Cohort study of risk factors of acute and chronic cardiovascular events in COVID-19 patients

Study type
Protocol
Date of Approval
Study reference ID
20_000265
Lay Summary

This research aims to inform patient management during the present COVID-19 coronavirus pandemic. Early findings suggest that patients with COVID-19 commonly experience conditions affecting the heart and blood vessels (cardiovascular conditions) such as heart failure. Acute heart failure often leads to very severe outcomes including death. We are also interested in understanding the risk factors for longer-term cardiovascular outcomes in COVID-19 patients such as chronic heart failure. Those with cardiovascular risk factors, such as high blood pressure, and who have experienced cardiovascular conditions in the past, seem to be at increased risk of poor COVID-19 outcomes. However, studies have reported several cases of cardiovascular events following a COVID-19 diagnosis in patients without a history of cardiovascular disease. It appears that the SARS-CoV-2 virus that causes COVID-19, might be capable of directly causing damage to the heart and more research is required to understand which patients are likely to benefit from dedicated, specialist cardiac care and monitoring. This study will use Clinical Practice Research Datalink (CPRD) data to collate cardiovascular risk factors in COVID-19 patients to assess their association with cardiovascular events including acute heart failure, chronic heart failure and death. We will analyse data from patients who have diagnoses of heart failure or other cardiovascular conditions, comparing risk factors and disease progression among those with a preceding COVID-19 diagnosis to those without.

Technical Summary

Cardiovascular risk factors and heart conditions have been associated with increased risk of poor COVID-19 outcomes. Several hospitalised COVID-19 patients have developed cardiovascular outcomes including acute heart failure, chronic heart failure, pulmonary edema and myocardial infarction. Pre-existing cardiovascular disease seems to be an important driver of COVID-19 severity, however other studies have noted serious cardiovascular outcomes in COVID-19 patients without a history of cardiovascular disease. SARS-CoV-2 could directly induce myocardial damage, potentially via the proinflammatory cytokine storm. We seek to improve evidence in this area for earlier identification of COVID-19 patients at high risk of cardiovascular outcomes who could benefit from dedicated cardiac monitoring and early referral to specialist teams. We will use the Clinical Practice Research Datalink (CPRD) Aurum and GOLD datasets to conduct a population cohort study, evaluating outcomes among patients with a COVID-19 diagnosis compared to a matched cohort without a COVID-19 diagnosis. Outcomes will be hospital readmission, mortality, diabetes events and cardiovascular events following COVID-19 diagnosis. Cox proportional hazards regression models will use hazards ratios to compare outcomes to a cohort of patients matched to the COVID-19 patients on practice, gender and year of birth and no COVID-19 diagnosis during the study period. Matched analyses will be adjusted for covariates including ethnicity; risk profiles between groups will be compared. Cardiovascular disease risk factors will be compiled including smoking status, blood pressure, cholesterol, diabetes and body mass index. Hospital admissions and cardiovascular events will be identified using the Hospital Episode Statistics Admitted Patient Care registry. We will use the Office for National Statistics (ONS) Death Registration Data for mortality data if possible, but note that the latest release (set 20) only covers up to June 2020. Should there be no further release prior to initiating our analysis, we will use the CPRD Aurum and GOLD death dates instead. A secondary analysis will evaluate longer-term cardiovascular effects of COVID-19 using CPRD data on relevant prescriptions including diuretics and anticoagulants.

Health Outcomes to be Measured

Primary analysis:
- Hospital admission.
- Mortality.
- Diabetes.
- Cardiovascular disease diagnoses.
Outcomes will be evaluated over the duration of the study period.

Secondary analysis
Chronic cardiovascular conditions following index dates among those surviving, measured according to prescriptions for:
- diuretics
- anticoagulants
- aspirin
- antihypertensive drugs
- antiplatelet drugs
- lipid lowering drugs (mainly statins).

Collaborators

Martin Gulliford - Chief Investigator - King's College London (KCL)
Emma Rezel-Potts - Corresponding Applicant - King's College London (KCL)

Linkages

Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation