Study Says CT Scan is More Predictive than Genetic Risk Factors for Coronary Heart Disease Risk

Despite coronary heart disease (CHD) having estimated heritability ranging between 40 to 60 percent, new research suggests the computed tomography (CT)-derived coronary artery calcium (CAC) score is more effective than the polygenic risk score for gauging CHD risk in middle-aged to older patients.^1,2

For the study, recently published in the Journal of the American Medical Association (JAMA), researchers examined multicenter data from a total of 3,208 adults drawn from cohort studies performed in the United States (median age of 61) and the Netherlands (median age of 67). In addition to comparing the CAC score to the polygenic risk score for predicting CHD risk, the study authors sought to ascertain the impact of either measure in combination with traditional risk factor assessment (i.e., pooled cohort equations (PCEs)) for CHD.

For the 10-year risk of incident CHD, the researchers noted the CAC score was associated with a 2.60 hazard ratio (HR) in comparison to 1.43 for the polygenic risk score. Adding the CAC score to PCEs resulted in a nine percent change in the C statistic for CHD risk assessment in comparison to a 2 percent change with adding the polygenic risk score, according to the study. The study authors also noted significant overall categorical net reclassification improvement (NRI) with the CAC score (19 percent) in comparison to the polygenic risk score (4 percent).²

“When the coronary artery calcium score was added to a traditional risk factor-based model, there was a statistically significant and clinically meaningful improvement in risk discrimination (increase in the C statistic) and risk stratification (NRI). In contrast, when the polygenic risk score was added to a traditional risk factor-based model, the change in risk discrimination and categorical net reclassification improvement was not statistically significant,” wrote lead study author Sadiya S. Khan, MD, MSc, an assistant professor of medicine (cardiology) and preventive medicine (epidemiology) at the Northwestern University Feinberg School of Medicine, and colleagues.

(Editor’s note: For related content, see “Five Takeaways from New Consensus Recommendations for CT Imaging and Reporting in Patients with CAD” and “Should Dual-Source CT be the New Standard for ER CCTA Assessment of Acute Chest Pain?”)

Noting that this may be the first study to compare the CAC score and the polygenic risk score for CHD risk assessment, the researchers pointed out that the median age for this study was in the 60s whereas previous research has found the polygenic risk score more advantageous than PCEs for adults between the ages of 40 and 49.^2,3

“ … It is possible that the polygenic risk score and coronary artery calcium score may each be clinically relevant at different life stages,” suggested Khan and colleagues.

In regard to study limitations, the researchers acknowledged that in order to perform a focused assessment of the additive benefits of the CAC score or the polygenic risk score to traditional risk factor models for CHD risk, they modified the PCEs for the Netherlands-based study, which may have biased the research findings.

Noting that the polygenic risk score has poor CHD risk discrimination for adults without European ancestry, Khan and colleagues said the study cohort was limited to White individuals or those of European ancestry, thus thwarting general extrapolation of the study findings to a broader diverse population. While the study includes up to 17 years of follow-up data, the authors noted the baseline exams, conducted in the early 2000s, may not be reflective of current clinical practice.

References

1. Pechlivanis S, Lehmann N, Hoffmann P, et al. Risk prediction for coronary heart disease by a genetic risk score – results from the Heinz Nixdorf Recall study. BMC Med Genet. 2020;21(1):178. doi: 10:1186/s12881-020-01113-y.

2. Khan SS, Post WS, Guo X, et al. Coronary artery calcium score and polygenic risk score for the prediction of coronary heart disease events. JAMA. 2023;329(20):1768-1777. doi:10.1001/jama.2023.7575.

3. Elliott J, Bodinier B, Bond TA, et al. Predictive accuracy of a polygenic risk score-enhanced prediction model vs. a clinical risk score for coronary artery disease. JAMA. 2020;323(7):636-645.