Primary Prevention of Cardiovascular Disease
Conditions
Keywords
Polygenic risk score, Cardiovascular risk, Genomic medicine, Cardiovascular disease, Intermediate cardiovascular risk, Primary prevention, Genetic risk stratification
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
Detailed description
Coronary artery disease (CAD) remains the leading cause of mortality worldwide. While current cardiovascular disease (CVD) prevention guidelines rely on clinical risk scores such as SCORE2, these tools may underestimate or overestimate risk in individuals with intermediate clinical risk. Polygenic risk scores (PRS) aggregate the effect of multiple common genetic variants and may provide additional predictive value when combined with traditional risk assessment. This randomized controlled trial evaluates whether incorporating a PRS for CAD (PRS-CAD) into clinical decision-making improves cardiovascular risk stratification and leads to better primary prevention in individuals with intermediate estimated 10-year cardiovascular risk. Participants aged 40-69 years with intermediate CVD risk based on the SCORE2 algorithm will be randomized 1:1 into two groups. In the intervention arm, the PRS-CAD will be calculated using a validated genome-wide algorithm and integrated with the SCORE2 risk to generate a combined PRS-CAD-SCORE2 estimate. Risk will be communicated to participants and their healthcare providers using a standardized, structured communication tool developed by the study team. Participants with elevated combined risk will be referred to lipid clinics for further evaluation. In the control arm, participants will receive standard SCORE2-based risk communication, without inclusion of genetic information. All participants will receive written lifestyle guidance . Physicians will receive the results in a structured format. The primary endpoint is the change in SCORE2 from baseline to 15 months. Secondary endpoints include changes in blood pressure, lipid levels, glucose, HbA1c, hs-CRP, BMI, weight, adherence to the Mediterranean diet (Predimed score), physical activity (IPAQ), tobacco abstinence, medication adherence (MARS), and psychological measures (DASS-21, motivation for change, satisfaction with risk communication). Prescription rates of statins and other preventive therapies, new diagnoses (e.g., diabetes), and new cardiovascular events will also be recorded. Epigenomic analyses will be conducted to explore interactions between genetic risk, lifestyle, and DNA methylation. All outcomes will be assessed at 15 months with blinded outcome assessment. The study aims to inform the clinical utility of integrating PRS into preventive cardiovascular care and support the move toward personalized medicine in primary prevention.
Interventions
DIAGNOSTIC_TESTPolygenic Risk Score for Coronary Artery Disease (PRS-CAD)
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.
BEHAVIORALStandardized Risk Communication Tool (SCORE2)
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.
Sponsors
University of Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
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).
Eligibility
Sex/Gender
ALL
Age
40 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* 40-69 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in SCORE2 between baseline and 18 months | 18 months | Mean change in SCORE2 cardiovascular risk score from baseline to 18-month follow-up, comparing the intervention (PRS-CAD + SCORE2) and control (SCORE2 only) arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in systolic blood pressure | Baseline to 18 months | Measured using validated automated oscillometric device at rest |
| Change in diastolic blood pressure | Baseline to 18 months | Measured using validated automated oscillometric device at rest |
| Change in total cholesterol | Baseline to 18 months | Measured via fasting venous blood sample |
| Change in HDL cholesterol (HDL-C) | Baseline to 18 months | Measured via fasting venous blood sample |
| Change in LDL cholesterol (LDL-C) | Baseline to 18 months | Measured via fasting venous blood sample |
| Change in triglyceride levels | Baseline to 18 months | Measured via fasting venous blood sample |
| Change in fasting glucose | Baseline to 18 months | Measured via fasting venous blood sample |
| Change in HbA1c | Baseline to 18 months | Measured via venous blood sample |
| Change in high-sensitivity C-reactive protein (hs-CRP) | Baseline to 18 months | Measured via fasting venous blood sample |
| Change in DNA methylation patterns | Baseline to 18 months | Assessment of genome-wide DNA methylation changes from peripheral blood samples. DNA methylation will be analyzed in relation to adherence to the Mediterranean diet (measured via Predimed 14-item questionnaire) and its interaction with polygenic risk scores for coronary artery disease. |
| Tobacco abstinence status | Baseline to 18 months | Self-reported smoking status assessed at follow-up |
| Change in body mass index (BMI) | Baseline to 18 months | Calculated using measured weight and height (kg/m²) |
| Change in body weight | Baseline to 18 months | Measured in kilograms using calibrated scale |
| Change in dietary adherence | Baseline to 18 months | Measured by the Predimed 14-item questionnaire (score range: 0-14; higher scores indicate greater adherence to the Mediterranean diet) |
| Change in physical activity level | Baseline to 18 months | Assessed using the International Physical Activity Questionnaire (IPAQ, long form; score expressed in MET-minutes/week; higher values indicate greater physical activity). |
| Change in medication adherence | Baseline to 18 months | Assessed using the Medication Adherence Report Scale (MARS, 5-item version) score range: 5-25; higher scores indicate better adherence. |
| Change in motivation for lifestyle change | Baseline to 18 months | Measured using the 32-item Readiness for Change Questionnaire; score range depends on subscale (e.g., Precontemplation, Contemplation, Action); higher scores indicate greater readiness for behavior change. |
| Change in psychological well-being | Baseline to 18 months | Assessed using the Depression Anxiety Stress Scale (DASS-21); each subscale score ranges from 0 to 42, with higher scores indicating greater severity of symptoms. |
| Participant satisfaction with the intervention | Baseline to 18 months | Measured via structured self-reported survey on a 5-point Likert scale (1 = not satisfied at all, 5 = very satisfied). |
| Number of visits to healthcare providers (HCPs) | Baseline to 18 months | Self-reported and verified via medical records when available |
| Initiation of new statin therapy | Baseline to 18 months | Number of participants with newly prescribed statins during follow-up period |
| Initiation of new antihypertensive therapy | Baseline to 18 months | Number of participants with newly prescribed antihypertensive medications during follow-up period |
| Initiation of new antidiabetic therapy | Baseline to 18 months | Number of participants with newly prescribed antidiabetic medications (oral or injectable) during follow-up period |
| Incidence of new cardiovascular events | Baseline to 18 months | Number of participants with new cardiovascular events defined as new diagnosis of myocardial infarction, stroke, or other major adverse cardiovascular event (MACE); verified through clinical records |
| Incidence of newly diagnosed diabetes mellitus | Baseline to 18 months | Number of participants with newly diagnosed type 2 diabetes confirmed by GP or medical record during follow-up |
Countries
Switzerland
Contacts
STUDY_CHAIRNicolas Rodondi, MD
University of Bern
Outcome results
None listed