Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales

Rochelle Knight; Venexia Walker; Samantha Ip; Jennifer A Cooper; Thomas Bolton; Spencer Keene; Rachel Denholm; Ashley Akbari; Hoda Abbasizanjani; Fatemeh Torabi; Efosa Omigie; Sam Hollings; Teri-Louise North; Renin Toms; Xiyun Jiang; Emanuele Di Angelantonio; Spiros Denaxas; Johan H Thygesen; Christopher Tomlinson; Ben Bray; Craig J Smith; Mark Barber; Kamlesh Khunti; George Davey Smith; Nishi Chaturvedi; Cathie Sudlow; William N Whiteley; Angela M Wood; Jonathan A C Sterne; CVD-COVID-UK/COVID-IMPACT Consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study

doi:10.1161/CIRCULATIONAHA.122.060785

Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales

Circulation. 2022 Sep 20;146(12):892-906. doi: 10.1161/CIRCULATIONAHA.122.060785. Epub 2022 Sep 19.

Authors

Rochelle Knight^#^{1

2

3

4}, Venexia Walker^#^{1

4}, Samantha Ip^#^{5

6}, Jennifer A Cooper^{1

2}, Thomas Bolton^{5

7

8}, Spencer Keene^{5

7}, Rachel Denholm^{1

2

9}, Ashley Akbari¹⁰, Hoda Abbasizanjani¹⁰, Fatemeh Torabi¹⁰, Efosa Omigie¹¹, Sam Hollings¹¹, Teri-Louise North¹, Renin Toms^{1

12}, Xiyun Jiang⁵, Emanuele Di Angelantonio^{5

7

13

14}, Spiros Denaxas^{15

16

17

18}, Johan H Thygesen¹⁶, Christopher Tomlinson^{16

19

17}, Ben Bray²⁰, Craig J Smith^{21

22}, Mark Barber²³, Kamlesh Khunti²⁴, George Davey Smith^{1

4}, Nishi Chaturvedi²⁵, Cathie Sudlow⁸, William N Whiteley^#^{26

27}, Angela M Wood^#^{5

7

13

14

28

29}, Jonathan A C Sterne^#^{1

2

9}; CVD-COVID-UK/COVID-IMPACT Consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study

Affiliations

¹ Department of Population Health Sciences, Bristol Medical School, University of Bristol, UK (R.K., V.W., J.A.C., R.D., T.-L.N., R.T., G.D.S., J.A.C.S.).
² NIHR Bristol Biomedical Research Centre, UK (R.K., J.A.C., R.D., J.A.C.S.).
³ NIHR Applied Research Collaboration West, Bristol, UK (R.K.).
⁴ MRC Integrative Epidemiology Unit, Bristol, UK (R.K., V.W., G.D.S.).
⁵ British Heart Foundation Cardiovascular Epidemiology Unit (S.I., T.B., S.K., X.J., E.D.A., A.M.W.), University of Cambridge, UK.
⁶ Centre for Cancer Genetic Epidemiology (S.I.), University of Cambridge, UK.
⁷ Department of Public Health and Primary Care, NIHR Blood and Transplant Research Unit in Donor Health and Genomics (T.B., S.K., E.D.A., A.M.W.), University of Cambridge, UK.
⁸ British Heart Foundation Data Science Centre (T.B., C.S.), London.
⁹ Health Data Research UK South-West, Bristol (R.D., J.A.C.S.).
¹⁰ Population Data Science, Swansea University Medical School, Swansea University, Wales, UK (A.A., H.A., F.T.).
¹¹ National Health Service Digital, Leeds, UK (E.O., S.H.).
¹² School of Health Sciences, Cardiff Metropolitan University, UK (R.T.).
¹³ British Heart Foundation Centre of Research Excellence (E.D.A., A.M.W.), University of Cambridge, UK.
¹⁴ Wellcome Genome Campus, Health Data Research UK Cambridge (E.D.A., A.M.W.).
¹⁵ Health Data Research UK (S.D.), London.
¹⁶ Institute of Health Informatics (S.D., J.H.T., C.T.), University College London, UK.
¹⁷ University College London Hospitals Biomedical Research Centre (C.T., S.D.), University College London, UK.
¹⁸ BHF Accelerator, London, UK (S.D.).
¹⁹ UK Research and Innovation Centre for Doctoral Training in AI-Enabled Healthcare Systems (C.T.), University College London, UK.
²⁰ School of Population Health and Environmental Sciences, King's College London, UK (B.B.).
²¹ Geoffrey Jefferson Brain Research Centre, Manchester Centre for Clinical Neurosciences, Northern Care Alliance National Health Service Foundation Trust, Salford Royal Hospital, UK (C.J.S.).
²² Division of Cardiovascular Sciences, Manchester Academic Health Science Centre, University of Manchester, UK (C.J.S.).
²³ Glasgow Caledonian University, UK (M.B.).
²⁴ Diabetes Research Centre, University of Leicester, UK (K.K.).
²⁵ MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science (N.C.), University College London, UK.
²⁶ Centre for Clinical Brain Sciences, University of Edinburgh, UK (W.N.W.).
²⁷ Nuffield Department of Population Health, University of Oxford, UK (W.N.W.).
²⁸ NIHR Cambridge Biomedical Research Centre, UK (A.M.W.).
²⁹ Cambridge Centre for AI in Medicine, UK (A.M.W.).

^# Contributed equally.

Abstract

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear.

Methods: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history.

Results: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses.

Conclusions: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

Keywords: COVID-19; electronic health records; myocardial infarction; pulmonary embolism; stroke; thrombosis; venous thrombosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
COVID-19 Vaccines
COVID-19* / complications
COVID-19* / epidemiology
Cohort Studies
Humans
SARS-CoV-2
Thrombosis* / complications
Thrombosis* / epidemiology
Vascular Diseases* / complications
Venous Thromboembolism* / etiology
Venous Thrombosis* / epidemiology
Wales / epidemiology

Substances

COVID-19 Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding