Kevin Kunzmann

How ACE2 Reduction Associated with Aging Affects COVID-19 Severity,

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A new perspective from a team of Maryland-based cardiovascular clinicians sheds insight on an often forgotten facet of the inherent COVID-19 risk carried by patients with cardiovascular history: the decline in angiotensin-converting enzyme 2 (ACE2) expression associated with aging, and the response of care most common in such patients.

In an essay published Friday morning, a trio of investigators-Majd AlGhatrif, MD, MA; Oscar Cingolani, MD; and Edward G. Lakatta, MD; of Johns Hopkins School of Medicine, the National Institute on Aging and National Institutes of Health-called for the urgent expansion of renin-angiotensin system (RAS)-based intervention assessment as part of the need for clinical understanding as to how lung complications are driving novel coronavirus (COVID-19) mortality worldwide.

As the team noted, ACE2 is not only prevalent in the pathogenesis of COVID-19, but is part of RAS signaling. Though data is scarce on the topic, it is known now that ACE2 is both targeted by SARS-CoV-2 in its entrances to cells and a critical player in anti-inflammation during RAS signaling-converting angiotensin II to angiotensin 1-7.

The age-associated decrease of ACE2 expression, which investigators have observed in the lungs of rats, is in line with “a constellation of major proinflammatory changes perpetrated by an age-associated increase in RAS signaling throughout the body,” the team wrote.

Such proinflammatory profiles are featured in patients with hypertension and diabetes-a pair of diseases highly common in older patients.

The increase of ACE2 in such patients with ACE inhibitors and angiotensin receptor blockers (ARBs) presents a paradox to investigators: how can ACE2 reduction in older, cardiovascular-risk patients put them at greater risk of COVID-19 severe symptoms when ACE2 is the gateway for the disease into cells?

The team pointed to data procured from the severe acute respiratory syndrome (SARS) epidemic of 2003, which most prominently affected persons in their 30s and 40s-despite these younger patients reporting lower disease severity and risk of mortality versus older people with pre-existing conditions.

“Similarly, in the COVID-19 pandemic, it is plausible that greater expression of ACE2 leads to higher predisposition to incur the disease,” they wrote.

Preliminary epidemiologic data from South Korea-the country with the greatest rate of population-wide testing for the disease-shows that younger adults are reporting the greatest rate of infection, despite perceived higher ACE2 levels. COVID-19 severity, however, has been observed in older patient populations, such as that of Italy’s.

“Hence, compared with young individuals, older persons with (cardiovascular disease) who already have reduced ACE2 levels will be expected to be more predisposed to exaggerated inflammation with further reduction in ACE2 expression in the context of COVID-19, manifesting with greater disease severity,” they explained.

The team hypothesized that SARS-CoV-2 binding to ACE2 creates an acutely exaggerated proinflammatory background, thereby predisposing older adults with hypertension and diabetes treated with ACE inhibitors and ARBs to correct ACE2 levels at a greater risk of disease severity and mortality.

This belief, they wrote, aligns with evidence of angiotensin II antagonists benefitting sepsis-associated acute lung injury.

Going forward, the team advised that clinicians continue treating patients with ACE inhibitors and ARB and pursue clinical investigations that consider RAS interventions for COVID-19 severity reduction.

The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease

Articles

Why Older Patients Are More At Risk for COVID-19 : A Decline In ACE2 Expression

US Adult E-Cigarette Use Climbing, Despite Cardiology Health Concerns

Electronic cigarette use has grown to approximately 1 in every 20 US adults, according to new findings presented virtually at the American College of Cardiology (ACC) 2020 Scientific Sessions this week.

An assessment of 930,000 surveyed US adults, conducted by Mahmoud Al Rifai, MD, MPH, cardiology fellow at Baylor College of Medicine and colleagues, showed that approximately 29,000 people identified as current e-cigarette users.

Investigators used data from the annual, large-scale phone survey Behavioral Risk Factor Surveillance System (BRFSS)-a four-decade data collection program designed to represent the characteristics and demographics of the US adult population.

Current e-cigarette use was defined as participants indicating they used e-cigarettes daily or on some days. Al Rifai and colleagues compared the 2018 findings-the most recently available data-to those reported in 2016.

When looking at e-cigarette and vaping use among subpopulations, investigators noted particularly greater rates among women (4.3% vs 3.3%), former smokers (7.9% vs 5.2%), and adults aged 45-54 years old (5.2% vs 3.9%).

Current use among people who use smokeless tobacco products nearly doubled in the observed 3 years (16.2% vs 9.2%).

The surveyed population rate from 2018 translated to about 10.8 million total US adults, investigators noted-an increase of a half-percentage point from 2016 results (4.8% vs 4.3%).

Though a three-year jump of just 0.5% may not sound significant, Al Rifai noted it does indicate a great amount of new e-cigarette users relative to the overall US population.

“Based on our findings, I think the trend is only going to go upward, but we don’t know yet what the long-term health effects are,” he said in a statement.

Al Rifai’s belief that such national tends reflect the increased marketing and advertisement of e-cigarette and vaping product makers to young adult audiences is evidenced by findings from earlier this year showing market-leading JUUL products constitute about two-thirds of the increasing annual e-cigarette dollar sales.

A pair of smaller-scale studies being presented virtually by ACC 2020 show potential association between vaping and heart disease. One-a blood sample-based assessment of non-smokers, smokers, and e-cigarette users-showed both e-cigarette and smoke tobacco users are significantly more affected by oxidative stress associated with heart artery plaque buildup than non-smokers.

Holly Middlekauff, MD, UCLA cardiologist and senior study author, said the findings show not only that circulating immune cells report greater oxidative stress in smokers and e-cigarette users, but that there are also more chronic inflammatory cells present.

“Our study suggests there is a continuum of harm, with non-users having the least amount of oxidative stress, electronic cigarette users showing an intermediate level and chronic tobacco smokers having the largest amount of oxidative stress,” Middlekauf noted in a statement.

Al Rifai called on a sense of urgency in conducting further research into the prevalence of vaping and its long-term implication on individual and public health metrics. As he noted, it’s been too soon to tell what that harm may be.

“Because e-cigarettes have only been around for about a decade, many large cohort studies have only just recently started incorporating e-cigarette information into their questionnaires,” he said. “Yet, the cumulative effects of e-cigarettes may take years to develop, especially in the context of cardiovascular disease.”

The study, "Trends in Prevalence of E-Cigarette Use Among U.S. Adults. Behavioral Risk Factor Surveillance System, 2016 And 2017," was presented at ACC 2020.

Author | Kevin Kunzmann

Articles

Why Older Patients Are More At Risk for COVID-19 : A Decline In ACE2 Expression

US Adult E-Cigarette Use Climbing, Despite Cardiology Health Concerns