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Objectives: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis., Methods: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS., Results: Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed., Conclusions: Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all-cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18-1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03-1.07; p < 0.001), and n-terminal pro-b-type natriuretic peptide (NT-proBNP; aOR = 1.90, 95% CI 1.38-2.62; p < 0.001) were independently associated with obstructive CAD. In the 25-months median follow-up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27-5.03; p = 0.008) and NT-proBNP (aOR = 1.50, 95% CI 1.01-2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01-1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT-pro-BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT-proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk-stratify adults with HS for incident CAD and MACE., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD)., Objectives: The authors determined whether biomarkers of inflammation and myocardial injury-interleukin (IL)-6 and high-sensitivity cardiac troponin (hs-cTn)-were associated with the presence and extent of CAD and were independent predictors of major adverse cardiovascular events (MACEs) in stable chest pain., Methods: Using participants from the PROMISE trial, the authors measured hs-cTn I and IL-6 concentrations and analyzed computed tomography angiography (CTA) images in the core laboratory for CAD characteristics: significant stenosis (≥70%), high-risk plaque (HRP), Coronary Artery Disease Reporting and Data System (CAD-RADS) categories, segment involvement score (SIS), and coronary artery calcium (CAC) score. The primary endpoint was a composite MACE (death, myocardial infarction, or unstable angina)., Results: The authors included 1,796 participants (age 60.2 ± 8.0 years; 47.5% men, median follow-up 25 months). In multivariable linear regression adjusted for atherosclerotic cardiovascular disease (ASCVD) risk, hs-cTn was associated with HRP, stenosis, CAD-RADS, and SIS. IL-6 was only associated with stenosis and CAD-RADS. hs-cTn above median (1.5 ng/L) was associated with MACEs in univariable analysis (HR: 2.1 [95% CI: 1.3-3.6]; P = 0.006), but not in multivariable analysis adjusted for ASCVD and CAD. IL-6 above median (1.8 ng/L) was associated with MACEs in multivariable analysis adjusted for ASCVD and HRP (HR: 1.9 [95% CI: 1.1-3.3]; P = 0.03), CAC (HR: 1.9 [95% CI: 1.0-3.4]; P = 0.04), and SIS (HR: 1.8 [95% CI: 1.0-3.2]; P = 0.04), but not for stenosis or CAD-RADS. In participants with nonobstructive CAD (stenosis 1%-69%), the presence of both hs-cTn and IL-6 above median was strongly associated with MACEs (HR: 2.5-2.7 after adjustment for CAD characteristics)., Conclusions: Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs, indicating that myocardial injury and inflammation may each contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)., Competing Interests: Funding Support and Author Disclosures The PROMISE trial was funded by grants R01HL098237, R01HL098236, R01HL98305, and R01HL098235 from the National Heart, Lung, and Blood Institute (NHLBI). The funding source had no role in the design and conduct of this study, study analyses and interpretation of the data, the drafting and editing of the manuscript and its final contents, approval of the manuscript, and the decision to submit the manuscript for publication. The views expressed in this article do not necessarily represent the official views of the NHLBI. This article was prepared while Dr Ginsburg was employed at Duke University. The opinions expressed in this article are the author’s own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. Dr Ferencik has received a grant from the American Heart Association, National Institutes of Health; and has received consulting fees from Biograph, Inc. Dr Bittner was supported by a grant from the National Institutes of Health/NHLBI (5K24HL113128). Dr Lu has received grant support from the American Roentgen Ray Society Scholarship during the conduct of the study; and has received personal fees from PQBypass outside of the submitted work. Dr Meyersohn was supported by National Institutes of Health/NHLBI (T32 HL076136). Dr Douglas has received grant support from HeartFlow; and has served on a data and safety monitoring board for GE HealthCare outside of the submitted work. Dr Hoffmann has received grants from the American College of Radiology Imaging Network and HeartFlow during the conduct of the study, and from Siemens Healthcare outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD., Background: Among stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed., Methods: In PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD., Results: Of 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007)., Conclusions: Advanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events., Competing Interests: Funding Support and Author Disclosures The PROMISE trial was supported by grants from the National Heart Lung and Blood Institute, Bethesda, Maryland: R01HL098237, R01HL098236, R01HL098305, and R01HL098235. Dr Taron is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation; TA 1438/1-2); and is on the Speakers Bureau for Siemens Healthcare, unrelated to this work. Dr Osborne has received grant support from the National Institutes of Health (KL2TR002542) and Intrinsic Imaging, for unrelated work. Dr Meyersohn has received support from the National Institutes of Health/National Heart, Lung, and Blood Institute (T32 HL076136). Dr Lu has received consulting fees with PQBypass, a research grant from the Nvidia Corporation Academic Program, work as a co-investigator on research funded by AstraZeneca and Kowa, and grant support from the American Heart Association Precision Medicine Institute (18UNPG34030172) and the Harvard University Center for AIDS Research (NIH/NIAID 5P30AI060354-14). Dr Ferencik has received grant support from the American Heart Association (13FTF16450001). Dr Pagidipati has received research grants from Amgen, AstraZeneca, Baseline Study, Boehringer Ingelheim, Duke Clinical Research Institute, Eli Lilly & Company, Novo Nordisk Pharmaceutical Company, Regeneron Pharmaceuticals, Sanofi, and Verily Sciences Research Company; and consulting fees from AstraZeneca, Boehringer Ingelheim, Esperion Therapeutics, Eli Lilly & Company, and Novo Nordisk Pharmaceutical Company. Dr Douglas has received a research grant from HeartFlow. Dr Hoffmann has received a grant from the National Institutes of Health (K24HL113128), research support on behalf of the Massachusetts General Hospital from Duke University, HeartFlow, Kowa Company, and MedImmune/AstraZeneca; and consulting fees from Duke University and Recor Medical unrelated to this research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Hepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated with risk of MACE independently of the presence and extent of baseline coronary artery disease, assessed by comprehensive contrast-enhanced computed tomography angiography (CTA)., Methods: We conducted a nested cohort study of 3756 subjects (mean age, 60.6 years; 48.4% men) who underwent coronary CTA at 193 sites in North America, from July 2010 through September 2013, as part of the PROMISE study, which included noninvasive cardiovascular analyses of symptomatic outpatients without coronary artery disease. Independent core laboratory readers measured hepatic and splenic attenuation, using non-contrast computed tomography images to identify steatosis, and evaluated coronary plaques and stenosis in coronary CTA images. We collected data on participants' cardiovascular risk factors, presence of metabolic syndrome, and body mass index. The primary endpoint was an adjudicated composite of MACE (death, myocardial infarction, or unstable angina) during a median follow-up time of 25 months., Results: Among the 959 subjects who had steatosis (25.5% of the cohort), 42 had MACE (4.4%), whereas among the 2797 subjects without steatosis, 73 had MACE (2.6%) (hazard ratio [HR] for MACE in subjects with steatosis, 1.69; 95% CI, 1.16-2.48; P = .006 for MACE in subjects with vs without steatosis). This association remained after adjustment for atherosclerotic cardiovascular disease risk scores, significant stenosis, and metabolic syndrome (adjusted HR, 1.72; 95% CI, 1.16-2.54; P = .007) or obesity (adjusted HR, 1.75; 95% CI, 1.19-2.59; P = .005). Steatosis remained independently associated with MACE after adjustment for all CTA measures of plaques and stenosis., Conclusions: Hepatic steatosis is associated with MACE independently of other cardiovascular risk factors or extent of coronary artery disease. Strategies to reduce steatosis might reduce risk of MACE. ClinicalTrials.gov no: NCT01174550., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Obesity and metabolic syndrome are associated with major adverse cardiovascular events (MACE). However, whether distinct metabolic phenotypes differ in risk for coronary artery disease (CAD) and MACE is unknown. We sought to determine the association of distinct metabolic phenotypes with CAD and MACE., Research Design and Methods: We included patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) who underwent coronary computed tomography (CT) angiography. Obesity was defined as a BMI ≥30 kg/m 2 and metabolically healthy as less than or equal to one metabolic syndrome component except diabetes, distinguishing four metabolic phenotypes: metabolically healthy/unhealthy and nonobese/obese (MHN, MHO, MUN, and MUO). Differences in severe calcification (coronary artery calcification [CAC] ≥400), severe CAD (≥70% stenosis), high-risk plaque (HRP), and MACE were assessed using adjusted logistic and Cox regression models., Results: Of 4,381 patients (48.4% male, 60.5 ± 8.1 years of age), 49.4% were metabolically healthy (30.7% MHN and 18.7% MHO) and 50.6% unhealthy (22.3% MUN and 28.4% MUO). MHO had similar coronary CT findings as compared with MHN (severe CAC/CAD and HRP; P > 0.36 for all). Among metabolically unhealthy patients, those with obesity had similar CT findings as compared with nonobese ( P > 0.10 for all). However, both MUN and MUO had unfavorable CAD characteristics as compared with MHN ( P ≤ 0.017 for all). A total of 130 events occurred during follow-up (median 26 months). Compared with MHN, MUN (hazard ratio [HR] 1.61 [95% CI 1.02-2.53]) but not MHO (HR 1.06 [0.62-1.82]) or MUO (HR 1.06 [0.66-1.72]) had higher risk for MACE., Conclusions: In patients with stable chest pain, four metabolic phenotypes exhibit distinctly different CAD characteristics and risk for MACE. Individuals who are metabolically unhealthy despite not being obese were at highest risk in our cohort., (© 2021 by the American Diabetes Association.)

Objectives: The purpose of this study was to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) to traditional stenosis categories and the coronary artery calcium score (CACS) for predicting cardiovascular events in patients with stable chest pain and suspected coronary artery disease (CAD)., Background: The 2016 CAD-RADS has been established to standardize the reporting of CAD on coronary CT angiography (CTA)., Methods: PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial participants' CTAs were assessed by a central CT core laboratory for CACS, traditional stenosis-based categories, and modified CAD-RADS grade including high-risk coronary plaque (HRP) features. Traditional stenosis categories and CAD-RADS grade were compared for the prediction of the composite endpoint of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 25 months. Incremental prognostic value over traditional risk factors and CACS was assessed., Results: In 3,840 eligible patients (mean age: 60.4 ± 8.2 years; 49% men), 3.0% (115) experienced events. CAD-RADS (concordance statistic [C-statistic] 0.747) had significantly higher discriminatory value than traditional stenosis-based assessments (C-statistic 0.698 to 0.717; all p for comparison ≤0.001). With no plaque (CAD-RADS 0) as the baseline, the hazard ratio (HR) for an event increased from 2.43 (95% confidence interval [CI]: 1.16 to 5.08) for CAD-RADS 1 to 21.84 (95% CI: 8.63 to 55.26) for CAD-RADS 4b and 5. In stepwise nested models, CAD-RADS added incremental prognostic value beyond ASCVD risk score and CACS (C-statistic 0.776 vs. 0.682; p < 0.001), and added incremental value persisted in all CACS strata., Conclusions: These data from a large representative contemporary cohort of patients undergoing coronary CTA for stable chest pain support the prognostic value of CAD-RADS as a standard reporting system for coronary CTA., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Increased attenuation of pericoronary adipose tissue (PCAT) around the proximal right coronary artery (RCA) from coronary computed tomography angiography (CTA) has been shown to be associated with coronary inflammation and improved prediction of cardiac death over plaque features. Our aim was to investigate whether PCAT CT attenuation is related to progression of coronary plaque burden., Methods and Results: We analysed CTA studies of 111 stable patients (age 59.2 ± 9.8 years, 77% male) who underwent sequential CTA (3.4 ± 1.6 years between scans) with identical acquisition protocols. Total plaque (TP), calcified plaque (CP), non-calcified plaque (NCP), and low-density non-calcified plaque (LD-NCP) volumes and corresponding burden (plaque volume × 100%/vessel volume) were quantified using semi-automated software. PCAT CT attenuation (HU) was measured around the proximal RCA, the most standardized method for PCAT analysis. Patients with an increase in NCP burden (n = 51) showed an increase in PCAT attenuation, whereas patients with a decrease in NCP burden (n = 60) showed a decrease {4.4 [95% confidence interval (CI) 2.6-6.2] vs. -2.78 (95% CI -4.6 to -1.0) HU, P < 0.0001}. Changes in PCAT attenuation correlated with changes in the burden of NCP (r = 0.55, P < 0.001) and LD-NCP (r = 0.24, P = 0.01); but not CP burden (P = 0.3). Increased baseline PCAT attenuation ≥-75 HU was independently associated with increase in NCP (odds ratio 3.07, 95% CI 1.4-7.0; P < 0.008) and TP burden on follow-up CTA., Conclusion: PCAT attenuation measured from routine CTA is related to the progression of NCP and TP burden. This imaging biomarker may help to identify patients at increased risk of high-risk plaque progression and allow monitoring of beneficial changes from medical therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: To update pretest probabilities (PTP) for obstructive coronary artery disease (CAD ≥ 50%) across age, sex, and clinical symptom strata, using coronary computed tomography angiography (CTA) in a large contemporary population of patients with stable chest pain referred to non-invasive testing., Methods and Results: We included patients enrolled in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial and randomized to CTA. Exclusively level III-certified readers, blinded to demographic and clinical data, assessed the prevalence of CAD ≥ 50% in a central core lab. After comparing the recent European Society of Cardiology-Diamond and Forrester PTP (ESC-DF) with the actual observed prevalence of CAD ≥ 50%, we created a new PTP set by replacing the ESC-DF PTP with the observed prevalence of CAD ≥ 50% across strata of age, sex, and type of angina. In 4415 patients (48.3% men; 60.5 ± 8.2 years; 78% atypical angina; 11% typical angina; 11% non-anginal chest pain), the observed prevalence of CAD ≥ 50% was 13.9%, only one-third of the average ESC-DF PTP (40.6; P < 0.001 for difference). The PTP in the new set ranged 2-48% and were consistently lower than the ESC-DF PTP across all age, sex, and angina type categories. Initially, 4284/4415 (97%) patients were classified as intermediate-probability by the ESC-DF (PTP 15-85%); using the PROMISE-PTP, 50.2% of these patients were reclassified to the low PTP category (PTP < 15%)., Conclusion: The ESC-DF PTP overestimate vastly the actual prevalence of CAD ≥ 50%. A new set of PTP, derived from results of non-invasive testing, may substantially reduce the need for non-invasive tests in stable chest pain., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background High-risk plaque (HRP) features as detected by coronary computed tomography angiography (CTA) predict acute coronary syndrome (ACS). We sought to determine whether coronary CTA-specific definitions of HRP improve discrimination of patients with ACS as compared with definitions from intravascular ultrasound (IVUS). Methods and Results In patients with suspected ACS, randomized to coronary CTA in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II) trial, we retrospectively performed semiautomated quantitative analysis of HRP (including remodeling index, plaque burden as derived by plaque area, low computed tomography attenuation plaque volume) and degree of luminal stenosis and analyzed the performance of traditional IVUS thresholds to detect ACS. Furthermore, we derived CTA-specific thresholds in patients with ACS to detect culprit lesions and applied those to all patients to calculate the discriminatory ability to detect ACS in comparison to IVUS thresholds. Of 472 patients, 255 patients (56±7.8 years; 63% men) had coronary plaque. In 32 patients (6.8%) with ACS, culprit plaques (n=35) differed from nonculprit plaques (n=172) with significantly greater values for all HRP features except minimal luminal area (significantly lower; all P<0.01). IVUS definitions showed good performance while minimal luminal area (odds ratio: 6.82; P=0.014) and plaque burden (odds ratio: 5.71; P=0.008) were independently associated with ACS but not remodeling index (odds ratio: 0.78; P=0.673). Optimized CTA-specific thresholds for plaque burden (area under the curve: 0.832 versus 0.676) and degree of stenosis (area under the curve: 0.826 versus 0.721) showed significantly higher diagnostic performance for ACS as compared with IVUS-based thresholds (all P<0.05) with borderline significance for minimal luminal area (area under the curve: 0.817 versus 0.742; P=0.066). Conclusions CTA-specific definitions of HRP features may improve the discrimination of patients with ACS as compared with IVUS-based definitions. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT01084239.

Background: Coronary artery calcification (CAC) may impair diagnostic assessment of coronary computed tomography angiography (CTA). We determined whether CAC affects efficiency of coronary CTA in patients with suspected acute coronary syndrome (ACS)., Methods and Results: This is a pooled analysis of ACRIN-PA (American College of Radiology Imaging Network-Pennsylvania) 4005 and the ROMICAT-II trial (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) comparing an initial coronary CTA strategy to standard of care in acute chest pain patients. In the CTA arms, we investigated appropriateness of downstream testing, cost, and diagnostic yield to identify patients with obstructive coronary artery disease on subsequent invasive coronary angiography across CAC score strata (Agatston score: 0, >0-10, >10-100, >100-400, >400). Out of 1234 patients (mean age 51±8.8 years), 80 (6.5%) had obstructive coronary artery disease (≥70% stenosis) and 68 (5.5%) had ACS. Prevalence of obstructive coronary artery disease (1%-64%), ACS (1%-44%), downstream testing (4%-72%), and total (2337-8484 US$) and diagnostic cost (2310-6678 US$) increased across CAC strata ( P <0.001). As the increase in testing and cost were lower than the increase of ACS rate in patients with CAC>400, cost to diagnose one ACS was lowest in this group (19 283 US$ versus 464 399 US$) as compared with patients without CAC. The diagnostic yield of invasive coronary angiography was highest in patients with CAC>400 (87% versus 38%)., Conclusions: Downstream testing, total, and diagnostic cost increased with increasing CAC, but were found to be appropriate because obstructive coronary artery disease and ACS were more prevalent in patients with high CAC. In patients with acute chest pain undergoing coronary CTA, cost-efficient testing and excellent diagnostic yield can be achieved even with high CAC burden., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01084239 and NCT00933400., (© 2017 American Heart Association, Inc.)

Rationale and Objectives: Cardiovascular (CV) disease is predominately influenced by CV risk factors and coronary computed tomography angiography (CTA) is capable of detecting early-stage coronary artery disease. We sought to determine the influence of CV risk factors on the prevalence of nonobstructive atherosclerosis in patients with normal-appearing coronary arteries in invasive coronary angiography (ICA)., Materials and Methods: In this retrospective analysis, we included 60 consecutive symptomatic patients, having undergone ICA and coronary CTA. Coronary dual source CTA was performed using electrocardiogram-triggered retrospective gated image acquisition at 40%-70% of RR interval (tube voltage 100-120 kV, tube current time product 320-440 mAs, 60 mL contrast, and flow rate 6 mL/s)., Results: Out of 60 patients (32 men, mean age 61 ± 11 years) with a normal coronary artery appearance in ICA, 45 (75%) patients showed atherosclerotic plaque in CTA. Plaque was present in 14 of 60 (23%) left main, 41 of 60 (68%) left anterior descending, 21 of 60 (35%) circumflex coronary arteries, and 24 of 60 (40%) right coronary arteries. More than 15% of all coronary artery segments showed detectable plaques. Interobserver agreement ranged from good to very good on a per-patient, per-vessel, and per-segment level. Patients with presence of plaque were significantly older (P = 0.005) and showed higher incidence of arterial hypertension (P = 0.019) as compared to individuals without coronary plaque in dual source computed tomography., Conclusions: The prevalence of coronary atherosclerosis by CTA is substantial in symptomatic patients with normal invasive coronary angiogram. Hypertension and older age significantly influence the prevalence of atherosclerotic plaque and highlight the importance of risk-modifying therapy., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)