Clinical trial NCT02157662: GISSI Outliers CAPIRE
Official title: Coronary Atherosclerosis in Outlier Subjects: Protective and Individual Risk Factor Evaluation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atherosclerosis
Lead sponsor: Gruppo di Ricerca GISSI
Sponsor class: OTHER
First posted: 2014-06-06
Enrollment: 544
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Male and female subjects between 45 and 75 years old who, in the absence of any previous clinical manifestations of ischemic heart disease, will undergo coronary arteries study.

Brief summary: The risk of developing clinical manifestations of ischemic heart disease is currently assessed by using integrated multifactorial prediction models based on the presence of non-modifiable risk factors, such as age, gender and a family history of early ischemic heart disease along with risk factors which are defined as conventional, such as arterial hypertension, hypercholesterolemia, cigarette smoking and diabetes mellitus.

However, if the relationship between risk factors and ischemic heart disease clinical manifestations shows some limitations, the relation between risk factors and the coronary atherosclerosis process underlying most ischemic syndromes seems to be even weaker.

In fact there is significant individual variability and the limits of such relationship are demonstrated by a non negligible number of subjects at the outliers of mean behaviour of the prediction model. At one outlier, in the presence of multiple risk factors, these subjects do not develop neither coronary events nor coronary atherosclerosis whereas, at the other, coronary events and disease occur in the absence of risk factors.This study aims at detecting new protection and susceptibility factors, thus enabling to formulate new etiopathogenetic hypotheses concerning coronary atherosclerosis and to identify new therapeutic targets.


Eligibility criteria: Inclusion Criteria:

* Group A: subjects with total absence of coronary atherosclerosis and 3 or more risk factors (reported by the subject or documented at the MDCT)
* Group B: subjects with diffuse coronary atherosclerosis extended to more than 5 of the 16 segments according to the American Heart Association classification and 0-1 risk factor (reported by the subject or documented at the MDCT) with the exclusion of patients with type 1 or type 2 diabetes mellitus as single risk factor.

Using the same criteria, two control populations will be selected, with a case:control 1:1 ratio, consisting in:

* Group C: subjects with total absence of coronary atherosclerosis and 0-1 risk factor (reported by the subject or documented at the MDCT)
* Group D: subjects with diffuse coronary atherosclerosis extended to more than 5 of the 16 segments according to the American Heart Association classification and 3 or more risk factors (reported by the subject or documented at the MDCT) with the exclusion of patients with type 1 or type 2 diabetes mellitus as single risk factor.

Exclusion Criteria:

* common contraindications to MDCT (chronic renal failure with serum creatinine \> 2.0 mg/dl, suspected pregnancy, arrhythmias, body mass index \> 40, allergy to iodized contrast agent).
* previous cardiovascular events (heart failure, acute myocardial infarction, unstable angina, chronic stable angina, previous percutaneous or surgery coronary revascularization) both clinically evident and found by conventional diagnostic methods previous performed.
* subjects which MDCT does not meet the quality control criteria defined below in the protocol.
* patients with previous documented or identified at the moment of MDCT such as dilated cardiomyopathy regardless of etiology, obstructive hypertrophic cardiomyopathy, atrial fibrillation, myocarditis and inflammatory vascular disease.

Primary outcomes:
measure: Number of patients in each Group with a cardiovascular Event
timeFrame: 5 years
Secondary outcomes:
measure: Polymorphisms associated with chromosome 9 in each patient
timeFrame: At enrollment visit
Other outcomes:
Locations:
city: Lido Di Camaiore
country: Italy
facility: Nuovo Ospedale Versilia - SC Cardiologia
state: Lucca
city: Fano
country: Italy
facility: Ospedale Santa Croce - U.O.C. Cardiologia
state: PU
city: Fermo
country: Italy
facility: Ospedale Civile Augusto Murri - U.O. Cardiologia
city: Massa
country: Italy
facility: IFC CNR - Ospedale Pasquinucci - U.O. Cardiologia Adulti
city: Modena
country: Italy
facility: Ospedale Policlinico - Divisione di Cardiologia
city: Parma
country: Italy
facility: Az. Ospedaliera Universitaria di Parma - U.O. Cardiologia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - U.O. Radiodiagnostica I
city: Pisa
country: Italy
facility: IFC CNR Fondazione Toscana G. Monasterio - S.A. Emodinamica
city: Udine
country: Italy
facility: AOU Santa Maria della Misericordia - Angiografia e Radiologia Interventistica
city: Lugano
country: Switzerland
facility: Cardiocentro Ticino - SRC
Study officials:
References:
citation: Magnoni M, Andreini D, Gorini M, Moccetti T, Modena MG, Canestrari M, Berti S, Casolo G, Gabrielli D, Marraccini P, Pontone G, Masson S, Latini R, Maggioni AP, Maseri A; CAPIRE Study Group. Coronary atherosclerosis in outlier subjects at the opposite extremes of traditional risk factors: Rationale and preliminary results of the Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation (CAPIRE) study. Am Heart J. 2016 Mar;173:18-26. doi: 10.1016/j.ahj.2015.11.017. Epub 2015 Dec 17.
citation: Magnoni M, Masson S, Andreini D, Moccetti T, Modena MG, Canestrari M, Berti S, Casolo G, Gabrielli D, Marraccini P, Pontone G, Latini R, Maggioni AP, Maseri A; CAPIRE Study Group. Usefulness of High-Sensitivity Cardiac Troponin T for the Identification of Outlier Patients With Diffuse Coronary Atherosclerosis and Low-Risk Factors. Am J Cardiol. 2016 May 1;117(9):1397-404. doi: 10.1016/j.amjcard.2016.02.002. Epub 2016 Feb 17.
citation: Andreini D, Magnoni M, Conte E, Masson S, Mushtaq S, Berti S, Canestrari M, Casolo G, Gabrielli D, Latini R, Marraccini P, Moccetti T, Modena MG, Pontone G, Gorini M, Maggioni AP, Maseri A; CAPIRE Investigators. Coronary Plaque Features on CTA Can Identify Patients at Increased Risk of Cardiovascular Events. JACC Cardiovasc Imaging. 2020 Aug;13(8):1704-1717. doi: 10.1016/j.jcmg.2019.06.019. Epub 2019 Aug 14.
citation: Ferrannini G, Manca ML, Magnoni M, Andreotti F, Andreini D, Latini R, Maseri A, Maggioni AP, Ostroff RM, Williams SA, Ferrannini E. Coronary Artery Disease and Type 2 Diabetes: A Proteomic Study. Diabetes Care. 2020 Apr;43(4):843-851. doi: 10.2337/dc19-1902. Epub 2020 Jan 27.
citation: Conte E, Andreini D, Magnoni M, Masson S, Mushtaq S, Berti S, Canestrari M, Casolo G, Gabrielli D, Latini R, Marraccini P, Moccetti T, Modena MG, Pontone G, Gorini M, Maggioni AP, Maseri A; CAPIRE Investigators, Steering Committee; Imaging Core Laboratory; Centralized biobank and biomarker core laboratory; Central ECG Reading; Psychologists CRF Group; Participating Centers and Investigators. Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study. J Cardiovasc Comput Tomogr. 2021 Jan-Feb;15(1):73-80. doi: 10.1016/j.jcct.2020.03.005. Epub 2020 Jun 11.
citation: Ferrannini E, Manca ML, Ferrannini G, Andreotti F, Andreini D, Latini R, Magnoni M, Williams SA, Maseri A, Maggioni AP. Differential Proteomics of Cardiovascular Risk and Coronary Artery Disease in Humans. Front Cardiovasc Med. 2022 Feb 4;8:790289. doi: 10.3389/fcvm.2021.790289. eCollection 2021.