Editorial
Assessment Timings of Polygenic Risk Score for Atherosclerotic Cardiovascular Disease
2024 Volume 31 Issue 7 Pages 1029-1030
Details
2024 Volume 31 Issue 7 Pages 1029-1030
See article vol. 31: 1058-1071
Because atherosclerotic cardiovascular disease (ASCVD) is a highly heritable trait, it is quite natural to explore the impact of human genetics on risk estimates for ASCVD. A part of this can be explained by the family history information where “positive” family history represents a two- to three-fold increased risk for ASCVD1). In addition, rare genetic variants, such as loss of function variants in the LDL receptor (LDLR), are associated with ASCVD via inherited hyper LDL cholesterolemia2, 3). Recently, a unique score—polygenic risk score (PRS)—comprising a set of common generic variants associated with a certain phenotype, including ASCVD, has been developed4, 5). In the research settings, this score reportedly has several great advantages: 1) PRS is associated with ASCVD independent of clinical risk factors, such as hypertension, diabetes, and smoking; 2) PRS can be assessed anytime after birth; 3) PRS is a continuous variable rather than dichotomous where we can use it as a “score”; 4) PRS is independent of family history information5). However, there are some concerns regarding its clinical use. First, it has not been verified in any randomized clinical trials. Typically, the assessment of PRS—and some associated therapies—is the intervention, and the assessments of classical clinical variables are the control in RCT. Second, studies suggest that PRS for ASVCD is not as useful as previously described, even when using a more advanced scheme of computing PRS6). Considerably, Kujala et al. investigated the impact of PRS on coronary artery disease among the independent study samples and found modest improvement of risk stratification via PRS beyond classical clinical risk factors, such as hypertension, diabetes, and smoking7). There are two major reasons for this unexpected observation. First, we should acknowledge that classical clinical risk factors are good at risk prediction for ASCVD8); it is usually difficult to find other factors beyond such variables. Second, the impact of genetic factors, including PRS is potentially larger in younger populations where clinical risk factors for ASCVD are covert (Fig.1). On the contrary, the impact of genetic factors should be small in older populations where classical clinical risk factors have more impact9, 10). In this regard, the mean age of the study population, who have many clinical complications including hypertension and dyslipidemia, was 64 years. Therefore, we need to be cautious when we discuss the clinical usefulness of genetic factors in ASCVD risk assessments.
Impact of genetic and clinical risk factors on ASCVD
Genetic factors, including PRS, appear useful in younger populations, while classical clinical risk factors are useful in older populations. More assessments of genetic factors should be considered in younger populations for better prevention for ASCVD.
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