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Importance: Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasive method of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care., Objective: To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors., Design, Setting, and Participants: This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months., Exposures: Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign)., Main Outcomes and Measures: The primary end point was an adjudicated composite of MACE (defined as death, myocardial infarction, or unstable angina)., Results: The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73; 95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences in MACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25-4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95% CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39)., Conclusions and Relevance: High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque., Trial Registration: clinicaltrials.gov Indentifier: NCT01174550.

Background: It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain., Objectives: The primary aim of this study was to determine whether high-risk plaque features, as detected by CTA in the emergency department (ED), may improve diagnostic certainty of ACS independently and incrementally to the presence of significant CAD and clinical risk assessment in patients with acute chest pain but without objective evidence of myocardial ischemia or myocardial infarction (MI)., Methods: We included patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial. Readers assessed coronary CTA qualitatively for the presence of nonobstructive CAD (1% to 49% stenosis), significant CAD (≥50% or ≥70% stenosis), and the presence of at least 1 of the high-risk plaque features (positive remodeling, low <30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic regression analysis, we determined the association of high-risk plaque with ACS (MI or unstable angina pectoris) during the index hospitalization and whether this was independent of significant CAD and clinical risk assessment., Results: Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image quality (mean age 53.9 ± 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5; unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%; nonobstructive CAD in 217 patients [46.0%] and significant CAD with ≥50% stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95% CI: 1.8 to 43.3; p = 0.006) after adjustment for ≥50% stenosis (OR: 38.6; 95% CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of cardiovascular risk factors). Similar results were observed after adjustment for ≥70% stenosis., Conclusions: In patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin, presence of high-risk plaques on coronary CTA increased the likelihood of ACS independent of significant CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

Objectives: The size of the heart may predict major cardiovascular events (MACE) in patients with stable chest pain. We aimed to evaluate the prognostic value of 3D whole heart volume (WHV) derived from non-contrast cardiac computed tomography (CT). Methods: Among participants randomized to the CT arm of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), we used deep learning to extract WHV, defined as the volume of the pericardial sac. We compared the WHV across categories of cardiovascular risk factors and coronary artery disease (CAD) characteristics and determined the association of WHV with MACE (all-cause death, myocardial infarction, unstable angina; median follow-up: 26 months). Results: In the 3798 included patients (60.5 ± 8.2 years; 51.5% women), the WHV was 351.9 ± 57.6 cm3/m2. We found smaller WHV in no- or non-obstructive CAD, women, people with diabetes, sedentary lifestyle, and metabolic syndrome. Larger WHV was found in obstructive CAD, men, and increased atherosclerosis cardiovascular disease (ASCVD) risk score (p < 0.05). In a time-to-event analysis, small WHV was associated with over 4.4-fold risk of MACE (HR (per one standard deviation) = 0.221; 95% CI: 0.068–0.721; p = 0.012) independent of ASCVD risk score and CT-derived CAD characteristics. In patients with non-obstructive CAD, but not in those with no- or obstructive CAD, WHV increased the discriminatory capacity of ASCVD and CT-derived CAD characteristics significantly. Conclusions: Small WHV may represent a novel imaging marker of MACE in stable chest pain. In particular, WHV may improve risk stratification in patients with non-obstructive CAD, a cohort with an unmet need for better risk stratification. Key Points: • Heart volume is easily assessable from non-contrast cardiac computed tomography. • Small heart volume may be an imaging marker of major adverse cardiac events independent and incremental to traditional cardiovascular risk factors and established CT measures of CAD. • Heart volume may improve cardiovascular risk stratification in patients with non-obstructive CAD. [ABSTRACT FROM AUTHOR]

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/m2 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. [ABSTRACT FROM AUTHOR]

Background and aims Total coronary artery calcium (CAC) burden is associated with an increased cardiovascular risk, while local CAC may represent stable plaques. We determined differences in relationship of total CAC with acute coronary syndrome (ACS) and local CAC with culprit lesions in patients with suspected ACS. Methods We performed computed tomography (CT) for CAC and CT angiography to assess the presence of significant stenosis and high-risk plaque (positive remodeling, low CT attenuation, napkin-ring sign, spotty calcium) in 37 patients with ACS and 223 controls. Total and segmental Agatston scores were measured. Culprit lesions were assessed in subjects with ACS. Results Patients (n = 260) with vs. without ACS had higher total CAC score (median 229, 25 th -75 th percentile 75–517 vs. 27, 25 th -75 th percentile 0–99, p <0.001), higher prevalence of significant stenosis (78% vs. 7%, p <0.001) and high-risk plaque (95% vs. 59%, p <0.001). In those with ACS, culprit (n = 41) vs. non-culprit (n = 200) lesions, had similar segmental CAC score (median 22, 25 th -75 th percentile 4–71 vs. 14, 25 th -75 th percentile 0–51; p = 0.37 ), but higher prevalence of significant stenosis (81% vs. 11%, p <0.001) and high-risk plaque (76% vs. 51%, p =0.005). Significant stenosis (odds ratio 40.2, 95%CI 15.6–103.9, p <0.001) and high-risk plaque (odds ratio 3.4, 95%CI 1.3–9.1, p =0.02), but not segmental CAC score (odds ratio 1.0, 95%CI 1.0–1.0, p =0.47), were associated with culprit lesions of ACS. Conclusions Total CAC burden was associated with ACS but segmental CAC was not associated with culprit lesions. Our findings suggest that total but not local CAC is a marker of ACS risk and support the hypothesis that extensive local CAC is a marker of plaque stability. [ABSTRACT FROM AUTHOR]