Troponins are regulatory proteins and part of the contractile apparatus that is integral to muscle contraction in skeletal and cardiac muscle but not smooth muscle and are important clinically because cardiac troponins (cTn) are sensitive indicators of myocyte injury and have become integral to the definition of myocardial infarction . There are several issues surrounding the significance of troponin and how it should be used, both for the assessment of cardiac disease and in settings of non-cardiac illness. This thesis examines a number of these areas of uncertainty. This thesis focuses initially on the analytical validation of troponin assays and I offer guidelines for a standardised approach to undertaking the verification of these analytical characteristics. I report on these characteristics for 2 highly sensitive assays and their application to a cardio-healthy population. In the second part of this thesis I focus on the physiology of troponin in the normal population. I describe studies undertaken with a cohort of healthy children and demonstrate the significance of population coning when determining the 99th percentile of the upper reference limit using 2 highly sensitive troponin assays. The final part of this thesis investigates the significance of troponin in the acute coronary syndrome (ACS) and non ACS setting. I offer a hypothesis suggesting that bleb formation is a mechanism for troponin release. I describe how improvements in sensitivity of troponin T assays allow better prognostic information regarding all cause mortality in end stage renal disease patients, demonstrate troponin release after strenuous exercise in elite cyclists and I describe a cross-sectional study looking at troponin concentrations in subjects with non cardiac illness and the general community. Using data mining techniques I demonstrate how the use of a new high sensitivity troponin I assay can offer greater assistance to the clinician in stratifying patients at risk of a major adverse cardiac event (MACE). I provide evidence that suggests the use of a multi-marker approach to identifying patients at risk is potentially viable.
|Date of Award
|Luby Simson (Supervisor), Peter E. Hickman (Supervisor) & Alice Richardson (Supervisor)