Heart disease, stroke and lower respiratory tract infections are among the global leading causes of ill-health and death. In 2017, cardiovascular disease (CVD) accounted for more than 160,000 deaths in the UK. Previous research has shown that people have a short-term risk of heart attack and stroke in the days after a serious respiratory infection, such as flu or pneumonia. This risk has mostly been found in older adults and those with pre-existing CVD.
This study aims to establish whether this risk also occurs in people without pre-existing CVD but who have raised cardiovascular risk, for example high blood pressure, which is suggestive of future CVD. Establishing such risk is important for UK vaccine policy; influenza and pneumococcal vaccination recommendations currently include people aged ?65 years and those with CVD, but not people aged <65 years with raised cardiovascular risk.
We will use routinely collected healthcare data in England to compare the occurrence of serious respiratory infections as well as subsequent cardiovascular events, such as heart attack or stroke, in people with a raised cardiovascular risk compared to people without raised risk.
The results from this study will inform future research to evaluate the impact of influenza and pneumococcal vaccination in populations with raised cardiovascular risk.
In the UK there are an estimated 7 million people living with CVD, for which the annual costs are estimated to be £19 billion. As the population ages and multimorbidity prevalence increases, stratified interventions are ever more important. The risk of cardiovascular complications after an acute systemic respiratory infection in people with raised cardiovascular risk but without established CVD is unknown. Quantifying any such increased risk will inform whether these groups should be considered for influenza and pneumococcal vaccination.
Our cohort study will use CPRD data linked to HES and ONS mortality data to increase ascertainment of respiratory and cardiovascular events. We will define cardiovascular risk by hypertension diagnosis and QRISK2 score. QRISK2 is a prediction algorithm for future CVD which utilises a range of risk factors, beyond hypertension, to determine risk. We will first calculate age-specific incidence rates for diagnosis of acute systemic respiratory infections by cardiovascular risk among adults aged 40 to 64 years. We will compare 1) people with hypertension to those without hypertension and 2) people with a QRISK2 score ?10% in ten years compared to those with a QRISK2 score <10%. We will then use Poisson regression models with Lexis expansion by age group and cardiovascular risk level to estimate incidence rates and rate ratios for 1) acute systemic respiratory infections including influenza-like illness and pneumonia, and 2) major acute cardiovascular events (MACE). Using Cox proportional hazards regression multivariable models, which adjust for potential confounders, we will then estimate the effect of cardiovascular risk on MACE after an acute systemic respiratory infection. In our definition of MACE we will include; myocardial infarction, unstable angina, left ventricular heart failure, stroke, transient ischaemic attack, acute limb ischaemia and cardiovascular death.
Primary
Aim 1 & 2: all-cause acute systemic respiratory tract infections. This includes clinical or confirmed diagnoses such as pneumonia, acute bronchitis, influenza / influenza-like illness (ILI), and other acute infections suggestive of lower respiratory tract improvement.
Aim 3 & 4: all-cause major adverse cardiovascular events (MACE). This includes; cardiovascular death, acute coronary syndrome (ACS) which captures both myocardial infarction (MI) and unstable angina, stroke, transient ischaemic attack (TIA), left ventricular heart failure and acute ischaemic limb.
Secondary
Aim 1 & 2:
Influenza / ILI
pneumonia
Aim 3 & 4 cause-specific acute cardiovascular events:
ACS,
stroke / TIA,
left ventricular heart failure,
acute ischaemic limb, and
cardiovascular death.
Charlotte Warren-Gash - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jennifer Davidson - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Amitava Banerjee - Collaborator - University College London ( UCL )
Daniel Grint - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Emily Herrett - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Harriet Forbes - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Helen McDonald - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jemma Walker - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Richard Pebody - Collaborator - Public Health England
Rohini Mathur - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Vanessa Saliba - Collaborator - Public Health England
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Townsend Score