Patients With Obesity-Related Hypertension Treated With Renin-Angiotensin-Aldosterone System Antagonists Exhibit Lower Mortality And Less Severe COVID-19: A Retrospective Study

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been found to exploit the cell’s ACE2 receptor for viral entry. Renin-angiotensin-aldosterone system (RAAS) antagonism with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) increases the expression of ACE2 receptors which, coupled with the metabolic changes associated with obesity-related hypertension, can make hypertensive patients with obesity more vulnerable to severe COVID-19. Although current evidence suggests that ACEI/ARB use does not increase risk of severe COVID-19 in the general population, potential interactions with obesity-related hypertension are unknown. Methods: We conducted a retrospective study of COVID-19 patients admitted to the University of Iowa Hospitals and Clinics between March 1st and July 8th, 2020. We included adults who are overweight (BMI ≥ 25 kg/m2) or obese (BMI ≥ 30 kg/m2) with hypertension treated as outpatients with or without ACEIs/ARBs. Patients without exposure to RAAS antagonists served as controls. We assessed mortality and the severity of COVID-19 reflected by admission to ICU and usage of supplemental O2, non-invasive ventilation, mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and vasopressors. Results: Of the 369 inpatients with COVID-19, we identified 138 exhibiting obesity-related hypertension who were then allocated into the control (n=59) and ACEI/ARB (n=79) groups. The BMIs between groups at baseline were not statistically significant (Control: 33.6 ± 0.96 vs. ACEI/ARB: 34.99 ± 0.97; p=.32). Women were less represented in the ACEI/ARB group (Control: 47% vs. ACEI/ARB: 24%). The controls had a substantially higher mortality rate (Control: 32.2% vs. ACEI/ARB: 15.1%). In regard to the severity of COVID-19, the ACEI/ARB cohort showed lower usage of supplemental O2 (Control: 52.5% vs. ACEI/ARB: 49.3%), mechanical ventilation (Control: 37.2% vs. ACEI/ARB: 1.2%), vasopressors (Control: 38.9% vs. ACEI/ARB: 31.6%), and had lower ICU admissions (Control: 57.6% vs. ACEI/ARB: 46.8%). However, the ACEI/ARB group had higher rates of: ECMO (Control: 0% vs. ACEI/ARB: 20.2%) and non-invasive ventilation (Control: 18.6% vs. ACEI/ARB: 20.2%). Of note, the rate of diabetes was higher in the ACEI/ARB cohort (Control: 45.7% vs. ACEI/ARB: 63.2%). Conclusion: Our results suggest that a history of RAAS antagonism is associated with lower mortality and less severity of COVID-19 in patients with obesity-related hypertension requiring hospital admission.