An analysis of 2 population-based cohorts suggests coronary artery calcium scores added to traditional risk-based models showed better discrimination than polygenic risk scores for CHD risk prediction.
New research suggests a coronary artery calcium score was associated with better discrimination than a polygenic risk score for the risk prediction of coronary heart disease (CHD) in middle-aged to older adults from the United States and Netherlands.1
The analysis showed a statistically significant and clinically meaningful improvement in both risk discrimination and risk stratification when the coronary artery calcium score was added to a traditional risk factor-based model.
“Finding the best way to identify who is at risk for developing heart disease can help determine what needs to be done to lower their risk,” Sadiya S. Khan, MD, MS, an assistant professor of medicine from the division of cardiology at Northwestern University Feinberg School of Medicine said in a statement.2 “This finding can help doctors and patients managing risk for heart disease, which is the leading cause of death in the United States.”
Khan and colleagues suggest that novel risk markers may improve risk estimation for cardiovascular disease (CVD) and particularly for CHD. Imaging of subclinical atherosclerosis with computer tomography (CT) to detect coronary artery calcium has been shown to be a predictor of future clinical CHD. Polygenic risk scores have additionally been a proposed tool to improve risk prediction and advance precision medicine as the estimated heritability of CHD is approximately 40% - 60%.
Despite coronary artery calcium being compared with other risk markers, no prior literature have directly compared the change in risk discrimination and reclassification with the addition of a coronary artery calcium score, polygenic risk score, or both to traditional risk factor scores (pooled cohort equations [PCEs]) measured in the same cohort. To better address this knowledge gap, the current analysis directly compared whether risk prediction is more precise with the addition of coronary arterial calcium score or polygenic risk score to current prediction models.
The analysis included data on participants aged 45 - 79 years without known CHD from 2 population-based cohort studies, the Multi-Ethnic Study of Atherosclerosis (MESA) and the Rotterdam Study. MESA recruited adults from 6 centers between July 2000 - September 2002, while the Rotterdam Study is an ongoing cohort of adults in Rotterdam, the Netherlands. All participants underwent interim in-person examinations approximately every 18 months and participated in annual telephone follow-up conversations to determine any hospitalizations or acute events.
Investigators assessed the change in model discrimination, calibration, and net reclassification improvement (at the recommended ACC/AHA PCE risk threshold of 7.5%) for the prediction of incident CHD events. Among 1991 participants from MESA and 1217 participants from the Rotterdam study, the mean age of participants was 61 and 68 years, respectively. Based on traditional risk factors, the median predicted atherosclerotic CVD risk was 6.99% in MESA and 5.93% in the Rotterdam Study.
Upon analysis, investigators found both coronary artery calcium and polygenic risk scores were significantly associated with the 10-year risk of incident CHD (hazard ratio [HR] per SD, 2.60; 95% CI, 2.08 - 3.26 and HR, 1.43; 95% CI, 1.20 - 1.71, respectively) in MESA. Additionally, in MESA, the C statistic associated with the coronary artery calcium score was 0.76 (95% CI, 0.71 - 0.79) and for the polygenic risk score was 0.69 (95% CI, 0.63 - 0.71).
Changes in the C statistic when coronary arterial calcium was added to the PCEs was 0.09 (95% CI, 0.06 - 0.13), but there was no significant change in the C statistic when the polygenic risk score was added to the PCEs. The overall categorical net reclassification improvement was found significant when the coronary artery calcium score (0.19; 95% CI, 0.06 - 0.28) was added to the PCEs, but not the polygenic risk score (0.04; 95% CI, -0.05 - 0.10).
Investigators noted the calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate, with χ2 <20 for all models examined. Moreover, the team indicated subgroup analysis stratified at the median age in both studies demonstrated similar results.
“These findings support recommendations to consider CT screening to calculate risk for heart disease in middle-aged patients when their degree of risk is uncertain or in the intermediate range,” Khan said.2