Genetic Test Disclosure for Coronary Artery Disease

(PROACT 1 Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Massachusetts General Hospital

Must not be taking: Statins, Colchicine, CY2P inhibitors

Disqualifiers: Cardiovascular disease, Liver disease, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial aims to see if telling middle-aged people with high genetic risk for heart disease about their risk helps them improve their 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 data supports the effectiveness of the treatment Polygenic risk-based detection of subclinical coronary atherosclerosis for coronary artery disease?

Research shows that polygenic risk scores, which assess inherited risk by analyzing many DNA variations, can help predict coronary artery disease and guide preventive treatments. These scores have been shown to indicate clinical responses to some therapies, suggesting they could improve prevention and treatment strategies for coronary artery disease. ^{1 2 3 4 5}

Is genetic testing for coronary artery disease safe for humans?

Genetic testing for coronary artery disease, including polygenic risk scores, has been widely studied and is generally considered safe for humans. However, the main concerns are about its clinical utility and the interpretation of results, rather than safety issues. ^{2 4 6 7 8}

How does the genetic test disclosure treatment for coronary artery disease differ from other treatments?

This treatment is unique because it involves disclosing a genetic risk score for coronary artery disease, which can help tailor prevention strategies by identifying individuals at higher risk based on their genetic makeup. Unlike traditional treatments that focus on managing symptoms or risk factors, this approach aims to improve prevention by using genetic information to guide clinical decisions. ^{1 2 3 5 6}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Polygenic risk-based detection of subclinical coronary atherosclerosis (Genetic Test)

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.

Participant Groups

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+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2018]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Clinical utility of polygenic risk scores for coronary artery disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Design and user experience testing of a polygenic score report: a qualitative study of prospective users. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Genetic Risk Assessment for Atherosclerotic Cardiovascular Disease: A Guide for the General Cardiologist. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Genetic testing for cardiovascular disease susceptibility: a useful clinical management tool or possible misinformation? [2009]

8. Ireland 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. [2022]