Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

The prognostic value of coronary artery calcium (CAC) scoring is well established and has been suggested for use to exclude significant coronary artery disease (CAD) for symptomatic individuals with CAD. Contrast-enhanced coronary computed tomographic angiography (CCTA) is an alternative modality that enables direct visualization of coronary stenosis severity, extent, and distribution. Whether CCTA findings of CAD add an incremental prognostic value over CAC in symptomatic individuals has not been extensively studied. We prospectively identified symptomatic patients with suspected but without known CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed by the method of Diamond and Forrester (D–F). CAC was measured by the method of Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque burden, distribution, and location. Plaque burden was determined by a segment stenosis score (SSS), which reflects the number of coronary segments with plaque, weighted for stenosis severity. Plaque distribution was established by a segment-involvement score (SIS), which reflects the number of segments with plaque irrespective of stenosis severity. Finally, a modified Duke prognostic index—accounting for stenosis severity, plaque distribution, and plaque location—was calculated. Nested Cox proportional hazard models for a composite endpoint of all-cause mortality and non-fatal myocardial infarction (D/MI) were employed to assess the incremental prognostic value of CCTA over CAC. A total of 8627 symptomatic patients (50% men, age 56 ± 12 years) followed for 25 months (interquartile range 17–40 months) comprised the study cohort. By CAC, 4860 (56%) and 713 (8.3%) patients had no evident calcium or a score of >400, respectively. By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved discrimination beyond D–F and clinical variables (area under the receiver-operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added sequentially to D–F, clinical variables, and CAC, all CCTA measures of CAD improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P < 0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic index (0.82, P < 0.0001). In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI.

Objective To prospectively assess the value of coronary CT angiography (CTA) in asymptomatic patients with high ‘a priori’ risk of coronary artery disease (CAD). Methods 711 consecutive asymptomatic patients (61.8 years; 40.1% female) with high ‘a priori’ risk of CAD were prospectively examined with a coronary calcium score (CCS) and CTA. Coronary arteries were evaluated for atherosclerotic plaque (non-calcified and calcified) and stenosis (mild 70%). Coronary Segment Involvement Score (SIS, total number of segments with plaque) and nc (non-calcified) SIS were calculated. Primary end points were major adverse cardiac events (ST-elevation MI, non-ST-elevation MI and cardiac death); secondary end points were coronary revascularisation and >50% stenosis by invasive angiography. Results Of 711 patients, 28.3% were negative for CAD and 71.7% positive (CAD+) by CTA (15.6% had plaques without stenosis, 23.9% mild, 10.7% intermediate and 21.5% high-grade stenosis). CCS zero prevalence was 306 (43%), out of those 100 (32.7%) had non-calcified plaque only. Mean follow-up period was 2.65 years. MACE rate was 0% in CAD negative and higher (1.2%) in CAD positive by CTA. Coronary revascularisation rate was 5.5%. Patients with SIS ≥5 had an HR of 6.5 (95% CI 1.6 to 25.8, p<0.013) for MACE, patients with ncSIS ≥1 had an HR of 2.4 (95% CI 1.2 to 4.6, p50% compared with invasive angiography was 92.9% (95% CI 83.0% to 98.1%). Negative predictive value of CTA was 99.4% (95% CI 98.3% to 99.8%) for combined end points. Conclusions CAD prevalence by CTA in asymptomatic high-risk patients is high. CCS zero does not exclude CAD. CTA is highly accurate to exclude CAD. Total coronary plaque burden and nc plaques, even if only one segment is involved, are associated with an increased risk of adverse outcome.

To date, the therapeutic benefit of revascularization vs. medical therapy for stable individuals undergoing invasive coronary angiography (ICA) based upon coronary computed tomographic angiography (CCTA) findings has not been examined. We examined 15 223 patients without known coronary artery disease (CAD) undergoing CCTA from eight sites and six countries who were followed for median 2.1 years (interquartile range 1.4–3.3 years) for an endpoint of all-cause mortality. Obstructive CAD by CCTA was defined as a ≥50% luminal diameter stenosis in a major coronary artery. Patients were categorized as having high-risk CAD vs. non-high-risk CAD, with the former including patients with at least obstructive two-vessel CAD with proximal left anterior descending artery involvement, three-vessel CAD, and left main CAD. Death occurred in 185 (1.2%) patients. Patients were categorized into two treatment groups: revascularization (n = 1103; 2.2% mortality) and medical therapy (n = 14 120, 1.1% mortality). To account for non-randomized referral to revascularization, we created a propensity score developed by logistic regression to identify variables that influenced the decision to refer to revascularization. Within this model (C index 0.92, χ2 = 1248, P < 0.0001), obstructive CAD was the most influential factor for referral, followed by an interaction of obstructive CAD with pre-test likelihood of CAD (P = 0.0344). Within CCTA CAD groups, rates of revascularization increased from 3.8% for non-high-risk CAD to 51.2% high-risk CAD. In multivariable models, when compared with medical therapy, revascularization was associated with a survival advantage for patients with high-risk CAD [hazards ratio (HR) 0.38, 95% confidence interval 0.18–0.83], with no difference in survival for patients with non-high-risk CAD (HR 3.24, 95% CI 0.76–13.89) (P-value for interaction = 0.03). In an intermediate-term follow-up, coronary revascularization is associated with a survival benefit in patients with high-risk CAD by CCTA, with no apparent benefit of revascularization in patients with lesser forms of CAD.

Background Sex differences in the calculation of coronary heart disease risk have been analysed extensively. However, data on coronary plaque morphology diverge. We analysed plaque characteristics in patients with suspected coronary artery disease (CAD) and defined prognostic factors using coronary computed tomography angiography (CCTA). Methods A total of 6,050 consecutive patients underwent CCTA and were enrolled in the registry. Patients with known CAD were excluded. The patients were propensity score matched (1:1 male:female) for age and known coronary risk factors. Coronary arteries were evaluated for stenosis, plaque types (non-calcified, mixed and calcified) and high-risk plaque features (napkin-ring sign, low-attenuation plaque, spotty calcifications, positive remodelling). Clinical follow-up was performed. Results A total of 1,050 patients (525 female, 525 male) in matched cohorts were selected for analysis. CCTA showed significantly higher calcium scores for males (mean 180.5 vs 67.8 AU, p < 0.0001) and a higher rate of CAD (66.0% vs 34.1%, p < 0.0001). In a total of 16,800 segments, males had significantly more plaques (861 vs 752, p < 0.0001) with a significantly larger proportion of calcified plaques, while females had more mixed and non-calcified plaques (33.5% vs 24.4%, p = 0.006 and 24.1% vs 13.6%, p = 0.22, respectively). After a mean follow-up of 5.6 years, major adverse cardiac event (MACE) rate was 5.3% in male and 1.9% in female patients (p < 0.05). The relative odds ratio for high-risk plaque features to predict MACE was higher in females. Conclusion Based on a higher relative risk for women with high-risk plaque features, the findings of our study support the increased importance of a differentiated qualitative plaque analysis to improve the risk stratification for both sexes.