Genetic Test Disclosure for Coronary Artery Disease

(PROACT 1 Trial)

Overseen By Roukoz Abou-Karam, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Statins, Colchicine, CY2P inhibitors

Disqualifiers: Cardiovascular disease, Liver disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how awareness of a high genetic risk for coronary artery disease affects heart health over a year. It targets individuals who have not developed heart disease but possess a high genetic marker indicating risk. Participants will learn about their genetic risk either immediately or after the study concludes. This trial may suit those without known heart disease but with a high genetic risk. As an unphased trial, it offers a unique opportunity to understand genetic risk and its potential impact on heart health.

Will I have to stop taking my current medications?

Yes, if you are currently taking LDL cholesterol lowering or anti-inflammatory medications, including colchicine, you will need to stop taking them to participate in this trial.

What prior data suggests that this genetic test disclosure is safe?

Research has shown that polygenic risk scores (PRS) can help identify individuals more likely to develop coronary artery disease (CAD). This involves using genetic information to predict the likelihood of heart problems. Studies have found that those with high PRS face a greater risk for CAD. This tool uses genetics to provide information about lifetime risk.

Regarding safety, no direct evidence from these studies indicates that sharing genetic risk results causes harm. The focus remains on predicting risk rather than offering a physical treatment. The trials aim to understand how knowing one's genetic risk influences lifestyle choices for heart health. Therefore, the main risks are psychological, such as feeling anxious after learning about one's genetic risk. However, research has not reported any significant negative events related to this disclosure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it focuses on using polygenic risk-based detection to identify subclinical coronary atherosclerosis. Unlike traditional methods like lifestyle changes, medications, or surgical interventions, this approach leverages genetic information to assess risk, potentially allowing for earlier and more personalized interventions. By tailoring prevention strategies based on an individual's genetic risk, this method could help reduce the onset of coronary artery disease more effectively than standard practices.

What evidence suggests that polygenic risk-based detection is effective for coronary artery disease?

Research has shown that polygenic risk scores (PRS) can identify individuals at higher risk for developing coronary artery disease (CAD). Those in the top 1% of these scores face nearly five times the risk of CAD, comparable to individuals with familial hypercholesterolemia. In this trial, participants in the intervention arm will receive their high polygenic risk result for coronary artery disease. This information may help predict early signs of CAD, where plaque accumulates in the arteries without yet causing symptoms. Early detection is crucial, as it might enable lifestyle changes or treatments to prevent serious heart issues. Overall, PRS is a promising tool for identifying individuals who may benefit from closer monitoring or preventive care. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for men and women aged 40-75 who have a high genetic risk for coronary artery disease but no history of cardiovascular diseases, severe liver or kidney conditions, or are on certain drugs. Pregnant or breastfeeding women and those with extreme obesity (BMI ≥ 40 kg/m2) are excluded.

Inclusion Criteria

I am between 40 and 75 years old and can give my consent.

My clinical test shows I have a high risk for coronary artery disease.

Exclusion Criteria

I have a history of heart or blood vessel disease.

I am pregnant, breastfeeding, or might become pregnant during the study.

My BMI is 40 or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants are assessed for baseline cardiovascular health and receive their polygenic risk result

1 visit

1 visit (in-person)

Intervention

Participants in the intervention group receive their high polygenic risk result for coronary artery disease

1 year

Control

Participants in the control group receive standard of care, with risk result disclosure deferred until study completion

1 year

Follow-up

Participants are monitored for changes in cardiovascular health over one year

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Polygenic risk-based detection of subclinical coronary atherosclerosis

Trial Overview The study tests the effect of informing participants about their high genetic risk for coronary artery disease to see if this knowledge leads to improved heart health over one year.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Participants will receive their high polygenic risk result for coronary artery disease.

Group II: Control Active Control 1 Intervention

Participants will receive standard of care, and disclosure of high polygenic risk result will be deferred until study completion.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Recent advancements in identifying genetic alleles linked to coronary artery disease have led to improved polygenic risk scores, which can predict the likelihood of developing the disease and inform treatment responses.

The review highlights the importance of careful validation and responsible clinical use of these polygenic risk scores for risk prediction, patient prioritization, and enhancing clinical trial designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of polygenic risk scores for coronary artery disease. Klarin, D., Natarajan, P.[2023]

The MI-GENES Study is designed to evaluate whether disclosing a genetic risk score (GRS) for coronary heart disease (CHD) can effectively lower low-density lipoprotein cholesterol (LDL-C) levels in participants, with an initial screening of 1000 individuals to identify those at high and average/low risk based on their GRS.

Participants will be randomized to receive either a conventional risk score or a GRS, followed by discussions about statin use, allowing researchers to assess changes in lipid levels, lifestyle factors, and psychosocial impacts over a 6-10 week period after risk disclosure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a randomized controlled trial of disclosing genomic risk of coronary heart disease: the Myocardial Infarction Genes (MI-GENES) study. Kullo, IJ., Jouni, H., Olson, JE., et al.[2018]

Genetic susceptibility tests for cardiovascular disease (CVD) are available to the public, but their effectiveness is questionable as they may not provide additional predictive value beyond existing risk factors like personal characteristics and plasma risk-trait levels.

For genetic tests to be truly useful in clinical management of CVD, they need to incorporate multiple functional variants and consider how these variants interact with environmental factors, which is currently a significant challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic testing for cardiovascular disease susceptibility: a useful clinical management tool or possible misinformation? Humphries, SE., Ridker, PM., Talmud, PJ.[2009]

Atherosclerotic cardiovascular disease (CVD), particularly coronary artery disease (CAD), remains a leading cause of death globally, despite improvements in risk factor management and medical therapies.

Recent advances in understanding the genetic factors associated with CAD may enhance prevention strategies, including better risk stratification, predicting treatment responses, and identifying new therapeutic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common genetic risk factors for coronary artery disease: new opportunities for prevention? Hamrefors, V.[2017]

A review of nine existing polygenic score reports revealed significant variability, highlighting the need for standardized approaches to disclose polygenic scores, particularly for coronary artery disease.

User feedback from interviews with ten individuals indicated that visual elements and clear word-based descriptions significantly enhance understanding of polygenic scores, suggesting that tailored reports could improve patient comprehension and engagement in their genomic information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and user experience testing of a polygenic score report: a qualitative study of prospective users. Brockman, DG., Petronio, L., Dron, JS., et al.[2022]

In a study of 5742 patients with symptomatic vascular disease, a genetic risk score (GRS) based on 30 genetic markers did not significantly enhance the prediction of 10-year cardiovascular event risk beyond traditional clinical assessments.

However, the GRS showed potential for improving risk prediction specifically in patients with stable atherosclerosis, suggesting it may be more useful for identifying first vascular events in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease. Weijmans, M., de Bakker, PI., van der Graaf, Y., et al.[2022]

Family history of atherosclerotic cardiovascular disease (CVD) significantly increases the risk of conditions like coronary heart disease and stroke, highlighting the importance of genetic factors in CVD.

Research is focusing on identifying specific genes and their interactions with environmental factors to improve CVD risk prediction and treatment, with recommendations for integrating genetic knowledge into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relevance of genetics and genomics for prevention and treatment of cardiovascular disease: a scientific statement from the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group. Arnett, DK., Baird, AE., Barkley, RA., et al.[2022]

Genetic testing has significantly improved the diagnosis of monogenic cardiovascular diseases, such as hypertrophic cardiomyopathy and familial hypercholesterolemia, leading to better patient management.

Polygenic risk scores (PRS) have been developed to assess the risk of more common cardiovascular diseases like atherosclerotic cardiovascular disease (ASCVD), but their added value to existing clinical risk prediction models remains debated, highlighting the need for further research in integrating genetic information into routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Risk Assessment for Atherosclerotic Cardiovascular Disease: A Guide for the General Cardiologist. Belanger, MJ., Kelly, EM., Tahir, UA., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05850091

Study Details | NCT05850091 | Polygenic Risk-based ... This is a double-blind randomized controlled trial of 200 individuals with high polygenic risk for coronary artery disease and subclinical plaque on coronary ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05819814

Polygenic Risk-based Detection of Subclinical Coronary ... The goal of this randomized controlled trial is to assess the impact of disclosing a high polygenic risk result for coronary artery disease on change in ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCGEN.121.003341

Polygenic Risk Score to Identify Subclinical Coronary ... Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40198844/

Assessing the Role of Polygenic Risk Scores in ... This study examines whether integrating PGS with SCORE2 improves the prediction of significant subclinical coronary atherosclerosis, defined as ...

5. mdpi.com mdpi.com/2035-8148/15/4/27

Polygenic Risk Scores and Coronary Artery Disease People in the top 1% of the score had almost a five-fold higher risk of CAD, similar to the risk seen with familial hypercholesterolemia. Overall, about 8% of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10842813/

Clinical applications of polygenic risk score for coronary artery ... First, CAD PRS is a static measure based on genetic information available from time of birth and as such provides information about lifetime risk, while CAC is ...