AbstractImportanceRecent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as animal studies indicate that these medications increase levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2. This has prompted clinicians to recommend discontinuing ACEIs and ARBs.ObjectiveTo examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS).Design, Setting, and ParticipantsA single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years) stratified by ACEIs (N = 699) or ARBs (N = 753) treatment.Main Outcomes and MeasuresThe AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m2), hypertension and type 2 diabetes (T2D) as well as serum levels of renin, ACE and ACE2.ResultsWhile renin and ACE levels were significantly raised in serum of individuals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected.Conclusions and RelevanceTreatment with ACEIs or ARBs does not raise ACE2 levels in serum. Therefore, the present study does not support the proposed discontinuation of these medications among patients affected with COVID-19.Key PointsQuestionDoes treatment with the antihypertensive medications angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) result in elevated levels of the cellular receptor for the coronavirus SARS-CoV-2, ACE2?FindingsIn a single center population-based cohort (AGES-RS), 699 and 753 individuals were either on ACEIs or ARBs treatment, respectively. The serum levels of the key enzymes in the renin-angiotensin system (RAS), renin, ACE and ACE2 were measured in 5457 subjects of the AGES-RS and their serum levels in individuals on ACEIs or ARBs treatment compared to those not using these medications. While renin and ACE were significantly raised in serum of ACEIs and ARBs users, the levels of ACE2 remained unaffected.MeaningThese results do not support the proposed routine discontinuation of ACEIs or ARBs among patients affected with COVID-19.
Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study
