JAMA Cardiology Viewpoint article focuses on COVID-19 and cardiovascular aging science

A new JAMA Cardiology Viewpoint article attempts to shed light on a mechanism that could explain why older adults with underlying cardiovascular disease are experiencing increased disease severity and higher mortality rates from COVID-19. Writing in the April 3 article, authors Majd AlGhatrif, M.D., and Edward G. Lakatta, Ph.D., of the Laboratory of Cardiovascular Science in NIA’s Intramural Research Program, and Oscar Cingolani, of the Johns Hopkins School of Medicine, propose that age-related changes in the renin-angiotensin system that induce an angiotensin proinflammatory response and a reduction in a key anti-inflammatory factor, angiotensin converting enzyme 2 (ACE2), may contribute to the higher risk for older adults with COVID-19. They also suggest that this mechanism could be a potential target to prevent COVID-19 disease progression.

The coronavirus gets inside an individual’s cells in the lungs and elsewhere via ACE2. This causes ACE2 to pivot from its anti-inflammatory activity, resulting in ramped up inflammation, which then worsens the lung injury from COVID-19.

Because people with heart disease, high blood pressure and heart failure often are prescribed angiotensin inhibitors that may increase ACE2 levels on cells, experts have worried that these medications may increase the entry of coronavirus into cells and elevate the risk of severe COVID-19. At the same time, doctors treating people with COVID-19 have noticed that people with pre-existing heart disease are at greater risk than others of developing severe lung inflammation and injury.

In the Viewpoint article, Drs. AlGhatrif, Cingolani and Lakatta apply their knowledge of cardiovascular aging science to suggest a novel approach.

“Based on previous animal research and preliminary epidemiological data from this pandemic, we advance a hypothesis that the predisposition of older individuals with cardiovascular disease to severe COVID-19 disease is in part due to an age-associated reduction in ACE2 level as a part of the larger pro-inflammatory changes in the renin-angiotensin system ,” said Dr. AlGhatrif. “The resulting low ACE2 baseline level in older individuals, when superimposed with further reduction in the context of COVID-19, yields a critical reduction of its anti-inflammatory effects, instigating acute inflammatory changes leading to acute lung injury.”

Therefore, the authors propose that using angiotensin blockers may prevent severe COVID-19, particularly in older adults with low baseline ACE2. The authors emphasize that the hypothesis needs to be tested in clinical trials with people who have COVID-19 to test the safety and efficacy of these medications in reducing the risk of developing severe lung disease.

Reference: AlGhatrif M, et al. The dilemma of coronavirus disease 2019, aging and cardiovascular disease: Insights from cardiovascular aging science. JAMA Cardiology. 2020; doi: 10.1001/jamacardio.2020.1329.