Research News

A history of COVID-19 is associated with a doubled risk of adverse cardiac events for as long as follow up information is available (three years after diagnosis), according to research led by Cleveland Clinic and the University of Southern California.

The risk among patients who were hospitalized for their COVID-19 was even higher. Further genetic analysis also revealed patients with a non-O blood type (i.e. A, B or AB) were twice as likely to experience an adverse cardiovascular event after being diagnosed with COVID-19 than those with an O-blood type.

The findings, published in Arteriosclerosis, Thrombosis, and Vascular Biology, advance our understanding of the connection between COVID-19 infection and heart disease. How long these risks persist without tapering off after initial infection is particularly noteworthy, says Stanley Hazen, MD, PhD, co-senior author on the study and Cleveland Clinic’s co-section head for Preventative Cardiology & Cardiovascular Rehabilitation.

“COVID-19 somehow provokes lasting changes in its hosts,” he says. “Whether that is epigenetics, or some other adaptive immune change or other effect — we don’t know. But it leads to much more than an upper respiratory tract infection. A better understanding of what it does at the molecular level can also potentially teach us about pathways linked to cardiovascular disease risk.”

Dr. Hazen and co-senior author Hooman Allayee, PhD, Keck School of Medicine of USC, have collaborated for over 15 years, resulting in more than 50 publications. Dr. Allayee is a computational biologist and geneticist with expertise in systems biology.

"Our data suggesting that risk of heart attacks and strokes was especially higher among COVID-19 patients with A, B, or AB blood types has significant clinical implications,” Dr. Allayee explains. “Given our collective observations and that 60% of the world's population have these non-O blood types, our study raises important questions about whether more aggressive cardiovascular risk reduction efforts should be considered, possibly by even taking into consideration an individual's genetic makeup."

Severe COVID-19 and heart disease prevention

Risk equivalents are used by clinicians to indicate the need for preventive care. Coronary artery disease (CAD) risk equivalents include heart attack, stroke, documented CAD by any imaging study, history of revascularization procedure (e.g. angioplasty, stent, coronary artery bypass graft surgery), history of diabetes and peripheral arterial disease. This study showed that a history of severe COVID-19 (requiring hospitalization) was associated with incident heart attack, stroke and death risk at least as strong or stronger than every CAD risk equivalent examined.

An example of preventative care would be if after seeing a hospital stay for COVID-19 in a patient’s history, a physician encourages preventive measures like changes to LDL (bad) cholesterol goals and medications, diet and exercise. The clinician could introduce or adjust doses of medications like statin therapy or antiplatelet prophylaxis therapy, Dr. Hazen says.

“Clinically, we have used ‘CAD risk equivalence’ as the threshold for escalating risk categories and intensifying global preventive cardiovascular disease risk-reducing efforts — such as lowering LDL cholesterol,” Dr. Hazen says. “Observation that severe COVID-19 infection is a CAD risk equivalent argues that we should consider taking that history into account when formulating cardiovascular disease preventive plans and goals.”

The authors wrote the findings show that the long-term risk associated with COVID-19 “continues to pose a significant public health burden” and that further investigation is needed.

“Worldwide over a billion people have already experienced Covid-19. The results reported are not a small effect in a small subgroup,” Dr. Hazen explains. “The results reported included nearly a quarter million people and point to a finding of global healthcare importance that promises to translate into a rise in cardiovascular disease worldwide.”  

Heart disease, blood type and COVID-19

Certain genetic variants already are linked to CAD, heart attack and COVID-19 risk. The researchers completed genetic analysis to see if any of these known variants contribute to elevated CAD risk after COVID-19.

None of the known genetic variants showed up as genetic drivers of cardiovascular events and COVID-19. Instead, the data highlighted an association between elevated risk and blood type.

Previous research has shown that people who have AB, A or B blood types were more susceptible to contracting COVID-19. This analysis showed patients with these blood types show an elevated risk of CAD after COVID-19 diagnosis compared to counterparts with O-type blood. AB, A and B blood types comprise more than half of the world’s population.

The association indicates a potential interaction between the virus and the piece of our genetic code that determines blood type and signals the need for further investigation into the genetic locus ABO and the cardiovascular system.  

“ABO is a carbohydrate group on the surface of cells, including red blood cells, that needs to be matched to prevent adverse reactions during a blood transfusion,” says Dr. Hazen. “However, that same carbohydrate group is also likely present on other cells in our body, so further understanding of how the ABO gene is linked to CVD risk is important — not just in a post-COVID-19 setting, but for CVD in general.”