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Background: Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein., Methods: REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score., Results: The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055)., Conclusions: Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015)., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Lung cancer screening with chest computed tomography (CT) prevents lung cancer death; however, fewer than 5% of eligible Americans are screened. CXR-LC, an open-source deep learning tool that estimates lung cancer risk from existing chest radiograph images and commonly available electronic medical record (EMR) data, may enable automated identification of high-risk patients as a step toward improving lung cancer screening participation., Objective: To validate CXR-LC using EMR data to identify individuals at high-risk for lung cancer to complement 2022 US Centers for Medicare & Medicaid Services (CMS) lung cancer screening eligibility guidelines., Design, Setting, and Participants: This prognostic study compared CXR-LC estimates with CMS screening guidelines using patient data from a large US hospital system. Included participants were persons who currently or formerly smoked cigarettes with an outpatient posterior-anterior chest radiograph between January 1, 2013, and December 31, 2014, with no history of lung cancer or screening CT. Data analysis was performed between May 2021 and June 2022., Exposures: CXR-LC lung cancer screening eligibility (previously defined as having a 3.297% or greater 12-year risk) based on inputs (chest radiograph image, age, sex, and whether currently smoking) extracted from the EMR., Main Outcomes and Measures: 6-year incident lung cancer., Results: A total of 14 737 persons were included in the study population (mean [SD] age, 62.6 [6.8] years; 7154 [48.5%] male; 204 [1.4%] Asian, 1051 [7.3%] Black, 432 [2.9%] Hispanic, 12 330 [85.2%] White) with a 2.4% rate of incident lung cancer over 6 years (361 patients with cancer). CMS eligibility could be determined in 6277 patients (42.6%) using smoking pack-year and quit-date from the EMR. Patients eligible by both CXR-LC and 2022 CMS criteria had a high rate of lung cancer (83 of 974 patients [8.5%]), higher than those eligible by 2022 CMS criteria alone (5 of 177 patients [2.8%]; P < .001). Patients eligible by CXR-LC but not 2022 CMS criteria also had a high 6-year incidence of lung cancer (121 of 3703 [3.3%]). In the 8460 cases (57.4%) where CMS eligibility was unknown, CXR-LC eligible patients had a 5-fold higher rate of lung cancer than ineligible (127 of 5177 [2.5%] vs 18 of 2283 [0.5%]; P < .001). Similar results were found in subgroups, including female patients and Black persons., Conclusions and Relevance: Using routine chest radiographs and other data automatically extracted from the EMR, CXR-LC identified high-risk individuals who may benefit from lung cancer screening CT.

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.)

Objectives: To investigate the association between directly measured density and morphology of coronary artery calcium (CAC) with cardiovascular disease (CVD) events, using computed tomography (CT)., Methods: Framingham Heart Study (FHS) participants with CAC in noncontrast cardiac CT (2002-2005) were included and followed until 2016. Participants with known CVD or uninterpretable CT scans were excluded. We assessed and correlated (Spearman) CAC density, CAC volume, and the number of calcified segments. Moreover, we counted morphology features including shape (cylindrical, spherical, semi-tubular, and spotty), location (bifurcation, facing pericardium, or facing myocardium), and boundary regularity. In multivariate Cox regression analyses, we associated all CAC characteristics with CVD events (CVD-death, myocardial infarction, stroke)., Results: Among 1330 included participants (57.8 ± 11.7 years; 63% male), 73 (5.5%) experienced CVD events in a median follow-up of 9.1 (7.8-10.1) years. CAC density correlated strongly with CAC volume (Spearman's ρ = 0.75; p < 0.001) and lower number of calcified segments (ρ = - 0.86; p < 0.001; controlled for CAC volume). In the survival analysis, CAC density was associated with CVD events independent of Framingham risk score (HR (per SD) = 2.09; 95%CI, 1.30-3.34; p = 0.002) but not after adjustment for CAC volume (p = 0.648). The extent of spherically shaped and pericardially sided calcifications was associated with fewer CVD events accounting for the number of calcified segments (HR (per count) = 0.55; 95%CI, 0.31-0.98; p = 0.042 and HR = 0.66; 95%CI, 0.45-0.98; p = 0.039, respectively)., Conclusions: Directly measured CAC density does not predict CVD events due to the strong correlation with CAC volume. The spherical shape and pericardial-sided location of CAC are associated with fewer CVD events and may represent morphological features related to stable coronary plaques., Key Points: • Coronary calcium density may not be independently associated with cardiovascular events. • Coronary calcium density correlates strongly with calcium volume. • Spherical shape and pericardial-sided location of CAC are associated with fewer CVD events.

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 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The ability to noninvasively assess arterial CD206+ macrophages may lead to improved understanding of human immunodeficiency virus (HIV)-associated cardiovascular disease., Methods: We trialed a novel macrophage-specific arterial imaging technique., Results: We demonstrated colocalization between technetium Tc 99m tilmanocept (99mTc-tilmanocept) and CD206+ macrophages ex vivo. In vivo application of 99mTc-tilmanocept single-photon emission computed tomography/computed tomography revealed high-level 99mTc-tilmanocept uptake across 20.4% of the aortic surface volume among HIV-infected subjects, compared with 4.3% among non-HIV-infected subjects (P = .009). Among all subjects, aortic high-level 99mTc-tilmanocept uptake was related to noncalcified aortic plaque volume (r = 0.87; P = .003) on computed tomographic angiography, and this relationship held when we controlled for HIV status., Conclusion: These first-in-human data introduce a novel macrophage-specific arterial imaging technique in HIV., Clinical Trials Registration: NCT02542371., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines are being applied to HIV-infected patients but have not been validated in this at-risk population, which is known to have a high prevalence of subclinical high-risk morphology (HRM) coronary atherosclerotic plaque., Objective: To compare recommendations for statins among HIV-infected subjects with/without HRM coronary plaque according to 2013 ACC/AHA versus 2004 Adult Treatment Panel III guidelines., Methods/design: Data from 108 HIV-infected subjects without known cardiovascular disease (CVD) or lipid-lowering treatment who underwent contrast-enhanced computed tomography angiography were analyzed. Recommendations for statin therapy according to 2013 versus 2004 guidelines were assessed among those with/without HRM coronary plaque., Results: Among all subjects, 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was 3.3% (1.6, 6.6), yet 36% of subjects had HRM coronary plaque. Among those with HRM coronary plaque, statins would be recommended for 26% by 2013 guidelines versus 10% by 2004 guidelines (P = 0.04). Conversely, among those without HRM coronary plaque, statins would be recommended for 19% by 2013 guidelines versus 7% by 2004 guidelines (P = 0.005). In multivariate modeling, while 10-year ASCVD risk score related to HRM coronary plaque burden (P = 0.02), so too did other factors not incorporated into 2013 guidelines., Conclusion: The 2013 ACC/AHA cholesterol guidelines recommend statin therapy for a higher percentage of subjects with and without HRM coronary plaque relative to 2004 guidelines. However, even by 2013 guidelines, statin therapy would not be recommended for the majority (74%) of HIV-infected subjects with subclinical HRM coronary plaque. Outcome studies are needed to determine the utility of new statin recommendations and the contribution of HRM coronary plaque to CVD events among HIV-infected subjects.