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INTEGRATION OF ARTERIAL ASSESSMENT INTO CLINICAL PRACTICE(Chairpersons: F Cosentino/A Gallino)
Carotid intima-media thickness (IMT) is a potential phenotype for early atherosclerosis. Because it is non-invasive and relatively easy to measure, it may become an excellent tool for use in large-scale population studies. Ultrasound measurements correlate well with histology, and increased IMT is associated with cardio-vascular risk factors, and with the presence of advanced atherosclerosis. IMT is being increasingly used to stratify individual risk and as an endpoint in interventional trials. Prof Schmidt reported on the need for a stringent methodological approach in using c-IMT for research and especially for future clinical use. He stressed the need for standardization and definition of the procedure(location of detection!), of automated detection of the measurement. The degree of carotid disease that appears to be of prognostic value is much subtler, and requires meticulous and detailed measurements of IMT through B-mode ultrasound. He stressed the variability of measurements performed at different anatomic landmarks (CCA/ICA) underlining how the lowest variability is located at the level of the CCA. These measurements can be achieved in a reproducible and reliable manner if sonographers and those taking the measurements are trained in a comprehensive and rigorous way and if consistency and reproducibility over time is consistent; these standards must be obtained for clinical trials(Stroke. 1996 Mar;27(3):480).He also underlined the need of meticulous following of a pre-specified protocol (Comp Meth. Biomed; 2002;67:27). He also mentioned the variations found in a recent paper examining the wall structure continuously throughout several heart cycles, where its role has not been completely elucitated. He further reported on the ability of c-IMT to predict future clinical cardiovascular endpoints in epidemiological trials and he referred to the large epidemiological meta-analysis of M-W. Lorenz (Circulation; 2007;115:459). Carotid IMT is a strong predictor of future cardiovascular events. The relative risk per IMT difference is higher for stroke than for myocardial infarction. In future IMT studies, ultrasound protocols should be standardized to published studies, whereas data for younger persons/patients are limited and more studies are required.
The number of patients presenting peripheral artery disease in Europe and in the US is estimated to be around 27 million. There is a need for a simple diagnostic test to identify this increasing population with a severe disease associated with high mortality and morbidity. This diagnostic test (Ankle-Brachial-Index) has already been available for > 30 years but is amazingly underused, considering that its accuracy, sensitivity and specificity are higher than mammography and PAP tests to detect breast and cervix cancer respectively. R Bahir emphasized the role of this extremely simple, bed-side, cost-effective diagnostic tool which can be taught within < 1 hour to a non MD operator and does not necessitate any special training. The universally accepted threshold to define normal from abnormal ABI is 0.9, defined usually as the highest value measured (although some prefer the mean ABI value). ABI is a formidable marker of cardiovascular risk, poly-vascular disease, function of health decline , and –last but not least – of health resource consumption. He emphasized the results of the recent milestone studies- the Get ABI study and the REACH Registry, the PARTNERS study( Circ 2009;120:2053 , EHJ 2009;30:2318) and the Cost-effectivness substudy of the REACH report by Mahagoney recently reported in JACC imaging. He finished by emphasizing the need to increase awareness of peripheral artery disease in the general population and in the medical arena.
Brachial artery flow-mediated dilation (FMD) serves as a measure of endothelial vasodilator function in humans (J Am Coll Cardiol. 2002; 39: 257–265). Experimental and clinical investigations suggest that development of endothelial dysfunction, including reduced NO bioavailability, may contribute to atherosclerosis and pathogenesis of cardiovascular disease (CVD) events(Circulation. 2002; 106: 640–642). Studies in humans show that endothelial dysfunction anticipates the development of clinically overt atherosclerosis in subjects with CVD risk factors such as smoking, hypertension, hyperlipidemia, diabetes mellitus, and obesity. Effective treatment of risk factors may reverse endothelial dysfunction, and studies in individuals with risk factors and high prevalence of CVD have shown that endothelial dysfunction identifies patients at risk for future events. Like for the other methods presented in this session, the same methodological preambles are valid for FMD: amongst others, training, adherence to a strict imaging protocol, and conditions of examination. The four main applications of this method are:1) Research purposes, where FMD has found a well defined place; as well as the following less established domains :2) Risk stratification of cardiovascular events; 3) risk stratification of patients with chest pain (JACC 2004;44:1636); 4) risk stratification in heart failure patients (JACC 2005; 46:1011).
Arterial stiffness is increasingly recognized as a surrogate end point for cardiovascular (CV) disease (Eur Heart J 2006;27:2588-2605). Apart from invasive methods, it can also be measured with noninvasive, reproducible, and relatively inexpensive techniques, and, thus, is suitable for large-scale studies. Arterial stiffness is associated with presence of CV risk factors and atherosclerotic disease (Heart 2006;92:1544-1550). Importantly, a number of studies examined the ability of arterial stiffness to predict the risk of future fatal and nonfatal CV events (myocardial infarction, stroke, revascularization, stroke, aortic syndromes) and total mortality (Hypertension 2010;55:799-805). Arterial elastic properties are increasingly used for risk stratification purposes in several populations, and recently, the European Society of Hypertension/European Society of Cardiology guidelines for the management of arterial hypertension suggested the measurement of aortic pulse wave velocity (PWV), which is considered the gold standard method for assessing aortic stiffness, as a tool for assessment of subclinical target organ damage (J Hypertens 2007;25:1105-1187). Vlachopoulos presented his recent data on systematic review and meta-analysis, pooling the aortic PWV data for 15,877 subjects from 17 available published studies who were followed up for a mean of 7.7 years. Within each patient group, the risk of CV events, CV mortality, and all-cause mortality in subjects with increased aortic PWV, which is considered as the gold standard index of aortic stiffness, is almost twice as high compared with the risk of subjects with lower aortic PWV. Importantly, the predictive value of increased arterial stiffness is larger in patients with higher risk disease states, such as renal disease. Although for each patient group exact values may differ slightly, for an increase in aortic PWV of 1 m/s or of 1 SD, the risk increases by more than 10% or 40%, respectively.
(J Am Coll Cardiol Img, 2008; 1:406-409) Molecular imaging is an emerging research field with the potential to detect CV disease in pre-clinical and early stages. It integrates disciplines of cell biology, clinical medicine, and signal transduction for adequate selection of tissues to be imaged, and synthetic biochemistry and bio-imaging sciences for characterization of the pathology in vivo. In contrast to current diagnostic techniques, molecular imaging uses noninvasive, quantitative, and repetitive strategy of imaging targeted biological processes at both cellular and subcellular levels within a living organism (Atlas of Nuclear Cardiology. 2nd edition. Philadelphia, PA: Current Medicine; 2005. pp. 253-276.). Due to recent advances in nanotechnology and engineering, molecular imaging has undergone important changes during its brief development period as a scientific discipline. By merging medical and computer technology, molecular imaging has made it possible to visually simplify the complexity of diseases. It offers the possibility to better understand pathophysiology, such as modification in metabolic states, cellular- or sub-cellular processes, receptor alterations, and genetic expression. To effectively establish the concept of molecular imaging, the feasibility of imaging in small transgenic animal models is essential. This has driven the development of advanced animal micro- imaging tools including micro-scale positron emission tomography, single-photon emission computed tomography, computed tomography, magnetic resonance imaging, high-frequency ultrasound. Fusion technology combining computed tomography, magnetic resonance imaging, or ultrasound imaging should provide both morphological and functional information, allowing a better localization of the process.
lntegration of arterial assessment into clinical practice
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