Study Affirms Higher CVD, Mortality Risks Among COVID-Positive Patients

Patients with COVID-19, especially those who are hospitalized, have a greater risk of dying or of developing a variety of adverse cardiovascular outcomes in the months that follow the initial infection, according to prospective data from the UK Biobank.

The findings, published online this week in Heart, confirm what’s already been seen in several prior studies from around the world, including a large analysis of the US Department of Veterans Affairs healthcare system.

Of note, the risk of venous thromboembolism (VTE) was greater in patients with COVID-19 than in uninfected controls even if they were not admitted or had COVID-19 listed as a secondary rather than a primary diagnosis in their hospitalization records.

“Greater attention to management of cardiovascular risk and low threshold for investigations of patients with past COVID-19 hospitalization are important in prevention and timely treatment of cardiovascular events,” lead author Zahra Raisi-Estabragh, MBChB, PhD (Queen Mary University of London, England), and colleagues write.

“The long-term sequelae of past COVID-19 exposure is emerging as a dominant public health concern,” they add. “Our findings highlight the increased cardiovascular risk of individuals with past infection, which are likely to be greater in countries with limited access to vaccination and thus greater population exposure to COVID-19. Furthermore, the long-term cardiovascular consequences reported in our study may be relevant in the context of future pandemics of similar viral infections.”

UK Biobank

For the study, the investigators turned to the UK Biobank, matching 17,871 participants who had COVID-19 between March 2020 and March 2021 with 35,742 who didn’t have COVID-19 then following them prospectively for an average of 141 days. In the overall matched cohort, median patient age was 65 and 53% of participants were women.

During follow-up, the rate of incident CVD or death was 9.0% among those with COVID-19 and 0.7% among controls, with rates of incident CVD of 3.0% and 0.5%, respectively. The most common cardiovascular diseases were atrial fibrillation (AF), VTE, and heart failure.

Most of the patients with COVID-19 (80%) were never hospitalized, and in these patients COVID-19 was associated with greater risks of VTE (HR 2.7; 95% CI 1.4-5.5) and all-cause death (HR 10.2; 95% CI 7.6-13.7) but none of the other outcomes of interest.

Most of the hospitalized patients had COVID-19 as their primary diagnosis, and in this group COVID-19 was associated with greater risks of all cardiovascular events and death compared with controls. That included cardiovascular events like MI, stroke, heart failure, AF, VTE, and pericarditis (hazard ratios ranging from 9.9 to 27.6), all-cause death (HR 118.0), CVD death (HR 8.8), and ischemic heart disease death (HR 14.1).

In general, hospitalized patients who had COVID-19 listed as a secondary diagnosis also had greater risks of all outcomes compared with controls, although there were too few cases of pericarditis for a formal assessment.

These heightened risks were most evident in the first 30 days after infection with SARS-CoV-2, but they could still be detected beyond that time point, with some variation across endpoints.

‘Remarkable and Clear’ Findings

Kevin Clerkin, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), lead author of a paper highlighting the intersection of COVID-19 and cardiovascular disease in the early days of the pandemic, said this new study confirms the link in a large database with a well-phenotyped group of patients.

The particularly strong associations seen between COVID-19 and VTE, heart failure, and stroke are indicative of the hypercoagulable state that has been seen in the context of SARS-CoV-2 infection, particularly during the first few waves of the pandemic, Clerkin told TCTMD.

The message is to “be very careful with your patients who come out of the hospital after COVID-19 who have cardiovascular disease,” he said, noting that the greatest danger is in the first 30 days. “While we celebrate our patients with COVID-19 getting better and getting out of the hospital, it’s still a vulnerable period and we should be extra cognizant of this.”

Even for patients who don’t have preexisting cardiovascular disease, it’s probably a good idea to be seen by a medical professional shortly after recovering from COVID-19 to potentially catch a developing issue, Clerkin advised.

In an accompanying editorial, Anda Bularga, MBChB (University of Edinburgh, Scotland), and colleagues call the findings of the study “remarkable and clear,” complementing evidence from prior studies showing a link between systemic inflammation secondary to respiratory tract infections and increased risks of cardiovascular events.

“However, the proportionately greater breadth and increase in cardiovascular events seen with COVID-19 are exceptional and suggest more than a simple inflammatory effect,” they write. “This has been hypothesized to relate to endothelial dysfunction or prothrombotic effects of COVID-19 in addition to typical cardiovascular risk factors and underlying previously unrecognized coronary or structural heart disease.”

Bularga et al highlight remaining questions around the optimal antithrombotic treatments in the setting of COVID-19, but say this new study “will inform how we now try to treat and to prevent the cardiovascular events associated with COVID-19 in the years to come.”