Year: 2020
Type: article
Abstract: The information conveyed by James Diaz, MD,1 in a recent letter to the editor ‘Hypothesis: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19’ 1 is inaccurate, misleading and potentially harmful to individuals taking angiotensin system blocking antihypertensive medicines. Diaz cites only one article 2 that investigated the effect of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) on ACE2. Moreover, he incorrectly cites this article 2 as indicating that both ACE inhibitors and ARBs increase ACE2 in animal models: ‘Intravenous infusions of ACEIs and ARBs in experimental animals increase the numbers of ACE2 receptors in the cardiopulmonary circulation’. He then amplifies this misinterpretation by extrapolating it to all tissues in humans: ‘Patients taking ACEIs or ARBs … are assumed to have increased numbers of ACE2 receptors throughout their cardiopulmonary circulations …’ ‘… patients treated with ACEIs and ARBS will have increased numbers of ACE2 receptors in their lungs for coronavirus S proteins to bind to, they may be at increased risk of severe disease outcomes due to SARS-CoV-2 infections’. Ferrario et al.2 administered drugs to a single (Lewis) strain of rats for 12 days in drinking water, not intravenously. They measured mRNA for ACE2 and ACE2-mediated metabolism of 125I-angiotensin II in the rats’ left ventricle. The largest increase in left ventricular ACE2 mRNA was caused by lisinopril, without any increase in ACE2-mediated metabolism of 125I-angiotensin II. Losartan caused a smaller increase in left ventricular ACE2 mRNA, while increasing ACE2-mediated metabolism of 125I-angiotensin II. Co-administration of lisinopril and losartan to the rats did not alter ACE2 mRNA, but increased ACE2-mediated metabolism of 125I-angiotensin II. Measurement of enzymatic activity used a very low substrate concentration, <10 nM, which could indicate an altered Km of the ACE2 for its substrate, versus an increase in ACE2 protein. So, based upon an ambiguous observation of alterations in left ventricular ACE2 mRNA and enzymatic activity in a single strain of rats, Diaz has aroused concern that persons taking ACE inhibitors and ARBs to control their hypertension may be at greater risk from SARS-CoV-2 infection. This is an indefensible speculation with the potential to harm hypertensive individuals who may eschew these medications, increasing their risk of cardiovascular morbidity. More disconcerting is the misinterpretation of the report by Guan et al.3 They do not provide any information in their report regarding patient use of antihypertensive medications, let alone whether or not they were taking ACE inhibitors or ARBS. The report by Guan et al.3 is completely irrelevant to the issue of whether ACE inhibitors or ARBs increase or decrease the risk of morbidity and mortality from SARS-CoV-2 infection. The American College of Cardiology, American Heart Association and the Heart Failure Society of America have advised patients who are taking ACE inhibitors and ARBs to continue doing so in the face of the current corona virus pandemic. https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19
Source: Journal of Travel Medicine
DOI: 10.1093/jtm/taaa045
Author: Robert C Speth
Institution: Nova Southeastern University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3014515133