The study, published in the European Heart Journal, also found that heart failure patients taking drugs such as angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs), did not have higher concentrations of the coronavirus gateway enzyme ACE2 in their blood.
"Our findings do not support the discontinuation of these drugs in COVID-19 patients as has been suggested by earlier reports," said Adriaan Voors, study co-author from the University of Groningen in the Netherlands.
Earlier studies had suggested that these drugs 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.
According to the current study, this is not the case, although it looked only at ACE2 concentrations in plasma, not in tissues such as lung tissue.
"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," Voors said.
"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," he added.
In the study, the researchers measured ACE2 concentrations in blood samples taken from two groups of heart failure patients from 11 European countries.
There were 1,485 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.
According to the study, the 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.
The researchers assessed the number of clinical factors that could play a role in ACE2 concentrations, including the use of ACE inhibitors, a history of chronic obstructive pulmonary disease, and coronary artery by-pass graft.
They found that male sex was the strongest predictor of elevated ACE2 concentrations.
In the index cohort, the scientists said ACE inhibitors were not associated with greater ACE2 plasma concentrations.
In the validation cohort, they said that ACE inhibitors and ARBs were associated with lower ACE2 concentrations.
"To the best of our knowledge, this is the first substantial study to examine the association between plasma ACE2 concentrations and the use of blockers of the renin-angiotensin-aldosterone system in patients with cardiovascular disease," Voors said.
The study, according to the researchers, found no evidence that ACE inhibitors and ARBs were linked to increased ACE2 concentrations in plasma.
"In fact, they predicted lower concentrations of ACE2 in the validation cohort, although we did not see this in the index cohort," Voors said.
Based on the findings, the scientists said the effect of the class of drugs called mineralocorticoid receptor antagonists (MRAs) on ACE2 concentrations is not clear since the weak increase in concentrations in the validation cohort was not seen in the index cohort.
Our findings do not suggest that MRAs should be discontinued in heart failure patients who develop COVID-19.
"They are a very effective treatment for heart failure and the hypothetical effects on viral infection should be weighed carefully against their proven benefits," Voors said.
According to the study, ACE2 is found not only in the lungs, but also the heart, kidneys, and the tissues lining blood vessels, and particularly at high levels in the testes.
The researchers speculate that its regulation in the testes might partially explain higher ACE2 concentrations in men, and why men are more vulnerable to COVID-19.
Citing a limitation of the study, the scientists said they only measured concentrations of ACE2 in plasma, not in tissues, so they cannot be sure that concentrations in the blood are similar to those seen in tissues.
The researchers also said its conclusions are mainly restricted to heart failure patients, and the patients did not have COVID-19.
So they said the study does not provide a direct link between the course of the disease and ACE2 plasma concentrations.
It is the ACE2 in the lung tissues that are thought to be important for viral infection of the lungs, not ACE2 concentrations in the blood, they added. VIS VISVIS