What is the association between COVID-19, cardiovascular disease, and mortality?

In a recent study published in Cardiovascular Research, researchers evaluated the association between COVID-19 (coronavirus disease 2019) and CVD (cardiovascular disease) and/or death.

Background

CVD symptoms have been reported in a considerable proportion of individuals with COVID-19, who exhibited cardiac structural and functional abnormalities such as myocardial injury and increased levels of cardiac tissue troponin. Improving the understanding of cardiovascular outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections could aid in identifying high-risk patients and providing tailored therapy to improve the standard of care.

About the study

In the present study, researchers investigated cardiac presentation among COVID-19 patients and those with long COVID.

The team identified SARS-CoV-2-positive from the United Kingdom (UK) Biobank database between March 16, 2020, and November 30, 2020, and followed them up for 18.0 months, through August 31, 2021. Based on sex and age, COVID-19 cases were matched with ≤10 individuals lacking SARS-CoV-2 infections (controls) of a historical group between March 16, 2018, and November 30, 2018, and a contemporary group between March 16, 2020, and November 30, 2020.

The team adjusted individual characteristics using propensity score-matching and MMWS (marginal mean weighting through stratification) for sex, age, body mass index, ethnicity, smoking, hypertension, diabetes, Charlson comorbidity index, hypertension, multiple deprivation index, and previous history of COVID-19 outcomes. Cox proportional hazard regression modeling was performed to assess the association between the development of cardiovascular disease and deaths within 3.0 weeks of diagnosis (during the acute period) and the period following that of acute COVID-19, and hazard ratios (HR) were calculated.

COVID-19 severity was based on data on critical care admissions and the type of healthcare support extended to each SARS-CoV-2-positive individual. Data of the participants, provided by the United Kingdom biobank, were linked to primary care (general practitioner level) data via England’s phoenix partnership and Egton medical data system through August 31, 2021.

In addition, data on hospitalized inpatients provided by the NHS (National Health Service) digital public health of Scotland and mortality records were linked to the data provided by the National Health Service of Wales, Scotland, and England, of the study participants. COVID-19 diagnoses were based on positive PCR (polymerase chain reaction) analysis reports or the international classification of diseases, 10^th revision (ICD-10) hospitalization codes U07.1 and U07.2 for COVID-19-associated diagnosis. Subgroup analyses were performed to evaluate cardiovascular and mortality risks based on COVID-19 severity and the sex of individuals.

Results

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During the acute period, in comparison to 75,790 contemporary controls and 75,774 historical controls, the cohort of 7,584 SARS-CoV-2-positive individuals demonstrated a significantly greater risk of cardiovascular disease (HR 4.30; HR 5.00) and any-cause deaths (HR: 81; HR: 68), respectively, in the short-term. During the period following the acute SARS-CoV-2 infection period, the cohort of 7, 139 COVID-19 patients exhibited a significantly greater risk of long-term cardiovascular disease (HR 1.40; HR 1.30) and any-cause deaths (HR: 5.00; HR 4.50) in comparison to 71,296 contemporary controls and 71,314 historical controls, respectively.

During the acute period, the incidence rate of SARS-CoV-2 infection-associated deaths was 700. Of note, the risk of DVT (deep vein thrombosis), AF (atrial fibrillation), and stroke was significantly greater in comparison to individuals belonging to the contemporary group (stroke: 10; AF: 8.0; DVT: 22) and the historical group (stroke: 5.0; AF: 6.0; DVT: 11). During the period following that of acute COVID-19, the incidence rate for SARS-CoV-2 infection-associated deaths was 12. Of note, unlike during the acute period, post-acute COVID-19 patients were at a significantly greater risk of pericarditis compared to contemporary control individuals (HR 4.6) and historical control individuals (HR 4.50).

In the subgroup analyses, severe COVID-19 patients showed a greater likelihood of developing major cardiovascular diseases and of any-cause death in comparison to non-severe COVID-19 cases, and the male sex was related to a greater risk of cardiovascular disease development in the acute COVID-19 period; however, during the post-acute period, the cardiovascular risks were largely comparable among males and females.

Probable mechanisms to explain long COVID cardiac pathophysiology include direct effects of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) receptor binding since the receptor, critical for SARS-CoV-2 entry, is present in cardiac tissues, including cardiac vasculature. SARS-CoV-2 might infect myocardial cells and other cardiac cells directly, underpinned by previously published histopathological findings of marked elevation in the infiltration of macrophages in myocardial tissues. 

Overall, the study findings showed that SARS-CoV-2 infections and long COVID increase the risks of cardiovascular disease development and death in the short- and long-term. The findings indicated that regular monitoring of cardiovascular disease-associated clinical presentation till ≤1.0-year post-COVID-19 recovery could benefit SARS-CoV-2-infected individuals, particularly males with severe COVID-19.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.