Predicting CHD risk in middle-aged to older adults: CAC score outperforms polygenic risk score
Coronary Artery Calcium Score and Polygenic Risk Score for the Prediction of Coronary Heart Disease Events
Introduction and methods
As conventional clinical risk scores, such as the American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equations (PCEs), are unable to precisely estimate the risk of CHD, novel risk markers are being sought out. Both coronary artery calcium scores and polygenic risk scores (PRSs) can be used to predict risk of clinical CHD [1-4], but they have not been directly compared in the same cohort.
Aim of the study
The authors evaluated the change in CHD risk prediction when a coronary artery calcium score, a PRS, or both were added to a traditional risk factor–based model in 2 cohorts of middle-aged to older adults.
Data from 2 observational population-based cohort studies of individuals of European ancestry aged 45–79 years who were free of clinical CHD at baseline were included: the MESA (Multi-Ethnic Study of Atherosclerosis) study (n=1991), conducted in the US , and the RS (Rotterdam Study) (n=1217), conducted in the Netherlands [6,7]. Median follow-up times were 16.0 years (IQR: 12.7–16.7) and 14.2 years (IQR: 11.3–14.9), respectively.
To calculate the predicted 10-year risk of atherosclerotic CVD for each participant, the 2013 ACC/AHA PCEs were applied, which incorporate traditional risk factors such as age, sex, and systolic blood pressure [8,9]. The coronary artery calcium score was calculated based on CT images, while the linkage-disequilibrium single-nucleotide polymorphism–reweighting approach was used to calculate the CHD PRS.
Model discrimination, calibration, and change in risk stratification, including net reclassification improvement (NRI; at recommended risk threshold of 7.5%), for prediction of incident CHD events were assessed.
The primary outcome was the change in model discrimination (ΔC statistic) when the coronary artery calcium score, PRS, or both were added to the PCEs.
- In the MESA study, the log (coronary artery calcium score+1) and PRS were associated with 10-year risk of incident CHD (HR per SD: 2.60; 95%CI: 2.08–3.26 and 1.43; 95%CI: 1.20–1.71, respectively).
- The Harrell C statistic was 0.76 (95%CI: 0.71–0.79) for the coronary artery calcium score and 0.69 (95%CI: 0.63–0.71) for the PRS.
- The change in the C statistic was 0.09 (95%CI: 0.06–0.13) when the coronary artery calcium score was added to the PCEs, 0.02 (95%CI: 0.00–0.04) when the PRS was added, and 0.10 (95%CI: 0.07–0.14) when both were added.
- Overall categorical NRI was significant when the coronary artery calcium score was added to the PCEs (0.19; 95%CI: 0.06–0.28) but not when the PRS was added (0.04; 95%CI: –0.05 to 0.10).
- Calibration of the PCEs and the models with coronary artery calcium score and/or PRS was adequate (all χ² <20).
- Similar patterns and estimates for the C statistic, change in C statistic, and NRI were observed with data from the RS study.
- Subgroup analysis stratified by median age in both studies (61 years in MESA study and 67 years in RS study) also showed similar findings.
In a study of 2 population-based cohorts of middle-aged to older adults of European ancestry, the coronary artery calcium score, but not a CHD PRS, showed improved risk discrimination and risk reclassification when added to a traditional model for CHD risk prediction. Combining both scores had no additional predictive utility compared with adding the coronary artery calcium score alone.
“This study directly addresses a key knowledge gap identified by the recent AHA Scientific Statement, among others, expressing a need to directly compare [PRSs] with coronary artery calcium scores for predicting risk of CHD”, according to the authors.