Relationship Between Preexisting Cardiovascular Disease and Death and Cardiovascular Outcomes in Critically Ill Patients With COVID-19

Alexi Vasbinder, Chelsea Meloche, Tariq U Azam, Elizabeth Anderson, Tonimarie Catalan, Husam Shadid, Hanna Berlin, Michael Pan, Patrick O'Hayer, Kishan Padalia, Pennelope Blakely, Ibrahim Khaleel, Erinleigh Michaud, Yiyuan Huang, Lili Zhao, Rodica Pop-Busui, Shruti Gupta, Kim Eagle, David E Leaf, Salim S Hayek, STOP-COVID Investigators‡, Carl P Walther, Samaya J Anumudu, Justin Arunthamakun, Kathleen F Kopecky, Gregory Milligan, Peter A McCullough, Thuy-Duyen Nguyen, Shaefi Shahzad, Megan L. Krajewski, Shankar Sidharth, Pannu Ameeka, Juan D Valencia, Sushrut S Waikar, Zoe A Kibbelaar, Shristi Upadhyay, Ambarish M. Athavale, Peter Hart, Ishaan Vohra, Adam Green, Jean-Sebastien Rachoin, Christa A Schorr, Lisa Shea, Daniel L Edmonston, Christopher L Mosher, Alexandre M Shehata, Zaza Coehn, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Samantha K Brenner, Walters Patricia, Ronaldo C Go, Keith M Rose, Miguel A Hernán, Rebecca Lisk, Amy M Zhou, Ethan C Kim, Huei Hsun Wen, Lili Chan, Kusum S Mathews, Steven G Coca, Deena R Altman, Aparna Saha, Howard Soh, Emily J Gallagher, Jing G Wang, Sonali Bose, Emily A Leven, Gohar Mosoyan, Girish N Nadkarni, Pattharawin Pattharanitima, Allon N Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J Kelly, Chirag R Parikh, Brian T Garibaldi, Celia P Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F Malik, Elena Cervantes, Samir Gautam, Mary C Mallappallil, Leon Boudourakis, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Ahoubim Afshin, H Bryant Nguyen, Meghan E Sise, Erik T Newman, Samah Abu Omar, Kapil K Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Ian A Strohbehn, Tanveer Shaukat, Kamal Omer, Wang Wei, Heather Yang, Jeffery O Boateng, Meghan Lee, Jiahua Li, Ariel L Mueller, Leslie F Thomas, Dheeraj Reddy Sirganagari, Pramod K Guru, Kianoush Kashani, Shahrzad Tehranian, Yan Zhou, Paul A Bergl, Jesus Rodriguez, Jatan A Shah, Mrigank S Gupta, Princy N Kumar, Deepa G Lazarous, Seble G Kassaye, Michal L Melamed, Tanya S Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang, Jyotsana Thakkar, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J Schenck, Soo Jung Cho, Maria Plataki, Sergio L Alvarez-Mulett, Luis G Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Macina Ashley, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, Anand Srivastava, Alexander S Leidner, Carlos Martinez, Jacqueline M Kruser, Richard G Wunderink, Alexander J Hodakowski, Juan Carlos Q Velez, Eboni G Price-Haywood, Luis A Matute-Trochez, Anna E Hasty, Muner MB Mohamed, Rupali S Avasare, David Zonies, Roberta Redfern, Nicholas S Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Farah Madhani-Lovely, Chris Rowan, Joy-Marie Hermes, Vasil Peev, Jochen Reiser, John J Byun, Andrew Vissing, Esha M Kapania, Zoe Post, Nilam P Patel, Anne K Sutherland, Amee Patrawalla, Diana G Finkel, Barbara A Danek, Sowminya Arikapudi, Jeffrey M Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Jag Sunderram, Sonika Puri, Jayanth S Vatson, Matthew T Scharf, Ayesha Ahmed, Ilya Berim, Shuchi Anand, Joseph E Levitt, Pablo Garcia, Suzanne M Boyle, Rui Song, Ali Arif, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A Sharshir, Vadym V Rusnak, Muhammad Imran Ali, Terri Peters, Kathy Hughes, Anip Bansal, Amber S Podoll, Michel Chonchol, Sunita Sharma, Ellen L Burnham, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E Albertson, Jason Y Adams, Steven Y Chang, Rebecca M Beutler, Carl E Schulze, Etienne Macedo, Harin Rhee, Kathleen D Liu, Vasantha K Jotwani, Jay L Koyner, Chintan V Shah, Vishal Jaikaransingh, Stephanie M Toth-Manikowski, Min J Joo, James P Lash, Javier A Neyra, Nourhan Chaaban, Alfredo Iardino, Elizabeth H Au, Jill H Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Alessia Fornoni, Hayley B Gershengorn, Rafey Feroze, Abbas Bitar, Jeff Leya, John P Donnelly, Andrew J Admon, Jennifer E Flythe, Matthew J Tugman, Emily H Chang, Brent R Brown, Todd A Miano, Amanda K Leonberg-Yoo, Ryan C Spiardi, Meaghan S Roche, Charles R Vasquez, Amar D Bansal, Natalie C Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P Kovesdy, Miklos Z Molnar, Ambreen Azhar, S Susan Hedayati, Mridula V Nadamuni, Shani Shastri, Duwayne L Willett, Samuel A P Short, Amanda D Renaghan, Kyle B Enfield, Pavan K Bhatraju, A Bilal Malik, Matthew W Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F Kao, Greg L Schumaker, Nitender Goyal, Anthony J Faugno, Greg L Schumaker, Caroline M Hsu, Asma Tariq, Leah Meyer, Ravi K Kshirsagar, Daniel E Weiner, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, Ugochukwu Ugwuowo, Alexi Vasbinder, Chelsea Meloche, Tariq U Azam, Elizabeth Anderson, Tonimarie Catalan, Husam Shadid, Hanna Berlin, Michael Pan, Patrick O'Hayer, Kishan Padalia, Pennelope Blakely, Ibrahim Khaleel, Erinleigh Michaud, Yiyuan Huang, Lili Zhao, Rodica Pop-Busui, Shruti Gupta, Kim Eagle, David E Leaf, Salim S Hayek, STOP-COVID Investigators‡, Carl P Walther, Samaya J Anumudu, Justin Arunthamakun, Kathleen F Kopecky, Gregory Milligan, Peter A McCullough, Thuy-Duyen Nguyen, Shaefi Shahzad, Megan L. Krajewski, Shankar Sidharth, Pannu Ameeka, Juan D Valencia, Sushrut S Waikar, Zoe A Kibbelaar, Shristi Upadhyay, Ambarish M. Athavale, Peter Hart, Ishaan Vohra, Adam Green, Jean-Sebastien Rachoin, Christa A Schorr, Lisa Shea, Daniel L Edmonston, Christopher L Mosher, Alexandre M Shehata, Zaza Coehn, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Samantha K Brenner, Walters Patricia, Ronaldo C Go, Keith M Rose, Miguel A Hernán, Rebecca Lisk, Amy M Zhou, Ethan C Kim, Huei Hsun Wen, Lili Chan, Kusum S Mathews, Steven G Coca, Deena R Altman, Aparna Saha, Howard Soh, Emily J Gallagher, Jing G Wang, Sonali Bose, Emily A Leven, Gohar Mosoyan, Girish N Nadkarni, Pattharawin Pattharanitima, Allon N Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J Kelly, Chirag R Parikh, Brian T Garibaldi, Celia P Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F Malik, Elena Cervantes, Samir Gautam, Mary C Mallappallil, Leon Boudourakis, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Ahoubim Afshin, H Bryant Nguyen, Meghan E Sise, Erik T Newman, Samah Abu Omar, Kapil K Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Ian A Strohbehn, Tanveer Shaukat, Kamal Omer, Wang Wei, Heather Yang, Jeffery O Boateng, Meghan Lee, Jiahua Li, Ariel L Mueller, Leslie F Thomas, Dheeraj Reddy Sirganagari, Pramod K Guru, Kianoush Kashani, Shahrzad Tehranian, Yan Zhou, Paul A Bergl, Jesus Rodriguez, Jatan A Shah, Mrigank S Gupta, Princy N Kumar, Deepa G Lazarous, Seble G Kassaye, Michal L Melamed, Tanya S Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang, Jyotsana Thakkar, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J Schenck, Soo Jung Cho, Maria Plataki, Sergio L Alvarez-Mulett, Luis G Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Macina Ashley, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, Anand Srivastava, Alexander S Leidner, Carlos Martinez, Jacqueline M Kruser, Richard G Wunderink, Alexander J Hodakowski, Juan Carlos Q Velez, Eboni G Price-Haywood, Luis A Matute-Trochez, Anna E Hasty, Muner MB Mohamed, Rupali S Avasare, David Zonies, Roberta Redfern, Nicholas S Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Farah Madhani-Lovely, Chris Rowan, Joy-Marie Hermes, Vasil Peev, Jochen Reiser, John J Byun, Andrew Vissing, Esha M Kapania, Zoe Post, Nilam P Patel, Anne K Sutherland, Amee Patrawalla, Diana G Finkel, Barbara A Danek, Sowminya Arikapudi, Jeffrey M Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Jag Sunderram, Sonika Puri, Jayanth S Vatson, Matthew T Scharf, Ayesha Ahmed, Ilya Berim, Shuchi Anand, Joseph E Levitt, Pablo Garcia, Suzanne M Boyle, Rui Song, Ali Arif, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A Sharshir, Vadym V Rusnak, Muhammad Imran Ali, Terri Peters, Kathy Hughes, Anip Bansal, Amber S Podoll, Michel Chonchol, Sunita Sharma, Ellen L Burnham, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E Albertson, Jason Y Adams, Steven Y Chang, Rebecca M Beutler, Carl E Schulze, Etienne Macedo, Harin Rhee, Kathleen D Liu, Vasantha K Jotwani, Jay L Koyner, Chintan V Shah, Vishal Jaikaransingh, Stephanie M Toth-Manikowski, Min J Joo, James P Lash, Javier A Neyra, Nourhan Chaaban, Alfredo Iardino, Elizabeth H Au, Jill H Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Alessia Fornoni, Hayley B Gershengorn, Rafey Feroze, Abbas Bitar, Jeff Leya, John P Donnelly, Andrew J Admon, Jennifer E Flythe, Matthew J Tugman, Emily H Chang, Brent R Brown, Todd A Miano, Amanda K Leonberg-Yoo, Ryan C Spiardi, Meaghan S Roche, Charles R Vasquez, Amar D Bansal, Natalie C Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P Kovesdy, Miklos Z Molnar, Ambreen Azhar, S Susan Hedayati, Mridula V Nadamuni, Shani Shastri, Duwayne L Willett, Samuel A P Short, Amanda D Renaghan, Kyle B Enfield, Pavan K Bhatraju, A Bilal Malik, Matthew W Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F Kao, Greg L Schumaker, Nitender Goyal, Anthony J Faugno, Greg L Schumaker, Caroline M Hsu, Asma Tariq, Leah Meyer, Ravi K Kshirsagar, Daniel E Weiner, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, Ugochukwu Ugwuowo

Abstract

Background: Preexisting cardiovascular disease (CVD) is perceived as a risk factor for poor outcomes in patients with COVID-19. We sought to determine whether CVD is associated with in-hospital death and cardiovascular events in critically ill patients with COVID-19.

Methods: This study used data from a multicenter cohort of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 68 centers across the United States from March 1 to July 1, 2020. The primary exposure was CVD, defined as preexisting coronary artery disease, congestive heart failure, or atrial fibrillation/flutter. Myocardial injury on intensive care unit admission defined as a troponin I or T level above the 99th percentile upper reference limit of normal was a secondary exposure. The primary outcome was 28-day in-hospital mortality. Secondary outcomes included cardiovascular events (cardiac arrest, new-onset arrhythmias, new-onset heart failure, myocarditis, pericarditis, or stroke) within 14 days.

Results: Among 5133 patients (3231 male [62.9%]; mean age 61 years [SD, 15]), 1174 (22.9%) had preexisting CVD. A total of 1178 (34.6%) died, and 920 (17.9%) had a cardiovascular event. After adjusting for age, sex, race, body mass index, history of smoking, and comorbidities, preexisting CVD was associated with a 1.15 (95% CI, 0.98-1.34) higher odds of death. No independent association was observed between preexisting CVD and cardiovascular events. Myocardial injury on intensive care unit admission was associated with higher odds of death (adjusted odds ratio, 1.93 [95% CI, 1.61-2.31]) and cardiovascular events (adjusted odds ratio, 1.82 [95% CI, 1.47-2.24]), regardless of the presence of CVD.

Conclusions: CVD risk factors, rather than CVD itself, were the major contributors to outcomes in critically ill patients with COVID-19. The occurrence of myocardial injury, regardless of CVD, and its association with outcomes suggests it is likely due to multiorgan injury related to acute inflammation rather than exacerbation of preexisting CVD.

Registration: NCT04343898; https://ichgcp.net/clinical-trials-registry/NCT04343898.

Keywords: COVID-19; cardiovascular disease; cardiovascular risk factors; inflammation; troponin.

Figures

Figure 1.
Figure 1.
Associations between cardiovascular disease, coronary artery disease, and congestive heart failure with 28-day mortality and cardiovascular events. Bar graphs depicting the odds ratio and 95% CIs for 28-day mortality (A) and cardiovascular events (B) using 4 different models. Model 0 was unadjusted. Model 1 was adjusted for age, race and ethnicity, and sex. Model 2 incorporated model 1 in addition to body mass index, smoking status, and history of preexisting diabetes, hypertension, and chronic kidney disease. Model 3 included the modified Sequential Organ Failure Assessment (SOFA) score. Based on model 3, neither cardiovascular disease, coronary artery disease nor congestive heart failure was associated with 28-day mortality.
Figure 2.
Figure 2.
Bar graphs comparing measures of COVID-19 illness severity by myocardial injury on admission for mechanical ventilation, modified Sequential Organ Failure Assessment (mSOFA) score, creatinine, and CRP (C-reactive protein). A, Proportion of patients on mechanical ventilation at intensive care unit (ICU) admission. B, C, and D, Compare the means of modified SOFA scores, creatinine, and CRP between patients with and without myocardial injury at ICU admission. Creatinine and CRP are log2 transformed.
Figure 3.
Figure 3.
Associations between troponin elevation on intensive care unit (ICU) admission and troponin fold change during hospitalization with 28-day mortality and cardiovascular events. Bar graphs depicting the odds ratios and 95% CIs for 28-day mortality (A) and cardiovascular events (B) based on acute cardiac injury on ICU admission categorized as troponin elevation 1–2x, 2–3x, 3–4x, and >4x the upper reference limit of normal vs no acute cardiac injury (reference) based on model 3. C and D, Odds ratios and 95% CIs based on the absolute fold change in troponin during hospitalization categorized as an absolute fold change of <1.29, 1.3%–9.3%, and >9.3% compared with patients with no elevated troponin measurements during hospitalization (reference) for 28-day mortality (C) and cardiovascular events (D) based on model 3.

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Source: PubMed

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