- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05169840
Genetic Risk Stratification for Primary Prevention of CAD in Men and Pre & Post-menopausal Women
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).
Study Overview
Status
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Jennine C Zumbuhl, RN, MSHA
- Phone Number: 480-728-3674
- Email: jennine.zumbuhl@dignityhealth.org
Study Contact Backup
- Name: Lori Wood, RN
- Email: lori.wood@dignityhealth.org
Study Locations
-
-
Arizona
-
Chandler, Arizona, United States, 85224
- Recruiting
- Chandler Regional Medical Center
-
Contact:
- Natalie Leon
- Phone Number: 480-728-8736
- Email: natalie.leon@dignityhealth.org
-
Contact:
- Jennine Zumbuhl, RN, MSHA
- Phone Number: 480-728-3674
-
Sub-Investigator:
- Roger Bies, MD
-
Gilbert, Arizona, United States, 85297
- Recruiting
- Mercy Gilbert Medical Center
-
Contact:
- Natalie Leon
- Phone Number: 480-728-8736
- Email: natalie.leon@dignityhealth.org
-
Contact:
- Jennifer Vermillion
- Phone Number: 480-728-9973
- Email: jennifer.vermillion@dignityhealth.org
-
Sub-Investigator:
- Nabil Dib, MD
-
Phoenix, Arizona, United States, 85013
- Recruiting
- St Joseph's Hospital and Medical Center
-
Contact:
- Lori Wood, RN
- Email: lori.wood@dignityhealth.org
-
Contact:
- Araceli Vidal, RN
- Phone Number: 602-406-1156
- Email: araceli.vidal@dignityhealth.org
-
Principal Investigator:
- Robert Roberts, MD
-
Sub-Investigator:
- Pallavi Bellamkonda, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Genetic Risk Score (GRS)
Time Frame: 2 years
|
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
|
Participant's response on the informed consent regarding their wish to learn about their genetic risk.
Time Frame: 2 years
|
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
|
Spread of the Genetic Risk Score (GRS) in Hispanics or African Americans vs those of European descent.
Time Frame: 2 years
|
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
|
Percentage of participants with a high Genetic Risk Score (GRS) who take action as a result.
Time Frame: 10 years
|
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
|
Collaborators and Investigators
Investigators
- Principal Investigator: Robert Roberts, MD, Dignity Health
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 19-500-384-50-17
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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