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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.

AimObstructive 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 resultsFrom 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).ConclusionsIndependent 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.

PurposeIn this cohort study, 5-year data from the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry (ie, CONFIRM) were examined to identify associations of baseline aspirin and statin use with mortality, major adverse cardiovascular events (MACE), and myocardial infarction (MI) in individuals without substantial (≥50%) stenosis.Materials and methodsIn this prospective cohort study, all participants in the registry underwent coronary CT angiography and were classified as having no detectable coronary plaque or having nonobstructive coronary artery disease (CAD) (1%-49% stenosis). Participants with obstructive (≥50%) stenosis were excluded from analysis. The study commenced in June 2003 and was completed in March 2016. All unadjusted and risk-adjusted analyses utilized the Cox proportional hazard model with hospital sites modeled using shared frailty.ResultsA total of 6386 participants with no detectable plaque or with nonobstructive CAD were included (mean age, 56.0 years ± 13.3 [SD], 52% men). The mean follow-up period was 5.66 years ± 1.10. Nonobstructive CAD (n = 2815, 44% of all participants included in the study) was associated with a greater risk of all-cause mortality (10.6% [298 of 2815] vs 4.8% [170 of 3571], P < .001) compared to those without CAD (n = 3571, 56%). Baseline aspirin and statin use was documented for 1415 and 1429 participants, respectively, with nonobstructive CAD, and for 1560 and 1565 participants without detectable plaque, respectively. In individuals with nonobstructive CAD, baseline aspirin use was not associated with a reduction in MACE (10.9% [102 of 936] vs 14.7% [52 of 355], P = .06), all-cause mortality (9.6% [95 of 991] vs 10.9% [46 of 424], P = .468), or MI (4.4% [41 of 936] vs 6.2% [22 of 355], P = .18). On multivariate risk-adjusted analysis, baseline statin use was associated with a lower rate of MACE (hazard ratio, 0.59; 95% CI: 0.40, 0.87; P = .007). Neither therapy improved clinical outcomes for participants with no detectable plaque.ConclusionIn participants with nonobstructive CAD, baseline use of statins, but not of aspirin, was associated with improved clinical outcomes. Neither therapy was associated with benefit in participants without plaque.Keywords: Aspirin, Statin, Coronary Artery Disease, CT Angiography, Nonobstructive Coronary Artery DiseaseClinical trial registration no. NCT01443637 Supplemental material is available for this article. © RSNA, 2022See also the commentary by Canan and Navar in this issue.

AimsThe 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 resultsFrom 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.ConclusionIn 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.

AimsIn patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and resultsPatients 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).ConclusionAmong 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.

AimsWe aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders.MethodsOut of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability.ResultsA total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265).ConclusionCoronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone.

AimsThere 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 resultsA 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 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).ConclusionIncreased 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 registrationhttps://clinicaltrials.gov/ct2/show/NCT01443637.

AimsSymptom-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 resultsThe 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

AimsThe 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 resultsFrom the prospective CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, we analysed CCTA results according to age 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

ObjectivesThis study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS).BackgroundCurrent risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification.MethodsA total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971).ResultsThe mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort.ConclusionsThe new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/).

BackgroundCoronary artery calcification is a marker of underlying atherosclerotic vascular disease. The absence of coronary artery calcification is associated with a low prevalence of obstructive coronary artery disease (CAD), but it cannot be ruled out completely. We sought to develop a clinical tool that can be added to Agatston score of zero to rule out obstructive CAD with high accuracy.MethodsWe developed a clinical score retrospectively from a cohort of 4903 consecutive patients with an Agatston score of zero. Patients with prior diagnosis of CAD, coronary percutaneous coronary intervention, or surgical revascularization were excluded. Obstructive CAD was defined as any epicardial vessel diameter narrowing of ≥50%. The score was validated using an external cohort of 4290 patients with an Agatston score of zero from a multinational registry.ResultsThe score consisted of 7 variables: age, sex, typical chest pain, dyslipidemia, hypertension, family history, and diabetes mellitus. The model was robust with an area under the curve of 0.70 (95% CI, 0.65-0.76) in the derivation cohort and 0.69 (95% CI, 0.65-0.72) in the validation cohort. Patients were divided into 3 risk groups based on the score: low (≤6), intermediate (7-13), and high (≥14). Patients who score ≤6 have a negative likelihood ratio of 0.42 for obstructive CAD, whereas those who score ≥14 have a positive likelihood ratio of >5.5 for obstructive CAD. The outcome was ruled out in >98% of patients with a score ≤6 in the validation cohort.ConclusionsWe developed a score that may be used to identify the likelihood of obstructive CAD in patients with an Agatston score of zero, which may be used to direct the need for additional testing. However, the results of this retrospective analysis are hypothesis generating and before clinical implementation should be validated in a trial with a prospectively collected data.

IntroductionNon-statin therapy (NST) is used as second-line treatment when statin monotherapy is inadequate or poorly tolerated.ObjectiveTo determine the association of NST with plaque composition, alone or in combination with statins, in patients undergoing coronary computed tomography angiography (coronary CTA).MethodsFrom the multicenter CONFIRM registry, we analyzed individuals who underwent coronary CTA with known lipid-lowering therapy status and without prior coronary artery disease at baseline. We created a propensity score for being on NST, followed by stepwise multivariate linear regression, adjusting for the propensity score as well as risk factors, to determine the association between NST and the number of coronary artery segments with each plaque type (non-calcified (NCP), partially calcified (PCP) or calcified (CP)) and segment stenosis score (SSS).ResultsOf the 27,125 subjects in CONFIRM, 4,945 met the inclusion criteria; 371 (7.5%) took NST. At baseline, patients on NST had more prevalent risk factors and were more likely to be on concomitant cardiac medications. After multivariate and propensity score adjustment, NST was not associated with plaque composition: NCP (0.07 increase, 95% CI: -0.05, 0.20; p = 0.26), PCP (0.10 increase, 95% CI: -0.10, 0.31; p = 0.33), CP (0.18 increase, 95% CI: -0.10, 0.46; p = 0.21) or SSS (0.45 increase, 95% CI: -0.02,0.93; p = 0.06). The absence of an effect of NST on plaque type was not modified by statin use (p for interaction > 0.05 for all).ConclusionIn this cross-sectional study, non-statin therapy was not associated with differences in plaque composition as assessed by coronary CTA.

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

AimsCoronary 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 resultsOf 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: 18-41 months), 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

Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (

IntroductionMachine learning (ML) is a field in computer science that demonstrated to effectively integrate clinical and imaging data for the creation of prognostic scores. The current study investigated whether a ML score, incorporating only the 16 segment coronary tree information derived from coronary computed tomography angiography (CCTA), provides enhanced risk stratification compared with current CCTA based risk scores.MethodsFrom the multi-center CONFIRM registry, patients were included with complete CCTA risk score information and ≥3 year follow-up for myocardial infarction and death (primary endpoint). Patients with prior coronary artery disease were excluded. Conventional CCTA risk scores (conventional CCTA approach, segment involvement score, duke prognostic index, segment stenosis score, and the Leaman risk score) and a score created using ML were compared for the area under the receiver operating characteristic curve (AUC). Only 16 segment based coronary stenosis (0%, 1-24%, 25-49%, 50-69%, 70-99% and 100%) and composition (calcified, mixed and non-calcified plaque) were provided to the ML model. A boosted ensemble algorithm (extreme gradient boosting; XGBoost) was used and the entire data was randomly split into a training set (80%) and testing set (20%). First, tuned hyperparameters were used to generate a trained model from the training data set (80% of data). Second, the performance of this trained model was independently tested on the unseen test set (20% of data).ResultsIn total, 8844 patients (mean age 58.0 ± 11.5 years, 57.7% male) were included. During a mean follow-up time of 4.6 ± 1.5 years, 609 events occurred (6.9%). No CAD was observed in 48.7% (3.5% event), non-obstructive CAD in 31.8% (6.8% event), and obstructive CAD in 19.5% (15.6% event). Discrimination of events as expressed by AUC was significantly better for the ML based approach (0.771) vs the other scores (ranging from 0.685 to 0.701), P

Aim:The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown. Methods and results:From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P  0.05, for all). Conclusions:Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

In the face of an increasing world population and a subsequent need for an increase in sustainable and healthy food production, low trophic species, such as oysters, emerge as a promising alternative. However, regional variations in oyster production techniques, market dynamics, and consumption patterns create challenges for both the global and local industry’s growth. In this study, a descriptive qualitative analysis of oyster markets across seven Atlantic regions was carried out. The Pacific oyster (Crassostrea gigas) was found to be farmed in most Atlantic regions except the US but is classified as invasive in Sweden and potentially invasive in South Africa. Other farmed and/or harvested species include native species (C. gasar and C. rhizophorae) in Brazil, the American cupped oyster (C. virginica) in the US, and the European flat oyster (Ostrea edulis) in France, Sweden, and the US. In Irish farms, Pacific oysters are primarily for export to European markets. The marine aquaculture sectors of Sweden, South Africa, and Namibia, as well as Brazil’s farming for C. gasar, were found to be underdeveloped. This study also observed a variation in licensing, property rights, and regulatory frameworks. Financial challenges for small businesses, ecological implications of seed production techniques, biosecurity risks, and public health considerations are emphasized as critical areas for attention. This study offers valuable insights into the selected markets and can serve as a useful resource for policymakers, aquaculture practitioners, and stakeholders in optimizing global shellfish industry strategies.

ObjectivesThis study sought to assess clinical outcomes associated with the novel Coronary Artery Disease-Reporting and Data System (CAD-RADS) scores used to standardize coronary computed tomography angiography (CTA) reporting and their potential utility in guiding post-coronary CTA care.BackgroundClinical decision support is a major focus of health care policies aimed at improving guideline-directed care. Recently, CAD-RADS was developed to standardize coronary CTA reporting and includes clinical recommendations to facilitate patient management after coronary CTA.MethodsIn the multinational CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, 5,039 patients without known coronary artery disease (CAD) underwent coronary CTA and were stratified by CAD-RADS scores, which rank CAD stenosis severity as 0 (0%), 1 (1% to 24%), 2 (25% to 49%), 3 (50% to 69%), 4A (70% to 99% in 1 to 2 vessels), 4B (70% to 99% in 3 vessels or ≥50% left main), or 5 (100%). Kaplan-Meier and multivariable Cox models were used to estimate all-cause mortality or myocardial infarction (MI). Receiver-operating characteristic (ROC) curves were used to compare CAD-RADS to the Duke CAD Index and traditional CAD classification. Referrals to invasive coronary angiography (ICA) after coronary CTA were also assessed.ResultsCumulative 5-year event-free survival ranged from 95.2% to 69.3% for CAD-RADS 0 to 5 (p < 0.0001). Higher scores were associated with elevations in event risk (hazard ratio: 2.46 to 6.09; p < 0.0001). The ROC curve for prediction of death or MI was 0.7052 for CAD-RADS, which was noninferior to the Duke Index (0.7073; p = 0.893) and traditional CAD classification (0.7095; p = 0.783). ICA rates were 13% for CAD-RADS 0 to 2, 66% for CAD-RADS 3, and 84% for CAD-RADS ≥4A. For CAD-RADS 3, 58% of all catheterizations occurred within the first 30 days of follow-up. In a patient subset with available medication data, 57% of CAD-RADS 3 patients who received 30-day ICA were either asymptomatic or not receiving antianginal therapy at baseline, whereas only 32% had angina and were receiving medical therapy.ConclusionsCAD-RADS effectively identified patients at risk for adverse events. Frequent ICA use was observed among patients without severe CAD, many of whom were asymptomatic or not taking antianginal drugs. Incorporating CAD-RADS into coronary CTA reports may provide a novel opportunity to promote evidence-based care post-coronary CTA.

BackgroundThe 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.MethodsIn the CONFIRM study, patients with normal or non-obstructive plaque (

BackgroundLeft 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 results1155 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 (70 years; P < 0.001) and in males from 155.22 ± 35.07 (70 years; P < 0.001).ConclusionOur findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values.

AimsTo identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA).Methods and resultsWe 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.ConclusionsEarly 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.

Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events.

Background and aimsCoronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA.MethodsFrom 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA.ResultsAmong 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9-5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1-2.9, p = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0

AimsTo 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 resultsPatients 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.ConclusionsThe 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.

Age-adjusted coronary artery disease (CAD) burden identified on coronary computed tomography angiography predicts major adverse cardiovascular event (MACE) risk; however, it seldom contributes to clinical decision making because of a lack of nomographic data. We aimed to develop clinically pragmatic age- and sex-specific nomograms of CAD burden using coronary computed tomography angiography and to validate their prognostic use. Patients prospectively enrolled in phase I of the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes) were included (derivation cohort: n=21,132; 46% female) to develop CAD nomograms based on age-sex percentiles of segment involvement score (SIS) at each year of life (40-79 years). The relationship between SIS age-sex percentiles (SIS%) and MACE (all-cause death, myocardial infarction, unstable angina, and late revascularization) was tested in a nonoverlapping validation cohort (phase II, CONFIRM registry; n=3030, 44% female) by stratifying patients into 3 SIS% groups (≤50th, 51-75th, and >75th) and comparing annualized MACE rates and time to MACE using multivariable Cox proportional hazards models adjusting for Framingham risk and chest pain typicality. Age-sex percentiles were well fitted to second-order polynomial curves (men: R2=0.86±0.12; women: R2=0.86±0.14). Using the nomograms, there were 1576, 965, and 489 patients, respectively, in the ≤50th, 51-75th, and >75th SIS% groups. Annualized event rates were higher among patients with greater CAD burden (2.1% [95% confidence interval: 1.7%-2.7%], 3.9% [95% confidence interval: 3.0%-5.1%], and 7.2% [95% confidence interval: 5.4%-9.6%] in ≤50th, 51-75th, and >75th SIS% groups, respectively; P75th SIS% group; P

AimsTraditional 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 resultsThe 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).ConclusionsMachine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone.

ObjectivesThe goal of this study was to determine the long-term prognostic value of coronary computed tomography angiography (CTA) among patients with diabetes mellitus (DM) compared with nondiabetic subjects.BackgroundThe long-term prognostic value of coronary CTA in patients with DM is not well established.MethodsPatients enrolled in the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry with 5-year follow-up data were identified. The extent and severity of coronary artery disease (CAD) were analyzed at baseline coronary CTA and in relation to outcomes between diabetic and nondiabetic patients. CAD according to coronary CTA was defined as none (0% stenosis), nonobstructive (1% to 49% stenosis), or obstructive (≥50% stenosis). Time to death (and in a subgroup, time to major adverse cardiovascular event) was estimated by using multivariable Cox proportional hazards models.ResultsA total of 1,823 patients were identified as having DM with 5-year clinical follow-up and were propensity-matched to 1,823 patients without DM (mean age 61.8 ± 10.9 years; 54.4% male). Patients with DM did not exhibit a heightened risk of death compared with the propensity-matched nondiabetic subjects in the absence of CAD on coronary CTA (risk-adjusted hazard ratio [HR] of DM: 1.32; 95% confidence interval [CI]: 0.78 to 2.24; p = 0.296). Patients with DM were at increased risk of dying compared with nondiabetic subjects in the setting of nonobstructive CAD (in the propensity-matched cohort: HR, 2.10; 95% CI: 1.43 to 3.09; p < 0.001) with a mortality risk greater than nondiabetic subjects with obstructive disease (p < 0.001). In a risk-adjusted hazard analysis among patients with DM, both per-patient obstructive CAD and nonobstructive CAD conferred an increase in all-cause mortality risk compared with patients without atherosclerosis on coronary CTA (nonobstructive disease-HR: 2.07; 95% CI: 1.33 to 3.24; p = 0.001; obstructive disease-HR: 2.22; 95% CI: 1.47 to 3.36; p < 0.001).ConclusionsAmong patients with DM, nonobstructive and obstructive CAD according to coronary CTA were associated with higher rates of all-cause mortality and major adverse cardiovascular events at 5 years, and this risk was significantly higher than in nondiabetic subjects. Importantly, patients with DM without CAD according to coronary CTA were at a risk comparable to that of nondiabetic subjects.

ObjectivesThe purpose of this study was to examine sex-specific associations, if any, between per-vessel coronary artery disease (CAD) extent and the risk of major adverse cardiovascular events (MACE) over a 5-year study duration.BackgroundThe presence and extent of CAD diagnosed by coronary computed tomography angiography (CTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of sex on these findings.Methods5,632 patients (mean age 60.2 ± 11.8 years, 36.5% women) from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry were followed for 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction.ResultsObstructive CAD was more prevalent in men (42% vs. 26%; p < 0.001), whereas women were more likely to have normal coronary arteries (43% vs. 27%; p < 0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and nonobstructive CAD (HR: 2.16 for women, 2.56 for men; p < 0.001 for both), obstructive 1-vessel CAD (HR: 3.69 and 2.66; p < 0.001), 2-vessel CAD (HR: 3.92 and 3.55; p < 0.001), and 3-vessel/left main CAD (HR: 5.94 and 4.44; p < 0.001). Further exploratory analyses of atherosclerotic burden did not identify sex-specific patterns predictive of MACE.ConclusionsIn a large prospective coronary CTA cohort followed long-term, we did not observe an interaction of sex for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by coronary CTA for the risk of MACE in both women and men.

Abstract Background There is considerable evidence that platelets contribute to cancer growth and metastatic dissemination. In recent studies, altered mean platelet volume (MPV) has been associated with prognosis in different types of cancer. However, the prognostic role of the MPV in head and neck squamous cell cancer (HNSCC) is currently discussed controversially. The present study was performed to analyze and further elucidate the prognostic significance of the MPV in HNSCC. Methods A total of 319 oropharyngeal squamous cell cancer (OPSCC) patients treated with radiotherapy at a tertiary academic center were enrolled in the present study. Kaplan–Meier method as well as uni- and multivariate Cox proportional hazards were used to evaluate the impact of MPV on cancer-specific survival (CSS), locoregional control (LC) and recurrence-free survival (RFS). Results The median MPV was 10.30 fL (mean 10.26 ± 1.17fL). Univariate analyses showed a significant association of the MPV with CSS (HR 0.85, 95% CI 0.74–0.98, p = 0.025), LC (HR 0.86, 95% CI 0.74–0.99, p = 0.034) and RFS (HR 0.87, 95% CI 0.76–0.996; p = 0.043). In multivariate analysis, the MPV remained an independent prognostic factor for CSS (HR 0.77, 95% CI 0.63–0.93, p = 0.008), LC (HR 0.80, 95% CI 0.65–0.98, p = 0.030), and RFS (HR 0.83, 95% CI 0.685–0.999, p = 0.049). Conclusions Our findings indicate that the MPV is a prognostic marker in OPSCC patients and may contribute to future individual risk assessment.

BackgroundCoronary computed tomography angiography (coronary CTA) can prognosticate outcomes in patients without modifiable risk factors over medium term follow-up. This ability was driven by major adverse cardiovascular events (MACE).ObjectiveDetermine if coronary CTA could discriminate risk of mortality with longer term follow-up. In addition we sought to determine the long-term relationship to MACE.MethodsFrom 12 centers, 1884 patients undergoing coronary CTA without prior coronary artery disease (CAD) or any modifiable CAD risk factors were identified. The presence of CAD was classified as none (0% stenosis), mild (1% to 49% stenosis) and obstructive (≥50% stenosis severity). The primary endpoint was all-cause mortality and the secondary endpoint was MACE. MACE was defined as the combination of death, nonfatal myocardial infarction, unstable angina, and late target vessel revascularization (>90 days).ResultsMean age was 55.6 ± 14.5 years. At mean 5.6 ± 1.3 years follow-up, 145(7.7%) deaths occurred. All-cause mortality demonstrated a dose-response relationship to the severity and number of coronary vessels exhibiting CAD. Increased mortality was observed for >1 segment non-obstructive CAD (hazard ratio [HR]:1.73; 95% confidence interval [CI]: 1.07-2.79; p = 0.025), obstructive 1&2 vessel CAD (HR: 1.70; 95% CI: 1.08-2.71; p = 0.023) and 3-vessel or left main CAD (HR: 2.87; 95% CI: 1.57-5.23; p = 0.001). Both obstructive CAD (HR: 6.63; 95% CI: 3.91-11.26; p 5 years) was predicted by the presence of more than 1 segment of non-obstructive plaque, obstructive 1- or 2-vessel CAD and 3 vessel/left main CAD. Any CAD, whether non-obstructive or obstructive, predicted MACE over the same time period.