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Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19
Ashwin Sunderraj1, Chloe Cho2, Xuan Cai3
1Graduate Medical Education, Northwestern University Feinberg School of Medicine, Chicago, IL.
Insights
Older age increases death risk in critically ill COVID-19 patients. Preexisting conditions and ICU factors slightly modify this, but age remains a strong predictor of mortality.
Area of Science:
- Critical care medicine
- Epidemiology
- Gerontology
Background:
- Older age is a significant risk factor for adverse outcomes in critically ill patients with COVID-19.
- The influence of preexisting comorbidities and acute physiological factors on the age-mortality association in this population remains under-investigated.
Purpose of the Study:
- To investigate the association between age and 28-day mortality in critically ill COVID-19 patients.
- To determine if preexisting comorbidities and acute physiological intensive care unit (ICU) factors modify the relationship between age and mortality.
Main Methods:
- A multicenter cohort study included 5,037 critically ill adults with COVID-19 admitted to ICUs across 68 US hospitals.
- Multivariable logistic regression was used to analyze the association between age (continuous variable) and 28-day in-hospital mortality.
- Effect modification by the number of risk factors (comorbidities and acute physiologic factors) was assessed using an interaction term.
Main Results:
- Age demonstrated a nonlinear, exponential association with 28-day mortality (p < 0.001) after adjusting for covariates.
- The number of preexisting comorbidities and acute physiologic ICU factors significantly modified the age-mortality association (p < 0.001).
- Despite modification, age maintained an exponential relationship with death across subgroups stratified by risk factor count.
Conclusions:
- Age is an independent exponential predictor of death in critically ill COVID-19 patients.
- While comorbidities and acute ICU factors modify this association, age remains a critical determinant of mortality.
- Further research is needed to elucidate the mechanisms driving increased mortality risk with older age in this patient group.
Abstract:
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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