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1. Incremental Value of Transthoracic Doppler Echocardiography‐Assessed Coronary Flow Reserve in Patients With Suspected Myocardial Ischemia Undergoing Myocardial Perfusion Scintigraphy

Author

Li‐Ming Gan, Sara Svedlund, Ann Wittfeldt, Charlotte Eklund, Sinsia Gao, Göran Matejka, Anders Jeppsson, Per Albertsson, Elmir Omerovic, and Amir Lerman

Subjects
adenosine, coronary blood flow reserve, echocardiography, myocardial perfusion imaging, prognosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundAdenosine‐assisted transthoracic Doppler‐derived coronary flow reserve (TDE‐CFR) reflects coronary vascular function. The prognostic and incremental value of left anterior descending coronary artery TDE‐CFR above myocardial perfusion scintigraphy in patients with suspected myocardial ischemia has not yet been studied. Methods and ResultsThree hundred seventy‐one patients (mean age, 62.3±8.7 years; 46.8% males) referred to myocardial perfusion scintigraphy attributed to suspected myocardial ischemia were included in the study. The TDE‐CFR result was blinded to the referring physician. Patients were followed up regarding major cardiovascular events, defined as cardiovascular death, myocardial infarction, or acute revascularization during a median follow‐up time of 4.5 years. A TDE‐CFR value of ≤2.0 was considered reduced. Major cardiovascular events occurred during follow‐up in 60 patients (16.2%). A reduced TDE‐CFR was detected in 76 patients (20.5%). Patients with reduced TDE‐CFR had an event rate of 36.8% compared to 10.8% in patients with normal TDE‐CFR (unadjusted hazard ratio, 4.63; 95% CI, 2.78–7.69; P

Published
2017
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3. Incremental Value of Transthoracic Doppler Echocardiography‐Assessed Coronary Flow Reserve in Patients With Suspected Myocardial Ischemia Undergoing Myocardial Perfusion Scintigraphy

Author

Göran Matejka, Anders Jeppsson, Per Albertsson, Sinsia Gao, Charlotte Eklund, Elmir Omerovic, Li-Ming Gan, Sara Svedlund, Amir Lerman, and Ann Wittfeldt

Subjects
coronary blood flow reserve, Male, Adenosine, Time Factors, Vasodilator Agents, Myocardial Ischemia, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Doppler echocardiography, 0302 clinical medicine, Ischemia, Risk Factors, Myocardial perfusion scintigraphy, Medicine, Coronary Heart Disease, echocardiography, 030212 general & internal medicine, Original Research, medicine.diagnostic_test, Myocardial Perfusion Imaging, Middle Aged, Echocardiography, Doppler, Fractional Flow Reserve, Myocardial, Cardiology, Disease Progression, Female, Radiology, Cardiology and Cardiovascular Medicine, Vascular function, Technetium Tc 99m Sestamibi, medicine.medical_specialty, Myocardial ischemia, Disease-Free Survival, 03 medical and health sciences, Myocardial perfusion imaging, Predictive Value of Tests, Internal medicine, Coronary Circulation, Ultrasound, Humans, In patient, Aged, Tomography, Emission-Computed, Single-Photon, Chi-Square Distribution, business.industry, Microcirculation, Coronary flow reserve, Multivariate Analysis, Feasibility Studies, prognosis, Radiopharmaceuticals, business
Abstract

Background Adenosine‐assisted transthoracic Doppler‐derived coronary flow reserve ( TDE ‐ CFR ) reflects coronary vascular function. The prognostic and incremental value of left anterior descending coronary artery TDE ‐ CFR above myocardial perfusion scintigraphy in patients with suspected myocardial ischemia has not yet been studied. Methods and Results Three hundred seventy‐one patients (mean age, 62.3±8.7 years; 46.8% males) referred to myocardial perfusion scintigraphy attributed to suspected myocardial ischemia were included in the study. The TDE ‐ CFR result was blinded to the referring physician. Patients were followed up regarding major cardiovascular events, defined as cardiovascular death, myocardial infarction, or acute revascularization during a median follow‐up time of 4.5 years. A TDE ‐ CFR value of ≤2.0 was considered reduced. Major cardiovascular events occurred during follow‐up in 60 patients (16.2%). A reduced TDE ‐ CFR was detected in 76 patients (20.5%). Patients with reduced TDE ‐ CFR had an event rate of 36.8% compared to 10.8% in patients with normal TDE ‐ CFR (unadjusted hazard ratio, 4.63; 95% CI, 2.78–7.69; P TDE ‐ CFR remained a significant independent predictor of major cardiovascular events. The major cardiovascular events rate was 7.5% in patients without myocardial perfusion scintigraphy‐detected myocardial ischemia and normal TDE ‐ CFR (n=200), 24.2% in patients without ischemia but with reduced TDE ‐ CFR (n=33), and 46.5% in patients with both myocardial perfusion scintigraphy–detected myocardial ischemia and a reduced TDE ‐ CFR (n=43; P Conclusions Coronary microvascular dysfunction, as determined by TDE ‐ CFR, is a strong independent predictor of cardiovascular events and adds incremental prognostic value compared with myocardial perfusion scintigraphy. The current study supports routine assessment of CFR in patients with suspected ischemic heart disease.

Published
2017

4. Non-invasive evaluation of coronary flow reserve with transthoracic Doppler echocardiography predicts the presence of significant stenosis in coronary arteries

Author

Sara Svedlund, Li-Ming Gan, Göran Matejka, Truls Råmunddal, Ann Wittfeldt, Per Albertsson, Oskar Angerås, Inger Haraldsson, and Elmir Omerovic

Subjects
Male, Working hours, medicine.medical_specialty, viruses, Doppler echocardiography, Coronary artery disease, Predictive Value of Tests, Internal medicine, medicine, Humans, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Non invasive, Coronary Stenosis, Coronary flow reserve, Middle Aged, medicine.disease, Coronary Vessels, Echocardiography, Doppler, Coronary heart disease, Fractional Flow Reserve, Myocardial, Coronary arteries, Stenosis, medicine.anatomical_structure, Echocardiography, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

[1] Dominguez-Rodriguez A, Abreu-Gonzalez P. The link between sleep duration and inflammation: effects on cardiovascular disease. Int J Cardiol 2014;173(3):600–1. [2] Cheng Y, DuCL, Hwang JJ, Chen IS, ChenMF, Su TC.Working hours, sleep duration and the risk of acute coronary heart disease: a case–control study ofmiddle-agedmen in Taiwan. Int J Cardiol 2014;171:419–22. [3] Kawada T. Working hours, sleep duration and risk of coronary heart disease. Int J Cardiol 2014;174(1):162.

Published
2014
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5. Annual report SWEDEHEART 2012

Author

Anna-Maria Wahlberg, Magdalena Alenström, Stina Udin, Tore Johansson, Anna Lundgren, Birgitta Romany Johansson, Carin Ekström, Nils Eriksson, Lisbeth Andersson, Hanna Eklund, Lotta Robertsson, Gunilla Bjerhag, Ann-Charlotte Gustavsson, Madelene Israelsson, Sofia Karlsson, Maria Westerlund, Yvonne Ek, Birgitta Stenbäck, Barbro Andersson, Elisabeth Andersson, Kristina Leppämäki, Anette Ramirez, Victoria Wallin, Alexandra Lundberg, Benny Sahlin, Hasse Mälberg, Maria Liljeroos, Caroline Gustafsson, Kerstin Nyström, Susanne Siklo, Eva Zelleroth, Finn Hjortevang, Kamaran Mohammed, Agneta Hellblad, Iwona Schön, Kristina Carlsson, Marita Ole´rs, Pär Lennart Ågren, Iwar Sjögren, Crister Zedigh, Kristina Eriksson, Kristina Sundkvist, Anna-Karin Thorsell, Ann-Kristin Kuoljok, Linda Liinanki, Mona Liljergren, Sara Turtola, Britt-Marie Nylander, Lena Nordvall, Malin Nilsson, Annelie Blomqvist, Håkan Sjöberg, Jenny Nylander, Linda Berglund, Linda Mossberg, Lars Svennberg, Espen Haugen, Lars Hellsten, Staffan Johansson, Birgitta Johansson, Pethra Larsson, Susanne Kellerth, Monika Bergström, Carola Gustafsson, Cecilia Nährström, Eva Evenås, Hanna Sundin, Helena Lönn, Johan Svensson, Moa Kihlgren, Per Larsson, Pirjo Palosaari, Susann Johansson, Malin Cedermark magnusson, Annica Ravn-Fischer, Ann Wittfeldt, Elisabeth Perers, Nina Hellberg, Mikael Holmberg, Bert Andersson, Berit Jangsten, Nedim Selimovic, Anna Enström, Göran Dellgren, Henrik Scherstén, Anna Biveby-Nilsson, Johan Lundberg, Elmir Omerovic, Petur Petursson, Per Albertsson, Carina Ankarstrand, Agneta Flinck, Titti Larsson, Maria Samuelsson, Peter Bergman, Lotten Nyström, Magnus Bågenholm, Anneli Linnér, Björn Hornestam, Helén Sjöland, Anne-Marie Kirkhoff, Hugo Månsson, Ida Karlsson, Maria Olausson, Charlotte Berne, Christina Backe, Ali Tabandeh, Ann-Charlotte Karlsson, Peter Hårdhammar, Sven-Erik Olsson, Henrik Persson, Ole Wagner, Henrik Wagner, Lennart Sandhall, Carina Wåhlander, Kristina Rova, Lina Fischer, Maria Nilsson, Mari Stjernberg, Sylvia Gustavsson, Camilla Hedberg, Jan Thollander, Katarina Collberg, Jörg Lauermann, Werner Puskar, Margareta Larsson, Ann Johansson, Lina Brindstedt, Marina Olofsson, Jörg Carlsson, Katarina Månsson, Ulla Jeppsson, Ingbritt Söderlind, Malinn Hultman, Sara Ronnelin, Carina Fredriksson, Gerd Skogman, Ingela Ågren, Inger Almroth, Sara Trege Nilsson, Gerd Pettersson, Ing-Marie Åkesson, Sofia Carlfelter, Jan Medin, Karim Mokhtar, Carl-Magnus Pripp, Linda Malmsten, Annelie Karlsson, Anna Lenberg, Annika Lettenström, Anna Jost-Widén, Gunilla Johnson, Håkan Ahlmark, Hannah Brevik, IngaLill Nordberg, Jessica Österberg-Persson, Jeanette Smedberg, Maria Eklund, Urban Haaga, Anne-Marie Henriksson, Mats Allared, Hans Olsson, Tage Nilsson, Lisa Juhlin, Karin Eriksson, Leif Hedquist, Ulla Lundin, Christin Jonsson, Monica Pedersen, Julia Marainen, Moa Bylund, Monica Alsterdal, Anna Sjöberg, Ewa Wigenstorp, Gunilla Peterzen, Kerstin Skeppstedt, Anette Berlin, Helena Wikström, Kerstin Pihl, Lehna Ferm, Petra Larsson, Vanja Johansson, Gunvor Finnas, Helen Ahlm, Anders Ekelind, Eva Larsson, Gull-Britt Eriksson, Veronica Sass, Åsa Johansson, Lennart Malmqvist, Lars Westin, Eydis Sigurjonsdottir, Frida Skuladottir, Maria Ottesen, Olga Birgitta Bjarnadottir, Gunnar Myrdal, Edda Traustadottir, Friðrika Sigvaldadóttir, Gerður Garðarsdóttir, Gudrun Valgeirsdottir, Sigurlaug Magnusdottir, Thora Bjornsdottir, Thorarinn Gudnason, Svava Matthiasdottir, Maria Jonsson, Ulrika Pettersson, Magnus Peterson, Karin Molander, Micael Larsson, Berit Samuelsson, Catarina Svensson, Elisabeth Augustsson, Evelin BertilssonFröjd, Joakim Alfredsson, Wolfgang Freter, Linda Lilja, Gunnel Andersson, Dimitrios Venetsanos, Anders Björkholm, Tim Tödt, Ulf Berglund, Niels Erik Nielsen, Jenny Johansson, Johanna Svensson, Rosie-Marie Larsson, Liselotte Lundmark, Gunilla Brolin, Annika Westergren, Anna Duckert, Vesna Steffan, Matthias Götberg, David Erlinge, Fredrik Scherstén, Göran Olivecrona, Jan Harnek, Per Bondesson, Pernilla Knutsson, Evy Stenlund, Peter Thorén, Siv Algotsson, Enisa Durakovic, Lisa Gustafsson, Marie Nilsson, Margareta Nilson, Pallonji Bhiladvala, Monica Håkansson, Carina Svensson, Ingela Olsson, Amelie Kjellstenius, Jenny Åslund, Linnéa Alledal, Nina Varblane, Victoria Nilsson, Maria Thudén, Siv-Britt Jensen, Elisabet Svensson, Maria Pettersson, Sanna Lindgren, Anita Pehrsson, Maria Olsson, Anneli Rudenäs, Eva Öhman, Stig-Åke Falk, Annelie Jaensson, Lena Thell, Annette Billqvist, Barbro Efraimsson-Nilsson, Ingalill Allansson, Malin Jansson, Ann Ingström, Christina Lundqvist, Ingela Nyström, Ingrid Bergman, Johan Ekman, Lena Carlson, Solveig Person, Ingrid Lindberg, Leif Thuesen, Erik Lindberg, Gunnilla Lundberg, Kerstin Hedberg, Inga-Lill Kotka, Anja Fogelberg, Anna Johansson, Lis Ståhl, Anders Kallryd, Agneta Ramén, Henrik Löfmark, Senait Fessahaie, Malin Brandrup-Wognsen, Claire Salomonsson, Petra Ardin, Eva Balcker, Filippa Högberg, Fredrik Högberg, Eva Hultin Ånnegård, Marcus Svensson, Marie Tornestedt, Inge Björkander, Cathrine Edström, Lars Eurenius, Ann Samnegård, Jonas Persson, Nikolaos Östlund Papadogeorgos, Habib Mir-Akbari, Görel Stengård, Elin Bacsovics Brolin, Katarina Brehmer, Fauzia Osman, Marie Törnblom, Katja Sundkvist, Caroline Kumhala, Ellinor Jonsson, Alexandra Yazar, Anwar Siddiqui, Andreas Rück, Loghman Henareh, Kerstin Cederlund, Ewa Lemberg, Elin Larsson, Amanda Persson, Karolin Andersson, Per Svensson, Fauzia A - Moalim, Ann Lundgren, Ellen Gustavsson-segerhag, Agneta Nordvall, Gunnel Söderlund, Christina Jarnert, Linda Mellbin, Torbjörn Ivert, Rikard Linder, Mattias Törnerud, Birgit Edén, Kristina Lockne, Sebastian Rennerskog, Jan Kosmack, Marianne Erlandsson, Pontus Lindroos, Armi Peltonen, Christine Creutziger, Ellinor Berglund, Marie Henriksson, Carina Ingeborn, Olov Collste, Mikael Aasa, Karin Karlsson, Ulla Andersson, Lis Kohlström Englund, Mia Henning, Anna-Greta Vinblad v Walter, Christina Nilsson, Helena Schilken, Inger Johansson, Ingrid Wallgren, Kristina Niemi, Oili Niva, Margareta Dofs, Agneta Johansson, Jan Haupt, Christina Näslund, Henrik Drewsen, Maria Söderlund, Birgitta Berts, Bo Lindvall, Daniel Wadell, Jens Jensen, Åsa Hedh, Karin Johnson, Cecilia Nikitin, Eva-Lena Eriksson, Elisabeth Westlund, Inger Karlsson, Peter Björkdahl, Radim Uher, Ulf Nyman, Troels Yndigegn, Anette Broberg, Linda Lamreus, Alexandra Söderström, Marianne Lång, Henrik Olsson, Madhat Hussien Al-Saadi, Emma Landén, Maria Holmgren, Tomas Rivera San Martin, Karin Nyström, Magnus Wahlin, Oskar Angerås, Johan Nilsson, Peter Eriksson, Anna Sundberg, Inger Sandström, Olov Duvernoy, Maria Andreasson, Johanna Ekström, Marie Essermark, Helena Wall, Elisabeth Marklund, Cecilia Östlund, Maria Willehadson, Christina Björklund, Axel Dimberg, Vitas Zemgulis, Agneta Olsson, Susanne Hagström, Carina Bergman, Annika Gunnarsson, My Huhta, Christina Svensson, Per Hultman, Christoph Varenhorst, Per Kvidal, Annika Stener Bengtsson, Ann-Lis Wännman, Lisbeth Nilsson, Tomas Andersson, Maritha Josefsson, Maria Morén, Lena Hultman-Berg, Anna-Karin Almqwist, Monica Cederblad, Katarina Ekberg, Gunilla Kvarnvik, Eston Jönsson, Annelie Hammerman, Pia Claesson, Gith Widerström, Sandra Pettersson Olsson, Åsa Hofvander, Martin Lindholm, Saman Saidi, Per Grimfjärd, Amra Kåregren, Madeleine Runesson, Anders Josefsson, Lena Henriksson-Fri, Miriam Johansson, Solgärd Gustavsson, Minna Markljung, Olle Bergström, Thomas Aronsson, Ewa Karlsson, Pernilla Boström, Sofia Hansson, Inger Andreasson, Lena Palmqvist, Anders Kähäri, Mats Lidén, Frida Oskarsson, Ingela Östman, Johanna Kronberg, Marie Johansson, Marie Thuresson, Håkan Geijer, Ole Fröbert, Thomas Kellerth, Maud Tillkvist, Kirsti Ajax, Fredrik Björklund, and Anna Björklund

Subjects
business.industry, media_common.quotation_subject, Incidence (epidemiology), Medicine, Infarction, Annual report, Cardiology and Cardiovascular Medicine, business, medicine.disease, Welfare, Deca, Demography, media_common
Abstract

According to Swedish National Board of Health and Welfare statistics, a dramatic decrease in both the incidence of and mortality from acute myo-cardial infarction has been seen in the past two deca...

Published
2014
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6. Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

Author

Xiaorui Han, Jingzhi Sun, Xiaoxia Wang, Zicai Liang, Chu-Jun Liu, Li-Ming Gan, Huiqing Cao, Xiao Zhou, and Ann Wittfeldt

Subjects
0301 basic medicine, Candidate gene, Biology, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Human Umbilical Vein Endothelial Cells, Humans, Gene silencing, Promoter Regions, Genetic, Molecular Biology, YY1 Transcription Factor, Genetics, Interleukin-6, Tumor Necrosis Factor-alpha, YY1, Interleukin-8, NF-kappa B, Endothelial Cells, RNA, NF-κB, Cell Biology, Non-coding RNA, Long non-coding RNA, 030104 developmental biology, chemistry, Cancer research, RNA, Long Noncoding, Chromatin immunoprecipitation, Signal Transduction, Research Paper
Abstract

Antisense Noncoding RNA in the INK4 Locus (ANRIL) is the prime candidate gene at Chr9p21, the well-defined genetic risk locus associated with multiple human diseases including coronary artery disease (CAD), while little is known regarding its role in the pathological processes. Endothelial dysfunction triggers atherosclerotic processes that are causatively linked to CAD. To evaluate the function of ANRIL in human endothelial cells (ECs), we examined ANRIL expression under pathological stimuli and found ANRIL was markedly induced by pro-inflammatory factors. Loss-of-function and chromatin immunoprecipitation approaches revealed that NF-κB mediates TNF-α induced ANRIL expression. RNA sequencing revealed that ANRIL silencing dysregulated expression of inflammatory genes including IL6 and IL8 under TNF-α treatment. We explored the regulatory mechanism of ANRIL on IL6/8 and found that Yin Yang 1 (YY1), an ANRIL binding transcriptional factor revealed by RNA immunoprecipitation, was required for IL6/8 expression under TNF-α treatment. YY1 was enriched at promoter loci of IL6/8 and ANRIL silencing impaired the enrichment, indicating a cooperation between ANRIL and YY1 in the regulation of inflammatory genes. For the first time, we establish the connection between ANRIL and NF-κB pathway and show that ANRIL regulates inflammatory responses through binding with YY1. The newly identified TNF-α-NF-κB-ANRIL/YY1-IL6/8 pathway enhances understanding of the etiology of CAD and provides potential therapeutic target for treatment of CAD.

Published
2016
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8. Reply: To PMID 23312702

Author

Li-Ming, Gan, Ann, Wittfeldt, Gunnar, Brandrup-Wognsen, J J J, van Giezen, Jenny, Jonasson, Sven, Nylander, and Håkan, Emanuelsson

Subjects
Male, Vasodilation, Adenosine, Humans, Coronary Vessels, Blood Flow Velocity
Published
2013

9. Reply

Author

van Giezen Jj, Håkan Emanuelsson, Li-Ming Gan, Sven Nylander, Jenny Jonasson, Gunnar Brandrup-Wognsen, and Ann Wittfeldt

Subjects
World Wide Web, Text mining, business.industry, Medicine, Cardiology and Cardiovascular Medicine, business
Published
2013
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10. Ticagrelor Enhances Adenosine-Induced Coronary Vasodilatory Responses in Humans

Author

Sven Nylander, Ann Wittfeldt, Håkan Emanuelsson, Gunnar Brandrup-Wognsen, Jenny Jonasson, Li-Ming Gan, and J.J.J. van Giezen

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Doppler echocardiography, Placebo, ticagrelor, Young Adult, Double-Blind Method, Internal medicine, medicine, Humans, Cross-Over Studies, coronary blood flow, medicine.diagnostic_test, business.industry, Area under the curve, Drug Synergism, Blood flow, dyspnea, Clopidogrel, Adenosine, Crossover study, Coronary Vessels, Up-Regulation, Vasodilation, adenosine, Anesthesia, Cardiology, Purinergic P2Y Receptor Antagonists, business, Cardiology and Cardiovascular Medicine, Ticagrelor, Blood Flow Velocity, medicine.drug
Abstract

ObjectivesThis study was undertaken to determine if ticagrelor augments adenosine-induced coronary blood flow and the sensation of dyspnea in human subjects.BackgroundTicagrelor is a P2Y12 receptor antagonist that showed superior clinical benefit versus clopidogrel in a phase III trial (PLATO [Platelet Inhibition and Patient Outcomes]). Ticagrelor has been shown to inhibit cell uptake of adenosine and enhance adenosine-mediated hyperemia responses in a dog model.MethodsIn this double-blind, placebo-controlled study, 40 healthy male subjects were randomized to receive a single dose of ticagrelor (180 mg) or placebo in a crossover fashion. Coronary blood flow velocity (CBFV) was measured by using transthoracic Doppler echocardiography at rest after multiple stepwise adenosine infusions given before and after study drug, and again after the infusion of theophylline.ResultsTicagrelor significantly increased the area under the curve of CBFV versus the adenosine dose compared with placebo (p = 0.008). There was a significant correlation between ticagrelor plasma concentrations and increases in the area under the curve (p < 0.001). In both treatment groups, the adenosine-induced increase in CBFV was significantly attenuated by theophylline, with no significant differences between subjects receiving ticagrelor or placebo (p = 0.39). Furthermore, ticagrelor significantly enhanced the sensation of dyspnea during adenosine infusion, and the effects were diminished by theophylline.ConclusionsTicagrelor enhanced adenosine-induced CBFV and the sensation of dyspnea in these healthy male subjects via an adenosine-mediated mechanism. (Study to Assess the Effect of Ticagrelor on Coronary Blood Flow in Healthy Male Subjects; NCT01226602)

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11. ADENOSINE MAY MEDIATE TICAGRELOR-INDUCED DYSPNEA

Author

Ann Wittfeldt, Jenny Jonasson, Sven Nylander, Li-Ming Gan, and Håkan Emanuelsson

Subjects
Acute coronary syndrome, business.industry, Antagonist, Pharmacology, medicine.disease, Adenosine, Reuptake, respiratory tract diseases, P2Y12, Medicine, In patient, business, Cardiology and Cardiovascular Medicine, Ticagrelor, medicine.drug
Abstract

Ticagrelor (T) is a reversibly binding, direct-acting, oral P2Y12 antagonist used for prevention of atherothrombotic events in patients with acute coronary syndrome. One of its known potential side-effects is dyspnea. In addition to its antiplatelet effects, T also blocks cellular adenosine reuptake

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