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Aims The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. Methods and results From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64–68 years vs. 52–56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6–20: HR 2.29 (1.69–3.10); score > 20: HR 6.71 (4.36–10.32) in women, and score 6–20: HR 1.64 (1.29–2.08); score > 20: HR 2.38 (1.73–3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P -interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6–20: HR 2.21 (1.57–3.11); score > 20: HR 6.11 (3.84–9.70) in women; score 6–20: HR 1.57 (1.19–2.09); score > 20: HR 2.25 (1.58–3.22) in men], with a significant interaction for the highest risk group (adjusted P -interaction = 0.004). Conclusion Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity. [ABSTRACT FROM AUTHOR]

Aim Obstructive coronary artery disease (CAD) in proximal coronary segments is associated with a poor prognosis. However, the relative importance of plaque location regarding the risk for major adverse cardiovascular events (MACE) in patients with non-obstructive CAD has not been well defined. Methods and results From the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter (CONFIRM) registry, 4644 patients without obstructive CAD were included in this study. The degree of stenosis was classified as 0 (no) and 1–49% (non-obstructive). Proximal involvement was defined as any plaque present in the left main or the proximal segment of the left anterior descending artery, left circumflex artery, and right coronary artery. Extensive CAD was defined as segment involvement score of >4. During a median follow-up of 5.2 years (interquartile range 4.1–6.0), 340 (7.3%) MACE occurred. Within the non-obstructive CAD group (n = 2065), proximal involvement was observed in 1767 (85.6%) cases. When compared to non-obstructive CAD patients without proximal involvement, those with proximal involvement had an increased MACE risk (log-rank P = 0.033). Multivariate Cox analysis showed when compared to patients with no CAD, proximal non-obstructive CAD was associated with increased MACE risk [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.47–2.45, P < 0.001] after adjusting for extensive CAD and conventional cardiovascular risk factors; however, non-proximal non-obstructive CAD did not increase MACE risk (HR 1.26, 95% CI 0.79–2.01, P = 0.339). Conclusions Independent of plaque extent, proximal coronary involvement was associated with increased MACE risk in patients with non-obstructive CAD. The plaque location information by coronary computed tomography angiography may provide additional risk prediction over CAD extent in patients with non-obstructive CAD. [ABSTRACT FROM AUTHOR]

Aims  The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea. Methods and results  From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for ≥5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 ± 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1–6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29–1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02–1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD. Conclusion  In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk. [ABSTRACT FROM AUTHOR]

Aims In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent. Methods and results Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N  = 1849) and non-obstructive CAD (N  = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3–4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3–2.2) and 1.4 (95% CI 1.1–1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P  = 0.248), while it did in non-obstructive CAD (log-rank P  = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P -interaction = 0.004). Conclusion Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both. [ABSTRACT FROM AUTHOR]

Aims There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men. Methods and results A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 ± 13.2 years in men and 59.5 ± 13.3 years in women, P  = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55–65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P  = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P  = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P  = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P  = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41–0.98, P  = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD). Conclusion Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT01443637. [ABSTRACT FROM AUTHOR]

Aims Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA). Methods and results The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD. A boosted ensemble algorithm (XGBoost) was used, with data split into a training set (80%) on which 10-fold cross-validation was done and a test set (20%). Performance was assessed of the (1) ML model (using 25 clinical and demographic features), (2) ML + CACS, (3) CAD consortium clinical score, (4) CAD consortium clinical score + CACS, and (5) updated Diamond-Forrester (UDF) score. The study population comprised of 13 054 patients, of whom 2380 (18.2%) had obstructive CAD (≥50% stenosis). Machine learning with CACS produced the best performance [area under the curve (AUC) of 0.881] compared with ML alone (AUC of 0.773), CAD consortium clinical score (AUC of 0.734), and with CACS (AUC of 0.866) and UDF (AUC of 0.682), P  < 0.05 for all comparisons. CACS, age, and gender were the highest ranking features. Conclusion A ML model incorporating clinical features in addition to CACS can accurately estimate the pretest likelihood of obstructive CAD on CCTA. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Aims The long-term prognostic value of coronary computed tomography angiography (CCTA)-identified coronary artery disease (CAD) has not been evaluated in elderly patients (≥70 years). We compared the ability of coronary CCTA to predict 5-year mortality in older vs. younger populations. Methods and results From the prospective CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, we analysed CCTA results according to age <70 years (n = 7198) vs. ≥70 years (n = 1786). The severity of CAD was classified according to: (i) maximal stenosis degree per vessel: none, non-obstructive (1–49%), or obstructive (>50%); (ii) segment involvement score (SIS): number of segments with plaque. Cox-proportional hazard models assessed the relationship between CCTA findings and time to mortality. At a mean 5.6 ± 1.1 year follow-up, CCTA-identified CAD predicted increased mortality compared with patients with a normal CCTA in both <70 years [non-obstructive hazard ratio (HR) confidence interval (CI): 1.70 (1.19–2.41); one-vessel: 1.65 (1.03–2.67); two-vessel: 2.24 (1.21–4.15); three-vessel/left main: 4.12 (2.27–7.46), P < 0.001] and ≥70 years [non-obstructive: 1.84 (1.15–2.95); one-vessel: HR (CI): 2.28 (1.37–3.81); two-vessel: 2.36 (1.33–4.19); three-vessel/left main: 2.41 (1.33–4.36), P = 0.014]. Similarly, SIS was predictive of mortality in both <70 years [SIS 1–3: 1.57 (1.10–2.24); SIS ≥4: 2.42 (1.65–3.57), P < 0.001] and ≥70 years [SIS 1–3: 1.73 (1.07–2.79); SIS ≥4: 2.45 (1.52–3.93), P < 0.001]. CCTA findings similarly predicted long-term major adverse cardiovascular outcomes (MACE) (all-cause mortality, myocardial infarction, and late revascularization) in both groups compared with patients with no CAD. Conclusion The presence and extent of CAD is a meaningful stratifier of long-term mortality and MACE in patients aged <70 years and ≥70 years old. The presence of obstructive and non-obstructive disease and the burden of atherosclerosis determined by SIS remain important predictors of prognosis in older populations. [ABSTRACT FROM AUTHOR]

Objective: Data describing clinical relevance of chronic total occlusion (CTO) identified by coronary CT angiography (CCTA) have not been reported to date. We investigated the prognosis of CTO on CCTA.Methods: We identified 22 828 patients without prior known coronary artery disease (CAD), who were followed for a median of 26 months. Based on CCTA, coronary lesions were graded as normal (no atherosclerosis), non-obstructive (1%-49%), moderate-to-severe (50%-99%) or totally occluded (100%). All-cause mortality, and major adverse cardiac events defined as mortality, non-fatal myocardial infarction and late coronary revascularisation (≥90 days after CCTA) were assessed.Results: The distribution of patients with normal coronaries, non-obstructive CAD, moderate-to-severe CAD and CTO was 10 034 (44%), 7965 (34.9%), 4598 (20.1%) and 231 (1%), respectively. The mortality rate per 1000 person-years of CTO patients was non-significantly different from patients with moderate-to-severe CAD (22.95; 95% CI 12.71 to 41.45 vs 14.46; 95% CI 12.34 to 16.94; p=0.163), and significantly higher than of those with normal coronaries and non-obstructive CAD (p<0.001 for both). Among 14 382 individuals with follow-up for the composite end point, patients with CTO had a higher rate of events than those with moderate-to-severe CAD (106.56; 95% CI 76.51 to 148.42 vs 65.45; 95% CI 58.01 to 73.84, p=0.009). This difference was primarily driven by an increase in late revascularisations in CTO patients (27 of 35 events). After multivariable adjustment, compared with individuals with normal coronaries, the presence of CTO conferred the highest risk for adverse cardiac events (14.54; 95% CI 9.11 to 23.20, p<0.001).Conclusions: The detection of CTO on non-invasive CCTA is associated with increased rate of late revascularisation but similar 2-year mortality as compared with moderate-to-severe CAD.Trial Registration Number: NCT01443637. [ABSTRACT FROM AUTHOR]

Background: The extent to which the presence and extent of subclinical atherosclerosis by coronary computed tomography angiography influences a potential mortality benefit of statin is unknown. We evaluated the relationship between statin therapy, mortality, and subclinical atherosclerosis. Methods: In the CONFIRM study, patients with normal or non-obstructive plaque (<50% diameter stenosis) for whom data on baseline statin use was available were included. Coronary artery calcium (CAC) was quantified using the Agatston score. The extent of non-obstructive coronary atherosclerosis was quantified using the segment involvement score (SIS). 8,016 patients were followed for a median of 2.5 years with analysis of all-cause mortality and major adverse cardiac events (MACE) including all-cause mortality, myocardial infarction, unstable angina, target vessel revascularization, and coronary artery disease-related hospitalization. Results: 1.2% of patients experienced all-cause mortality. Patients not on baseline statin therapy had a stepwise increased risk of all-cause mortality by CAC (relative to CAC = 0; CAC 1–99: hazard ratio [HR] 1.65, CAC 100–299: HR 2.19, and CAC≥300: HR 2.98) or SIS (relative to SIS = 0; SIS 1: HR 1.62, SIS 2–3: 2.48 and SIS≥4: 2.95). Conversely, in patients on baseline statin therapy, there was no significant increase in mortality risk with increasing CAC (p value for interaction = 0.049) or SIS (p value for interaction = 0.007). The incidence of MACE was 2.1%. Similar to the all-cause mortality, the risk of MACE was increased with CAC or SIS strata in patient not on baseline statin therapy. However, this relation was not observed in patient on baseline statin therapy. Conclusion: In individuals with non-obstructive coronary artery disease, increased risk of adverse events occurs with increasing CAC or SIS who are not on baseline statin therapy. Statin therapy is associated with a mitigation of risk of cardiac events in the presence of increasing atherosclerosis, with no particular threshold of disease burden. [ABSTRACT FROM AUTHOR]

Extent of coronary atherosclerotic disease (CAD) burden on coronary computed tomography angiography (CCTA) as measured by segment involvement score (SIS) has a prognostic value. We sought to investigate the incremental prognostic value of ‘age adjusted SIS’ (aSIS), which may be a marker of premature atherosclerosis and vascular age. Consecutive patients were prospectively enrolled into the CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicentre) multinational observational study. Patients were followed for the outcome of all-cause death. aSIS was calculated on CCTA for each patient, and its incremental prognostic value was evaluated. A total of 22,211 patients [mean age 58.5 ± 12.7 years, 55.8% male) with a median follow-up of 27.3 months (IQR 17.8, 35.4)] were identified. After adjustment for clinical factors and presence of obstructive CAD, higher aSIS was associated with increased death on multivariable analysis, with hazard ratio (HR) 2.40 (1.83-3.16, p < 0.001), C-statistic 0.723 (0.700-0.756), net reclassification improvement (NRI) 0.36 (0.26-0.47, p < 0.001), and relative integrated discrimination improvement (IDI) 0.33 (p = 0.009). aSIS had HR 3.48 (2.33-5.18, p < 0.001) for mortality in those without obstructive CAD, compared to HR 1.79 (1.25-2.58, p = 0.02) in those with obstructive CAD. In conclusion, aSIS has an incremental prognostic value to traditional risk factors and obstructive CAD, and may enhance CCTA risk stratification. [ABSTRACT FROM AUTHOR]

Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value= 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults. [ABSTRACT FROM AUTHOR]

Background Left ventricular (LV) volumetric and functional parameters measured with cardiac computed tomography (cardiac CT) augment risk prediction and discrimination for future mortality. Gender- and age-specific standard values for LV dimensions and systolic function obtained by 64-slice cardiac CT are lacking. Methods and results 1155 patients from the Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry (54.5% males, mean age 53.1±12.4 years, range: 18-92 years) without known coronary artery disease (CAD), structural heart disease, diabetes, or hypertension who underwent cardiac CT for various indications were categorized according to age and sex. A cardiac CT data acquisition protocol was used that allowed volumetric measuring of LV function. Image interpretation was performed at each site. Patients with significant CAD(>50% stenosis) on cardiac CT were excluded from the analysis. Overall, mean left ventricular ejection fraction (LVEF) was higher in women when compared with men (66.6±7.7% vs. 64.6±8.1%, P < 0.001). This gender-difference in overall LVEF was caused by a significantly higher LVEF in women ≥70 years when compared with men ≥70 years (69.95±8.89% vs. 65.50±9.42%, P = 0.004). Accordingly, a significant increase in LVEF was observed with age (P = 0.005 for males and P < 0.001 for females), which was more pronounced in females (5.21%) than in males (2.6%). LV end-diastolic volume decreased in females from 122.48±27.87 (<40 years) to 95.56±23.17 (>70 years; P < 0.001) and in males from 155.22±35.07 (<40 years) to 130.26±27.18 (>70 years; P < 0.001). Conclusion Our findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values. [ABSTRACT FROM AUTHOR]

Aims To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary- computed tomographic angiography (CCTA). Methods and results We examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (n = 1171) and medical therapy (n = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (P for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11-0.47) and 5 years (HR 0.31, 95% CI 0.18-0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22-0.93) but not 5 years (HR 0.63, 95% CI 0.33-1.20). For low-risk CAD, there was no survival benefit at either time point. Conclusions Early revascularization was associated with reduced 1-year mortality in intermediate- and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD. [ABSTRACT FROM AUTHOR]

Aims To investigate the long-term performance of the CONFIRM score for prediction of all-cause mortality in a large patient cohort undergoing coronary computed tomography angiography (CCTA). Methods and results Patients with a 5-year follow-up from the international multicentre CONFIRM registry were included. The primary endpoint was all-cause mortality. The predictive value of the CONFIRM score over clinical risk scores (Morise, Framingham, and NCEP ATP III score) was studied in the entire patient population as well as in subgroups. Improvement in risk prediction and patient reclassification were assessed using categorical net reclassification index (NRI) and integrated discrimination improvement (IDI). During a median follow-up period of 5.3 years, 982 (6.5%) of 15 219 patients died. The CONFIRM score outperformed the prognostic value of the studied three clinical risk scores (c-indices: CONFIRM score 0.696, NCEP ATP III score 0.675, Framingham score 0.610, Morise score 0.606; c-index for improvement CONFIRM score vs. NCEP ATP III score 0.650, P < 0.0001). Application of the CONFIRM score allowed reclassification of 34% of patients when compared with the NCEP ATP III score, which was the best clinical risk score. Reclassification was significant as revealed by categorical NRI (0.06 with 95% CI 0.02 and 0.10, P = 0.005) and IDI (0.013 with 95% CI 0.01 and 0.015, P < 0.001). Subgroup analysis revealed a comparable performance in a variety of patient subgroups. Conclusions The CONFIRM score permits a significantly improved prediction of mortality over clinical risk scores for >5 years after CCTA. These findings are consistent in a large variety of patient subgroups. [ABSTRACT FROM AUTHOR]

Aims Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. Methods and results The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P< 0.001). Conclusions Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone. [ABSTRACT FROM AUTHOR]

Objective: Minimal data are available regarding the long-term mortality risk of subclinical atherosclerosis using coronary artery calcium (CAC) scoring among patients with a family history (FH) of coronary artery disease (CAD). The aim of the present analysis was to assess the prognostic utility of CAC scoring among cohorts of young and older patients with and without a FH of CAD.Methods: A total of 9715 consecutive asymptomatic patients, free of known CAD, underwent CAC scoring for cardiovascular risk assessment. The primary end point was all-cause mortality, with a median follow-up of 14.6 years. Unadjusted and risk-factor adjusted Cox proportional hazard modelling was employed. We calculated the area under the curve (AUC) from receiver operating characteristics analysis.Results: 15-year all-cause mortality rates ranged from 4.7% to 25.0% for FH patients and from 5.0% to 38.0% for non-FH patients with CAC scores of 0 to >400 (p<0.0001). Effect modification by age altered the mortality risk of CAC among FH patients. For patients aged >60 years with FH of CAD, there was a significant improvement in the AUC with CAC over CAD risk factors (AUC: 0.539 vs 0.725, p<0.001). No such improvement was observed in FH patients aged <60 years (AUC: 0.636 vs 0.626, p=0.67).Conclusion: CAC effectively stratified mortality risk of patients with and without FH of CAD. However, for younger and lower-risk FH cohorts, CAC screening did not provide additive prognostic information beyond that of the traditional cardiac risk factors. [ABSTRACT FROM AUTHOR]

Aims Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA. Methods and results The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9 ± 12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD (HR 0.95,95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance. Conclusion In our study population, survival after 5 years of follow-up did not differ significantly between patients with left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations. [ABSTRACT FROM AUTHOR]

Background: The extent of coronary artery calcification (CAC) and near-term adverse clinical outcomes are strongly related through 5 years of follow-up. Objective: To describe the ability of CAC scores to predict long-term mortality in persons without symptoms of coronary artery disease. Design: Observational cohort. Setting: Single-center, outpatient cardiology laboratory. Patients: 9715 asymptomatic patients. Measurements: Coronary artery calcification scoring and binary risk factor data were collected. The primary end point was time to all-cause mortality (median follow-up, 14.6 years). Univariable and multivariable Cox proportional hazards models were used to compare survival distributions. The net reclassification improvement statistic was calculated. Results: In Cox models adjusted for risk factors for coronary artery disease, the CAC score was highly predictive of all-cause mortality (P < 0.001). Overall 15-year mortality rates ranged from 3% to 28% for CAC scores from 0 to 1000 or greater (P < 0.001). The relative hazard for all-cause mortality ranged from 1.68 for a CAC score of 1 to 10 (P < 0.001) to 6.26 for a score of 1000 or greater (P < 0.001). The categorical net reclassification improvement using cut points of less than 7.5% to 22.5% or greater was 0.21 (95% Cl, 0.16 to 0.32). Limitations: Data collection was limited to a single center with generalizability limitations. Only binary risk factor data were available, and CAC was only measured once. Conclusion: The extent of CAC accurately predicts 15-year mortality in a large cohort of asymptomatic patients. Long-term estimates of mortality provide a unique opportunity to examine the value of novel biomarkers, such as CAC, in estimating important patient outcomes. [ABSTRACT FROM AUTHOR]

Objective Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA). Method Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease and results (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06=1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65-4.45, P < 0.001). [ABSTRACT FROM AUTHOR]

Aims We evaluated coronary artery disease (CAD) extent, severity, and major adverse cardiac events (MACEs) in never, past, and current smokers undergoing coronary CT angiography (CCTA). Methods and results We evaluated 9456 patients (57.1±12.3 years, 55.5% male) without known CAD (1588 current smokers; 2183 past smokers who quit ≥3 months before CCTA; and 5685 never smokers). By risk-adjusted Cox proportional-hazards models, we related smoking status to MACE (all-cause death or non-fatal myocardial infarction).We further performed 1:1:1 propensity matching for 1000 in each group evaluate event risk among individuals with similar age, gender,CAD risk factors, and symptom presentation. During a mean follow-up of 2.8±1.9 years, 297 MACE occurred. Compared with never smokers, current and past smokers had greater atherosclerotic burden including extent of plaque defined as segments with any plaque (2.1±2.8 vs. 2.6±3.2 vs. 3.1±3.3, P < 0.0001) and prevalence of obstructive CAD [1-vessel disease (VD): 10.6% vs. 14.9% vs. 15.2%, P < 0.001; 2-VD: 4.4% vs. 6.1% vs. 6.2%, P = 0.001; 3-VD: 3.1% vs. 5.2% vs. 4.3%, P < 0.001]. Compared with never smokers, current smokers experienced higher MACE risk [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.4-2.6, P < 0.001], while past smokers did not (HR 1.2, 95% CI 0.8-1.6, P = 0.35). Among matched individuals, current smokers had higher MACE risk (HR 2.6, 95% CI 1.6-4.2, P < 0.001), while past smokers did not (HR 1.3, 95% CI 0.7-2.4, P = 0.39). Similar findings were observed for risk of all-cause death. Conclusion Among patients without known CAD undergoing CCTA, current and past smokers had increased burden of atherosclerosis compared with never smokers; however, risk of MACE was heightened only in current smokers. [ABSTRACT FROM AUTHOR]

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p<0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p>0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Aim Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown. Methods and results From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0–10, 11–100, 101–400, 401–1000, >1000. For CCTA analysis, the number of obstructive vessels—as defined by the per-patient presence of a ≥50% luminal stenosis—was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) χ2, C-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th–75th percentile, 17–30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LRχ2, 25.34; increment in C-statistic, 0.24; NRI, 0.62, all P < 0.001), but not among those with CACS ≤100 (all P > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS. Conclusion Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS. [ABSTRACT FROM PUBLISHER]

Background: Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD. Methods: From the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic angiography were prospectively enrolled and followed for a median of 2.1 years. Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary stenosis) a luminal stenosis. CAC scores were calculated using the Agatston method. Univariable and multivariable Cox proportional hazard models were employed to estimate all-cause mortality and/or myocardial infarction (MI). Four-year death and death or MI rates were 1.9% and 3.3%. Results: Of the 4,380 patients with no luminal stenosis, 86% had CAC scores of <10 while those with a luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC score of ≥100. Among patients with no luminal stenosis, CAC was not predictive of all-cause mortality ( P = .44). However, among patients with a luminal stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to ≥400 ( P < .0001). The mortality hazard was 6.0 ( P = .004) and 13.3 ( P < .0001) for patients with a CAC score of 100-399 and ≥400. In patients with a luminal stenosis, CAC remained independently predictive in all-cause mortality ( P < .0001) and death or MI ( P < .0001) in multivariable models containing CAD risk factors and presenting symptoms. Conclusions: CAC allows for the identification of those at an increased hazard for death or MI in symptomatic patients with nonobstructive disease. From the CONFIRM registry, the extent of CAC was an independent estimator of long-term prognosis among symptomatic patients with luminal stenosis and may further define risk and guide preventive strategies in patients with nonobstructive CAD. [ABSTRACT FROM AUTHOR]

Aims Prior studies evaluating the prognostic utility of cardiac CT angiography (CCTA) have been largely constrained to an all-cause mortality endpoint, with other cardiac endpoints generally not reported. To this end, we sought to determine the relationship of extent and severity of coronary artery disease (CAD) by CCTA to risk of incident major adverse cardiac events (MACEs) (defined as death, myocardial infarction, and late revascularization). Methods and results We identified subjects without prior known CAD who underwent CCTA and were followed for MACE. CAD by CCTA was defined as none (0% luminal stenosis), mild (1–49% luminal stenosis), moderate (50–69% luminal stenosis), or severe (≥70% luminal stenosis), and ≥50% luminal stenosis was considered as obstructive. CAD severity was judged on per-patient, per-vessel, and per-segment basis. Time to MACE was estimated using univariable and multivariable Cox proportional hazards models. Among 15 187 patients (57 ± 12 years, 55% male), 595 MACE events (3.9%) occurred at a 2.4 ± 1.2 year follow-up. In multivariable analyses, an increased risk of MACE was observed for both non-obstructive [hazard ratio (HR) 2.43, P < 0.001] and obstructive CAD (HR: 11.21, P < 0.001) when compared with patients with normal CCTA. Risk-adjusted MACE increased in a dose–response relationship based on the number of vessels with obstructive CAD ≥50%, with increasing hazards observed for non-obstructive (HR: 2.54, P < 0.001), obstructive one-vessel (HR: 9.15, P < 0.001), two-vessel (HR: 15.00, P < 0.001), or three-vessel or left main (HR: 24.53, P < 0.001) CAD. Conclusion Among individuals without known CAD, non-obstructive, and obstructive CAD are associated with higher MACE rates, with different risk profiles based on age. [ABSTRACT FROM PUBLISHER]

Aims 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. Methods and results 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). Conclusion In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI. [ABSTRACT FROM PUBLISHER]

Background: Short-term risk scores, such as the Framingham risk score (FRS), frequently classify younger patients as low risk despite the presence of uncontrolled cardiovascular risk factors. Among patients with low FRS, estimation of lifetime risk is associated with significant differences in coronary arterial calcium scores (CACS); however, the relationship of lifetime risk to coronary atherosclerosis on coronary CT angiography (CCTA) and prognosis has not been studied. Methods and Results: We evaluated asymptomatic 20-60-year-old patients without diabetes or known coronary artery disease (CAD) within an international CT registry who underwent ≥64-slice CCTA. Patients with low FRS (<10%) were stratified as low (<39%) or high (≥39%) lifetime CAD risk, and compared for the presence and severity of CAD and prognosis for death, myocardial infarction, and late coronary revascularization (>90 days post CCTA). 1,863 patients of mean age of 47 years were included, with 48% of the low FRS patients at high lifetime risk. Median follow-up was 2.0 years. Comparing low-to-high lifetime risk, respectively, the prevalence of any CAD was 32% vs 41% ( P < .001) and ≥50% stenosis was 7.4% vs 9.6% ( P = .09). For those with CAD, subjects at low vs high lifetime risk had lower CACS (median 12 [IQR 0-94] vs 38 [IQR 0.05-144], P = .02) and less purely calcified plaque, 35% vs 45% ( P < .001). Prognosis did not differ due to low number of events. Conclusion: Assessment of lifetime risk among patients at low FRS identified those with the increase in CAD prevalence and severity and a higher proportion of calcified plaque. [ABSTRACT FROM AUTHOR]

Aims Obesity is associated with the presence of coronary artery disease (CAD) risk factors and cardiovascular events. We examined the relationship between body mass index (BMI) and the presence, extent, severity, and risk of CAD in patients referred for coronary computed tomographic angiography (CCTA). Methods and results We evaluated 13 874 patients from a prospective, international, multicentre registry of individuals without known CAD undergoing CCTA. We compared risk factors, CAD findings, and risk of all-cause mortality and non-fatal myocardial infarction (MI) amongst individuals with underweight (18.5–20.0 kg/m2), normal (20.1–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2) BMI. The mean follow-up was 2.4 ± 1.2 years with 143 deaths and 193 MIs. Among underweight, normal weight, overweight, and obese individuals, there was increasing prevalence of diabetes (7 vs.10% vs. 12 vs. 19%), hypertension (37 vs. 40% vs. 46 vs. 59%), and hyperlipidaemia (48 vs. 52% vs. 56 vs. 56%; P < 0.001 for trend). After multivariable adjustment, BMI was positively associated with the prevalence of any CAD [odds ratio (OR) 1.25 per +5 kg/m2, 95% confidence interval (CI): 1.20–1.30, P < 0.001] and obstructive (≥50% stenosis) CAD (OR: 1.13 per +5 kg/m2, 95% CI: 1.08–1.19, P < 0.001); a higher BMI was also associated with an increased number of segments with plaque (+0.26 segments per +5 kg/m2, 95% CI: 0.22–0.30, P < 0.001). Larger BMI categories were associated with an increase in all-cause mortality (P = 0.004), but no difference in non-fatal MI. After multivariable adjustment, a higher BMI was independently associated with increased risk of MI (hazards ratio: 1.28 per +5 kg/m2, 95% CI: 1.12–1.45, P < 0.001). Conclusions Amongst patients with suspected CAD referred for CCTA, individuals with increased BMI have greater prevalence, extent, and severity of CAD that is not fully explained by the presence of traditional risk factors. A higher BMI is independently associated with increased risk of intermediate-term risk of myocardial infarction. [ABSTRACT FROM PUBLISHER]

Aims 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. Methods and results 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). Conclusion 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. [ABSTRACT FROM PUBLISHER]

Aims To determine if coronary artery calcium (CAC) scoring is independently predictive of mortality in young adults and in the elderly population and if a young person with high CAC has a higher mortality risk than an older person with less CAC. Methods and results We studied a cohort of 44 052 asymptomatic patients referred for CAC scans for cardiovascular risk stratification. All-cause mortality rates (MRs) were calculated after stratifying by age groups (<45, 45–54, 55–64, 65–74, and ≥75) and CAC score (0, 1–100, 100–400, and >400). Multivariable Cox regression models were constructed to assess the independent value of CAC for predicting all-cause mortality in the <45- and ≥75-year-old age groups. The MR increased in both the <45- and ≥75-year-old age groups with an increasing CAC group. After multivariable adjustment, increasing CAC remained independently predictive of increased mortality compared with CAC = 0 [<45 age group, hazard ratio (95% confidence interval): CAC = 1–100, 2.3 (1.2–4.2); CAC = 100–400, 7.4 (3.3–16.6); CAC > 400, 34.6 (15.5–77.4); ≥75 age group: CAC = 1–100, 7.0 (2.4–20.8); CAC = 100–400, 9.2 (3.2–26.5); CAC > 400, 16.1 (5.8–45.1)]. Persons <45 years old with CAC = 100–400 and CAC > 400 had 2- and 10-fold increased MRs, respectively, compared with persons ≥75 with no CAC. Individuals ≥75 years old with CAC = 0 had a 5.6-year survival rate of 98%, similar to those in other age groups with CAC = 0 (5.6-year survival, 99%). Conclusion The value of CAC for predicting mortality extends to both elderly patients and those <45 years old. Elderly persons with no CAC have a lower MR than younger persons with high CAC. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--We examined the prevalence, extent, severity, and prognosis of coronary artery disease (CAD) in individuals with and without diabetes (DM) who are similar in CAD risk factors. RESEARCH DESIGN AND METHODS--We identified 23,643 consecutive individuals without known CAD undergoing coronary computed tomography angiography. A total of 3,370 DM individuals were propensity matched in a 1-to-2 fashion to 6,740 unique non-DM individuals. CAD was defined as none, nonobstructive (1-49% stenosis), or obstructive ($50% stenosis). All-cause mortality was assessed by risk-adjusted Cox proportional hazards models. RESULTS--At a 2.2-year follow-up, 108 (3.2%) and 115 (1.7%) deaths occurred among DM and non-DM individuals, respectively. Compared with non-DM individuals, DM individuals possessed higher rates of obstructive CAD (37 vs. 27%) and lower rates of having normal arteries (28 vs. 36%) (P < 0.0001). CAD extent was higher for DM versus non-DM individuals for obstructive one-vessel disease (19 vs. 14%), two-vessel disease (9 vs. 7%), and three-vessel disease (9 vs. 5%) (P < 0.0001 for comparison), with higher per-segment stenosis in the proximal and mid-segments of every coronary artery (P < 0.001 for all). Compared with non-DM individuals with no CAD, risk of mortality for DM individuals was higher for those with no CAD (hazard ratio 3.63 [95% CI 1.67-7.91]; P = 0.001), nonobstructive CAD (5.25 [2.56-10.8]; P < 0.001), one-vessel disease (6.39 [2.98-13.7]; P < 0.0001), two-vessel disease (12.33 [5.62227.1]; P < 0.0001), and three-vessel disease (13.25 [6.15-28.6]; P < 0.0001). CONCLUSIONS--Compared with matched non-DM individuals, DM individuals possess higher prevalence, extent, and severity of CAD. At comparable levels of CAD, DM individuals experience higher risk of mortality compared with non-DM individuals. [ABSTRACT FROM AUTHOR]

Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a novel non-invasive method for detection of coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. In addition to its high diagnostic performance, prior studies have shown that CCTA can provide important prognostic information, although these prior studies have been generally limited to small cohorts at single centers. The Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter registry, or CONFIRM, is a large, prospective, multinational, dynamic observational cohort study of patients undergoing CCTA. This registry currently represents more than 32,000 consecutive adults suspected of having CAD who underwent ≥64-detector row CCTA at 12 centers in 6 countries between 2005 and 2009. Based on its large sample size and adequate statistical power, the data derived from CONFIRM registry have and will continue to provide key answers to many important topics regarding CCTA. Based on its multisite international national design, the results derived from CONFIRM should be considered as more generalizable than prior smaller single-center studies. This article summarizes the current status of several studies from CONFIRM registry. [ABSTRACT FROM AUTHOR]

Aims: Early reports indicate a prognostic value of coronary artery disease (CAD) detection by coronary computed tomographic angiography (CCTA), although studies have been limited by small samples in single centres. Coronary computed tomographic angiographic measures of left ventricular ejection fraction (LVEF) to add incremental prognostic value beyond CAD detection have not been examined. [ABSTRACT FROM PUBLISHER]

Aims To determine the extent and prognostic significance of coronary artery calcium in asymptomatic smokers and non-smokers. Population data are available on the prognostic impact of smoking on atherosclerotic imaging measurements of the carotid and peripheral arteries. Limited data are available on the impact of cigarette smoking on the prognostic value of coronary calcium. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate the use of electron beam tomography (EBT) screening to predict allcause mortality in a large cohort of asymptomatic women and men. Methods and Results. We obtained mortality information from the National Death Index in 10,377 asymptomatic individuals (40% women) referred by primary care physicians for coronary calcification screening. The average follow-up period was 5 ± 3.5 years. Univariable and multivariable Cox proportional hazard models were developed to predict all-cause mortality. Women had a lower prevalence of coronary calcification and smaller calcification scores than men (p < 0.0001). Death rates were higher among older, diabetic, hypertensive, and currently smoking individuals both in women and in men. In unadjusted (chi-square = 82, p < 0.0001) as well as risk-adjusted (chi-square = 7, p = 0.007) Cox survival models, women had a greater probability of death than men in each strata of calcification. Relative risk (RR) ratios were increased 3.0-fold, 5.5-fold, and 5.5-fold, respectively, for women compared with men with coronary calcification scores of 101-399, 400-1000, and >1000 (p < 0.0001). Using receiver operating characteristics (ROC) curve analyses to assess coronary calcification added incremental prognostic value to Framingham risk scores (p < 0.0001). Conclusions. In this cohort of asymptomatic women, coronary calcification screening provided incremental prognostic information after adjustment for traditional risk factors. EBT may be a useful tool for risk stratification in women, where the early diagnosis of coronary heart disease (CHD) remains a strong challenge. [ABSTRACT FROM AUTHOR]

Background: The coronary artery calcium (CAC) score is an independent predictor of coronary heart disease. We sought to combine information from the CAC score with information from conventional cardiac risk factors to produce post-test risk estimates, and to determine whether the score may add clinically useful information. Methods: We measured the independent cross-sectional associations between conventional cardiac risk factors and the CAC score among asymptomatic persons referred for non-contrast electron beam computed tomography. Using the resulting multivariable models and published CAC score-specific relative risk estimates, we estimated post-test coronary heart disease risk in a number of different scenarios. Results: Among 9341 asymptomatic study participants (age 35-88 years, 40% female), we found that conventional coronary heart disease risk factors including age, male sex, self-reported hypertension, diabetes and high cholesterol were independent predictors of the CAC score, and we used the resulting multivariable models for predicting post-test risk in a variety of scenarios. Our models predicted, for example, that a 60-year-old non-smoking non-diabetic women with hypertension and high cholesterol would have a 47% chance of having a CAC score of zero, reducing her 10-year risk estimate from 15% (per Framingham) to 6-9%; if her score were over 100, however (a 17% chance), her risk estimate would be markedly higher (25-51% in 10 years). In low risk scenarios, the CAC score is very likely to be zero or low, and unlikely to change management. Conclusion: Combining information from the CAC score with information from conventional risk factors can change assessment of coronary heart disease risk to an extent that may be clinically important, especially when the pre-test 10-year risk estimate is intermediate. The attached spreadsheet makes these calculations easy. [ABSTRACT FROM AUTHOR]