Imaging In Cardiovascular Disease

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Biomarkers have been used for decades as surrogates to support the approval of drugs for the treatment of atherosclerotic cardiovascular disease. A considerable body of corroborative angiographic and carotid ultrasound imaging data show that drugs which diminish low density lipoprotein cholesterol (LDL-C), nonHDL-C and atherogenic triglycerides can slow plaque progression and cause plaque regression, which has been demonstrated in outcome studies to lead to reduced morbidity and mortality. Recent progress in the pathophysiology and pharmacology of atherosclerosis has resulted in novel drug molecules with mechanisms of action that directly target specific processes happening in the vessel wall. As a result, there has been a surge in research to validate and qualify novel vessel wall imaging biomarkers that could potentially be used as surrogates, alongside soluble biomarkers, to increase the efficiency of selection and subsequent speed of registration of safe and effective new medicines without waiting for the outcome of extensive long-term trials [23-27].

The time-dependent biology of atherosclerotic progression in the vessel wall has been well-characterized creating the opportunity to target therapeutic intervention by stage of disease and tailor the selection of imaging technologies for the evaluation of drug effects. It has been suggested that in the formative stages endothelial function could be evaluated, in the adaptive stages subclinical plaque shown by wall thickening and plaque volume, and in the clinical stage frank coronary disease through measurements of myocardial function and perfusion. The extent and reversal of disease may be studied noninvasively in the carotid blood vessels using ultrasound [28, 29] or invasively in the coronary arteries employing intravascular techniques [30-32]. MRI [33] and high resolution CT [34,35] may also be used. Myocardial perfusion can be studied using SPECT or PET [36] (the latter gives sensitive measures of microvascular perfusion). All these imaging modalities can also be used to study experimental models of atherosclerosis and so provide excellent translational research tools. The opportunity to apply a diverse range of imaging techniques to this important medical problem first seemed to be a strength but unfortunately has become somewhat of a weakness as competition rather than consensus on the best technique to use for registration of drugs has occurred.

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