Managing cardiovascular disease and risk in Covid-19 patients in primary care medicine

Date of Approval
Application Number
Lay Summary
Over the last months, the world has experienced a global outbreak of Covid-19. Covid-19 fortunately leads to a mild viral respiratory infection in most patients. However, about 10% of affected patients will develop critical illness, leading to death in some of them. Development of critical illness appears to be strongly linked with cardiovascular disease, as exemplified by the observation that most hospitalized patients are known with cardiovascular disease or its risk factors like diabetes and obesity. Also, we know that deterioration into critical illness occurs often very rapidly, likely due to inflammation of the vessel wall and formation of blood clots that obstruct blood flow of the lungs. Too often, it then is too late to stop this ‘perfect storm’ of uncontrolled inflammation and thrombosis and only supportive care (e.g. mechanical ventilation) can be provided.
With this proposal, we aim to test the hypothesis that cardiovascular involvement with Covid-19 should be targeted early in primary care in order to be successful in mitigating cardiovascular risk and complications in these patients. As part of this consortium, this study specifically aims to develop a tool that helps to identify cardiovascular high-risk patients with Covid-19 already in primary care, before critical illness has developed. General practitioners can use this tool to ‘flag’ high-risk patients, monitor them more closely, timely refer them to a hospital, or prescribe preventive cardiovascular medication earlier (‘moon shot’).
Technical Summary
From late 2019 onwards, the spread of the novel corona virus SARS-CoV-2 reached pandemic proportions. While the resulting infectious disorder Covid-19 showed a mild disease course in most patients, a small proportion of patients developed critical illness, necessitating oxygen admission or ICU admission with mechanical ventilation, and sometimes leading to death. Early studies showed a clear association of Covid-19 with cardiovascular disease. From an epidemiological aspect, there were clear observations showing an overrepresentation of patients with a history of cardiovascular disease and metabolic risk factors (e.g. diabetes and obesity) in those entering hospital care. Pathophysiological explanations for these observations might involve endothelial involvement, vascular leakage, hypercoagulability and thrombosis in Covid-19 patients with critical illness.
The large population of Covid-19 patients treated in primary care, however, is less well studied, although in this setting timely targeting cardiovascular involvement in Covid-19 might prevent deterioration. This study aims to estimate the incidence of cardiac and thrombo-vascular complications in patients with Covid-19 seen in primary care. Incidence rates will be presented as number of events per 90 person days of follow-up since point of first contact with primary care. Next, we aim to develop a prognostic prediction model in these patients to quantify absolute risks of cardiac and thrombo-vascular complications. Multivariable logistic regression will be performed to obtain adjusted odds ratios with corresponding confidence margins of the relevant predictors of cardiac and thrombo-vascular complications. Last, this study aims to estimate the relative effectiveness of antithrombotic treatment in patients with Covid-19 for preventing these aforementioned adverse outcomes. Potential confounding by indication will be addressed using propensity scoring methods.
Ultimately, this study helps general practitioners to identify patients at high risk of critical illness, monitor them more closely, timely refer them to a hospital, or prescribe preventive cardiovascular medication earlier.
Health Outcomes to be Measured
For this study, the main outcome consists of cardiac and thrombo-vascular complications, including:
• Transient ischaemic attack (TIA)
• Ischaemic stroke
• Atrial fibrillation (AF)
• Peripheral artery disease (PAD)
• Acute coronary syndrome (ACS), consisting of acute myocardial infarction (AMI) and unstable angina
• Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE);

Olaf Klungel - Chief Investigator - Utrecht University

Patrick Souverein - Corresponding Applicant - Utrecht University

Geert-Jan Geersing - Collaborator - UMC Utrecht

Hendrika van den Ham - Collaborator - Utrecht University

Sander van Doorn - Collaborator - UMC Utrecht

HES Admitted Patient Care