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Author(s): D. O. Bittner [sup.1] , M. Goeller [sup.1] , Y. Zopf [sup.2] , S. Achenbach [sup.1] , M. Marwan [sup.1] Author Affiliations: (1) Department of Cardiology, Friedrich-Alexander University Erlangen-Nürnberg [...], Objectives Coronary artery calcification (CAC) can reliably predict cardiovascular events. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to inhibit vascular calcification on a cellular level and in animal models, however, the correlation in humans is controversial. Methods In symptomatic patients, CAC was quantified according to Agatstons' method using non-contrast coronary CT. We assessed the association of EPA and DHA with early-onset coronary atherosclerosis, defined as presence of CAC above the 75th Agatston-Score (AS) percentile in sex adjusted age categories. Erythrocyte fatty acid composition was analyzed with a standardized methodology. The percentage of EPA and DHA in relation to all fatty acids present in the erythrocyte membrane is regarded the Omega-3 Index®. Results Among 71 patients, 51 were below and 20 were above the 75th AS-percentile. No differences were seen in age, gender, cardiovascular risk factors, and relevant medication. In univariable analysis, significantly lower values for EPA (0.77%[0.63; 0.97] vs. 0.93%[0.72; 1.21]; p = 0.045), DHA (4.90%[4.12; 5.57] vs. 5.50%[4.58; 6.52]; p = 0.038) and the Omega-3 Index (5.73%[4.75; 6.35] vs. 6.22%[5.46; 7.71]; p = 0.034) were seen in patients above the 75th AS-percentile. All other fatty acids showed no significant differences. In multivariable analysis, the Omega-3 Index showed a significant inverse association with early onset of CAC (OR: 0.533 (95%CI: 0.303-0.938; p = 0.029)), independent of age, gender, statin use, and creatinine level (all p > 0.05). Conclusions Low levels of EPA and DHA (Omega-3 Index) are associated with early-onset coronary atherosclerosis. This finding needs to be validated in larger cohorts and might help understand the beneficial cardiovascular effects of omega-3 fatty acids.

Background: Plaque quantification from coronary computed tomography angiography has emerged as a valuable predictor of cardiovascular risk. Deep learning can provide automated quantification of coronary plaque from computed tomography angiography. We determined per-patient age- and sex-specific distributions of deep learning-based plaque measurements and further evaluated their risk prediction for myocardial infarction in external samples., Methods: In this international, multicenter study of 2803 patients, a previously validated deep learning system was used to quantify coronary plaque from computed tomography angiography. Age- and sex-specific distributions of coronary plaque volume were determined from 956 patients undergoing computed tomography angiography for stable coronary artery disease from 5 cohorts. Multicenter external samples were used to evaluate associations between coronary plaque percentiles and myocardial infarction., Results: Quantitative deep learning plaque volumes increased with age and were higher in male patients. In the combined external sample (n=1847), patients in the ≥75th percentile of total plaque volume (unadjusted hazard ratio, 2.65 [95% CI, 1.47-4.78]; P =0.001) were at increased risk of myocardial infarction compared with patients below the 50th percentile. Similar relationships were seen for most plaque volumes and persisted in multivariable analyses adjusting for clinical characteristics, coronary artery calcium, stenosis, and plaque volume, with adjusted hazard ratios ranging from 2.38 to 2.50 for patients in the ≥75th percentile of total plaque volume., Conclusions: Per-patient age- and sex-specific distributions for deep learning-based coronary plaque volumes are strongly predictive of myocardial infarction, with the highest risk seen in patients with coronary plaque volumes in the ≥75th percentile., Competing Interests: Dr Miller has received consulting fees and research support from Pfizer. S. Cadet, Dr Slomka, Dr Dey, and Dr Berman received software royalties from Cedars-Sinai Medical Center and report equity in APQ Health Inc. outside of the current work. Dr Berman, Dr Slomka, and Dr Dey hold a patent (US8885905B2/WO2011069120A1, Method and System for Plaque Characterization). Dr Grodecki reports grants or contracts from the Foundation for Polish Science and Polish Society of Cardiology. Dr Kwan reports partial effort support from the Doris Duke Charitable Foundation Grant. Dr Kuronuma is supported by grants from The Society of Nuclear Medicine and Molecular Imaging Wagner-Torizuka Fellowship and Nihon University School of Medicine Alumni Association. S. Cadet reports financial support from the Miriam and Sheldon G Adelson Medical Research Foundation Grant. Dr Nicholls reports grants or contracts from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and consulting fees from AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr Dweck reports consulting fees from Novartis, Jupiter Bioventures, and Silence Therapeutics; and payment or honoraria from Pfizer and Novartis. Dr Newby reports a grant from the British Heart Foundation (RE/24/130012, CH/09/002, and RG/F/22/110093) and Wellcome Trust. Dr Williams has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. The other authors report no conflicts.

Objectives: This study aims to assess the attenuation of pericoronary adipose tissue (PCAT) surrounding the proximal right coronary artery (RCA) in patients with aortic stenosis (AS) and undergoing transcatheter aortic valve replacement (TAVR). RCA PCAT attenuation is a novel computed tomography (CT)-based marker for evaluating coronary inflammation. Coronary artery disease (CAD) in TAVR patients is common and usually evaluated prior to intervention. The most sensible screening method and consequential treatment approach are unclear and remain a matter of ceaseless discussion. Thus, interest remains for safe and low-demand predictive markers to identify patients at risk for adverse outcomes postaortic valve replacement., Methods: This single-center retrospective study included patients receiving a standard planning CT scan prior to TAVR. Conventional CAD diagnostic tools, such as coronary artery calcium score and significant stenosis via invasive coronary angiography and coronary computed tomography angiography, were determined in addition to RCA PCAT attenuation using semiautomated software. These were assessed for their relationship with major adverse cardiovascular events (MACE) during a 24-month follow-up period., Results: From a total of 62 patients (mean age: 82 ± 6.7 years), 15 (24.2%) patients experienced an event within the observation period, 10 of which were attributed to cardiovascular death. The mean RCA PCAT attenuation was higher in patients enduring MACE than that in those without an endpoint (-69.8 ± 7.5 vs. -74.6 ± 6.2, P  = 0.02). Using a predefined cutoff of >-70.5 HU, 20 patients (32.3%) with high RCA PCAT attenuation were identified, nine (45%) of which met the endpoint within 2 years after TAVR. In a multivariate Cox regression model including conventional CAD diagnostic tools, RCA PCAT attenuation prevailed as the only marker with significant association with MACE ( P  = 0.02). After dichotomization of patients into high- and low-RCA PCAT attenuation groups, high attenuation was related to greater risk of MACE (hazard ration: 3.82, P  = 0.011)., Conclusion: RCA PCAT attenuation appears to have predictive value also in a setting of concomitant AS in patients receiving TAVR. RCA PCAT attenuation was more reliable than conventional CAD diagnostic tools in identifying patients at risk for MACE ., Competing Interests: DML reports personal fees from Boston Scientific. VOP and EN have received speaker fees from Bayer AG and Siemens Healthineers as well as educational grants from Bayer AG and NeoSoft. DD has received software royalties from Cedars-Sinai Medical Center and has a patent. CB received speaker fees from Siemens Healthineers. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Steyer, Mas-Peiro, Leistner, Puntmann, Nagel, Dey, Goeller, Koch, Booz, Vogl and Martin.)

Background: Increased pericoronary adipose tissue (PCAT) attenuation derived from coronary computed tomography (CT) angiography (CTA) relates to coronary inflammation and cardiac mortality. We aimed to investigate the association between CT-derived characterization of different cardiac fat compartments and myocardial ischemia as assessed by computed fractional flow reserve (FFRCT)., Methods: In all, 133 patients (median 64 y, 74% male) with coronary artery disease (CAD) underwent CTA including FFRCT measurement followed by invasive FFR assessment (FFRINVASIVE). CT attenuation and volume of PCAT were quantified around the proximal right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX). Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT; all intrathoracic adipose tissue outside the pericardium) were quantified in noncontrast cardiac CT datasets., Results: Median FFRCT was 0.86 [0.79, 0.91] and median FFRINVASIVE was 0.87 [0.81, 0.93]. Subjects with the presence of myocardial ischemia (n=26) defined by an FFRCT-threshold of ≤0.75 showed significantly higher RCA PCAT attenuation than individuals without myocardial ischemia (n=107) (-75.1±10.8 vs. -81.1±10.6 HU, P=0.011). In multivariable analysis adjusted for age, body mass index, sex and risk factors, increased RCA PCAT attenuation remained a significant predictor of myocardial ischemia. Between individuals with myocardial ischemia compared with individuals without myocardial ischemia, there was no significant difference in the volume and CT attenuation of EAT and PAT or in the PCAT volume of RCA, LAD, and LCX., Conclusions: Increased RCA PCAT attenuation is associated with the presence of myocardial ischemia as assessed by FFR, while PCAT volume, EAT, and PAT are not., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Various pro- and anti-inflammatory biomarkers are involved in the process of atherosclerosis. We analyzed the association of different biomarkers with coronary plaque volume and vulnerable plaque subcomponents., Methods: In 301 patients undergoing coronary CT angiography (CTA), total coronary plaque volume (TPV) and subcomponents including non-calcified plaque volume (NCPV) and vulnerable plaque burden were quantified using semi-automated software. Serum was analyzed for various cytokines., Results: Out of 301 patients, 207 (69%) were male. The mean age was 59 ± 10 years. Patients were divided using the median of TPV, NCPV and vulnerable plaque burden. In univariable analysis, patients with high TPV, high NCPV and high vulnerable plaque burden showed significant higher serum levels for IFNƔ, IL-1a, -2, -4, -10 and -17 and significant lower levels for IL-8 and MCP-1 (all p < 0.05). Multivariable analysis showed positive associations between high vulnerable plaque burden, IL-1a (OR 2.60, p = 0.001) and Eotaxin (OR 1.89, p = 0.020), and inverse association to MCP-1 (OR 0.33, p < 0.001), independent of age, gender and CVRF. In exploratory subanalyses, patients with presence of atherosclerosis (n = 247; 82%) showed significantly higher levels of IL-17 in all subgroups with high vulnerable plaque burden, irrespective of overall plaque volume (all p < 0.001)., Conclusions: The cytokine profile significantly differs between patients with high and low coronary plaque volume. IL-1a and IL-17 seem to play a major proatherogenic role in vulnerable plaque formation, whereas MCP-1 paradoxically portends protective effects. Longitudinal studies with serial cytokine testing are needed to identify potential targets for therapeutic interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H 2 S) is considered a potentially neuroprotective substance, but the most effective route of application and the underlying mechanism remain to be determined., Methods: Ischemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). H 2 S was then applied by inhalation (80 ppm at 0, 1.5, and 3 h after reperfusion) or by intravenous administration of the slow-releasing H 2 S donor GYY 4137. After 24 h, the retinas were harvested for Western blotting, qPCR, and immunohistochemical staining. Retinal ganglion cell survival was evaluated 7 days after ischemia., Results: Both inhalative and intravenously delivered H 2 S reduced retinal ganglion cell death with a better result from inhalative application. H 2 S inhalation for 1.5 h, as well as GYY 4137 treatment, increased p38 phosphorylation. Both forms of application enhanced the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhalation showed a significant increase at all three time points. H 2 S treatment also reduced apoptotic and inflammatory markers, such as caspase-3, intracellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). The protective effect of H 2 S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H 2 S also reduced the heat shock response including heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) and the expression of radical scavengers such as superoxide dismutases (SOD1, SOD2) and catalase., Conclusion: Hydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H 2 S and intravenous GYY 4137 administrations can improve neuronal cell survival.

Objectives: The aim of this study was to precisely phenotype culprit and nonculprit lesions in myocardial infarction (MI) and lesions in stable coronary artery disease (CAD) using coronary computed tomography angiography (CTA)-based radiomic analysis., Background: It remains debated whether any single coronary atherosclerotic plaque within the vulnerable patient exhibits unique morphology conferring an increased risk of clinical events., Methods: A total of 60 patients with acute MI prospectively underwent coronary CTA before invasive angiography and were matched to 60 patients with stable CAD. For all coronary lesions, high-risk plaque (HRP) characteristics were qualitatively assessed, followed by semiautomated plaque quantification and extraction of 1,103 radiomic features. Machine learning models were built to examine the additive value of radiomic features for discriminating culprit lesions over and above HRP and plaque volumes., Results: Culprit lesions had higher mean volumes of noncalcified plaque (NCP) and low-density noncalcified plaque (LDNCP) compared with the highest-grade stenosis nonculprits and highest-grade stenosis stable CAD lesions (NCP: 138.1 mm 3 vs 110.7 mm 3 vs 102.7 mm 3 ; LDNCP: 14.2 mm 3 vs 9.8 mm 3 vs 8.4 mm 3 ; both P trend  < 0.01). In multivariable linear regression adjusted for NCP and LDNCP volumes, 14.9% (164 of 1,103) of radiomic features were associated with culprits and 9.7% (107 of 1,103) were associated with the highest-grade stenosis nonculprits (critical P < 0.0007) when compared with highest-grade stenosis stable CAD lesions as reference. Hierarchical clustering of significant radiomic features identified 9 unique data clusters (latent phenotypes): 5 contained radiomic features specific to culprits, 1 contained features specific to highest-grade stenosis nonculprits, and 3 contained features associated with either lesion type. Radiomic features provided incremental value for discriminating culprit lesions when added to a machine learning model containing HRP and plaque volumes (area under the receiver-operating characteristic curve 0.86 vs 0.76; P = 0.004)., Conclusions: Culprit lesions and highest-grade stenosis nonculprit lesions in MI have distinct radiomic signatures compared with lesions in stable CAD. Within the vulnerable patient may exist individual vulnerable plaques identifiable by coronary CTA-based precision phenotyping., Competing Interests: Funding Support and Author Disclosures This study was supported in part by grants from the National Heart, Lung, and Blood Institute (1R01HL133616 and 1R01HL148787-01A1). Outside of the current work, Drs Cadet, Slomka, and Dey have received software royalties from Cedars-Sinai Medical Center. Drs Slomka and Dey hold a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization). 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: We evaluated the influence of image reconstruction kernels on the diagnostic accuracy of CT-derived fractional flow reserve (FFR CT ) compared to invasive FFR in patients with coronary artery disease., Methods: Sixty-nine patients, in whom coronary CT angiography was performed and who were further referred for invasive coronary angiography with FFR measurement via pressure wire, were retrospectively included. CT data sets were acquired using a third-generation dual-source CT system and rendered with medium smooth (Bv40) and sharp (Bv49) reconstruction kernels. FFR CT was calculated on-site using prototype software. Coronary stenoses with invasive FFR ≤ 0.80 were classified as significant. Agreement between FFR CT and invasive FFR was determined for both reconstruction kernels., Results: One hundred analyzed vessels in 69 patients were included. Twenty-five vessels were significantly stenosed according to invasive FFR. Using a sharp reconstruction kernel for FFR CT resulted in a significantly higher correlation with invasive FFR (r = 0.74, p < 0.01 vs. r = 0.58, p < 0.01; p = 0.04) and a higher AUC in ROC curve analysis to correctly identify/exclude significant stenosis (AUC = 0.92 vs. AUC = 0.82 for sharp vs. medium smooth kernel, respectively, p = 0.02). A FFR CT value of ≤ 0.8 using a sharp reconstruction kernel showed a sensitivity of 88% and a specificity of 92% for detecting ischemia-causing lesions, resulting in a diagnostic accuracy of 91%. The medium smooth reconstruction kernel performed worse (sensitivity 60%, specificity 89%, accuracy 82%)., Conclusion: Compared to invasively measured FFR, FFR CT using a sharp image reconstruction kernel shows higher diagnostic accuracy for detecting lesions causing ischemia, potentially altering decision-making in a clinical setting., Key Points: • Image reconstruction parameters influence the diagnostic accuracy of simulated fractional flow reserve derived from coronary computed tomography angiography. • Using a sharp kernel image reconstruction algorithm delivers higher diagnostic accuracy compared to medium smooth kernel image reconstruction (gold standard invasive fractional flow reserve)., (© 2021. The Author(s).)

Background: Atherosclerotic plaque quantification from coronary CT angiography (CCTA) enables accurate assessment of coronary artery disease burden and prognosis. We sought to develop and validate a deep learning system for CCTA-derived measures of plaque volume and stenosis severity., Methods: This international, multicentre study included nine cohorts of patients undergoing CCTA at 11 sites, who were assigned into training and test sets. Data were retrospectively collected on patients with a wide range of clinical presentations of coronary artery disease who underwent CCTA between Nov 18, 2010, and Jan 25, 2019. A novel deep learning convolutional neural network was trained to segment coronary plaque in 921 patients (5045 lesions). The deep learning network was then applied to an independent test set, which included an external validation cohort of 175 patients (1081 lesions) and 50 patients (84 lesions) assessed by intravascular ultrasound within 1 month of CCTA. We evaluated the prognostic value of deep learning-based plaque measurements for fatal or non-fatal myocardial infarction (our primary outcome) in 1611 patients from the prospective SCOT-HEART trial, assessed as dichotomous variables using multivariable Cox regression analysis, with adjustment for the ASSIGN clinical risk score., Findings: In the overall test set, there was excellent or good agreement, respectively, between deep learning and expert reader measurements of total plaque volume (intraclass correlation coefficient [ICC] 0·964) and percent diameter stenosis (ICC 0·879; both p<0·0001). When compared with intravascular ultrasound, there was excellent agreement for deep learning total plaque volume (ICC 0·949) and minimal luminal area (ICC 0·904). The mean per-patient deep learning plaque analysis time was 5·65 s (SD 1·87) versus 25·66 min (6·79) taken by experts. Over a median follow-up of 4·7 years (IQR 4·0-5·7), myocardial infarction occurred in 41 (2·5%) of 1611 patients from the SCOT-HEART trial. A deep learning-based total plaque volume of 238·5 mm 3 or higher was associated with an increased risk of myocardial infarction (hazard ratio [HR] 5·36, 95% CI 1·70-16·86; p=0·0042) after adjustment for the presence of deep learning-based obstructive stenosis (HR 2·49, 1·07-5·50; p=0·0089) and the ASSIGN clinical risk score (HR 1·01, 0·99-1·04; p=0·35)., Interpretation: Our novel, externally validated deep learning system provides rapid measurements of plaque volume and stenosis severity from CCTA that agree closely with expert readers and intravascular ultrasound, and could have prognostic value for future myocardial infarction., Funding: National Heart, Lung, and Blood Institute and the Miriam & Sheldon G Adelson Medical Research Foundation., Competing Interests: Declaration of interests SC, PJS, DD, and DSB received software royalties from Cedars-Sinai Medical Center outside of the current work. DSB, PJS, and DD hold a single patent (US8885905B2/WO2011069120A1, Method and System for Plaque Characterisation). KP reports a non-financial advisory role with Kardiollytics. KG reports grants or contracts from the Foundation for Polish Science and Polish Society of Cardiology. ACK reports partial effort support from the Doris Duke Charitable Foundation Grant. KK reports grants or contracts from The Society of Nuclear Medicine and Molecular Imaging Wagner-Torizuka Fellowship and Nihon University School of Medicine Alumni Association. ET is supported by a grant from the British Heart Foundation. SC reports financial support from the Miriam & Sheldon G Adelson Medical Research Foundation Grant. SJN reports grants or contracts from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and consulting fees from AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. MDw reports consulting fees from Novartis, Jupiter Bioventures, and Silence Therapeutics; and payment or honoraria from Pfizer and Novartis. DEN reports a grant from the British Heart Foundation and Wellcome Trust. MCW reports a grant from the British Heart Foundation; declares payment or honoraria from Cannon Medical Systems; and a leadership or fiduciary roles with British Society of Cardiovascular Imaging, Society of Cardiovascular Computed Tomography, and European Society of Cardiovascular Radiology. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The ischemia-reperfusion injury (IRI) of neuronal tissue, such as the brain and retina, leads to possible cell death and loss of function. Current treatment options are limited, but preliminary observations suggest a protective effect of hydrogen sulfide (H 2 S). However, the dosage, timing, and mechanism of inhaled H 2 S treatment after IRI requires further exploration., Methods: We investigated possible neuroprotective effects of inhaled H 2 S by inducing retinal ischemia-reperfusion injury in rats for the duration of 1 h (120 mmHg), followed by the administration of hydrogen sulfide (H 2 S) for 1 h at different time points (0, 1.5, and 3 h after the initiation of reperfusion) and at different H 2 S concentrations (120, 80, and 40 ppm). We quantified the H 2 S effect by conducting retinal ganglion cell counts in fluorogold-labeled animals 7 days after IRI. The retinal tissue was harvested after 24 h for molecular analysis, including qPCR and Western blotting. Apoptotic and inflammatory mediators, transcription factors, and markers for oxidative stress were investigated. Histological analyses of the retina and the detection of inflammatory cytokines in serum assays were also performed., Results: The effects of inhaled H 2 S were most evident at a concentration of 80 ppm administered 1.5 h after IRI. H 2 S treatment increased the expression of anti-apoptotic Bcl-2, decreased pro-apoptotic Bax expression, reduced the release of the inflammatory cytokines IL-1β and TNF-α, attenuated NF-κB p65, and enhanced Akt phosphorylation. H 2 S also downregulated NOX4 and cystathionine β-synthase. Histological analyses illustrated a reduction in TNF-α in retinal ganglion cells and lower serum levels of TNF-α in H 2 S-treated animals after IRI., Conclusion: After neuronal IRI, H 2 S mediates neuroprotection in a time- and dose-dependent manner. The H 2 S treatment modulated transcription factor NF-κB activation and reduced retinal inflammation.

Background: Increased attenuation of pericoronary adipose tissue (PCAT) around the right coronary artery (RCA) derived from coronary CTA might detect coronary inflammation. We investigated a potential association between RCA PCAT attenuation and serum levels of atherosclerosis-relevant cytokines and MACE (coronary revascularization, myocardial infarction and/or cardiac death)., Methods: Blood samples of 293 clinically stable individuals (59.0 ​± ​9.8 years, 69% males) were analyzed for atherosclerosis-relevant cytokines including interleukin (IL)-2, IL- 4, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-17, TNF-a, IP-10, CRP, MCP-1, MIP-1a, Eotaxin and GM-CSF. Subjects also underwent coronary calcium scoring (CCS) followed by CTA. PCAT CT attenuation was measured around the RCA using semi-automated software. Increased RCA PCAT attenuation was defined as PCAT attenuation above the 75th percentile (>-73.5 HU). To assess MACE, 232 individuals were followed for a mean duration of 9.6 ​± ​2.1 years., Results: In patients with increased RCA PCAT attenuation the serum levels of MCP-1 were increased (p ​< ​0.01), whereas levels of anti-inflammatory mediators IL-4 and -13 were significantly reduced (each p ​< ​0.05). Adipocytokine MCP-1 (r ​= ​0.23, p ​< ​0.01) and pro-inflammatory mediator IL-7 (r ​= ​0.12, p ​= ​0.04) showed a mild positive correlation with RCA PCAT attenuation, whereas anti-inflammatory mediators Il-4, -10 and -13 correlated inversely (each r < -0.12, each p ​< ​0.05). 40/232 patients experienced MACE during follow-up. In multivariable Cox regression analysis increased RCA PCAT attenuation was shown to be an independent predictor of MACE (HR 2.01, p ​= ​0.044)., Conclusions: Increased RCA PCAT CT attenuation shows a weak association with serum levels of selected atherosclerosis-relevant inflammatory biomarkers. Increased RCA PCAT attenuation is an independent predictor of MACE and may potentially guide future prevention strategies in stable patients., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)