Proactive Cardiovascular Prevention Strategy in Subjects With High Genetic Risk (EstPerMedCV)

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

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.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Primary Prevention
• Intervention / Treatment: Other: CVD risk estimation incorporating the PRS and guideline based preventive interventions.; Other: Standard GP care

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre
  • Tartu, Estonia, 50406
    • Tartu University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Proactive CVD prevention; 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.; Total CVD risk estimation using SCORE plus PRS and European Society of Cardiology (ESC) CVD prevention guideline based interventions.
ACTIVE_COMPARATOR: Usual care; Usual GP care (opportunistic CVD risk estimation and prevention upon usual GP contacts).	Other: Standard GP care; Usual GP care (opportunistic CVD prevention)

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

Collaborators and Investigators

• Sponsor: Alar Irs
• Collaborators: Tartu University Hospital; North Estonia Regional Hospital
• Investigators: Principal Investigator: Margus Viigimaa, MD, PhD, University of Tartu

Publications and helpful links

Helpful Links

• Study general information and contacts

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2019
• Primary Completion (ANTICIPATED): November 30, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: February 19, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (ACTUAL): March 2, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 2, 2020
• Last Update Submitted That Met QC Criteria: February 27, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Polygenic risk score
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: EstPerMed CV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No