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145 results on '"Kraaijeveld, Adriaan"'

101. Rationale and design of amphilimus sirolimus-eluting stents versus zotarolimus-eluting stents in all-comers requiring percutaneous coronary intervention (ReCre8): A multicenter randomized clinical trial

Author

Rozemeijer, Rik, primary, Stein, Mèra, additional, Frambach, Peter, additional, Voskuil, Michiel, additional, Kraaijeveld, Adriaan O., additional, Rodríguez-Olivares, Ramón, additional, Timmers, Leo, additional, Pereira, Bruno, additional, Rittersma, Saskia Z., additional, Agostoni, Pierfrancesco, additional, Doevendans, Pieter A., additional, and Stella, Pieter R., additional

Published
2017
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104. TCT-267 Clinical outcomes of diabetic patients treated with an amphilimus-eluting stent and a short duration of dual antiplatelet therapy in routine clinical practice: first results of the Utrecht Cre8 (U-Cre8) Registry

Author

Rozemeijer, Rik, primary, Stein, Mera, additional, Voskuil, Michiel, additional, Kraaijeveld, Adriaan, additional, Timmers, Leo, additional, Rodríguez-Olivares, Ramon, additional, Rittersma, Saskia, additional, and Stella, Pieter, additional

Published
2016
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105. TCT-606 Can we justify conservative treatment in adults with Anomalous Coronary Artery Originating from the Opposite Sinus of Valsalva (ACAOS) with inter-arterial course (IAC)?

Author

Driesen, Bart, primary, Voskuil, Michiel, additional, Sieswerda, Gertjan, additional, Schoof, Paul, additional, Meijboom, Folkert, additional, Haas, Felix, additional, Krings, Gregor, additional, Stella, Pieter, additional, Kraaijeveld, Adriaan, additional, and Doevendans, Pieter, additional

Published
2016
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106. TCT-26 Comparison of everolimus-eluting and paclitaxel-eluting coronary stents in patients undergoing primary percutaneous coronary intervention: 5 year follow-up from the COMPARE I trial

Author

Vlachojannis, Georgios J., primary, Royaards, Kees-Jan, additional, Koper, Marielle A., additional, Kraaijeveld, Adriaan O., additional, Boxma-de Klerk, Bianca M, additional, Wassing, Jochem, additional, van der Ent, Martin, additional, and Smits, Pieter C., additional

Published
2014
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109. Quaking, an RNA-Binding Protein, Is a Critical Regulator of Vascular Smooth Muscle Cell Phenotype

Author

van der Veer, Eric P., primary, de Bruin, Ruben G., additional, Kraaijeveld, Adriaan O., additional, de Vries, Margreet R., additional, Bot, Ilze, additional, Pera, Tonio, additional, Segers, Filip M., additional, Trompet, Stella, additional, van Gils, Janine M., additional, Roeten, Marko K., additional, Beckers, Cora M., additional, van Santbrink, Peter J., additional, Janssen, Anique, additional, van Solingen, Coen, additional, Swildens, Jim, additional, de Boer, Hetty C., additional, Peters, Erna A., additional, Bijkerk, Roel, additional, Rousch, Mat, additional, Doop, Merijn, additional, Kuiper, Johan, additional, Schalij, Martin Jan, additional, van der Wal, Allard C., additional, Richard, Stéphane, additional, van Berkel, Theo J.C., additional, Pickering, J. Geoffrey, additional, Hiemstra, Pieter S., additional, Goumans, Marie Jose, additional, Rabelink, Ton J., additional, de Vries, Antoine A.F., additional, Quax, Paul H.A., additional, Jukema, J. Wouter, additional, Biessen, Erik A.L., additional, and van Zonneveld, Anton Jan, additional

Published
2013
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110. Abstract 532: The RNA-binding Protein Quaking Critically Regulates Vascular Smooth Muscle Cell Phenotype

Author

van der Veer, Eric P, primary, de Bruin, Ruben G, additional, Kraaijeveld, Adriaan O, additional, de Vries, Margreet R, additional, Pera, Tonio, additional, Segers, Filip M, additional, Trompet, Stella, additional, van Gils, Janine M, additional, Roeten, Marko K, additional, Beckers, Cora M, additional, van Santbrink, Peter J, additional, Janssen, Anique, additional, van Solingen, Coen, additional, Swildens, Jim, additional, de Boer, Hetty C, additional, Bot, Ilze, additional, Peters, Erna A, additional, Rousch, Mat, additional, Doop, Merijn, additional, Schalij, Martin Jan, additional, van der Wal, Allard C, additional, Richard, Stehpane, additional, van Berkel, Theo J, additional, Pickering, J. G, additional, Hiemstra, Pieter S, additional, Goumans, Marie Jose, additional, Rabelink, Ton J, additional, de Vries, Antoine A, additional, Quax, Paul H, additional, Jukema, J. W, additional, Biessen, Erik A, additional, and van Zonneveld, Anton Jan, additional

Published
2013
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112. Chemokines CCL3/MIP1α, CCL5/RANTES and CCL18/PARC are Independent Risk Predictors of Short-Term Mortality in Patients with Acute Coronary Syndromes

Author

de Jager, Saskia C. A., primary, Bongaerts, Brenda W. C., additional, Weber, Michael, additional, Kraaijeveld, Adriaan O., additional, Rousch, Mat, additional, Dimmeler, Stefanie, additional, van Dieijen-Visser, Marja P., additional, Cleutjens, Kitty B. J. M., additional, Nelemans, Patty J., additional, van Berkel, Theo J. C., additional, and Biessen, Erik A. L., additional

Published
2012
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114. CCL3 (MIP-1α) levels are elevated during acute coronary syndromes and show strong prognostic power for future ischemic events

Author

de Jager, Saskia C.A., primary, Kraaijeveld, Adriaan O., additional, Grauss, Robert W., additional, de Jager, Wilco, additional, Liem, Su-San, additional, van der Hoeven, Bas L., additional, Prakken, Berent J., additional, Putter, Hein, additional, van Berkel, Theo J.C., additional, Atsma, Douwe E., additional, Schalij, Martin J., additional, Jukema, J. Wouter, additional, and Biessen, Erik A.L., additional

Published
2008
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115. Outcome and Predictors for Mortality in Patients with Cardiogenic Shock: A Dutch Nationwide Registry-Based Study of 75,407 Patients with Acute Coronary Syndrome Treated by PCI.

Author

Karami, Mina, Peters, Elma J., Lagrand, Wim K., Houterman, Saskia, den Uil, Corstiaan A., Engström, Annemarie E., Otterspoor, Luuk C., Ottevanger, Jan Paul, Ferreira, Irlando A., Montero-Cabezas, Jose M., Sjauw, Krischan, van Ramshorst, Jan, Kraaijeveld, Adriaan O., Verouden, Niels J. W., Lipsic, Erik, Vlaar, Alexander P., Henriques, Jose P. S., Bonello, Laurent, and Reiner, Zeljko

Subjects
ACUTE coronary syndrome, CARDIOGENIC shock, FORECASTING, PERCUTANEOUS coronary intervention, TREATMENT effectiveness
Abstract

It is important to gain more insight into the cardiogenic shock (CS) population, as currently, little is known on how to improve outcomes. Therefore, we assessed clinical outcome in acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with and without CS at admission. Furthermore, the incidence of CS and predictors for mortality in CS patients were evaluated. The Netherlands Heart Registration (NHR) is a nationwide registry on all cardiac interventions. We used NHR data of ACS patients treated with PCI between 2015 and 2019. Among 75,407 ACS patients treated with PCI, 3028 patients (4.1%) were identified with CS, respectively 4.3%, 3.9%, 3.5%, and 4.3% per year. Factors associated with mortality in CS were age (HR 1.02, 95%CI 1.02–1.03), eGFR (HR 0.98, 95%CI 0.98–0.99), diabetes mellitus (DM) (HR 1.25, 95%CI 1.08–1.45), multivessel disease (HR 1.22, 95%CI 1.06–1.39), prior myocardial infarction (MI) (HR 1.24, 95%CI 1.06–1.45), and out-of-hospital cardiac arrest (OHCA) (HR 1.71, 95%CI 1.50–1.94). In conclusion, in this Dutch nationwide registry-based study of ACS patients treated by PCI, the incidence of CS was 4.1% over the 4-year study period. Predictors for mortality in CS were higher age, renal insufficiency, presence of DM, multivessel disease, prior MI, and OHCA. [ABSTRACT FROM AUTHOR]

Published
2021
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116. Renin-Angiotensin System inhibitors and mortality among diabetic patients with STEMI undergoing mechanical reperfusion during the COVID Pandemic

Author

Luca, Giuseppe De, Nardin, Matteo, Algowhary, Magdy, Uguz, Berat, Oliveira, Dinaldo C, Ganyukov, Vladimir, Zimbakov, Zan, Cercek, Miha, Okkels, Lisette, LOH, Poay Huan, Calmac, Lucian, i Ferrer, Gerard Roura, Quadros, Alexandre, Milewski, Marek, D'Uccio, Fortunato Scotto, von Birgelen, Clemens, Versaci, Francesco, Berg, Jurrien Ten, Casella, Gianni, Lung, Aaron Wong Sung, Kala, Petr, Gil, José Luis Díez, Carrillo, Xavier, Dirksen, Maurits, Becerra-Munoz, Victor M., Kang-yin Lee, Michael, Juzar, Dafsah Arifa, Joaquim, Rodrigo de Moura, Paladino, Roberto, Milicic, Davor, Davlouros, Periklis, Bakraceski, Nikola, Zilio, Filippo, Donazzan, Luca, Kraaijeveld, Adriaan, Galasso, Gennaro, Arpad, Lux, Lucia, Marinucci, Vincenzo, Guiducci, Menichelli, Maurizio, Scoccia, Alessandra, Yamac, Aylin Hatice, Mert, Kadir Ugur, Rios, Xacobe Flores, Kovarnik, Tomas, Kidawa, Michal, Moreu, Josè, Flavien, Vincent, Fabris, Enrico, Martínez-Luengas, Iñigo Lozano, Boccalatte, Marco, Ojeda, Francisco Bosa, Arellano-Serrano, Carlos, Caiazzo, Gianluca, Cirrincione, Giuseppe, Kao, Hsien-Li, Forés, Juan Sanchis, Vignali, Luigi, Pereira, Helder, Manzo, Stephane, Ordoñez, Santiago, Özkan, Alev Arat, Scheller, Bruno, Lehtola, Heidi, Teles, Rui, Mantis, Christos, Antti, Ylitalo, Silveira, João António Brum, Zoni, Rodrigo, Bessonov, Ivan, Savonitto, Stefano, Kochiadakis, George, Alexopulos, Dimitrios, Uribe, Carlos E, Kanakakis, John, Faurie, Benjamin, Gabrielli, Gabriele, Barrios, Alejandro Gutierrez, Bachini, Juan Pablo, Rocha, Alex, Tam, Rodriguez, Alfredo, Lukito, Antonia Anna, Saint-Joy, Veauthyelau, Tuccillo, Gustavo Pessah Andrea, Cortese, Giuliana, Parodi, Guido, Burgadha, Mohammed Abed, Kedhi, Elvin, Lamelas, Pablo, Suryapranata, Harry, and Verdoia, Monica

Abstract

During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment.

Published
2021
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118. Sex-specific differences in cytokine signaling pathways in circulating monocytes of cardiovascular disease patients.

Author

Lu, Chang, Donners, Marjo M.P.C., Karel, Joël, de Boer, Hetty, van Zonneveld, Anton Jan, den Ruijter, Hester, Jukema, J. Wouter, Kraaijeveld, Adriaan, Kuiper, Johan, Pasterkamp, Gerard, Cavill, Rachel, Perales-Patón, Javier, Ferrannini, Ele, Goossens, Pieter, and Biessen, Erik A.L.

Subjects
*MONOCYTES, *CELLULAR signal transduction, *CARDIOVASCULAR diseases, *CORONARY artery disease, *CYTOKINES
Abstract

This study aims to identify sex-specific transcriptional differences and signaling pathways in circulating monocytes contributing to cardiovascular disease. We generated sex-biased gene expression signatures by comparing male versus female monocytes of coronary artery disease (CAD) patients (n = 450) from the Center for Translational Molecular Medicine–Circulating Cells Cohort. Gene set enrichment analysis demonstrated that monocytes from female CAD patients carry stronger chemotaxis and migratory signature than those from males. We then inferred cytokine signaling activities based on CytoSig database of 51 cytokine and growth factor regulation profiles. Monocytes from females feature a higher activation level of EGF, IFN1, VEGF, GM-CSF, and CD40L pathways, whereas IL-4, INS, and HMGB1 signaling was seen to be more activated in males. These sex differences were not observed in healthy subjects, as shown for an independent monocyte cohort of healthy subjects (GSE56034, n = 485). More pronounced GM-CSF signaling in monocytes of female CAD patients was confirmed by the significant enrichment of GM–CSF–activated monocyte signature in females. As we show these effects were not due to increased plasma levels of the corresponding ligands, sex-intrinsic differences in monocyte signaling regulation are suggested. Consistently, regulatory network analysis revealed jun-B as a shared transcription factor activated in all female-specific pathways except IFN1 but suppressed in male-activated IL-4. We observed overt CAD-specific sex differences in monocyte transcriptional profiles and cytokine- or growth factor-induced responses, which provide insights into underlying mechanisms of sex differences in CVD. [Display omitted] • Sex differences in transcriptomes and signaling exist in CAD patients' monocytes. • Female CAD patients' monocytes harbor a stronger migration signature than males. • IL-4, INS, and HMGB1 signaling is augmented in male patient monocytes. • EGF, IFN1, VEGF, GM-CSF, and CD40L signaling is up in female patients' monocytes. [ABSTRACT FROM AUTHOR]

Published
2023
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119. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Author

Stavroula Kanoni, Sarah E. Graham, Yuxuan Wang, Ida Surakka, Shweta Ramdas, Xiang Zhu, Shoa L. Clarke, Konain Fatima Bhatti, Sailaja Vedantam, Thomas W. Winkler, Adam E. Locke, Eirini Marouli, Greg J. M. Zajac, Kuan-Han H. Wu, Ioanna Ntalla, Qin Hui, Derek Klarin, Austin T. Hilliard, Zeyuan Wang, Chao Xue, Gudmar Thorleifsson, Anna Helgadottir, Daniel F. Gudbjartsson, Hilma Holm, Isleifur Olafsson, Mi Yeong Hwang, Sohee Han, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M. Brumpton, Humaira Rasheed, Aki S. Havulinna, Yogasudha Veturi, Jennifer Allen Pacheco, Elisabeth A. Rosenthal, Todd Lingren, QiPing Feng, Iftikhar J. Kullo, Akira Narita, Jun Takayama, Hilary C. Martin, Karen A. Hunt, Bhavi Trivedi, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E. Miller, Archie Campbell, Kuang Lin, Iona Y. Millwood, Asif Rasheed, George Hindy, Jessica D. Faul, Wei Zhao, David R. Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Ananyo Choudhury, Dhriti Sengupta, Anubha Mahajan, Michael R. Brown, Weihua Zhang, Ketian Yu, Ellen M. Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian’an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Andrew R. Wood, Yingji Ji, Zishan Gao, Simon Haworth, Noha A. Yousri, Ruth E. Mitchell, Jin Fang Chai, Mette Aadahl, Anne A. Bjerregaard, Jie Yao, Ani Manichaikul, Chii-Min Hwu, Yi-Jen Hung, Helen R. Warren, Julia Ramirez, Jette Bork-Jensen, Line L. Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Pala Mauro, Floris Matteo, Aaron F. McDaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T. Møllehave, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Claudia Lamina, Lukas Forer, Markus Scholz, Tessel E. Galesloot, Jonathan P. Bradfield, Sanni E. Ruotsalainen, EWarwick Daw, Joseph M. Zmuda, Jonathan S. Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A. Brody, Miguel Vazquez-Moreno, Mary F. Feitosa, Mary K. Wojczynski, Zhe Wang, Michael H. Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W. Benjamins, Jorgen Engmann, Noah L. Tsao, Anurag Verma, Roderick C. Slieker, Ken Sin Lo, Nuno R. Zilhao, Phuong Le, Marcus E. Kleber, Graciela E. Delgado, Shaofeng Huo, Daisuke D. Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Ayşe Demirkan, Hampton L. Leonard, Jonathan Marten, Mirjam Frank, Börge Schmidt, Laura J. Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Suraj S. Nongmaithem, Swati Bayyana, Heather M. Stringham, Marguerite R. Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R. H. J. Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A. Lange, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N. Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C. Warner, Ya Xing Wang, Wen B. Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A. Kentistou, Bernhard Banas, Giuseppe Giovanni Nardone, Karina Meidtner, Lawrence F. Bielak, Jennifer A. Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Maria Pina Concas, Simona Vaccargiu, Peter J. van der Most, Niina Pitkänen, Brian E. Cade, Sander W. van der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Amy R. Bentley, Ayo P. Doumatey, Adebowale A. Adeyemo, Jong Young Lee, Eva R. B. Petersen, Aneta A. Nielsen, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W. Rayner, Carol A. Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hidalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O. Obura, Jessica van Setten, Xiaoyin Li, Jingjing Liang, Hua Tang, Natalie Terzikhan, Jae Hun Shin, Rebecca D. Jackson, Alexander P. Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Takahisa Kawaguchi, Joachim Thiery, Joshua C. Bis, Lenore J. Launer, Huaixing Li, Mike A. Nalls, Olli T. Raitakari, Sahoko Ichihara, Sarah H. Wild, Christopher P. Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S. Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Dominique de Kleijn, Gert J. de Borst, Eung Kweon Kim, Hieab H. H. Adams, M. Arfan Ikram, Xiaofeng Zhu, Folkert W. Asselbergs, Adriaan O. Kraaijeveld, Joline W. J. Beulens, Xiao-Ou Shu, Loukianos S. Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W. Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E. Pennell, Trevor A. Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M. Heid, Klaus J. Stark, Martina E. Zimmermann, Henry Völzke, Georg Homuth, Michele K. Evans, Alan B. Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E. Hoefer, Susan Redline, Katja Pahkala, Albertine J. Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Sharon L. R. Kardia, Patricia A. Peyser, Norihiro Kato, Matthias B. Schulze, Giorgia Girotto, Carsten A. Böger, Bettina Jung, Peter K. Joshi, David A. Bennett, Philip L. De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J. Caulfield, Patricia B. Munroe, Xiuqing Guo, Marina Ciullo, Jost B. Jonas, Nilesh J. Samani, Jaakko Kaprio, Päivi Pajukanta, Teresa Tusié-Luna, Carlos A. Aguilar-Salinas, Linda S. Adair, Sonny Augustin Bechayda, H. Janaka de Silva, Ananda R. Wickremasinghe, Ronald M. Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke Iden Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G. Wilson, Lars Lind, Chew-Kiat Heng, Amanda E. Nelson, Yvonne M. Golightly, James F. Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J. Scott, D. C. Rao, Donna K. Arnett, Steven C. Hunt, Mark Walker, Heikki A. Koistinen, Giriraj R. Chandak, Josep M. Mercader, Maria C. Costanzo, Dongkeun Jang, Noël P. Burtt, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, EShyong Tai, Rob M. van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F. Reilly, Amy Jayne McKnight, Frank Kee, Karl-Heinz Jöckel, Mark I. McCarthy, Colin N. A. Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M. van Duijn, Zi-Bing Jin, Jia Qu, Haretsugu Hishigaki, Xu Lin, Winfried März, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M.‘t Hart, Petra J. M. Elders, Scott M. Damrauer, Meena Kumari, Mika Kivimaki, Pim van der Harst, Tim D. Spector, Ruth J. F. Loos, Michael A. Province, Esteban J. Parra, Miguel Cruz, Bruce M. Psaty, Ivan Brandslund, Peter P. Pramstaller, Charles N. Rotimi, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F. A. Grant, Lambertus A. L. M. Kiemeney, Jacqueline de Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W. Franks, Allan Linneberg, J. Wouter Jukema, Amit V. Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Cucca Francesco, Dennis O. Mook-Kanamori, Ko Willems van Dijk, Hugh Watkins, David P. Strachan, Niels Grarup, Peter Sever, Neil Poulter, Lee-Ming Chuang, Jerome I. Rotter, Thomas M. Dantoft, Fredrik Karpe, Matt J. Neville, Nicholas J. Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Hengtong Li, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T. Hattersley, Nancy L. Pedersen, Patrik K. E. Magnusson, Dorret I. Boomsma, Allegonda H. M. Willemsen, LAdrienne Cupples, Joyce B. J. van Meurs, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J. Wareham, Claudia Langenberg, Eleftheria Zeggini, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C. Chambers, Jaspal S. Kooner, Paul S. de Vries, Alanna C. Morrison, Scott Hazelhurst, Michèle Ramsay, Kari E. North, Martha Daviglus, Peter Kraft, Nicholas G. Martin, John B. Whitfield, Shahid Abbas, Danish Saleheen, Robin G. Walters, Michael V. Holmes, Corri Black, Blair H. Smith, Aris Baras, Anne E. Justice, Julie E. Buring, Paul M. Ridker, Daniel I. Chasman, Charles Kooperberg, Gen Tamiya, Masayuki Yamamoto, David A. van Heel, Richard C. Trembath, Wei-Qi Wei, Gail P. Jarvik, Bahram Namjou, M. Geoffrey Hayes, Marylyn D. Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Bong-Jo Kim, Unnur Thorsteinsdottir, Kari Stefansson, Jifeng Zhang, YEugene Chen, Yuk-Lam Ho, Julie A. Lynch, Daniel J. Rader, Philip S. Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J. O’Donnell, John M. Gaziano, Peter W. F. Wilson, Timothy M. Frayling, Joel N. Hirschhorn, Sekar Kathiresan, Karen L. Mohlke, Yan V. Sun, Andrew P. Morris, Michael Boehnke, Christopher D. Brown, Pradeep Natarajan, Panos Deloukas, Cristen J. Willer, Themistocles L. Assimes, Gina M. Peloso, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Medicum, Institute for Molecular Medicine Finland, Complex Disease Genetics, Samuli Olli Ripatti / Principal Investigator, HUSLAB, Epigenetics of Complex Diseases and Traits, Department of Medicine, Helsinki University Hospital Area, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Faculty Common Matters (Faculty of Social Sciences), Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Tampere University, Primary Health Care, Clinical Medicine, Department of Clinical Chemistry, TAYS Heart Centre, Department of Clinical Physiology and Nuclear Medicine, Epidemiology and Data Science, APH - Aging & Later Life, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, General practice, APH - Digital Health, Lee Kong Chian School of Medicine (LKCMedicine), Peloso, Gina M [0000-0002-5355-8636], Apollo - University of Cambridge Repository, Epidemiology, Department of Marketing Management, Erasmus MC other, Radiology & Nuclear Medicine, Kanoni, Stavroula, Graham, Sarah E, Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Zajac, Greg J M, Wu, Kuan-Han H, Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T, Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Havulinna, Aki S, Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A, Lingren, Todd, Feng, Qiping, Kullo, Iftikhar J, Narita, Akira, Takayama, Jun, Martin, Hilary C, Hunt, Karen A, Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Rasheed, Asif, Hindy, George, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R, Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M, Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian'An, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achillea, Hottenga, Jouke Jan, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A, Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Flori, Mcdaid, Aaron F, Marques-Vidal, Pedro, Wielscher, Matthia, Trompet, Stella, Sattar, Naveed, Møllehave, Line T, Munz, Matthia, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Luka, Scholz, Marku, Galesloot, Tessel E, Bradfield, Jonathan P, Ruotsalainen, Sanni E, Daw, Ewarwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Vazquez-Moreno, Miguel, Feitosa, Mary F, Wojczynski, Mary K, Wang, Zhe, Preuss, Michael H, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Tsao, Noah L, Verma, Anurag, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Le, Phuong, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L, Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, Smyth, Laura J, Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlo, Lyssenko, Valeriya, Nongmaithem, Suraj S, Bayyana, Swati, Stringham, Heather M, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R H J, Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N, Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C, Wang, Ya Xing, Wei, Wen B, Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A, Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F, Smith, Jennifer A, Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J, Pitkänen, Niina, Cade, Brian E, van der Laan, Sander W, Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R, Doumatey, Ayo P, Adeyemo, Adebowale A, Lee, Jong Young, Petersen, Eva R B, Nielsen, Aneta A, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W, Wang, Carol A, Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O, van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D, Reiner, Alexander P, Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C, Launer, Lenore J, Li, Huaixing, Nalls, Mike A, Raitakari, Olli T, Ichihara, Sahoko, Wild, Sarah H, Nelson, Christopher P, Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S, Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J, Kim, Eung Kweon, Adams, Hieab H H, Ikram, M Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline W J, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Loui, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E, Mori, Trevor A, Lieb, Wolfgang, Franke, Andre, Ohlsson, Clae, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M, Stark, Klaus J, Zimmermann, Martina E, Völzke, Henry, Homuth, Georg, Evans, Michele K, Zonderman, Alan B, Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E, Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J, Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L R, Peyser, Patricia A, Kato, Norihiro, Schulze, Matthias B, Girotto, Giorgia, Böger, Carsten A, Jung, Bettina, Joshi, Peter K, Bennett, David A, De Jager, Philip L, Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morri, Caulfield, Mark J, Munroe, Patricia B, Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B, Samani, Nilesh J, Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A, Adair, Linda S, Bechayda, Sonny Augustin, de Silva, H Janaka, Wickremasinghe, Ananda R, Krauss, Ronald M, Wu, Jer-Yuarn, Zheng, Wei, Hollander, Anneke Iden, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G, Lind, Lar, Heng, Chew-Kiat, Nelson, Amanda E, Golightly, Yvonne M, Wilson, James F, Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J, Rao, D C, Arnett, Donna K, Hunt, Steven C, Walker, Mark, Koistinen, Heikki A, Chandak, Giriraj R, Mercader, Josep M, Costanzo, Maria C, Jang, Dongkeun, Burtt, Noël P, Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, Eshyong, van Dam, Rob M, Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F, Mcknight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, Mccarthy, Mark I, Palmer, Colin N A, Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M, Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M 't, Elders, Petra J M, Damrauer, Scott M, Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth J F, Province, Michael A, Parra, Esteban J, Cruz, Miguel, Psaty, Bruce M, Brandslund, Ivan, Pramstaller, Peter P, Rotimi, Charles N, Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F A, Kiemeney, Lambertus A L M, de Graaf, Jacqueline, Loeffler, Marku, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W, Linneberg, Allan, Jukema, J Wouter, Khera, Amit V, Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O, van Dijk, Ko Willem, Watkins, Hugh, Strachan, David P, Grarup, Niel, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, Rotter, Jerome I, Dantoft, Thomas M, Karpe, Fredrik, Neville, Matt J, Timpson, Nicholas J, Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T, Pedersen, Nancy L, Magnusson, Patrik K E, Boomsma, Dorret I, Willemsen, Allegonda H M, Cupples, Ladrienne, van Meurs, Joyce B J, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C, Kooner, Jaspal S, de Vries, Paul S, Morrison, Alanna C, Hazelhurst, Scott, Ramsay, Michèle, North, Kari E, Daviglus, Martha, Kraft, Peter, Martin, Nicholas G, Whitfield, John B, Abbas, Shahid, Saleheen, Danish, Walters, Robin G, Holmes, Michael V, Black, Corri, Smith, Blair H, Baras, Ari, Justice, Anne E, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Kooperberg, Charle, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A, Trembath, Richard C, Wei, Wei-Qi, Jarvik, Gail P, Namjou, Bahram, Hayes, M Geoffrey, Ritchie, Marylyn D, Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Yeugene, Ho, Yuk-Lam, Lynch, Julie A, Rader, Daniel J, Tsao, Philip S, Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J, Gaziano, John M, Wilson, Peter W F, Frayling, Timothy M, Hirschhorn, Joel N, Kathiresan, Sekar, Mohlke, Karen L, Sun, Yan V, Morris, Andrew P, Boehnke, Michael, Brown, Christopher D, Natarajan, Pradeep, Deloukas, Pano, Willer, Cristen J, Assimes, Themistocles L, and Peloso, Gina M

Subjects
Genome-wide association study, Medizin, Polymorphism, Single Nucleotide, Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Sex Characteristics, Phenotype, Lipids/genetics, Genetic Pleiotropy, Cholesterol, GWAS, Genetics, Lipids, Genetic, SDG 3 - Good Health and Well-being, Medicine [Science], 112 Statistics and probability, Medicinsk genetik, Genome-wide Association Study, Gwas, 1184 Genetics, developmental biology, physiology, 3126 Surgery, anesthesiology, intensive care, radiology, 3142 Public health care science, environmental and occupational health, 3141 Health care science, FOS: Biological sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 3111 Biomedicine, Medical Genetics
Abstract

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry metaanalysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) R01HL127564 R01HL142711, Wellcome Trust 201543/B/16/Z 202802/Z/16/Z, European Commission HEALTH-F2-2013-601456 608765 786833, TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation NNF15CC0018486, American Diabetes Association 1-19-ICTS-068, Academy of Finland 312062 Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation, Finnish innovation fund Sitra (EW) Finska Lakaresallskapet, American Heart Association 15POST24470131 17POST33650016, University of Bristol NIHR Biomedical Research Centre BRC-1215-2001, MRC & WT 217065/Z/19/Z, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) MC_UU_00011, CRUK Integrative Cancer Epidemiology Programme C18281/A19169, Medical Research Council UK (MRC) MC_UU_00011/1, UK National Institute for Health Research Academic Clinical Fellowship, American Heart Association 18CDA34110116, Miguel Servet contract from the ISCIII Spanish Health Institute CP17/00142, European Social Fund (ESF), Westlake Education Foundation, British Heart Foundation FS/14/66/3129 Z01HG200362 R01HL142302 R01HL105756

Published
2022

120. ULTrasound-guided TRAnsfemoral puncture in COmplex Large bORe PCI: study protocol of the UltraCOLOR trial

Author

Thomas A Meijers, Alexander Nap, Adel Aminian, Joseph Dens, Koen Teeuwen, Jan-Peter van Kuijk, Marleen van Wely, Thomas Schmitz, Yoann Bataille, Adriaan O Kraaijeveld, Vincent Roolvink, Renicus S Hermanides, Thijs L Braber, Niels van Royen, Maarten A H van Leeuwen, Meijers, Thomas A., Nap, Alexander, Aminian, Adel, DENS, Jo, Teeuwen, Koen, Van Kuijk, Jan-Peter, van Wely, Marleen, Schmitz, Thomas, BATAILLE, Yoann, Kraaijeveld, Adriaan O., Roolvink, Vincent, Hermanides, Renicus S., Braber, Thijs L., van Royen, Niels, van Leeuwen, Maarten A. H., Cardiology, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Coronary heart disease, Femoral Artery, Ischaemic heart disease, Percutaneous Coronary Intervention, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Coronary intervention, Humans, General Medicine, Punctures, Vascular Diseases, Ultrasonography, Interventional
Abstract

IntroductionAlthough recently published evidence favours transradial access (TRA) when using large-bore guiding catheters for percutaneous coronary intervention (PCI) of complex coronary lesions, the femoral artery will still be used in a considerate proportion of patients undergoing complex PCI, especially in PCI of chronic total occlusions (CTO). Ultrasound-guided puncture of the femoral artery may reduce clinically relevant access site complications, but robust evidence is lacking up to date.Methods and analysisA total of 542 patients undergoing complex PCI, defined as PCI of CTO, complex bifurcation, heavy calcified lesion or left main, in which the 7-F or 8-F transfemoral access is required, will be randomised to ultrasound-guided puncture or fluoroscopy-guided puncture. The primary outcome is the incidence of the composite end-point of clinically relevant access site related bleeding and/or vascular complications requiring intervention. Access site complications and major adverse cardiovascular events up to 1 month will also be compared between both groups.Ethics and disseminationEthical approval for the study was granted by the local Ethics Committee (‘Medisch Ethische Toetsing Commissie Isala Zwolle’) for all Dutch sites, ‘Comité Medische Ethiek Ziekenhuis Oost-Limburg’ for Hospital Oost-Limburg, ‘Comité d’éthique CHU-Charleroi—ISPPC’ for Centre Hospilatier Universitaire de Charleroi and ‘Ethik Kommission de Ärztekammer Nordrhein’ for Elisabeth-Krankenhaus). The trial outcomes will be published in peer-reviewed journals of the concerned literature. Theultrasound guidedtransfemoral access incomplexlarge bore PCI trial has been administered in the ClinicalTrials.gov database, reference number:NCT03846752.Registration detailsClinicalTrials.gov identifier:NCT03846752.

Published
2022

121. Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI

Author

Giuseppe De Luca, Pierre Deharo, Pierfrancesco Agostoni, Gabriele Gabrielli, Francisco Bosa Ojeda, Ylitalo Antti, Lisette Okkels Jensen, Bor Wilbert, Luigi Vignali, Fortunato Scotto Di Uccio, Dariusz Dudek, Marco Boccalatte, Monica Verdoia, Edouard Benit, Gianni Casella, Heidi Lehtola, Alessandra Scoccia, Tim Kinnaird, Massimo Siviglia, Raul Moreno, Vladimir Ganyukov, Arpad Lux, Mika Laine, Adrian P. Banning, Santiago Camacho-Freiere, Guido Parodi, José Moreu, Michał Kidawa, Miha Cercek, Victor Becerra, Stephane Manzo, Elvin Kedhi, Marija Vavlukis, Filippo Zilio, Ciro De Simone, Nikola Bakraceski, Xavier Carrillo, Giuseppe Uccello, Maurizio Menichelli, Gerard Rourai Ferrer, Dimitrios Alexopoulos, Benjamin Faurie, Jurriën M. ten Berg, Lucia Marinucci, Juan Sanchis Forés, Giovanni Amoroso, Sébastien Levesque, Bernardo Tuccillo, Enrico Fabris, Peter Ludman, Rui Campante Teles, Wojtek Wojakowski, Leonardo Spedicato, Lucian Calmac, Yves Cottin, Maurits T. Dirksen, Petr Kala, Thomas W Johnson, Xacobe Flores Rios, Gianluca Caiazzo, Clemens van Birgelen, Francesco Versaci, Alexander Ijsselmuiden, Luca Donazzan, Kees-Jan Royaards, Adriaan O. Kraaijeveld, Alejandro Gutierrez Barrios, Gennaro Galasso, Vincenzo Guiducci, Julinda Mehilli, Giuseppe Cirrincione, Andrea Santucci, Giuliana Cortese, José Luis Díez Gil, Iñigo Lozano Martínez-Luengas, Bruno Scheller, Periklis Davlouros, Tomas Kovarnik, Arturo García-Touchard, Pieter C. Smits, De Luca, G., Verdoia, M., Cercek, M., Jensen, L. O., Vavlukis, M., Calmac, L., Johnson, T., Ferrer, G. R., Ganyukov, V., Wojakowski, W., Kinnaird, T., van Birgelen, C., Cottin, Y., Ijsselmuiden, A., Tuccillo, B., Versaci, F., Royaards, K. -J., Berg, J. T., Laine, M., Dirksen, M., Siviglia, M., Casella, G., Kala, P., Diez Gil, J. L., Banning, A., Becerra, V., De Simone, C., Santucci, A., Carrillo, X., Scoccia, A., Amoroso, G., Lux, A., Kovarnik, T., Davlouros, P., Mehilli, J., Gabrielli, G., Rios, X. F., Bakraceski, N., Levesque, S., Cirrincione, G., Guiducci, V., Kidawa, M., Spedicato, L., Marinucci, L., Ludman, P., Zilio, F., Galasso, G., Fabris, E., Menichelli, M., Garcia-Touchard, A., Manzo, S., Caiazzo, G., Moreu, J., Fores, J. S., Donazzan, L., Vignali, L., Teles, R., Benit, E., Agostoni, P., Bosa Ojeda, F., Lehtola, H., Camacho-Freiere, S., Kraaijeveld, A., Antti, Y., Boccalatte, M., Deharo, P., Martinez-Luengas, I. L., Scheller, B., Alexopulos, D., Moreno, R., Kedhi, E., Uccello, G., Faurie, B., Gutierrez Barrios, A., Di Uccio, F. S., Wilbert, B., Smits, P., Cortese, G., Parodi, G., Dudek, D., banning, adrian/0000-0002-2842-7861, GUIDUCCI, VINCENZO/0000-0002-0833-2785, vavlukis, marija/0000-0002-4479-6691, Bor, Willem L/0000-0002-3253-5961, DAVLOUROS, PERIKLIS/0000-0002-1439-1992, Uccello, Giuseppe/0000-0002-6163-8468, Kidawa, Michal/0000-0002-5000-6561, [De Luca, Giuseppe] Univ Piemonte Orientale, Div Cardiol, Azienda Osped Univ Maggiore Carita, Novara, Italy, [Verdoia, Monica] Osped Inferm Biella, ASL Biella, Div Cardiol, Biella, Italy, [Cercek, Miha] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia, [Jensen, Lisette Okkels] Odense Univ Hosp, Div Cardiol, Odense, Denmark, [Vavlukis, Marija] Ss Cyril & Methodius Univ, Med Fac, Univ Clin Cardiol, Skopje, North Macedonia, [Calmac, Lucian] Clin Emergency Hosp Bucharest, Bucharest, Romania, [Johnson, Tom] Univ Hosp Bristol NHSFT, Bristol Heart Inst, Div Cardiol, Bristol, Avon, England, [Johnson, Tom] Univ Bristol, Bristol, Avon, England, [Ferrer, Gerard Rourai] Hosp Univ Bellvitge, Heart Dis Inst, Intervent Cardiol Unit, Barcelona, Spain, [Ganyukov, Vladimir] State Res Inst Complex Issues Cardiovasc Dis, Div Cardiol, Kemerovo, Russia, [Wojakowski, Wojtek] Med Univ Silezia, Div Cardiol, Katowice, Poland, [Kinnaird, Tim] Univ Hosp Wales, Div Cardiol, Cardiff, Wales, [van Birgelen, Clemens] Thoraxctr Twente, Dept Cardiol, Med Spectrum Twente, Enschede, Netherlands, [Cottin, Yves] Univ Hosp, Div Cardiol, Dijon, France, [IJsselmuiden, Alexander] Amphia Hosp, Div Cardiol, Breda, Netherlands, [Tuccillo, Bernardo] Osped Mare, Div Cardiol, Naples, Italy, [Di Uccio, Fortunato Scotto] Osped Mare, Div Cardiol, Naples, Italy, [Versaci, Francesco] Osped Santa Maria Goretti, Div Cardiol, Latina, Italy, [Royaards, Kees-Jan] Maasstad Ziekenhuis, Div Cardiol, Rotterdam, Netherlands, [Smits, Pieter] Maasstad Ziekenhuis, Div Cardiol, Rotterdam, Netherlands, [Ten Berg, Jurrien] St Antonius Hosp, Div Cardiol, Nieuwegein, Netherlands, [Wilbert, Bor] St Antonius Hosp, Div Cardiol, Nieuwegein, Netherlands, [Laine, Mika] Helsinki Univ Cent Hosp, Div Cardiol, Helsinki, Finland, [Dirksen, Maurits] Northwest Clin, Div Cardiol, Alkmaar, Netherlands, [Siviglia, Massimo] Osped Riuniti Reggio Calabria, Div Cardiol, Reggio Di Calabria, Italy, [Casella, Gianni] Osped Maggiore Bologna, Div Cardiol, Bologna, Italy, [Kala, Petr] Masaryk Univ, Univ Hosp Brno, Med Fac, Brno, Czech Republic, [Diez Gil, Jose Luis] H Univ & Politecn La Fe, Valencia, Spain, [Banning, Adrian] John Radcliffe Hosp, Oxford, England, [Becerra, Victor] Hosp Clin Univ Virgen Victoria, Malaga, Spain, [De Simone, Ciro] Clin Villa Fiori, Div Cardiol, Acerra, Italy, [Santucci, Andrea] Osped Santa Maria Misericordia, Perugia, Italy, [Carrillo, Xavier] Hosp Germans Triasi Pujol, Badalona, Spain, [Scoccia, Alessandra] Osped St Anna, Div Cardiol, Ferrara, Italy, [Amoroso, Giovanni] Onze Lieve Vrouwe Gasthuis OLVG, Amsterdam, Netherlands, [Lux, Arpad] Mastricht Univ, Med Ctr, Maastricht, Netherlands, [Kovarnik, Tomas] Charles Univ Hosp, Prague, Czech Republic, [Davlouros, Periklis] Patras Univ Hosp, Invas Cardiol & Congenital Heart Dis, Patras, Greece, [Mehilli, Julinda] Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Munich, Germany, [Gabrielli, Gabriele] Azienda Osped Univ, Intervent Cardiol Unit, Osped Riuniti, Ancona, Italy, [Rios, Xacobe Flores] Complexo Hosp Univ La Coruna, La Coruna, Spain, [Bakraceski, Nikola] Ctr Cardiovasc Dis, Ohrid, North Macedonia, [Levesque, Sebastien] CHU Poitiers, Univ Hosp, Poitiers, France, [Cirrincione, Giuseppe] Osped Civ Arnas, Div Cardiol, Palermo, Italy, [Guiducci, Vincenzo] AUSL IRCCS, Reggio Emilia, Italy, [Kidawa, Michal] Med Univ Lodz, Cent Hosp, Lodz, Poland, [Spedicato, Leonardo] Osped Santa Maria Misericordia, Div Cardiol, Udine, Italy, [Marinucci, Lucia] Osped Riuniti Marche Nord, Div Cardiol, Azienda Osped, Pesaro, Italy, [Ludman, Peter] Univ Hosp Birmingham, Birmingham, W Midlands, England, [Zilio, Filippo] Osped Santa Chiara, Trento, Italy, [Galasso, Gennaro] Osped San Giovanni Dio Ruggi Aragona, Div Cardiol, Salerno, Italy, [Fabris, Enrico] Univ Ospedali Riuniti, Azienda Osped, Trieste, Italy, [Menichelli, Maurizio] Osped F Spaziani, Div Cardiol, Frosinone, Italy, [Garcia-Touchard, Arturo] Hosp Puerta Hierro, Div Cardiol, Majadahonda, Spain, [Manzo, Stephane] Paris 07 Univ, CHU Lariboisiere, AP HP, Div Cardiol,INSERM,UMRS 942, Paris, France, [Caiazzo, Gianluca] Osped G Moscati, Div Cardiol, Aversa, Italy, [Moreu, Jose] Complejo Hosp Toledo, Div Cardiol, Toledo, Spain, [Sanchis Fores, Juan] Hosp Clin Univ Valencia, Div Cardiol, Valencia, Spain, [Donazzan, Luca] Osped S Maurizio Bolzano, Div Cardiol, Bolzano, Italy, [Vignali, Luigi] Azienda Osped Sanitaria, Intervent Cardiol Unit, Parma, Italy, [Teles, Rui] Hosp Santa Cruz, Div Cardiol, CHLO Carnaxide, Lisbon, Portugal, [Benit, Edouard] Jessa Ziekenhuis, Div Cardiol, Hasselt, Belgium, [Agostoni, Pierfrancesco] Ziekenhuis Netwerk Antwerpen ZNA Middelheim, Div Cardiol, Antwerp, Belgium, [Bosa Ojeda, Francisco] Hosp Univ Canarias, Div Cardiol, Santa Cruz De Tenerife, Spain, [Lehtola, Heidi] Oulu Univ Hosp, Div Cardiol, Oulu, Finland, [Camacho-Freiere, Santiago] Juan Ramon Jimenez Hosp, Div Cardiol, Huelva, Spain, [Kraaijeveld, Adriaan] UMC Utrecht, Div Cardiol, Utrecht, Netherlands, [Antti, Ylitalo] Univ Hosp, Heart Ctr, Div Cardiol, Turku, Finland, [Boccalatte, Marco] Osped Santa Maria Grazie, Div Cardiol, Pozzuoli, Italy, [Deharo, Pierre] Aix Marseille Univ, CHU Timone, Div Cardiol, Marseille, France, [Lozano Martinez-Luengas, Inigo] Hosp Cabuenes, Div Cardiol, Gijon, Spain, [Scheller, Bruno] Univ Saarland, Div Cardiol Clin & Expt Intervent Cardiol, Homburg, Germany, [Alexopoulos, Dimitrios] Attikon Univ Hosp, Div Cardiol, Athens, Greece, [Moreno, Raul] Hosp Paz, Div Cardiol, Madrid, Spain, [Kedhi, Elvin] St Jan Hosp, Div Cardiol, Brugge, Belgium, [Uccello, Giuseppe] Osped A Manzoni Lecco, Div Cardiol, Lecce, Italy, [Faurie, Benjamin] Grp Hosp Mutualiste Grenoble, Div Cardiol, Grenoble, France, [Gutierrez Barrios, Alejandro] Hosp Puerta Mar, Div Cardiol, Cadiz, Spain, [Cortese, Giuliana] Univ Padua, Dept Stat Sci, Padua, Italy, [Parodi, Guido] Azienda Osped Univ Sassari, Sassari, Italy, [Dudek, Dariusz] Jagiellonian Univ Med Coll, Inst Cardiol, Krakow, Poland, RS: Carim - H01 Clinical atrial fibrillation, and Cardiologie

Subjects
Male, Internationality, medical decision-making, medicine.medical_treatment, 030204 cardiovascular system & hematology, Rate ratio, COVID-19 (coronavirus), Settore MED/06, 0302 clinical medicine, Pandemic, Percutaneous Coronary Intervention/statistics & numerical data, Medicine, Viral, 030212 general & internal medicine, Myocardial infarction, Registries, Acute myocardial-infarction, Original Investigation, STEMI, ST-segment elevation myocardial infarction, Middle Aged, 3. Good health, Europe, fibrinolysis, Female, COVID-19, primary angioplasty, STEMI, Aged, Humans, Percutaneous Coronary Intervention, Retrospective Studies, ST Elevation Myocardial Infarction, Coronavirus Infections, Pandemics, Pneumonia, Viral, Cardiology and Cardiovascular Medicine, Editorial Comment, ACUTE MYOCARDIAL-INFARCTION, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Primary angioplasty, IRR, incidence rate ratio, Europe/epidemiology, 03 medical and health sciences, Betacoronavirus, cardiovascular diseases, Mortality, PCI, percutaneous coronary intervention, DES, drug-eluting stent(s), business.industry, ST Elevation Myocardial Infarction/mortality, PPCI, primary PCI, SARS-CoV-2, MORTALITY, Percutaneous coronary intervention, Retrospective cohort study, Pneumonia, medicine.disease, Confidence interval, ST-segment elevation myocardial infarction, CI, confidence interval, Emergency medicine, COVID-19, STEMI, primary angioplasty, ACS, acute coronary syndrome, business
Abstract

Background The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. Objectives The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment. Methods This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. Results A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p, Central Illustration

Published
2020

122. Impact of Smoking Status on Mortality in STEMI Patients Undergoing Mechanical Reperfusion for STEMI: Insights from the ISACS-STEMI COVID-19 Registry

Author

Giuseppe De Luca, Magdy Algowhary, Berat Uguz, Dinaldo C. Oliveira, Vladimir Ganyukov, Zan Zimbakov, Miha Cercek, Lisette Okkels Jensen, Poay Huan Loh, Lucian Calmac, Gerard Roura i Ferrer, Alexandre Quadros, Marek Milewski, Fortunato Scotto D’Uccio, Clemens von Birgelen, Francesco Versaci, Jurrien Ten Berg, Gianni Casella, Aaron Wong Sung Lung, Petr Kala, José Luis Díez Gil, Xavier Carrillo, Maurits Dirksen, Victor M. Becerra-Munoz, Michael Kang-yin Lee, Dafsah Arifa Juzar, Rodrigo de Moura Joaquim, Roberto Paladino, Davor Milicic, Periklis Davlouros, Nikola Bakraceski, Filippo Zilio, Luca Donazzan, Adriaan Kraaijeveld, Gennaro Galasso, Lux Arpad, Marinucci Lucia, Guiducci Vincenzo, Maurizio Menichelli, Alessandra Scoccia, Aylin Hatice Yamac, Kadir Ugur Mert, Xacobe Flores Rios, Tomas Kovarnik, Michal Kidawa, Josè Moreu, Flavien Vincent, Enrico Fabris, Iñigo Lozano Martínez-Luengas, Marco Boccalatte, Francisco Bosa Ojeda, Carlos Arellano-Serrano, Gianluca Caiazzo, Giuseppe Cirrincione, Hsien-Li Kao, Juan Sanchis Forés, Luigi Vignali, Helder Pereira, Stephane Manzo, Santiago Ordoñez, Alev Arat Özkan, Bruno Scheller, Heidi Lehtola, Rui Teles, Christos Mantis, Ylitalo Antti, João António Brum Silveira, Rodrigo Zoni, Ivan Bessonov, Stefano Savonitto, George Kochiadakis, Dimitrios Alexopulos, Carlos E. Uribe, John Kanakakis, Benjamin Faurie, Gabriele Gabrielli, Alejandro Gutierrez Barrios, Juan Pablo Bachini, Alex Rocha, Frankie Chor-Cheung Tam, Alfredo Rodriguez, Antonia Anna Lukito, Veauthyelau Saint-Joy, Gustavo Pessah, Andrea Tuccillo, Giuliana Cortese, Guido Parodi, Mohamed Abed Bouraghda, Elvin Kedhi, Pablo Lamelas, Harry Suryapranata, Matteo Nardin, Monica Verdoia, De Luca, Giuseppe, Algowhary, Magdy, Uguz, Berat, Oliveira, Dinaldo C, Ganyukov, Vladimir, Zimbakov, Zan, Cercek, Miha, Jensen, Lisette Okkel, Loh, Poay Huan, Calmac, Lucian, Ferrer, Gerard Roura I, Quadros, Alexandre, Milewski, Marek, Scotto D'Uccio, Fortunato, von Birgelen, Clemen, Versaci, Francesco, Ten Berg, Jurrien, Casella, Gianni, Wong Sung Lung, Aaron, Kala, Petr, Díez Gil, José Lui, Carrillo, Xavier, Dirksen, Maurit, Becerra-Munoz, Victor M, Lee, Michael Kang-Yin, Juzar, Dafsah Arifa, Joaquim, Rodrigo de Moura, Paladino, Roberto, Milicic, Davor, Davlouros, Perikli, Bakraceski, Nikola, Zilio, Filippo, Donazzan, Luca, Kraaijeveld, Adriaan, Galasso, Gennaro, Arpad, Lux, Lucia, Marinucci, Vincenzo, Guiducci, Menichelli, Maurizio, Scoccia, Alessandra, Yamac, Aylin Hatice, Ugur Mert, Kadir, Flores Rios, Xacobe, Kovarnik, Toma, Kidawa, Michal, Moreu, Josè, Vincent, Flavien, Fabris, Enrico, Martínez-Luengas, Iñigo Lozano, Boccalatte, Marco, Bosa Ojeda, Francisco, Arellano-Serrano, Carlo, Caiazzo, Gianluca, Cirrincione, Giuseppe, Kao, Hsien-Li, Sanchis Forés, Juan, Vignali, Luigi, Pereira, Helder, Manzo, Stephane, Ordoñez, Santiago, Özkan, Alev Arat, Scheller, Bruno, Lehtola, Heidi, Teles, Rui, Mantis, Christo, Antti, Ylitalo, Silveira, João António Brum, Zoni, Rodrigo, Bessonov, Ivan, Savonitto, Stefano, Kochiadakis, George, Alexopulos, Dimitrio, Uribe, Carlos E, Kanakakis, John, Faurie, Benjamin, Gabrielli, Gabriele, Barrios, Alejandro Gutierrez, Bachini, Juan Pablo, Rocha, Alex, Tam, Frankie Chor-Cheung, Rodriguez, Alfredo, Lukito, Antonia Anna, Saint-Joy, Veauthyelau, Pessah, Gustavo, Tuccillo, Andrea, Cortese, Giuliana, Parodi, Guido, Bouraghda, Mohamed Abed, Kedhi, Elvin, Lamelas, Pablo, Suryapranata, Harry, Nardin, Matteo, Verdoia, Monica, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H01 Clinical atrial fibrillation, and YAMAÇ, AYLİN HATİCE

Subjects
ACUTE MYOCARDIAL-INFARCTION, myocardial infarction, smoking paradox, percutaneous coronary intervention, COVID-19, Temel Tıp Bilimleri, Medicine (miscellaneous), Assessment and Diagnosis, Sağlık Bilimleri, Temel Bilgi ve Beceriler, Genel Tıp, Fundamental Medical Sciences, Pathophysiology, Clinical Medicine (MED), TIP, GENEL & DAHİLİ, Hàbit de fumar, Health Sciences, Internal Medicine, Klinik Tıp (MED), ST-SEGMENT ELEVATION, Aile Sağlığı, MEDICINE, GENERAL & INTERNAL, Dahiliye, Patofizyoloji, OUTCOMES, Klinik Tıp, Fundamentals and Skills, Smoking, EXTENT, General Medicine, CLINICAL MEDICINE, Değerlendirme ve Teşhis, Tıp, TIME, Infart de miocardi, THROMBOLYTIC THERAPY, CARDIOVASCULAR-DISEASE, General Health Professions, Medicine, CORONARY-ARTERY-DISEASE, Tıp (çeşitli), CIGARETTE-SMOKING, Family Practice, Genel Sağlık Meslekleri, SMOKERS
Abstract

The so-called "smoking paradox", conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.

Published
2022

123. Renin-Angiotensin System inhibitors and mortality among diabetic patients with STEMI undergoing mechanical reperfusion during the COVID Pandemic

Author

Giuseppe De Luca, Matteo Nardin, Magdy Algowhary, Berat Uguz, Dinaldo C Oliveira, Vladimir Ganyukov, Zan Zimbakov, Miha Cercek, Lisette Okkels Jensen, Poay Huan LOH, Lucian Calmac, Gerard Roura Ferrer, Alexandre Quadros, Marek Milewski, Fortunato Scotto di Uccio, Clemens von Birgelen, Francesco Versaci, Jurrien Ten Berg, Gianni Casella, Aaron Wong Sung Lung, Petr Kala, José Luis Díez Gil, Xavier Carrillo, Maurits Dirksen, Victor M. Becerra-Munoz, Michael Kang-yin Lee, Dafsah Arifa Juzar, Rodrigo de Moura Joaquim, Roberto Paladino, Davor Milicic, Periklis Davlouros, Nikola Bakraceski, Filippo Zilio, Luca Donazzan, Adriaan Kraaijeveld, Gennaro Galasso, Arpad Lux, Lucia Marinucci, Vincenzo Guiducci, Maurizio Menichelli, Alessandra Scoccia, Aylin Hatice Yamac, Kadir Ugur Mert, Xacobe Flores Rios, Tomas Kovarnik, Michal Kidawa, Josè Moreu, Vincent Flavien, Enrico Fabris, Iñigo Lozano Martínez-Luengas, Marco Boccalatte, Francisco Bosa Ojeda, Carlos Arellano-Serrano, Gianluca Caiazzo, Giuseppe Cirrincione, Hsien-Li Kao, Juan Sanchis Forés, Luigi Vignali, Helder Pereira, Stephane Manzo, Santiago Ordoñez, Alev Arat Özkan, Bruno Scheller, Heidi Lehtola, Rui Teles, Christos Mantis, Ylitalo Antti, João António Brum Silveira, Rodrigo Zoni, Ivan Bessonov, Stefano Savonitto, George Kochiadakis, Dimitrios Alexopulos, Carlos E Uribe, John Kanakakis, Benjamin Faurie, Gabriele Gabrielli, Alejandro Gutierrez Barrios, Juan Pablo Bachini, Alex Rocha, Frankie Chor-Cheung Tam, Alfredo Rodriguez, Antonia Anna Lukito, Veauthyelau Saint-Joy, Gustavo Pessah, Andrea Tuccillo, Giuliana Cortese, Guido Parodi, Mohammed Abed Bouraghda, Elvin Kedhi, Pablo Lamelas, Harry Suryapranata, Monica Verdoia, De Luca, Giuseppe, Nardin, Matteo, Algowhary, Magdy, Uguz, Berat, Oliveira, Dinaldo C, Ganyukov, Vladimir, Zimbakov, Zan, Cercek, Miha, Jensen, Lisette Okkel, Loh, Poay Huan, Calmac, Lucian, Roura Ferrer, Gerard, Quadros, Alexandre, Milewski, Marek, Scotto di Uccio, Fortunato, von Birgelen, Clemen, Versaci, Francesco, Ten Berg, Jurrien, Casella, Gianni, Lung, Aaron Wong Sung, Kala, Petr, Díez Gil, José Lui, Carrillo, Xavier, Dirksen, Maurit, Becerra-Munoz, Victor M, Lee, Michael Kang-Yin, Juzar, Dafsah Arifa, de Moura Joaquim, Rodrigo, Paladino, Roberto, Milicic, Davor, Davlouros, Perikli, Bakraceski, Nikola, Zilio, Filippo, Donazzan, Luca, Kraaijeveld, Adriaan, Galasso, Gennaro, Lux, Arpad, Marinucci, Lucia, Guiducci, Vincenzo, Menichelli, Maurizio, Scoccia, Alessandra, Yamac, Aylin Hatice, Mert, Kadir Ugur, Flores Rios, Xacobe, Kovarnik, Toma, Kidawa, Michal, Moreu, Josè, Flavien, Vincent, Fabris, Enrico, Martínez-Luengas, Iñigo Lozano, Boccalatte, Marco, Bosa Ojeda, Francisco, Arellano-Serrano, Carlo, Caiazzo, Gianluca, Cirrincione, Giuseppe, Kao, Hsien-Li, Sanchis Forés, Juan, Vignali, Luigi, Pereira, Helder, Manzo, Stephane, Ordoñez, Santiago, Arat Özkan, Alev, Scheller, Bruno, Lehtola, Heidi, Teles, Rui, Mantis, Christo, Antti, Ylitalo, Brum Silveira, João António, Zoni, Rodrigo, Bessonov, Ivan, Savonitto, Stefano, Kochiadakis, George, Alexopulos, Dimitrio, Uribe, Carlos E, Kanakakis, John, Faurie, Benjamin, Gabrielli, Gabriele, Gutierrez Barrios, Alejandro, Bachini, Juan Pablo, Rocha, Alex, Tam, Frankie Chor-Cheung, Rodriguez, Alfredo, Lukito, Antonia Anna, Saint-Joy, Veauthyelau, Pessah, Gustavo, Tuccillo, Andrea, Cortese, Giuliana, Parodi, Guido, Bouraghda, Mohammed Abed, Kedhi, Elvin, Lamelas, Pablo, Suryapranata, Harry, Verdoia, Monica, RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Centro de Estudos de Doenças Crónicas (CEDOC)

Subjects
Renin-angiotensin system inhibitors, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, COVID-19, 030204 cardiovascular system & hematology, STEMI, RC648-665, Diseases of the endocrine glands. Clinical endocrinology, Article, Renin-angiotensin system inhibitor, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Text mining, SDG 3 - Good Health and Well-being, 030220 oncology & carcinogenesis, Internal medicine, Pandemic, Renin–angiotensin system, Internal Medicine, Cardiology, Medicine, business
Abstract

Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment.Methods: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients.Results: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p < 0.0001), consistently both in 2019 and in 2010.Conclusions: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection.Trial registration number: NCT04412655.

Published
2021

124. Improving treatment planning in cardiac intervention

Author

Hart, E.A., Chamuleau, Steven, Doevendans, Pieter A., Kraaijeveld, Adriaan, and University Utrecht

Subjects
MitraClip, Carcinoid Heart Disease, Anticoagulant Bridging, Mitral Regurgitation
Abstract

In this thesis, challenges associated with interventions in cardiac disease are discussed. In the age of personalized medicine and informed decision making the role of adequate treatment planning is steadily increasing. Novel techniques and insights are developed at a rapid pace and contribute to improved procedural success rates and patient safety. Despite a multitude of advancements in recent years, peri-procedural challenges are still at large and need to be addressed. As a result, the importance of the multidisciplinary heart team is growing and cannot be exonerated from clinical practice. New techniques, multidisciplinary approaches, and computer-based simulations are developing and are inseparable from the future. New insights present with new challenges, but new challenges may also provide new insights.

Published
2018

125. Intracardiac echocardiography-guided biopsies for right-sided intracardiac tumors: An optimized diagnostic algorithm and case illustrations.

Author

Teske AJ, Jimenez-Rodriguez GM, Kraaijeveld AO, Broekhuizen LN, van Osch D, Gort EH, Rhenen AV, Harst PV, and Voskuil M

Abstract

Intracardiac tumors, though uncommon, necessitate a swift and accurate diagnosis for personalized treatment and prognosis estimation. While multi-modality imaging often determines the etiology of these cardiac masses, histological confirmation remains essential for definitive diagnosis and its specific treatment. Since cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount. The least invasive strategy would be to achieve this by means of endomyocardial biopsy (EMB); however real-time additional imaging is essential to reduce the risk of perforation/tamponade and to minimize sampling error. Intracardiac echocardiography (ICE) emerges as an excellent tool to achieve this goal preventing procedural complications and reducing the likelihood of sampling errors obtaining a definitive histopathological diagnosis in all cases. This paper outlines our diagnostic algorithm for optimal patient selection, details three illustrative cases, and elucidates the steps to acquire histopathology via percutaneous transvenous biopsy with ICE guidance in patients with right-sided cardiac tumors. Given the rarity of intracardiac tumors, we advocate these patients be managed by a dedicated multidisciplinary cardio-oncology team including an interventional cardiologist., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Published
2024
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126. Impact of symptom duration and mechanical circulatory support on prognosis in cardiogenic shock complicating acute myocardial infarction.

Author

Klein F, Crooijmans C, Peters EJ, van 't Veer M, Timmermans MJC, Henriques JPS, Verouden NJW, Kraaijeveld AO, Bunge JJH, Lipsic E, Sjauw KD, van Geuns RM, Dedic A, Dubois EA, Meuwissen M, Danse P, Bleeker G, Montero-Cabezas JM, Ferreira IA, Brouwer J, Teeuwen K, and Otterspoor LC

Abstract

Background: Mortality rates in patients with cardiogenic shock complicating acute myocardial infarction (AMICS) remain high despite advancements in AMI care. Our study aimed to investigate the impact of prehospital symptom duration on the prognosis of AMICS patients and those receiving mechanical circulatory support (MCS)., Methods and Results: We conducted a retrospective cohort study with data registered in the Netherlands Heart Registration. A total of 1,363 patients with AMICS who underwent percutaneous coronary intervention between 2017 and 2021 were included. Patients presenting after out-of-hospital cardiac arrest were excluded. Most patients were male (68%), with a median age of 69 years (IQR 61-77), predominantly presenting with ST-elevation myocardial infarction (86%). The overall 30-day mortality was 32%. Longer prehospital symptom duration was associated with a higher 30-day mortality with the following rates: < 3 h, 26%; 3-6 h, 29%; 6-24 h, 36%; ≥ 24 h, 46%; p < 0.001. In a subpopulation of AMICS patients with MCS (n = 332, 24%), symptom duration of > 24 h was associated with significantly higher mortality compared to symptom duration of < 24 h (59% vs 45%, p = 0.029). Multivariate analysis identified > 24 h symptom duration, age and in-hospital cardiac arrest as predictors of 30-day mortality in MCS patients., Conclusion: Prolonged prehospital symptom duration was associated with significantly increased 30-day mortality in patients presenting with AMICS. In AMICS patients treated with MCS, a symptom duration of > 24 h was an independent predictor of poor survival. These results emphasise the critical role of early recognition and intervention in the prognosis of AMICS patients., (© 2024. The Author(s).)

Published
2024
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127. Ultrasound-guided versus fluoroscopy-guided large-bore femoral access in PCI of complex coronary lesions: the international, multicentre, randomised ULTRACOLOR Trial.

Author

Meijers TA, Nap A, Aminian A, Schmitz T, Dens J, Teeuwen K, van Kuijk JP, van Wely M, Bataille Y, Kraaijeveld AO, Roolvink V, Dambrink JE, Gosselink ATM, Hermanides RS, Ottervanger JP, Tsilingiris I, van den Buijs DMF, van Royen N, and van Leeuwen MAH

Subjects
Humans, Male, Female, Aged, Fluoroscopy, Middle Aged, Treatment Outcome, Punctures, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease therapy, Coronary Artery Disease surgery, Hemorrhage etiology, Hemorrhage prevention & control, Aged, 80 and over, Percutaneous Coronary Intervention methods, Femoral Artery diagnostic imaging, Ultrasonography, Interventional methods
Abstract

Background: Transfemoral access is often used when large-bore guide catheters are required for percutaneous coronary intervention (PCI) of complex coronary lesions, especially when large-bore transradial access is contraindicated. Whether the risk of access site complications for these procedures may be reduced by ultrasound-guided puncture is unclear., Aims: We aimed to show the superiority of ultrasound-guided femoral puncture compared to fluoroscopy-guided access in large-bore complex PCI with regard to access site-related Bleeding Academic Research Consortium 2, 3 or 5 bleeding and/or vascular complications requiring intervention during hospitalisation., Methods: The ULTRACOLOR Trial is an international, multicentre, randomised controlled trial investigating whether ultrasound-guided large-bore femoral access reduces clinically relevant access site complications compared to fluoroscopy-guided large-bore femoral access in PCI of complex coronary lesions., Results: A total of 544 patients undergoing complex PCI mandating large-bore (≥7 Fr) transfemoral access were randomised at 10 European centres (median age 71; 76% male). Of these patients, 68% required PCI of a chronic total occlusion. The primary endpoint was met in 18.9% of PCI with fluoroscopy-guided access and 15.7% of PCI with ultrasound-guided access (p=0.32). First-pass puncture success was 92% for ultrasound-guided access versus 85% for fluoroscopy-guided access (p=0.02). The median time in the catheterisation laboratory was 102 minutes versus 105 minutes (p=0.43), and the major adverse cardiovascular event rate at 1 month was 4.1% for fluoroscopy-guided access and 2.6% for ultrasound-guided access (p=0.32)., Conclusions: As compared to fluoroscopy-guided access, the routine use of ultrasound-guided access for large-bore transfemoral complex PCI did not significantly reduce clinically relevant bleeding or vascular access site complications. A significantly higher first-pass puncture success rate was demonstrated for ultrasound-guided access., Clinicaltrials: gov identifier: NCT04837404.

Published
2024
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128. ECPELLA as a bridge-to-decision in refractory cardiogenic shock: a single-centre experience.

Author

Balder JW, Szymanski MK, van Laake LW, van der Harst P, Meuwese CL, Ramjankhan FZ, van der Meer MG, Hermens JAJM, Voskuil M, de Waal EEC, Donker DW, Oerlemans MIFJ, and Kraaijeveld AO

Abstract

Background: In refractory cardiogenic shock, temporary mechanical support (tMCS) may be crucial for maintaining tissue perfusion and oxygen delivery. tMCS can serve as a bridge-to-decision to assess eligibility for left ventricular assist device (LVAD) implantation or heart transplantation, or as a bridge-to-recovery. ECPELLA is a novel tMCS configuration combining venoarterial extracorporeal membrane oxygenation with Impella. The present study presents the clinical parameters, outcomes, and complications of patients supported with ECPELLA., Methods: All patients supported with ECPELLA at University Medical Centre Utrecht between December 2020 and August 2023 were included. The primary outcome was 30-day mortality, and secondary outcomes were LVAD implantation/heart transplantation and safety outcomes., Results: Twenty patients with an average age of 51 years, and of whom 70% were males, were included. Causes of cardiogenic shock were acute heart failure (due to acute coronary syndrome, myocarditis, or after cardiac surgery) or chronic heart failure, respectively 70 and 30% of cases. The median duration of ECPELLA support was 164 h (interquartile range 98-210). In 50% of cases, a permanent LVAD was implanted. Cardiac recovery within 30 days was seen in 30% of cases and 30-day mortality rate was 20%. ECPELLA support was associated with major bleeding (40%), haemolysis (25%), vascular complications (30%), kidney failure requiring replacement therapy (50%), and Impella failure requiring extraction (15%)., Conclusion: ECPELLA can be successfully used as a bridge to LVAD implantation or as a bridge-to-recovery in patients with refractory cardiogenic shock. Despite a significant number of complications, 30-day mortality was lower than observed in previous cohorts., (© 2024. The Author(s).)

Published
2024
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129. CCL18 aggravates atherosclerosis by inducing CCR6-dependent T-cell influx and polarization.

Author

Singh A, Kraaijeveld AO, Curaj A, Wichapong K, Hammerich L, de Jager SCA, Bot I, Atamas SP, van Berkel TJC, Jukema JW, Comerford I, McColl SR, Mees B, Heemskerk JWM, Nicolaes GAF, Hackeng T, Liehn EA, Tacke F, and Biessen EAL

Subjects
Animals, Humans, Mice, Disease Models, Animal, Mice, Inbred C57BL, Jurkat Cells, Plaque, Atherosclerotic immunology, Mice, Knockout, Male, T-Lymphocytes immunology, T-Lymphocytes metabolism, Th17 Cells immunology, Th17 Cells metabolism, Female, Mice, Knockout, ApoE, Atherosclerosis immunology, Atherosclerosis metabolism, Receptors, CCR6 metabolism, Receptors, CCR6 genetics, Chemokines, CC metabolism, Chemokines, CC genetics
Abstract

Introduction: The CC chemokine ligand 18 (CCL18) is a chemokine highly expressed in chronic inflammation in humans. Recent observations of elevated CCL18 plasma levels in patients with acute cardiovascular syndromes prompted an investigation into the role of CCL18 in the pathogenesis of human and mouse atherosclerosis., Methods and Results: CCL18 was profoundly upregulated in ruptured human atherosclerotic plaque, particularly within macrophages. Repeated administration of CCL18 in Western-type diet-fed ApoE -/- mice or PCSK9 mut -overexpressing wild type (WT) mice led to increased plaque burden, enriched in CD3 + T cells. In subsequent experimental and molecular modeling studies, we identified CCR6 as a functional receptor mediating CCL18 chemotaxis, intracellular Ca 2+ flux, and downstream signaling in human Jurkat and mouse T cells. CCL18 failed to induce these effects in vitro in murine spleen T cells with CCR6 deficiency. The ability of CCR6 to act as CCL18 receptor was confirmed in vivo in an inflammation model, where subcutaneous CCL18 injection induced profound focal skin inflammation in WT but not in CCR6 -/- mice. This inflammation featured edema and marked infiltration of various leukocyte subsets, including T cells with a Th17 signature, supporting CCR6's role as a Th17 chemotactic receptor. Notably, focal overexpression of CCL18 in plaques was associated with an increased presence of CCR6 + (T) cells., Discussion: Our studies are the first to identify the CCL18/CCR6 axis as a regulator of immune responses in advanced murine and human atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Singh, Kraaijeveld, Curaj, Wichapong, Hammerich, de Jager, Bot, Atamas, van Berkel, Jukema, Comerford, McColl, Mees, Heemskerk, Nicolaes, Hackeng, Liehn, Tacke and Biessen.)

Published
2024
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130. The value of computed tomography for head trauma in patients presenting with out-of-hospital cardiac arrest before emergency percutaneous coronary intervention.

Author

Bosch L, Rittersma SZH, van der Worp BH, Kraaijeveld AO, Vlachojannis G, van der Harst P, and Voskuil M

Abstract

Introduction: Out-of-hospital cardiac arrest (OHCA) caused by an ST-elevation myocardial infarction (STEMI) is often accompanied by a sudden loss of consciousness that may cause the patient to collapse with resulting head trauma, leading to a suspicion of possible intracranial haemorrhage. To rule out intracranial haemorrhage before emergency percutaneous coronary intervention (PCI), emergency computed tomography (CT) of the head might be useful but also causes a delay in percutaneous STEMI treatment., Methods: The medical records of all adult patients that presented with OHCA to the emergency department (ED) of the University Medical Centre Utrecht (UMCU), the Netherlands between 16 February 2020 and 16 February 2022 were reviewed., Results: A total of 263 patients presented to the ED with an OHCA; 50 presented with a STEMI requiring emergency PCI. Thirty-nine (78%) patients with a STEMI were immediately referred to the catheterisation laboratory and 11 (22%) STEMI patients underwent a CT scan prior to emergency angiography; in no case was PCI deferred on the basis of the CT findings. The dominant indication for CT of the head was collapse, reported by 10 patients and resulting in a visible traumatic head injury in 7 patients. In none of the patients was intracranial haemorrhage detected. However, there was a delay between presentation to the ED and arrival at the catheterisation laboratory in patients who underwent CT of the head (mean 63 ± 25 min) before emergency PCI compared to patients without a CT scan (mean 37 ± 21 min)., Conclusion: CT of the head did not result in a diagnosis of intracranial haemorrhage or deferral of PCI but did delay PCI treatment for STEMI in patients presenting with OHCA., (© 2023. The Author(s).)

Published
2024
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131. Identification of a gene network driving the attenuated response to lipopolysaccharide of monocytes from hypertensive coronary artery disease patients.

Author

Lu C, Donners MMPC, de Baaij JBJ, Jin H, Otten JJT, Manca M, van Zonneveld AJ, Jukema JW, Kraaijeveld A, Kuiper J, Pasterkamp G, Mees B, Sluimer JC, Cavill R, Karel JMH, Goossens P, and Biessen EAL

Subjects
Humans, Monocytes metabolism, Gene Regulatory Networks, Lipopolysaccharides pharmacology, Arteries metabolism, Serine metabolism, Threonine genetics, Protein Serine-Threonine Kinases metabolism, Kruppel-Like Transcription Factors genetics, Coronary Artery Disease metabolism, Hypertension genetics
Abstract

Introduction: The impact of cardiovascular disease (CVD) risk factors, encompassing various biological determinants and unhealthy lifestyles, on the functional dynamics of circulating monocytes-a pivotal cell type in CVD pathophysiology remains elusive. In this study, we aimed to elucidate the influence of CVD risk factors on monocyte transcriptional responses to an infectious stimulus., Methods: We conducted a comparative analysis of monocyte gene expression profiles from the CTMM - CIRCULATING CELLS Cohort of coronary artery disease (CAD) patients, at baseline and after lipopolysaccharide (LPS) stimulation. Gene co-expression analysis was used to identify gene modules and their correlations with CVD risk factors, while pivotal transcription factors controlling the hub genes in these modules were identified by regulatory network analyses. The identified gene module was subjected to a drug repurposing screen, utilizing the LINCS L1000 database., Results: Monocyte responsiveness to LPS showed a highly significant, negative correlation with blood pressure levels (ρ< -0.4; P<10 -80 ). We identified a ZNF12/ZBTB43-driven gene module closely linked to diastolic blood pressure, suggesting that monocyte responses to infectious stimuli, such as LPS, are attenuated in CAD patients with elevated diastolic blood pressure. This attenuation appears associated with a dampening of the LPS-induced suppression of oxidative phosphorylation. Finally, we identified the serine-threonine inhibitor MW-STK33-97 as a drug candidate capable of reversing this aberrant LPS response., Conclusions: Monocyte responses to infectious stimuli may be hampered in CAD patients with high diastolic blood pressure and this attenuated inflammatory response may be reversed by the serine-threonine inhibitor MW-STK33-97. Whether the identified gene module is a mere indicator of, or causal factor in diastolic blood pressure and the associated dampened LPS responses remains to be determined., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Donners, de Baaij, Jin, Otten, Manca, van Zonneveld, Jukema, Kraaijeveld, Kuiper, Pasterkamp, Mees, Sluimer, Cavill, Karel, Goossens and Biessen.)

Published
2024
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132. SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion.

Author

De Luca G, Algowhary M, Uguz B, Oliveira DC, Ganyukov V, Zimbakov Z, Cercek M, Okkels Jensen L, Loh PH, Calmac L, Roura I Ferrer G, Quadros A, Milewski M, Scotto Di Uccio F, von Birgelen C, Versaci F, Ten Berg J, Casella G, Wong Sung Lung A, Kala P, Díez Gil JL, Carrillo X, Dirksen M, Becerra-Munoz VM, Kang-Yin Lee M, Juzar DA, de Moura Joaquim R, De Simone C, Milicic D, Davlouros P, Bakraceski N, Zilio F, Donazzan L, Kraaijeveld A, Galasso G, Arpad L, Marinucci L, Guiducci V, Menichelli M, Scoccia A, Yamac AH, Ugur Mert K, Flores Rios X, Kovarnik T, Kidawa M, Moreu J, Flavien V, Fabris E, Lozano Martínez-Luengas I, Boccalatte M, Bosa Ojeda F, Arellano-Serrano C, Caiazzo G, Cirrincione G, Kao HL, Sanchis Forés J, Vignali L, Pereira H, Manzo-Silbermann S, Ordoñez S, Arat Özkan A, Scheller B, Lehtola H, Teles R, Mantis C, Antti Y, Brum Silveira JA, Bessonov I, Zoni R, Savonitto S, Kochiadakis G, Alexopoulos D, Uribe CE, Kanakakis J, Faurie B, Gabrielli G, Gutierrez Barrios A, Bachini JP, Rocha A, Tam FC, Rodriguez A, Lukito AA, Bellemain-Appaix A, Pessah G, Cortese G, Parodi G, Burgadha MA, Kedhi E, Lamelas P, Suryapranata H, Nardin M, and Verdoia M

Abstract

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older ( P = .002), less often active smokers ( P = .002), and hypercholesterolemic ( P = .006), they presented more often later than 12 h ( P = .037), more often to the hub and were more often in cardiogenic shock ( P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow ( P = .029) and more thrombectomy ( P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2023
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133. Author Correction: The power of genetic diversity in genome-wide association studies of lipids.

Author

Graham SE, Clarke SL, Wu KH, Kanoni S, Zajac GJM, Ramdas S, Surakka I, Ntalla I, Vedantam S, Winkler TW, Locke AE, Marouli E, Hwang MY, Han S, Narita A, Choudhury A, Bentley AR, Ekoru K, Verma A, Trivedi B, Martin HC, Hunt KA, Hui Q, Klarin D, Zhu X, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Ruotsalainen SE, Havulinna AS, Veturi Y, Feng Q, Rosenthal EA, Lingren T, Pacheco JA, Pendergrass SA, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Hindy G, Rasheed A, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Willemsen G, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Yao J, Manichaikul A, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Sidore C, Fiorillo E, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Thuesen BH, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Feitosa MF, Wojczynski MK, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Kember RL, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Leonard HL, Marten J, Schmidt B, Arendt M, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Ahmed M, Jackson AU, Yousri NA, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Chai X, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Hung YJ, Chen S, Liu F, Yang J, Kentistou KA, Gorski M, Brumat M, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Xue C, Zhang J, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, Lee J, van der Laan SW, Chitrala KN, Weiss S, Zimmermann ME, Lee JY, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hildalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Schwander K, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Highland HM, Young KL, Kawaguchi T, Thiery J, Bis JC, Nadkarni GN, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, Bhatti KF, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Chen YE, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Kato N, Schulze MB, Girotto G, Jung B, Böger CA, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Yajnik CS, Mercader JM, Tusié-Luna T, Aguilar-Salinas CA, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Lu F, Qu J, Hishigaki H, Lin X, März W, Parra EJ, Cruz M, Gudnason V, Tardif JC, Lettre G, 't Hart LM, Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Psaty BM, Brandslund I, Pramstaller PP, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Cucca F, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Justice AE, Baras A, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Thorsteinsdottir U, Stefansson K, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Rotimi CN, Hazelhurst S, Ramsay M, Trembath RC, van Heel DA, Tamiya G, Yamamoto M, Kim BJ, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Natarajan P, Peloso GM, Brown CD, Morris AP, Assimes TL, Deloukas P, Sun YV, and Willer CJ

Published
2023
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134. Complications following transcatheter edge-to-edge mitral valve repair: Personal experience and review of the literature.

Author

Maj D, Jasińska-Gniadzik K, Kopiec T, Wieteska M, Gąsecka A, Rdzanek A, Kraaijeveld AO, Pujdak K, Grabowski M, and Pietrasik A

Subjects
Humans, Mitral Valve surgery, Surgical Instruments, Cardiac Catheterization methods, Treatment Outcome, Mitral Valve Insufficiency surgery, Heart Valve Prosthesis Implantation methods, Cardiac Surgical Procedures methods
Abstract

Mitral valve dysfunction affects around 2% of the population and its incidence is still increasing, making it the second most common valvular heart disease, after aortic stenosis. Depending on the etiology of the disease, it can be classified into primary or secondary mitral regurgitation. The first line of treatment is optimal medical therapy. If ineffective, mitral valve intervention can be considered. For patients disqualified from surgical treatment, transcatheter edge-to-edge repair with the use of MitraClip may be considered. Over 100,000 MitraClip procedures have been performed which makes this the most established transcatheter technique for the treatment of severe mitral regurgitation. The aim of this review is to discuss the technical details of the MitraClip procedure, clinical evidence regarding the efficacy of MitraClip, complications related to the clip implantation alongside with acute complications based on the currently available evidence and clinical experience.

Published
2023
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135. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Author

Kanoni S, Graham SE, Wang Y, Surakka I, Ramdas S, Zhu X, Clarke SL, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Yousri NA, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Hwu CM, Hung YJ, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw E, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Vazquez-Moreno M, Feitosa MF, Wojczynski MK, Wang Z, Preuss MH, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Tsao NL, Verma A, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Frank M, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Bayyana S, Stringham HM, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Nardone GG, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Liang J, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Mercader JM, Costanzo MC, Jang D, Burtt NP, Villalpando CG, Orozco L, Fornage M, Tai E, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Qu J, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, Hart LM', Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Chuang LM, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, Willemsen AHM, Cupples L, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen Y, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson PWF, Frayling TM, Hirschhorn JN, Kathiresan S, Mohlke KL, Sun YV, Morris AP, Boehnke M, Brown CD, Natarajan P, Deloukas P, Willer CJ, Assimes TL, and Peloso GM

Subjects
Humans, Sex Characteristics, Phenotype, Lipids genetics, Polymorphism, Single Nucleotide, Genetic Pleiotropy, Genome-Wide Association Study, Genetic Predisposition to Disease
Abstract

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery., Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism., Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk., (© 2022. The Author(s).)

Published
2022
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136. A saturated map of common genetic variants associated with human height.

Author

Yengo L, Vedantam S, Marouli E, Sidorenko J, Bartell E, Sakaue S, Graff M, Eliasen AU, Jiang Y, Raghavan S, Miao J, Arias JD, Graham SE, Mukamel RE, Spracklen CN, Yin X, Chen SH, Ferreira T, Highland HH, Ji Y, Karaderi T, Lin K, Lüll K, Malden DE, Medina-Gomez C, Machado M, Moore A, Rüeger S, Sim X, Vrieze S, Ahluwalia TS, Akiyama M, Allison MA, Alvarez M, Andersen MK, Ani A, Appadurai V, Arbeeva L, Bhaskar S, Bielak LF, Bollepalli S, Bonnycastle LL, Bork-Jensen J, Bradfield JP, Bradford Y, Braund PS, Brody JA, Burgdorf KS, Cade BE, Cai H, Cai Q, Campbell A, Cañadas-Garre M, Catamo E, Chai JF, Chai X, Chang LC, Chang YC, Chen CH, Chesi A, Choi SH, Chung RH, Cocca M, Concas MP, Couture C, Cuellar-Partida G, Danning R, Daw EW, Degenhard F, Delgado GE, Delitala A, Demirkan A, Deng X, Devineni P, Dietl A, Dimitriou M, Dimitrov L, Dorajoo R, Ekici AB, Engmann JE, Fairhurst-Hunter Z, Farmaki AE, Faul JD, Fernandez-Lopez JC, Forer L, Francescatto M, Freitag-Wolf S, Fuchsberger C, Galesloot TE, Gao Y, Gao Z, Geller F, Giannakopoulou O, Giulianini F, Gjesing AP, Goel A, Gordon SD, Gorski M, Grove J, Guo X, Gustafsson S, Haessler J, Hansen TF, Havulinna AS, Haworth SJ, He J, Heard-Costa N, Hebbar P, Hindy G, Ho YA, Hofer E, Holliday E, Horn K, Hornsby WE, Hottenga JJ, Huang H, Huang J, Huerta-Chagoya A, Huffman JE, Hung YJ, Huo S, Hwang MY, Iha H, Ikeda DD, Isono M, Jackson AU, Jäger S, Jansen IE, Johansson I, Jonas JB, Jonsson A, Jørgensen T, Kalafati IP, Kanai M, Kanoni S, Kårhus LL, Kasturiratne A, Katsuya T, Kawaguchi T, Kember RL, Kentistou KA, Kim HN, Kim YJ, Kleber ME, Knol MJ, Kurbasic A, Lauzon M, Le P, Lea R, Lee JY, Leonard HL, Li SA, Li X, Li X, Liang J, Lin H, Lin SY, Liu J, Liu X, Lo KS, Long J, Lores-Motta L, Luan J, Lyssenko V, Lyytikäinen LP, Mahajan A, Mamakou V, Mangino M, Manichaikul A, Marten J, Mattheisen M, Mavarani L, McDaid AF, Meidtner K, Melendez TL, Mercader JM, Milaneschi Y, Miller JE, Millwood IY, Mishra PP, Mitchell RE, Møllehave LT, Morgan A, Mucha S, Munz M, Nakatochi M, Nelson CP, Nethander M, Nho CW, Nielsen AA, Nolte IM, Nongmaithem SS, Noordam R, Ntalla I, Nutile T, Pandit A, Christofidou P, Pärna K, Pauper M, Petersen ERB, Petersen LV, Pitkänen N, Polašek O, Poveda A, Preuss MH, Pyarajan S, Raffield LM, Rakugi H, Ramirez J, Rasheed A, Raven D, Rayner NW, Riveros C, Rohde R, Ruggiero D, Ruotsalainen SE, Ryan KA, Sabater-Lleal M, Saxena R, Scholz M, Sendamarai A, Shen B, Shi J, Shin JH, Sidore C, Sitlani CM, Slieker RC, Smit RAJ, Smith AV, Smith JA, Smyth LJ, Southam L, Steinthorsdottir V, Sun L, Takeuchi F, Tallapragada DSP, Taylor KD, Tayo BO, Tcheandjieu C, Terzikhan N, Tesolin P, Teumer A, Theusch E, Thompson DJ, Thorleifsson G, Timmers PRHJ, Trompet S, Turman C, Vaccargiu S, van der Laan SW, van der Most PJ, van Klinken JB, van Setten J, Verma SS, Verweij N, Veturi Y, Wang CA, Wang C, Wang L, Wang Z, Warren HR, Bin Wei W, Wickremasinghe AR, Wielscher M, Wiggins KL, Winsvold BS, Wong A, Wu Y, Wuttke M, Xia R, Xie T, Yamamoto K, Yang J, Yao J, Young H, Yousri NA, Yu L, Zeng L, Zhang W, Zhang X, Zhao JH, Zhao W, Zhou W, Zimmermann ME, Zoledziewska M, Adair LS, Adams HHH, Aguilar-Salinas CA, Al-Mulla F, Arnett DK, Asselbergs FW, Åsvold BO, Attia J, Banas B, Bandinelli S, Bennett DA, Bergler T, Bharadwaj D, Biino G, Bisgaard H, Boerwinkle E, Böger CA, Bønnelykke K, Boomsma DI, Børglum AD, Borja JB, Bouchard C, Bowden DW, Brandslund I, Brumpton B, Buring JE, Caulfield MJ, Chambers JC, Chandak GR, Chanock SJ, Chaturvedi N, Chen YI, Chen Z, Cheng CY, Christophersen IE, Ciullo M, Cole JW, Collins FS, Cooper RS, Cruz M, Cucca F, Cupples LA, Cutler MJ, Damrauer SM, Dantoft TM, de Borst GJ, de Groot LCPGM, De Jager PL, de Kleijn DPV, Janaka de Silva H, Dedoussis GV, den Hollander AI, Du S, Easton DF, Elders PJM, Eliassen AH, Ellinor PT, Elmståhl S, Erdmann J, Evans MK, Fatkin D, Feenstra B, Feitosa MF, Ferrucci L, Ford I, Fornage M, Franke A, Franks PW, Freedman BI, Gasparini P, Gieger C, Girotto G, Goddard ME, Golightly YM, Gonzalez-Villalpando C, Gordon-Larsen P, Grallert H, Grant SFA, Grarup N, Griffiths L, Gudnason V, Haiman C, Hakonarson H, Hansen T, Hartman CA, Hattersley AT, Hayward C, Heckbert SR, Heng CK, Hengstenberg C, Hewitt AW, Hishigaki H, Hoyng CB, Huang PL, Huang W, Hunt SC, Hveem K, Hyppönen E, Iacono WG, Ichihara S, Ikram MA, Isasi CR, Jackson RD, Jarvelin MR, Jin ZB, Jöckel KH, Joshi PK, Jousilahti P, Jukema JW, Kähönen M, Kamatani Y, Kang KD, Kaprio J, Kardia SLR, Karpe F, Kato N, Kee F, Kessler T, Khera AV, Khor CC, Kiemeney LALM, Kim BJ, Kim EK, Kim HL, Kirchhof P, Kivimaki M, Koh WP, Koistinen HA, Kolovou GD, Kooner JS, Kooperberg C, Köttgen A, Kovacs P, Kraaijeveld A, Kraft P, Krauss RM, Kumari M, Kutalik Z, Laakso M, Lange LA, Langenberg C, Launer LJ, Le Marchand L, Lee H, Lee NR, Lehtimäki T, Li H, Li L, Lieb W, Lin X, Lind L, Linneberg A, Liu CT, Liu J, Loeffler M, London B, Lubitz SA, Lye SJ, Mackey DA, Mägi R, Magnusson PKE, Marcus GM, Vidal PM, Martin NG, März W, Matsuda F, McGarrah RW, McGue M, McKnight AJ, Medland SE, Mellström D, Metspalu A, Mitchell BD, Mitchell P, Mook-Kanamori DO, Morris AD, Mucci LA, Munroe PB, Nalls MA, Nazarian S, Nelson AE, Neville MJ, Newton-Cheh C, Nielsen CS, Nöthen MM, Ohlsson C, Oldehinkel AJ, Orozco L, Pahkala K, Pajukanta P, Palmer CNA, Parra EJ, Pattaro C, Pedersen O, Pennell CE, Penninx BWJH, Perusse L, Peters A, Peyser PA, Porteous DJ, Posthuma D, Power C, Pramstaller PP, Province MA, Qi Q, Qu J, Rader DJ, Raitakari OT, Ralhan S, Rallidis LS, Rao DC, Redline S, Reilly DF, Reiner AP, Rhee SY, Ridker PM, Rienstra M, Ripatti S, Ritchie MD, Roden DM, Rosendaal FR, Rotter JI, Rudan I, Rutters F, Sabanayagam C, Saleheen D, Salomaa V, Samani NJ, Sanghera DK, Sattar N, Schmidt B, Schmidt H, Schmidt R, Schulze MB, Schunkert H, Scott LJ, Scott RJ, Sever P, Shiroma EJ, Shoemaker MB, Shu XO, Simonsick EM, Sims M, Singh JR, Singleton AB, Sinner MF, Smith JG, Snieder H, Spector TD, Stampfer MJ, Stark KJ, Strachan DP, 't Hart LM, Tabara Y, Tang H, Tardif JC, Thanaraj TA, Timpson NJ, Tönjes A, Tremblay A, Tuomi T, Tuomilehto J, Tusié-Luna MT, Uitterlinden AG, van Dam RM, van der Harst P, Van der Velde N, van Duijn CM, van Schoor NM, Vitart V, Völker U, Vollenweider P, Völzke H, Wacher-Rodarte NH, Walker M, Wang YX, Wareham NJ, Watanabe RM, Watkins H, Weir DR, Werge TM, Widen E, Wilkens LR, Willemsen G, Willett WC, Wilson JF, Wong TY, Woo JT, Wright AF, Wu JY, Xu H, Yajnik CS, Yokota M, Yuan JM, Zeggini E, Zemel BS, Zheng W, Zhu X, Zmuda JM, Zonderman AB, Zwart JA, Chasman DI, Cho YS, Heid IM, McCarthy MI, Ng MCY, O'Donnell CJ, Rivadeneira F, Thorsteinsdottir U, Sun YV, Tai ES, Boehnke M, Deloukas P, Justice AE, Lindgren CM, Loos RJF, Mohlke KL, North KE, Stefansson K, Walters RG, Winkler TW, Young KL, Loh PR, Yang J, Esko T, Assimes TL, Auton A, Abecasis GR, Willer CJ, Locke AE, Berndt SI, Lettre G, Frayling TM, Okada Y, Wood AR, Visscher PM, and Hirschhorn JN

Subjects
Humans, Gene Frequency genetics, Genome, Human genetics, Genome-Wide Association Study, Haplotypes genetics, Linkage Disequilibrium genetics, Europe ethnology, Sample Size, Phenotype, Body Height genetics, Polymorphism, Single Nucleotide genetics, Chromosome Mapping
Abstract

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries., (© 2022. The Author(s).)

Published
2022
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137. Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

Author

De Luca G, Nardin M, Algowhary M, Uguz B, Oliveira DC, Ganyukov V, Zimbakov Z, Cercek M, Okkels Jensen L, Loh PH, Calmac L, Roura Ferrer G, Quadros A, Milewski M, Scotto di Uccio F, von Birgelen C, Versaci F, Ten Berg J, Casella G, Wong Sung Lung A, Kala P, Díez Gil JL, Carrillo X, Dirksen M, Becerra-Munoz VM, Lee MK, Arifa Juzar D, de Moura Joaquim R, Paladino R, Milicic D, Davlouros P, Bakraceski N, Zilio F, Donazzan L, Kraaijeveld A, Galasso G, Lux A, Marinucci L, Guiducci V, Menichelli M, Scoccia A, Yamac AH, Ugur Mert K, Flores Rios X, Kovarnik T, Kidawa M, Moreu J, Flavien V, Fabris E, Martínez-Luengas IL, Boccalatte M, Bosa Ojeda F, Arellano-Serrano C, Caiazzo G, Cirrincione G, Kao HL, Sanchis Forés J, Vignali L, Pereira H, Manzo S, Ordoñez S, Özkan AA, Scheller B, Lehtola H, Teles R, Mantis C, Antti Y, Brum Silveira JA, Zoni R, Bessonov I, Savonitto S, Kochiadakis G, Alexopoulos D, Uribe CE, Kanakakis J, Faurie B, Gabrielli G, Gutierrez Barrios A, Bachini JP, Rocha A, Tam FC, Rodriguez A, Lukito AA, Saint-Joy V, Pessah G, Tuccillo A, Cortese G, Parodi G, Bouraghda MA, Kedhi E, Lamelas P, Suryapranata H, and Verdoia M

Subjects
Aged, Hospital Mortality, Humans, Pandemics, Registries, Retrospective Studies, SARS-CoV-2, Treatment Outcome, COVID-19 epidemiology, Percutaneous Coronary Intervention adverse effects, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive epidemiology, Pulmonary Disease, Chronic Obstructive therapy, ST Elevation Myocardial Infarction diagnosis, ST Elevation Myocardial Infarction epidemiology, ST Elevation Myocardial Infarction therapy
Abstract

Background: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study., Methods: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents., Results: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups., Conclusion: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity., Trial Registration Number: NCT04412655 (2nd June 2020)., (© 2022. The Author(s).)

Published
2022
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138. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

Author

Ramdas S, Judd J, Graham SE, Kanoni S, Wang Y, Surakka I, Wenz B, Clarke SL, Chesi A, Wells A, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Lee WJ, Hsiung CA, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Schönherr S, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Le P, Feitosa MF, Wojczynski MK, Hemerich D, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Noah TL, Verma A, Slieker RC, Lo KS, Zilhao NR, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Emmel C, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Sankareswaran A, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Morgan A, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, He KY, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Ida Chen YD, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Walker M, Scott LJ, Koistinen HA, Chandak GR, Mercader JM, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Lu F, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, T Hart LM, Elders PJM, Rader DJ, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney L, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, Willems van Dijk K, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Huey-Herng Sheu W, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ikram A, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Tuomilehto J, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen YE, Ho YL, Lynch JA, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Struan Grant, Natarajan P, Sun YV, Morris AP, Deloukas P, Peloso G, Assimes TL, Willer CJ, Zhu X, and Brown CD

Subjects
Chromatin genetics, Genomics, Humans, Lipids genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
Abstract

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology., Competing Interests: Declaration of interests G.C.-P. is currently an employee of 23andMe Inc. M.J.C. is the Chief Scientist for Genomics England, a UK Government company. B.M. Psaty serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. G. Thorleifsson, A.H., D.F.G., H. Holm, U.T., and K.S. are employees of deCODE/Amgen Inc. V.S. has received honoraria for consultations from Novo Nordisk and Sanofi and has an ongoing research collaboration with Bayer Ltd. M. McCarthy has served on advisory panels for Pfizer, NovoNordisk, and Zoe Global and has received honoraria from Merck, Pfizer, Novo Nordisk, and Eli Lilly and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. M. McCarthy and A. Mahajan are employees of Genentech and holders of Roche stock. M.S. receives funding from Pfizer Inc. for a project unrelated to this work. M.E.K. is employed by SYNLAB MVZ Mannheim GmbH. W.M. has received grants from Siemens Healthineers, grants and personal fees from Aegerion Pharmaceuticals, grants and personal fees from AMGEN, grants from Astrazeneca, grants and personal fees from Sanofi, grants and personal fees from Alexion Pharmaceuticals, grants and personal fees from BASF, grants and personal fees from Abbott Diagnostics, grants and personal fees from Numares AG, grants and personal fees from Berlin-Chemie, grants and personal fees from Akzea Therapeutics, grants from Bayer Vital GmbH , grants from bestbion dx GmbH, grants from Boehringer Ingelheim Pharma GmbH Co KG, grants from Immundiagnostik GmbH, grants from Merck Chemicals GmbH, grants from MSD Sharp and Dohme GmbH, grants from Novartis Pharma GmbH, grants from Olink Proteomics, and other from Synlab Holding Deutschland GmbH, all outside the submitted work. A.V.K. has served as a consultant to Sanofi, Medicines Company, Maze Pharmaceuticals, Navitor Pharmaceuticals, Verve Therapeutics, Amgen, and Color Genomics; received speaking fees from Illumina and the Novartis Institute for Biomedical Research; received sponsored research agreements from the Novartis Institute for Biomedical Research and IBM Research, and reports a patent related to a genetic risk predictor (20190017119). S. Kathiresan is an employee of Verve Therapeutics and holds equity in Verve Therapeutics, Maze Therapeutics, Catabasis, and San Therapeutics. He is a member of the scientific advisory boards for Regeneron Genetics Center and Corvidia Therapeutics; he has served as a consultant for Acceleron, Eli Lilly, Novartis, Merck, Novo Nordisk, Novo Ventures, Ionis, Alnylam, Aegerion, Haug Partners, Noble Insights, Leerink Partners, Bayer Healthcare, Illumina, Color Genomics, MedGenome, Quest, and Medscape; and he reports patents related to a method of identifying and treating a person having a predisposition to or afflicted with cardiometabolic disease (20180010185) and a genetics risk predictor (20190017119). D.K. accepts consulting fees from Regeneron Pharmaceuticals. D.O.M.-K. is a part-time clinical research consultant for Metabolon, Inc. D. Saleheen has received support from the British Heart Foundation, Pfizer, Regeneron, Genentech, and Eli Lilly pharmaceuticals. P.N. reports investigator-initated grants from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis, personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Novartis, Roche / Genentech, is a co-founder of TenSixteen Bio, is a scientific advisory board member of Esperion Therapeutics, geneXwell, and TenSixteen Bio, and spousal employment at Vertex, all unrelated to the present work. The spouse of C.J.W. is employed by Regeneron., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2022
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139. Clinically Significant Incidental Findings on CT Imaging During TAVI Work-up: A Systematic Review and Meta-Analysis.

Author

Ko K, Zwetsloot PP, Voskuil M, Stella P, Leiner T, and Kraaijeveld A

Subjects
Aged, Aged, 80 and over, Aortic Valve diagnostic imaging, Aortic Valve surgery, Humans, Incidental Findings, Retrospective Studies, Risk Factors, Tomography, X-Ray Computed, Treatment Outcome, Aortic Valve Stenosis diagnosis, Aortic Valve Stenosis surgery, Transcatheter Aortic Valve Replacement adverse effects, Transcatheter Aortic Valve Replacement methods
Abstract

Background: The transcatheter aortic valve implantation (TAVI) population is mostly elderly and frail. Clinically significant incidental findings (SIFs) are commonly encountered in the work-up of TAVI patients. This is a systematic review of current literature on the occurrence of SIFs on computed tomography (CT) imaging preceding TAVI and their association with mortality, delayed planning, and procedure cancellation., Methods: A systematic search on Medline, Embase, and Cochrane resulted in 19 retrospective studies (published from 2010-2020) reporting SIFs in the work-up for TAVI. A total of 6358 individuals from 19 studies were analyzed, with mean age of 80 years and sex equally divided. A random-effects meta-analysis was performed, with weighting based on study size., Results: Pooled prevalence of patients with SIF was 22.2% (95% confidence interval [CI], 17.8-26.6) and most findings (48.3%) were found in the lungs. Pooled prevalence of new malignancies was 3.4% (95% CI, 2.5-4.4). Higher mortality in patients with SIF was only found in studies with a follow-up period >4 years (hazard ratio, 1.5-1.7). TAVI was more frequently cancelled in patients with SIF vs those with no SIF (ranges, 10.1%-47.1% vs 5.2%-37.0%, respectively). SIF did not delay time to TAVI (ranges, 6-91 days in SIF patients vs 4-81 days in non-SIF patients)., Conclusion: SIFs are common in patients screened for TAVI. SIF is associated with a higher risk of TAVI cancellation and with increased mortality risk over the long term, which should be taken into consideration in decision making. These findings may help inform patients and aid patient selection.

Published
2022
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140. The power of genetic diversity in genome-wide association studies of lipids.

Author

Graham SE, Clarke SL, Wu KH, Kanoni S, Zajac GJM, Ramdas S, Surakka I, Ntalla I, Vedantam S, Winkler TW, Locke AE, Marouli E, Hwang MY, Han S, Narita A, Choudhury A, Bentley AR, Ekoru K, Verma A, Trivedi B, Martin HC, Hunt KA, Hui Q, Klarin D, Zhu X, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Ruotsalainen SE, Havulinna AS, Veturi Y, Feng Q, Rosenthal EA, Lingren T, Pacheco JA, Pendergrass SA, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Hindy G, Rasheed A, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Willemsen G, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Yao J, Manichaikul A, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Sidore C, Fiorillo E, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Thuesen BH, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Feitosa MF, Wojczynski MK, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Kember RL, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Leonard HL, Marten J, Schmidt B, Arendt M, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Ahmed M, Jackson AU, Yousri NA, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Chai X, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Hung YJ, Chen S, Liu F, Yang J, Kentistou KA, Gorski M, Brumat M, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Xue C, Zhang J, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, Lee J, van der Laan SW, Chitrala KN, Weiss S, Zimmermann ME, Lee JY, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hildalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Schwander K, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Highland HM, Young KL, Kawaguchi T, Thiery J, Bis JC, Nadkarni GN, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, Bhatti KF, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Chen YE, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Kato N, Schulze MB, Girotto G, Jung B, Böger CA, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Yajnik CS, Mercader JM, Tusié-Luna T, Aguilar-Salinas CA, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Lu F, Qu J, Hishigaki H, Lin X, März W, Parra EJ, Cruz M, Gudnason V, Tardif JC, Lettre G, 't Hart LM, Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Psaty BM, Brandslund I, Pramstaller PP, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Cucca F, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Justice AE, Baras A, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Thorsteinsdottir U, Stefansson K, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Rotimi CN, Hazelhurst S, Ramsay M, Trembath RC, van Heel DA, Tamiya G, Yamamoto M, Kim BJ, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Natarajan P, Peloso GM, Brown CD, Morris AP, Assimes TL, Deloukas P, Sun YV, and Willer CJ

Subjects
Genetic Predisposition to Disease genetics, Humans, Linkage Disequilibrium, Multifactorial Inheritance, Polymorphism, Single Nucleotide genetics, Population Groups, Cardiovascular Diseases genetics, Genome-Wide Association Study methods
Abstract

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2021
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141. Renin-angiotensin system inhibitors and mortality among diabetic patients with STEMI undergoing mechanical reperfusion during the COVID-19 pandemic.

Author

De Luca G, Nardin M, Algowhary M, Uguz B, Oliveira DC, Ganyukov V, Zimbakov Z, Cercek M, Jensen LO, Loh PH, Calmac L, Roura Ferrer G, Quadros A, Milewski M, Scotto di Uccio F, von Birgelen C, Versaci F, Ten Berg J, Casella G, Lung AWS, Kala P, Díez Gil JL, Carrillo X, Dirksen M, Becerra-Munoz VM, Lee MK, Juzar DA, de Moura Joaquim R, Paladino R, Milicic D, Davlouros P, Bakraceski N, Zilio F, Donazzan L, Kraaijeveld A, Galasso G, Lux A, Marinucci L, Guiducci V, Menichelli M, Scoccia A, Yamac AH, Mert KU, Flores Rios X, Kovarnik T, Kidawa M, Moreu J, Flavien V, Fabris E, Martínez-Luengas IL, Boccalatte M, Bosa Ojeda F, Arellano-Serrano C, Caiazzo G, Cirrincione G, Kao HL, Sanchis Forés J, Vignali L, Pereira H, Manzo S, Ordoñez S, Arat Özkan A, Scheller B, Lehtola H, Teles R, Mantis C, Antti Y, Brum Silveira JA, Zoni R, Bessonov I, Savonitto S, Kochiadakis G, Alexopulos D, Uribe CE, Kanakakis J, Faurie B, Gabrielli G, Gutierrez Barrios A, Bachini JP, Rocha A, Tam FC, Rodriguez A, Lukito AA, Saint-Joy V, Pessah G, Tuccillo A, Cortese G, Parodi G, Bouraghda MA, Kedhi E, Lamelas P, Suryapranata H, and Verdoia M

Abstract

Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment., Methods: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients., Results: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p  = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p  < 0.0001), consistently both in 2019 and in 2010., Conclusions: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection., Trial Registration Number: NCT04412655., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Masson SAS.)

Published
2021
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142. Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry.

Author

De Luca G, Debel N, Cercek M, Jensen LO, Vavlukis M, Calmac L, Johnson T, Ferrer GR, Ganyukov V, Wojakowski W, Kinnaird T, von Birgelen C, Cottin Y, IJsselmuiden A, Tuccillo B, Versaci F, Royaards KJ, Berg JT, Laine M, Dirksen M, Siviglia M, Casella G, Kala P, Díez Gil JL, Banning A, Becerra V, De Simone C, Santucci A, Carrillo X, Scoccia A, Amoroso G, Van't Hof AW, Kovarnik T, Tsigkas G, Mehilli J, Gabrielli G, Rios XF, Bakraceski N, Levesque S, Cirrincione G, Guiducci V, Kidawa M, Spedicato L, Marinucci L, Ludman P, Zilio F, Galasso G, Fabris E, Menichelli M, Garcia-Touchard A, Manzo S, Caiazzo G, Moreu J, Forés JS, Donazzan L, Vignali L, Teles R, Benit E, Agostoni P, Ojeda FB, Lehtola H, Camacho-Freiere S, Kraaijeveld A, Antti Y, Boccalatte M, Deharo P, Martínez-Luengas IL, Scheller B, Varytimiadi E, Moreno R, Uccello G, Faurie B, Gutierrez Barrios A, Milewski M, Bruwiere E, Smits P, Wilbert B, Di Uccio FS, Parodi G, Kedhi E, and Verdoia M

Subjects
Humans, Registries, Reperfusion, Retrospective Studies, SARS-CoV-2, Treatment Outcome, COVID-19, Percutaneous Coronary Intervention adverse effects, ST Elevation Myocardial Infarction diagnosis, ST Elevation Myocardial Infarction surgery
Abstract

Background and Aims: SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI)., Methods: We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure., Results: Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors., Conclusions: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Published
2021
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143. Impact of renin-angiotensin system inhibitors on mortality during the COVID Pandemic among STEMI patients undergoing mechanical reperfusion: Insight from an international STEMI registry.

Author

De Luca G, Cercek M, Okkels Jensen L, Bushljetikj O, Calmac L, Johnson T, Gracida Blancas M, Ganyukov V, Wojakowski W, von Birgelen C, IJsselmuiden A, Tuccillo B, Versaci F, Ten Berg J, Laine M, Berkout T, Casella G, Kala P, López Ledesma B, Becerra V, Padalino R, Santucci A, Carrillo X, Scoccia A, Amoroso G, Lux A, Kovarnik T, Davlouros P, Gabrielli G, Flores Rios X, Bakraceski N, Levesque S, Guiducci V, Kidawa M, Marinucci L, Zilio F, Galasso G, Fabris E, Menichelli M, Manzo S, Caiazzo G, Moreu J, Sanchis Forés J, Donazzan L, Vignali L, Teles R, Agostoni P, Bosa Ojeda F, Lehtola H, Camacho-Freiere S, Kraaijeveld A, Antti Y, Visconti G, Lozano Martínez-Luengas I, Scheller B, Alexopulos D, Moreno R, Kedhi E, Uccello G, Faurie B, Gutierrez Barrios A, Scotto Di Uccio F, Wilbert B, Cortese G, Dirksen MT, Parodi G, and Verdoia M

Subjects
Aged, COVID-19 therapy, Female, Hospitalization, Humans, Male, Middle Aged, Pandemics, Percutaneous Coronary Intervention, Prognosis, Registries, Renin-Angiotensin System, ST Elevation Myocardial Infarction therapy, COVID-19 Drug Treatment, Antihypertensive Agents therapeutic use, COVID-19 mortality, Myocardial Reperfusion, SARS-CoV-2, ST Elevation Myocardial Infarction mortality
Abstract

Background: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study., Methods: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission., Results: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51-0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33-0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084-0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect., Conclusions: This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Published
2021
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144. Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression.

Author

de Bruin RG, Shiue L, Prins J, de Boer HC, Singh A, Fagg WS, van Gils JM, Duijs JM, Katzman S, Kraaijeveld AO, Böhringer S, Leung WY, Kielbasa SM, Donahue JP, van der Zande PH, Sijbom R, van Alem CM, Bot I, van Kooten C, Jukema JW, Van Esch H, Rabelink TJ, Kazan H, Biessen EA, Ares M Jr, van Zonneveld AJ, and van der Veer EP

Subjects
Animals, Atherosclerosis metabolism, Atherosclerosis pathology, Cell Differentiation, Foam Cells cytology, Foam Cells metabolism, Gene Expression Regulation, Humans, Macrophages cytology, Macrophages metabolism, Mice, Models, Biological, Models, Genetic, Monocytes cytology, Monocytes metabolism, RNA, Messenger metabolism, RNA, Messenger physiology, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Macrophages physiology, Monocytes physiology, RNA Splicing, RNA-Binding Proteins physiology
Abstract

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.

Published
2016
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145. CCL3 (MIP-1 alpha) levels are elevated during acute coronary syndromes and show strong prognostic power for future ischemic events.

Author

de Jager SC, Kraaijeveld AO, Grauss RW, de Jager W, Liem SS, van der Hoeven BL, Prakken BJ, Putter H, van Berkel TJ, Atsma DE, Schalij MJ, Jukema JW, and Biessen EA

Subjects
Acute Coronary Syndrome blood, Aged, Angina, Unstable blood, Animals, Chemokine CCL3 blood, Cohort Studies, Disease Models, Animal, Female, Forecasting, Humans, Male, Mice, Middle Aged, Myocardial Infarction blood, Myocardial Ischemia blood, Pilot Projects, Prognosis, Prospective Studies, Acute Coronary Syndrome diagnosis, Chemokine CCL3 biosynthesis, Myocardial Ischemia diagnosis
Abstract

As chemokines are considered instrumental in thrombotic plaque rupture and erosion as well as in ischemia-reperfusion injury processes, we aimed to identify previously unknown chemokines associated with acute coronary syndromes. Plasma of 44 patients with acute myocardial infarction (AMI) and 22 controls were profiled for a panel of chemokines by multiplex analysis. Levels of CCL3 were prospectively verified in 54 patients with unstable angina pectoris (UAP). An AMI mouse model was used to assess the relationship between differentially expressed chemokines and myocardial ischemia. CCL3 levels were significantly elevated in AMI vs. controls (P=0.02) albeit, that adjustment for confounding factors attenuated this association. In support of a direct association with cardiac ischemia CCL3 levels were also seen to be elevated in patients with UAP at baseline and significantly down-regulated after 180 days (P<0.001). Importantly, baseline upper quartile levels were strongly correlated with future acute coronary syndromes (Likelihood Ratio 11.5; P<0.01). Furthermore circulating levels of CCL3 were significantly enhanced after AMI in mice (P=0.02), while CCR5(+) T-cell numbers were increased as well, suggestive of CCL3 driven T-cell homing towards the ischemic area. CCL3 levels are elevated during ACS and released upon ischemia. Since CCL3 specifically predicts future cardiovascular events, it may serve as a predictive biomarker.

Published
2008
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