Microsoft word - fp7.verona5.en.doc

(Preliminary) Title of the
and objectives (1000

Despite significant advances in the diagnosis and the treatment of cardiovascular disease, acute coronary syndromes are the first manifestation of atherosclerotic disease in more than 50% of subjects (1,2). Therefore, screening for subclinical atherosclerosis with non-invasive imaging modalities is an area of growing interest in intermediate-risk patients as evaluated by coronary prediction algorithms (3). Furthermore it has been demonstrated that the carotid intima-media thickness (IMT) (4,5), the endothelial dysfunction (6) and the Agatston coronary artery calcium (CAC) score (7,8) have a high predictive value for cardiovascular events. More recently, multislice computed tomography (MSCT) has allowed for the detection of not only coronary artery calcification but also coronary artery stenosis It is clear as well that oxidative stress and inflammation have a major role in every single step of atherosclerosis (11). Several studies demonstrated that the atherosclerotic plaques that are more prone to rupture, the “soft” plaques, are characterized by large plaque volumes and large necrotic cores that are covered by attenuated fibrous cap often inflamed with monocyte- macrophage infiltration (11,12). Since disruption of an atherosclerotic plaque is responsible for at least two-thirds of acute coronary events (13,14) and vulnerable plaques are often sizable, not abundant and located proximally in major vessels, an effort to detect vulnerable plaques appears of pivotal In asymptomatic patients at intermediate risk of developing - the plaque composition (soft, intermediate and calcified - possible relationships between endothelial dysfunction, carotid IMT, traditional risk factors for atherosclerosis, inflammation and oxidative stress parameters and the plaque composition and We will select at least 100 intermediate/high risk patients, both males and females, aged 35-75. These patients will be enrolled, after signed written consent to take part to the study, in the Internal Medicine, Cardiology and Surgery Units of the Verona - Absence of typical or atypical chest pain - more than two risk factors for ischemic heart disease (smoke, hypertension, obesity, diabetes, hyperomocysteinemia, family history) with calculated cardiovascular risk > 10% - previous significant CAD, previous percutaneous intervention or - Calculation of cardiovascular risk (Progetto CUORE) (15) - Laboratory routine tests: plasma glucose, insulinemia, glycosilated haemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, homocysteinemia, creatinine, - Inflammatory circulating parameters (hs-PCR, adhesion molecules and proinflammatory cytokines) and oxidative stress parameters (oxidized phospholipids, oxidized LDL, ADMA, - From circulating monocytes: quantitative definition of expression of oxidative stress and inflammatory genes (with - Endothelium-dependent flow-mediated dilation of brachial If coronary stenosis >50% at CA-MSCT: - Stress test (ergometric test or dipyridamole provocative test); If stress test positive for inducible ischemia: - Percutaneous coronary intervention (PCI) with virtual histology 1. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326:310–318. 2. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 3. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), JAMA 2001; 285:2486– 4. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol 1997; 146:483–494. 5. Kablak-Ziembicka A, Tracz W, Przewlocki T, Pieniazek P, Sokolowski A, Konieczynska M Association of increased carotid intima-media thickness with the extent of coronary artery 6. Vita JA, Keaney F, Jr. Endothelial function: a barometer for cardiovascular risk? Circulation 2002; 106:640–642. 7. Budoff MJ, Georgiou D, Brody A, Agatston AS, Kennedy J, Wolfkiel C, Stanford W, Shields P, Lewis RJ, Janowitz WR, Rich S, Brundage BH (1996) Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study. Circulation 93:898–904. 8. Guerci AD, Spadaro LA, Goodman KJ, Lledo-Perez A, Newstein D, Lerner G, Arad Y (1998) Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease. J Am Coll Cardiol 32:673–679. 9. Komatsu S, Hirayama A, Omori Y, Ueda Y, Mizote I, Fujisawa Y, Kiyomoto M, Higashide T, Kodama K. Detection of coronary plaque by computed tomography with a novel plaque analysis system, 'Plaque Map', and comparison with intravascular ultrasound and angioscopy. Circ J. 2005;69:72-77. 10. Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, Inoue K, Okumura M, Ishii J, Anno H, Virmani R, Ozaki Y, Hishida H, Narula J. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. 11. Libby P, Ridker PM.: Inflammation and Atherothrombosis. Journal of the American College of Cardiology 2006; 48:A33- 12. Narula J, Finn AV, Demaria AN. Picking plaques that pop. J 13. Davies MJ. The composition of coronary-artery plaques N 14. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 15. Palmieri L, Panico S, Vanuzzo al., per il Gruppo di ricerca del Progetto CUORE, La valutazione del rischio cardiovascolare globale assoluto: il punteggio individuale del Progetto CUORE. Ann Ist Super Sanità 2004; 40(4). FP7 Topic
HEALTH-2009-2.1.2-1: Systems biology approaches for basic
biological processes relevant to health and disease. FP7-
HEALTH-2009-two-stage or HEALTH-2009-2.4.2-1:
Improved or new therapeutic approaches for the treatment of
heart failure. FP7-HEALTH-2009-single-stage

Foreseen project duration

Type of partners you are

Partners who share the objectives in order to increase the looking for and their
number of recruited patients and/or want to evaluate other expected roles in the
possible determinants of plaque instability
Contact details:

38 Rue d' Arlon B-1000 BRUXELLES Tel. 32(0)2/234.36.00 Fax. 32(0)2/230.92.66 e-mail: [email protected]


Mi-12-011 87.89

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