Coronary Artery Calcium Score and Polygenic Risk Score for the Prediction of Coronary Heart Disease Events

Abstract

Importance: Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts.

Objective: To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model.

Design, setting, and participants: Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands.

Exposure: Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score.

Main outcomes and measures: Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed.

Results: The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years).

Conclusions and relevance: In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.

Figure 1.. Study Flow Diagram for the Analytic Samples From the Multi-Ethnic Study of Atherosclerosis and the Rotterdam Study

^aParticipants may be excluded for more than 1 reason. CHD indicates coronary heart disease; CT computed tomography; and CVD, cardiovascular disease.

Figure 2.. Incident Coronary Heart Disease Stratified by Traditional Risk Factor Score, Coronary Artery Calcium Score, and Polygenic Risk Score: Multi-Ethnic Study of Atherosclerosis and the Rotterdam Study

For a definition of atherosclerotic CVD risk, coronary artery calcium score, polygenic risk score as applied to MESA and the Rotterdam Study, see the footnotes in Table 1.

Figure 3.. Receiver Operator Characteristic Curves and C Statistics for Prediction of Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis and the Rotterdam Study

For a definition of atherosclerotic cardiovascular disease (ASCVD) risk, coronary artery calcium (CAC) score, polygenic risk score (PRS) as applied to the Multi-Ethnic Study of Atherosclerosis and the Rotterdam Study, see the footnotes in Table 1.