tetano
Editor, Senior Moderator
Crit Care Med
. 2022 May 19.
doi: 10.1097/CCM.0000000000005589. Online ahead of print.
Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19
Genevieve L Y Rocheleau[SUP] 1 [/SUP], Terry Lee[SUP] 2 [/SUP], Yassene Mohammed[SUP] 3 4 [/SUP], David Goodlett[SUP] 3 5 6 [/SUP], Kevin Burns[SUP] 7 [/SUP], Matthew P Cheng[SUP] 8 [/SUP], Karen Tran[SUP] 9 [/SUP], David Sweet[SUP] 10 [/SUP], John Marshall[SUP] 11 [/SUP], Arthur S Slutsky[SUP] 11 [/SUP], Srinivas Murthy[SUP] 12 [/SUP], Joel Singer[SUP] 2 [/SUP], David M Patrick[SUP] 13 [/SUP], Bin Du[SUP] 14 [/SUP], Zhiyong Peng[SUP] 15 [/SUP], Todd C Lee[SUP] 8 [/SUP], John H Boyd[SUP] 1 16 [/SUP], Keith R Walley[SUP] 1 16 [/SUP], Francois Lamontagne[SUP] 17 [/SUP], Robert Fowler[SUP] 18 [/SUP], Brent W Winston[SUP] 19 [/SUP], Greg Haljan[SUP] 20 [/SUP], Donald C Vinh[SUP] 8 [/SUP], Alison McGeer[SUP] 21 [/SUP], David Maslove[SUP] 22 [/SUP], Santiago Perez Patrigeon[SUP] 22 [/SUP], Puneet Mann[SUP] 23 [/SUP], Kathryn Donohoe[SUP] 23 [/SUP], Geraldine Hernandez[SUP] 23 [/SUP], James A Russell[SUP] 1 16 [/SUP], for ARBs CORONA I Investigators
Affiliations
Abstract
Objectives: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components.
Design: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup (n = 46), recorded d-dimer (n = 967), comparing males with females.
Setting: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces.
Patients: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included.
Interventions: None.
Measurements and main results: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation (p = 0.006) and vasopressors (p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females.
Conclusions: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.
. 2022 May 19.
doi: 10.1097/CCM.0000000000005589. Online ahead of print.
Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19
Genevieve L Y Rocheleau[SUP] 1 [/SUP], Terry Lee[SUP] 2 [/SUP], Yassene Mohammed[SUP] 3 4 [/SUP], David Goodlett[SUP] 3 5 6 [/SUP], Kevin Burns[SUP] 7 [/SUP], Matthew P Cheng[SUP] 8 [/SUP], Karen Tran[SUP] 9 [/SUP], David Sweet[SUP] 10 [/SUP], John Marshall[SUP] 11 [/SUP], Arthur S Slutsky[SUP] 11 [/SUP], Srinivas Murthy[SUP] 12 [/SUP], Joel Singer[SUP] 2 [/SUP], David M Patrick[SUP] 13 [/SUP], Bin Du[SUP] 14 [/SUP], Zhiyong Peng[SUP] 15 [/SUP], Todd C Lee[SUP] 8 [/SUP], John H Boyd[SUP] 1 16 [/SUP], Keith R Walley[SUP] 1 16 [/SUP], Francois Lamontagne[SUP] 17 [/SUP], Robert Fowler[SUP] 18 [/SUP], Brent W Winston[SUP] 19 [/SUP], Greg Haljan[SUP] 20 [/SUP], Donald C Vinh[SUP] 8 [/SUP], Alison McGeer[SUP] 21 [/SUP], David Maslove[SUP] 22 [/SUP], Santiago Perez Patrigeon[SUP] 22 [/SUP], Puneet Mann[SUP] 23 [/SUP], Kathryn Donohoe[SUP] 23 [/SUP], Geraldine Hernandez[SUP] 23 [/SUP], James A Russell[SUP] 1 16 [/SUP], for ARBs CORONA I Investigators
Affiliations
- PMID: 35607951
- DOI: 10.1097/CCM.0000000000005589
Abstract
Objectives: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components.
Design: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup (n = 46), recorded d-dimer (n = 967), comparing males with females.
Setting: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces.
Patients: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included.
Interventions: None.
Measurements and main results: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation (p = 0.006) and vasopressors (p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females.
Conclusions: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.