PARTNER SEARCH 01/10/2008 (Preliminary) Title of the
POSSIBLE DETERMINANTS OF PLAQUE INSTABILITY
ASSESSED BY MULTISLICE COMPUTED TOMOGRAPHY
IN ASYMPTOMATIC INTERMEDIATE-RISK PATIENT
Outline of the project idea and objectives (1000 words)
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 D.et 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]
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PARTNER SEARCH 01/10/2008