underlying cardiovascular risk and major adverse cardiovascular events after acute CORD-Papers-2022-06-02 (Version 1)

Title: Underlying cardiovascular risk and major adverse cardiovascular events after acute respiratory infection: a population-based cohort study of over 4.2 million individuals in England 2008-2018
Abstract: Background While acute respiratory infections (ARIs) can lead to cardiovascular complications the effect of underlying cardiovascular risk profile on ARI incidence and cardiovascular complications in those without established cardiovascular disease (CVD) is unknown. Whether to consider individuals at raised cardiovascular risk a priority group for vaccination against respiratory infections therefore remains unclear. Methods We conducted a cohort study in individuals aged 40-64 years without established CVD or a chronic health condition eligible for influenza vaccination using Clinical Practice Research Datalink GOLD and Aurum data from 01/09/2008-31/08/2018 linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England. We classified cardiovascular risk based on diagnosed hypertension and overall predicted cardiovascular risk estimated using QRISK2 score ([]10% compared with <10%). Using multivariable Poisson regression models we obtained incidence rate ratios (IRR) for ARI. Among individuals who had an ARI we then used multivariable Cox regression to obtain hazard ratios (HR) for the risk of major adverse cardiovascular events (MACE) within one year of infection. Findings 4212930 individuals were included; 12.5% had hypertension and 14.4% had a QRISK2 score []10%. After adjusting for confounders patients with hypertension (IRR 1.04 95% CI 1.03-1.05) or QRISK2 score []10% (IRR 1.39 1.37-1.40) had a higher incidence of ARI. Of the 442408 individuals with an ARI 4196 had a MACE within one year of infection. After adjustment hypertension (HR 1.98 1.83-2.15) and QRISK2 score []10% (HR 3.65 3.42-3.89) were associated with substantial increased risk of a MACE after infection. Interpretation People without diagnosed CVD but who have raised cardiovascular risk measured by diagnosed hypertension or in particular overall predicted cardiovascular risk have increased incidence of both ARI and cardiovascular complications following an ARI.
Published: 2021-03-20
DOI: 10.1101/2021.03.18.21253890
DOI_URL: http://doi.org/10.1101/2021.03.18.21253890
Author Name: Davidson J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/davidson_j
Author Name: Banerjee A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/banerjee_a
Author Name: Smeeth L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/smeeth_l
Author Name: McDonald H I
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mcdonald_h_i
Author Name: Grint D J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/grint_d_j
Author Name: Herrett E
Author link: https://covid19-data.nist.gov/pid/rest/local/author/herrett_e
Author Name: Forbes H J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/forbes_h_j
Author Name: Pebody R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/pebody_r
Author Name: Warren Gash C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/warren_gash_c
sha: 7ae815ba60eb11067987edd5e02d9e8572c61e6a
license: medrxiv
source_x: MedRxiv
url: http://medrxiv.org/cgi/content/short/2021.03.18.21253890v1?rss=1
has_full_text: TRUE
Keywords Extracted from Text Content: People 442,408 3·42-3·89 cardiovascular IRR individuals 1·37-1·40 1·83-2·15 4,196 Office Patient Care patients ≥ people C.W.-G. medRxiv endothelial antiplatelet prescriptions aspirin Endothelial NHS splenic between-database men vascular cells 773,362 https://doi.org/10.1101/2021.03.18.21253890 doi 554·4 Mixed/Other blood COVID-19 1·07-1·16 UK Biobank coronary SCCS 3·9 People 3,439,568 acute respiratory infections coronavirus 586,147 55-59 179,062 UK EHRs QRISK3 cardiovascular 1·29-1·43 1·34-2·33 liver left ventricular heart [1] [2] [3] [4] NCT02831608 347,418 ≥ 526,480 heart 2·25-2·40 1·37-1·40 SARS-CoV-2 post-pneumonia individuals kidney statin antiplatelet UKRI 2·56-3·30 204,493 ‡Results medRxiv preprint patients patient two-to alcohol 2·46-3·90 1·11-1·19 1·51-2·72 female myocardial 2·38-3·93 IQR=1·6-7·6 pro-coagulant Patient Care (HES APC LRT 1·01-1·23 HES 0·96-1·00 HES APC ARIs ONS 1·81-2·43 S. pneumoniae IQR=40-53 442,408
Extracted Text Content in Record: First 5000 Characters:Background While acute respiratory infections (ARIs) can lead to cardiovascular complications, the effect of underlying cardiovascular risk profile on ARI incidence and cardiovascular complications in those without established cardiovascular disease (CVD) is unknown. Whether to consider individuals at raised cardiovascular risk a priority group for vaccination against respiratory infections therefore remains unclear. Methods We conducted a cohort study in individuals aged 40-64 years without established CVD or a chronic health condition eligible for influenza vaccination, using Clinical Practice Research Datalink GOLD and Aurum data from 01/09/2008-31/08/2018 linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England. We classified cardiovascular risk based on diagnosed hypertension and overall predicted cardiovascular risk estimated using QRISK2 score (≥10% compared with <10%). Using multivariable Poisson regression models, we obtained incidence rate ratios (IRR) for ARI. Among individuals who had an ARI, we then used multivariable Cox regression to obtain hazard ratios (HR) for the risk of major adverse cardiovascular events (MACE) within one year of infection. Findings 4,212,930 individuals were included; 12·5% had hypertension and 14·4% had a QRISK2 score ≥ 10%. After adjusting for confounders, patients with hypertension (IRR 1·04, 95% CI 1·03-1·05) or QRISK2 score ≥ 10% (IRR 1·39, 1·37-1·40) had a higher incidence of ARI. Of the 442,408 individuals with an ARI, 4,196 had a MACE within one year of infection. After adjustment, hypertension (HR 1·98, 1·83-2·15) and QRISK2 score ≥ 10% (HR 3·65, 3·42-3·89) were associated with substantial increased risk of a MACE after infection. Interpretation People without diagnosed CVD but who have raised cardiovascular risk, measured by diagnosed hypertension or, in particular, overall predicted cardiovascular risk, have increased incidence of both ARI and cardiovascular complications following an ARI. The coronavirus (COVID- 19) pandemic has expedited research on the role of acute respiratory infections (ARIs) in triggering cardiovascular complications. Before the pandemic, multiple observational studies identified ARIs increased the risk of myocardial infarction (MI) and stroke. In self-controlled case series (SCCS) studies, using large electronic health record (EHR) datasets, MI and stroke risks were elevated two-to six-fold in the days following clinically-diagnosed ARI and influenza-like illness (ILI), with risk remaining for up to one month. 1, 2 Laboratory-confirmed organisms, including Streptococcus pneumonia and influenza virus, cause consistent cardiovascular triggering effects. 3, 4 Observational studies and the few randomized controlled trials (RCTs) available show pneumococcal and influenza vaccines reduce the incidence of cardiovascular complications. [5] [6] [7] A meta-analysis of secondary prevention RCTs found influenza vaccination reduced cardiovascular mortality by 55%. 7 While not as widely researched, with no RCT evidence, a meta-analysis of observational studies in individuals ≥ 65 years found pneumococcal vaccination reduced the odds of acute coronary syndrome (ACS) by 17%. 5 People without established cardiovascular disease (CVD) but with underlying cardiovascular risk are not typically recommended to receive seasonal influenza or pneumococcal vaccines by organizations such as the World Health Organization, the European Centre for Disease Prevention and Control, or in England, Public Health England. Public Health England recommends one-time polysaccharide pneumococcal vaccine and seasonal influenza vaccines for adults aged ≥ 65 years or <65 years with specific underlying health conditions, including those with chronic heart disease. 8 Cohort studies have previously demonstrated an association between high blood pressure and cardiovascular complications in individuals as young as 40. 9, 10 Although blood pressure is an essential predictor of cardiovascular risk, it is only one component. Cardiovascular risk scores are increasingly used to predict the individual likelihood, most commonly 10-year risk, of future CVD based on multiple factors. QRISK2, now updated to a newer version called QRISK3, is embedded in UK primary care clinical management systems. 11 The National Institute for Health and Care Excellence recommends QRISK2 for CVD risk assessment and management. 12 Our study aimed to investigate how raised cardiovascular risk, defined by diagnosed hypertension and QRISK2 score, modified the occurrence of ARI and major adverse cardiovascular events (MACE) after an ARI using ten years of linked EHR data from England. A better understanding of risk factors for severe outcomes after ARI will inform stratified prevention and treatment strategies. We conducted a retrospective cohort study using anonymized coded primary care data from the Clinical Practice Research Datalink (CPRD) databa
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