risk of acute respiratory infection and acute cardiovascular events following acute CORD-Papers-2022-06-02 (Version 1)

Title: Risk of acute respiratory infection and acute cardiovascular events following acute respiratory infection among adults with increased cardiovascular risk in England between 2008 and 2018: a retrospective population-based cohort study
Abstract: BACKGROUND: Although acute respiratory infections can lead to cardiovascular complications the effect of underlying cardiovascular risk on the incidence of acute respiratory infections and cardiovascular complications following acute respiratory infection in individuals without established cardiovascular disease is unknown. We aimed to investigate whether cardiovascular risk is associated with increased risk of acute respiratory infection and acute cardiovascular events after acute respiratory infection using 10 years of linked electronic health record (EHR) data in England. METHODS: In this retrospective population-based cohort study we used EHRs from primary care providers registered on the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases in England. Eligible individuals were aged 4064 years did not have established cardiovascular disease or a chronic health condition that would make them eligible for influenza vaccination were registered at a general practice contributing to the CPRD and had linked Hospital Episode Statistics Admitted Patient Care data in England from Sept 1 2008 to Aug 31 2018. We classified cardiovascular risk on the basis of diagnosed hypertension and overall predicted cardiovascular risk estimated by use of the QRISK2 risk-prediction tool (comparing a score of 10% [increased risk] with a score of <10% [low risk]). Using multivariable Poisson regression models we calculated incidence rate ratios (IRRs) for systemic acute respiratory infection. Among individuals who had an acute respiratory infection we used multivariable Cox regression to calculate hazard ratios (HRs) for the risk of acute cardiovascular events within 1 year of infection. FINDINGS: We identified 6 075 321 individuals aged 4064 years with data in the CPRD and linked data in the Hospital Episode Statistics Admitted Patient Care database between Sept 1 2008 and Aug 31 2018. Of these individuals 4 212 930 (including 526 480 [125%] with hypertension and 607 087 [144%] with a QRISK2 score of 10%) were included in the assessment of the incidence of acute respiratory infection. After adjusting for confounders (age sex ethnicity socioeconomic status body-mass index alcohol consumption smoking status and consultation frequency in the hypertension analysis; and alcohol consumption and consultation frequency in the QRISK2 analysis) the incidence of acute respiratory infection was higher in individuals with hypertension than those without (IRR 104 [95% CI 103105]) and higher in those with a QRISK2 score of 10% or higher than in those with a QRISK2 score of less than 10% (139 [137140]). Of the 442 408 individuals who had an acute respiratory infection 4196 (09%) had an acute cardiovascular event within 1 year of infection. After adjustment (for age sex ethnicity socioeconomic status body-mass index alcohol consumption and smoking status in the hypertension analysis; and for alcohol consumption in the QRISK2 analysis) hypertension (HR 198 [95% CI 183215]) and a QRISK2 score of 10% or higher (365 [342389]) were associated with a substantially increased risk of acute cardiovascular events after acute respiratory infection. INTERPRETATION: People with increased cardiovascular risk but without diagnosed cardiovascular disease measured by diagnosed hypertension or overall predicted cardiovascular risk could benefit from influenza and pneumococcal vaccine prioritisation to reduce their risk of both acute respiratory infection and cardiovascular complications following an acute respiratory infection. FUNDING: British Heart Foundation and the Wellcome Trust.
Published: 2021-11-22
Journal: Lancet Digit Health
DOI: 10.1016/s2589-7500(21)00203-x
DOI_URL: http://doi.org/10.1016/s2589-7500(21)00203-x
Author Name: Davidson Jennifer A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/davidson_jennifer_a
Author Name: Banerjee Amitava
Author link: https://covid19-data.nist.gov/pid/rest/local/author/banerjee_amitava
Author Name: Smeeth Liam
Author link: https://covid19-data.nist.gov/pid/rest/local/author/smeeth_liam
Author Name: McDonald Helen I
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mcdonald_helen_i
Author Name: Grint Daniel
Author link: https://covid19-data.nist.gov/pid/rest/local/author/grint_daniel
Author Name: Herrett Emily
Author link: https://covid19-data.nist.gov/pid/rest/local/author/herrett_emily
Author Name: Forbes Harriet
Author link: https://covid19-data.nist.gov/pid/rest/local/author/forbes_harriet
Author Name: Pebody Richard
Author link: https://covid19-data.nist.gov/pid/rest/local/author/pebody_richard
Author Name: Warren Gash Charlotte
Author link: https://covid19-data.nist.gov/pid/rest/local/author/warren_gash_charlotte
sha: 3077555868fc1f9a43070604729fee004870606e
license: cc-by
license_url: https://creativecommons.org/licenses/by/4.0/
source_x: Medline; PMC
source_x_url: https://www.medline.com/https://www.ncbi.nlm.nih.gov/pubmed/
pubmed_id: 34823706
pubmed_id_url: https://www.ncbi.nlm.nih.gov/pubmed/34823706
pmcid: PMC8628002
pmcid_url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628002
url: https://www.ncbi.nlm.nih.gov/pubmed/34823706/ https://doi.org/10.1016/s2589-7500(21)00203-x
has_full_text: TRUE
Keywords Extracted from Text Content: 38DF.00 Patients 1·48-2·54 O. emphysema between-database 5·4 alpha 5 lung inhaled steroids atrial cardiovascular risk 4 SNOMED anti-hypertensives stem cell HPRU 2·49-3·70 B (QRISK2) ClinRisk Antihypertensives women 5·6 better-controlled alcohol sickle cell death (1 646,574 patients immunosuppressants serum cholesterol 12·3 spleen cystic CKD cardiovascular ≥40 kg/m 2 antiplatelet glomerular high density lipoprotein cholesterol Lower respiratory 1·48-3·71 cell ≥65 Q. People SNOMED Aurum FS/18/71/33938 https://qrisk.org/ QRISK2=79 solid organ Anti-hypertensives ONS UK oesophageal varices neurone bone marrow https://zenodo.org/record/3981238 inpatients antiplatelets CKD stages 3-5 Azathioprine cerebral palsy pulmonary £ Heart B n=4,035 liver blood limb biliary atresia statin heart kidney vascular QRISK2=0 LRT oral steroids n=57,800 18_218 ARIs SCCS HPRU codelists corticosteroid statins people coronary heart myocardial antiplatelets (n=519,130) line learning/intellectual patients cholesterol/HDL left ventricular heart QRISK2=6 renal patient Methotrexate CPRD00040222 GOLD/Aurum ‡Results systolic blood pressure hypertension=0 HES CKD stages 3-5. Patients patients cardiovascular patient B
Extracted Text Content in Record: First 5000 Characters:Any previous clinical diagnosis, major intervention for, or clinical review specific to CVD including heart disease (congenital or otherwise), heart failure, stroke or transient ischaemic attack. Chronic liver disease Any previous clinical diagnosis of, or clinical review specific to, chronic liver disease including cirrhosis, oesophageal varices, biliary atresia and chronic hepatitis. Chronic kidney disease (CKD) Any previous clinical diagnosis of, or clinical review specific to, CKD stages 3-5, history of dialysis or renal transplant. Or with estimated glomerular filtration rate to classify CKD stages 3-5. 1 Only stages 4-5 excluded from sensitivity analysis using pneumococcal vaccine recommendations. Chronic respiratory disease (not asthma) Any previous clinical diagnosis of, or clinical review specific to, chronic respiratory disease, including chronic obstructive pulmonary disease, emphysema, bronchitis, cystic fibrosis, or fibrosing interstitial lung diseases. Asthma Any previous clinical diagnosis of, or clinical review specific to, asthma with at least two prescriptions of inhaled steroids in the year before baseline. Or any previous hospitalisation for asthma. Not excluded from sensitivity analysis using pneumococcal vaccine recommendations. Chronic neurological disease Any previous clinical diagnosis of, or clinical review specific to, a neurological disease such as Parkinson's disease, motor neurone disease, multiple sclerosis (MS), cerebral palsy, dementia or a learning/intellectual disability. Not excluded from sensitivity analysis using pneumococcal vaccine recommendations. Any previous diagnosis of, or clinical review specific to, diabetes mellitus, or with a prescription for medication used to treat diabetes. Only treated diabetes excluded from sensitivity analysis using pneumococcal vaccine recommendations. Asplenia/sickle cell disease Any previous clinical diagnosis of, or clinical review specific to, asplenia or dysfunction of the spleen (including sickle cell disease but not sickle cell trait). Severe obesity Latest body mass index before baseline was ≥40 kg/m 2 . Not excluded from sensitivity analysis using pneumococcal vaccine recommendations. Any previous clinical diagnosis of, or clinical review specific to, HIV, solid organ transplant or other permanent immunosuppression (such as genetic conditions compromising immune function). Previous clinical diagnosis of, or clinical review specific to, aplastic anaemia or haematological malignancy, or receiving a bone marrow or stem cell transplant in the 2 years before baseline. Previous clinical diagnosis of, or clinical review specific to, other/unspecified immune deficiency or receiving chemotherapy or radiotherapy in the year before baseline. Prescription of biological therapy or at least 2 prescriptions for oral steroids or other immunosuppressants including DMARDS, Methotrexate, Azathioprine, or corticosteroid injections in the year before baseline. Records containing ARI codes were identified in both CPRD and HES. All ARI codes were used to define the primary outcome (ARI) and subsets were used to define the secondary outcomes of influenza/influenza-like-illness (ILI) and pneumonia. To account for multiple consultations related to one illness, CPRD or HES records dated within 28 days of each other were regarded as part of the same illness-episode. The earliest record in the episode determined the date of illness for the primary outcome of ARI and for the secondary outcome of influenza/ILI. By comparison, for the secondary outcome of pneumonia, the earliest record which was coded as pneumonia determined the date of illness. Figure A below illustrates the episode structure. Influenza/ILI and pneumonia episodes were structured differently to account for the aetiological differences in the conditions. In an episode where there was an influenza/ILI record, but this was not the first record, it is likely that the original presentation was due to influenza/ILI but not identified as such at the time. Conversely, pneumonia can develop and worsen over time from the original infection. In analysis of ARI outcomes, to account for multiple episodes of illness per patient, an "observation" period ended at the date of ARI and a new "observation" period begin. In analysis of acute cardiovascular events after ARI, an ARI episode triggered a one-year follow-up. Further ARI episodes which occurred in that further up were counted and adjusted for in analysis. An individual's QRISK2 score is calculated based on age, sex, ethnicity, deprivation score from linked Townsend data, diabetes, family history of coronary heart disease in a first degree relative <60 years, atrial fibrillation, chronic kidney disease stage 4 or 5, rheumatoid arthritis, ratio of total serum cholesterol to high density lipoprotein cholesterol, systolic blood pressure, treated hypertension, body-mass index, and smoking status. 2 The complete QRISK2 algorithm used to calculate score has
Keywords Extracted from PMC Text: https://github.com/jenAdavidson/cvrisk_mace_ari appendix p 14 ≥40 HES APC myocardial Between-database heart appendix p 19 appendix p 3 women splenic 50–54 EHRs UK diabetes.24 CW-G. JAD statins 1·09 [0·91–1·30] appendix p 15 influenza.14 appendix p 16 alcohol antiplatelet prescriptions appendix p 18 appendix p 5 kidney cardiovascular events.3 antiplatelets [1–60] urinary tract [BMI 25·0–29·9 kg/m2] [1–159] statins 2·22 [1·83–2·69] left ventricular heart appendix p 7 results.24 coronary condition.9 aspirin liver Streptococcus pneumoniae [1–156] antiplatelets 0·86 antiplatelets 1·82 [1·36–2·44] care.28 vascular cells infection.25 cardiovascular QRISK212 appendix " [BMI 30·0–39·9 kg/m2] atherosclerosis.26 A blood [BMI 18·5–24·9 kg/m2] appendix p 11 people CW-G Patient Care (HES APC statins 3·93 study.2 antiplatelet drugs appendix p 8) statins Patients female appendix p 17 appendix pp 12–13 1 986 337 SARS-CoV-2 3·9 45–49 cardiac statin 50·5 PubMed appendix p 6 UK Biobank peripheral vascular arterial ONS patients NCT02831608 COVID-19 vaccines appendix p 10 antiplatelet individuals AstraZeneca limb patient antiplatelets 3·68 [3·45–3·93]; figure 2 4·81 [3·99–5·81] men 55–59 endothelial 5·8 statins 2·14 [1·98–2·32] COVID-19 60–64 age.11 Blood pressure antiplatelets 2·05 [1·91–2·21])
Extracted PMC Text Content in Record: First 5000 Characters:The COVID-19 pandemic has expedited research on cardiovascular complications following systemic acute respiratory infection. Before the pandemic, observational studies showed that acute respiratory infections increased the risk of myocardial infarction and stroke. In self-controlled case-series using large electronic health record (EHR) datasets, risk of myocardial infarction and stroke was elevated by 2–6 times in the days following clinically diagnosed acute respiratory infection, with the risk remaining elevated for up to 1 month.1, 2 A range of organisms, including Streptococcus pneumoniae and the influenza virus, are known to trigger cardiovascular events.3, 4 Research in context Evidence before this study Before the COVID-19 pandemic, self-controlled case-series estimated a 2–6 times transient increase in the risk of myocardial infarction and stroke following a range of clinically diagnosed or laboratory-confirmed acute respiratory infections. These studies did not explore whether these effects were modified by underlying cardiovascular risk. We searched PubMed using the search terms "*hypertensi*" OR "cardiovascular risk" AND "influenza" OR "pneumonia" OR "respiratory infection" AND "cardiovascular event" OR "myocardial infarction" OR "acute coronary syndrome" OR "stroke" OR "heart failure" for primary research studies and reviews investigating the effect of underlying cardiovascular risk on cardiovascular complications after acute respiratory infection published in any language, from database inception to Jan 25, 2021. Of 421 studies identified, three presented estimates for the effect of cardiovascular risk on cardiovascular complications after acute respiratory infection. One prospective cohort study of individuals with community-acquired pneumonia from five North American medical centres in 1991–94 showed that arterial hypertension was associated with an increased odds of cardiac complications (new or worsening heart failure, new or worsening arrhythmias, or myocardial infarction) within 30 days of a diagnosis of community-acquired pneumonia. The second study used clinical records from Beijing, China, to explore risk factors for cardiovascular complications after hospitalisation for community-acquired pneumonia in 2013–15, and found that patients hospitalised with community-acquired pneumonia who had cardiovascular complications had a significantly higher prevalence of hypertension than those without cardiovascular complications. The final study used UK primary care electronic health records (EHRs) to identify individuals who had a myocardial infarction or stroke in 1995–2004 and matched (on year of birth, sex, primary care practice, and calendar time) controls. The authors found that individuals who had an acute respiratory infection in the previous month had an increased odds of having a first myocardial infarction or stroke, regardless of background cardiovascular risk. The effect of underlying cardiovascular risk on cardiovascular complications after acute respiratory infection therefore remains unclear. We also did a search of PubMed on Sept 28, 2021, using the search terms "*hypertensi*" OR "cardiovascular risk" AND "influenza" OR "pneumonia" OR "respiratory infection". We searched for research articles or reviews published in any language between database inception and Jan 1, 2021. Of the 2175 studies identified, one presented estimates for the effect that cardiovascular risk has on the incidence of acute respiratory infections itself. The study used UK Biobank data to show that hypertension was independently associated with an increased risk of acute lower respiratory infections, particularly pneumonia. Added value of this study Using primary and secondary care EHRs from more than 4·2 million individuals in England, we found that the incidence of acute respiratory infection, particularly pneumonia, was higher in those with increased cardiovascular risk, defined as diagnosed hypertension or a QRISK2 10-year risk score of 10% or more. In addition, individuals with increased cardiovascular risk also had an elevated risk of acute cardiovascular events after an acute respiratory infection. This risk was more pronounced when QRISK2 score, which incorporates multiple factors associated with cardiovascular disease onset, was used rather than a diagnosis of hypertension alone. Therefore, QRISK2 provides a practical method to identify individuals at risk of cardiovascular complications after acute respiratory infection and to thereby prevent early-onset cardiovascular disease. Implications of all the available evidence Our analyses and the available evidence to date indicate that individuals with increased cardiovascular risk have a higher risk of acute respiratory infection, and that these infections are more likely to trigger acute cardiovascular events than in those without increased cardiovascular risk. These findings highlight the importance of managing and reducing cardiovascular risk to red
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