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Men have higher concentrations of ACE2 in their blood than women. As ACE2 enables coronavirus to infect cells, the findings may explain why men are more susceptible to COVID-19 infection than women. The study, published in the European Heart Journal today, also found that heart failure patients taking drugs targeting the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), did not have higher concentrations of ACE2 in their blood.
Dr Adriaan Voors (MD-PhD), Professor of Cardiology at the University Medical Center Groningen (The Netherlands), who led the study, said: “Our findings do not support the discontinuation of these drugs in COVID-19 patients as has been suggested by earlier reports.” Some recent research suggested that RAAS inhibitors might increase concentrations of ACE2 in plasma – the liquid part of blood – thereby increasing the risk of COVID-19 for cardiovascular patients taking these drugs. The current study indicates that this is not the case, although it looked only at ACE2 concentrations in plasma, not in tissues such as lung tissue. In addition, the study cannot provide definitive evidence on the effects of RAAS inhibitors in patients with COVID-19. Its conclusions are mainly restricted to heart failure patients, and the patients did not have COVID-19, so the researchers cannot provide a direct link between the course of the disease and ACE2 plasma concentrations. Prof Voors said: “ACE2 is a receptor on the surface of cells. It binds to the coronavirus and allows it to enter and infect healthy cells after it is has been modified by another protein on the surface of the cell, called TMPRSS2. High levels of ACE2 are present in the lungs and, therefore, it is thought to play a crucial role in the progression of lung disorders related to COVID-19.”
The researchers measured ACE2 concentrations in blood samples taken from two groups of heart failure patients from 11 European countries. There were 1485 men and 537 women in the first group, the index cohort, which was designed to test the researchers’ hypotheses and research questions. Then the researchers validated their findings in a second group of 1123 men and 575 women, the validation cohort. The median (average) age of the participants in the index cohort was 69 years for men and 75 years for women, and in the validation cohort it was 74 and 76 years, respectively. When the researchers looked at a number of clinical factors that could play a role in ACE2 concentrations, including the use of ACE inhibitors, ARBs and mineralocorticoid receptor antagonists (MRAs), as well as a history of chronic obstructive pulmonary disease, coronary artery by-pass graft and atrial fibrillation, they found that male sex was the strongest predictor of elevated ACE2 concentrations. In the index cohort, ACE inhibitors, ARBS and MRAs were not associated with greater ACE2 plasma concentrations, and in the validation cohort, ACE inhibitors and ARBs were associated with lower ACE2 concentrations, while MRAs were only weakly associated with higher concentrations.
Published in European Heart J. (May 10, 2020):
