GISSI Outliers CAPIRE

NCT02157662 | Completed

• 1 other identifier: K10
• Study Type: observational
• Target: 544
• Locations: 2 countries
• Sites: 10

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.

Conditions

Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Number of patients in each Group with a cardiovascular Event

  5 years

Secondary Outcomes (1)

• Polymorphisms associated with chromosome 9 in each patient

  At enrollment visit

Study Arms (4)

No coronary disease and risk factors >=3

Coronary disease and risk factors 0-1

Diffuse coronary atherosclerosis extended to more than 5 of the 16 segments according to the American Heart Association classification38 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.

No coronary disease and risk factors 0-1

Coronary disease and risk factors >=3

Subjects with diffuse coronary atherosclerosis extended to more than 5 of the 16 segments according to the American Heart Association classification38 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

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Group A: subjects with total absence of coronary atherosclerosis and 3 or more risk factors (reported by the subject or documented at the MDCT)
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo di Ricerca GISSI: lead

Study Sites (10)

Nuovo Ospedale Versilia - SC Cardiologia

Lido di Camaiore, Lucca, Italy

Location

Ospedale Santa Croce - U.O.C. Cardiologia

Fano, PU, Italy

Location

Ospedale Civile Augusto Murri - U.O. Cardiologia

Fermo, Italy

Location

IFC CNR - Ospedale Pasquinucci - U.O. Cardiologia Adulti

Massa, Italy

Location

Ospedale Policlinico - Divisione di Cardiologia

Modena, Italy

Location

Az. Ospedaliera Universitaria di Parma - U.O. Cardiologia

Parma, Italy

Location

Azienda Ospedaliero Universitaria Pisana - U.O. Radiodiagnostica I

Pisa, Italy

Location

IFC CNR Fondazione Toscana G. Monasterio - S.A. Emodinamica

Pisa, Italy

Location

AOU Santa Maria della Misericordia - Angiografia e Radiologia Interventistica

Udine, Italy

Location

Cardiocentro Ticino - SRC

Lugano, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 26920592 BACKGROUND

• 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.

  PMID: 26976791 BACKGROUND

• 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.

  PMID: 31422137 BACKGROUND

• 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.

  PMID: 31988066 BACKGROUND

• 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.

  PMID: 32563713 BACKGROUND

• Magnoni M, Andreini D, Andreotti F, Latini R, Maseri A, Nicoletti A, Maggioni AP, Caligiuri G. Leukocyte-shed soluble CD31 unmasks coronary disease in low-risk outliers and provides source-specific inflammatory signatures of vulnerable plaques. Atherosclerosis. 2025 Aug;407:120410. doi: 10.1016/j.atherosclerosis.2025.120410. Epub 2025 Jun 13.

  PMID: 40543300 DERIVED

• 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.

  PMID: 35187107 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood and serum. Lipid profile Metabolic profile (HbA1c, HOMA index) inflammatory profile (CRP, LP-PLA, pentraxine 3, MCP-1, IL-8, IL-10, IL-5, P-selectin, ICAM, VCAM-1, CD40L, TIMP-1, MMP Genetic profile: chromosome polymorphism 9 (9p21)

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2014
• First Posted: June 6, 2014
• Study Start: January 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: September 13, 2023
• Last Updated: September 18, 2023

Record last verified: 2023-09

Locations

IT (9); CH (1)