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      Influenza Infection and Risk of Acute Myocardial Infarction in England and Wales: A CALIBER Self-Controlled Case Series Study

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          Abstract

          Background.  An association between infections and vascular events has been observed, but the specific effect of influenza and influenza-like illnesses on triggering acute myocardial infarction (AMI) is unclear.

          Methods.  Episodes of first AMI from 1 January 2003 through 31 July 2009 were identified using linked anonymized electronic medical records from the Myocardial Ischaemia National Audit Project and the General Practice Research Database. Self-controlled case series analysis was used to investigate AMI risks after consultation for acute respiratory infection. Infections were stratified by influenza virus circulation, diagnostic code, and vaccination status to assess whether influenza was more likely than other infections to trigger AMI.

          Results.  Of 22 024 patients with acute coronary syndrome, 11 208 met the criterion of having had their first AMI at the age of ≥40 years, and 3927 had also consulted for acute respiratory infection. AMI risks were significantly raised during days 1–3 after acute respiratory infection (incidence ratio, 4.19 [95% confidence interval, 3.18–5.53], with the effect tapering over time. The effect was greatest in those aged ≥80 years ( P = .023). Infections occurring when influenza was circulating and those coded as influenza-like illness were associated with consistently higher incidence ratios for AMI ( P = .012).

          Conclusions.  Influenza and other acute respiratory infections can act as a trigger for AMI. This effect may be stronger for influenza than for other infections.

          Clinical trials registration.  NCT01106196.

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          Most cited references43

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          Universal definition of myocardial infarction.

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            Validity of diagnostic coding within the General Practice Research Database: a systematic review.

            The UK-based General Practice Research Database (GPRD) is a valuable source of longitudinal primary care records and is increasingly used for epidemiological research. To conduct a systematic review of the literature on accuracy and completeness of diagnostic coding in the GPRD. Systematic review. Six electronic databases were searched using search terms relating to the GPRD, in association with terms synonymous with validity, accuracy, concordance, and recording. A positive predictive value was calculated for each diagnosis that considered a comparison with a gold standard. Studies were also considered that compared the GPRD with other databases and national statistics. A total of 49 papers are included in this review. Forty papers conducted validation of a clinical diagnosis in the GPRD. When assessed against a gold standard (validation using GP questionnaire, primary care medical records, or hospital correspondence), most of the diagnoses were accurately recorded in the patient electronic record. Acute conditions were not as well recorded, with positive predictive values lower than 50%. Twelve papers compared prevalence or consultation rates in the GPRD against other primary care databases or national statistics. Generally, there was good agreement between disease prevalence and consultation rates between the GPRD and other datasets; however, rates of diabetes and musculoskeletal conditions were underestimated in the GPRD. Most of the diagnoses coded in the GPRD are well recorded. Researchers using the GPRD may want to consider how well the disease of interest is recorded before planning research, and consider how to optimise the identification of clinical events.
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              Risk of myocardial infarction and stroke after acute infection or vaccination.

              There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events. Copyright 2004 Massachusetts Medical Society.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                jinfdis
                The Journal of Infectious Diseases
                Oxford University Press
                0022-1899
                1537-6613
                1 December 2012
                9 October 2012
                9 October 2012
                : 206
                : 11
                : 1652-1659
                Affiliations
                [1 ]Centre for Infectious Disease Epidemiology, Research Department of Infection & Population Health
                [2 ]Department of Epidemiology & Public Health, University College London
                [3 ]Department of Infectious Disease Epidemiology
                [4 ]Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine
                [5 ]Barts and the London School of Medicine and Dentistry, London
                [6 ]Department of Mathematics & Statistics, Open University , Milton Keynes, United Kingdom
                Author notes

                Presented in part: European Scientific Working Group on Influenza Conference, Malta, 12 September 2011, Abstract no. A1030; University College London Graduate School Research Poster Competition, London, United Kingdom, 28 February 2012.

                Correspondence: Charlotte Warren-Gash, MRCP, UCL Research Department of Infection & Population Health, Royal Free Hospital, Rowland Hill St, London NW3 2PF, United Kingdom ( c.warren-gash@ 123456ucl.ac.uk ).
                Article
                jis597
                10.1093/infdis/jis597
                3488196
                23048170
                33e90e40-cc5a-4524-9382-764a03b7f40b
                © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 April 2012
                : 16 July 2012
                Categories
                Major Articles and Brief Reports
                Viruses
                Editor's choice

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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