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Jennifer A Davidson,1 Amitava Banerjee,2 Helen Strongman,1 Emily Herrett,1 Liam Smeeth,1 Judith Breuer,3 Charlotte Warren-Gash1 1Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK; 2Institute of Health Informatics, University College London, London, UK; 3Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UKCorrespondence: Charlotte Warren-Gash, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK, Tel +44 20 7927 2796, Email charlotte.warren-gash1@lshtm.ac.ukPurpose: To assess the risk of incident cardiovascular outcomes after COVID-19 by level of cardiovascular risk in waves one and two of the pandemic in England in 2020.Patients and methods: We conducted a self-controlled case-series study among adults aged 40– 84 years with no pre-existing cardiovascular disease using linked data from the Clinical Practice Research Datalink. We generated season-adjusted incidence ratios (IRs) for first acute cardiovascular event after SARS-CoV-2 infection compared with baseline time before and > 91 days after infection. We used composite and individual acute cardiovascular event outcomes including myocardial infarction, major ventricular arrhythmia, left ventricular heart failure, and ischemic stroke. We stratified by cardiovascular risk, using diagnosed hypertension and QRISK3 predicted risk, and by wave one and two of the pandemic.Results: We included 1762 individuals, 76.6% had a QRISK3 score ≥ 10% and 59.4% had hypertension. The risk of any cardiovascular event was elevated in the 1– 7 days after infection (IR 7.14 [95% CI 6.06– 8.41]) and, while the effect size tapered, the risk remained for 15– 28 days after infection (1.74 [1.33– 2.26]). Risks were similar for individual event type, differing by level of cardiovascular risk, and in wave one and two of the pandemic. &#x2003Conclusion: SARS-CoV-2 infection is associated with early elevations in the risk of first acute cardiovascular event, across cardiovascular risk levels and in both wave one and two of the pandemic. Prevention of COVID-19 is important to avert cardiovascular complications.Graphical Abstract: Keywords: acute coronary syndrome, COVID-19, electronic health records, epidemiology, heart failure

Jasbir Dhaliwal,1– 6 Meltem Tuna,1 Baiju R Shah,1,7,8 Sanjay Murthy,1,9,10 Emily Herrett,4 Anne M Griffiths,2,3 Eric I Benchimol1– 3,8 1ICES, Toronto, ON, Canada; 2SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada; 3Department of Paediatrics, University of Toronto, Toronto, ON, Canada; 4London School of Hygiene and Tropical Medicine, London, UK; 5Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati, OH, USA; 6Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; 7Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 8Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; 9The Ottawa Hospital IBD Centre, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada; 10Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, CanadaCorrespondence: Jasbir DhaliwalPediatrics, University of Cincinnati, Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Secondary Appointments in Division of Biomedical Informatics and James M Anderson Center for Health Systems Excellence, 3333 Burnet Avenue, Cincinnati, OH, 45229, USATel +15133789468Email Jasbir.dhaliwal@cchmc.orgBackground: Inflammatory bowel disease (IBD) is now a global disease with incidence increasing throughout Asia.Aim: To determine the incidence of IBD among South Asians and Chinese people residing in Ontario, Canada’s most populous province.Methods: All incident cases of IBD in children (1994– 2015) and adults (1999– 2015) were identified from population-based health administrative data. We classified South Asian and Chinese ethnicity using immigration records and surnames. We determined standardized incidence of IBD and adjusted incidence rate ratio (aIRR) in South Asians and Chinese compared to the general population.Results: Among 16,230,638 people living in Ontario, standardized incidence of IBD per 100,000 person-years was 24.7 (95% CI 24.4– 25.0), compared with 14.6 (95% CI 13.7– 15.5) in 982,472 South Asians and with 5.4 (95% CI 4.8– 5.9) in 764,397 Chinese. The risk of IBD in South Asians was comparable to the general population after adjusting for immigrant status and confounders (aIRR 1.03, 95% CI 0.96– 1.10). South Asians had a lower risk of Crohn’s disease (CD) (aIRR 0.66, 95% CI 0.60– 0.77), but a higher risk of ulcerative colitis (UC) (aIRR 1.47, 95% CI 1.34– 1.61). Chinese people had much lower rates of IBD (aIRR 0.24, 95% CI 0.20– 0.28), CD (aIRR 0.21, 95% CI 0.17– 0.26), and UC (aIRR 0.28, 95% CI 0.23– 0.25).Conclusion: Canadians of South Asian ethnicity had a similarly high risk of developing IBD compared to other Canadians, and a higher risk of developing UC, a finding distinct from the Chinese population. Our findings indicate the importance of genetic and environmental risk factors in people of Asian origin who live in the Western world.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, incidence, ethnicity, epidemiology, South Asian, Chinese

Ann D Morgan,1 Emily Herrett,2 Bianca L De Stavola,2 Liam Smeeth,2 Jennifer K Quint1,2 1Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK; 2Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK Background: It is generally accepted that people with chronic obstructive pulmonary disease (COPD) are at increased risk of vascular disease, including venous thromboembolism (VTE). While it is plausible that the risk of arterial and venous thrombotic events is greater still in certain subgroups of patients with COPD, such as those with more severe airflow limitation or more frequent exacerbations, these associations, in particular those between venous events and COPD severity or exacerbation frequency, remain largely untested in large population cohorts.Methods: A total of 3,594 patients with COPD with a first VTE event recorded during January 1, 2004 to December 31, 2013, were identified from the Clinical Practice Research Datalink dataset and matched on age, sex, and general practitioner practice (1:3) to patients with COPD with no history of VTE (n=10,782). COPD severity was staged by degree of airflow limitation (ie, GOLD stage) and by COPD medication history. Frequent exacerbators were defined as patients with COPD with ≥2 exacerbations in the 12-month period prior to their VTE event (for cases) or their selection as a control (for controls). Conditional logistic regression was used to estimate the association between disease severity or exacerbation frequency and VTE.Results: After additional adjustment for nonmatching confounders, including body mass index, smoking, and heart-related comorbidities, there was evidence for an association between increased disease severity and VTE when severity was measured either in terms of lung function impairment (odds ratio [OR]moderate:mild =1.16; 95% confidence intervals [CIs] =1.03, 1.32) or medication usage (ORsevere:mild/moderate =1.17; 95% CIs =1.06, 1.26). However, there was no evidence to suggest that frequent exacerbators were at greater risk of VTE compared with infrequent exacerbators (OR =1.06; 95% CIs =0.97, 1.15).Conclusion: COPD severity defined by airflow limitation or medication usage, but not exacerbation frequency, appears to be associated with VTE events in people with COPD. This finding highlights the disconnect between disease activity and severity in COPD. Keywords: COPD, venous thromboembolism, Clinical Practice Research Datalink, frequent exacerbators

Claire Windsor,1 Emily Herrett,1 Liam Smeeth,1 Jennifer Kathleen Quint1,2 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK; 2Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK Background: Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of stroke than the general population. Chronic inflammation associated with COPD is thought to contribute to this risk. Exacerbations of COPD are associated with a rise in inflammation, suggesting that there may be an association between exacerbation frequency and the risk of stroke. This study examined that association.Methods: Using the UK Clinical Practice Research Datalink, COPD patients with a first stroke between January 2004 and December 2013 were identified as cases and matched on age, sex, and general practice to controls with COPD but without a stroke (6,441 cases and 19,323 controls). Frequent exacerbators (FEs) were defined as COPD patients with ≥2 exacerbations, and infrequent exacerbators (IEs) have ≤1 exacerbation in the year prior to their stroke. Conditional logistic regression was used to estimate the association between exacerbation frequency and stroke overall, and by stroke subtype (hemorrhagic, ischemic, or transient ischemic attack). Exacerbations were also categorized into 0, 1, 2, or ≥3 exacerbations in the year prior to stroke.Results: There was no evidence that FE had an increased odds of stroke compared to IE (OR [odds ratio] =0.95, 95% CI [confidence interval] =0.89–1.01). There was strong evidence that the risk of stroke decreased with each exacerbation of COPD experienced per year (Ptrend =0.003). In the subgroup analysis investigating stroke subtype, FE had 33% lower odds of hemorrhagic stroke than IE (OR =0.67, 95% CI =0.51–0.88, P=0.003). No association was found within other stroke types.Conclusion: This study found no evidence of a difference in the odds of stroke between IE and FE, suggesting that exacerbation frequency is unlikely to be the reason for increased stroke risk among COPD patients. Further research is needed to explore the association through investigation of stroke risk and the severity, duration, treatment of exacerbations, and concurrent treatment of cardiovascular risk factors. Keywords: COPD exacerbations, stroke, frequent exacerbators, infrequent exacerbators