UC San Diego

Objectives

The goal of this study was to assess the utility of a genetic risk score (GRS) in targeted coronary artery calcium (CAC) screening among young individuals.

Background

Early CAC screening and preventive therapy may reduce long-term risk of a coronary heart disease (CHD) event. However, identifying younger individuals at increased risk remains a challenge. GRS for CHD are age independent and can stratify individuals on various risk trajectories.

Methods

Using 142 variants associated with CHD events, we calculated a GRS in 1,927 individuals in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort (aged 32 to 47 years) and 6,600 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (aged 44 to 87 years). We assessed GRS utility to predict CAC presence in the CARDIA cohort and stratify individuals of varying risk for CAC presence over the lifetime in both cohorts.

Results

The GRS predicted CAC presence in CARDIA males. It was not predictive in CARDIA females, which had a CAC prevalence of 6.4%. In combined analysis of the CARDIA and MESA cohorts, the GRS was predictive of CAC in both males and females and was used to derive an equation for the age at which CAC probability crossed a predetermined threshold. When assessed in combination with traditional risk factors, the GRS further stratified individuals. For individuals with an equal number of traditional risk factors, probability of CAC reached 25% approximately 10 years earlier for those in the highest GRS quintile compared to the lowest.

Conclusions

The GRS may be used to target high-risk younger individuals for early CAC screening.