10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study)

Abstract

Background: Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed.

Objectives: The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors.

Methods: Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study).

Results: Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate.

Conclusions: An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.

Keywords: atherosclerosis; coronary disease; epidemiology; risk prediction.

Central Illustration. MESA CHD Risk Score Using Coronary Artery Calcium: Calibration of the MESA CHD Risk Score

The Central Illustration presents the observed versus the predicted event rates. Predicted risks were divided into 10 equal sized bins for MESA and HNR. For DHS, only 5 bins were used due to the smaller sample size.

Figure 1. Discrimination of the MESA CHD Risk Score within the Development Cohort

The first panel displays the Receiver-Operator Characteristic (ROC) curves for the risk scores with and without CAC applied within the MESA cohort. The second panel displays a boxplot of the predicted 10-year CHD probabilities for each score stratified by event status. The shaded box covers the middle 50% of the data, with a line at the median.

Figure 2. Online Risk Score Calculator

A screenshot of the online risk score calculator available at http://www.mesa-nhlbi.org/. Here we see the calculator being used for an older man with fairly favorable risk factor profile but zero CAC. Under a risk score without CAC, 10-year estimated CHD risk is 9.3%, due in large part to their age. Once we factor in that they have no detectable CAC, estimated risk is only 3.1%.