Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19

Ashwin Sunderraj; Chloe Cho; Xuan Cai; Shruti Gupta; Rupal Mehta; Tamara Isakova; David E. Leaf; Anand Srivastava

doi:10.1097/CCE.0000000000000755

Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19

Ashwin Sunderraj, Chloe Cho, Xuan Cai, Shruti Gupta, Rupal Mehta, Tamara Isakova, David E. Leaf, Anand Srivastava^*

^*Corresponding author for this work

Medicine, Nephrology Division

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

OBJECTIVES: Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity <0.001) after adjustment for covariates that included demographics, preexisting comorbidities, acute physiologic ICU factors, number of ICU beds, and treatments for COVID-19. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and 28-day mortality (p for interaction <0.001), but this effect modification was modest as age still had an exponential relationship with death in subgroups stratified by the number of risk factors. CONCLUSIONS: In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19.

Original language	English (US)
Pages (from-to)	E0755
Journal	Critical Care Explorations
Volume	4
Issue number	9
DOIs	https://doi.org/10.1097/CCE.0000000000000755
State	Published - Aug 29 2022

Funding

Dr. Srivastava reports personal fees from Horizon Therapeutics, PLC, AstraZeneca, Bayer, CVS Caremark, and Tate & Latham (medicolegal consulting). Dr. Gupta receives research funding from GE HealthCare and BTG International. Ms. Cho received research funding from Northwestern University’s Summer Internship Grant Program (SIGP). Dr. Gupta is supported by National Institute of Health (NIH) grant K23DK125672. Dr. Mehta is supported by the NIH grant K23HL150236. Dr. Leaf is supported by NIH grants R01HL144566 and R01DK125786. Dr. Srivastava is supported by NIH grant K23DK120811 and core resources from the George M. O’Brien Kidney Research Center at Northwestern University (NU-GoKIDNEY) P30DK114857. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Keywords

COVID-19
age
critical care
death
risk factors

ASJC Scopus subject areas

Critical Care and Intensive Care Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/CCE.0000000000000755

Cite this

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title = "Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19",

abstract = "OBJECTIVES: Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity <0.001) after adjustment for covariates that included demographics, preexisting comorbidities, acute physiologic ICU factors, number of ICU beds, and treatments for COVID-19. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and 28-day mortality (p for interaction <0.001), but this effect modification was modest as age still had an exponential relationship with death in subgroups stratified by the number of risk factors. CONCLUSIONS: In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19.",

keywords = "COVID-19, age, critical care, death, risk factors",

author = "Ashwin Sunderraj and Chloe Cho and Xuan Cai and Shruti Gupta and Rupal Mehta and Tamara Isakova and Leaf, {David E.} and Anand Srivastava",

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T1 - Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19

AU - Sunderraj, Ashwin

AU - Cho, Chloe

AU - Cai, Xuan

AU - Gupta, Shruti

AU - Mehta, Rupal

AU - Isakova, Tamara

AU - Leaf, David E.

AU - Srivastava, Anand

PY - 2022/8/29

Y1 - 2022/8/29

N2 - OBJECTIVES: Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity <0.001) after adjustment for covariates that included demographics, preexisting comorbidities, acute physiologic ICU factors, number of ICU beds, and treatments for COVID-19. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and 28-day mortality (p for interaction <0.001), but this effect modification was modest as age still had an exponential relationship with death in subgroups stratified by the number of risk factors. CONCLUSIONS: In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19.

AB - OBJECTIVES: Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity <0.001) after adjustment for covariates that included demographics, preexisting comorbidities, acute physiologic ICU factors, number of ICU beds, and treatments for COVID-19. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and 28-day mortality (p for interaction <0.001), but this effect modification was modest as age still had an exponential relationship with death in subgroups stratified by the number of risk factors. CONCLUSIONS: In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19.

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Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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