Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study

Abstract

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.

Fig. 1. Estimated number of COVID-19 cases identified by community testing in England between January 2020 and January 2022.

The start and end of follow-up for each cohort, the periods during which different variants were dominant and the times that mass testing became available and vaccination rollout commenced are shown. Code and underlying data are available in the following repository: https://github.com/grpEHR/covid_variants.

Fig. 2. Maximally adjusted hazard ratios and 95% CIs comparing the incidence of arterial thrombotic and venous thrombotic events after versus before or without a COVID-19 diagnosis, in the pre-vaccination, vaccinated and unvaccinated cohorts, overall and by COVID-19 severity.

Upper panels: Maximally adjusted hazard ratios and 95% CIs for arterial thrombotic events. Lower panels: Maximally adjusted hazard ratios and 95% CIs for venous thrombotic events. Left panels: all COVID-19 diagnoses: Middle panels: hospitalised COVID-19. Right panels: non-hospitalised COVID-19. The numbers of people in the pre-vaccination, vaccinated and unvaccinated cohorts were 18,210,937; 13,572,399 and 3,161,485 respectively. The numbers of COVID-19 diagnoses were 1,150,299 (75,667 hospitalised) in the pre-vaccination cohort, 844,235 (15,342 hospitalised) in the vaccinated cohort and 162,103 (9250 hospitalised) in the unvaccinated cohort. Maximally adjusted hazard ratios and 95% CIs are plotted at the median time of the outcome event within each follow up period in each cohort. Events on the day of COVID-19 diagnosis (day 0) were excluded. The numerical values of hazard ratios and their 95% CIs are displayed in Tables 3 and 4.

Fig. 3. Maximally adjusted hazard ratios and 95% CIs comparing the incidence of arterial thrombotic, venous thrombotic, and other vascular events after versus before or without a COVID-19 diagnosis, in the pre-vaccination, vaccinated and unvaccinated cohorts.

Upper left panel: Acute myocardial infarction. Upper right panel: Ischaemic stroke. Second row left panel: Pulmonary embolism. Second-row right panel: Deep vein thrombosis. Third row left panel: Heart failure. Third row right panel: Angina. Lower left panel: Transient ischaemic attack. Lower right panel: Subarachnoid haemorrhage and haemorrhagic stroke. The numbers of people in the pre-vaccination, vaccinated and unvaccinated cohorts were 18,210,937; 13,572,399 and 3,161,485, respectively. The numbers of COVID-19 diagnoses was 1,150,299 in the pre-vaccination cohort, 844,235 in the vaccinated cohort and 162,103 in the unvaccinated cohort. Maximally adjusted hazard ratios and 95% CIs are plotted at the median time of the outcome event within each follow-up period in each cohort. Events on the day of COVID-19 diagnosis (day 0) were excluded. The numerical values of hazard ratios and 95% CIs are displayed in Tables 3, 4 and 5.

Fig. 4. Estimated absolute increase in the risk of arterial thrombotic and venous thrombotic events over time since COVID-19 diagnosis, compared with no COVID-19 diagnosis, in the pre-vaccination, vaccinated and unvaccinated cohorts.

Upper panels: Estimated absolute increase in risk for arterial thrombotic events. Lower panels: Estimated absolute increase in risk for venous thrombotic events. Left panels: pre-vaccination cohort. Middle panels: vaccinated cohort. Right panels: unvaccinated cohort. The numbers of people in the pre-vaccination, vaccinated and unvaccinated cohorts were 18,210,937; 13,572,399 and 3,161,485 respectively. The number of COVID-19 diagnoses was 1,150,299 in the pre-vaccination cohort, 844,235 in the vaccinated cohort and 162,103 in the unvaccinated cohort. Increases in risks were estimated within sex and age groups, and the estimated overall increase in risk is the average of these (shown in black), weighted according to the proportions in each sex and age group in the pre-vaccination cohort. Estimated excess events at 28 weeks are displayed in Table S9.