Abstract
Purpose: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. Materials and methods: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality. Results: 49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33–1.39];1.47 [1.43–1.50], respectively). Conclusions: Patients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes.
Original language | English |
---|---|
Article number | 154318 |
Number of pages | 13 |
Journal | Journal of Critical Care |
Volume | 77 |
DOIs | |
Publication status | Published - Oct 2023 |
Externally published | Yes |
Keywords
- Complications
- COVID-19
- Major adverse cardiovascular events (MACE)
- Mortality
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In: Journal of Critical Care, Vol. 77, 154318, 10.2023.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol
T2 - A prospective, multinational, observational study
AU - Reyes, Luis Felipe
AU - Garcia-Gallo, Esteban
AU - Murthy, Srinivas
AU - Fuentes, Yuli V.
AU - Serrano, Cristian C.
AU - Ibáñez-Prada, Elsa D.
AU - Lee, James
AU - Rojek, Amanda
AU - Citarella, Barbara Wanjiru
AU - Gonçalves, Bronner P.
AU - Dunning, Jake
AU - Rätsep, Indrek
AU - Viñan-Garces, Andre Emilio
AU - Kartsonaki, Christiana
AU - Rello, Jordi
AU - Martin-Loeches, Ignacio
AU - Shankar-Hari, Manu
AU - Olliaro, Piero L.
AU - Merson, Laura
AU - Abbas, Ali
AU - Abdukahil, Sheryl Ann
AU - Abdulkadir, Nurul Najmee
AU - Abe, Ryuzo
AU - Abebrese, Franklina Korkor
AU - Abel, Laurent
AU - Abrous, Amal
AU - Absil, Lara
AU - Acharya, Subhash
AU - Acker, Andrew
AU - Adewhajah, Francisca
AU - Adrião, Diana
AU - Al Ageel, Saleh
AU - Ahmed, Shakeel
AU - Ainscough, Kate
AU - Aisa, Tharwat
AU - Akimoto, Takako
AU - Akmal, Ernita
AU - Alalqam, Razi
AU - Al-Dabbous, Tala
AU - Alegesan, Senthilkumar
AU - Alex, Beatrice
AU - Alexandre, Kévin
AU - Al-Fares, Abdulrahman
AU - Alfoudri, Huda
AU - Ali, Imran
AU - Alidjnou, Kazali Enagnon
AU - Aliudin, Jeffrey
AU - Alkhafajee, Qabas
AU - Allavena, Clotilde
AU - Allou, Nathalie
AU - Altaf, Aneela
AU - Alves, João
AU - Alves, João Melo
AU - Alves, Rita
AU - Amaral, Maria
AU - Amira, Nur
AU - Ampaw, Phoebe
AU - Andini, Roberto
AU - Andréjak, Claire
AU - Andréjak, Claire
AU - Angheben, Andrea
AU - Angoulvant, François
AU - Ankrah, Sophia
AU - Ansart, Séverine
AU - Anthonidass, Sivanesen
AU - Antonelli, Massimo
AU - Apriyana, Ardiyan
AU - Arabi, Yaseen
AU - Aragao, Irene
AU - Arancibia, Francisco
AU - Araujo, Carolline
AU - Arcadipane, Antonio
AU - Archambault, Patrick
AU - Arenz, Lukas
AU - Arlet, Jean Benoît
AU - Arnold-Day, Christel
AU - Arora, Lovkesh
AU - Arora, Rakesh
AU - Artaud-Macari, Elise
AU - Aryal, Diptesh
AU - Asensio, Angel
AU - Ashraf, Muhammad
AU - Ashraf, Sheharyar
AU - Asif, Namra
AU - Asim, Mohammad
AU - Assie, Jean Baptiste
AU - Asyraf, Amirul
AU - Atique, Anika
AU - Attanyake, A. M.Udara Lakshan
AU - Auchabie, Johann
AU - Auger, Christelle Chantalat
AU - Aumaitre, Hugues
AU - Auvet, Adrien
AU - Azemar, Laurène
AU - Azoulay, Cecile
AU - Bach, Benjamin
AU - Bachelet, Delphine
AU - Badr, Claudine
AU - Baig, Nadia
AU - Baillie, J. Kenneth
AU - Bak, Erica
AU - Bakakos, Agamemnon
AU - Bakar, Nazreen Abu
AU - Bal, Andriy
AU - Balakrishnan, Mohanaprasanth
AU - Balan, Valeria
AU - Balazote, Pablo Serrano
AU - Bandoh, Irene
AU - Banheiro, Bruno Sarmento
AU - Bani-Sadr, Firouzé
AU - Barbalho, Renata
AU - Barclay, Wendy S.
AU - Barnett, Saef Umar
AU - Barnikel, Michaela
AU - Barrasa, Helena
AU - Barrelet, Audrey
AU - Barrigoto, Cleide
AU - Barrio, Noelia García
AU - Bartoli, Marie
AU - Baruch, Joaquín
AU - Bashir, Mustehan
AU - Basmaci, Romain
AU - Basri, Muhammad Fadhli Hassin
AU - Bassi, Gianluigi Li
AU - Battaglini, Denise
AU - Bauer, Jules
AU - Beane, Abigail
AU - Bedossa, Alexandra
AU - Bedu-Addo, Ama Kwakyewaa
AU - Bee, Ker Hong
AU - Begum, Husna
AU - Behilill, Sylvie
AU - Beishuizen, Albertus
AU - Bekken, Gry Kloumann
AU - Beljantsev, Aleksandr
AU - Bellemare, David
AU - Beltrame, Anna
AU - Beltrão, Beatriz Amorim
AU - Beluze, Marine
AU - Benech, Nicolas
AU - Benjiman, Lionel Eric
AU - Benkerrou, Dehbia
AU - Bennett, Suzanne
AU - Benny, Binny
AU - Bento, Luís
AU - Berdal, Jan Erik
AU - Van Den Berge, Marcel
AU - Bergeaud, Delphine
AU - Bergin, Hazel
AU - Bermejo, Carlos Lumbreras
AU - Bermúdez, Juan Luis Cruz
AU - Bertoli, Giulia
AU - Bertolino, Lorenzo
AU - Bessis, Simon
AU - Bevilcaqua, Sybille
AU - Bezulier, Karine
AU - Bhatt, Amar
AU - Bhavsar, Krishna
AU - Bianco, Claudia
AU - Bidin, Farah Nadiah
AU - Le Bihan, Clément
AU - Bisoffi, Zeno
AU - Bissuel, François
AU - Biston, Patrick
AU - Bitker, Laurent
AU - Blanco-Schweizer, Pablo
AU - Blier, Catherine
AU - Bloos, Frank
AU - Blot, Mathieu
AU - Blumberg, Lucille
AU - Boccia, Filomena
AU - Bodenes, Laetitia
AU - Bogaert, Debby
AU - Boivin, Anne Hẽlène
AU - Bolaños, Isabela
AU - Bolze, Pierre Adrien
AU - Bompart, François
AU - Bonney, Joe
AU - Borges, Diogo
AU - Borie, Raphaël
AU - Botelho-Nevers, Elisabeth
AU - Bouadma, Lila
AU - Bouchaud, Olivier
AU - Bouchez, Sabelline
AU - Bouhmani, Dounia
AU - Bouhour, Damien
AU - Bouiller, Kévin
AU - Bouillet, Laurence
AU - Bouisse, Camile
AU - Boureau, Anne Sophie
AU - Bourke, John
AU - Bouscambert, Maude
AU - Bousquet, Aurore
AU - Bouziotis, Jason
AU - Boxma, Bianca
AU - Boyer-Besseyre, Marielle
AU - Boylan, Maria
AU - Bozza, Fernando Augusto
AU - Braconnier, Axelle
AU - Braga, Cynthia
AU - Brazzi, Luca
AU - Breen, Dorothy
AU - Breen, Patrick
AU - Brewster, David
AU - Brickell, Kathy
AU - Brien, Fionnuala O.
AU - Le Bris, Cyril
AU - De Brito, Carlos Alexandre Antunes
AU - Browne, Shaunagh
AU - Brusse-Keizer, Marjolein
AU - Buchtele, Nina
AU - Buisson, Marielle
AU - Burhan, Erlina
AU - Burrell, Aidan
AU - Bustos, Ingrid G.
AU - Cabie, André
AU - Cabral, Susana
AU - Cabrita, Joana Alves
AU - Caceres, Eder
AU - Cadoz, Cyril
AU - Callaghan, Annmarie O.
AU - De La Calle, Guillermo Maestro
AU - Calligy, Kate
AU - Calvache, Jose Andres
AU - Camões, João
AU - Campana, Valentine
AU - Campbell, Paul
AU - Canepa, Cecilia
AU - Cantero, Mireia
AU - Caraux-Paz, Pauline
AU - Cardellino, Chiara Simona
AU - Cardoso, Filipa
AU - Cardoso, Filipe
AU - Cardoso, Nelson
AU - Cardoso, Sofia
AU - Carelli, Simone
AU - Carlier, Nicolas
AU - Carmoi, Thierry
AU - Carney, Gayle
AU - Fraser, John F.
AU - McArthur, Colin
AU - Neto, Ary Serpa
AU - Nichol, Alistair D.
AU - Parke, Rachael
AU - Peake, Sandra L.
AU - Reid, Liadain
AU - Trapani, Tony
AU - Udy, Andrew
AU - Webb, Steve
AU - Williams, Patricia J.
AU - The ISARIC Characterisation Group
N1 - Funding Information: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [ 215091/Z/18/Z , 222410/Z/21/Z , 225288/Z/22/Z and 220757/Z/20/Z ]; the Bill & Melinda Gates Foundation [ OPP1209135 ]; the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund ( 0009109 ); CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and the coordination in Canada by Sunnybrook Research Institute ; endorsement of the Irish Critical Care- Clinical Trials Group, co-ordination in Ireland by the Irish Critical Care- Clinical Trials Network at University College Dublin and funding by the Health Research Board of Ireland [ CTN-2014-12 ]; the COVID clinical management team, AIIMS , Rishikesh, India; the COVID-19 Clinical Management team, Manipal Hospital Whitefield , Bengaluru, India; Cambridge NIHR Biomedical Research Centre ; the dedication and hard work of the Groote Schuur Hospital Covid ICU Team and supported by the Groote Schuur nursing and University of Cape Town registrar bodies coordinated by the Division of Critical Care at the University of Cape Town ; the Liverpool School of Tropical Medicine and the University of Oxford ; the dedication and hard work of the Norwegian SARS-CoV-2 study team and the Research Council of Norway grant no 312780 , and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner; Imperial NIHR Biomedical Research Centre ; the Comprehensive Local Research Networks (CLRNs) of which PJMO is an NIHR Senior Investigator ( NIHR201385 ); Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme ( FP7/2007-2013 ) and EFPIA companies, in-kind contribution; Stiftungsfonds zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM; Italian Ministry of Health “Fondi Ricerca corrente–L1P6” to IRCCS Ospedale Sacro Cuore–Don Calabria; Australian Department of Health grant ( 3273191 ); Gender Equity Strategic Fund at University of Queensland , Artificial Intelligence for Pandemics ( A14PAN ) at University of Queensland , the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009 ), the Prince Charles Hospital Foundation, Australia; grants from Instituto de Salud Carlos III , Ministerio de Ciencia, Spain; Brazil, National Council for Scientific and Technological Development Scholarship number 303953/2018–7 ; the Firland Foundation , Shoreline, Washington, USA; the French COVID cohort ( NCT04262921 ) is sponsored by INSERM and is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n° 20-0424 ); a grant from foundation Bevordering Onderzoek Franciscus ; the South Eastern Norway Health Authority and the Research Council of Norway ; Institute for Clinical Research (ICR) , National Institutes of Health (NIH) supported by the Ministry of Health Malaysia; preparedness work conducted by the Short Period Incidence Study of Severe Acute Respiratory Infection; the U.S. DoD Armed Forces Health Surveillance Division, Global Emerging Infectious Diseases Branch to the U.S Naval Medical Research Unit No. TWO (NAMRU-2) (Work Unit #: P0153_21_N2). These authors would like to thank Vysnova Partners, Inc. for the management of this research project. The Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit is funded by the Wellcome Trust. Funding Information: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z and 220757/Z/20/Z]; the Bill & Melinda Gates Foundation [OPP1209135]; the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109); CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and the coordination in Canada by Sunnybrook Research Institute; endorsement of the Irish Critical Care- Clinical Trials Group, co-ordination in Ireland by the Irish Critical Care- Clinical Trials Network at University College Dublin and funding by the Health Research Board of Ireland [CTN-2014-12]; the COVID clinical management team, AIIMS, Rishikesh, India; the COVID-19 Clinical Management team, Manipal Hospital Whitefield, Bengaluru, India; Cambridge NIHR Biomedical Research Centre; the dedication and hard work of the Groote Schuur Hospital Covid ICU Team and supported by the Groote Schuur nursing and University of Cape Town registrar bodies coordinated by the Division of Critical Care at the University of Cape Town; the Liverpool School of Tropical Medicine and the University of Oxford; the dedication and hard work of the Norwegian SARS-CoV-2 study team and the Research Council of Norway grant no 312780, and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner; Imperial NIHR Biomedical Research Centre; the Comprehensive Local Research Networks (CLRNs) of which PJMO is an NIHR Senior Investigator (NIHR201385); Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies, in-kind contribution; Stiftungsfonds zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM; Italian Ministry of Health “Fondi Ricerca corrente–L1P6” to IRCCS Ospedale Sacro Cuore–Don Calabria; Australian Department of Health grant (3273191); Gender Equity Strategic Fund at University of Queensland, Artificial Intelligence for Pandemics (A14PAN) at University of Queensland, the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009), the Prince Charles Hospital Foundation, Australia; grants from Instituto de Salud Carlos III, Ministerio de Ciencia, Spain; Brazil, National Council for Scientific and Technological Development Scholarship number 303953/2018–7; the Firland Foundation, Shoreline, Washington, USA; the French COVID cohort (NCT04262921) is sponsored by INSERM and is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424); a grant from foundation Bevordering Onderzoek Franciscus; the South Eastern Norway Health Authority and the Research Council of Norway; Institute for Clinical Research (ICR), National Institutes of Health (NIH) supported by the Ministry of Health Malaysia; preparedness work conducted by the Short Period Incidence Study of Severe Acute Respiratory Infection; the U.S. DoD Armed Forces Health Surveillance Division, Global Emerging Infectious Diseases Branch to the U.S Naval Medical Research Unit No. TWO (NAMRU-2) (Work Unit #: P0153_21_N2). These authors would like to thank Vysnova Partners, Inc. for the management of this research project. The Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit is funded by the Wellcome Trust.This work uses data provided by patients and collected by the NHS as part of their care and supports #DataSavesLives. The data used for this research were obtained from ISARIC4C. We are extremely grateful to the 2648 frontline NHS clinical and research staff and volunteer medical students who collected these data in challenging circumstances, and the generosity of the patients and their families for their individual contributions in these difficult times. The COVID-19 Clinical Information Network (CO-CIN) data was collated by ISARIC4C Investigators. Data and Material provision were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE), (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award ISBRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. We also acknowledge the support of Jeremy J Farrar and Nahoko Shindo.Srinivas Murthy declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research. Ignacio Martin-Loeches declared lectures for Gilead, Thermofisher, MSD; advisory board participation for Fresenius Kabi, Advanz Pharma, Gilead, Accelerate, and Merck; and consulting fees for Gilead outside of the submitted work. These sponsors have not involvement in this manuscript. All the other authors do not have conflicts of interest to disclose. Funding Information: This work uses data provided by patients and collected by the NHS as part of their care and supports #DataSavesLives. The data used for this research were obtained from ISARIC4C. We are extremely grateful to the 2648 frontline NHS clinical and research staff and volunteer medical students who collected these data in challenging circumstances, and the generosity of the patients and their families for their individual contributions in these difficult times. The COVID-19 Clinical Information Network (CO-CIN) data was collated by ISARIC4C Investigators. Data and Material provision were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059 ), and the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE), (award 200907 ), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927 ), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153 ), NIHR Biomedical Research Centre at Imperial College London (award ISBRC-1215-20013 ), and NIHR Clinical Research Network providing infrastructure support. We also acknowledge the support of Jeremy J Farrar and Nahoko Shindo. Publisher Copyright: © 2023 The Authors
PY - 2023/10
Y1 - 2023/10
N2 - Purpose: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. Materials and methods: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality. Results: 49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33–1.39];1.47 [1.43–1.50], respectively). Conclusions: Patients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes.
AB - Purpose: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. Materials and methods: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality. Results: 49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33–1.39];1.47 [1.43–1.50], respectively). Conclusions: Patients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes.
KW - Complications
KW - COVID-19
KW - Major adverse cardiovascular events (MACE)
KW - Mortality
UR - http://www.scopus.com/inward/record.url?scp=85158882967&partnerID=8YFLogxK
U2 - 10.1016/j.jcrc.2023.154318
DO - 10.1016/j.jcrc.2023.154318
M3 - Article
C2 - 37167775
AN - SCOPUS:85158882967
SN - 0883-9441
VL - 77
JO - Journal of Critical Care
JF - Journal of Critical Care
M1 - 154318
ER -