Association of COVID-19 with arterial and venous vascular diseases: a population-wide cohort study of 48 million adults in England and Wales

Abstract

ImportanceThe long-term effects of COVID-19 on the incidence of vascular diseases are unclear.ObjectiveTo quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease.DesignCohort study based on population-wide linked electronic health records, with follow up from January 1st to December 7th 2020.Setting and participantsAdults registered with an NHS general practice in England or Wales and alive on January 1st 2020.ExposuresTime since diagnosis of COVID-19 (categorised as 0-6 days, 1-2 weeks, 3-4, 5-8, 9-12, 13-26 and 27-49 weeks since diagnosis), with and without hospitalisation within 28 days of diagnosis.Main outcomes and measuresPrimary outcomes were arterial thromboses (mainly acute myocardial infarction and ischaemic stroke) and venous thromboembolic events (VTE, mainly pulmonary embolism and lower limb deep vein thrombosis). We also studied other vascular events (transient ischaemic attack, haemorrhagic stroke, heart failure and angina). Hazard ratios were adjusted for demographic characteristics, previous disease diagnoses, comorbidities and medications.ResultsAmong 48 million adults, 130,930 were and 1,315,471 were not hospitalised within 28 days of COVID-19. In England, there were 259,742 first arterial thromboses and 60,066 first VTE during 41.6 million person-years follow-up. Adjusted hazard ratios (aHRs) for first arterial thrombosis compared with no COVID-19 declined rapidly from 21.7 (95% CI 21.0-22.4) to 3.87 (3.58-4.19) in weeks 1 and 2 after COVID-19, 2.80 (2.61-3.01) during weeks 3-4 then to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE declined from 33.2 (31.3-35.2) and 8.52 (7.59-9.58) in weeks 1 and 2 to 7.95 (7.28-8.68) and 4.26 (3.86-4.69) during weeks 3-4 and 5-8, then 2.20 (1.99-2.44) and 1.80 (1.50-2.17) during weeks 13-26 and 27-49 respectively. aHRs were higher, for longer after diagnosis, after hospitalised than non-hospitalised COVID-19. aHRs were also higher among people of Black and Asian than White ethnicity and among people without than with a previous event. Across the whole population estimated increases in risk of arterial thromboses and VTEs were 2.5% and 0.6% respectively 49 weeks after COVID-19, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses.Conclusions and RelevanceHigh rates of vascular disease early after COVID-19 diagnosis decline more rapidly for arterial thromboses than VTEs but rates remain elevated up to 49 weeks after COVID_19. These results support continued policies to avoid COVID-19 infection with effective COVID-19 vaccines and use of secondary preventive agents in high-risk patients.Key pointsQuestionIs COVID-19 associated with higher long-term incidence of vascular diseases?FindingsIn this cohort study of 48 million adults in England and Wales, COVID-19 was associated with higher incidence, that declined with time since diagnosis, of both arterial thromboses [week 1: adjusted HR [aHR] 21.7 (95% CI 21.0-22.4) weeks 27-49: aHR 1.34 (1.21-1.48)] and venous thromboembolism [week 1: aHR 33.2 (31.3-35.2), weeks 27–49 1.80 (1.50-2.17)]. aHRs were higher, for longer, after hospitalised than non-hospitalised COVID-19. The estimated excess number of arterial thromboses and venous thromboembolisms was 10,500.MeaningAvoidance of COVID-19 infection through vaccination, and use of secondary preventive agents after infection in high-risk patients, may reduce post-COVID-19 acute vascular diseases.

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

“…The phenotypes presented have already enabled other analyses with highly relevant public health policy implications, such as assessing the association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, and thrombocytopenic events, 15 assessing the use of antithrombotic medication on COVID-19 outcomes, 16 and studying the incidence of vascular diseases after COVID-19 infection. 17 Our study expands the literature in several key ways. To our knowledge, this is the largest study in terms of sample size and data fidelity to create and evaluate computable COVID-19 phenotypes by leveraging multiple sources of linked data at the national level spanning electronic health records, administrative health-care billing data, disease audits, and national registers.…”

Risk of arterial and venous thromboses after COVID-19

“…The incidence of venous and arterial events was higher in older people, and the risk of death after venous and arterial events was higher in people who had been diagnosed with or tested positive for COVID-19 than in people without COVID-19. In other studies, the cumulative excess risks up to 49 weeks after a COVID-19 diagnosis or positive test in linked primary and secondary care databases in England were 25 per 1000 for arterial and six per 1000 for venous thromboses, 6 and the cumulative risk of venous events in Sweden up to 30 days after a COVID-19 diagnosis or positive test was about two per 1000. 7…”

Effectiveness of BNT162b2 booster doses in England: an observational study in OpenSAFELY-TPP

“…However, it is unclear whether these general risk factors would also confound the estimates of effectiveness against COVID-19 related outcomes. COVID-19 vaccination, including booster vaccination, may protect against deaths that are not coded as due to COVID-19 by preventing harms of severe COVID-19, such as acute myocardial infarction and stroke(9,10). We are unable to compare our non-COVID-19 death results with other recent studies of booster effectiveness, because those studies did not report on non-COVD-19 death.…”