Health Improvements by Understanding the Determinants of Residual Risk in Coronary Artery Disease and New Targets for Prevention and Treatment

NCT06601153 | Recruiting

• 1 other identifier: PNRR-MAD-2022-12376550
• Study Type: observational
• Target: 961
• Locations: 1 country
• Sites: 2

Brief Summary

Current medical treatments, in patients with stable coronary artery disease (CAD), mainly target established risk factors and are able to reduce morbidity and mortality but still leave a substantial residual risk of coronary artery disease progression and events. The main hypothesis of this study is that metabolic derangement, including pre-diabetes, elevated levels of triglycerides, low levels and functionality of high-density lipoprotein cholesterol, often associated with a chronic inflammatory state, is a currently unrecognized and undertreated conditon which could be the most relevant determinant of residual risk. The goal of HURRICANE observational study is to discover specific individual genetic/molecular profiles subtending emerging cardiometabolic and vascular risk patterns and associating with a more severe and progressive coronary artery disease. We will thus develop and preliminary validate new predictive models for the recognition of high-risk patients and explore possible new targets for individualized preventive treatment. The severity, extent and progression of coronary plaques will be assessed by qualitative and quantitative analysis of cardiac computed tomography (CCT) performed in retrospective and prospective cohorts of patients with stable coronary disease.

Conditions

Coronary Arterial Disease (CAD)

Keywords

coronary artery disease (CAD); cardiac CT (CCT); cardiovascular risk factors; atherogenic dyslipidemia; insulin resistance (IR); molecular medicine; genetics.

Outcome Measures

Primary Outcomes (1)

• Primary Objective

  The primary objective is the development (retrospective study) and validation (prospective study) of new integrated clinical and molecular/genetic predictive models of severity and extent of CAD defined by CCT in patients with stable disease. Developed models will be extended (prospective study) to the prediction of progression (at 1-year follow-up) of CAD phenotypes occurring despite OMT. The hypothesis is that these models, including specific molecular markers (assessed by traditional laboratory as well as by "omics" approaches) of emerging cardiometabolic and vascular risk, could predict CAD severity/extent and progression more accurately than other traditional risk models.

  In the prospective Study patients will be evaluated at baseline and follow-up within a18 months time frame.

Secondary Outcomes (1)

• Secondary Objective

  In the prospective Study selected groups of patients will be evaluated at baseline and follow-up within a18 months time frame.

Study Arms (2)

Retrospective cohort of 561 patients with suspected CAD

All patients with suspected CAD with available blood samples stored in bio-banks and interpretable CCT stored in imaging repositories.

Diagnostic Test: Cardiac CT

Prospective cohort od 400 patients with suspected CAD

All patients with suspected CAD in whom with blood samples will be collected and stored in bio-banks and CCT will be acquired and stored in imaging repositories.

Diagnostic Test: Cardiac CT

Interventions

Cardiac CT DIAGNOSTIC_TEST

Cardiac CT to characterize coronary atherosclerosis

Also known as: Computed Tomography Coronary Angiography

Prospective cohort od 400 patients with suspected CAD; Retrospective cohort of 561 patients with suspected CAD

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

RETROSPECTIVE STUDY From the 684 patients with suspected or known stable CAD, referred to IRCCS SYNLAB SDN in Naples between July 2018 and March 2022 for clinically indicated CCT and enrolled in a previous study (Observational Study 7/18 OSS SDN), 376 patients meeting all eligibility criteria are included in the HURRICANE retrospective study population. From the 263 patients with suspected or known stable CAD, undergoing CCT at FTGM in Pisa from September 2012 to October 2913 and enrolled in a previous study (SMARTool, HORIZON 2020-689068), 185 patients meeting all eligibility criteria complete the HURRICANE retrospective study population. PROSPECTIVE STUDY The population of the prospective longitudinal study will include 400 patients referred at IRCCS SYNLAB SDN in Naples and FTGM in Pisa, over a 12 months period, to a clinically indicated CCT for suspected CAD, meeting all eligibility criteria and signing a written informed consent.

You may qualify if:

• patients with known or suspected stable CAD who underwent CCT for the registered studies "SMARTool" or "Studio di biomarcatori in vivo ed in vitro"
• fully accessible CCT image files and whole blood and plasma/serum aliquots stored in BioBank
• written informed consent

You may not qualify if:

• overt heart failure (NYHA Class III-IV) and/or reduced systolic LV function (LVEF\<40%)
• relevant comorbid conditions limiting expected survival to less than 1 year
• CCT exam of suboptimal quality
• PROSPECTIVE STUDY
• patients with suspected stable CAD clinically referred for a first diagnostic CCT
• fully accessible CCT image files and whole blood and plasma/serum aliquots stored in BioBank
• written informed consent
• history of previous CAD or major cardiovascular events
• overt heart failure (NYHA Class III-IV) and/or reduced systolic LV function (LVEF\<40%)
• relevant comorbid conditions limiting expected survival to less than 1 year
• CCT exam of suboptimal quality

Sponsors & Collaborators

• Fondazione Toscana Gabriele Monasterio: lead
• CNR Institute of Clinical Physiology, Pisa, Italy: collaborator
• IRCCS SYNLAB SDN, Naples, Italy: collaborator

Study Sites (2)

Fondazione Toscana Gabriele Monasterio

Pisa, Italy, 56124, Italy

RECRUITING

Irccs Synlab Sdn

Napoli, 80121, Italy

RECRUITING

Related Publications (7)

• Cademartiri F, Meloni A, Pistoia L, Degiorgi G, Clemente A, Gori C, Positano V, Celi S, Berti S, Emdin M, Panetta D, Menichetti L, Punzo B, Cavaliere C, Bossone E, Saba L, Cau R, Grutta L, Maffei E. Dual-Source Photon-Counting Computed Tomography-Part I: Clinical Overview of Cardiac CT and Coronary CT Angiography Applications. J Clin Med. 2023 May 23;12(11):3627. doi: 10.3390/jcm12113627.

  PMID: 37297822 BACKGROUND

• Neglia D, Liga R, Gimelli A, Podlesnikar T, Cvijic M, Pontone G, Miglioranza MH, Guaricci AI, Seitun S, Clemente A, Sumin A, Vitola J, Saraste A, Paunonen C, Sia CH, Paleev F, Sade LE, Zamorano JL, Maroz-Vadalazhskaya N, Anagnostopoulos C, Macedo F, Knuuti J, Edvardsen T, Cosyns B, Petersen SE, Magne J, Laroche C, Berle C, Popescu BA, Delgado V; EURECA Investigators. Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry. Eur Heart J. 2023 Jan 7;44(2):142-158. doi: 10.1093/eurheartj/ehac640.

  PMID: 36452988 BACKGROUND

• Neglia D, Caselli C, Maffei E, Cademartiri F, Meloni A, Bossone E, Saba L, Lee SE, Sung JM, Andreini D, Al-Mallah MH, Budoff MJ, Chinnaiyan K, Choi JH, Chun EJ, Conte E, Gottlieb I, Hadamitzky M, Kim YJ, Lee BK, Leipsic JA, Marques H, de Araujo Goncalves P, Pontone G, Shin S, Stone PH, Samady H, Virmani R, Narula J, Shaw LJ, Bax JJ, Lin FY, Min JK, Chang HJ. Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study. Circ Cardiovasc Imaging. 2024 Jul;17(7):e016481. doi: 10.1161/CIRCIMAGING.123.016481. Epub 2024 Jul 16.

  PMID: 39012946 BACKGROUND

• Caselli C, De Caterina R, Smit JM, Campolo J, El Mahdiui M, Ragusa R, Clemente A, Sampietro T, Clerico A, Liga R, Pelosi G, Rocchiccioli S, Parodi O, Scholte A, Knuuti J, Neglia D; EVINCI and SMARTool. Triglycerides and low HDL cholesterol predict coronary heart disease risk in patients with stable angina. Sci Rep. 2021 Oct 20;11(1):20714. doi: 10.1038/s41598-021-00020-3.

  PMID: 34671067 BACKGROUND

• Neglia D, Aimo A, Lorenzoni V, Caselli C, Gimelli A. Triglyceride-glucose index predicts outcome in patients with chronic coronary syndrome independently of other risk factors and myocardial ischaemia. Eur Heart J Open. 2021 Jul 24;1(1):oeab004. doi: 10.1093/ehjopen/oeab004. eCollection 2021 Aug.

  PMID: 35919094 BACKGROUND

• Di Giorgi N, Michelucci E, Smit JM, Scholte AJHA, El Mahdiui M, Knuuti J, Buechel RR, Teresinska A, Pizzi MN, Roque A, Poddighe R, Parodi O, Pelosi G, Caselli C, Neglia D, Rocchiccioli S. A specific plasma lipid signature associated with high triglycerides and low HDL cholesterol identifies residual CAD risk in patients with chronic coronary syndrome. Atherosclerosis. 2021 Dec;339:1-11. doi: 10.1016/j.atherosclerosis.2021.11.013. Epub 2021 Nov 11.

  PMID: 34801858 BACKGROUND

• Caselli C, Occhipinti M, Pane K, De Gori C, Rocchiccioli S, Botto N, Prontera C, Cavaliere C, Ragusa R, Vecoli C, Sansone F, Passaro E, Ceccherini E, Morlando A, Clemente A, Franzese M, Maffei E, Punzo B, Gimelli A, Cademartiri F, Neglia D. Health improvements by understanding residual risk in coronary artery disease and new targets for prevention/treatment: rationale and research protocol of the HURRICANE project. Eur Heart J Open. 2025 Jan 28;5(1):oeaf005. doi: 10.1093/ehjopen/oeaf005. eCollection 2025 Jan.

  PMID: 39949422 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum and whole blood samples

MeSH Terms

Conditions

Coronary Artery Disease; Insulin Resistance

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Danilo Neglia, MD, PhD

  Fondazione Toscana Gabriele Monasterio

  STUDY CHAIR

Central Study Contacts

Danilo Neglia, MD, PhD

CONTACT

+393355857594; dneglia@ftgm.it

Maria Sole Morelli, PhD

CONTACT

+393498337562; msmorelli@ftgm.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 15, 2024
• First Posted: September 19, 2024
• Study Start: July 7, 2023
• Primary Completion: October 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

IT (2)