Polygenic Risk Score to Optimize Primary Prevention in Intermediate Risk Population (PERSONAL)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 205
- 试验地点
- 2
- 主要终点
- Change in SCORE2 between baseline and 18 months
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
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).
入排标准
- 年龄范围
- 40 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Polygenic Risk Score Combined with SCORE2
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.
干预措施: Polygenic Risk Score for Coronary Artery Disease (PRS-CAD) (Diagnostic Test)
Polygenic Risk Score Combined with SCORE2
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.
干预措施: Standardized Risk Communication Tool (SCORE2) (Behavioral)
SCORE2-Based Risk Assessment
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.
干预措施: Standardized Risk Communication Tool (SCORE2) (Behavioral)
结局指标
主要结局
Change in SCORE2 between baseline and 18 months
时间窗: 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.
次要结局
- Change in systolic blood pressure(Baseline to 18 months)
- Change in diastolic blood pressure(Baseline to 18 months)
- Change in total cholesterol(Baseline to 18 months)
- Change in HDL cholesterol (HDL-C)(Baseline to 18 months)
- Change in LDL cholesterol (LDL-C)(Baseline to 18 months)
- Change in triglyceride levels(Baseline to 18 months)
- Change in fasting glucose(Baseline to 18 months)
- Change in HbA1c(Baseline to 18 months)
- Change in high-sensitivity C-reactive protein (hs-CRP)(Baseline to 18 months)
- Change in DNA methylation patterns(Baseline to 18 months)
- Tobacco abstinence status(Baseline to 18 months)
- Change in body mass index (BMI)(Baseline to 18 months)
- Change in body weight(Baseline to 18 months)
- Change in dietary adherence(Baseline to 18 months)
- Change in physical activity level(Baseline to 18 months)
- Change in medication adherence(Baseline to 18 months)
- Change in motivation for lifestyle change(Baseline to 18 months)
- Change in psychological well-being(Baseline to 18 months)
- Participant satisfaction with the intervention(Baseline to 18 months)
- Number of visits to healthcare providers (HCPs)(Baseline to 18 months)
- Initiation of new statin therapy(Baseline to 18 months)
- Initiation of new antihypertensive therapy(Baseline to 18 months)
- Initiation of new antidiabetic therapy(Baseline to 18 months)
- Incidence of new cardiovascular events(Baseline to 18 months)
- Incidence of newly diagnosed diabetes mellitus(Baseline to 18 months)