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Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0002-0253-5928
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.ORCID iD: 0000-0002-5756-7791
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2021 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 398, no 10300, p. 599-607Article in journal (Refereed) Published
Abstract [en]

Background: COVID-19 is a complex disease targeting many organs. Previous studies highlight COVID-19 as a probable risk factor for acute cardiovascular complications. We aimed to quantify the risk of acute myocardial infarction and ischaemic stroke associated with COVID-19 by analysing all COVID-19 cases in Sweden.

Methods: This self-controlled case series (SCCS) and matched cohort study was done in Sweden. The personal identification numbers of all patients with COVID-19 in Sweden from Feb 1 to Sept 14, 2020, were identified and cross-linked with national inpatient, outpatient, cancer, and cause of death registers. The controls were matched on age, sex, and county of residence in Sweden. International Classification of Diseases codes for acute myocardial infarction or ischaemic stroke were identified in causes of hospital admission for all patients with COVID-19 in the SCCS and all patients with COVID-19 and the matched control individuals in the matched cohort study. The SCCS method was used to calculate the incidence rate ratio (IRR) for first acute myocardial infarction or ischaemic stroke following COVID-19 compared with a control period. The matched cohort study was used to determine the increased risk that COVID-19 confers compared with the background population of increased acute myocardial infarction or ischaemic stroke in the first 2 weeks following COVID-19.

Findings: 86 742 patients with COVID-19 were included in the SCCS study, and 348 481 matched control individuals were also included in the matched cohort study. When day of exposure was excluded from the risk period in the SCCS, the IRR for acute myocardial infarction was 2·89 (95% CI 1·51–5·55) for the first week, 2·53 (1·29–4·94) for the second week, and 1·60 (0·84–3·04) in weeks 3 and 4 following COVID-19. When day of exposure was included in the risk period, IRR was 8·44 (5·45–13·08) for the first week, 2·56 (1·31–5·01) for the second week, and 1·62 (0·85–3·09) for weeks 3 and 4 following COVID-19. The corresponding IRRs for ischaemic stroke when day of exposure was excluded from the risk period were 2·97 (1·71–5·15) in the first week, 2·80 (1·60–4·88) in the second week, and 2·10 (1·33–3·32) in weeks 3 and 4 following COVID-19; when day of exposure was included in the risk period, the IRRs were 6·18 (4·06–9·42) for the first week, 2·85 (1·64–4·97) for the second week, and 2·14 (1·36–3·38) for weeks 3 and 4 following COVID-19. In the matched cohort analysis excluding day 0, the odds ratio (OR) for acute myocardial infarction was 3·41 (1·58–7·36) and for stroke was 3·63 (1·69–7·80) in the 2 weeks following COVID-19. When day 0 was included in the matched cohort study, the OR for acute myocardial infarction was 6·61 (3·56–12·20) and for ischaemic stroke was 6·74 (3·71–12·20) in the 2 weeks following COVID-19.

Interpretation: Our findings suggest that COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke. This indicates that acute myocardial infarction and ischaemic stroke represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19. 

Place, publisher, year, edition, pages
Elsevier, 2021. Vol. 398, no 10300, p. 599-607
National Category
Public Health, Global Health and Social Medicine Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:umu:diva-186849DOI: 10.1016/S0140-6736(21)00896-5ISI: 000684589500018PubMedID: 34332652Scopus ID: 2-s2.0-85112397272OAI: oai:DiVA.org:umu-186849DiVA, id: diva2:1587395
Funder
Region Västerbotten, RV-836351Region Västerbotten, RV-939769Available from: 2021-08-24 Created: 2021-08-24 Last updated: 2026-05-29Bibliographically approved
In thesis
1. Cardiovascular complications following covid-19: population-based register studies
Open this publication in new window or tab >>Cardiovascular complications following covid-19: population-based register studies
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Kardiovaskulära komplikationer efter COVID-19 : populations-baserade registerstudier
Abstract [en]

Background and Aim: COVID-19 is a multiorgan disease and there has been increasing reports of cardiovascular complications. However, previous studies have shown conflicting results and have mainly included hospitalized individuals with severe disease. The aim of this thesis was to estimate the risk of incident cardiovascular disease following COVID-19. 

Material and Methods: This project was based on Swedish national register data from all individuals who tested positive for SARS-CoV-2 between February 1st, 2020, and May 25th, 2021. Outcomes were events of incident cardiovascular disease, recorded as ICD-10 codes in the National Patient Register. Self-controlled case series (SCCS) studies and matched cohort studies were performed to determine the relative risks for a new onset cardiovascular event following COVID-19. Moreover, a data-simulation study was performed to investigate features that could introduce bias in the SCCS studies: the "day zero-effect", i.e., a high incidence of events at the COVID-19 date; and the increase in mortality due to cardiovascular events.

Results: In the SCCS studies, the risk of cardiovascular disease was significantly increased compared to the control period as follows: up to 14 days after COVID-19 for acute myocardial infarction; up to 1 month for ischemic stroke; up to 3 months for deep vein thrombosis; up to 6 months for pulmonary embolism; up to 2 months for bleeding and for atrial tachycardias; up to 6 months for paroxysmal supraventricular tachycardias; and up to 14 days for bradyarrhythmias. In the matched cohort studies, COVID-19 was associated with an approximately 3- and 4-fold increase in the risk of acute myocardial infarction and ischemic stroke, respectively, during day 1-14 after the infection. During day 1-30 following the infection, the increase in risk was 5-fold for deep vein thrombosis; 33-fold for pulmonary embolism; 2-fold for bleeding; 12-fold for atrial tachycardias; 5-fold for paroxysmal supraventricular tachycardias; and 3-fold for bradyarrhythmias. The relative risks were higher in older individuals with comorbidities, with more severe COVID-19, and during the first months of the pandemic. Unvaccinated individuals had a higher risk of arrhythmias. In the data-simulation study, bias was introduced by including "day-zero events" in the analyses. Moreover, the extended rather the traditional SCCS model was more appropriate to minimize possible bias introduced by the increase in mortality due to cardiovascular events.

Conclusion: There is an increased risk of cardiovascular complications in individuals with COVID-19, especially in individuals with severe disease. These findings highlight the value of diagnostic and prophylactic strategies in individuals with COVID-19, such as risk factor control or thromboprophylaxis, and the value of vaccination. 

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2023. p. 107
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2228
Keywords
COVID-19, SARS-COV-2, cardiovascular disease, nationwide, register, matched cohort study, self-controlled case series study
National Category
Cardiology and Cardiovascular Disease Public Health, Global Health and Social Medicine
Research subject
cardiovascular disease; Epidemiology; Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-213958 (URN)9789180700047 (ISBN)9789180700030 (ISBN)
Public defence
2023-09-29, Hörsal E04, byggnad 6E, målpunkt R-1, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2023-09-08 Created: 2023-09-01 Last updated: 2025-02-20Bibliographically approved

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Katsoularis, IoannisFonseca Rodriguez, OsvaldoLindmark, KristerConnolly-Andersen, Anne-Marie

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