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Transcription Factor GATA4 Regulates Cell Type–Specific Splicing Through Direct Interaction With RNA in Human Induced Pluripotent Stem Cell–Derived Cardiac Progenitors Circulation (IF 39.918) Pub Date : 2022-08-08 Lili Zhu, Krishna Choudhary, Barbara Gonzalez-Teran, Yen-Sin Ang, Reuben Thomas, Nicole R. Stone, Lei Liu, Ping Zhou, Chenchen Zhu, Hongmei Ruan, Yu Huang, Shibo Jin, Angelo Pelonero, Frances Koback, Arun Padmanabhan, Nandhini Sadagopan, Austin Hsu, Mauro W. Costa, Casey A. Gifford, Joke van Bemmel, Ruth Hüttenhain, Vasanth Vedantham, Bruce R. Conklin, Brian L. Black, Benoit G. Bruneau, Lars Steinmetz
Background:GATA4 (GATA-binding protein 4), a zinc finger–containing, DNA-binding transcription factor, is essential for normal cardiac development and homeostasis in mice and humans, and mutations in this gene have been reported in human heart defects. Defects in alternative splicing are associated with many heart diseases, yet relatively little is known about how cell type– or cell state–specific
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Multinational Federated Learning Approach to Train ECG and Echocardiogram Models for Hypertrophic Cardiomyopathy Detection Circulation (IF 39.918) Pub Date : 2022-08-02 Shinichi Goto, Divyarajsinhji Solanki, Jenine E. John, Ryuichiro Yagi, Max Homilius, Genki Ichihara, Yoshinori Katsumata, Hanna K. Gaggin, Yuji Itabashi, Calum A. MacRae, Rahul C. Deo
Background:Novel targeted treatments increase the need for prompt hypertrophic cardiomyopathy (HCM) detection. However, its low prevalence (0.5%) and resemblance to common diseases present challenges that may benefit from automated machine learning–based approaches. We aimed to develop machine learning models to detect HCM and to differentiate it from other cardiac conditions using ECGs and echocardiograms
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Sleep-Disordered Breathing and Cardiac Arrhythmias in Adults: Mechanistic Insights and Clinical Implications: A Scientific Statement From the American Heart Association Circulation (IF 39.918) Pub Date : 2022-08-01 Reena Mehra, Mina K. Chung, Brian Olshansky, Dobromir Dobrev, Chandra L. Jackson, Vaishnavi Kundel, Dominik Linz, Nancy S. Redeker, Susan Redline, Prashanthan Sanders, Virend K. Somers, on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, and Stroke Council
Sleep-disordered breathing (SDB), characterized by specific underlying physiological mechanisms, comprises obstructive and central pathophysiology, affects nearly 1 billion individuals worldwide, and is associated with excessive cardiopulmonary morbidity. Strong evidence implicates SDB in cardiac arrhythmogenesis. Immediate consequences of SDB include autonomic nervous system fluctuations, recurrent
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Identification of a Gain-of-Function LIPC Variant as a Novel Cause of Familial Combined Hypocholesterolemia Circulation (IF 39.918) Pub Date : 2022-07-28 Wieneke Dijk, Mathilde Di Filippo, Sander Kooijman, Robin van Eenige, Antoine Rimbert, Amandine Caillaud, Aurélie Thedrez, Lucie Arnaud, Amanda Pronk, Damien Garçon, Thibaud Sotin, Pierre Lindenbaum, Enrique Ozcariz Garcia, Jean-Paul Pais de Barros, Laurence Duvillard, Karim Si-Tayeb, Nuria Amigo, Jean-Yves Le Questel, Patrick C.N. Rensen, Cedric Le May, Philippe Moulin, Bertrand Cariou
BACKGROUND:Atherosclerotic cardiovascular disease is the main cause of mortality worldwide and is strongly influenced by circulating low-density lipoprotein (LDL) cholesterol levels. Only a few genes causally related to plasma LDL cholesterol levels have been identified so far, and only 1 gene, ANGPTL3, has been causally related to combined hypocholesterolemia. Here, our aim was to elucidate the genetic
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Donor Macrophages Modulate Rejection After Heart Transplantation Circulation (IF 39.918) Pub Date : 2022-07-26 Benjamin J. Kopecky, Hao Dun, Junedh M. Amrute, Chieh-Yu Lin, Andrea L. Bredemeyer, Yuriko Terada, Peter O. Bayguinov, Andrew L. Koenig, Christian C. Frye, James A.J. Fitzpatrick, Daniel Kreisel, Kory J. Lavine
BACKGROUND:Cellular rejection after heart transplantation imparts significant morbidity and mortality. Current immunosuppressive strategies are imperfect, target recipient T cells, and have adverse effects. The innate immune response plays an essential role in the recruitment and activation of T cells. Targeting the donor innate immune response would represent the earliest interventional opportunity
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Predictive Utility of a Validated Polygenic Risk Score for Long-Term Risk of Coronary Heart Disease in Young and Middle-Aged Adults Circulation (IF 39.918) Pub Date : 2022-07-26 Sadiya S. Khan, Courtney Page, Daniel M. Wojdyla, Yosef Y. Schwartz, Philip Greenland, Michael J. Pencina
BACKGROUND:Understanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies.METHODS:Data from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study
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Nuclear Receptor NR1D1 Regulates Abdominal Aortic Aneurysm Development by Targeting the Mitochondrial Tricarboxylic Acid Cycle Enzyme Aconitase-2 Circulation (IF 39.918) Pub Date : 2022-07-26 Ling-Yue Sun, Yu-Yan Lyu, Heng-Yuan Zhang, Zhi Shen, Guan-Qiao Lin, Na Geng, Yu-Li Wang, Lin Huang, Ze-Hao Feng, Xiao Guo, Nan Lin, Song Ding, An-Cai Yuan, Lan Zhang, Kun Qian, Jun Pu
BACKGROUND:Metabolic disorder increases the risk of abdominal aortic aneurysm (AAA). NRs (nuclear hormone receptors) have been increasingly recognized as important regulators of cell metabolism. However, the role of NRs in AAA development remains largely unknown.METHODS:We analyzed the expression profile of the NR superfamily in AAA tissues and identified NR1D1 (NR subfamily 1 group D member 1) as
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Management of Atrial Fibrillation Across the Spectrum of Heart Failure With Preserved and Reduced Ejection Fraction Circulation (IF 39.918) Pub Date : 2022-07-25 Yogesh N.V. Reddy, Barry A. Borlaug, Bernard J. Gersh
Atrial fibrillation (AF) is the most common arrhythmia among patients with heart failure (HF), and HF is the most common cause of death for patients presenting with clinical AF. AF is frequently associated with pathological atrial myocardial dysfunction and remodeling, a triad that has been called atrial myopathy. AF can be the cause or consequence of clinical HF, and the directionality varies between
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Highlights From the Circulation Family of Journals Circulation (IF 39.918) Pub Date : 2022-07-25
Highlights from the June issues of the subspecialty journals span a variety of topics. The safety of pulsed field ablation, a novel technology for atrial fibrillation, is reported in Circulation: Arrhythmia and Electrophysiology. Associations of truncating variants in the desmosomal gene with arrhythmogenic right ventricular cardiomyopathy from the UK Biobank are analyzed in Circulation: Genomic and
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Correction to: Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure Circulation (IF 39.918) Pub Date : 2022-07-25
In the article by Borlaug et al, “Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure,” which published in the May 24, 2022, issue of the journal (Circulation.2022; 145:1592-1604. DOI: 10.1161/CIRCULATIONAHA.122.059486), a correction is needed. The disclosures of one the authors, Dr Scott Solomon, was inadvertently excluded from the disclosures
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Correction to: Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency Circulation (IF 39.918) Pub Date : 2022-07-25
In the article by Dou et al, “Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency,” which published in the December 14, 2021, issue of the journal (Circulation.2021;144:1940-1954. DOI: 10.1161/CIRCULATIONAHA.121.056414), a correction is needed. The disclosures of one the authors, Dr Pradeep Natarajan, was inadvertently excluded from the disclosures statement in the
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Long-Term Leisure-Time Physical Activity Intensity and All-Cause and Cause-Specific Mortality: A Prospective Cohort of US Adults Circulation (IF 39.918) Pub Date : 2022-07-25 Dong Hoon Lee, Leandro F.M. Rezende, Hee-Kyung Joh, NaNa Keum, Gerson Ferrari, Juan Pablo Rey-Lopez, Eric B. Rimm, Fred K. Tabung, Edward L. Giovannucci
Background: The 2018 physical activity guidelines for Americans recommend a minimum of 150 to 300 min/wk of moderate physical activity (MPA), 75 to 150 min/wk of vigorous physical activity (VPA), or an equivalent combination of both. However, it remains unclear whether higher levels of long-term VPA and MPA are, independently and jointly, associated with lower mortality.Methods: A total of 116221 adults
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Community-Based, Cluster-Randomized Pilot Trial of a Cardiovascular Mobile Health Intervention: Preliminary Findings of the FAITH! Trial Circulation (IF 39.918) Pub Date : 2022-07-18 LaPrincess C. Brewer, Sarah Jenkins, Sharonne N. Hayes, Ashok Kumbamu, Clarence Jones, Lora E. Burke, Lisa A. Cooper, Christi A. Patten
Background:African Americans continue to have suboptimal cardiovascular health (CVH) based on the American Heart Association Life’s Simple 7 (LS7), 7 health-promoting behaviors and biological risk factors (eg, physical activity, blood pressure). Innovative, community-level interventions in partnership with trusted institutions such as African American churches are potential means to improve CVH in
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Disparities in Cardiovascular Mortality Between Black and White Adults in the United States, 1999 to 2019 Circulation (IF 39.918) Pub Date : 2022-07-18 Ashley N. Kyalwazi, Eméfah C. Loccoh, LaPrincess C. Brewer, Elizabeth O. Ofili, Jiaman Xu, Yang Song, Karen E. Joynt Maddox, Robert W. Yeh, Rishi K. Wadhera
Background:Black adults experience a disproportionately higher burden of cardiovascular risk factors and disease in comparison with White adults in the United States. Less is known about how sex-based disparities in cardiovascular mortality between these groups have changed on a national scale over the past 20 years, particularly across geographic determinants of health and residential racial segregation
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Racial and Ethnic Differences in All-Cause and Cardiovascular Disease Mortality: The MESA Study Circulation (IF 39.918) Pub Date : 2022-07-18 Wendy S. Post, Karol E. Watson, Spencer Hansen, Aaron R. Folsom, Moyses Szklo, Steven Shea, R. Graham Barr, Gregory Burke, Alain G. Bertoni, Norrina Allen, James S. Pankow, Joao A.C. Lima, Jerome I. Rotter, Joel D. Kaufman, W. Craig Johnson, Richard A. Kronmal, Ana V. Diez-Roux, Robyn L. McClelland
Background:Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis).Methods:MESA recruited
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Polygenic Risk Scores for Cardiovascular Disease: A Scientific Statement From the American Heart Association Circulation (IF 39.918) Pub Date : 2022-07-18 Jack W. O’Sullivan, Sridharan Raghavan, Carla Marquez-Luna, Jasmine A. Luzum, Scott M. Damrauer, Euan A. Ashley, Christopher J. O’Donnell, Cristen J. Willer, Pradeep Natarajan, on behalf of the American Heart Association Council on Genomic and Precision Medicine, Council on Clinical Cardiology, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiovascular Radiology and Intervention
Cardiovascular disease is the leading contributor to years lost due to disability or premature death among adults. Current efforts focus on risk prediction and risk factor mitigation‚ which have been recognized for the past half-century. However, despite advances, risk prediction remains imprecise with persistently high rates of incident cardiovascular disease. Genetic characterization has been proposed
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Effect of Patient-Reported Preprocedural Physical and Mental Health on 10-Year Mortality After Percutaneous or Surgical Coronary Revascularization Circulation (IF 39.918) Pub Date : 2022-07-18 Masafumi Ono, Patrick W. Serruys, Scot Garg, Hideyuki Kawashima, Chao Gao, Hironori Hara, Mattia Lunardi, Rutao Wang, Neil O’Leary, Joanna J. Wykrzykowska, Jan J. Piek, Michael J. Mack, David R. Holmes, Marie-Claude Morice, Arie Pieter Kappetein, Daniel J.F.M. Thuijs, Thilo Noack, Friedrich W. Mohr, Piroze M. Davierwala, John A. Spertus, David J. Cohen, Yoshinobu Onuma, for the SYNTAX Extended Survival
BACKGROUND:Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical
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Cardiomyocyte-Specific Long Noncoding RNA Regulates Alternative Splicing of the Triadin Gene in the Heart Circulation (IF 39.918) Pub Date : 2022-07-18 Yuanbiao Zhao, Andrew S. Riching, Walter E. Knight, Congwu Chi, Lindsey J. Broadwell, Yanmei Du, Mostafa Abdel-Hafiz, Amrut V. Ambardekar, David C. Irwin, Catherine Proenza, Hongyan Xu, Leslie A. Leinwand, Lori A. Walker, Kathleen C. Woulfe, Michael R. Bristow, Peter M. Buttrick, Kunhua Song
BACKGROUND:Abnormalities in Ca2+ homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role in Ca2+ homeostasis in cardiomyocytes. Alternative splicing of a single triadin gene produces multiple triadin isoforms. The cardiac-predominant isoform, mouse MT-1 or human Trisk32, is encoded by triadin exons 1 to 8. In humans, mutations in the triadin gene that
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Elucidating the Clinical Implications and Pathophysiology of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Call to Action: A Science Advisory From the American Heart Association Circulation (IF 39.918) Pub Date : 2022-07-11 Evan L. Brittain, Thenappan Thenappan, Jessica H. Huston, Vineet Agrawal, Yen-Chun Lai, Debra Dixon, John J. Ryan, Eldrin F. Lewis, Margaret M. Redfield, Sanjiv J. Shah, Bradley A. Maron, on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Lifestyle and Cardiometabolic
This science advisory focuses on the need to better understand the epidemiology, pathophysiology, and treatment of pulmonary hypertension in patients with heart failure with preserved ejection fraction. This clinical phenotype is important because it is common, is strongly associated with adverse outcomes, and lacks evidence-based therapies. Our goal is to clarify key knowledge gaps in pulmonary hypertension
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Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition Circulation (IF 39.918) Pub Date : 2022-07-11 Yuliya Lytvyn, Karen Kimura, Nuala Peter, Vesta Lai, Josephine Tse, Leslie Cham, Bruce A. Perkins, Nima Soleymanlou, David Z.I. Cherney
BACKGROUND:The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration.METHODS:Thirty patients (out of 31 randomized) completed this double-blind, placebo-controlled, crossover trial
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Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial Circulation (IF 39.918) Pub Date : 2022-07-11 Yanfang Wang, Lin Feng, Guo Zeng, Huilian Zhu, Jianqin Sun, Pei Gao, Jihong Yuan, Xi Lan, Shuyi Li, Yanfang Zhao, Xiayan Chen, Hongli Dong, Si Chen, Zhen Li, Yidan Zhu, Ming Li, Xiang Li, Zhenquan Yang, Huijuan Li, Hai Fang, Gaoqiang Xie, Pao-Hwa Lin, Junshi Chen, Yangfeng Wu
Background:More than one-fifth of the world’s population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation.Methods:A multicenter, patient- and outcome assessor–blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines
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Deformation of Transcatheter Aortic Valve Prostheses: Implications for Hypoattenuating Leaflet Thickening and Clinical Outcomes Circulation (IF 39.918) Pub Date : 2022-07-08 Miho Fukui, Vinayak N. Bapat, Santiago Garcia, Marshall W. Dworak, Go Hashimoto, Hirotomo Sato, Mario Gössl, Maurice Enriquez-Sarano, John R. Lesser, João L. Cavalcante, Paul Sorajja
BACKGROUND:Although transcatheter aortic valve replacement (TAVR) therapy continues to grow, there have been concerns about the occurrence of hypoattenuating leaflet thickening (HALT), which may affect prosthesis function or durability. This study aimed to examine prosthesis frame factors and correlate their extent to the frequency of HALT and clinical outcomes.METHODS:We prospectively examined 565
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Assessment of Clinical Worsening End Points as a Surrogate for Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Circulation (IF 39.918) Pub Date : 2022-07-08 Élodie Tremblay, Camille Gosselin, Vicky Mai, Annie C. Lajoie, Roubi Kilo, Jason Weatherald, Yves Lacasse, Sebastien Bonnet, Jean-Christophe Lega, Steeve Provencher
BACKGROUND:Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for mortality in PAH trials, and whether the various CW components were similar in terms of frequency of occurrence, treatment-related relative risk (RR) reduction, and importance to patients.METHODS:We searched MEDLINE, Embase
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Characteristics of Heart Failure With Preserved Ejection Fraction Across the Range of Left Ventricular Ejection Fraction Circulation (IF 39.918) Pub Date : 2022-07-08 Sebastian Rosch, Karl-Patrik Kresoja, Christian Besler, Karl Fengler, Anne Rebecca Schöber, Maximilian von Roeder, Christian Lücke, Matthias Gutberlet, Karin Klingel, Holger Thiele, Karl-Philipp Rommel, Philipp Lurz
BACKGROUND:Recent trial data suggest that stratification of patients with heart failure with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) provides a means for dissecting different treatment responses. However, the differential pathophysiologic considerations have rarely been described.METHODS:This prospective, single-center study analyzed consecutive symptomatic
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Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles Circulation (IF 39.918) Pub Date : 2022-07-08 Mohammed Rabiul Hosen, Philip Roger Goody, Andreas Zietzer, Xu Xiang, Sven Thomas Niepmann, Alexander Sedaghat, Vedat Tiyerili, Ramesh Chennupati, Joseph B. Moore IV, Reinier A. Boon, Shizuka Uchida, Jan-Malte Sinning, Sebastian Zimmer, Eicke Latz, Nikos Werner, Georg Nickenig, Felix Jansen
BACKGROUND:Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a specific role for circulating microRNAs (miRNAs) in the
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Escalating and De-escalating Temporary Mechanical Circulatory Support in Cardiogenic Shock: A Scientific Statement From the American Heart Association Circulation (IF 39.918) Pub Date : 2022-07-07 Bram J. Geller, Shashank S. Sinha, Navin K. Kapur, Marie Bakitas, Leora B. Balsam, Joanna Chikwe, Deborah G. Klein, Ajar Kochar, Sofia C. Masri, Daniel B. Sims, Graham C. Wong, Jason N. Katz, Sean van Diepen, on behalf of the American Heart Association Acute Cardiac Care and General Cardiology Committee of the Council on Clinical Cardiology, Council on Cardiopulmonary, Critical Care, Perioperative
The use of temporary mechanical circulatory support in cardiogenic shock has increased dramatically despite a lack of randomized controlled trials or evidence guiding clinical decision-making. Recommendations from professional societies on temporary mechanical circulatory support escalation and de-escalation are limited. This scientific statement provides pragmatic suggestions on temporary mechanical
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Correction to: Genetic Landscape of the ACE2 Coronavirus Receptor Circulation (IF 39.918) Pub Date : 2022-07-05
In the article by Yang et al, “Genetic Landscape of the ACE2 Coronavirus Receptor” which published in the May 3, 2022, issue of the journal (Circulation. 2021;145:1398–1411. doi: 10.1161/CIRCULATIONAHA.121.057888), a correction is needed. The incorrect author was listed in the first line of the Disclosures section. The Disclosures should read as follows: Dr Butterworth has received grants outside of
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Restoration of Cardiomyogenesis in Aged Mouse Hearts by Voluntary Exercise Circulation (IF 39.918) Pub Date : 2022-07-06 Carolin Lerchenmüller, Ana Vujic, Sonja Mittag, Annie Wang, Charles P. Rabolli, Chiara Heß, Fynn Betge, Ashraf Y. Rangrez, Malay Chaklader, Christelle Guillermier, Frank Gyngard, Jason D. Roh, Haobo Li, Matthew L. Steinhauser, Norbert Frey, Beverly Rothermel, Christoph Dieterich, Anthony Rosenzweig, Richard T. Lee
Background:The human heart has limited capacity to generate new cardiomyocytes and this capacity declines with age. Because loss of cardiomyocytes may contribute to heart failure, it is crucial to explore stimuli of endogenous cardiac regeneration to favorably shift the balance between loss of cardiomyocytes and the birth of new cardiomyocytes in the aged heart. We have previously shown that cardiomyogenesis
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High-Sensitivity Cardiac Troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guidelines for the Evaluation and Diagnosis of Acute Chest Pain Circulation (IF 39.918) Pub Date : 2022-07-01 Yader Sandoval, Fred S. Apple, Simon A. Mahler, Richard Body, Paul O. Collinson, Allan S. Jaffe, on behalf of the International Federation of Clinical Chemistry and Laboratory Medicine Committee on the Clinical Application of Cardiac Biomarkers
The 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance guidelines for the evaluation and diagnosis of acute chest pain make important recommendations that include the recognition of high-sensitivity
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Trials and Tribulations of Randomized Clinical Trials Circulation (IF 39.918) Pub Date : 2022-07-01 Robert A. Harrington
Appropriately designed and conducted randomized clinical trials (RCTs) are foundational for the practice of evidence-based medicine, including the regulatory approval of therapeutics and the inclusion of those therapies in clinical practice guidelines. Broadly defined, RCTs can be considered in 2 categories: explanatory or mechanistic trials that examine the effect of an intervention on biological
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Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab Circulation (IF 39.918) Pub Date : 2022-06-30 Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz
BACKGROUND:Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain.METHODS:The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment
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Detection of G Protein–Coupled Receptor Autoantibodies in Postural Orthostatic Tachycardia Syndrome Using Standard Methodology Circulation (IF 39.918) Pub Date : 2022-06-29 Juliette Hall, Kate M. Bourne, Steven Vernino, Viktor Hamrefors, Isabella Kharraziha, Jan Nilsson, Robert S. Sheldon, Artur Fedorowski, Satish R. Raj
BACKGROUND:Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein–coupled receptors between patients
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Status of Cardiovascular Health in US Adults and Children Using the American Heart Association's New "Life's Essential 8" Metrics: Prevalence Estimates from the National Health and Nutrition Examination Survey (NHANES), 2013-2018 Circulation (IF 39.918) Pub Date : 2022-06-29 Donald M. Lloyd-Jones, Hongyan Ning, Darwin Labarthe, LaPrincess Brewer, Garima Sharma, Wayne Rosamond, Randi E. Foraker, Terrie Black, Michael A. Grandner, Norrina B. Allen, Cheryl Anderson, Helen Lavretsky, Amanda M. Perak
Background: The American Heart Association (AHA) recently published an updated algorithm for quantifying cardiovascular health (CVH)—the "Life's Essential 8™" score. We quantified US levels of CVH using the new score.Methods: We included non-pregnant, non-institutionalized individuals ages 2 through 79 years who were free of cardiovascular disease from the National Health and Nutrition Examination
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Life’s Essential 8: Updating and Enhancing the American Heart Association’s Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association Circulation (IF 39.918) Pub Date : 2022-06-29 Donald M. Lloyd-Jones, Norrina B. Allen, Cheryl A.M. Anderson, Terrie Black, LaPrincess C. Brewer, Randi E. Foraker, Michael A. Grandner, Helen Lavretsky, Amanda Marma Perak, Garima Sharma, Wayne Rosamond, on behalf of the American Heart Association
In 2010, the American Heart Association defined a novel construct of cardiovascular health to promote a paradigm shift from a focus solely on disease treatment to one inclusive of positive health promotion and preservation across the life course in populations and individuals. Extensive subsequent evidence has provided insights into strengths and limitations of the original approach to defining and
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Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF) Circulation (IF 39.918) Pub Date : 2022-06-29 P. Christian Schulze, Jürgen Bogoviku, Julian Westphal, Pawel Aftanski, Franz Haertel, Sissy Grund, Stephan von Haehling, Ulrike Schumacher, Sven Möbius-Winkler, Martin Busch
Background:Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear.Methods:In
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Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes Circulation (IF 39.918) Pub Date : 2022-06-28 Gerasimos Filippatos, Javed Butler, Dimitrios Farmakis, Faiez Zannad, Anne Pernille Ofstad, João Pedro Ferreira, Jennifer B. Green, Julio Rosenstock, Sven Schnaidt, Martina Brueckmann, Stuart J. Pocock, Milton Packer, Stefan D. Anker, on behalf of the EMPEROR-Preserved Trial Committees and Investigators
BACKGROUND:Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated.METHODS:Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy
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Identification of Pathogenic Immune Cell Subsets Associated With Checkpoint Inhibitor–Induced Myocarditis Circulation (IF 39.918) Pub Date : 2022-06-28 Han Zhu, Francisco X. Galdos, Daniel Lee, Sarah Waliany, Yuhsin Vivian Huang, Julia Ryan, Katherine Dang, Joel W. Neal, Heather A. Wakelee, Sunil A. Reddy, Sandy Srinivas, Lih-Ling Lin, Ronald M. Witteles, Holden T. Maecker, Mark M. Davis, Patricia K. Nguyen, Sean M. Wu
Background:Immune checkpoint inhibitors (ICIs) are monoclonal antibodies used to activate the immune system against tumor cells. Despite therapeutic benefits, ICIs have the potential to cause immune-related adverse events such as myocarditis, a rare but serious side effect with up to 50% mortality in affected patients. Histologically, patients with ICI myocarditis have lymphocytic infiltrates in the
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Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy Circulation (IF 39.918) Pub Date : 2022-06-28 Paul M Ridker, Nader Rifai, Jean MacFadyen, Robert J. Glynn, Lixia Jiao, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Jean-Claude Tardif, Christie M. Ballantyne, R. Preston Mason, Deepak L. Bhatt
Background:REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl—Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with use of icosapent ethyl compared with pharmaceutical grade mineral oil. The mechanisms underlying this benefit remain uncertain. We explored whether treatment allocation in REDUCE-IT might affect a series of biomarkers in
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Novel Smooth Muscle Ca2+-Signaling Nanodomains in Blood Pressure Regulation Circulation (IF 39.918) Pub Date : 2022-06-27 Yen-Lin Chen, Zdravka Daneva, Maniselvan Kuppusamy, Matteo Ottolini, Thomas M. Baker, Eliska Klimentova, Soham A. Shah, Jennifer D. Sokolowski, Min S. Park, Swapnil K. Sonkusare
BACKGROUND:Ca2+ signals in smooth muscle cells (SMCs) contribute to vascular resistance and control blood pressure. Increased vascular resistance in hypertension has been attributed to impaired SMC Ca2+ signaling mechanisms. In this regard, transient receptor potential vanilloid 4 (TRPV4SMC) ion channels are a crucial Ca2+ entry pathway in SMCs. However, their role in blood pressure regulation has
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Socioeconomic Deprivation: An Important, Largely Unrecognized Risk Factor in Primary Prevention of Cardiovascular Disease Circulation (IF 39.918) Pub Date : 2022-06-24 Dorien M. Kimenai, Leah Pirondini, John Gregson, David Prieto, Stuart J. Pocock, Pablo Perel, Tilly Hamilton, Paul Welsh, Archie Campbell, David J. Porteous, Caroline Hayward, Naveed Sattar, Nicholas L. Mills, Anoop S.V. Shah
Background:Socioeconomic deprivation is associated with higher cardiovascular morbidity and mortality. Whether deprivation status should be incorporated in more cardiovascular risk estimation scores remains unclear. This study evaluates how socioeconomic deprivation status affects the performance of 3 primary prevention cardiovascular risk scores.Methods:The Generation Scotland Scottish Family Health
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Effects of Coronary Artery Disease–Associated Variants on Vascular Smooth Muscle Cells Circulation (IF 39.918) Pub Date : 2022-06-23 Charles U. Solomon, David G. McVey, Catherine Andreadi, Peng Gong, Lenka Turner, Paulina J. Stanczyk, Sonja Khemiri, Julie C. Chamberlain, Wei Yang, Tom R. Webb, Christopher P. Nelson, Nilesh J. Samani, Shu Ye
BACKGROUND:Genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease (CAD). However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. Evidence suggests that the genetic influence on CAD susceptibility may act partly through vascular smooth muscle cells (VSMCs)
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Around and Around…A Wide Complex Tachycardia Circulation (IF 39.918) Pub Date : 2022-06-21 Ricardo Avendaño, Nimrod Lavi, Lynda E. Rosenfeld
A 58-year-old male with a history of type 2 diabetes, hypertension, chronic kidney disease, a severe ischemic cardiomyopathy (left ventricular [LV] ejection fraction 19%), paroxysmal atrial fibrillation, and ventricular tachycardia (VT) which had been treated with amiodarone and a defibrillator, was admitted with worsening heart failure and palpitations. He was found to be volume overloaded with acute
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Cost-Effectiveness of Catheter Ablation Versus Antiarrhythmic Drug Therapy in Atrial Fibrillation: The CABANA Randomized Clinical Trial Circulation (IF 39.918) Pub Date : 2022-06-21 Derek S. Chew, Yanhong Li, Patricia A. Cowper, Kevin J. Anstrom, Jonathan P. Piccini, Jeanne E. Poole, Melanie R. Daniels, Kristi H. Monahan, Linda Davidson-Ray, Tristram D. Bahnson, Hussein R. Al-Khalidi, Kerry L. Lee, Douglas L. Packer, Daniel B. Mark, for the CABANA Investigators
BACKGROUND:In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup
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Allograft Rejection Surveillance In Heart Transplantation: Is There a Better Way? Circulation (IF 39.918) Pub Date : 2022-06-21 James C Fang,Omar Wever-Pinzon
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Rivaroxaban 2.5 mg Twice Daily Plus Aspirin Reduces Venous Thromboembolism in Patients With Chronic Atherosclerosis. Circulation (IF 39.918) Pub Date : 2022-06-21 Nana Pogosova,Jacqueline Bosch,Deepak L Bhatt,Keith A A Fox,Stuart J Connolly,Marco Alings,Peter Verhamme,Eva Muehlhofer,Olga Shestakovska,Salim Yusuf,John W Eikelboom
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First Pig-to-Human Heart Transplant Marks a Milestone in Xenotransplantation. Circulation (IF 39.918) Pub Date : 2022-06-21 Bridget M Kuehn
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Can Early Ablation of Ventricular Tachycardia Improve Survival? Circulation (IF 39.918) Pub Date : 2022-06-21 Arvindh N Kanagasundram,Travis D Richardson,William G Stevenson
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Association of Extreme Heat and Cardiovascular Mortality in the United States: A County-Level Longitudinal Analysis From 2008 to 2017 Circulation (IF 39.918) Pub Date : 2022-06-21 Sameed Ahmed M. Khatana, Rachel M. Werner, Peter W. Groeneveld
Background:Extreme-heat events are increasing as a result of climate change. Prior studies, typically limited to urban settings, suggest an association between extreme heat and cardiovascular mortality. However, the extent of the burden of cardiovascular deaths associated with extreme heat across the United States and in different age, sex, or race and ethnicity subgroups is unclear.Methods:County-level
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Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort Circulation (IF 39.918) Pub Date : 2022-06-20 Eric Van Belle, Nicolas Debry, Flavien Vincent, Grégory Kuchcinski, Charlotte Cordonnier, Antoine Rauch, Emmanuel Robin, Fanny Lassalle, François Pontana, Cédric Delhaye, Guillaume Schurtz, Emmanuelle JeanPierre, Natacha Rousse, Caterina Casari, Hugues Spillemaeker, Sina Porouchani, Thibault Pamart, Tom Denimal, Xavier Neiger, Basile Verdier, Laurent Puy, Alessandro Cosenza, Francis Juthier, Marjorie
Background:Cerebral microbleeds (CMBs) have been observed in healthy elderly people undergoing systematic brain magnetic resonance imaging. The potential role of acute triggers on the appearance of CMBs remains unknown. We aimed to describe the incidence of new CMBs after transcatheter aortic valve replacement (TAVR) and to identify clinical and procedural factors associated with new CMBs including
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Frequency of Screening-Detected Intracranial Aneurysms in Patients With Loeys-Dietz Syndrome. Circulation (IF 39.918) Pub Date : 2022-06-17 Anna L Huguenard,Gabrielle W Johnson,Joshua W Osbun,Ralph G Dacey,Alan C Braverman
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Frequency, Penetrance, and Variable Expressivity of Dilated Cardiomyopathy–Associated Putative Pathogenic Gene Variants in UK Biobank Participants Circulation (IF 39.918) Pub Date : 2022-06-16 Ravi A. Shah, Babken Asatryan, Ghaith Sharaf Dabbagh, Nay Aung, Mohammed Y. Khanji, Luis R. Lopes, Stefan van Duijvenboden, Anthony Holmes, Daniele Muser, Andrew P. Landstrom, Aaron Mark Lee, Pankaj Arora, Christopher Semsarian, Virend K. Somers, Anjali T. Owens, Patricia B. Munroe, Steffen E. Petersen, C. Anwar A. Chahal, on behalf of the Genotype-First Approach Investigators
Background:There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features
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Premature Complexes and Blocked P Wave Circulation (IF 39.918) Pub Date : 2022-06-13 Ethan Morgan, John Anderson, Amit Noheria
A 59-year-old woman presented to the emergency department after her primary care provider discovered an abnormal ECG at an office visit (Figure 1). She had been experiencing intermittent atypical chest pain for months. Thorough ischemic work-up was unremarkable, although the patient was found to have mild global left ventricular systolic dysfunction with preserved chamber size and borderline left atrial
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Higher Incidence of Chromosomal Aberrations in Operators Performing a Large Volume of Endovascular Procedures Circulation (IF 39.918) Pub Date : 2022-06-13 Mohamed A. Abdelhalim, Ashish Patel, Jayne Moquet, Prakash Saha, Alberto Smith, Christophe Badie, Rhona Anderson, Elizabeth Ainsbury, Bijan Modarai
Cardiovascular interventions using x-ray guidance are increasing in both volume and complexity. The long-term biological effects of chronic low-dose radiation exposure in operators performing these procedures are, however, largely unknown. Occupational safety limits are based on physical dosimetry only and do not consider individual biological sensitivity to radiation. We previously reported DNA damage
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Correction to: Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity Circulation (IF 39.918) Pub Date : 2022-06-14
In the article by Reynolds et al, “Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity” which published online on September 9, 2021 and appeared in the September 28, 2021, issue of Circulation (Circulation. 2021;144:1024–1038. doi: 10.1161/CIRCULATIONAHA.120.049755), corrections are needed. The analysis population for CAD and outcomes is correct as stated, at 2475
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Expanding the Therapeutic World of Tryptophan Metabolism. Circulation (IF 39.918) Pub Date : 2022-06-13 Gregory A Wyant,Javid Moslehi
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At the Crossroad Between Skeletal and Cardiac Muscle Cells. Circulation (IF 39.918) Pub Date : 2022-06-13 Christopher R deFilippi,Abdulla A Damluji
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Environmental Triggers of Acute Coronary Syndromes. Circulation (IF 39.918) Pub Date : 2022-06-13 Nicholas L Mills,C Arden Pope
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What Does the American Heart Association Do (and How Can You Help)? Circulation (IF 39.918) Pub Date : 2022-06-13 Donald M Lloyd-Jones
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Differences in Comorbidities Explain Black–White Disparities in Outcomes After Femoropopliteal Endovascular Intervention Circulation (IF 39.918) Pub Date : 2022-06-13 Anna K. Krawisz, Sahana Natesan, Rishi K. Wadhera, Siyan Chen, Yang Song, Robert W. Yeh, Michael R. Jaff, Jay Giri, Howard Julien, Eric A. Secemsky
Background:Black adults have a higher incidence of peripheral artery disease and limb amputations than White adults in the United States. Given that peripheral endovascular intervention (PVI) is now the primary revascularization strategy for peripheral artery disease, it is important to understand whether racial differences exist in PVI incidence and outcomes.Methods:Data from fee-for-service Medicare
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Left-Sided Degenerative Valvular Heart Disease in Type 1 and Type 2 Diabetes Circulation (IF 39.918) Pub Date : 2022-06-09 Araz Rawshani, Naveed Sattar, Darren K. McGuire, Oskar Wallström, Ulf Smith, Jan Borén, Göran Bergström, Elmir Omerovic, Annika Rosengren, Björn Eliasson, Deepak L. Bhatt, Aidin Rawshani
Background:The role of diabetes in the development of valvular heart disease, and, in particular, the relation with risk factor control, has not been extensively studied.Methods:We included 715 143 patients with diabetes registered in the Swedish National Diabetes Register and compared them with 2 732 333 matched controls randomly selected from the general population. First, trends were analyzed with