In a recent study published in Nature Medicine*, researchers estimated the risk and one-year burden of a set of pre-specified cardiovascular outcomes in a cohort of coronavirus disease 2019 (COVID-19)-infected patients who survived the acute phase of illness.

Study: Long-term cardiovascular outcomes of COVID-19. Image Credit: Kateryna Kon/Shutterstock

Although well described, the cardiovascular complications associated with Long COVID are not well characterized in previous studies. While these studies have investigated cardiovascular outcomes in the post-acute phase of the COVID-19, they have only assessed these risks in hospitalized individuals (constituting a minority of COVID-19-infected people) over a short follow-up period. Moreover, they have not covered all possible cardiovascular outcomes extensively.

Studies comprehensively investigating incidences of cardiovascular diseases post-acute COVID-19 for 12 months and covering a diverse spectrum of care settings are rare. Addressing this knowledge gap will draw attention to cardiovascular health and inform policymakers to devise care pathways for those surviving the acute episode of COVID-19.

The study

In the present study, researchers used the electronic healthcare databases of the US Department of Veterans Affairs to enroll 162,690 participants into the COVID-19 group, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 March 2020 and 15 January 2021. However, they examined cardiovascular outcomes in only 153,760 participants who were alive 30 days after the positive COVID-19 test.

They built two control groups, a contemporary and a historical cohort, comprising 5,637,647 and 5,859,411 individuals, respectively, with no evidence of SARS-CoV-2 infection. Although individuals of the historical control group used the US Veterans Health Administration (VHA) system in 2017, they never encountered the COVID-19 pandemic.

The researchers followed up with all three cohorts longitudinally to estimate the risks and 12-month burdens of incident cardiovascular outcomes across all the cohorts. These estimates also accounted for the patient care settings, namely non-hospitalized, hospitalized, and admitted to the intensive care units (ICUs). Median follow-up time in the COVID-19, contemporary control, and historical control groups was 347, 348, and 347 days, respectively. 

The researchers ascertained composite cardiovascular outcomes beyond 30 days after the COVID-19-positive test until the end of follow-up (12 months). The assessment covered several cardiovascular outcomes, including cerebrovascular disorders, inflammatory heart diseases, dysrhythmias, ischemic heart disease, heart failure, thrombotic disorders, and major adverse cardiovascular events (MACE) — a composite of myocardial infarction, stroke, and all-cause mortality.

Study findings

SARS-CoV-2-infected participants, regardless of age, sex, ethnicity, and other cardiovascular risk factors, such as obesity, diabetes, and hypertension, were at increased risk of suffering from several cardiovascular diseases. Therefore, those who survived the first 30 days of COVID-19 (acute phase of COVID-19) exhibited an increased risk of stroke, atrial fibrillation, pericarditis with hazard ratios (HRs) of 1.52, 1.71, and 1.85, respectively. Notably, the risk and excess burden of adverse cardiovascular outcomes extended up to 1 year.

The findings provided scientific evidence that these risks might manifest even in people at low risk of cardiovascular disease. However, the risks and associated burdens exhibited a gradual increase across the severity scale of the acute phase of COVID-19 among non-hospitalized, hospitalized, and individuals admitted to ICUs.

The analyses made it evident that the risk and associated burdens of cardiovascular outcomes were high even among those not hospitalized during the acute phase of COVID-19. The study barred participants at the time of vaccination and used controlling for vaccination as a time-varying co-variate to demonstrate that the increased risk of myocarditis and pericarditis was significant in unvaccinated people. These conditions were evident regardless of one's vaccination status.

Conclusions 

The study findings highlighted the need for implementing strategies to control primary SARS-CoV-2 infections to prevent Long COVID and its countless complications, including the risk of severe cardiovascular diseases. 

Additionally, the authors recommended that global health systems should be prepared to handle a vast number of potentially affected people as the study reported a 12-month burden of cardiovascular diseases. These conditions not only have long-lasting consequences on people and health systems but may also have broad consequences on socioeconomic conditions and life expectancy, and addressing these challenges associated with Long COVID will require a coordinated global response strategy.

Future studies should investigate underlying mechanistic pathways responsible for the development of cardiovascular diseases in the post-acute phase of COVID-19. A deeper understanding of these mechanisms will help inform the development of strategies to prevent cardiovascular manifestations among people with COVID-19.