Early Detection of Coronary Artery Disease by Polygenic and Metabolic Risk Scoring

Study Overview
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Brief Summary
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The overall goal of this study is to develop a combined polygenic risk score (PRS) and metabolic risk score (MRS) and determine its impact on selecting community members for CCS. The trial component of this study will compare the use of these scores to motivate people to adhere to therapy, an ongoing challenge for clinicians, by providing feedback in a meaningful form to both the clinicians and the patients.

Detailed Description
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Patients undergoing a polygenic risk score (PRS), metabolic risk score (MRS) and coronary calcium score (CCS) will be randomized to receive PRS and CCS information and followed for the reduction of risk over 12 months. This information will provide information about how to motivate people to adhere to therapy, by providing feedback in a meaningful form to both the clinicians and the patients.

Official Title
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Early Detection of Coronary Artery Disease by Polygenic and Metabolic Risk Scoring in at Risk Patients: Comparison With Coronary Computed Tomography

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Diagnostic Test: Polygenic Risk Score
* Diagnostic Test: Coronary Calcium Score


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asymptomatic subjects age 40-70y Statin naïve TC ≤ 6.5 mmol/L and LDLC <5 mmol/L, and 5 year Australian risk ≥2%. Exclusion Criteria: Symptomatic coronary, cerebrovascular, or peripheral vascular disease Intolerance of statins or currently on statins for any length of time Pre-existing muscle disease (eg polymyositis, fibromyalgia) - this may be confused with myalgia from statins Patients on drugs that increase the risk of myopathy/rhabdomyolysis such as cyclosporine and strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, and HIV/hepatitis C protease inhibitors) Atrial fibrillation (interferes with CTCA) Chronic kidney disease on haemodialysis (because of vascular calcification) or GFR <50ml/min per 1.73m2 using the Modification of Diet in Renal Disease (MDRD) formula Inability to provide informed consent Major systemic illness eg. malignancy; rheumatoid arthritis Women of child bearing potential (due to performance of CT) Poorly controlled hypertension: SBP> 200 and or DBP > 100 Severe psychiatric disorder (eg bipolar depression; psychosis) Patients eligible for treatment based on current Australian guidelines (5 year risk >15%) Patients eligible for treatment based on current PBS thresholds TC >7.5 mmol/l and other criteria (see below).

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization to provision of PRS-based or CCS-based risk
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRS score group<br>Risk information provided on the basis of Polygenic Risk Score combined with the Pooled Cohort Equation | Diagnostic Test: Polygenic Risk Score<br>* Risk description to patient based on PRS<br>|
| Active Comparator: CCS score group<br>Risk information provided on the basis of Coronary Calcium Score combined with the Pooled Cohort Equation | Diagnostic Test: Coronary Calcium Score<br>* Risk description to patient based on CCS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiovascular risk in each group | Change in cardiovascular risk (expressed as pooled cohort equation 10-year risk percentage) from baseline to follow-up | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication adherence in each group | Proportion of lipid-lowering tablets taken | 12 months |