Aim: To examine the occurrence of cardiovascular disease risk factors, previously diagnosed atherosclerotic disease, new ischaemic events and prescriptions issued in the period prior to first myocardial infarction (MI) and their association with outcomes at the time of and after MI. Methods: This thesis describes studies using linked CALIBER data from four UK sources: the General Practice Research Database, Hospital Episode Statistics, the Myocardial Ischaemic National Audit Project and Office for National Statistics mortality data. Linkage of these sources created a large, rich longitudinal dataset, allowing reconstruction of the patient journey before and after first MI. Quality of MI recording across the four data sources was first assessed and three further studies examined atherosclerotic disease, risk factor and drug exposures in the period preceding MI. Results: Despite an increased rate of ischaemic coronary presentations in the 90 days prior to MI, over half of first MI patients were unheralded by atherosclerotic disease diagnoses (56.5% (55.6-57.4%)). However, the great majority of people with no prior diagnosed atherosclerotic disease had identifiable vascular disease risk factors or had recent presentations with chest pain. Survival analysis showed that patients with new ischaemic presentations shortly before MI - possible clinical correlates of ischaemic preconditioning - had less severe infarcts and improved survival in the first seven days after MI (Hazard Ratio for coronary heart disease mortality 0.64 (0.57-0.73), P<0.001) compared to patients without previously recorded ischaemia. However, in the longer term ischaemic presentations shortly before MI were associated with poorer survival. Prescription of aspirin for primary prevention in the pre-MI period was also marker for attenuated MI severity, but with no effect on mortality or infarct size. There was no association between statin use for primary prevention and outcomes at MI. Conclusions: The novel prospective data used in this thesis have provided the opportunity to obtain new insights into MI as the first manifestation of ischaemic heart disease
