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Aims/hypothesis: Inhibitors of dipeptidyl peptidase-IV (DPP-IV), such as sitagliptin, increase glucagon-like peptide-1 (GLP-1) concentrations and are current treatment options for patients with type 2 diabetes mellitus. As patients with diabetes exhibit a high risk of developing severe atherosclerosis, we investigated the effect of sitagliptin on atherogenesis in Apoe mice. Methods: Apoe mice were fed a high-fat diet and treated with either sitagliptin or placebo for 12 weeks. Plaque size and plaque composition were analysed using Oil Red O staining and immunohistochemistry. Furthermore, in vitro experiments with the modified Boyden chamber and with gelatine zymography were performed to analyse the effects of GLP-1 on isolated human monocyte migration and metalloproteinase-9 (MMP-9) release. Results: Treatment of Apoe mice with sitagliptin significantly reduced plaque macrophage infiltration (the aortic root and aortic arch both showing a 67% decrease; p < 0.05) and plaque MMP-9 levels (aortic root showing a 69% and aortic arch a 58% reduction; both p < 0.01) compared with controls. Moreover, sitagliptin significantly increased plaque collagen content more than twofold (aortic root showing an increase of 58% and aortic arch an increase of 73%; both p < 0.05) compared with controls but did not change overall lesion size (8.1 ± 3.5% vs 5.1 ± 2.5% for sitagliptin vs controls; p = NS). In vitro, pretreatment of isolated human monocytes with GLP-1 significantly decreased cell migration induced by both monocyte chemotactic protein-1 and by the protein known as regulated on activation, normal T cell expressed and secreted (RANTES) in a concentration-dependent manner. Furthermore, GLP-1 significantly decreased MMP-9 release from isolated human monocyte-derived macrophages. Conclusions/interpretation: Sitagliptin reduces plaque inflammation and increases plaque stability, potentially by GLP-1-mediated inhibition of chemokine-induced monocyte migration and macrophage MMP-9 release. The effects observed may provide potential mechanisms for how DPP-IV inhibitors could modulate vascular disease in high-risk patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

The normal heart responds to changes in its metabolic milieu by changing relative oxidation rates of energy-providing substrates. We hypothesized that this flexibility is lost when genetically obese rats are fed a high-caloric, high-fat "Western" diet (WD). Male Zucker obese (ZO) and Zucker lean (ZL) rats were fed either control or WD composed of 10 kcal% and 45 kcal% fat, respectively, for 7 or 28 days. Cardiac triglycerides and mRNA transcript levels were measured in situ. Substrate oxidation rates and cardiac power were measured ex vivo. Hearts from ZO rats fed WD for 7 days showed decreased cardiac power and increased cardiac triglyceride content, but no change in oleate oxidation rates or mRNA transcript levels of pyruvate dehydrogenase kinase-4 (PDK-4), uncoupling protein-3 (UCP-3), and mitochondrial (MTE-1) and cytosolic thioesterase-1(CTE-1). When fed WD for 28 days, ZO rats showed no further decrease in cardiac power and no further increase in intramyocardial triglyceride levels compared to ZO rats fed the same diet for 7 days only, but did show significantly increased oleate oxidation rates and transcript levels of CTE-1, MTE-1, PDK-4, and UCP-3. In contrast, hearts from ZL rats fed WD showed increased rates of oleate oxidation and increased transcript levels of the fatty acid responsive genes investigated, and no further deterioration of contractile function. We conclude that exposing a genetic model of obesity to the nutrient stress of WD results in an early reversible loss of metabolic flexibility of the heart that is accompanied by contractile dysfunction. [ABSTRACT FROM AUTHOR]

Abstract Background The increasing understanding of atherosclerosis as an important risk factor for the development of acute ischemic events like ischemic stroke has stimulated increasing interest in non-invasive assessment of the structure, composition and burden of plaque depositions in the carotid artery wall. Vessel wall imaging by means of cardiovascular magnetic resonance (CMR) is conventionally done by 2D dual inversion recovery (DIR) techniques, which often fail in covering large volumes of interest as required in plaque burden assessment. Although the technique has been extended to 2D multislice imaging, its straight extension to 3D protocols is still limited by the prolonged acquisition times and incomplete blood suppression. A novel approach for rapid overview imaging of large sections of the carotid artery wall at isotropic spatial resolutions is presented, which omits excitation of the epiglottis. By the interleaved acquisition of two 3D stacks with the proposed motion sensitized segmented steady-state black-blood gradient echo technique (MSDS) the coverage of the carotid artery trees on both sides in reasonable scan times is enabled. Results 10 patients were investigated with the proposed technique and compared to conventional transversal DIR turbo spin and gradient echo approaches centered at the height of the carotid bifurcation. In all MSDS experiments sufficient black-blood contrast could be obtained over the entire covered volumes. The contrast to noise ratio between vessel and suppressed blood was improved by 73% applying the motion sensitizing technique. In all patients the suspicious areas of vessel wall thickening could be clearly identified and validated by the conventional local imaging approach. The average assessable vessel wall segment length was evaluated to be 18 cm. While in 50% of the cases motion artifacts could be appreciated in the conventional images, none were detected for the MSDS technique. Conclusion The proposed technique enables the time efficient coverage of large areas of the carotid arteries without compromising wall-lumen CNR to get an overview about detrimental alterations of the vessel wall. Thickening of the vessel wall can be identified and the suspicious segments can be targeted for subsequent high-resolution CMR. The exclusion of the epiglottis may further facilitate reduction of swallowing induced motion artifacts.

Background: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV)., Methods: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria., Results: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis., Conclusions: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants., (© 2023. The Author(s).)

Introduction: Chronic kidney disease (CKD) is an important cardiovascular risk factor. However, the relationship between CKD and myocardial strain as a parameter of myocardial function is still incompletely understood, particularly in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance imaging (CMR) feature tracking allows to analyze myocardial strain with high reproducibility. Therefore, the aim of the present study was to assess the relationship between CKD and myocardial strain as described by CMR in patients with ICM., Methods: We retrospectively performed CMR-based myocardial strain analysis in 89 patients with ICM and different stages of CKD, classified according to the KDIGO stages. In all patients, global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) analysis of left ventricular myocardium were performed. Furthermore, segmental longitudinal (SLS), circumferential (SCS) and radial strain (SRS) according to the AHA 16/17-segment model was determined., Results: Creatinine levels (GLS: r = 0.46, p < 0.001; GCS: r = 0.34, p = 0.001; GRS: r = - 0.4, p < 0.001), urea levels (GLS: r = 0.34, p = 0.001; GCS: r = 0.30, p = 0.005; GRS: r = - 0.31, p = 0.003) as well as estimated glomerular filtration rate (GLS: r = -0.40, p < 0.001; GCS: r = - 0.27, p = 0.012; GRS r = 0.34, p < 0.001) were significantly associated with global strains as determined by CMR. To further investigate the relationship between CKD and myocardial dysfunction, segmental strain analysis was performed: SLS was progressively impaired with increasing severity of CKD (KDIGO-1: - 11.93 ± 0.34; KDIGO-5: - 7.99 ± 0.38; p < 0.001 for KDIGO-5 vs. KDIGO-1; similar data for SCS and SRS). Interestingly, myocardial strain was impaired with CKD in both segments with and without scarring. Furthermore, in a multivariable analysis, eGFR was independently associated with GLS following adjustment for LV-EF, scar burden, diabetes, hypertension, age, gender, LV mass or LV mass index., Conclusion: CKD is related to impaired LV strain as assessed by CMR in patients with ICM. In our cohort, this relationship is independent of LV-EF, the extent of myocardial scarring, diabetes, hypertension, age, gender, LV mass or LV mass index., (© 2023. The Author(s).)

Competing Interests: Disclosures None.

Introduction: Myocardial infarction without obstructive coronary artery disease (MINOCA) is a heterogeneous clinical condition presenting with myocardial necrosis not due to an obstruction of a major coronary artery. Recently, a relevant role of coronary microvascular dysfunction (CMD) in the pathogenesis of MINOCA has been suggested; however, data on this are scarce. Particularly, it is unclear if CMD is equally present in all subtypes of MINOCA or differentially identifies one or more of these conditions. Therefore, the aim of this study was to assess CMD in all three coronary vessels of MINOCA patients, relating it with the clinical subtype., Methods: We retrospectively assessed coronary microvascular function in all three coronary territories by means of angiography-based index of microvascular resistance (aIMR) in 92 patients (64 with working diagnosis of MINOCA, 28 control patients). To further assess the association of CMD with MINOCA subtypes, MINOCA patients were subdivided according to clinical data in coronary cause (n = 13), takotsubo (n = 13), infiltrative or inflammatory cardiomyopathy (n = 9) or unclear (n = 29)., Results: Patients with working diagnosis of MINOCA showed a significantly elevated average aIMR compared to control patients (30.5 ± 7.6 vs. 22.1 ± 5.9, p < 0.001) as a marker of a relevant CMD; these data were consistent in all vessels. Among MINOCA subtypes, no significant difference in average aIMR could be detected between patients with coronary cause (33.2 ± 6.6), takotsubo cardiomyopathy (29.2 ± 6.9), infiltrative or inflammatory cardiomyopathy (28.1 ± 6.8) or unclear cause (30.6 ± 8.5; p = 0.412). Interestingly, aIMR was significantly elevated in the coronary vessel supplying the diseased myocardium compared with other vessels (31.9 ± 11.4 vs. 27.8 ± 8.2, p = 0.049)., Conclusion: Coronary microvascular dysfunction is a hallmark of all MINOCA subtypes. This study adds to the pathophysiological understanding of MINOCA and sheds light into the role of CMD in MINOCA., (© 2023. The Author(s).)

Introduction: Ischemia with no obstructive coronary disease (INOCA) is a frequent phenomenon in the cath lab. A possible cause is coronary microvascular dysfunction (CMD), which may be assessed by invasive testing with possible complications; therefore, less invasive approaches have emerged, such as the angiography-derived index of microvascular resistance (aIMR). The aim of our study was to investigate the association of single-vessel aIMR as a measure of CMD with areas of INOCA in stress testing., Methods: We measured aIMR in 286 vessels from 102 patients undergoing both stress cMRI and coronary angiography. Groups were (a) INOCA group (93 vessels, 32 patients); (b) coronary artery disease (CAD) control group (116 vessels, 42 patients) with ischemia due to relevant stenosis; and (c) control group (77 vessels, 28 patients) without ischemia or relevant stenosis., Results: INOCA patients presented higher mean aIMR (28.3 ± 5.7) compared to both CAD patients (17.4 ± 5.7, p < 0.001) and controls (22.1 ± 5.9, p < 0.001). Furthermore, in INOCA patients aIMR was significantly increased (33.0 ± 8.1 vs. 25.8 ± 6.3, p = 0.021) in vessels with vs. without ischemia. Single vessel aIMR presented a very good diagnostic efficiency in detecting INOCA [AUC 0.865 (0.804-0.925), optimal cut-off 27.1, p < 0.001]., Conclusion: CMD, as assessed by 3-vessel aIMR, co-localizes with and may explain the presence of ischemia in stress-cMRI in INOCA., Competing Interests: The 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., (Copyright © 2022 Milzi, Dettori, Lubberich, Burgmaier, Marx, Reith and Burgmaier.)

Introduction: Previously, an association between anatomic left main stem (LMS) lesion parameters, as described by intravascular ultrasound (IVUS) and fractional flow reserve (FFR), was shown. Quantitative flow ratio (QFR) is a novel, promising technique which can assess functional stenosis relevance based only on angiography. However, as little is known about the relationship between anatomic LMS parameters and QFR, it was thus investigated in this study. Methods: In 53 patients with LMS disease, we tested the association between anatomic assessment using OCT (n = 28) or IVUS (n = 25) on the one hand and functional assessment as determined by QFR on the other hand. LMS-QFR was measured using a dedicated approach, averaging QFR over left anterior descending (LAD) and circumflex (LCX) and manually limiting segment of interest to LMS. Results: The minimal luminal area of the LMS (LMS-MLA) as measured by intravascular imaging showed a consistent correlation with QFR (R = 0.61, p < 0.001). QFR could predict a LMS-MLA < 6 mm2 with very good diagnostic accuracy (AUC 0.919) and a LMS-MLA < 4.5 mm2 with good accuracy (AUC 0.798). Similar results were obtained for other stenosis parameters. Conclusions: QFR might be a valuable tool to assess LMS disease. Further studies focusing on patient outcomes are needed to further validate the effectiveness of this approach., Competing Interests: The authors declare no conflict of interest

Despite scientific and clinical advances during the last 50 years cardiovascular disease continues to be the main cause of death worldwide. Especially patients with diabetes display a massive increased cardiovascular risk compared to patients without diabetes. Over the last two decades we have learned that cardiometabolic and cardiovascular diseases are driven by inflammation. Despite the fact that the gastrointestinal tract is one of the largest leukocyte reservoirs of our bodies, the relevance of gut immune cells for cardiovascular disease is largely unknown. First experimental evidence suggests an important relevance of immune cells in the intestinal tract for the development of metabolic and cardiovascular disease in mice. Mice specifically lacking gut immune cells are protected against obesity, diabetes, hypertension and atherosclerosis. Importantly antibody mediated inhibition of leukocyte homing into the gut showed similar protective metabolic and cardiovascular effects. Targeting gut immune cells might open novel therapeutic approaches for the treatment of cardiometabolic and cardiovascular diseases., Competing Interests: Author FK served as a consultant to Bayer and Novo Nordisk and served as a speaker for Novo Nordisk. Author NM has received support for clinical trial leadership from Boehringer Ingelheim, Novo Nordisk, served as a consultant to Bayer, Boehringer Ingelheim, Merck, Novo Nordisk, AstraZeneca, BMS, received grant support from Boehringer Ingelheim, Merck, Novo Nordisk, and served as a speaker for Bayer, Boehringer Ingelheim, Merck, Novo Nordisk, Lilly, BMS, and AstraZeneca. Author ML received grants and personal fees from Boehringer Ingelheim, MSD, Novo Nordisk and personal fees from Amgen, Sanofi, Astra Zeneca, Bayer, Lilly, Daiichi Sankyo, Novarits, Amarin. 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., (Copyright © 2022 Ganesh, van der Vorst, Spiesshöfer, He, Burgmaier, Findeisen, Lehrke, Swirski, Marx and Kahles.)

Aims: Smokers are at increased risk of cardiovascular events. However, the exact mechanisms through which smoking influences cardiovascular disease resulting in accelerated atherosclerosis and vascular calcification are unknown. The aim of this study was to investigate effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification and to elucidate underlying mechanisms., Methods and Results: We assessed vascular calcification of 62 carotid lesions of both smoking and non-smoking patients using ex vivo micro-computed tomography (µCT) scanning. Calcification was present more often in carotid plaques of smokers (n = 22 of 30, 73.3%) compared to non-smokers (n = 11 of 32, 34.3%; P < 0.001), confirming higher atherosclerotic burden. The difference was particularly profound for microcalcifications, which was 17-fold higher in smokers compared to non-smokers. In vitro, nicotine-induced human primary VSMC calcification, and increased osteogenic gene expression (Runx2, Osx, BSP, and OPN) and extracellular vesicle (EV) secretion. The pro-calcifying effects of nicotine were mediated by Ca2+-dependent Nox5. SiRNA knock-down of Nox5 inhibited nicotine-induced EV release and calcification. Moreover, pre-treatment of hVSMCs with vitamin K2 ameliorated nicotine-induced intracellular oxidative stress, EV secretion, and calcification. Using nicotinic acetylcholine receptor (nAChR) blockers α-bungarotoxin and hexamethonium bromide, we found that the effects of nicotine on intracellular Ca2+ and oxidative stress were mediated by α7 and α3 nAChR. Finally, we showed that Nox5 expression was higher in carotid arteries of smokers and correlated with calcification levels in these vessels., Conclusion: In this study, we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD)., Methods: Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator., Results: Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness < 65 μm (odds ratio = 1.32 per each 10 μmol/L mannose change [95% confidence interval, 1.05-1.65]) and was an independent predictor of death (hazard ratio for mannose≥vs < 84.6 μmol/L: 4.0(95%CI, 1.4-11.3), p = 0.006)., Conclusion: The current data add novel evidence that high mannose is a signature of CAD with a vulnerable plaque phenotype, consistently across measures of severity of vessel involvement and independent of the traditional correlates of CVD, and that it is an independent predictor of incident adverse outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: In patients with acute myocardial infarction (AMI) and multivessel coronary disease, revascularization of non-culprit lesions guided by proof of ischemia usually requires staged ischemia testing. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in AMI patients is unknown. In this study, we tested the diagnostic value of QFR based on acute angiograms (aQFR) during AMI to assess the hemodynamic relevance of non-culprit lesions., Methods: We retrospectively assessed the diagnostic efficiency of aQFR in 280 vessels from 220 patients, comparing it with staged ischemia testing using elective coronary angiography with FFR (n = 47), stress cardiac MRI (n = 200) or SPECT (n = 33)., Results: aQFR showed a very good diagnostic efficiency (AUC = 0.887, 95% CI 0.832-0.943, p < 0.001) in predicting ischemia of non-culprit lesions, significantly superior to coronary lesion's geometry as assessed by quantitative coronary angiography. The optimal cut-off for aQFR to predict ischemia was 0.80 (sensitivity = 83.7%, specificity = 86.1%). Maintaining a predefined level of 95% sensitivity and specificity, we created a decision model based on aQFR: lesions with aQFR ≤ 0.75 should be treated, lesions with aQFR ≥ 0.92 do not yield any hemodynamic relevance, and lesions in the "grey zone" (aQFR 0.75-0.92) benefit from further ischemia testings. This model would allow to reduce staged ischemia tests by 46.8% without a relevant loss in diagnostic efficiency., Conclusion: Our data demonstrate that aQFR allows an effective assessment of hemodynamic relevance of non-culprit lesions in AMI and may guide interventions of non-culprit coronary lesions., (© 2021. The Author(s).)

Quantitative flow ratio (QFR) is a novel method to assess the relevance of coronary stenoses based only on angiographic projections. We could previously show that QFR is able to predict the hemodynamic relevance of non-culprit lesions in patients with myocardial infarction. However, it is still unclear whether QFR is also associated with the extent and severity of ischemia, which can effectively be assessed with imaging modalities such as cardiac magnetic resonance (CMR). Thus, our aim was to evaluate the associations of QFR with both extent and severity of ischemia. We retrospectively determined QFR in 182 non-culprit coronary lesions from 145 patients with previous myocardial infarction, and compared it with parameters assessing extent and severity of myocardial ischemia in staged CMR. Whereas ischemic burden in lesions with QFR > 0.80 was low (1.3 ± 5.5% in lesions with QFR ≥ 0.90; 1.8 ± 7.3% in lesions with QFR 0.81-0.89), there was a significant increase in ischemic burden in lesions with QFR ≤ 0.80 (16.6 ± 15.6%; p < 0.001 for QFR ≥ 0.90 vs. QFR ≤ 0.80). These data could be confirmed by other parameters assessing extent of ischemia. In addition, QFR was also associated with severity of ischemia, assessed by the relative signal intensity of ischemic areas. Finally, QFR predicts a clinically relevant ischemic burden ≥ 10% with good diagnostic accuracy (AUC 0.779, 95%-CI: 0.666-0.892, p < 0.001). QFR may be a feasible tool to identify not only the presence, but also extent and severity of myocardial ischemia in non-culprit lesions of patients with myocardial infarction.

Introduction: Although the relationship between the geometry of coronary stenosis and the presence of myocardial ischemia is well known, the association between stenosis geometry and severity and/or extent of ischemia is still unexplored. Thus, we investigated this relationship using optical coherence tomography (OCT) to assess stenosis parameters and cardiac magnetic resonance imaging (CMR) to determine both extent and severity of ischemia., Methods: We analyzed 55 lesions from 51 patients with stable angina. Pre-interventionally, all patients underwent OCT-analysis of stenosis morphology as well as CMR to determine both the extent and severity of myocardial ischemia., Results: Percent area stenosis (%AS) was significantly associated with ischemic burden (r = 0.416, p = 0.003). Similar results could be obtained for other stenosis parameters as well as for several other parameters assessing the extent of ischemia. Furthermore, OCT-derived stenosis parameters were associated with the product of ischemic burden and severity of ischemia (%AS: r = 0.435, p = 0.002; similar results for other parameters). A Poiseuille's-law-modelled combination of stenosis length and minimal lumen diameter yielded a good diagnostic efficiency (AUC 0.787) in predicting an ischemic burden >10%., Conclusions: Our data highlight the key role of the geometry of coronary lesions in determining myocardial ischemia.

Plaque rupture occurs if stress within coronary lesions exceeds the protection exerted by the fibrous cap overlying the necrotic lipid core. However, very little is known about the biomechanical stress exerting this disrupting force. Employing optical coherence tomography (OCT), we generated plaque models and performed finite-element analysis to simulate stress distributions within the vessel wall in 10 ruptured and 10 non-ruptured lesions. In ruptured lesions, maximal stress within fibrous cap (peak cap stress [PCS]: 174 ± 67 vs. 52 ± 42 kPa, p<0.001) and vessel wall (maximal plaque stress [MPS]: 399 ± 233 vs. 90 ± 95 kPa, p=0.001) were significantly higher compared to non-ruptured plaques. Ruptures arose in the immediate proximity of maximal stress concentrations (angular distances: 21.8 ± 30.3° for PCS vs. 20.7 ± 23.7° for MPS); stress concentrations excellently predicted plaque rupture (area under the curve: 0.940 for PCS, 0.950 for MPS). This prediction of plaque rupture was superior to established vulnerability features such as fibrous cap thickness or macrophage infiltration. In conclusion, OCT-based finite-element analysis effectively assesses plaque biomechanics, which in turn predicts plaque rupture in patients. This highlights the importance of morpho-mechanic analysis assessing the disrupting effects of plaque stress., Competing Interests: AM, EL, RD, KB, NM, SR, MB No competing interests declared, (© 2021, Milzi et al.)

Background: Quantitative flow ratio (QFR) is a novel method for assessing hemodynamic relevance of a coronary lesion based on angiographic projections without the need of a pressure wire. Various studies demonstrated that QFR consistently related to fractional flow reserve (FFR); however, it is still unclear to what extent QFR reflects intraluminal stenosis parameters. Given that optical coherence tomography (OCT) is currently the gold standard to assess intraluminal stenosis parameters, we investigated the relationship between OCT-derived lesion geometry and QFR. Methods: We determined QFR in 97 lesions from 87 patients who underwent coronary angiography and OCT due to stable angina. QFR was measured with proprietary software and compared with OCT-based assessment of intraluminal stenosis parameters as well as lesion morphology. Results: Mean QFR was 0.79 ± 0.10. QFR demonstrated a consistent association with FFR (R = 0.834, p < 0.001). Interestingly, QFR was associated with OCT-derived parameters such as minimal lumen area (MLA, R = 0.390, p = 0.015), percent area stenosis (R = 0.412, p < 0.001), minimal lumen diameter (MLD, R = 0.395, p < 0.001), and percent diameter stenosis (R = 0.400, p < 0.001). Both minimal luminal area (ROC = 0.734, optimal cut-off 1.75 mm 2 ) and minimal luminal diameter (ROC = 0.714, optimal cut-off 1.59 mm) presented a good diagnostic accuracy in diagnosing hemodynamic relevance (QFR ≤ 0.80). There was no significant association between QFR and anatomic features of plaque vulnerability. Conclusion: OCT-derived intraluminal stenosis parameters are related to QFR values and predict hemodynamic lesion relevance. The data supports the validity of QFR as 3D-vessel reconstruction method to assess coronary physiology without the need of a pressure wire.

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased cardiovascular risk related at least in part to a more vulnerable plaque phenotype. However, patients with T2DM exhibit also an increased risk following percutaneous coronary intervention (PCI). It is unknown if plaque vulnerability of a treated lesion influences cardiovascular outcomes in patients with T2DM. In this study, we aimed to assess the association of plaque morphology as determined by optical coherence tomography (OCT) with cardiovascular outcome following PCI in high-risk patients with T2DM., Methods: 81 patients with T2DM and OCT-guided PCI were recruited. Pre-interventional OCT and systematic follow-up of median 66.0 (IQR = 8.0) months were performed., Results: During follow-up, 24 patients (29.6%) died. The clinical parameters age (HR 1.16 per year, 95% CI 1.07-1.26, p < 0.001), diabetic polyneuropathy (HR 3.58, 95% CI 1.44-8.93, p = 0.006) and insulin therapy (HR 3.25, 95% CI 1.21-8.70, p = 0.019) predicted mortality in T2DM patients independently. Among OCT parameters only calcium-volume-index (HR 1.71 per 1000°*mm, 95% CI 1.21-2.41, p = 0.002) and lesion length (HR 1.93 per 10 mm, 95% CI 1.02-3.67, p = 0.044) as parameters describing atherosclerosis extent were significant independent predictors of mortality. However, classical features of plaque vulnerability, such as thickness of the fibrous cap, the extent of the necrotic lipid core and the presence of macrophages had no significant predictive value (all p = ns)., Conclusion: Clinical parameters including those describing diabetes severity as well as OCT-parameters characterizing atherosclerotic extent but not classical features of plaque vulnerability predict mortality in T2DM patients following PCI. These data suggest that PCI may provide effective plaque sealing resulting in limited importance of local target lesion vulnerability for future cardiovascular events in high-risk patients with T2DM.

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4-15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort.

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events and present more severe coronary artery disease (CAD). The Gensini and COURAGE scores are established angiographic instruments to assess CAD severity, which may also predict future cardiovascular risk. However, it is unclear if these scores are able to depict the increased risk of patients with T2DM and stable CAD (T2DM-SAP)., Methods: We performed quantitative coronary angiography and assessed the Gensini and COURAGE scores in 124 patients with T2DM-SAP. Angiographic data were compared to patients with stable angina without T2DM (Non-DM-SAP, n = 74), and to patients with acute coronary syndrome and T2DM (T2DM-ACS, n = 53)., Results: T2DM-SAP patients had similar Gensini and COURAGE-scores compared to Non-DM-SAP-patients (Gensini: 14.44 ± 27.34 vs 11.49 ± 26.99, p = 0.465; COURAGE: 3.48 ± 4.49 vs 3.60 ± 4.72, p = 0.854). In contrast, T2DM-SAP patients had significantly lower Gensini (14.44 ± 27.34 vs 30.94 ± 48.74, p = 0.003) and lower COURAGE (3.48 ± 4.49 vs 5.30 ± 4.63, p = 0.016) scores compared to T2DM-ACS-patients., Conclusion: Both the Gensini and the COURAGE score fail to predict the high cardiovascular risk of patients with T2DM-SAP. Therefore, these scores should be used with caution in the assessment of future risk of patients with T2DM. However, among T2DM-ACS patients, both scores are increased, reflecting the high cardiovascular risk in this patient population.

Background: Out of hospital cardiac arrest (OHCA) is common and associated with low survival rates. Guidelines propose a fast work-up after OHCA including coronary angiography (CA) but little is known about the actual outcome of those patients who undergo immediate CA after OHCA with suspected cardiac origin., Aim: The aim of this retrospective single-center study was to evaluate the short-term outcomes and predictors of in-hospital mortality in patients who underwent immediate CA after OHCA with suspected cardiac origin., Methods: We included all consecutive patients with OHCA who underwent immediate CA between January 2011 and December 2015. We defined immediate CA after OHCA as angiography within 2 hr after admission., Results: Two hundred and nineteen consecutive patients with OHCA were included. Fifty six patients (26%) underwent CA without previous return of spontaneous circulation (ROSC) and with ongoing CPR using the LUCAS-device. One hundred and forty nine patients (67%) died in hospital. Of the 56 patients with CA with ongoing CPR, 55 died and only 1 patient survived to hospital discharge. In a multivariate analysis, older age (OR = 2.03, 95%CI 1.35-3.03; p = .001), initial shockable rhythm (OR = 0.28, 95%CI 0.07-1.13; p = .076), CA with ongoing CPR (OR = 11.63, 95%CI 1.20-122.55; p = .035), and initial arterial pH (OR = 0.008, 95%CI 0.00-0.228; p < .005) remained as independent predictors for in-hospital mortality., Conclusions: In this study older age, metabolic derangement on admission, initial nonshockable rhythm and failure to achieve ROSC before admission predicted in-hospital mortality. While CA with ongoing CPR with the LUCAS-device was feasible, mortality in patients without previous ROSC was extremely high, questioning whether this approach is medically useful., (© 2019 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)

The outcome of extremely low-birth-weight (ELBW) and very low-birth-weight (VLBW) infants has substantially improved in recent years. As acute kidney injury is frequent in these infants due to various risk factors, there is an increasing demand for renal replacement therapy in these patients. Data on that topic, however, are scarce. We review the available literature on that topic and report our experience on temporary dialysis in three extremely immature infants (two ELBW and one VLBW) with acute kidney failure. Peritoneal dialysis (PD) was performed for 19, 23, and 44 days until recovery of native renal function. At recent follow-up of 18 and 24 months, two patients are in good clinical condition with chronic kidney disease stages 1 and 4, respectively. One patient deceased at the age of 12 months due to secondary liver failure. The dialysis regimen applied in our study differed significantly from older infants with extremely short dwell times and accordingly high numbers of daily cycles. The use of rigid acute PD catheters was associated with less catheter-related complications (leakage, dislocation, and obstruction) as compared to ascites drainage catheters. In summary, PD was technically feasible and effective also in extremely immature infants, but frequent adjustments of dialysis regimens and high numbers of daily cycles posed immense efforts on both, parents and medical staff.

Background: Coronary calcification is associated with high risk for cardiovascular events. However, its impact on plaque vulnerability is incompletely understood. In the present study we defined the intrinsic calcification angle (ICA) as the angle externally projected by a vascular calcification and analyzed its role as novel feature of coronary plaque vulnerability in patients with type 2 diabetes., Methods: Optical coherence tomography was used to determine ICA in 219 calcifications from 56 patients with stable coronary artery disease (CAD) and 143 calcifications from 36 patients with acute coronary syndrome (ACS). We then used finite elements analysis to gain mechanistic insight into the effects of ICA., Results: Minimal (139.8 ± 32.8° vs. 165.6 ± 21.6°, p < 0.001) and mean ICA (164.1 ± 14.3° vs. 176.0 ± 8.4°, p < 0.001) were lower in ACS vs. stable CAD patients. Mean ICA predicted ACS with very good diagnostic efficiency (AUC = 0.840, 95% CI 0.797-0.882, p < 0.001, optimal cut-off 175.9°); younger age (OR 0.95 per year, 95% CI 0.92-0.98, p = 0.002), male sex (OR 2.18, 95% CI 1.41-3.38, p < 0.001), lower HDL-cholesterol (OR 0.82 per 10 mg/dl, 95% CI 0.68-0.98, p = 0.029) and ACS (OR 14.71, 95% CI 8.47-25.64, p < 0.001) were determinants of ICA < 175.9°. A lower ICA predicted ACS (OR for 10°-variation 0.25, 95% CI 0.13-0.52, p < 0.001) independently from fibrous cap thickness, presence of macrophages or extension of lipid core. In finite elements analysis we confirmed that lower ICA causes increased stress on a lesion's fibrous cap; this effect was potentiated in more superficial calcifications and adds to the destabilizing role of smaller calcifications., Conclusion: Our clinical and mechanistic data for the first time identify ICA as a novel feature of coronary plaque vulnerability.

Background: Treatment of in-stent restenosis (ISR) is still a clinical challenge in interventional cardiology. Paclitaxel-coated balloons (PCBs) are an attractive therapeutic option for ISR. There are several different types of PCBs available for percutaneous coronary intervention, but to date, comparative data between different types of PCBs for the treatment of ISR are scarce., Patients and Methods: This single centre, nonrandomized, retrospective study under real-world condition included 194 patients with 194 ISR treated by repeat percutaneous coronary intervention with PCBs. The primary end point was major adverse cardiac events (MACEs), defined as cardiac death, myocardial infarction and need for target lesion revascularization (TLR) at 1 year. Secondary end points were MACE and TLR at long-term follow-up., Results: Baseline clinical and angiographic parameters were comparable between the two groups. Patients in the iopromide-based PCB and butyryl-tri-hexyl citrate (BTHC)-PCB groups were followed up for 32.2±20.5 and 24.2±13.3 months, respectively (P=0.001). MACEs at 1-year follow-up were 15.0 and 15.8% (P=0.879) for the BTHC-PCB and iopromide-based PCB groups, respectively. TLR, myocardial infarction and cardiac death for BTHC-PCB versus iopromide-based PCB at 1-year follow-up were 9.6 versus 11.8%, P=0.622; 5.3 versus 3.9%, P=0.640; and 5.3 versus 3.9%, P=0.640, respectively. If complete follow-up periods were included in the analysis, BTHC-PCB and iopromide-based PCB had comparable rates of MACE (P=0.835) and TLR (P=0.792)., Conclusion: BTHC-PCB and iopromide-based PCB had comparable rates of MACE and TLR for the treatment of ISR at 1-year and long-term follow-up.

Background: The presence of plaque macrophages and microcalcifications are acknowledged features of plaque vulnerability. Experimental data suggest that microcalcifications promote inflammation and macrophages foster microcalcifications. However, co-localization of plaque macrophages and calcification (ColocCaMa) in coronary segments and its impact on plaque phenotype and lesion vulnerability is unexplored., Methods: Plaque morphology including ColocCaMa of calcified coronary target segments in patients with stable coronary artery disease (n = 116) was analyzed using optical coherence tomography (OCT) prior to coronary intervention. Therefore we considered macrophages co-localized with calcification if their distance in an OCT frame was <100μm and OCT-defined microcalcifications with a calcium arc <22.5°., Results: ColocCaMa was present in 29/116(25.0%) coronary segments. Calcium burden was greater (calcium volume index:1731±1421°*mm vs. 963±984°*mm, p = 0.002) and calcifications were more superficial (minimal thickness of the fibrous cap overlying the calcification 35±37μm vs. 64±72μm, p = 0.005) in the presence of ColocCaMa. Segments with ColocCaMa demonstrated a higher incidence of newly suggested features of plaque vulnerability, with a 3.5-fold higher number of OCT-defined microcalcifications (0.7±1.0 vs. 0.2±0.6, p = 0.022) and a 6.7-fold higher incidence of plaque inflammation (macrophage volume index:148.7±248.3°*mm vs. 22.2±57.4°*mm, p<0.001). Clinically, intima-media thickness (IMT) in carotid arteries was increased in patients with ColocCaMa (1.02±0.30mm vs. 0.85±0.18, p = 0.021). In a multivariate model, IMT (OR1.76 for 100μm, 95%CI 1.16-2.65, p = 0.007), HDL-cholesterol (OR0.36 for 10mg/dl, 95%CI 0.16-0.84, p = 0.017), calcium volume index (OR1.07 for 100°*mm, 95%CI 1.00-1.14, p = 0.049), macrophage volume index (OR5.77 for 100°*mm, 95%CI 2.04-16.3, p = 0.001) and minimal luminal area (OR3.41, 95%CI 1.49-7.78, p = 0.004) were independent predictors of ColocCaMa., Conclusion: Plaque macrophages co-localize with calcifications in coronary target segments and this is associated with high-risk morphological features including microcalcifications and macrophage infiltration as well as with greater calcification burden. Our data may add to the understanding of the relationship between plaque macrophages, vascular calcification and their clinical impact., Competing Interests: The authors have declared that no competing interests exist.

Background: The minimal fibrous cap thickness overlying the necrotic lipid core as well as the presence of macrophages are established characteristics of coronary plaque vulnerability. Recently, the presence of microcalcifications has emerged as a novel feature of vulnerable lesions. However, clinical and plaque morphological predictors of microcalcifications are unknown., Methods: In patients with stable coronary artery disease, analysis of plaque morphology (n = 112) was performed using optical coherence tomography prior to coronary intervention to assess predictors of microcalcifications., Results: Microcalcifications were present in 21/112 (18.7%) lesions. Segments with microcalcifications showed a higher total number of calcifications per lesion (6.7 ± 3.0 vs. 3.2 ± 2.5, p < 0.001), a lower percent area stenosis (70.9 ± 11.1 vs. 76.2 ± 9.7%, p = 0.028), and a higher frequency of macrophage infiltration (66.7 vs. 37.4%, p = 0.014). In lesions with vs. without microcalcifications, macrophage infiltration was characterized by a wider macrophage angle (31.1° ± 34.4° vs. 13.7° ± 20.6°, p = 0.003), a higher macrophage index (105.6 ± 269.0 vs. 31.6 ± 66.5° mm, p = 0.020), and an increased frequency of calcium-macrophage co-localization (47.6 vs. 15.6%, p = 0.001). In multivariable logistic regression analysis, the total number of calcifications per lesion (OR 1.53, 95% CI 1.23-1.91, p < 0.001), average macrophage angle (OR 1.28 for 10°-variation, 95% CI 1.03-1.60, p = 0.024), and percent area stenosis (OR 0.59 for 10% increase, 95% CI 0.34-1.04, p = 0.070) were independent predictors for the presence of microcalcifications, whereas the latter did not reach statistical significance., Conclusion: Microcalcifications are related to a less advanced stenosis severity and to extensive plaque inflammation, but not to clinical parameters. Our data may add to the understanding and role of microcalcifications in coronary artery lesions.

Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis., Study Design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life., Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys., Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by the gut after food intake leading to pancreatic insulin secretion and glucose lowering. Beyond its role in glucose control, GLP-1 was found in mice and men to beneficially modulate the process of atherosclerosis, which has been linked to improved cardiovascular outcome of patients with diabetes at high cardiovascular risk treated with GLP-1 receptor agonists. However, little is known on the role of the other main incretin in the cardiovascular system. The aim of this study was to characterize GIP in atherosclerotic cardiovascular disease., Methods and Results: Serum concentrations of GIP were assessed in 731 patients who presented for elective coronary angiography at the University Hospital Aachen. While GIP concentrations were not associated with coronary artery disease (CAD), we found 97 patients with PAD (peripheral artery disease) vs. 634 without PAD to have higher circulating GIP levels (413.0 ± 315.3 vs. 332.7 ± 292.5 pg/mL, p = 0.0165). GIP levels were independently related to PAD after multivariable adjustment for CAD, age, sex, BMI, hypertension, diabetes, CRP, WBC, and smoking. To investigate the functional relevance of elevated GIP levels in human atherosclerotic disease, we overexpressed GIP (1-42) in ApoE -/- mice fed a Western diet for 12 weeks using an adeno-associated viral vector system. GIP overexpression led to reduced atherosclerotic plaque macrophage infiltration and increased collagen content compared to control (LacZ) with no change in overall lesion size, suggesting improved plaque stability. Mechanistically, we found GIP treatment to reduce MCP-1-induced monocyte migration under In vitro conditions. Additionally, GIP prevented proinflammatory macrophage activation leading to reduced LPS-induced IL-6 secretion and inhibition of MMP-9 activity, which was attributable to GIP dependent inhibition of NfκB, JNK-, ERK, and p38 in endotoxin activated macrophages., Conclusion: Elevated concentrations of the incretin hormone GIP are found in patients with atherosclerotic cardiovascular disease, while GIP treatment attenuates atherosclerotic plaque inflammation in mice and abrogates inflammatory macrophage activation in vitro. These observations identified GIP as a counterregulatory vasoprotective peptide, which might open new therapeutic avenues for the treatment of patients with high cardiovascular risk., (Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events, which usually arise from the rupture of a vulnerable coronary plaque. The minimal fibrous cap thickness (FCT) overlying a necrotic lipid core is an established predictor for plaque rupture. Recently, coronary calcification has emerged as a relevant feature of plaque vulnerability. However, the impact of T2DM on these morphological plaque parameters is largely unexplored. Therefore, this study aimed to compare differences of coronary plaque morphology in patients with and without T2DM with a particular focus on coronary calcification., Methods: In 91 patients (T2DM = 56, non-T2DM = 35) with 105 coronary de novo lesions (T2DM = 56, non-T2DM = 49) plaque morphology and calcification were analyzed using optical coherence tomography (OCT) prior to coronary intervention., Results: Patients with T2DM had a lower minimal FCT (80.4 ± 27.0 µm vs. 106.8 ± 27.8 µm, p < 0.001) and a higher percent area stenosis (77.9 ± 8.1% vs. 71.7 ± 11.2%, p = 0.001) compared to non-diabetic subjects. However, patients with and without T2DM had a similar total number of calcifications (4.0 ± 2.6 vs. 4.2 ± 3.1, p = ns) and no significant difference was detected in the number of micro- (0.34 ± 0.79 vs. 0.31 ± 0.71), spotty (2.11 ± 1.77 vs. 2.37 ± 1.89) or macro-calcifications (1.55 ± 1.13 vs. 1.53 ± 0.71, all p = ns). The mean calcium arc (82.3 ± 44.8° vs. 73.7 ± 31.6), the mean thickness of calcification (0.54 ± 0.13 mm vs. 0.51 ± 0.15 mm), the mean calcified area (0.99 ± 0.72 mm 2 vs. 0.78 ± 0.49 mm 2 ), the mean depth of calcification (172 ± 192 μm vs. 160 ± 76 μm) and the cap thickness overlying the calcification (50 ± 71 μm vs. 62 ± 61 μm) did not differ between the diabetic and non-diabetic groups (all p = ns)., Conclusion: T2DM has an impact on the minimal FCT of the coronary target lesion, but not on localization, size, shape or extent of calcification. Thus, the minimal FCT overlying the necrotic lipid core but not calcification is likely to contribute to the increased plaque vulnerability observed in patients with T2DM.

Cardiac transthyretin-related (ATTR) amyloidosis is a severe cardiomyopathy for which therapeutic approaches are currently under development. Because non-invasive imaging techniques such as cardiac magnetic resonance imaging and echocardiography are non-specific, the diagnosis of ATTR amyloidosis is still based on myocardial biopsy. Thus, diagnosis of ATTR amyloidosis is difficult in patients refusing myocardial biopsy. Furthermore, myocardial biopsy does not allow 3D-mapping and quantification of myocardial ATTR amyloid. In this report we describe a 99m Tc-DPD-based molecular imaging technique for non-invasive single-step diagnosis, three-dimensional mapping and semiquantification of cardiac ATTR amyloidosis in a patient with suspected amyloid heart disease who initially rejected myocardial biopsy. This report underlines the clinical value of SPECT-based nuclear medicine imaging to enable non-invasive diagnosis of cardiac ATTR amyloidosis, particularly in patients rejecting biopsy.

Medical history  We report on a 51-year-old male patient with thoracic pain of acute onset with radiation in the left arm. His cardiovascular risk factors include obesity, smoking and arterial hypertension. Investigations  ECG showed no signs of ischemia. The blood test revealed increasing troponin (37 pg/ml; Norm < 14 pg/ml). Therefore we performed cardiac catheterization. The RIVA demonstrated a medial filling defect. Use of OCT imaging showed intimal rupture associated with thrombus. Treatment and course  The lesion was stented with a drug eluting stent. We initiated a medication with aspirin, ticagrelor, metoprolol and simvastatin. Conclusion  Coronary thrombosis of our patient was caused by spontaneous coronary artery dissection (SCAD). SCAD is an important differential diagnosis in patients with ACS. Further prospective studies and guideline recommendations are needed in the future., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Annexin A5 (anxA5) is involved in processes which are crucial in atherogenesis. However, anxA5's relationship with atherosclerotic lesion extension and plaque composition in high-risk patients with type 2 diabetes remains unclear. Thus, we characterized the association between circulating anxA5 levels with atherosclerotic burden and coronary plaque composition in diabetes mellitus patients., Methods: Intima-media thickness was determined in 96 diabetes mellitus patients with stable coronary artery disease. Furthermore, intracoronary optical coherence tomography was performed in 106 lesions to determine plaque composition., Results: AnxA5 plasma levels of patients with intima-media thickening were higher (3.49 ± 2.19 ng/mL) compared to patients with normal intima-media thickness (2.24 ± 1.67 ng/mL, p = 0.002). Furthermore, anxA5 was associated with intima-media thickening on univariable [odds ratio = 1.445 (1.106-1.889), p = 0.007] and multivariable [odds ratio = 1.643 (1.166-2.314), p = 0.005] logistic regression analysis when adjusted for multiple cardiovascular risk factors and biomarkers. Furthermore, receiver operating characteristic analysis demonstrated that anxA5 predicted intima-media thickening with low-moderate diagnostic efficiency [area under the curve = 0.700 (0.592-0.808)]. In contrast, there was no association between anxA5 levels and coronary plaque composition as assessed by optical coherence tomography including the presence of lipid, calcified, fibrous plaque or the minimal thickness of the fibrous cap overlying the necrotic lipid core ( p = ns)., Conclusion: Circulating anxA5 levels are associated with carotid intima-media thickness but not coronary plaque composition in high-risk patients with diabetes mellitus.