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 |
| Journal | Journal of Critical Care |
| Volume | 77 |
| DOIs | |
| State | Published - Oct 2023 |
Bibliographical note
Publisher Copyright:© 2023 The Authors
Funding
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 F\u00F6rderung der Bek\u00E4mpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM; Italian Ministry of Health \u201CFondi Ricerca corrente\u2013L1P6\u201D to IRCCS Ospedale Sacro Cuore\u2013Don 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\u20137; 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\u00B020-0424); 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. 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 F\u00F6rderung der Bek\u00E4mpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM; Italian Ministry of Health \u201CFondi Ricerca corrente\u2013L1P6\u201D to IRCCS Ospedale Sacro Cuore\u2013Don 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\u20137 ; 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\u00B0 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.
| Funders | Funder number |
|---|---|
| Vysnova Partners, Inc. | |
| Merck | |
| Michigan Institute for Clinical and Health Research | |
| Kementerian Kesihatan Malaysia | |
| Health Research Foundation and Innovative Medicines Canada | |
| Instituto de Salud Carlos III | |
| Institut national de la santé et de la recherche médicale | |
| Artificial Intelligence for Pandemics | |
| Italian Ministry of Health “Fondi Ricerca corrente | |
| Ministère des Affaires Sociales et de la Santé | |
| Groote Schuur Hospital Covid ICU | |
| Irish Critical Care- Clinical Trials Group | |
| Prince Charles Hospital Foundation | |
| Gilead Sciences | |
| National Institutes of Health | |
| South Eastern Norway Health Authority and the Research Council of Norway | |
| COVID-19 Clinical Management team | |
| National Institute for Health Research Health Protection Research Unit | |
| University of Queensland | |
| Manipal Hospital Whitefield | |
| foundation Bevordering Onderzoek Franciscus | |
| University of Cape Town | |
| University College Dublin | |
| Manchester Biomedical Research Centre | |
| University of Oxford | |
| Lao-Oxford-Mahosot Hospital-Wellcome Trust | |
| HPRU | |
| Foreign, Commonwealth and Development Office | |
| UK Research and Innovation | |
| Wellcome Trust | 220757/Z/20/Z, 220757, 215091/Z/18/Z, 225288, 225288/Z/22/Z, 222410/Z/21/Z, 222410, 215091 |
| Medical Research Council | MC_PC_19059 |
| PHRC | 20-0424 |
| Ministerio de Ciencia | 303953/2018–7 |
| National Institute for Health and Care Research | CO-CIN-01 |
| Norges Forskningsråd | NIHR201385, 312780 |
| Imperial College London | 200927 |
| Australian Department of Health | 3273191 |
| Innovative Medicines Initiative | 115523 |
| Firland Foundation | NCT04262921 |
| Australian Research Council | CE170100009 |
| Bill and Melinda Gates Foundation | 0009109, OPP1209135 |
| Seventh Framework Programme | APCOV22BGM |
| Public Health England | 200907 |
| Liverpool Experimental Cancer Medicine Centre | C18616/A25153 |
| Canadian Institutes of Health Research | OV2170359 |
| U.S. DoD Armed Forces Health Surveillance Division, Global Emerging Infectious Diseases Branch | P0153_21_N2 |
| Health Research Board | CTN-2014-12 |
| NIHR Biomedical Research Centre at Imperial College London | ISBRC-1215-20013 |
Keywords
- COVID-19
- Complications
- Major adverse cardiovascular events (MACE)
- Mortality
