Genetic Risk Stratification for Primary Prevention of CAD in Men and Pre & Post-menopausal Women

Coronary Artery Disease Clinical Trial

Official title:

Genetic Risk Stratification for Primary Prevention of CAD in Men and Pre & Post-menopausal Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05169840
• Other study ID #: 19-500-384-50-17
• Status: Recruiting
• Start date: August 23, 2021
• Est. completion date: June 15, 2024

Study information

• Verified date: February 2023
• Source: St. Joseph's Hospital and Medical Center, Phoenix
• Contact: Jennine C Zumbuhl, RN, MSHA
• Phone: 480-728-3674
• Email: jennine.zumbuhl[@]dignityhealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators propose to genotype males and females at age 40 years and older, who are asymptomatic and without known heart disease (N=2000). DNA from a blood sample will be genotyped for millions of genetic risk variants for CAD by Baylor College of Medicine Human Genome Sequencing Center Clinical Laboratory (HGSC-CL) in a CLIA-approved laboratory.

The overall objective after 2 years is to determine if genetic screening for risk of CAD in asymptomatic men and women has the discriminatory power to detect those at highest risk who would potentially benefit most from appropriate primary prevention. It will also determine whether the GRS is appropriate for different ethnic and race groups such as Hispanics, African Americans and Whites, and to what extent those individuals knowing that they are at higher risk, are more likely to seek further advice on management of the risks (either through changes in lifestyle or therapy).

Description:

Coronary artery disease (CAD) is an epidemic, being the most common cause of death in the world. CAD is preventable as shown by clinical trials that reduce conventional risk factors such as hypercholesterolemia. Epidemiologists have claimed 40-60% of pre-disposition to CAD is genetic. In 2007, the investigators and the Icelandic group independently identified the first genetic risk variant for CAD, 9p21. Through the formation of an international consortium, the investigators have now identified over 200 genetic risk variants predisposing to CAD. Utilizing a genetic risk score (GRS) based on these variants for CAD, several studies have retrospectively documented the risk stratification for primary or secondary prevention of CAD to be superior and relatively independent of, conventional risk factors. Studies in over 1 million individuals show those with the highest genetic risk exhibit up to a 4-fold increased risk of CAD. More importantly, those with a high GRS and a more favorable lifestyle experienced 50% reduction in cardiac events. In the high risk group one needs to treat only 13 individuals with statin therapy to prevent one cardiac event. The GRS detects those at high risk who will benefit most from primary prevention. The myth that one cannot treat genetic predisposition has been dispelled. While secondary prevention of CAD has been successful, application of primary prevention has until now lacked a risk marker to detect those who would benefit most. Given only 47% of the population will experience a cardiac event, administering preventive therapy, such as statin, to everyone would be unnecessarily expensive and inappropriate. Since the GRS is determined at birth, and does not change during one lifetime it is close to ideal for primary prevention. GRS detects among asymptomatic individuals at any age those at high-risk for CAD, who will benefit most from preventive therapy.

The investigators propose to genotype males and females at age 40 years and older, who are asymptomatic and without known heart disease (N=2000). DNA from a blood sample will be genotyped for millions of genetic risk variants for CAD by Baylor College of Medicine Human Genome Sequencing Center Clinical Laboratory (HGSC-CL) in CLIA-approved laboratories.

The derived GRS will be added to the conventional risk score using the American College of Cardiology/American Heart Association's (AHA) Pooled Cohort Atherosclerotic Cardiovascular Disease (ASCVD) Risk Equation. In the female cohort, investigators will also be screening for female-specific risk factors that have been added to the ACC/AHA 2018 Blood Cholesterol Guidelines to be used as risk enhancers. Everyone at high risk, will be referred to their physician for further management and given the opportunity for genetic counseling by a member of the research team. Completion of the 2 year recruitment will meet the objectives, however, an annual follow-up will be obtained by electronic survey via REDCap, letter or phone call over a 10 year period as it may provide information on long term genetic prediction.

The overall objective after 2 years is to determine if genetic screening for risk of CAD in asymptomatic men and women has the discriminatory power to detect those at highest risk who would potentially benefit most from appropriate primary prevention. It will also determine whether the GRS is appropriate for different ethnic and race groups such as Hispanics, African Americans and Whites, and to what extent those individuals knowing that they are at higher risk, are more likely to seek further advice on management of the risks (either through changes in lifestyle or therapy). The investigators expect to complete recruitment in two years and prove that the GRS is appropriate for clinical application and can detect individuals that have a 50% or more increase in risk for CAD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: June 15, 2024
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 60 Years

Eligibility

Inclusion Criteria:

• Males 40 to 60 years of age

• Females 40 to 60 years of age

• No known cardiovascular disease

• Willing and able to sign consent

Exclusion Criteria:

• Prisoners

• Prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)

• Known ischemia on non-invasive testing

• Ischemic cerebrovascular event

• Peripheral arterial disease

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Genetic Predisposition to Disease
• Myocardial Ischemia

Intervention

Other:
• Genetic Risk Score for Coronary Artery Disease
Blood samples will be genotyped for million of genetic risk variants for Coronary Artery Disease (CAD)

Locations

Country	Name	City	State
United States	Chandler Regional Medical Center	Chandler	Arizona
United States	Mercy Gilbert Medical Center	Gilbert	Arizona
United States	St Joseph's Hospital and Medical Center	Phoenix	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
St. Joseph's Hospital and Medical Center, Phoenix	Chandler Regional Medical Center, Mercy Gilbert Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic Risk Score (GRS)	The GRS will be calculated by summing the product of the number of risk variants inherited by each individual times their associated Coronary Artery Disease risk. The score will be classified into low, intermediate and high.	2 years
Primary	Participant's response on the informed consent regarding their wish to learn about their genetic risk.	Participants will be asked on the informed consent whether they would like to learn about their calculated genetic risk and will provide a yes or no answer.	2 years
Primary	Spread of the Genetic Risk Score (GRS) in Hispanics or African Americans vs those of European descent.	Since previous studies utilizing the GRS have been predominately in white individuals of European descent data will be stratified to determine if the GRS has the same risk stratification power in Hispanics and African Americans vs those of European descent.	2 years
Primary	Percentage of participants with a high Genetic Risk Score (GRS) who take action as a result.	Participants with a high GRS will be asked at follow up whether they have followed through on recommendations to seek further care, started any new therapies and/or if they have made lifestyle changes as a result. This will be assessed annually for 10 years.	10 years