Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

Abstract

Background: Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored.

Methods: From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1-49%, 50-69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) - inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) - and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification.

Results: Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61-3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75-3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09-1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18-2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29-2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05-1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06).

Conclusion: For asymptomatic diabetic individuals, CCTA measures of CAD severity confer incremental risk prediction, discrimination and reclassification on a per-patient, per-vessel and per-segment basis.

Keywords: Coronary CT angiography; Coronary artery calcium score; Coronary artery disease; Major adverse cardiac events.

Fig. 1

(A) Kaplan–Meier curves for event-free survival from death, nonfatal myocardial infarction, and late target vessel revascularization. (B) Kaplan–Meier curves for event-free survival from death and nonfatal myocardial infarction.

Fig. 2

Area under the receiver operating characteristics curve for future major adverse cardiac events. Model A represents age, gender and traditional CHD risk factors. Model B is inclusive of all variables in Model A plus coronary artery calcium score. Model C is inclusive of all variables in Model B plus number of obstructive coronary artery epicardial vessels.

Fig. 3

Reclassification by the number of vessels with obstructive CAD as stratified by the coronary artery calcium score. Reclassification is defined by the integrated discrimination improvement (IDI) index for patients stratified by coronary artery calcium score. The box represents the value, and the vertical bars represent the 95% confidence interval.