Polygenic Risk Score for Optimizing Primary Prevention in Intermediate-Risk Populations

NCT07039123 | Recruiting DMC

• 1 other identifier: PERSONAL-2025-00601
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to determine whether incorporating a polygenic risk score (PRS) can optimize primary cardiovascular disease prevention in individuals with intermediate cardiovascular risk. The main questions it aims to answer are:

• Can a polygenic risk score improve risk stratification in intermediate-risk individuals?
• Does disclosing polygenic risk information to patients and physicians lead to better preventive interventions (e.g., statin use, lifestyle changes)? Researchers will compare outcomes in participants with PRS disclosure versus standard risk assessment to see if PRS-guided prevention leads to improved cardiovascular risk management. Participants will:
• Undergo baseline cardiovascular risk assessment
• Provide a blood sample for PRS calculation
• Complete follow-up visits for lifestyle counseling, medication review, and risk reassessment

Conditions

Primary Prevention of Cardiovascular Disease

Keywords

Polygenic risk score; Cardiovascular risk; Genomic medicine; Cardiovascular disease; Intermediate cardiovascular risk; Primary prevention; Genetic risk stratification

Outcome Measures

Primary Outcomes (1)

• Change in SCORE2 between baseline and 15 months

  Mean change in SCORE2 cardiovascular risk score from baseline to 15-month follow-up, comparing the intervention (PRS-CAD + SCORE2) and control (SCORE2 only) arms.

  15 months

Secondary Outcomes (25)

• Change in systolic blood pressure

  Baseline to 15 months

• Change in diastolic blood pressure

  Baseline to 15 months

• Change in total cholesterol

  Baseline to 15 months

• Change in HDL cholesterol (HDL-C)

  Baseline to 15 months

• Change in LDL cholesterol (LDL-C)

  Baseline to 15 months

Study Arms (2)

Polygenic Risk Score Combined with SCORE2

EXPERIMENTAL

Participants in this arm will receive cardiovascular risk assessment using a combination of traditional clinical risk factors (SCORE2 algorithm) and a polygenic risk score for coronary artery disease (PRS-CAD). The combined risk (PRS-CAD-SCORE2) will be communicated using a structured communication tool developed by the study team. Participants and their healthcare providers will receive the results, and those with elevated risk will be referred to a lipid consultation. Lifestyle guidance and educational materials will also be provided.

Diagnostic Test: Polygenic Risk Score for Coronary Artery Disease (PRS-CAD); Behavioral: Standardized Risk Communication Tool (SCORE2)

SCORE2-Based Risk Assessment

ACTIVE COMPARATOR

Participants in this arm will receive standard cardiovascular risk assessment using the SCORE2 algorithm only. Risk results will be communicated using the same structured communication tool, without inclusion of genetic information. No polygenic risk score will be calculated or disclosed. Participants and their healthcare providers will receive the standard risk results and general lifestyle recommendations.

Behavioral: Standardized Risk Communication Tool (SCORE2)

Interventions

Polygenic Risk Score for Coronary Artery Disease (PRS-CAD) DIAGNOSTIC_TEST

A polygenic risk score will be calculated based on genome-wide genotyping and combined with SCORE2 clinical risk factors to estimate personalized cardiovascular risk. The combined risk (PRS-CAD-SCORE2) will be communicated to participants and their healthcare providers using a standardized communication tool. Participants with elevated risk will be referred to a lipid clinic.

Polygenic Risk Score Combined with SCORE2

Standardized Risk Communication Tool (SCORE2) BEHAVIORAL

Participants will receive risk communication based solely on clinical risk factors using the SCORE2 algorithm. The same structured communication tool will be used (without genetic data), along with general lifestyle guidance.

Polygenic Risk Score Combined with SCORE2; SCORE2-Based Risk Assessment

Eligibility Criteria

• Age: 40 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Intermediate cardiovascular risk based on SCORE2 or SCORE2-Diabetes
• Able to give informed consent (understanding German or French or with an interpreter)
• Written Informed Consent

You may not qualify if:

• Patient treated under lipid-lowering therapy (defined as statin, ezetimib, bempedoïc acid, PCSK-9 inhibitors)
• History of previous cardiovascular disease: coronary artery disease (CAD), peripheral artery disease and ischemic stroke (including transitory ischemic stroke).
• Chronic kidney disease (CKD) define as an estimated glomerular filtration rate (eGFR) of less than 30 ml/min or less than 60 ml/min with albuminuria patients with diabetes and end organ damage (classified as very high risk according to ESC guidelines).
• Other participation in a clinical study related to CV risk or lifestyle interventions (e.g. diet, smoking cessation...)
• Life expectancy of less than one year

Sponsors & Collaborators

• University of Bern: lead

Study Sites (2)

University of Bern, Institute of Primary Health Care (BIHAM)

Bern, 3012, Switzerland

RECRUITING

University of Lausanne, Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Switzerland

NOT YET RECRUITING

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Related Links

• UK government consultation paper outlining a national strategy to shift healthcare towards prevention, including the potential role of genomics and polygenic risk scores in personalized disease prevention.
• Heart Age Calculator
• Readiness for Change Questionnaire

MeSH Terms

Conditions

Genetic Risk Score; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nicolas Rodondi, MD

  University hospital of Bern

  STUDY CHAIR

Central Study Contacts

Elisavet Moutzouri, MD, PhD

CONTACT

+41792725451; elisavet.moutzouri@extern.insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Study nurse/Research Fellow providing the information of cardiovascular risk at baseline will be masked. Patients will be masked as both groups will receive genetic results (intervention group during the study, control group at the end of the study).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: June 26, 2025
• Study Start: July 8, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)