In mild cases of COVID, blood clot risk is higher

By Dr. Chinta SidharthanReviewed by Benedette Cuffari, M.Sc.Oct 27 2022

In a recent study published in the journal Heart, researchers examine the association between the coronavirus disease 2019 (COVID-19) and increased cardiovascular outcomes and mortality sequelae.

Study: Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank. Image Credit: Artem Oleshko / Shutterstock.com

Background

Previous studies have reported a predominant pattern of COVID-19 sequelae involving debilitating fatigue and persistent cardiac, neurological, digestive, renal, pulmonary, and muscular problems. This phenomenon is commonly referred to as “long COVID” and often persists for several months following recovery from severe COVID-19.

While many studies have examined the cardiovascular outcomes after recovery from COVID-19, none have examined the differential risks based on COVID-19 severity. Furthermore, many of these have been retrospective studies.

Therefore, examining whether the increased risk of cardiovascular complications associated with COVID-19 depends on the severity of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infections is essential.

About the study

In the present study, researchers used data from 17,871 United Kingdom Biobank participants between the ages of 40 and 69 years to investigate associations between COVID-19 and cardiovascular outcomes and mortality sequelae. A matched uninfected group of controls was also included in the study. A baseline assessment was performed for all participants.

COVID-19 incidence was defined based on primary care disease codes, Hospital Episode Statistics records, or a positive antigen or polymerase chain reaction (PCR) test. Propensity score variables such as age, body mass index, sex, ethnicity, Townsend deprivation index, smoking behavior, and comorbidities such as diabetes, ischemic heart disease, hypertension, and high cholesterol were included in the analysis.

Cardiovascular disease outcomes were identified from the Hospital Episode Statistics and death registration records and included stroke, myocardial infarction, thromboembolism, heart failure, pericarditis, atrial fibrillation, all-cause mortality, and mortality due to cardiovascular disease and ischemic heart disease. Study participants were monitored from the first episode of an outcome until the end of the follow-up or death.

The association between COVID-19 and each outcome was estimated using Cox proportional hazard regression. The entire U.K. Biobank cohort was also used to perform a sensitivity analysis, with COVID-19 exposure considered a time-varying covariate. Four COVID-19 status levels were assessed ranging from unexposed to secondary hospital diagnosis.

Study findings

An increased risk of myocardial infarction, stroke, atrial fibrillation, heart failure, pericarditis, venous thromboembolism, all-cause mortality, and death due to ischemic heart disease and cardiovascular disease was associated with COVID-19 hospitalizations. In contrast, non-hospitalized COVID-19 patients were at a higher risk of only venous thromboembolisms and all-cause mortality.

Though cardiovascular risks were higher in the 30 days following recovery from COVID-19 as compared to the control group, the risk remained higher beyond the month following recovery. Furthermore, as compared to uninfected controls, hospitalized COVID-19 patients had a 27 times greater likelihood of developing venous thromboembolism and a 21.5 times higher risk of heart failure. Severe COVID-19 requiring hospitalization increased the risk of all-cause mortality by 118 times as compared to non-hospitalized patients.

The observations of increased venous thromboembolism risk in hospitalized and non-hospitalized COVID-19 patients alike are similar to other studies conducted in Scotland, Sweden, and the United States. The National Institute of Health and Care Excellence in the U.K. recommends a prophylactic treatment with low molecular weight heparin to hospitalized and home-isolated COVID-19 patients.

Increased incidence of myocardial infarction and stroke post-recovery among hospitalized COVID-19 patients was also consistent with previous retrospective and prospective analyses performed in Sweden and Denmark, respectively.

One previous retrospective cohort study similarly reported that an increased risk of ischemic heart disease was associated with hospitalized COVID-19 patients but not with influenza cases, thus suggesting a strong correlation between COVID-19 and cardiovascular outcomes. Several studies have hypothesized coagulopathy, vascular damage, and cytokine-mediated persistent immune responses as possible mechanisms of cardiovascular sequelae.

In contrast to the current study findings, a prospective analysis from the U.S. found an association between non-hospitalized COVID-19 cases and an increased risk of various cardiovascular conditions. The authors believe that this could be due to baseline differences among the U.K. and U.S. populations. Furthermore, impaired access to healthcare in the U.S, which let non-acute cardiac symptoms like stable angina worsen into acute events such as myocardial infarctions, may also contribute to these differences.

Nevertheless, these discrepancies highlight the need for longitudinal studies monitoring the cardiovascular conditions of mild-to-moderate COVID-19 cases that do not require hospitalization.

Conclusions

The study findings suggest a significant association between severe COVID-19 and increased risk of cardiovascular outcomes including myocardial infarction, heart failure, stroke, venous thromboembolism, arterial fibrillation, and cardiovascular and ischemic heart disease-related mortality. In contrast, mild cases of COVID-19 not requiring hospitalization were associated with a higher risk of venous thromboembolism and all-cause mortality only.