Title: Preventing infection-related cardiovascular disease in primary care
Funder: Department of Health and Social Care

Abstract: Research questions Q1) Which patients are at risk of respiratory infection-related cardiovascular disease? Q2) What are the effects of aspirin on respiratory infection-related cardiovascular disease? And does respiratory infection affect risk of bleeding when taking aspirin? Q3) What are the effects of using influenza immunisation for primary prevention of cardiovascular disease in primary care?BackgroundRespiratory infection (chest infections and influenza) can trigger heart attacks and strokes (cardiovascular disease - CVD). Studies estimate respiratory infections cause over ten thousand CVD deaths per year in the UK, but current CVD prevention strategies do not consider infections.If we could identify people at risk of infection-related CVD we might use existing treatments such as aspirin and influenza vaccine, which are currently used for secondary prevention. Currently we can't identify patients at risk, and don't know the effects of these interventions on infection-related CVD. Aspirin works for primary prevention, but the risk of bleeding outweighs the benefit. A short course of aspirin during a chest infection might prevent CVD with a lower bleeding risk. Influenza vaccine works in secondary prevention, so might benefit high-risk patients. AimTo develop new strategies to prevent infection-related cardiovascular events in primary care Objectives One: Develop a prediction model for infection-related cardiovascular diseaseTwo: Externally validate the prediction model for infection-related CVD Three: Estimate the benefits and harms of aspirin in respiratory infections Four: Estimate the impact of expanding influenza vaccine coverage on preventing CVD MethodsData sources: Anonymised, routinely collected medical records from UK primary care linked to hospital data Population: Adult patients registered in primary care Primary outcome: Infection-related CVD events. This composite outcome comprises acute CVD events within the high-risk period following systemic respiratory infection (30 days) Adverse outcomes: Major bleeding, PPI group developed side effects list Sample size: Initial count: 16,000 events Missing data: Multiple imputation Predictors: Cardiovascular risk (QRisk score), patient demographics, chronic disease status, blood results, and preventative medications Statistical analyses: Objectives 1&2: Model building: logistic and Cox regression. Variable selection by a-priori knowledge, supplemented by bootstrapping. Fractional polynomials to model continuous variables. Exploration of 'off the shelf' machine learning algorithms (boosting and support vector machines). Development in CPRD Aurum and validation in CPRD gold/RCGP RSC. Statistical analyses: Objectives 3&4: Classical statistics (regression), instrumental variable methods (physician preference and vaccination effectiveness, with assessment of instrument validity. Doubly robust propensity score methods (inverse probability weighting with adjustment for propensity score). Timelines for delivery Thesis by 60 months. Objective one and two by 18 months, objective three by 36 months and four by 52 months.Anticipated impactObjectives one and two will allow GPs and researchers to identify high-risk patients. In future, a data-enabled trial of aspirin in respiratory infection could change practice. This trial would be based on objective three. Objective four may influence influenza vaccine allocation directly, as observational studies are the basis of vaccine allocation in the UK. Dissemination Three academic papers. Wider patient and public involvement, media, social media engagement. Engagement of clinical practice by implementing automated prediction tools.

Lay abstract: Aim: To prevent heart attacks and strokes following chest infections Background: I work in the NHS as a GP, and I work in a heart clinic (cardiology). Sadly heart attacks and strokes cause more than a quarter of all deaths. Many more heart attacks and strokes are not fatal. They can cause long-term health problems and disability. Chest infections can trigger heart attacks and strokes. The risk is highest for a few days, but lasts for a month after a chest infection. We think about ten thousand people die from heart attacks and strokes related to chest infections each year. Doctors like me try to prevent heart attacks and strokes. At the moment we don't take chest infections into account. I aim to change this, so that we can prevent heart attacks and strokes triggered by chest infections. I will do four 'data science' projects using millions of anonymous GP records. Health data science uses 'big data' to answer medical research questions. I will run statistical models on computers to answer my research questions.Two projects will try to identify patients at risk of a heart attack or stroke following a chest infection. Two more projects will look at ways we could prevent high-risk people with chest infections going on to have a heart attack or stroke. Project one: A computer-based tool to identify people at risk of heart attacks and strokes when they have a chest infection. We don't know who is at risk of heart attacks following chest infections. GPs already use risk tools to work out patient's risk over the next ten years. Existing tools don't take infection into account. My new tool will build on existing ones. I will compare different versions to find the best one.Project two: Testing the new tool. I will test the tool to see how well it works in a different set of GP records.Project three: The benefits and harms of aspirin during chest infections. We know that aspirin (a 'blood-thinning' drug) prevents heart attacks. We recommend an aspirin every day for patients who survive a heart attack. Unfortunately taking aspirin also causes bleeding. The risk of bleeding can be worse than the benefit. This is why we only give aspirin to patients after their first heart attack.Taking aspirin during chest infections might prevent the first heart attack or stroke. A shorter course of aspirin may have a smaller risk of bleeding. To find out I will look at what happened to patients with chest infections who took aspirin compared to those who didn't. I will see how many had heart attacks, strokes, or serious bleeding. I will use statistical models to take account of other factors. Project 4: Influenza vaccine to prevent first heart attacks. Influenza vaccine is one of the best things we can do after a heart attack to prevent further ones. We don't know if 'flu vaccine prevents heart attacks for patients who have never had one.At the moment GPs check their patient's risk of heart attacks with a tool, and if it is high offer statins (cholesterol lowering drugs), but not vaccines. I will look at the records of patients who are at risk. I will compare what happened to them if they had vaccine or not. I will see how many had heart attacks and strokes, whilst taking into account other factors. After these projects: If aspirin or vaccines seem to work, we could use or test them in clinical trials. If they are harmful, we will know not to use these approaches.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;3.3 NUTRITION AND CHEMOPREVENTION;3.4 VACCINES
Health categories: CARDIOVASCULAR;STROKE