The role of influenza as a trigger for acute myocardial infarction

Lead Research Organisation: University College London
Department Name: Immunology and Molecular Pathology

Abstract

Influenza (flu) is one of many viruses that cause respiratory symptoms in winter. In most people flu is a mild illness that may result in a trip to the GP or time off work. In the elderly and other vulnerable people, flu may cause a serious or even life-threatening respiratory illness. Now new evidence suggests that some respiratory infections may trigger other more serious conditions such as heart attacks. We do not yet know if this is true for flu. If it is, flu may be more dangerous than previously believed for people at risk from heart attacks such as smokers or those with high blood pressure.

We will study whether flu triggers heart attacks and, if so, how often this happens. We will look at whether vaccinating people against influenza also protects them from heart attacks. To do this we will analyse medical records from a large general practice database as well as studying recent influenza infection in patients hospitalised for heart attacks.

If flu does trigger heart attacks then we may be able to prevent some of these, either by vaccinating more people against flu or by treating people with antiviral drugs when they develop a flu-like illness.

Technical Summary

The role of influenza as a trigger for acute myocardial infarction

Background Recent evidence suggests that acute respiratory infections may trigger acute myocardial infarction (MI). However few studies examine whether influenza, rather than general respiratory infections, specifically triggers MI. Existing studies are limited by diagnostic misclassification, underestimation of the community burden of respiratory illness and problems caused by residual confounding. Larger studies are needed using different study designs in different populations to overcome these weaknesses.

Aims & Objectives This research aims to investigate the role of influenza as a trigger for MI, to determine the burden of MI attributable to influenza and to examine whether influenza vaccination protects against MI. The fellowship will provide training in clinical, epidemiological and statistical research methods relevant to the epidemiology, detection, impact and control of a specific communicable disease.

Design 1) Self-controlled case series analysis of influenza-like illness (ILI) in patients experiencing MI using national primary care data. 2) Case control study of serologically-confirmed influenza and recent ILI in patients hospitalised for MI.

Methodology
Self-controlled case series study Primary care records from The Health Improvement Network (THIN) will be used in conjunction with national surveillance data on ILI and virological investigation of ILI. Cases: all patients with acute MI diagnosed in the influenza season (1st Oct- 1st Apr). Relative incidence of MI in the 28 days after ILI will be compared to baseline risk periods for each individual. Statistical models will include levels of influenza activity and influenza vaccination status as parameters.
Case control study Cases: patients hospitalised for acute MI during the influenza season. Controls: patients hospitalised for acute surgical conditions with no recent history of MI, frequency matched for gender. I will collect demographic and clinical information by computer-assisted interview and obtain a blood sample for detection of influenza antibodies from all patients. Multiple logistic regression models will be used to examine the relationship between recent ILI or serologically confirmed influenza and MI.

Scientific and medical opportunities Cardiovascular disease - predominantly due to MI - is the UK‘s leading cause of death. Influenza is very common even in a low prevalence influenza season. If influenza triggers MI, many MIs may be prevented through widening indications for influenza vaccination or treating influenza cases promptly with antivirals. This has implications for health in both the UK and developing countries where access to cardiology services is often limited.

Publications

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Warren-Gash C (2014) Comparing complications of pandemic and seasonal influenza is complicated. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Warren-Gash C (2012) Diagnosing Influenza for Research in Opticon1826

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Warren-Gash C (2013) Influenza and ischaemic heart disease: research challenges and future directions. in Heart (British Cardiac Society)

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Warren-Gash C (2010) Influenza and myocardial infarction. in Expert review of cardiovascular therapy

 
Guideline Title Prevention and control of seasonal influenza with vaccines
Description Evidence to support flu vaccine for chronic conditions
Geographic Reach North America 
Policy Influence Type Citation in clinical guidelines
 
Guideline Title Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine...for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit
Description Guideline for influenza treatment in ICU
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
 
Guideline Title Guidelines for the Primary Prevention of Stroke: A guideline for health professionals from the American Heart Association/ American Stroke Association
Description Stroke prevention guideline
Geographic Reach North America 
Policy Influence Type Citation in clinical guidelines
 
Description ESWI Young Scientist Award scheme
Amount € 1,000 (EUR)
Organisation European Scientific Working group on Influenza (ESWI) 
Sector Charity/Non Profit
Country European Union (EU)
Start 09/2011 
End 10/2011
 
Title Case control samples 
Description A case control study is currently being carried out in which blood and nasal swab samples are being collected from participants 
Type Of Material Biological samples 
Provided To Others? No  
Impact This study provided additional evidence for the association between influenza-like illness and myocardial infarction and was published in BMJ Open 2013; 3(5). 
 
Description CALIBER 
Organisation University College London
Department Research Department of Epidemiology and Public Health
Country United Kingdom 
Sector Academic/University 
PI Contribution I designed, conducted, analysed and wrote up a self-controlled case series study using linked GPRD-MINAP data in association with CALIBER.
Collaborator Contribution CALIBER provided the linked data as well as input into study methods and advice on drafting the manuscript
Impact As before: 1 paper (JID 2012) 2 presentations 1) Poster presentation at UCL Graduate School Research Poster Competition, Feb 2012 (First Prize winner) 2) Oral presentation at the ESWI conference, Malta, Sept 2011 (awarded Young Scientist grant to attend conference)
Start Year 2009
 
Description Hong Kong 
Organisation University of Hong Kong
Department School of Public Health and Department of Community Medicine
Country Hong Kong 
Sector Academic/University 
PI Contribution I designed a joint observational study using UK and Hong Kong MI and influenza surveillance data. I travelled to the University of Hong Kong where I worked for a month on this analysis. I then wrote a research paper, which was co-authored by my supervisors at UCL and LSHTM as well as collaborators at the Health Protection Agency and in Hong Kong. Based on this collaboration I was then offered a position as external examiner to the University of Hong Kong MPH programme for 2014 to 2016
Collaborator Contribution My collaborators hosted a placement for me in Hong Kong. Hong Kong partners also provided data, supervision and co-authored a paper which has been published in the Journal of Infectious Diseases.
Impact 1 paper (JID 2011) 2 poster presentations: 1) Poster presentation at Options for Control of Influenza conference, Hong Kong, Sept 2010 2) Poster presentation at the Shape of Science symposium, Manchester, July 2010
Start Year 2010
 
Description LSHTM 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Epidemiology and Population Health
Country United Kingdom 
Sector Academic/University 
PI Contribution I have designed and carried out several complementary research studies examining the role of influenza as a trigger for acute myocardial infarction, with statistical and supervisory input from partners at LSHTM during my PhD. I then developed intermediate fellowship proposals with an LSHTM sponsor and several LSHTM collaborators. When this fellowship was successfully funded, I moved to join the research group at LSHTM on October 31 2016.
Collaborator Contribution My second PhD supervisor and statistical collaborator were from LSHTM. My LSHTM sponsor and collaborators contributed to design of my intermediate fellowship applications.
Impact This was an active collaboration until October 2016 when I moved to LSHTM full time to pursue my research. PhD research: 4 papers (Lancet ID 2009, Expert Rev Cardiovasc Ther 2010, JID 2011, JID 2012) 5 presentations at local, national and international conferences 1) Poster presentation at the Annual Society for Social Medicine conference, London, Sept 2012 2) Poster presentation at UCL Graduate School Research Poster Competition, Feb 2012 (First Prize winner) 3) Oral presentation at the ESWI conference, Malta, Sept 2011 (awarded Young Scientist grant to attend conference) 4) Poster presentation at Options for Control of Influenza conference, Hong Kong, Sept 2010 5) Poster presentation at the Shape of Science symposium, Manchester, July 2010
Start Year 2009
 
Description Open University 
Organisation Open University
Country United Kingdom 
Sector Academic/University 
PI Contribution I worked with Dr Heather Whitaker at the Open University on a self-controlled case series analysis using linked primary care records. I conducted an analysis and prepared a paper for publication. Dr Whitaker has continued to advise our team on using this method in subsequent analyses.
Collaborator Contribution Dr Whitaker provided statistical support and guidance.
Impact 1. Paper published in Journal of Infectious Diseases 2012. 2. Academy of Medical Sciences starter grants for clinical lecturers awarded 2014-2016 for a different piece of work using the same methodology.. 3. Abstract published in the Lancet, 2017 based on this latest work. 4.Paper published in European Respiratory journal 2018. This collaboration is between statistics, epidemiology and public health.
Start Year 2009
 
Description PHE (formerly HPA) 
Organisation Public Health England
Department Centre of Infectious Disease Surveillance and Control
Country United Kingdom 
Sector Public 
PI Contribution During my PhD I designed the studies for which HPA data were used. I carried out data management, analysis and wrote relevant papers, with input from supervisors and collaborators. Afterwards, in partnership with PHE I developed a successful grant application to the Academy of Medical Sciences for a Starter Grant for Clinical Lecturers. Our team obtained regulatory approvals, wrote the study protocol, conducted analyses and wrote a paper based on this work, which has recently been published in Clinical Infectious Diseases (Jan 2018).
Collaborator Contribution During my PhD, partners at the HPA provided influenza surveillance data, which were used in two studies - the self-controlled case series of myocardial infarction incidence after influenza using primary care data and the ecological time series analysis comparing influenza rates with MI hospitalisations and deaths in England & Wales and Hong Kong. PHE provided intellectual input into the design of a study that was awarded the Academy of Medical Sciences grant. They provided a dataset for analysis for this study as well as support in interpreting findings.
Impact 1 successful grant application (Academy of Medical Sciences 2015-2016). 3 papers (JID 2011; JID 2012; CID 2018). Several local, national and international presentations: 1) Oral presentation at Informatics for Health, Manchester, April 2017 2) Poster presentation at the Academy of Medical Sciences winter meeting, London, Nov 2016 3) Poster presentation at UCL Graduate School Research Poster Competition, Feb 2012 (First Prize winner) 4) Oral presentation at the ESWI conference, Malta, Sept 2011 (awarded Young Scientist grant to attend conference) 5) Poster presentation at Options for Control of Influenza conference, Hong Kong, Sept 2010 6) Poster presentation at the Shape of Science symposium, Manchester, July 2010
Start Year 2010
 
Description Royal Free Hospital 
Organisation Royal Free London NHS Foundation Trust
Department Cardiology
Country United Kingdom 
Sector Hospitals 
PI Contribution I carried out a case control study based at the Royal Free Hospital investigating recent influenza in patients with acute myocardial infarction compared to surgical control patients. I applied for ethical and R&D approval, set up collaborations with laboratories and clinical personnel, wrote the protocol and designed study materials, recruited patients, collected data from them, managed and analysed data and am in the process of writing up data for publication.
Collaborator Contribution At the Royal Free, my clinical collaborators assisted with setting up the study, provided information on the best ways to recruit patients, helped to identify potential research participants, advised on suitability of recruitment of individual subjects, gave information sheets to patients and collected some samples. My laboratory collaborators processed, stored and analysed samples and provided me with laboratory data. All will be involved in approving the final research paper.
Impact 1 paper: Influenza-like illness in acute myocardial infarction patients during the winter wave of the influenza A H1N1 pandemic in London: a case control study. Warren-Gash C, Geretti AM, Hamilton G et al. BMJ Open. 2013 May; 3(5). 1 poster presentation at the Annual Meeting of the Society for Social Medicine, London, September 2012 This was a multi-disciplinary collaboration involving cardiology, virology, surgery, epidemiology and public health.
Start Year 2009
 
Description Flu! Decipher my data 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Schools
Results and Impact Around 16 schools were submitting data in any one week.

The activity was popular and will continue this year
Year(s) Of Engagement Activity 2011
 
Description Media briefings 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Dr andrew Hayward (my primary PhD supervisor) was interviewed on the Today programme on radio 4 about results of our pubished systematic review. We also responded to enquiries from a number of journalists

Unsure
Year(s) Of Engagement Activity 2009
 
Description Podcast for Naked Scientist 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I was interviewed for a podcast by a member of the Naked Scientists team about my work on influenza and myocardial infarction. This will be available online.

Unsure
Year(s) Of Engagement Activity 2011