THE CVRISK-IT STUDY

At the heart of prevention: integrated approaches for personalized cardiovascular prevention

 

 

BACKGROUND

Risk prediction models for cardiovascular disease, such as SCORE2 and SCORE2-OP, which estimate the global disease risk by considering various individual modifiable and non-modifiable risk factors (age, gender, smoking habits, blood pressure, cholesterol levels), are essential for the prevention of cardiovascular diseases.

However, in certain circumstances, clinical guidelines recommend considering other factors known as “risk modifiers”.
Initial evidence suggests that elements such as genetic data and imaging as additional information on cardiovascular risk may improve personalized interventions and adherence to the doctor’s advice on lifestyle and treatment.

However, even though theoretical models predict a positive impact on health-related behaviors, the studies conducted so far lacked reliability and did not allow for clearly identifying the benefits and risks of incorporating these “risk modifiers” into the global cardiovascular risk assessment.

The randomized and controlled CVRISK-IT intervention study aims to answer the following questions:
– What is the value of integrating more precise and personalized information (e.g., imaging data and genetic information) on specific “risk modifiers” into the global cardiovascular risk estimation, alongside lifestyle advice and treatment?
– For people and the doctors assisting them, can this integration truly promote lifestyle changes and improve clinical outcomes in terms of risk reduction?

 

STUDY DESIGN AND OBJECTIVES

For this purpose, the study will enroll a large sample of 30,000 healthy individuals, aged between 40 and 80, with no history of cardiovascular diseases or type 2 diabetes, recruited from IRCCS and other centers, as well as volunteer organizations across Italy.

The project, of which the study is the core, will utilize innovative IT tools, a new informed consent process, and a relational digital platform to enhance participant engagement and motivation in the study, and more generally, to raise awareness among people.

The main goal of the study is to assess the benefits of including “risk modifiers” in the global cardiovascular risk assessment. These include the hereditary component of risk (assessed using the so-called polygenic risk scores), the presence and amount of coronary calcium (identified via non-contrast CT angiography), and the analysis of the carotid artery (through Doppler ultrasound) to detect any signs of subclinical organ damage.

The first phase of the study will involve the entire sample of 30,000 people, who will undergo assessments over 12 months based on the most advanced cardiovascular risk prediction models (SCORE2/SCORE2-OP risk charts).

In the second phase, subjects identified as having low, moderate, or high risk will be randomized to receive specific information and personalized counseling on how to maintain a healthy lifestyle, based on their estimated cardiovascular risk profile. Subjects with very high risk, however, will exit the trial and be directed toward standard preventive treatment as outlined by the guidelines.

 

PARTICIPATING IRCCS

  • IRCCS Policlinico San Donato
  • IRCCS Centro Cardiologico Monzino
  • IRCCS Fondazione Policlinico San Matteo
  • IRCCS Fondazione Policlinico Universitario A. Gemelli
  • IRCCS Istituto Clinico Humanitas
  • IRCCS Istituto Nazionale di Riposo e Cure per Anziani – INRCA
  • IRCCS Istituto Mediterraneo per i trapianti e Terapie ad Alta Specializzazione (ISMETT)
  • IRCCS Istituti Clinici Scientifici Maugeri S.p.A. Società Benefit
  • IRCCS Istituto Auxologico Italiano
  • IRCCS Istituto di Ricerche Farmacologiche Mario Negri
  • IRCCS Multimedica
  • IRCCS Istituto Neurologico Mediterraneo NEUROMED
  • IRCCS Fondazione Cà Granda – Ospedale Maggiore Policlinico
  • IRCCS Ospedale Policlinico San Martino
  • IRCCS Ospedale San Raffaele
  • IRCCS San Raffaele Roma
  • IRCCS SDN Istituto di Ricerca Diagnostica e Nucleare

 

MEASURED OUTCOMES

  • Primary short-term outcome: 12-month post-randomization variation in cardiovascular disease risk based on SCORE2/SCORE2-OP risk charts.
  • Secondary short-term outcomes: 12-month variations in objective risk factors (cholesterol levels, blood pressure, smoking), in the prescription and adherence to cardiovascular preventive medications, and in the assessment of organ damage, using imaging or kidney function diagnostics, across different subgroups.
  • Long-term outcomes: variation in the incidence of cardiovascular diseases, particularly non-fatal myocardial infarction or non-fatal stroke, cardiovascular-specific mortality, and total mortality.

NEW RELATIONAL DIGITAL PLATFORM

In parallel with the main objectives, the project aims to develop an innovative model of interaction with participants through a secure and transparent platform, strictly adhering to current national privacy regulations and European laws.

The project will also implement a communication and dissemination strategy targeting multiple audiences: the pool of potentially eligible and recruited participants, external physicians and healthcare providers, as well as actors in the cardiovascular ecosystem, institutions, and the general public.

This system is structured into the following phases:

  • Education and awareness: raising awareness through multichannel campaigns.
  • Patient engagement: personalized engagement in the prevention pathway (App and digital media, engagement questionnaire);
  • Relationship management: one-to-one relationship management pre/post prevention pathway.
  • Follow-up, satisfaction, reputation, and trust: follow-up on cardiovascular prevention, satisfaction, reputation, and trust.
  • Measuring relationship results and process optimization: measuring health and relationship outcomes and continuous process optimization, using advanced analytics and machine learning to profile the audience’s needs and manage all interactions and information in a personalized way, also leveraging generative AI.

ORGANIZATIONAL MODEL: THE WORK PACKAGES

Per realizzare uno studio tanto ampio e ambizioso, gli IRCCS della Rete Cardiologica che vi partecipano hanno progettato e realizzato un’articolata struttura organizzativa e di lavoro, basata su sei diversi Work Packages, vale a dire gruppi di lavoro organizzati per obiettivi, dedicati a gestire i vari aspetti e le diverse fasi del progetto.

WP1: COORDINAMENTO E MANAGEMENT DEL PROGETTO

IRCCS Policlinico San Donato

Durante l’intero periodo di attuazione del progetto, il WP1 garantirà i processi necessari per la realizzazione e il monitoraggio delle attività previste, stabilendo un accordo consortile con i partner e pianificando una serie di incontri che faciliteranno la collaborazione e il coordinamento tra i partner. Un’azione completa di comunicazione-diffusione, coinvolgimento e relazione sostenuta nel tempo sarà attuata per creare un ambiente favorevole all’engagement.

WP2: CARATTERISTICHE DELLA POPOLAZIONE DI STUDIO E STRATEGIA DI ARRUOLAMENTO

IRCCS Istituto di Ricerche Farmacologiche Mario Negri

Il WP2 avrà il compito di:
– l’istituire un modello Hub&Spoke attraverso la stipula di contratti con centri non IRCCS per l’arruolamento e la creazione di una rete di reclutamento;
– reclutare i circa 30.000 partecipanti alla fase 1;
– raccogliere i questionari e delle informazioni previste;
– raccogliere i campioni di sangue per il calcolo dello SCORE2 (colesterolo totale, colesterolo HDL e per il biobanking);
– stimare il rischio di malattie cardiovascolari (SCORE2 e SCORE2-OP).

WP3: L’IMPORTANZA DELLE BIORISORSE DI POPOLAZIONE E DEL BIOBANKING PER LA RICERCA CLINICA

IRCCS Istituto Neurologico Mediterraneo NEUROMED e IRCCS Policlinico San Donato

L’obiettivo del WP3 sarà quello di garantire la creazione di una raccolta di campioni (ad esempio, tutti i pellet cellulari, il plasma e il siero) e dei relativi dati adatti agli scopi di questo progetto. Inoltre, l’implementazione del QMS già esistente della Biobanca Diffusa  BBDCARDIO, della Rete Cardiologica, consentirà la raccolta e l’archiviazione di diversi campioni biologici e dei relativi dati raccolti secondo criteri comuni e programmi di armonizzazione specifici. Gli strumenti più appropriati (marcatori e saggi) che possono essere utilizzati per valutare le variazioni pre-analitiche dei campioni saranno definiti per una migliore standardizzazione tra i laboratori del BBDCARDIO per migliorare il SGQ del BBCARDIO e garantire la riproducibilità, la tracciabilità e la conservazione di alta qualità.

WP4: NUOVI INTERVENTI PER LA PREVISIONE DEL RISCHIO CARDIOVASCOLARE

IRCCS Centro Cardiologico Monzino

Il WP4 avrà il compito di fornire prove importanti sull’utilità dell’integrazione dei dati di previsione del rischio basati sulla genetica o sulla diagnostica per immagini con la stima del rischio di CVD mediante l’algoritmo SCORE2 o SCORE2 OP in individui identificati a rischio di CVD basso-moderato o elevato mediante il solo calcolo dell’algoritmo.

WP5: FOLLOW-UP E RACCOLTA DEI RISULTATI

IRCCS Istituto Auxologico Italiano

Il WP5 dovrà definire approcci e strategie per una raccolta efficiente ed efficace di risultati a breve e lungo termine. Ciò comporterà la definizione e la standardizzazione di Standard Operating Procedures (SOP) efficienti e in grado di massimizzare la raccolta di endpoint in tutti i partecipanti.

WP6: RANDOMIZZAZIONE E ANALISI DEI DATI

IRCCS Multimedica

Lo studio CVRISK-IT è stato progettato per valutare l’efficacia della fornitura di nuovi e diversi tipi di informazioni aggiuntive sul rischio di CVD sui cambiamenti a breve termine dei fattori di rischio e sugli esiti legati alla salute in un arco di tempo più lungo. Il WP6 e la Fase 2 dello Studio dovrebbero dimostrare che fornire informazioni aggiuntive sul rischio cardiovascolare potrebbe indurre i pazienti a migliorare il loro comportamento e a migliorare gli esiti a breve e lungo termine.

 

EXPECTED BENEFITS

The study, which will be the largest of its kind conducted in our country, is highly innovative, as it has the potential to significantly influence cardiovascular screening practices in Italy, helping to redefine cardiovascular disease prevention strategies.

Additionally, it opens the door to further discoveries: thanks to the collected material, the database and widespread biobank of the Cardiological Network (BBDCardio) will be significantly enriched, which can be used for future research on health and chronic diseases in Italy.

Finally, by raising awareness in a large population about translational and implementation research, the study is expected to have a direct impact on healthcare practices, ultimately improving the lives of many.

 

“I’m convinced that the CVRISK-IT study will be a big step towards personalised and more effective cardiovascular prevention. If the study results are confirmed, integrating new risk assessment approaches, such as polygenic risk scores and imaging data, will open up new possibilities in our fight against heart and vessel diseases”.

Lorenzo Menicanti, President of the Cardiology Network

 

 

REFERENCES
  • L’uso dei farmaci in Italia. Rapporto Nazionale. Anno 2021.
  • Causes of death statistics. 2021.
  • Patel AP, Wang M, Ruan Y, et al. Nat Med. 2023 Jul;29(7):1793-1803.
  • SCORE2 working group and ESC Cardiovascular risk collaboration. Eur Heart J. 2021 Jul 1;42(25):2439-2454.
  • SCORE2-OP working group and ESC Cardiovascular risk collaboration. Eur Heart J. 2021 Jul 1;42(25):2455-2467.
  • Visseren FLJ, Mach F, Smulders YM, et al. Eur Heart J. 2021 Sep 7;42(34):3227-3337.