COVID-19 grant award for urgently needed cardiovascular research

Investigators from Kaiser Permanente Southern California, led by Jaejin An, PhD, are among 12 scientific teams selected by the American Heart Association to fast-track research on heart and brain health related to COVID-19.

The team will study the risks associated with taking antihypertensive medications in patients with confirmed COVID-19 infection and high blood pressure.

“In conversations with clinicians, a lot of questions came up about why hypertension is a risk factor for COVID-19, and whether medications might be associated with those risks,” said Dr. An. “These are important questions for clinicians treating patients with hypertension—they need to make decisions about how to treat their patients”

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are widely used medications for treating high blood pressure, or hypertension.

Conflicting information fuels need for research

Some research suggests that patients taking these specific classes of medications may be at increased risk for severe COVID-19 because these medications upregulate angiotensin-converting enzyme 2 (ACE2) receptors, the point of entry for SARS-CoV-2 virus into humans. Other research suggests that ACE inhibitors or ARBs protect against COVID-19; the virus worsens lung injury by decreasing ACE2, but ACE inhibitors or ARBs reverse this pathway by upregulating ACE2.

Because of the current lack of scientific evidence, the AHA, the Heart Failure Society of America, and the American College of Cardiology currently advocate that patients with hypertension continue taking their ACE inhibitors and ARBs as prescribed. More evidence is urgently needed to determine how to appropriately treat patients with hypertension during the COVID-19 pandemic.

Dr. Jaejin An headshot

Dr. Jaejin An

In the funded study, researchers from Kaiser Permanente Southern California will compare the risk for COVID-19 infection between patients with hypertension treated with ACE inhibitors or ARBs and patients treated with other classes of medications for high blood pressure (such as calcium channel blockers, thiazide diuretics, and beta-blockers). In patients with confirmed COVID-19 infection, the researchers will compare the severity of the illness by comparing admittance to an intensive care unit, use of mechanical ventilation, and mortality between the 2 medication groups.

The Kaiser Permanente Southern California research proposal was among more than 750 submitted for the COVID-19 and Its Cardiovascular Impact Rapid Response Grant initiative of the AHA, one of the largest responses to a single-topic request for applications at the granting agency.

Researchers and clinicians collaborate on proposal for rapid research

The study findings could have an immediate impact on clinical guidance for patients taking medications for high blood pressure. “It will be very interesting to see how the study results will influence clinical guidelines and help clinicians decide how to manage hypertension,” said Dr. An. ”One way or the other—whether we see an increased risk or not—the findings will inform practice.”

The proposal came together in about one week, with input from scientists, clinicians, biostatisticians, and research support staff. Typically, it might take several months to put together this kind of proposal.

Clinical collaborators include Angeline Ong-Su, MD, (Family Medicine); Mingsum Lee, MD, (Cardiology); John Sim, MD, (Nephrology); Jeffrey Brettler, MD (Internal Medicine); and John Martin, MD, (Internal Medicine).

Co-investigators from R&E include Kristi Reynolds, PhD, MPH; Michael Gould, MD, MS; Hui Zhou, PhD, MS, and Matthew Mefford, PhD. Staff from the Division of Epidemiologic Research and the Central Business Office also played a key role in putting together the proposal on an expedited timeline, including Teresa Harrison, SM; Tiffany Luong, MPH; Jackie Godoy, MRA; and Diane Robinson, MPA.

This is one of many research studies and grants going on at Kaiser Permanente Southern California aimed at learning more about COVID-19 in order to inform clinical practice and public healthy to improve prevention, treatment, and survival during these unprecedented times.