prognostic differences between MI types, these results highlight the importance of differentiating MI types among PLWH.
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- 2021
15. ADAMTS7 Knockdown in Context: Emerging Therapeutic Targets in Atherothrombosis
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Edward B. Thorp and Matthew J. Feinstein
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Genetics ,Gene knockdown ,Physiology ,business.industry ,Mutation (genetic algorithm) ,Medicine ,Context (language use) ,Cardiology and Cardiovascular Medicine ,business - Published
- 2021
16. Immune Dysregulation in Myocardial Fibrosis, Steatosis, and Heart Failure: Current Insights from HIV and the General Population
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Arjun Sinha and Matthew J. Feinstein
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Adult ,0301 basic medicine ,Population ,HIV Infections ,Bioinformatics ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Fibrosis ,Virology ,medicine ,Humans ,030212 general & internal medicine ,Risk factor ,education ,Heart Failure ,education.field_of_study ,business.industry ,Immune dysregulation ,medicine.disease ,030104 developmental biology ,Infectious Diseases ,Heart failure ,Dysbiosis ,Myocardial fibrosis ,Steatosis ,business - Abstract
HIV is an independent risk factor for heart failure (HF). Cardiac imaging studies in people with HIV (PWH) have identified myocardial pathologies, namely fibrosis and steatosis, that likely contribute to the higher risk of HF. In this review, we survey existing epidemiological, clinical, and mechanistic literature to identify potential pathways that may contribute to the burden of myocardial fibrosis and steatosis among PWH. Multiple cohort studies over the past 20 years have demonstrated a roughly 2-fold higher risk of incident HF in PWH, as well as a disproportionate burden of myocardial fibrosis and steatosis in PWH without HF. Both myocardial fibrosis and steatosis are known contributors to HF in adults without HIV. Pathways involving the NLRP3 inflammasome, TGF-β1, and adipocyte dysfunction are known to play a crucial role in the development of myocardial fibrosis and steatosis. Upregulation of these pathways in HIV due to direct effects of viral proteins, persistent immune dysregulation, gut epithelial breakdown and dysbiosis, and toxicities from antiretroviral therapy may contribute to myocardial dysfunction in HIV. Understanding these pathways may lead to more precise diagnostic and therapeutic targets to curb HF in PWH. During the past three decades, observational and mechanistic studies have provided important insights into risk factors and pathways that may contribute to the increased HF risk in PWH. Future work is needed to characterize these pathways more precisely in mechanistic studies of PWH, with the goal of ultimately deriving valuable targets for prevention, early diagnosis, and treatment of HF in PWH.
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- 2021
17. Association of Low CD4/CD8 Ratio With Adverse Cardiac Mechanics in Lymphopenic HIV-Infected Adults
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Greg Robby, Harry Mystakelis, Elizabeth Laidlaw, Irini Sereti, Arjun Sinha, Yolanda Mejia, Maura Manion, Adovich S. Rivera, Adam Rupert, Virginia Sheikh, and Matthew J. Feinstein
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Adult ,CD4-Positive T-Lymphocytes ,medicine.medical_specialty ,Heart Diseases ,CD4-CD8 Ratio ,MEDLINE ,HIV Infections ,CD8-Positive T-Lymphocytes ,Article ,Text mining ,Immune Reconstitution Inflammatory Syndrome ,Risk Factors ,Lymphopenia ,Hiv infected ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Extramural ,business.industry ,Middle Aged ,Infectious Diseases ,Low CD4+/CD8+ ratio ,HIV-1 ,business ,Cardiac mechanics - Published
- 2020
18. Comparison of Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Prescribing in Patients With Diabetes Mellitus With and Without Cardiovascular Disease
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Hawkins C. Gay, Jingzhi Yu, Stephen D. Persell, Jeffrey A. Linder, Anand Srivastava, Tamara Isakova, Mark D. Huffman, Sadiya S. Khan, R. Kannan Mutharasan, Lucia C. Petito, Matthew J. Feinstein, Sanjiv J. Shah, Clyde W. Yancy, Abel N. Kho, and Faraz S. Ahmad
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Cardiology and Cardiovascular Medicine - Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in patients with type 2 diabetes mellitus (T2DM). We sought to describe trends in prescribing for SGLT2is and GLP1-RAs in diverse care settings, including (1) the outpatient clinics of a midwestern integrated health system and (2) small- and medium-sized community-based primary care practices and health centers in 3 midwestern states. We included adults with T2DM and ≥1 outpatient clinic visit. The outcomes of interest were annual active prescription rates for SGLT2is and GLP1-RAs (separately). In the integrated health system, 22,672 patients met the case definition of T2DM. From 2013 to 2019, the overall prescription rate for SGLT2is increased from 1% to 15% (absolute difference [AD] 14%, 95% confidence interval [CI] 13% to 15%, p0.01). The GLP1-RA prescription rate was stable at 10% (AD 0%, 95% CI -1% to 1%, p = 0.9). In community-based primary care practices, 43,340 patients met the case definition of T2DM. From 2013 to 2017, the SGLT2i prescription rate increased from 3% to 7% (AD 4%, 95% CI 3% to 6%, p0.01), whereas the GLP1-RA prescription rate was stable at 2% to 3% (AD 1%, 95% CI -1 to 1%, p = 0.40). In a fully adjusted regression model, non-Hispanic Black patients had lower odds of SGLT2i or GLP1-RA prescription (odds ratio 0.56, 95% CI 0.34 to 0.89, p = 0.016). In conclusion, the increase in prescription rates was greater for SGLT2is than for GLP1-RAs in patients with T2DM in a large integrated medical center and community primary care practices. Overall, prescription rates for eligible patients were low, and racial disparities were observed.
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- 2022
19. The causal relationship between HIV-1 infection and the spectrum of Coronavirus disease 2019: a Mendelian randomisation study
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Ziyan Ma, Qiaosen Chen, Jingwen He, Matthew J Feinstein, Matthew J Mimiaga, and Hongbo Jiang
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There is currently little available evidence about the causal relationship between HIV infection and Coronavirus disease 2019 (COVID-19), and these relationships may differ across populations and socioeconomic contexts. In this study, two-sample Mendelian randomisation analyses were conducted using summary-level data from genome-wide association studies of the European ancestry population. We initially examined the causality from HIV-1 infection to the spectrum of COVID-19 [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalisation, and very severe respiratory disease]. Then we additionally tested the causality from socioeconomic-position (SEP) indicators (educational attainment and household income) to HIV-1 infection, and from educational attainment and household income to the spectrum of COVID-19. We also tested the causality from HIV-1 infection to body height as a negative control. Null causality from HIV-1 infection to the spectrum of COVID-19 was found. The risk of HIV-1 infection significantly decreased as educational attainment and household income increased. Higher educational attainment was causally associated with lower odds of the spectrum of COVID-19. Higher household income was causally associated with lower odds of COVID-19 hospitalisation and very severe respiratory disease. Negative control shared a similar result with the estimates between HIV-1 infection and the spectrum of COVID-19. We concluded that HIV-1 infection was not causally associated with SARS-CoV-2 infection, COVID-19 hospitalisation, and very severe respiratory disease. Reduction in socioeconomic inequality could potentially ameliorate COVID-19-related and HIV-related health inequities.
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- 2022
20. Phenotypic Presentations of Heart Failure Among Patients With Chronic Inflammatory Diseases
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Daniel L, Underberg, Adovich S, Rivera, Arjun, Sinha, and Matthew J, Feinstein
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Cardiology and Cardiovascular Medicine - Abstract
ObjectiveCharacterize incident heart failure (HF) phenotypes among patients with various chronic inflammatory diseases (CIDs).BackgroundSeveral CIDs are associated with increased HF risk, but differences in HF phenotypes across CIDs are incompletely understood. No prior studies to our knowledge have manually adjudicated HF phenotypes across a CID spectrum.MethodsWe screened for patients with—and controls without—CIDs who had possible HF, then hand-adjudicated HF endpoints. Possible HF resulted from a single HF administrative code; HF was deemed definite/probable vs. absent using standardized, validated criteria. We queried adjudicated HF patients' charts to define specific HF phenotypes, then compared clinical, demographic, and HF phenotypic characteristics for HF patients with specific CIDs vs. non-CID controls using Fisher's exact test.ResultsOut of 415 possible HF patients, 192 had definite/probable HF. Significant differences in HF phenotypes existed across CIDs. Isolated right-sided HF was present in 27.8% of patients with SSc and adjudicated HF, which is more than twice as common as it was in any other CID. Left ventricular systolic dysfunction was most common in patients with HIV and lupus (SLE); mean LVEF was 45.0% ± 18.6% for HIV and 41.3% ± 17.1% for SLE, but was 57.7% ± 10.7% for SSc. Those with HIV and multiple CIDs were most likely to have coronary artery disease.ConclusionsDifferent CIDs present with different phenotypes of physician-adjudicated HF, potentially reflecting different underlying inflammatory pathophysiologies. Larger studies are needed to confirm these findings, as are mechanistic studies focused on understanding specific immunoregulatory contributors to HF.
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- 2022
21. Abstract 060: Association Of Antecedent Statin Use With Outcomes Of People With Covid-19 Admitted At Northwestern Medicine Health System
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Adovich Rivera, Omar Al-Heeti, Lucia Petito, Janna L Williams, Matthew J Feinstein, Babafemi Taiwo, and Chad Achenbach
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Several observational studies have found that antecedent statin use (i.e., use prior to getting admitted) was associated with lower mortality risk in hospitalized COVID-19 patients, but this is not a consistent finding. Differences maybe due to covariate imbalance, model misspecification, or selection bias. Objective: Estimate the association of antecedent statin use with adverse outcomes (in-hospital death, intubation, ICU admission) in patients admitted for COVID-19 in an academic health system in Chicago. Methods: We analyzed electronic health records from an academic health system in Chicago (Mar ‘20-Mar ‘21) comparing rates of adverse events (composite and per outcome) between antecedent users and non-users. Eligible individuals were ≥40 years old in Illinois, admitted for ≥24 hours, and tested positive for COVID-19 in the 30 days before to 7 days after admission. Antecedent use is defined as existence of statins prescription ≥30 days before admission. We used augmented inverse probability weighting (AIPW) with targeted maximum likelihood estimation to improve covariate balance and estimate the risk difference. Compared to standard methods, this approach allowed use of machine learning models and is doubly robust to misspecification. Results: Of 6267 admitted, 1337 (20%) were antecedent users. Users tend to be older, male, White, smoke, and have a comorbidity. Unadjusted analysis showed significantly higher rates of negative outcomes in non-users except in-hospital death. Analysis using AIPW improved covariate balance and showed that users had significantly lower rates of the composite outcome (RD: -3.9%, 95%CI: -6.0, -1.9) and ICU admissions (RD: -4.0, 95%CI: -7.0, -1.0). No differences in intubation and mortality rates were detected. Conclusion: Antecedent statin use is associated with lower risk of ICU admissions but not with intubation or in-hospital mortality. We were not able to confirm the mortality benefit detected by prior studies nor any differences in rates of intubations.
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- 2022
22. Different transmission routes and the risk of advanced HIV disease: A systematic review and network meta-analysis of observational studies
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Yuhan Lyu, Matthew J. Feinstein, Yangyang She, Qiaosen Chen, Yi Yang, Ding Zeng, Xiao Gong, and Hongbo Jiang
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lcsh:R5-920 ,education.field_of_study ,business.industry ,010102 general mathematics ,Population ,MEDLINE ,General Medicine ,Odds ratio ,medicine.disease ,01 natural sciences ,Men who have sex with men ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Environmental health ,Meta-analysis ,medicine ,Observational study ,030212 general & internal medicine ,0101 mathematics ,lcsh:Medicine (General) ,business ,education ,Research Paper ,Sex work - Abstract
Background A substantial proportion of people living with HIV (PLHIV) present for care with advanced HIV disease (AHD), which may result in difficulty reaching the “90–90–90” target to end AIDS in 2030. We assessed the risk of AHD for different transmission routes to summarize the evidence for priority prevention strategies for key populations. Methods Observational studies published before September 10th, 2019 in the PubMed, EMBASE, Web of Science and Chinese electronic databases were analysed. The outcomes of interest were the number of PLHIV and AHD patients and their associated transmission routes. We assessed the risk of AHD among the different transmission routes using the multi-armed network meta-analysis based on the Bayesian method. The associations between AHD and regional policies for sex work and compulsory drug treatment were estimated using ecological linear regression. Findings One hundred and one articles were included, covering 1,297,872 PLHIV with 478,830 patients who developed AHD. The network analysis revealed that among PLHIV, heterosexual contact was associated with the highest risk of AHD, followed by injection drug use (odds ratio [OR]=0•56, 95% credible interval [CrI] 0•47–0•68), and men who have sex with men (OR=0•54, 95% CrI 0•46–0•63). Regions that criminalized sex work and compulsory drug treatment had higher risks for AHD than those that did not. Interpretation Our findings suggest HC is at a higher risk of AHD compared to IDU and MSM. This justifies the need to expand prevention campaigns and maintain efforts to increase HIV testing in the heterosexual population.
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- 2019
23. Changes in proportionate cardiovascular mortality in patients with chronic infectious and inflammatory conditions in the United States, 1999–2018
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Jacob W. Groenendyk, Adovich S. Rivera, Arjun Sinha, Donald M. Lloyd-Jones, and Matthew J. Feinstein
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Adult ,Inflammation ,Male ,Multidisciplinary ,Science ,Middle Aged ,Infections ,Risk Assessment ,Article ,United States ,Cardiovascular diseases ,Rheumatic diseases ,Risk factors ,Chronic Disease ,Humans ,Medicine ,Female ,HIV infections ,Retrospective Studies - Abstract
Treatment options for several chronic infectious and inflammatory conditions have expanded in recent years. This may have implications for evolving competing risks for chronic inflammation-associated comorbidities, including cardiovascular diseases (CVDs). Yet sparse data exist on patterns over time in cardiovascular mortality for chronic infectious and inflammatory conditions. We used data from the Centers for Disease Control and Prevention 1999–2018 Multiple Causes of Death database to investigate patterns in CVD mortality from January 1, 1999 to December 31, 2018 in several infectious and inflammatory conditions. Specifically, we determined age-adjusted proportionate CVD mortality separately for patients with the following conditions (as well as the general population): hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel diseases (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Proportionate CVD mortality differed significantly in 1999 and 2018 for each condition compared with the general population (p
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- 2021
24. HIV and Cardiovascular Disease: From Insights to Interventions
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Matthew J, Feinstein
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Inflammation ,Invited Review ,Cardiovascular Diseases ,Risk Factors ,virus diseases ,Humans ,HIV Infections - Abstract
Individuals with HIV have elevated risks for cardiovascular diseases (CVDs) ranging from myocardial infarction to heart failure. Our understanding of this heightened HIV-associated cardiovascular risk has evolved over the past 2 decades. In the early era of antiretroviral therapy (ART), concern existed that ART was the primary driver of cardiovascular risk. However, it has become increasingly apparent that HIV-related viremia, immune dysregulation, and inflammation are primary drivers of HIV-associated cardiovascular risk, along with traditional cardiovascular risk factors such as tobacco smoking. Indeed, early and effective ART blunts risk for CVDs among individuals with HIV. Despite these improvements in HIV-associated cardiovascular risk, questions remain regarding how to optimally predict, prevent, and treat CVDs among individuals with HIV. Efforts are underway to define more precisely which diagnostic and therapeutic strategies will be most effective in curbing HIV-associated CVDs.
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- 2021
25. Abstract 11820: Physician-Adjudicated Heart Failure Phenotypes Among Patients With Chronic Inflammatory Diseases
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Daniel Underberg, Adovich Rivera, Arjun Sinha, and Matthew J Feinstein
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Objective: To characterize clinical phenotypes of incident heart failure (HF) among patients with various chronic inflammatory diseases (CIDs). Background: Several CIDs are associated with increased HF risk, but differences in HF phenotypes across CIDs are incompletely understood. No prior studies to our knowledge have adjudicated HF phenotypes with physician chart review across a spectrum of CIDs. Methods: We screened for patients with CIDs (and controls without CIDs) who had possible HF in a large urban medical system, then performed physician adjudication of HF endpoints. Possible HF was based on the intentionally sensitive criterion of a single inpatient or outpatient administrative code for HF; we then determined if HF was definite/probable vs. not present using standardized, validated criteria. Charts of patients with adjudicated HF were queried to define specific HF phenotypes. We then compared clinical, demographic, and HF phenotypic characteristics for HF patients with specific CIDs vs. non-CID controls using Fisher’s exact test. Results: Out of 415 patients with at least one code for HF, 192 had definite/probable HF. We observed significant differences in HF phenotypes across CIDs (Table 1). Isolated right-sided HF was more than twice as common in patients with scleroderma (27.8%) than in any other CID. Left ventricular systolic dysfunction was most common in patients with HIV and lupus (SLE); mean LVEF was 45.0% ± 18.6% for HIV and 41.3% ± 17.1% for SLE, while it was 57.7% ± 10.7% for scleroderma. Those with HIV and multiple CIDs were most likely to have coronary artery disease. Conclusions: Different CIDs are associated with different phenotypic presentations of physician-adjudicated HF, which may reflect different underlying inflammatory pathophysiologies. Future studies in larger, multi-center cohorts are needed to confirm these findings, as are mechanistic studies focused on understanding specific immunoregulatory contributors to HF.
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- 2021
26. Abstract 11002: Assessing Widening Disparities in Hba1c and Systolic Blood Pressure Re-Testing During the Covid-19 Pandemic in LGBTQ+ Focused Federally Qualified Health Centers in Chicago
- Author
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Adovich Rivera, Megan Plank, Matthew J Feinstein, Laura Rusie, and Lauren B Beach
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: The COVID-19 pandemic caused disruptions in the health services delivery, especially among vulnerable populations. We assessed if the pandemic widened disparities in care for cardiometabolic conditions in a LGBTQ+-focused federally qualified health system in Chicago. Hypothesis: Disparities in monitoring cardiometabolic conditions present in 2019 worsened in 2020. Methods: We analyzed electronic health records from Howard Brown Health. We assessed HbA1c re-testing and control (≤9%) in 2019 and 2020 among people with diabetes (DM) and ≥1 HbA1c test in the prior year (2018 for 2019, 2019 for 2020) (n2019=818, n2020=1033). A similar assessment was done for hypertension (HTN) with systolic blood pressure (SBP) (n2019=2813, n2020=3660). Comparisons per demographic group per year were done using logistic regression adjusting for socio-demographic variables. Results: Re-testing rates declined from 2019 to 2020 for both HbA1c and SBP overall and across all groups. Adjusted analysis showed gay people with DM had higher rates of HbA1c re-testing than people of other sexual orientations in 2019 and experienced a significantly lower re-testing rate decline in 2020. Adjusted analysis for SBP showed that white (vs Hispanic) and straight (vs gay) people with HTN had lower SBP re-testing rates in 2019 and 2020. Rates of controlled SBP ( Conclusion: The pandemic had mixed impacts on cardiometabolic service disparities in a large LGBTQ+-focused health system. Disparities by sexual orientation for HbA1c widened during the pandemic. Similar worsening was not found for systolic blood pressure, nor for other demographic groups.
- Published
- 2021
27. Long-Term Trajectories of Left Ventricular Ejection Fraction in Patients With Chronic Inflammatory Diseases and Heart Failure: An Analysis of Electronic Health Records
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Faraz S. Ahmad, Jane E. Wilcox, Arjun Sinha, Edward B. Thorp, Matthew J. Feinstein, Adovich S. Rivera, and Donald M. Lloyd-Jones
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cardiomyopathy ,Inflammation ,Health records ,Ventricular Function, Left ,Article ,Pathogenesis ,Risk Factors ,Internal medicine ,Psoriasis ,medicine ,Electronic Health Records ,Humans ,In patient ,Aged ,Heart Failure ,Ejection fraction ,business.industry ,Stroke Volume ,Middle Aged ,medicine.disease ,Echocardiography ,Heart failure ,Chronic Disease ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Immune regulation and inflammation play a role in the pathogenesis and progression of acute and chronic heart failure (HF). Although the clinical course of acute, severe inflammatory cardiomyopathy is well described, the effects of chronic systemic inflammation on cardiovascular function over time are less clear. To investigate this question, we compared trajectories over time in left ventricular ejection fraction for patients with HF with different chronic inflammatory diseases (CIDs): HIV, systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, inflammatory bowel disease, and/or psoriasis. Methods: Using a database of patients receiving care in a large metropolitan health care system since January 1, 2000, we analyzed serial, clinically indicated echocardiograms from patients with HF with CIDs and frequency-matched patients with HF without CIDs. We included patients with ≥3 serial echocardiograms (N=974; median 6.1 years between first and most recent echo). We assessed left ventricular ejection fraction trajectories over time using latent trajectory models, then investigated differences in left ventricular ejection fraction trajectories for specific CID subtypes compared with controls. Results: Overall, the majority of patients studied (N=687; 70.5%) had left ventricular ejection fraction trajectories consistent with HF with preserved or midrange EF, whereas 255 (26.2%) had HF with reduced EF and 32 (3.3%) had HF with recovered EF. Compared with non-CID controls with HF, patients with rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus were significantly more likely than controls to have HF with preserved or midrange EF whereas patients with HIV were significantly more likely to have HF with reduced EF. Conclusions: Among patients with HF with CIDs, distinct left ventricular ejection fraction trajectory patterns associate with different specific individual CIDs. This highlights the heterogeneity of HF subtypes and changes over time across different CIDs.
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- 2021
28. Ideal Cardiovascular Health: Distribution, Determinants and Relationship with Health Status among People Living with HIV in Urban Tanzania
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Theresia A. Ottaru, Gideon P. Kwesigabo, Zeeshan Butt, Adovich S. Rivera, Pilly Chillo, Helen Siril, Lisa R. Hirschhorn, Matthew J. Feinstein, and Claudia Hawkins
- Subjects
Adult ,Community and Home Care ,Cross-Sectional Studies ,Cardiovascular Diseases ,Risk Factors ,Epidemiology ,Health Status ,Humans ,Blood Pressure ,cardiovascular health index ,ideal cardiovascular health ,cardiovascular diseases ,HIV ,Tanzania ,Cardiology and Cardiovascular Medicine - Abstract
Background: Ageing adults living with HIV (ALHIV) have increased risk of cardiovascular diseases as a result of HIV-infection-related chronic immune activation and inflammatory responses. Cardiovascular health index (CVHI) is a valid and relatively simple index for assessing the cardiovascular health (CVH) of the general population. Use of this index among ALHIV in Sub Saharan Africa, a resource-restricted setting where it could be mostly beneficial, remains limited. Understanding of the distribution and associated factors may inform the design of optimal interventions to improve CVH of ALHIV.Objective: We aimed to assess the distribution and factors associated with CVHI scores among ALHIV in an urban setting in Tanzania.Methods: A cross-sectional study was conducted among ALHIV on antiretroviral therapy at six HIV clinics in Dar-es-Salaam, Tanzania. We summed the score of each of the seven CVHI metric to obtain the overall CVHI score and assessed the distribution of the score by sex. We then categorized the overall score into ideal (5–7), intermediate (3–4) and poor (
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- 2022
29. HIV, Subclinical Cardiovascular Disease, and Clinical Progression
- Author
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Matthew J, Feinstein
- Subjects
Cardiovascular Diseases ,Asymptomatic Diseases ,Disease Progression ,Humans ,HIV Infections ,General Medicine ,Original Investigation - Abstract
IMPORTANCE: HIV-associated cardiovascular disease is increasing in prevalence, but its mechanisms remain poorly understood. OBJECTIVE: To systematically review data from advanced cardiovascular imaging studies evaluating computed tomographic coronary angiography, positron emission tomography (PET), and cardiac magnetic resonance (MR), in people living with HIV compared with uninfected individuals. DATA SOURCES: Three databases and Google Scholar were searched for studies assessing cardiovascular pathology using computed tomographic coronary angiography, cardiac MR, PET, and HIV from inception to February 11, 2022. STUDY SELECTION: Two reviewers selected original studies without any restrictions on design, date, or language, investigating HIV and cardiovascular pathology. DATA EXTRACTION AND SYNTHESIS: One investigator extracted data checked by a second investigator. Prevalence ratios (PRs) and differences in inflammation among people living with HIV and uninfected individuals were qualitatively synthesized in terms of cardiovascular pathology. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. MAIN OUTCOMES AND MEASURES: Primary outcomes were computed tomographic coronary angiography–defined moderate to severe (≥50%) coronary stenosis, cardiac MR–defined myocardial fibrosis identified by late gadolinium enhancement, and PET-defined vascular and myocardial target to background ratio. Prevalence of moderate to severe coronary disease, as well as myocardial fibrosis, and PRs compared with uninfected individuals were reported alongside difference in vascular target to background ratio. RESULTS: Forty-five studies including 5218 people living with HIV (mean age, 48.5 years) and 2414 uninfected individuals (mean age, 49.1 years) were identified. Sixteen studies (n = 5107 participants) evaluated computed tomographic coronary angiography; 16 (n = 1698), cardiac MRs; 10 (n = 681), vascular PET scans; and 3 (n = 146), both computed tomographic coronary angiography and vascular PET scans. No studies originated from low-income countries. Regarding risk of bias, 22% were classified as low; 47% moderate; and 31% high. Prevalence of moderate to severe coronary disease among those with vs without HIV ranged from 0% to 52% and 0% to 27%, respectively, with PRs ranging from 0.33 (95% CI, 0.01-15.90) to 5.19 (95% CI, 1.26-21.42). Prevalence of myocardial fibrosis among those with vs without HIV ranged from 5% to 84% and 0% to 68%, respectively, with PRs ranging from 1.01 (95% CI, 0.85-1.21) to 17.35 (95% CI, 1.10-274.28). Differences in vascular target to background ratio among those with vs without HIV ranged from 0.06 (95% CI, 0.01-0.11) to 0.37 (95% CI, 0.02-0.72). CONCLUSIONS AND RELEVANCE: In this systematic review of studies of advanced cardiovascular imaging, the estimates of the associations between HIV and cardiovascular pathologies demonstrated large amounts of heterogeneity. The findings provide a summary of the available data but may not be representative of all individuals living with HIV, including those from low-income countries with higher HIV endemicity.
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- 2022
30. Abstract P176: Proportionate Cardiovascular Mortality Patterns Among Patients With Inflammatory Disease In The United States, 1999-2018
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Arjun Sinha, Matthew J. Feinstein, Jacob Groenendyk, and Adovich S. Rivera
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medicine.medical_specialty ,business.industry ,Physiology (medical) ,Clinical course ,medicine ,Inflammation ,Disease ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business ,Cardiovascular mortality - Abstract
Introduction: Novel therapies have changed the clinical course of several chronic viral and inflammatory conditions over the past two decades. As the morbidity burden of these conditions has changed, competing risks for end-organ diseases including cardiovascular diseases (CVDs) may have likewise evolved. We therefore aimed to investigate changes in the relative burden of CVD mortality over the past two decades across several chronic infectious and inflammatory conditions. Hypothesis: Changes in proportionate CVD-related mortality over the past two decades differ across distinct infectious and inflammatory conditions. Methods: We analyzed 1999-2018 Multiple Causes of Death data from the Centers of Disease Control and Prevention. For several chronic infectious and inflammatory conditions, we analyzed patterns in age-adjusted cardiovascular proportionate mortality, defined as the fraction of deaths in a calendar year with CVD as the underlying cause. We compared age-adjusted proportionate CVD mortality, stratified by sex, for systemic lupus erythematosus (SLE), hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel disease (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic sclerosis (SSc). Results: Proportionate CVD mortality in the general population decreased from 40.9% of 2319606 deaths (1999) to 30.6% of 2778169 deaths (2018), whereas it increased for chronic viral conditions (HCV: 7.0% to 10.2%; HIV: 1.9% to 6.7%) and changed little in SLE (15.3% to 14.4%). Patterns of decreasing proportionate CVD mortality over time were similar for IBD and RA as in the general population. Conclusions: Patterns in proportionate CVD mortality over the past 20 years vary considerably for different chronic infectious and inflammatory conditions. The underlying contributions of infectious and inflammatory burden, off-target effects of therapies, and dynamic changes in competing mortality risk merit further study.
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- 2021
31. Coronary Artery Disease Manifestations in HIV: What, How, and Why
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Arjun Sinha and Matthew J. Feinstein
- Subjects
medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Prevalence ,HIV Infections ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Article ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Insulin resistance ,Epidemiology ,Humans ,Medicine ,030212 general & internal medicine ,Myocardial infarction ,business.industry ,Immunity ,virus diseases ,medicine.disease ,Anti-Retroviral Agents ,Immunology ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment ,Dyslipidemia - Abstract
Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.
- Published
- 2019
32. Associations Between HIV Serostatus and Cardiac Structure and Function Evaluated by 2-Dimensional Echocardiography in the Multicenter AIDS Cohort Study
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Sabina A. Haberlen, Todd T. Brown, Jared W. Magnani, Ann-Margret Ervin, Katherine C. Wu, Henrique Doria de Vasconcellos, Matthew J. Budoff, Joao A.C. Lima, Wendy S. Post, Matthew J. Feinstein, and Carlos Malvestutto
- Subjects
Male ,medicine.medical_specialty ,Heart Ventricles ,antiretroviral therapy ,Diastole ,Multicenter AIDS Cohort Study ,030204 cardiovascular system & hematology ,HIV Antibodies ,Cardiorespiratory Medicine and Haematology ,subclinical cardiovascular disease ,Ventricular Function, Left ,Imaging ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Internal medicine ,Cardiovascular Disease ,Medicine ,Humans ,echocardiography ,030212 general & internal medicine ,Prospective Studies ,Original Research ,Aged ,Heart Failure ,Acquired Immunodeficiency Syndrome ,Ejection fraction ,business.industry ,Inflammatory Heart Disease ,virus diseases ,HIV ,Stroke Volume ,Middle Aged ,medicine.disease ,AIDS ,Cross-Sectional Studies ,atria ,Cardiology ,End-diastolic volume ,HIV/AIDS ,Female ,diastolic dysfunction ,Transthoracic echocardiogram ,cardiac remodeling ,Cardiology and Cardiovascular Medicine ,business ,Heart failure with preserved ejection fraction ,Serostatus ,Follow-Up Studies - Abstract
Background We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2‐dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross‐sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction 3 versus Conclusions HIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.
- Published
- 2021
33. Nonclassical Monocytes (CD14dimCD16+) Are Associated With Carotid Intima-Media Thickness Progression for Men but Not Women: The Multi-Ethnic Study of Atherosclerosis-Brief Report
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Colleen M. Sitlani, Sally A. Huber, Richard A. Kronmal, Joseph A.C. Delaney, James H. Stein, Nels C. Olson, Kenneth Rice, Coleen A. McNamara, Ani Manichaikul, Margaret F. Doyle, Alan L. Landay, Russell P. Tracy, Stephen S. Rich, Bruce M. Psaty, Alison E. Fohner, Susan R. Heckbert, Catherine C. Hedrick, and Matthew J. Feinstein
- Subjects
Carotid Artery Diseases ,Male ,Myeloid ,Time Factors ,Ethnic group ,Lipopolysaccharide Receptors ,Monocytes ,Risk Factors ,Epidemiology ,Common carotid artery ,Prospective Studies ,Aged, 80 and over ,education.field_of_study ,Middle Aged ,Flow Cytometry ,medicine.anatomical_structure ,Phenotype ,cardiovascular system ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Disease Progression ,Female ,epidemiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Lineage (genetic) ,carotid intima-media thickness ,Population ,Inflammation ,GPI-Linked Proteins ,Risk Assessment ,Immunophenotyping ,Sex Factors ,Predictive Value of Tests ,medicine.artery ,medicine ,Humans ,cardiovascular diseases ,education ,Aged ,business.industry ,Receptors, IgG ,United States ,Intima-media thickness ,inflammation ,Case-Control Studies ,Immunology ,atherosclerosis ,business ,Biomarkers ,Clinical and Population Studies - Abstract
Supplemental Digital Content is available in the text., Objective: Few studies of population-based cohorts have investigated prospective associations of lymphoid and myeloid cell subsets in cardiovascular disease onset and progression. The purpose of this analysis was to determine associations of prespecified myeloid and lymphoid lineage cell subsets with common carotid artery intima-media thickness (IMT) progression. Approach and Results: We performed a prospective case-cohort study of 1195 participants from the Multi-Ethnic Study of Atherosclerosis who had peripheral blood mononuclear cells stored from the baseline examination. Key exposure variables were prespecified subsets of lymphoid and myeloid lineage immune cells, phenotyped by multicolor flow cytometry. The primary outcome was progression from baseline (Exam 1) to year 10 (Exam 5) in common carotid IMT. Higher proportions of nonclassical monocytes (CD14dimCD16++) were significantly associated with IMT progression over 10 years, but classical monocytes (CD14++CD16−), CD4+CD28− T cells, and T helper cells producing IL-17 (interleukin 17; T helper 17 cells) were not associated with significant changes in IMT over 10 years. There were significant interactions between monocyte subsets and sex with respect to IMT progression: in sex-stratified analyses, nonclassical monocytes were associated with significant IMT progression and classical monocytes were associated with significant IMT regression for men, whereas there were no significant associations of monocyte subsets with IMT change for women. Conclusions: Nonclassical monocytes were associated with progression of carotid IMT. There were significant sex differences in associations of monocyte subsets with IMT progression: for men, nonclassical monocytes were associated with IMT progression and classical monocytes were associated with regression, whereas these associations were null for women.
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- 2021
34. Association of immune cell subsets with cardiac mechanics in the Multi-Ethnic Study of Atherosclerosis
- Author
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Sally A. Huber, Nels C. Olson, Arjun Sinha, Bruce M. Psaty, Margaret F. Doyle, Adovich S. Rivera, Matthew J. Feinstein, Russel Tracy, Sanjiv J. Shah, Alison E. Fohner, Joseph A.C. Delaney, Joao A.C. Lima, and Colleen M. Sitlani
- Subjects
Male ,medicine.medical_specialty ,Heart Ventricles ,Immunology ,Cardiology ,Magnetic Resonance Imaging, Cine ,Monocytes ,Cohort Studies ,Immunomodulation ,symbols.namesake ,Ventricular Dysfunction, Left ,Immune system ,Risk Factors ,T-Lymphocyte Subsets ,Internal medicine ,medicine ,Humans ,Heart Failure ,Innate immunity ,Innate immune system ,Lung ,Ventricular Remodeling ,business.industry ,General Medicine ,Organ Size ,Middle Aged ,medicine.disease ,Atherosclerosis ,Peripheral ,Bonferroni correction ,medicine.anatomical_structure ,Heart Disease Risk Factors ,Heart failure ,Cohort ,symbols ,Female ,Clinical Medicine ,Serostatus ,business - Abstract
Background Immunomodulatory therapy may help prevent heart failure (HF). Data on immune cells and myocardial remodeling in older adults with cardiovascular risk factors are limited. Methods In the Multi-Ethnic Study of Atherosclerosis cohort, 869 adults had 19 peripheral immune cell subsets measured and underwent cardiac MRI during the baseline exam, of which 321 had assessment of left ventricular global circumferential strain (LV-GCS). We used linear regression with adjustment for demographics, cardiovascular risk factors, and cytomegalovirus serostatus to evaluate the cross-sectional association of immune cell subsets with left ventricular mass index (LVMI) and LV-GCS. Results The average age of the cohort was 61.6 ± 10.0 years and 53% were women. Higher proportions of γ/δ T cells were associated with lower absolute (worse) LV-GCS (–0.105% [95% CI –0.164%, –0.046%] per 1 SD higher proportion of γ/δ T cells, P = 0.0006). This association remained significant after Bonferroni’s correction. Higher proportions of classical monocytes were associated with worse absolute LV-GCS (–0.04% [95% CI –0.07%, 0.00%] per 1 SD higher proportion of classical monocytes, P = 0.04). This did not meet significance after Bonferroni’s correction. There were no other significant associations with LV-GCS or LVMI. Conclusion Pathways associated with γ/δ T cells may be potential targets for immunomodulatory therapy targeted at HF prevention in populations at risk. Funding Contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and grant R01 HL98077 from the National Heart, Lung, and Blood Institute/NIH and grants KL2TR001424, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences/NIH.
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- 2021
35. Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA)
- Author
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Susan R. Heckbert, Alan L. Landay, Bruce M. Psaty, Russell P. Tracy, Matthew J. Feinstein, Sally A. Huber, Joseph A.C. Delaney, Alison E. Fohner, Colleen M. Sitlani, Nels C. Olson, Margaret F. Doyle, and University of Manitoba
- Subjects
Male ,lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,CD14 ,Adaptive immunity ,Blood Pressure ,030204 cardiovascular system & hematology ,Monocytes ,Immunophenotyping ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Lymphocytes ,Intraepithelial Lymphocytes ,Aged ,030304 developmental biology ,Aged, 80 and over ,Innate immunity ,0303 health sciences ,business.industry ,T helper cell ,Middle Aged ,Prognosis ,medicine.disease ,Acquired immune system ,Cryopreserved cells ,Immunity, Innate ,United States ,Confidence interval ,Killer Cells, Natural ,Phenotype ,Blood pressure ,medicine.anatomical_structure ,Longitudinal cohort study ,lcsh:RC666-701 ,Case-Control Studies ,Hypertension ,Systolic blood pressure ,Cardiology ,Female ,Γδ T cells ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,Research Article - Abstract
Background Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP). Methods We assayed immune cells from cryopreserved samples collected at the baseline examination (2000–2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level. Results The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34–3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82–2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14++CD16−) was associated with 2.01 mmHG (95% CI 0.79–3.24) lower average systolic blood pressure. There were no associations of CD4+ T helper cell subsets with average systolic blood pressure. Conclusion These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.
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- 2021
36. Multihit Interactions of Antigens, Immune Responses, and Comorbidities in Cardiovascular Disease Pathogenesis: Methods and Potential Mechanisms
- Author
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Matthew J, Feinstein
- Subjects
Cardiovascular Diseases ,Histocompatibility Antigens Class II ,virus diseases ,Humans ,Comorbidity ,Antigens ,Article - Abstract
OBJECTIVE: To determine the effects of human immunodeficiency virus (HIV) serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection (PLWH) and HIV− controls. APPROACH AND RESULTS: We used participant level data from 9 studies: 7 included PLWH (2 treatment-naïve) and 4 had HIV− controls. Brachial artery (BA) flow-mediated dilation (FMD) was measured using a standardized ultrasound imaging protocol with central reading. After data harmonization, multiple linear regression was used to examine the effects of HIV-serostatus, HIV disease severity measures, and cardiovascular disease (CVD) risk factors on FMD. Of 2533 participants, 986 were PLWH (mean 44.4 [standard deviation 11.8] years old) and 1547 were HIV− controls (42.9 [12.2] years old). The strongest and most consistent associates of FMD were BA diameter, age, sex, and body-mass index. The effect of HIV+ serostatus on FMD was strongly influenced by kidney function. In the highest tertile of creatinine (1.0 mg/dL), the effect of HIV+ serostatus was strong (β=−1.59%, 95%CI −2.58 to −0.60%, p=0.002), even after covariate adjustment (β=−1.36%, 95%CI −2.46 to −0.47%, p=0.003). In the lowest tertile (0.8 mg/dL), the effect of HIV+ serostatus was strong (β=−1.90%, 95%CI −2.58 to −1.21%, p
- Published
- 2020
37. Abstract 13792: Association of Immunocompromised State With Coronary Microvascular Dysfunction in Patients With Well-controlled HIV
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Leah Rethy, Ravi B. Patel, Li-Ming Gan, Christopher Konstantelos, Matthew J. Feinstein, Juliet Ryan, Joseph Kern, Sanjiv J. Shah, Jay A Pandit, Stephen J Dvorak, Arjun Sinha, Babafemi Taiwo, Chad J. Achenbach, and Michael Angarone
- Subjects
medicine.medical_specialty ,Immunologic Factors ,business.industry ,Human immunodeficiency virus (HIV) ,Inflammation ,Disease ,Coronary microcirculation ,medicine.disease_cause ,Immune Dysfunction ,Physiology (medical) ,Internal medicine ,medicine ,Cardiology ,In patient ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction: Patients with HIV have an elevated risk of cardiovascular disease (CVD) that may be partially driven by inflammation and residual immune dysfunction despite treatment with antiretroviral therapy (ART). Coronary microvascular dysfunction (CMD) is an important pathophysiological link between inflammation, immune dysfunction, and CVD and may provide mechanistic insight into CVD risk among HIV+ patients. Methods: We recruited 3 groups of adults aged 40-80 years free of CVD: HIV with evidence of prior/current immunocompromise (n=17), HIV without immunocompromise (n=19), and HIV- controls. All HIV+ participants were on ART and had suppressed viral loads. All controls were on HIV pre-exposure prophylaxis (PrEP). Immunocompromise was defined as nadir CD4 count Results: Of 51 individuals who underwent CFR testing, median (IQR) age was 54 (46-58) and 92% were male. CFR was 3.71 (2.90-4.72) in controls, 3.49 (2.52-4.20) in HIV+/ immunocompromise-, and 2.35 (2.12-2.92) in HIV+/ immunocompromise+ (p=0.002). CMD was present in 7% of controls, 21% of HIV+/immunocompromise-, and 53% of HIV+/immunocompromise+ (p= 0.01). Compared with controls, HIV+/immunocompromise+ was significantly associated with lower CFR after multivariable adjustment ( Table ). Conclusions: HIV+ patients with current/prior immunocompromise free of CVD had high prevalence of CMD and had significantly lower CFR compared with controls on PrEP. Future studies should investigate CMD as a possible target for CVD prevention in HIV+ patients, particularly those with a prior or current immunocompromised state.
- Published
- 2020
38. Abstract 16122: Comparative Risk of Incident Coronary Heart Disease Across Multiple Chronic Inflammatory Diseases
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Arjun Sinha, Anna Pawlowski, Yvonne C. Lee, Matthew DeBerge, Adovich S. Rivera, Edward B. Thorp, Donald M. Lloyd-Jones, Matthew J. Feinstein, Chad J. Achenbach, Sameer Prasada, Simran Chadha, and Rosalind Ramsey-Goldman
- Subjects
Pathogenesis ,business.industry ,Physiology (medical) ,Medicine ,Inflammation ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Bioinformatics ,Coronary heart disease - Abstract
Introduction: Inflammation plays an important role in the pathogenesis of coronary heart disease (CHD). Chronic inflammatory diseases (CIDs) may serve as models to provide insights into the relationships between immune dysfunction, inflammation, and CHD. To investigate this further, we analyzed the risk of incident CHD across different CIDs. Methods: We created a cohort of individuals with CIDs and non-CID controls (frequency-matched on demographics and CHD risk factors), free of baseline CHD, receiving regular outpatient care in a large medical system from 2000 to 2019. CIDs included psoriasis, rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and inflammatory bowel disease (IBD). CHD was defined as myocardial infarction (MI), angina, or coronary revascularization. We used adjusted hazards models to determine incident CHD risk for each CID relative to controls. We also analyzed incident CHD risk by severity of inflammation (baseline C-reactive protein) or immune dysfunction (baseline CD4 T cell level in HIV). Results: Of 18,129 individuals with CIDs and 18,988 controls, there were 1,011 incident CHD events over a median of 3.5 years. After adjusting for demographics and CHD risk factors, CHD risk was significantly elevated in SLE [hazard ratio (HR) 2.85, 95% confidence interval (CI) 2.19-3.71, p Conclusions: Our results show that SLE, SSc, HIV, and RA were associated with significantly elevated risks of incident CHD and MI. Higher levels of inflammation or immune dysfunction were associated with heightened CHD risk within CIDs.
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- 2020
39. Abstract 13456: Association of Chronic Inflammatory Diseases With Incident Atrial Fibrillation
- Author
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Rod S. Passman, Adovich S. Rivera, Yoshihiro Tanaka, Arjun Sinha, Ravi B. Patel, and Matthew J. Feinstein
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medicine.medical_specialty ,business.industry ,Physiology (medical) ,Internal medicine ,medicine ,Cardiology ,Inflammation ,Atrial fibrillation ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,Pathophysiology - Abstract
Introduction: Inflammation plays a vital role on the pathophysiology of atrial fibrillation (AF). Although it is hypothesized that chronic inflammatory diseases (CIDs) may increase the risk for incident AF, data are scarce regarding whether CIDs are associated with incidence of AF. Objectives: To determine associations of CIDs with incident AF in a large cohort comprised of patients with multiple different CIDs. Methods: Patients who visited outpatient clinic regularly due to CIDs (human immunodeficiency virus infection, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic sclerosis [SSc], and systemic lupus erythematosus [SLE]) and frequency-matched controls (in regular primary care/general medicine clinic) were extracted from the Northwestern electronic health records between 1/1/2000-1/1/2019. Multiple imputation was used for imputing missing values and all following statistical analyses. Cumulative incidence of AF was estimated by the Kaplan Meier Curve, and adjusted Cox proportional hazard models were used to compute hazard ratio (HR) for each CID. Results: We analyzed a total number of 37,601 patients (18,847 CIDs and 19,871 controls without CIDs, median age 48.4 years, male 43%). During a median follow-up period of 3.6 years, 1076 cases (2.9%) of incident AF were observed. After adjusting for covariates included in CHARGE-AF risk score, baseline year, insurance type, baseline hypertension, and estimated glomerular filtration rate, both SSc (HR, 2.29: 95% confidence interval [CI], 1.72 - 3.06; p < 0.01) and SLE (HR, 2.18; 95% CI, 1.65 - 2.90; p < 0.01) were associated with a significantly elevated incidence of AF (Table). Conclusions: Patients with SSc or SLE had a significantly elevated incidence of AF after multivariable adjustment. Future studies should investigate mechanisms underlying these findings to generate both disease-specific knowledge and more generalizable knowledge regarding inflammatory contributors to AF.
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- 2020
40. Abstract 14337: Antihypertensive Class and Cardiovascular Outcomes in Patients With HIV and Hypertension
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Raymond R. Townsend, Sanjiv J. Shah, Adam P. Bress, Chad J. Achenbach, Jordana B. Cohen, Leah Rethy, and Matthew J. Feinstein
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Class (computer programming) ,medicine.medical_specialty ,business.industry ,Physiology (medical) ,Human immunodeficiency virus (HIV) ,medicine ,Health services research ,In patient ,Cardiology and Cardiovascular Medicine ,medicine.disease_cause ,Intensive care medicine ,business ,Cardiovascular outcomes - Abstract
Background: People with HIV(PWH) have a high risk of hypertension and hypertension-related cardiovascular diseases (CVD). Objectives: Given unique pathways contributing to hypertension among PWH, we sought to determine whether antihypertensive class was associated with CVD events in PWH. Methods: Among veterans with HIV and new onset hypertension (2000-2019), we used propensity score-matching with Cox regression to evaluate the risk of CVD events (ischemic heart disease, heart failure, stroke) or death by initial antihypertensive class. In supplementary analyses we used marginal structural modeling to account for time-updated antihypertensive class and confounding. Results: Among 8041 PWH with hypertension, 24% were initiated on angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEi/ARB) monotherapy, 23% on thiazide/thiazide-like diuretic monotherapy, 13% on β-blocker monotherapy, and 11% on calcium channel blocker (CCB) monotherapy. Median (IQR) follow-up was 6.5 (3.2-10.5) years and 25% experienced a CVD event. In propensity score-matched analyses, β-blockers, but not CCBs or thiazide/thiazide-like diuretics, were associated with an increased risk of 1) CVD or death 2)incident CVD or death and 3)incident CVD compared with ACEs/ARBs (Incident CVD: HR [95% CI] β-blockers 1.90 [1.24, 2.89]; CCBs 1.02 [0.77, 1.34]; diuretics 1.06 [0.86,1.31]; Figure) . Similar risks were associated with β-blockers in time-updated analyses. In veterans without CKD, initial ACEi/ARB use carried a lower risk of incident heart failure compared with all other classes. Conclusions: We observed high rates of CVD events in PWH with hypertension, and a high prevalence of β-blocker use for initial hypertension management, even among those without indications. Our findings highlight the potential harm associated with β-blockers and the possible benefit associated with ACEI/ARBs for hypertension management in PWH.
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- 2020
41. Abstract 15919: Latent Trajectory Patterns of Left Ventricle Ejection Fraction Among Heart Failure Patients With Chronic Inflammatory Disease: Longitudinal Analysis of Electronic Health Records
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Adovich S. Rivera, Arjun Sinha, Donald M. Lloyd-Jones, Anna Pawlowski, and Matthew J. Feinstein
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Cardiomyopathy ,Inflammation ,medicine.disease ,Chronic inflammatory disease ,Pathogenesis ,medicine.anatomical_structure ,Ventricle ,Physiology (medical) ,Internal medicine ,Heart failure ,medicine ,Cardiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Heart Function Tests - Abstract
Background: Immune regulation and inflammation play a role in the pathogenesis and progression of acute and chronic heart failure (HF). While overt inflammatory cardiomyopathy is a well-described clinical entity marked by acute cardiac dysfunction and relatively high rates of recovery, trajectories in cardiac function among people with chronically heightened systemic inflammation are less clear. We hypothesized that there are differences in trajectories of left ventricular ejection fraction among HF patients with different chronic inflammatory diseases (CIDs): human immunodeficiency virus (HIV), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. Methods: We analyzed serial echocardiographic data from people with CIDs and HF who had at least three echocardiograms (n=974) at a large academic medical center. We identified latent trajectories patterns of LVEF using latent class trajectory models, then described clinical differences across the different trajectories. We then used multinomial regression to test if CID type and other baseline variables were associated with different trajectories. Results: We observed three major LVEF trajectories which paralleled known HF subtypes: preserved/intermediate EF (HFp/iEF, 687, 70.5%), reduced EF (HFrEF, 255, 26.2%), and recovered EF (HFrecEF, 32, 3.3%). These trajectories corresponded closely to accepted clinical definitions. For example, 30/32 (94%) patients in the HFrecEF trajectory had LVEF Conclusions: Among people with HF and CIDs, different trajectories of LVEF are associated with different CIDs and clinical characteristics. This may have implications for therapy and prognosis of HF in CIDs.
- Published
- 2020
42. 'I feel fine. Do I really need to take a cholesterol pill?'
- Author
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Arvind Nishtala and Matthew J. Feinstein
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medicine.medical_specialty ,chemistry.chemical_compound ,chemistry ,business.industry ,Cholesterol ,Family medicine ,Pill ,virus diseases ,Medicine ,business - Abstract
With widespread antiretroviral therapy (ART) accessibility and uptake, HIV has transitioned in many ways to a chronic condition marked by heightened risks of non-communicable diseases. Several clinical and epidemiological studies over the past two decades have demonstrated elevated risks for cardiovascular diseases (CVDs) among people with HIV. These risks appear to be particularly elevated among people with histories of long periods of uncontrolled viremia and CD4 lymphopenia, and dovetail with traditional risk factors (such as smoking) that are common among people with HIV. This chapter presents a discussion of the evolving epidemiology, clinical manifestations, and putative mechanisms of CVDs among people with HIV.
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- 2020
43. Types of Stroke Among People Living With HIV in the United States
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Robin M. Nance, Susan R. Heckbert, Tigran Avoundjian, Michael S. Saag, Rizwan Kalani, Felicia C. Chow, Greg Barnes, William B. Lober, Barbara N. Harding, Matthew J. Feinstein, Joseph A.C. Delaney, Greer A. Burkholder, Amanda L. Willig, David L. Tirschwell, Joseph J. Eron, Sonia Napravnik, Andrew Huffer, Joseph R. Zunt, Mari M. Kitahata, Heidi M. Crane, William C. Mathews, Richard D. Moore, Christina M. Marra, Bridget M. Whitney, Kyra J. Becker, Justin McReynolds, and Emily L. Ho
- Subjects
Adult ,Male ,medicine.medical_specialty ,Clinical cohort ,Clinical Sciences ,Human immunodeficiency virus (HIV) ,Large vessel ,HIV Infections ,030312 virology ,stroke subtypes ,medicine.disease_cause ,Sepsis ,Cohort Studies ,03 medical and health sciences ,Clinical Research ,Risk Factors ,Virology ,Diabetes mellitus ,Internal medicine ,ischemic stroke ,medicine ,hemorrhagic stroke ,Humans ,Pharmacology (medical) ,cardiovascular diseases ,Stroke ,0303 health sciences ,business.industry ,Prevention ,Neurosciences ,HIV ,Middle Aged ,medicine.disease ,Atherosclerosis ,stroke ,United States ,Brain Disorders ,CD4 Lymphocyte Count ,Good Health and Well Being ,Infectious Diseases ,Cohort ,Hypertension ,Public Health and Health Services ,HIV/AIDS ,Female ,business ,Hiv disease - Abstract
Background Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes. Setting CNICS, a U.S. multisite clinical cohort of PLWH in care. Methods We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort. Results Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes. Conclusion Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH.
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- 2020
44. Bone marrow-derived AXL tyrosine kinase promotes mitogenic crosstalk and cardiac allograft vasculopathy
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Joseph R. Leventhal, Samantha Schroth, Jiao Jing Wang, Joseph M. Forbess, J. Andrew Wasserstrom, Mohammed Javeed I. Ansari, Zheng Jenny Zhang, Matthew DeBerge, Arjun Sinha, Kristofor Glinton, Matthew J. Feinstein, Edward B. Thorp, Jon W. Lomasney, Xunrong Luo, and Emily Fisher
- Subjects
0301 basic medicine ,Graft Rejection ,Male ,Myeloid ,medicine.medical_treatment ,Muscle, Smooth, Vascular ,Mice ,0302 clinical medicine ,Myocytes, Cardiac ,Cells, Cultured ,Mice, Inbred BALB C ,Graft Survival ,Flow Cytometry ,Transplant rejection ,medicine.anatomical_structure ,Echocardiography ,030220 oncology & carcinogenesis ,cardiovascular system ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Tyrosine kinase ,Pulmonary and Respiratory Medicine ,Adult ,Cell type ,Myocytes, Smooth Muscle ,Inflammation ,Bone Marrow Cells ,Article ,03 medical and health sciences ,Cell surface receptor ,Proto-Oncogene Proteins ,medicine ,Animals ,Humans ,Transplantation, Homologous ,Cell Proliferation ,Transplantation ,business.industry ,Growth factor ,Receptor Protein-Tyrosine Kinases ,medicine.disease ,Axl Receptor Tyrosine Kinase ,Disease Models, Animal ,030104 developmental biology ,Gene Expression Regulation ,Cancer research ,Heart Transplantation ,RNA ,Surgery ,Bone marrow ,business - Abstract
Cardiac Allograft Vasculopathy (CAV) is a leading contributor to late transplant rejection. Although implicated, the mechanisms by which bone marrow-derived cells promote CAV remain unclear. Emerging evidence implicates the cell surface receptor tyrosine kinase AXL to be elevated in rejecting human allografts. AXL protein is found on multiple cell types, including bone marrow-derived myeloid cells. The causal role of AXL from this compartment and during transplant is largely unknown. This is important because AXL is a key regulator of myeloid inflammation. Utilizing experimental chimeras deficient in the bone marrow-derived Axl gene, we report that Axl antagonizes cardiac allograft survival and promotes CAV. Flow cytometric and histologic analyses of Axl-deficient transplant recipients revealed reductions in both allograft immune cell accumulation and vascular intimal thickness. Co-culture experiments designed to identify cell-intrinsic functions of Axl uncovered complementary cell-proliferative pathways by which Axl promotes CAV-associated inflammation. Specifically, Axl-deficient myeloid cells were less efficient at increasing the replication of both antigen-specific T cells and vascular smooth muscle cells (VSMCs), the latter a key hallmark of CAV. For the latter, we discovered that Axl-was required to amass the VSMC mitogen Platelet-Derived Growth Factor. Taken together, our studies reveal a new role for myeloid Axl in the progression of CAV and mitogenic crosstalk. Inhibition of AXL-protein, in combination with current standards of care, is a candidate strategy to prolong cardiac allograft survival.
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- 2020
45. Abstract P324: Differences in Incident Diabetes Mellitus and Atherosclerotic Cardiovascular Disease in Chronic Inflammatory Diseases
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Simran Chadha, Anna Pawlowski, Matthew J. Feinstein, Donald M. Lloyd-Jones, and Adovich S. Rivera
- Subjects
medicine.medical_specialty ,Cvd risk ,business.industry ,Atherosclerotic cardiovascular disease ,Immunologic Factors ,Inflammation ,medicine.disease ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,medicine ,Relative magnitude ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction: Several chronic inflammatory diseases (CID) are associated with elevated risks for cardiovascular diseases (CVDs). However, the relative magnitude of elevated CVD risk may differ considerably between chronic inflammatory diseases. Hypothesis: We hypothesized that not all CIDs are associated with elevated risk for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD), and that magnitudes of increased CVD risk differ considerably across CIDs. Methods: We estimated the incidence of DM and ASCVD in 18,373 patients with any of six CIDs [human immunodeficiency virus infection (HIV), Irritable bowel disease (IBD), psoriasis, rheumatoid arthritis (RA), scleroderma, and systemic lupus erythematosus (SLE)] in regular outpatient care, as well as controls without CIDs in regular primary care, in a large metropolitan health system since January 1 st , 2000. We assessed incidence of outcomes in patients with each CID compared to controls using quasi-Poisson regression adjusting for age, sex, insurance status, and common CVD risk factors. A 90-day blanking period was applied for identifying incident cases. Results: Psoriasis, HIV, male sex, black race, Hispanic ethnicity, and being on public insurance were all associated with significantly elevated risks for DM (Figure). HIV, RA, scleroderma, SLE, male sex, and public insurance were all associated with significantly elevated risks for ASCVD. The magnitude of increased risk for ASCVD was similarly high for HIV (incidence rate ratio 1.79, 95% confidence interval 1.57-2.05), scleroderma (1.79, 1.42-2.27), and SLE (1.95, 1.59-2.39). Conclusion: Several, but not all, CIDs are associated with elevated risks for DM and ASCVD, but the magnitude of risk elevation differs depending on the CID. These data demonstrate the importance of nuanced approaches to understanding CID- and inflammation-associated CVD risks.
- Published
- 2020
46. Abstract P413: Latent Class Trajectory Modeling Identifies Distinct Clinical Phenotypes in a Cohort of Patients With Elevated Troponin Levels
- Author
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Lucia C. Petito, Anna Pawlowski, Donald M. Lloyd-Jones, Matthew J. Feinstein, Daniel Schneider, Lowie Van Assche, and Michael C. Wang
- Subjects
medicine.medical_specialty ,Cardiac troponin ,biology ,business.industry ,medicine.disease ,Troponin ,Phenotype ,Physiology (medical) ,Internal medicine ,Cohort ,biology.protein ,Cardiology ,Medicine ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction: Clinicians widely use cardiac troponins I and T, sensitive and specific biomarkers of myocardial damage, as diagnostic criteria for myocardial infarction (MI). A common approach, dichotomizing based on whether troponin levels meet thresholds for MI, may miss meaningful heterogeneity in degree and pattern of troponin elevation, with wider clinical implications. Hypothesis: Using latent class trajectory modeling (LCTM) with patients’ patterns of troponin elevations will yield trajectories that represent clinically and prognostically distinct groups of patients. Methods: We used Northwestern Medicine’s Enterprise Data Warehouse to identify patients with at least 3 troponin measurements of which at least one was elevated during their inpatient stay. We built a LCTM to capture troponin trajectories from 13,432 patients with 65,162 measurements since 2000, using Bayesian Information Criterion to select the final model (# of classes varied from 3-7). We then described the clinical and prognostic factors associated with trajectory class membership. Results: LCTM identified 3 troponin trajectories: stable low (77.3%), moderate rise (9.5%), and severe rise-fall (13.2%). The average posterior probability of assignment was >0.95 for all classes. The low group had the most comorbidities vs moderate/severe groups, including cancer (21.9% vs 13.9%/11.3%), heart failure (12.6% vs 8.9%/7.5%), and COPD (15.0% vs 11.8%/10.1%). The moderate/severe rising trajectories had a greater rate of clinically-diagnosed MI than the stable group (34.5%/44.1% vs 5.6%), with relatively more ST-elevation MI in the severe group (19.8% vs 5.3%) and Non-ST-elevation MI in the moderate group (29.3% vs 24.3%). One-year mortality was greatest in the low group vs moderate/severe groups (25.5% vs 21.4%/18.8%). Conclusions: In a cohort of hospitalized patients with elevated troponins, LCTM identified 3 distinct, clinically interpretable troponin trajectories which were associated with differing clinical phenotypes.
- Published
- 2020
47. Coronary Microvascular Dysfunction in HIV: A Review
- Author
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Arjun Sinha, Chad J. Achenbach, Leah Rethy, Matthew J. Feinstein, and Sanjiv J. Shah
- Subjects
medicine.medical_specialty ,Endothelium ,Anti-HIV Agents ,coronary flow reserve ,coronary microvascular function ,MEDLINE ,Human immunodeficiency virus (HIV) ,HIV Infections ,Inflammation ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Risk Assessment ,Pathophysiology ,endothelial dysfunction ,03 medical and health sciences ,0302 clinical medicine ,Coronary Circulation ,Internal medicine ,Contemporary Review ,Clinical Studies ,Mechanisms ,Animals ,Humans ,Medicine ,030212 general & internal medicine ,Endothelial dysfunction ,business.industry ,Extramural ,Microcirculation ,HIV ,Coronary flow reserve ,Cardiovascular Agents ,Prognosis ,medicine.disease ,Coronary Vessels ,medicine.anatomical_structure ,Cardiovascular Diseases ,Heart Disease Risk Factors ,inflammation ,Endothelium/Vascular Type/Nitric Oxide ,Cardiology ,Endothelium, Vascular ,Inflammation Mediators ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment - Published
- 2020
48. Heart Failure and Human Immunodeficiency Virus
- Author
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Gerald S. Bloomfield, Chris T. Longenecker, and Matthew J. Feinstein
- Subjects
business.industry ,Heart failure ,Human immunodeficiency virus (HIV) ,Medicine ,business ,medicine.disease ,medicine.disease_cause ,Virology - Published
- 2020
49. Contributors
- Author
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E. Dale Abel, Luigi Adamo, Shah R. Ali, Larry A. Allen, George L. Bakris, Gerald S. Bloomfield, Robert O. Bonow, Biykem Bozkurt, Michael R. Bristow, Angela L. Brown, Heiko Bugger, John C. Burnett, Javed Butler, John D. Carroll, Adam Castaño, Anna Marie Chang, Jay N. Cohn, Wilson S. Colucci, Louis J. Dell’Italia, Anita Deswal, Adam D. DeVore, Abhinav Diwan, Hilary M. DuBrock, Shannon M. Dunlay, Nina Dzhoyashvili, Gregory A. Ewald, Justin A. Ezekowitz, James C. Fang, Savitri Fedson, Matthew J. Feinstein, G. Michael Felker, John D. Ferguson, Victor A. Ferrari, Carlos M. Ferrario, James D. Flaherty, John S. Floras, Viorel G. Florea, Hanna K. Gaggin, Barry Greenberg, Joshua M. Hare, Adrian F. Hernandez, Joseph A. Hill, Nasrien E. Ibrahim, James L. Januzzi, Susan M. Joseph, Daniel P. Judge, Andrew M. Kahn, Andreas P. Kalogeropoulos, David A. Kass, John Keaney, Ahsan A. Khan, Paul J. Kim, Jon A. Kobashigawa, Evan P. Kransdorf, Eric V. Krieger, Nicholas T. Lam, Daniel J. Lenihan, Gregory Y.H. Lip, Chris T. Longenecker, W. Robb MacLellan, Douglas L. Mann, Ali J. Marian, Daniel D. Matlock, Mathew S. Maurer, Dennis M. McNamara, Robert J. Mentz, Marco Metra, Carmelo A. Milano, Arunima Misra, Joshua D. Mitchell, Alan R. Morrison, Adam Nabeebaccus, Kenta Nakamura, Jose Nativi-Nicolau, Doan T.M. Ngo, Kelsie E. Oatmen, Peter S. Pang, Lampros Papadimitriou, Walter J. Paulus, Tamar S. Polonsky, J. David Port, Florian Rader, Loheetha Ragupathi, Margaret M. Redfield, Michael W. Rich, Joseph G. Rogers, John J. Ryan, Hesham A. Sadek, Can Martin Sag, Ashley A. Sapp, Douglas B. Sawyer, P. Christian Schulze, Ajay M. Shah, Eduard Shantsila, Jagmeet P. Singh, Albert J. Sinusas, Karen Sliwa, Francis G. Spinale, Simon Stewart, Carmen Sucharov, Martin St. John Sutton, Aaron L. Sverdlov, Michael J. Toth, Anne Marie Valente, Loek van Heerebeek, Jasmina Varagic, Ronald G. Victor, Ian Webb, Adam R. Wende, David Whellan, and Dominik M. Wiktor
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- 2020
50. Association between human immunodeficiency virus serostatus and the prevalence of atrial fibrillation
- Author
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Elsayed Z. Soliman, Matthew J. Feinstein, Hiroshi Ashikaga, Todd T. Brown, Sabina A. Haberlen, Ngozi Osuji, Katherine C. Wu, Wendy S. Post, Jared W. Magnani, and Mallory D. Witt
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cross-sectional study ,Observational Study ,HIV Infections ,arrhythmia ,Young Adult ,Acquired immunodeficiency syndrome (AIDS) ,Risk Factors ,Internal medicine ,Ethnicity ,Prevalence ,medicine ,Humans ,atrial fibrillation ,Stroke ,Aged ,heart diseases ,human immunodeficiency virus ,business.industry ,Age Factors ,virus diseases ,Atrial fibrillation ,General Medicine ,Odds ratio ,Middle Aged ,Viral Load ,medicine.disease ,United States ,Cross-Sectional Studies ,atrial flutter ,Cohort ,business ,Serostatus ,Viral load ,Research Article - Abstract
Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study. A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV–) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors. HIV+ men were younger than HIV– men (median 55.5 vs 61.7 years, P
- Published
- 2021
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