Proactive Cardiovascular Prevention Strategy in Subjects With High Genetic Risk

Study Overview
=================
Brief Summary
-----------------
A polygenic risk score (PRS) will be developed and implemented into the primary care digital work-flow. 1000 study subjects with no known cardiovascular disease, diabetes or statin treatment and with high PRS (men of 30-65, women of 40-70 years of age) will be recruited from amongst the gene donors of Estonian Biobank (Estonian Genome Center at the University of Tartu). Subjects will be randomised to proactive primary preventive intervention incorporating provision of PRS information or usual care (opportunistic preventive strategy). Subjects in intervention group will be actively contacted and invited to a general practitioner (GP) based prevention intervention of total cardiovascular risk scoring and guideline recommended preventive measures. Subjects in control group will be observed for 12 month and then invited to a GP visit and provided the same information and advice as the intervention group. The impact of PRS on total 10 year cardiovascular disease (CVD) risk scoring will be assessed, the change in total 10 year CVD risk during the intervention will be measured and the difference in total 10 year CVD risk between the groups at month 12 will be reported. Satisfaction of subjects and GPs with the intervention will also be assessed as well as cost-effectiveness of the intervention.

Detailed Description
-----------------
A polygenic risk score (PRS) will be developed and implemented into the primary care digital work-flow. 1000 study subjects with no known cardiovascular disease, diabetes or statin treatment and with high PRS (men of 30-65, women of 40-70 years of age) will be recruited from amongst the gene donors of Estonian Biobank (Estonian Genome Center at the University of Tartu). Subjects will be randomised to proactive primary preventive intervention incorporating provision of PRS information or usual care (opportunistic preventive strategy). Subjects in intervention group will be actively contacted and invited to a GP based prevention intervention of total cardiovascular risk scoring and guideline recommended preventive measures. Subjects in control group will be observed for 12 month and then invited to a GP visit and provided the same information and advice as the intervention group. The impact of PRS on total 10 year CVD risk scoring will be assessed, the change in total 10 year CVD risk during the intervention will be measured and the difference in total 10 year CVD risk between the groups at month 12 will be reported. Satisfaction of subjects and GPs with the intervention will also be assessed as well as cost-effectiveness of the intervention.

Official Title
-----------------
Implementability and Health Impact of Proactive Cardiovascular Prevention Strategy in Subjects With High Genetic Risk: a Randomized Pilot Study

Conditions
-----------------
Cardiovascular Diseases, Primary Prevention

Intervention / Treatment
-----------------
* Other: CVD risk estimation incorporating the PRS and guideline based preventive interventions.
* Other: Standard GP care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male 30-65 years or female 40-70 years No history of ischemic heart disease, stroke, TIA or PAD in electronic health record No cholesterol lowering treatment No history of diabetes High PRS of CVD No physical or mental conditions precluding informed consent or participation Exclusion Criteria: History of ischemic heart disease, stroke, transitory ischemic attack (TIA) or peripheral artery disease (PAD) in electronic health record Cholesterol lowering treatment History of diabetes No consent to participate

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Large simple randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proactive CVD prevention<br>Proactive invitation to total CVD risk estimation incorporating the PRS and provision of guideline based preventive interventions. | Other: CVD risk estimation incorporating the PRS and guideline based preventive interventions.<br>* Total CVD risk estimation using SCORE plus PRS and European Society of Cardiology (ESC) CVD prevention guideline based interventions.<br>|
| Active Comparator: Usual care<br>Usual GP care (opportunistic CVD risk estimation and prevention upon usual GP contacts). | Other: Standard GP care<br>* Usual GP care (opportunistic CVD prevention)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total 10 year cardiovascular disease (CVD) risk | SCORE (Systematic COronary Risk Evaluation), estimates fatal cardiovascular disease events over a ten-year period in %. Employs categories of 1) low (calculated SCORE <1%) 2) moderate-risk (calculated SCORE1% to <5%), 39 ) high-risk (calculated SCORE5% to <10%) and 3) very-high-risk (calculated SCORE ≥10%). Conroy RM , Pyorala K, Fitzgerald AP et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur H J2003;24:987-1003. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment initiation (first prescription) or dose escalation (new prescription with a higher dose) of CVD preventive pharmacotherapy | New prescription or a dose escalation of any anti-hypertensive, lipid lowering, anti-platelet or anti-smoking medicinal product. | 12 months | 
| Adherence to CVD prevention recommendations | Adherence to CVD prevention recommendations - proportion of patients adhering to lifestyle advice as recorded by GP. | 12 months | 
| Systolic blood pressure | Sitting systolic blood pressure measured by automated device at GP office, mmHg | 12 months | 
| Diastolic blood pressure | Sitting diastolic blood pressure measured by automated device at GP office, mmHg | 12 months | 
| Total cholesterol | mmol/L | 12 months | 
| LDL cholesterol | mmol/L | 12 months | 
| BMI | Body mass index, height (m) and weight (kg) combined (kg/m2) | 12 months | 
| Waist circumference | cm, measured at GP office | 12 months | 
| Smoking status | Self-reported smoking status as recorded at GP office | 12 months | 
| Physical activity | Self-reported physical activity, min/week, as recorded at GP office | 12 months | 
| Satisfaction of gene donors with intervention | Satisfaction of gene donors with intervention - descriptive questionnaire, analysed qualitatively | 12 months | 
| Satisfaction of GPs with intervention | Satisfaction of GPs with intervention - descriptive questionnaire, analysed qualitatively | 12 months | 
| Cost-effectiveness of intervention | Incremental cost-effectiveness ratio (EUR/QALY): cost of intervention combined in an economic model with lifetime benefit (number of quality adjusted life years modelled based on change in total CVD risk, measured as primary endpoint). | 12 months, modelled over lifetime | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polygenic risk score