Cardiovascular disease* is the leading cause of death and illness globally. Preventive therapies can avoid or delay the occurrence of cardiovascular events, provided that one can diagnose individuals at risk and intervene before problems manifest. Recent scientific developments have established that inflammation** has a prominent role in the development of cardiovascular diseases; but routine screening of inflammatory markers to assess cardiovascular risk in the general population is currently unfeasible. It is known however that certain diseases cause high and chronic (i.e. prolonged) inflammation, and patients affected by these conditions may be at increased risk of cardiovascular events. Yet, studies so far have been limited by the relatively modest absolute numbers of patients affected, so that for many of these conditions evidence is insufficient to guide clinical decisions.
The present research proposal aims to take advantage of the very large size and rich information provided by the CPRD (Clinical Practice Research Datalink) database to address these knowledge gaps and to investigate the associations between chronic inflammatory conditions and cardiovascular disorders.
A better understanding of cardiovascular risks associated with chronic inflammatory conditions may help guidelines and clinicians to focus on patients for which screening and treatments are more likely to have an effect and improve the prevention of cardiovascular diseases.
* Cardiovascular diseases refer to diseases that involve the heart or blood vessels.
** Inflammation is the bodys response to an infection or injury. Inflammation typically causes tissues to swell and lose their original function.
Background: Markers of inflammation are associated with increased risk of cardiovascular disorders (CVD). Certain conditions are known to be associated with high and chronic inflammation, yet evidence of increased CVD risk in these patients is limited and differences between conditions have not been compared.
Objectives: To quantify the incidence and prevalence of chronic inflammatory and cardiovascular conditions (objective 1), to investigate whether patients with chronic inflammatory conditions are at increased risk of incidence (objective 2) and severity (objective 3) of CVD, and to examine how risks vary by individual disease, type of disease, age, and sex.
Study design and setting: Longitudinal population-based study using anonymised electronic health records.
Main outcomes: Chronic inflammatory conditions (CIC): Addison; ankylosing spondylitis; asthma; Coeliac; COPD; gout; Graves; Hashimoto thyroiditis; inflammatory bowel disease; insulin dependent diabetes; multiple sclerosis; myasthenia gravis; osteoarthritis; psoriasis; polymyalgia rheumatica; primary biliary cirrhosis; pernicious anaemia; rheumatoid arthritis; Sjogrens; systemic lupus erythematosus; systemic sclerosis; vasculitis; and vitiligo. Cardiovascular disorders: aortic stenosis; aortic aneurysm; cardiac arrythmias; heart failure; ischaemic heart disease; stroke; peripheral arterial disease; venous thromboembolism or pulmonary embolism; and valve disorders.
Methods: (1) incidence and prevalence of CIC and CVD conditions in the general population; (2) incidence rates of CVD events in patients with and without CIC; and (3) cause-specific 1-year mortality rates following an incident CVD event in patients with and without CIC. Associations between CIC and CVD will be examined using random-effects Poisson regression models accounting for clustering between practices and patient characteristics (incl. age, sex, socioeconomic status, comorbidities, CVD risk factors). Analyses will be performed for individual diseases and stratified by disease category, age, and sex.
Expected outcomes: Identification of high-risk populations may lead to more targeted screening and treatment strategies and improve the prevention of cardiovascular diseases.
Chronic inflammatory conditions: The proposed analysis will investigate chronic inflammatory conditions (CIC). These include auto-immune conditions: Chronic inflammatory conditions (CIC): Addisons disease; ankylosing spondylitis; Coeliac disease; Graves disease; Hashimoto thyroiditis; inflammatory bowel disease (Crohn disease and ulcerative colitis); insulin dependent diabetes; multiple sclerosis; myasthenia gravis; psoriasis; polymyalgia rheumatica; primary biliary cirrhosis; pernicious anaemia; rheumatoid arthritis; Sjogrens; systemic lupus erythematosus; systemic sclerosis; vasculitis; and vitiligo; as well as other conditions associated with strong and chronic inflammatory load: asthma, chronic obstructive pulmonary disease, gout and osteoarthritis. These diseases were selected in light of their chronic nature and enhanced inflammatory burden, alongside their relatively high prevalence in the general population. Diagnoses will be extracted from patients primary and secondary care records.
Cardiovascular diseases: The proposed analysis will consider the following cardiovascular disorders (CVD): aortic stenosis; aortic aneurysm; cardiac arrythmias; heart failure; ischaemic heart disease; stroke; peripheral arterial disease; venous thromboembolism or pulmonary embolism; and valve disorders. These diseases were selected to broadly reflect the spectrum of CVD. Some of the conditions (e.g. ischaemic heart disease or aortic stenosis) are linked to atherosclerosis for which the involvement of inflammation is well known.21 For others (e.g. atrial fibrillation or aortic aneurysm), influence of inflammation is less well established. Diseases will be considered individually and as a composite outcome of all CVD combined. Diagnoses will be extracted from patients primary and secondary care records.
Cause-specific mortality: The proposed research will investigate cause-specific mortality as recorded in death certificates from the Office for National Statistics (ONS). The cause of death will be defined as the first reported cause in each patients death certificate.
Cause-specific mortality and hospitalisations: The proposed research will investigate hospital admissions from Hospital Episodes Statistics (HES) data. The cause of hospitalization will be defined as the primary discharge diagnosis.
Nathalie Conrad - Chief Investigator - KU Leuven University
Nathalie Conrad - Corresponding Applicant - KU Leuven University
Geert Molenberghs - Collaborator - KU Leuven University
Geert Verbeke - Collaborator - KU Leuven University
Geraldine Cambridge - Collaborator - University College London ( UCL )
Iain McInnes - Collaborator - University of Glasgow
Jan Verbakel - Collaborator - KU Leuven University
John McMurray - Collaborator - University of Glasgow
Kamlesh Khunti - Collaborator - University of Leicester
Kazem Rahimi - Collaborator - University of Oxford
Laura Goetschalckx - Collaborator - KU Leuven University
Naveed Sattar - Collaborator - University of Glasgow
Peter Taylor - Collaborator - Cardiff University
Shivani Misra - Collaborator - Imperial College London
Thomas Callender - Collaborator - University College London ( UCL )
Kamlesh Khunti - Collaborator - University of Leicester
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation