Objectives: 1) To visualize the pathways through which individuals transition from full health to death, along intermediating cardiovascular diagnoses. 2) To use the visualization to identify potential prognostic subtypes. 3) To describe the predictors of these subtypes, especially the role of biomarkers and comorbidities/multimorbidity. 4) To evaluate the causality of any biomarkers identified.
Participants: Baseline participants (ca 2 million patients from CPRD, who at entry between 1997-2010 are aged 30+) are followed up for morbidity and mortality with CPRD, HES, ONS and MINAP databases, to identify 22 cardiovascular outcomes (including coronary, stroke, and arrythmic events) and one non-cardiovascular outcome (major haemorrhage).
Methods: 1-2) Alluvial diagrams will be used to describe the progression of participants from health to death. 3) Classical Cox survival models will be adapted to identify which predictors describe each subtype. 4) Mendelian Randomization will be applied to data (probably the UK Biobank) for causal inference.
We are not aware of previous work that used electronic healthcare record data, to identify subtypes of disease progression. Thus if our results are validated by future studies, it could hold methodological value in demonstrating the utility of these methods for analyzing large-scale EHR datasets to identify phenotypic subtypes of disease.
Fatal outcomes: coronary heart disease death; cardiac arrest; other cardiovascular disease death; non-cardiovascular disease death Non-fatal outcomes: Cardiovascular disease states: stable angina; unstable angina; STEMI; NSTEMI; other coronary heart disease; transient ischaemic attack; ischaemic stroke; subarachnoid haemorrhage; intracerebral haemorrhage; other stroke; mitral valve disease; aortic valve disease; other valve disease; atrial fibrillation ; other conduction disorder; peripheral vascular disease; abdominal aortic aneurysm; heart failure ; miscellaneous cardiovascular diseases; Net use of healthcare services
Harry Hemingway - Chief Investigator - University College London ( UCL )
Taavi Tillmann - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Alireza Moayyeri - Collaborator - UCB Pharma SA - UK
Amitava Banerjee - Collaborator - University College London ( UCL )
David Prieto-Merino - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Maria Pikoula - Collaborator - University College London ( UCL )
Riyaz Patel - Collaborator - Barts Health and UCLH NHS Trusts
Spiros Denaxas - Collaborator - University College London ( UCL )