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.