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

Highlights

• We examined 400 asymptomatic diabetic patients without known coronary artery disease (CAD) who underwent both coronary CT angiography (CCTA) and coronary artery calcium scoring (CACS)

• We examined the predictive value of CCTA findings over traditional clinical risk scoring and CACS.

• Beyond clinical risk factors and CACS, CCTA findings of coronary artery disease extent and severity added prediction, discrimination and reclassification for identification of diabetic individuals at risk of incident major adverse cardiovascular events.

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.

Introduction

The prevalence of diabetes mellitus is rapidly increasing worldwide, with a projected prevalence of more than 350 million individuals by 2030 [1]. While diabetics have been traditionally considered a coronary heart disease (CHD) equivalent [2], studies using coronary artery calcium scoring (CACS) have observed a high percentage of diabetic individuals to possess no coronary calcium, a finding associated with low future cardiovascular risk. These studies of CACS have also shown that this test augments prediction of CHD risk in asymptomatic diabetic individuals beyond consideration non-diabetes CHD risk factors. As an example, a high proportion of diabetics have a CAC score of 0, which is associated with an excellent prognosis. In contrast, for every increasing non-zero category of CACS, the risk is higher for a diabetic than a non-diabetic patient. Thus, current professional societal guidelines endorse the use of diagnostic testing for selected asymptomatic individuals by means of stress testing [3], [4] or coronary artery calcium scoring (CACS) [5].

Coronary computed tomographic angiography (CCTA) is a non-invasive test that demonstrates high diagnostic performance for the detection and exclusion of any atherosclerosis as well as anatomically obstructive CAD [6], [7], [8], [9]. In the general population of asymptomatic patients undergoing CCTA scanning, CCTA findings have not shown more effective risk stratification than CACS. However, whether CCTA represents a more effective method for risk assessment than CACS in selected higher risk asymptomatic patients – such as those with diabetes – is unknown.

From a consecutive cohort of individuals within a large prospective international multicenter observational cohort study, we evaluated whether CAD identified by CCTA would offer incremental risk assessment over CHD risk factors and CACS for asymptomatic diabetic individuals.