Investigating the effect of cardiovascular risk level on severe outcomes of COVID-19

Date of Approval: 
2020-12-15 00:00:00
Lay Summary: 
The COVID-19 pandemic has led to more than one million deaths worldwide. Many deaths from COVID-19 infection have occurred in people with underlying health conditions such as heart disease. Damage to the heart has also been seen among people who have died from COVID-19. We do not yet know exactly which groups of people are most at risk of developing heart problems or dying after COVID-19. However, it is likely that people whose cardiovascular risk level is already raised, e.g. because they have high blood pressure, may be at higher risk. Currently though, these people are not included in any lists of vulnerable groups and so will not be prioritised to receive a future COVID-19 vaccine. In this study, we aim to investigate whether adults aged 40 years or over who are at raised cardiovascular risk because of factors such as high blood pressure have a greater chance of dying or developing heart problems after COVID-19 infection than those with low cardiovascular risk levels. We will use anonymous data from GP and hospital records and laboratories to compare rates of heart problems and deaths after COVID-19 infection, controlling for factors such as other underlying health conditions. We will carry out two research studies with different designs to improve confidence in our results. This will help policymakers to understand which groups should be prioritised for COVID-19 vaccine.
Technical Summary: 
The COVID-19 pandemic has led to >one million deaths worldwide. Hospitalisations and deaths are common among patients with cardiovascular disease or risk factors such as hypertension, while myocardial injury is frequently observed among severe COVID-19 cases and is strongly associated with mortality. A wide range of other respiratory viruses and bacteria can trigger acute cardiovascular events among vulnerable groups. Nevertheless, people at raised cardiovascular risk but without existing cardiovascular disease have not been identified as a risk group for severe COVID-19 by Public Health England. Information is urgently needed on the risk of adverse outcomes after infection for those at raised cardiovascular risk to ensure that policymakers have the best evidence to target a future COVID-19 vaccine appropriately. We aim to investigate the effect of having a raised cardiovascular risk level, defined initially by QRISK3 score and then by hypertension status, or by the presence of existing cardiovascular disease, on severe outcomes of COVID-19. We will use linked data from general practices, hospital admissions and national laboratory and hospital surveillance for COVID-19 to compare mortality rates and the rates of major adverse cardiovascular events after laboratory-confirmed infection among those aged 40 years or over with differing levels of cardiovascular risk. After describing incidence rates of the outcomes by cardiovascular risk group, we will carry out a cohort study using multivariable Cox proportional hazards regression to calculate hazard ratios for each outcome after COVID-19 infection in the different risk groups. We will then conduct a complementary self-controlled case series study, which implicitly controls for the effect of fixed confounding factors, by level of cardiovascular risk to triangulate results. We will finally carry out a series of sensitivity analyses including exploring the effect of clinical and suspected COVID-19 infection among those without laboratory test results to check the robustness of our models.
Health Outcomes to be Measured: 
Cohort study: Primary outcome: Death attributable to COVID-19, using the definition of death within 28 days of a positive test used by the Department of Health and Social Care. Secondary outcomes: • Hospitalisation due to COVID-19, defined by COVID-19 in the primary diagnosis field of any episode recorded in Hospital Episode Statistics. • Admission to an intensive care unit (ICU) due to COVID-19, defined by laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during or prior to ICU admission recorded in the COVID-19 Hospitalisation in England Surveillance System (CHESS). • Need for respiratory support due to COVID-19, defined as receipt of oxygen by mask or prongs, non-invasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation recorded in CHESS. • Major adverse cardiovascular event (composite of acute coronary syndrome i.e. myocardial infarction and unstable angina, ischaemic stroke, acute left ventricular failure, major ventricular arrhythmia, cardiovascular death) • Acute coronary syndrome (subdivided into myocardial infarction and unstable angina) • Ischaemic stroke • Acute left ventricular failure • Major ventricular arrhythmia • Cardiovascular death Self-controlled case series study: Primary outcome: major adverse cardiovascular event (composite of acute coronary syndrome i.e. myocardial infarction and unstable angina, ischaemic stroke, acute left ventricular failure, major ventricular arrhythmia) Secondary outcomes: • Acute coronary syndrome (subdivided into myocardial infarction and unstable angina) • Ischaemic stroke • Acute left ventricular failure • Major ventricular arrhythmia
Application Number: 
20_000135
Collaborators: 

Charlotte Warren-Gash - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Charlotte Warren-Gash - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Amitava Banerjee - Collaborator - University College London ( UCL )
Emily Herrett - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Harriet Forbes - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Helen Strongman - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jennifer Davidson - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Judith Breuer - Collaborator - University College London ( UCL )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )

Linkages: 
CHESS (Hospitalisation in England Surveillance System);HES Admitted Patient Care;ONS Death Registration Data;Patient Level Townsend Score;SGSS (Second Generation Surveillance System);COVID-19 Linkages