Cardiovascular disease (CVD) is the leading cause of mortality worldwide accounting for almost a third of all deaths. Nearly 18 million people around the world die from this disease each year with coronary artery disease (CAD) causing myocardial infarction, and stroke accounting for 80% of the mortality. The most frequently used test when screening for CAD is the cardiac stress test. This is performed by using exercise modalities (treadmill, cycle ergometer or arm ergometer) or by using pharmacological agents to induce cardiac stress. Beyond acknowledged contraindications to terminate these tests, there has been much debate regarding a suitable measure of sufficient cardiac stress. For many years age-predicted maximum heart rate (APMHR) has been accepted as an appropriate termination point consistent with significant cardiac stress in those without a positive indication of CAD. Surprisingly, this practice has not been validated in the setting of screening for CAD. Rate pressure product (RPP) (heart rate x systolic blood pressure) however has been demonstrated as an accurate indirect measure of myocardial oxygen consumption and therefore work of the heart. While RPP is frequently reported as a surrogate measure for cardiovascular (CV) or microvascular function, it is not commonly used as a measure of sufficient cardiac stress. The overall aim of the studies reported in this thesis was to evaluate RPP as a suitable diagnostic and prognostic measure of CV outcome in patients screened for CAD both during exercise and pharmacological stress. RPP demonstrated valuable diagnostic and prognostic outcomes during exercise, showing significant superiority to predict CV events to the widely used APMHR. Chapter 1 of this thesis briefly introduces the reader to the research subject. The 2nd chapter provides a literature review on RPP with a focus in the setting of CAD. Chapter 3 discusses the research aims and significance of the project in the clinical setting and wider community. Chapter 4 describes the general methodology used in this research with emphasis on the standardisation of the testing procedures employed throughout. Chapter 5 looks at the RPP response comparing the use of handrail support and no handrail support during exercise treadmill testing (ETT). While overall there was no difference in maximum RPP (MRPP) with and without handrail support, those unfamiliar with treadmill exercise produced a significantly greater MRPP with support (7.5% increase). When extrapolated to a clinical population this could be useful in screening for CAD when the goal of the ETT is to elicit maximal cardiac work. Chapter 6 explores the utility of RPP as a diagnostic and prognostic variable for future CV events in patients with reduced functional capacity during ETT. A cut point for RPP was revealed above which very few CV events were documented during a 5- year follow-up, potentially alleviating the need for downstream testing in this group. Furthermore, RPP outperformed APMHR when comparisons between these 2 variables were made. The 7th chapter evaluates RPP, APMHR and heart rate reserve (HRR), as diagnostic and prognostic predictors of future CV events. Unlike earlier studies this chapter reports the utilisation of pharmacological myocardial stress with dobutamine. We demonstrated HRR to be an excellent predictor of future CV events in those performing an otherwise negative dobutamine stress echocardiogram (DSE). In doing so we identified the shortcomings of RPP and APMHR in this setting. We believe this is the first study to demonstrate this. Chapter 8 describes the final experimental study performed aiming to confirm the findings of chapter 6. This study comprised a much larger cohort than reported in chapter 6 and included additional echocardiographic findings. Unlike chapter 6 where only those with reduced functional capacity were included, the current study involved all negative tests performed during the collection period. Remarkably, the RPP cut point demonstrating the best predictive outcome, was nearly identical to that noted in chapter 6. Furthermore, failure to produce the cut-off value for RPP was the strongest predictor of CV events during follow-up. Similarly, to the findings in chapter 6, APMHR was found to be inferior to RPP for the detection of future CV events. Chapter 9 is comprised of a case study series drawn from the experimental studies reported in chapters 6 to 8. The cases were selected to display the strengths and weaknesses of RPP in the setting of coronary compensatory mechanisms (collateralisation, non-dominant flow and balanced ischemia) that inadvertently mask myocardial ischemia during exercise testing. The individual cases discussed demonstrated the effective use of MRPP in conjunction with maximum fatigue in unmasking ischemia in these complex scenarios albeit with associated caveats. In conclusion, the work reported in this thesis demonstrates RPP during ETT to be superior to APMHR as a diagnostic and prognostic predictor of future CV events. The results herein warrant further investigation in this area to validate the use of RPP in clinical decision-making in patients screened for CAD.