COVID-19 Tied to Increased Risk for CV Events and Death

Ashley Lyles

October 28, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

COVID-19 infection is associated with an elevated risk for incident cardiovascular disease events and death compared with those with no history of COVID-19, a retrospective analysis shows.

The risk for adverse outcomes and death was highest among those hospitalized for COVID-19, but, in those not hospitalized, there was still an increased risk for venous thromboembolism (VTE) and mortality after infection.

Notably, events with the largest risks for those hospitalized for COVID were stroke, VTE, and heart failure, but increases were also seen in incident atrial fibrillation (AF), pericarditis, and myocardial infarction (MI), Zahra Raisi-Estabragh, Queen Mary University of London, United Kingdom, and colleagues reported.

The risk for cardiovascular disease events and mortality was "almost entirely confined to those requiring hospitalization and [was] highest in the first 30 days post infection but remained augmented for a prolonged period thereafter," the authors concluded.

The results were published online October 24 in the journal Heart.

The study team set out to assess the relationship between incident cardiovascular events and COVID-19 using data from the UK Biobank.

They evaluated 35,742 propensity score-matched uninfected controls and 17,871 participants with a history of COVID-19. Females accounted for 55.3% of the whole UK Biobank cohort, and their median age was 69 years. The researchers followed the patients from March 2020 to the time of a cardiovascular event, until a patient died, or until March 2021.

Of the 17,871 COVID-19 cases included in the study, 14,304 didn't require hospitalization, 866 patients were found to have COVID-19 but were hospitalized for other conditions, and 2701 required hospital admission for their COVID infection.

The investigators identified COVID-19 cases with health record data. They then propensity score–matched each Biobank case to two uninfected controls based on high cholesterol, smoking, sex, age, ethnicity, diabetes, deprivation, smoking, body mass index, and hypertension.

Ischemic heart disease death, VTE, all-cause mortality, pericarditis, cardiovascular mortality, MI, AF, heart failure, and stroke were all among the incident outcomes assessed. Over a mean prospective follow-up period of 141 days, the researchers estimated the relationships between COVID-19 and each outcome using Cox proportional hazards regression.

In nonhospitalized cases of COVID-19, they found an increased risk for death (hazard ratio [HR], 10.23; P < .0001) and incident VTE (HR, 2.74; P = .004) compared with matched uninfected controls.

Patients hospitalized primarily for their COVID-19 infection (2701) had increased risk for "all outcomes considered," the authors write. The largest effect sizes were seen for stroke (HR, 17.5; P < .0001), VTE (HR, 27.6; P < .0001), and heart failure (HR, 21.6; P < .0001), but higher risks were also seen for incident AF, which was increased by almost 15-fold, they note. Pericarditis increased by 14-fold, and there was a 10-fold increase in MI in the hospitalized COVID patients compared with uninfected controls. 

Finally, among patients hospitalized for other issues and found to have COVID-19 as a secondary diagnosis (n = 866), there was an increased risk for all incident outcomes compared with those without infection. While their risk for all-cause death was lower than for those hospitalized primarily for COVID-19, the risk for death from cardiovascular or ischemic heart disease was higher, as was incident MI and AF risk.  

"Currently, the National Institute [for] Health and Care Excellence recommends prophylactic low molecular weight heparin for VTE prevention in hospitalized patients with COVID-19 and in patients who would otherwise be admitted to hospital (eg, hospital at home) for a minimum of 7 days," the authors note, consistent with similar recommendations from the British Thoracic Society and the American Society of Hematology. "Our results indicate that the risk of VTE is also increased in non-hospitalized individuals," they write.

Limitations of the study include residual confounding from comorbidities not accounted for in the matching method, lack of consideration for the effects of cardiovascular prescription drugs like angiotensin-converting enzyme inhibitors or statins, and possible underestimation of adverse cardiovascular risk given the relatively healthy UK Biobank cohort, the study authors noted.

Further, the study does not account for other possible modifying factors like multiple infection exposures, effects of COVID-19 vaccinations, and new variants, the investigators added.

More investigation is needed to determine the timeframe over which cardiovascular risk is elevated after COVID-19, the study authors noted.

"Future studies are needed to address whether specific interventions are needed to mitigate the risk of venous thromboembolism associated with COVID-19," they conclude.

Expert Commentary

These results fall into line with the existing literature, noted Anda Bularga, MD, David Newby, MD, PhD, and Andrew R. Chapman, MD, all from The University of Edinburgh, United Kingdom, in an accompanying editorial.

Before the COVID-19 pandemic, systemic inflammation due to respiratory tract infections was a well-known risk factor for stroke and incident MI, with a four-time greater risk reported in an assessment of 5 million patients within 3 days of diagnosis of lower respiratory tract infection as documented in the UK General Practice Research Database, the editorialists noted.

Comparable results have been reported in numerous contexts, such as infective exacerbation of chronic obstructive pulmonary disease, where there is a noteworthy risk for early cardiovascular events that is also elevated in hospitalized patients, they added.

"The prothrombotic effects of COVID-19 do raise the question of whether antithrombotic strategies are required to prevent this large excess of events."

Perhaps a larger question to consider is if the use of antithrombotic treatments, including anticoagulant or antiplatelet therapies, should be considered in all patients, they write.  

"Clearly, duration of therapy is relevant, and these data do question whether 7 days of prophylactic anticoagulation is sufficient for patients with COVID-19," the editorialists concluded.  

Srihari S. Naidu, MD, professor of medicine at New York Medical College in Valhalla, who was not involved in the study, commented on the results for | Medscape Cardiology.

"We have to be much more vigilant about these patients even after 30 days," he said. "For the more common cardiovascular events that we may ascribe to just normal underlying cardiovascular disease but really, based on this data, it is being heightened or increased because of an ongoing likely inflammatory prothrombotic effect that has lingering consequences after 30 days."

Naidu noted that future research should look at more recent waves and variants of COVID-19. "My suspicion is that the risk will be much lower," he added. "That would provide some reassurance that if you didn't get COVID-19 during that first year, that COVID now is a more benign disease."

Heart. Published online October 24, 2022. Full text, Editorial

Naidu reported no relevant financial relationships.

Ashley Lyles is an award-winning medical journalist. She is a graduate of New York University's Science, Health, and Environmental Reporting Program. Previously, she studied professional writing at Michigan State University. Her work has appeared in outlets like The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, Insider, and Tonic (Health by Vice), among other publications.

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