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Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

With the enormous progress in the field of cardiovascular imaging in recent years, computed tomography (CT) has become readily available to phenotype atherosclerotic coronary artery disease. New analytical methods using artificial intelligence (AI) enable the analysis of complex phenotypic information of atherosclerotic plaques. In particular, deep learning-based approaches using convolutional neural networks (CNNs) facilitate tasks such as lesion detection, segmentation, and classification. New radiotranscriptomic techniques even capture underlying bio-histochemical processes through higher-order structural analysis of voxels on CT images. In the near future, the international large-scale Oxford Risk Factors And Non-invasive Imaging (ORFAN) study will provide a powerful platform for testing and validating prognostic AI-based models. The goal is the transition of these new approaches from research settings into a clinical workflow. In this review, we present an overview of existing AI-based techniques with focus on imaging biomarkers to determine the degree of coronary inflammation, coronary plaques, and the associated risk. Further, current limitations using AI-based approaches as well as the priorities to address these challenges will be discussed. This will pave the way for an AI-enabled risk assessment tool to detect vulnerable atherosclerotic plaques and to guide treatment strategies for patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CA is founder, shareholder and director of Caristo Diagnostics Ltd, a CT-image analysis company. CA is the inventor of patents US10695023B2, US11393137B2, GB2018/1818049.7, GR20180100490, and GR20180100510, these are licensed to Caristo Diagnostics. CA has a leadership role in British Atherosclerosis Society and participates in several European commission Marie Curie Panels, and has received honoraria from Amarin, Covance and Slience Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The fat attenuation index (FAI) measured using coronary computed tomography angiography (CCTA) enables the direct evaluation of pericoronary adipose tissue composition and vascular inflammation. We aimed to investigate the association of fractional flow reserve (FFR) and plaque vulnerability with coronary inflammation., Methods: Patients with suspected coronary artery disease (CAD) who underwent CCTA and invasive FFR measurements within 90-day were included. A cloud-based medical device, CaRi-Heart, serves as a surrogate tool for evaluating coronary inflammation based on FAI by analyzing CCTA images. The correlations between CCTA-defined plaque characteristics, invasive coronary angiographic and physiologic assessments, and CaRi-Heart risk were analyzed. The primary endpoint was the patient-oriented composite outcome (POCO) consisting of all-cause death, any myocardial infarction, and any revascularization., Results: A total of 564 patients (median age 67.0 years; 75.4 ​% men) were included. There were no significant differences in quantitative and qualitative plaque characteristics or FFR between the high- and low-CaRi-Heart risk groups (i.e., ≥5 ​% and <5 ​%). During the median follow-up of 3.2 years [1.13-4.73 years], CaRi-Heart risk ≥5 ​% was associated with a significantly higher rate of POCO compared to CaRi-Heart risk <5 ​% (0.9 ​% vs. 10.1 ​%, P ​= ​0.037). The CaRi-Heart risk was an independent predictor of POCO as a continuous (adjusted HR 1.016, 95 ​% CI 1.005-0.027, P ​= ​0.004) and categorical variable (CaRi-Heart risk ≥5 ​%, adjusted HR 2.949, 95 ​% CI 1.182-7.360, P ​= ​0.021), regardless of high-risk plaque characteristics and FFR., Conclusion: Coronary inflammation risk assessed using CaRi-Heart risk provides independent prognostic information regardless of plaque vulnerability and physiologic stenosis in patients with CAD., Competing Interests: Declaration of competing interest Dr Bon-Kwon Koo received an Institutional Research Grant from Abbott Vascular and Philips Volcano. Dr. Joon Hyung Doh received a Research Grant from Philips Volcano. All other authors declare that there is no conflict of interest relevant to the submitted work. Dr Tomlins is an employee of Caristo Diagnostics Ltd. Dr Antoniades is a founder, shareholder, and director of Caristo Diagnostics Ltd, a CT-image analysis company., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population., Methods: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population., Findings: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events., Interpretation: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators., Funding: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre., Competing Interests: Declaration of interests AT has received research funding from National Institute of Health and Care Research (NIHR) Oxford Health Biomedical Research Center and NIHR Applied Research Collaboration Oxford. AKa has received grants from Lantheus Medical USA and honoraria from Bracco UK/Philips Medical. BM has received honoraria from Chiesi, Sanofi, Novartis, and Boston Scientific. CA has a leadership role in British Atherosclerosis Society, and participates in several European Commission Marie Curie panels, has received honoraria from Amarin and Covance, and has received consulting fees from Slience Therapeutics. DA has a leadership role in the Spontaneous Coronary Artery Dissection Study group, is inventor of patents related to a cardiac assist device (EP3277337A1, PCT/GB2017/050877), and has received grant support from AstraZeneca and Abbott Vascular, and consulting fees from General Electric. EM has received research support from the NHS AI award. EN has a leadership role in the Society of Cardiovascular Computed Tomography and has received consulting fees from Caristo Diagnostics. EKO is a stock option holder of Caristo Diagnostics, is co-founder of Evidence2Health, and is inventor of patents (WO2018078395A1, WO2020058713A1, US17/720,068, 63/619,241, 63/177,117, 63/580,137, 63/606,203, and 63/562,335). JD has a leadership role and has received consulting fees from Novo Nordisk, has received honoraria from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer. JR has a leadership role in Heart & Lung Imaging, has received consulting fees from NHSX and HeartFlow, and honoraria from Sanofi, Aidence, and 4-C. KMC has received consulting fees from Caristo Diagnostics. MD has received consulting fees from Bristol Myers Squibb, Tenaya Therapeutics, and VizAL, and has participated on an advisory board for Caristo Diagnostics. NSa receives royalties from a patent (PCT/GB2015/052359). PL has received research support from National Heart, Lung and Blood Institute, Simard Fund, and RRM Charitable Fund, grants from Novartis, Novo Nordisk, and Genentech, honoraria from Pri-Med and Medtelligence, has a leadership role in XBiotech, is the inventor of patents (US20240043525A1, US20220041710A1 and US20220389090A1), and has advisory roles for Novartis, DalCor, XBiotech, TenSixteen Bio, and Soley Therapeutics. RB has a leadership role in the Society of Cardiovascular Computed Tomography, has received grants from Amgen, Novartis, and Nanox AI, and consulting fees from Caristo Diagnostics and Heartflow. SEP has a leadership role for the European Association of Cardiovascular Imaging, has received consulting fees from Circle Cardiovascular Imaging, and holds an advisory role for PROTEUS Trial. PT, YS, and MS are employees of Caristo Diagnostics. SN, KMC, and CA are founders, shareholders, and directors of Caristo Diagnostics, a CT-image analysis company. CA is the inventor of patents US10695023B2, US11393137B2, GB2018/1818049.7, GR20180100490, and GR20180100510. ASA, SN, and KMC are co-inventors of patent US10695023B2. These are licensed to Caristo Diagnostics. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Directional deep brain stimulation (DBS) electrodes are increasingly used, but conventional computed tomography (CT) is unable to directly image segmented contacts owing to physics-based resolution constraints. Postoperative electrode segment orientation assessment is necessary because of the possibility of significant deviation during or immediately after insertion. Photon-counting detector (PCD) CT is a relatively novel technology that enables high resolution imaging while addressing several limitations intrinsic to CT. We show how PCD CT can enable clear in vivo imaging of DBS electrodes, including segmented contacts and markers for all major lead manufacturers., Materials and Methods: We describe postoperative imaging and reconstruction protocols we have developed to enable optimal lead visualization. PCD CT images were obtained of directional leads from the three major manufacturers and fused with preoperative 3T magnetic resonance imaging (MRI). Radiation dosimetry also was evaluated and compared with conventional imaging controls. Orientation estimates from directly imaged leads were compared with validated software-based reconstructions (derived from standard CT imaging artifact analysis) to quantify congruence in alignment and directional orientation., Results: High-fidelity images were obtained for 15 patients, clearly indicating the segmented contacts and directional markers both on CT alone and when fused to MRI. Our routine imaging protocol is described. Ionizing radiation doses were significantly lower than with conventional CT. For most leads, the directly imaged lead orientations and depths corresponded closely to those predicted by CT artifact-based reconstructions. However, unlike direct imaging, the software reconstructions were susceptible to 180° error in orientation assessment., Conclusions: High-resolution photon-counting CT can very clearly image segmented DBS electrode contacts and directional markers and unambiguously determine lead orientation, with lower radiation than in conventional imaging. This obviates the need for further imaging and may facilitate anatomically tailored directional programming., Competing Interests: Conflict of interest Alexander L. Green reports consulting fees from Abbott and has received travel support from Medtronic, Boston Scientific, and Abbott. James J. FitzGerald reports consulting fees from Abbott and Boston Scientific and has participated on data safety monitoring boards for Medtronic and Herantis. James Manfield reports travel support from Boston Scientific and Abbott. Nagaraja Sarangmat has received travel support from Medtronic and Boston Scientific. The remaining authors reported no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented., Objectives: This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care., Methods: The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value., Results: External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI: 1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post-cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01)., Conclusions: Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification., Competing Interests: Funding Support and Author Disclosures This study received support from the British Heart Foundation (grant TG/19/2/34831) and the European Union Commission Horizon 2020 program via the Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation (MAESTRIA) Consortium (grant 965286). Drs Siddique, Tomlins, and Shirodaria are employees of Caristo Diagnostics Ltd. Dr Williams has received support from the British Heart Foundation (grant FS/ICRF/20/26002); and has served on the Speakers Bureau for Canon Medical Systems. Dr Adlam has received support from the Leicester National Institute of Health Research Biomedical Research Centre; has received research funding and in-kind support for unrelated research from AstraZeneca Inc; has received an educational grant from Abbott Vascular Inc to support a clinical research fellow for unrelated research; and has also conducted consultancy for GE Inc to support research funds for unrelated research. Drs Shirodaria, Neubauer, Channon, and Antoniades are founders, shareholders, and directors of Caristo Diagnostics Ltd, a CT-image analysis company. Dr Antoniades has received support from the British Heart Foundation (grants CH/F/21/90009, TG/19/2/34831, and RG/F/21/110040), Innovate UK (grant 104472), and the National Consortium of Intelligent Medical Imaging through the Industry Strategy Challenge Fund (Innovate UK grant 104688); and is also the inventor of patents US10,695,023B2, PCT/GB2017/053262, GB2018/1818049.7, GR20180100490, and GR20180100510, which are licensed through exclusive license to Caristo Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to systematically explore the added value of biomarkers of vascular inflammation for cardiovascular prognostication on top of clinical risk factors., Background: Measurement of biomarkers of vascular inflammation is advocated for the risk stratification for coronary heart disease (CHD)., Methods: We systematically explored published reports in MEDLINE for cohort studies on the prognostic value of common biomarkers of vascular inflammation in stable patients without known CHD. These included common circulating inflammatory biomarkers (ie, C-reactive protein, interleukin-6 and tumor necrosis factor-a, arterial positron emission tomography/computed tomography and coronary computed tomography angiography-derived biomarkers of vascular inflammation, including anatomical high-risk plaque features and perivascular fat imaging. The main endpoint was the difference in c-index (Δ[c-index]) with the use of inflammatory biomarkers for major adverse cardiovascular events (MACEs) and mortality. We calculated I 2 to test heterogeneity. This study is registered with PROSPERO (CRD42020181158)., Results: A total of 104,826 relevant studies were screened and a final of 39 independent studies (175,778 individuals) were included in the quantitative synthesis. Biomarkers of vascular inflammation provided added prognostic value for the composite endpoint and for MACEs only (pooled estimate for Δ[c-index]% 2.9, 95% CI: 1.7-4.1 and 3.1, 95% CI: 1.8-4.5, respectively). Coronary computed tomography angiography-related biomarkers were associated with the highest added prognostic value for MACEs: high-risk plaques 5.8%, 95% CI: 0.6 to 11.0, and perivascular adipose tissue (on top of coronary atherosclerosis extent and high-risk plaques): 8.2%, 95% CI: 4.0 to 12.5). In meta-regression analysis, the prognostic value of inflammatory biomarkers was independent of other confounders including study size, length of follow-up, population event incidence, the performance of the baseline model, and the level of statistical adjustment. Limitations in the published literature include the lack of reporting of other metrics of improvement of risk stratification, the net clinical benefit, or the cost-effectiveness of such biomarkers in clinical practice., Conclusions: The use of biomarkers of vascular inflammation enhances risk discrimination for cardiovascular events., Competing Interests: Funding Support and Author Disclosures Dr Antoniades is a founder and shareholder of Caristo Diagnostics Ltd, a company that specialized in computed tomography imaging diagnostics. 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.)

The association between thrombosis and acute coronary syndromes is well established. Inflammation and activation of innate and adaptive immunity are another important factor implicated in atherosclerosis. However, the exact interactions between thrombosis and inflammation in atherosclerosis are less well understood. Accumulating data suggest a firm interaction between these two key pathophysiologic processes. Pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-6 and interleukin-1, have been implicated in the thrombotic cascade following plaque rupture and myocardial infarction. Furthermore, cell adhesion molecules accelerate not only atheromatosis but also thrombosis formation while activated platelets are able to trigger leukocyte adhesion and accumulation. Additionally, tissue factor, thrombin, and activated coagulation factors induce the release of pro-inflammatory cytokines such as prostaglandin and C reactive protein, which may further induce von Willebrand factor secretion. Treatments targeting immune activation (i.e. interleukin-1 inhibitors, colchicine, statins, etc.) may also beneficially modulate platelet activation while common anti-thrombotic therapies appear to attenuate the inflammatory process. Taken together in the context of cardiovascular diseases, thrombosis and inflammation should be studied and managed as a common entity under the concept of thrombo-inflammation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Perivascular adipose tissue (PVAT) surrounding the human coronary arteries, secretes a wide range of adipocytokines affecting the biology of the adjacent vascular wall in a paracrine way. However, we have recently found that PVAT also behaves as a sensor of signals coming from the vascular wall, to which it reacts by changing its morphology and secretory profile. Indeed, vascular inflammation, a key feature of vascular disease pathogenesis, leads to the release of inflammatory signals that disseminate into local fat, inducing local lipolysis and inhibiting adipogenesis. This ability of PVAT to sense inflammatory signals from the vascular wall, can be used as a "thermometer" of the vascular wall, allowing for non-invasive detection of coronary inflammation. Vascular inflammation induces a shift of PVAT's composition from lipid to aqueous phase, resulting into increased computed tomography (CT) attenuation around the inflamed artery, forming a gradient with increasing attenuation closer to the inflamed coronary artery wall. These spatial changes in PVAT's attenuation are easily detected around culprit lesions during acute coronary syndromes. A new biomarker designed to captured these spatial changes in PVAT's attenuation around the human coronary arteries, the Fat Attenuation Index (FAI), has additional predictive value in stable patients for cardiac mortality and non-fatal heart attacks, above the prediction provided by the current state of the art that includes risk factors, calcium score and presence of high risk plaque features. The use of perivascular FAI in clinical practice may change the way we interpret cardiovascular CT angiography, as it is applicable to any coronary CT angiogram, and it offers dynamic information about the inflammatory burden of the coronary arteries, providing potential guidance for preventive measures and invasive treatments., (Copyright © 2019 [The Author/The Authors]. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this systematic review was to explore the diagnostic accuracy of various cardiovascular magnetic resonance (CMR) index tests for the diagnosis of acute myocarditis in adult patients., Background: Acute myocarditis remains one of the most challenging diagnoses in cardiology. CMR has emerged as the diagnostic tool of choice to detect acute myocardial injury and necrosis in patients with suspected myocarditis., Methods: We considered all diagnostic cohort and case-control studies. We searched MEDLINE, EMBASE, Cochrane Library, SCOPUS, and Web of Science up to April 21, 2017. We used the Quality Assessment of Diagnostic Accuracy Studies-2 tool to assess the quality of included studies. PROSPERO registration number CRD42017055778 was used., Results: Twenty-two studies were included in the systematic review. Because significant heterogeneity exists among the studies, we only present hierarchical receiver operator curves. The areas under the curve (AUC) for each index test were for T1 mapping 0.95 (95% confidence interval [CI]: 0.93 to 0.97), for T2 mapping 0.88 (95% CI: 0.85 to 0.91), for extracellular volume fraction (ECV) 0.81 (95% CI: 0.78 to 0.85), for increased T2 ratio/signal 0.80 (95% CI: 0.76 to 0.83), for late gadolinium enhancement (LGE) 0.87 (95% CI: 0.84 to 0.90), for early gadolinium enhancement (EGE) 0.78 (95% CI: 0.74 to 0.81), and for the Lake Louise criteria (LLC) 0.81 (95% CI: 0.77 to 0.84). Native T1 mapping had superior diagnostic accuracy across all index tests. The AUC of T2 mapping was greater than the AUC of increased T2 ratio/signal and EGE, whereas ECV showed no superiority compared with other index tests. LGE had better diagnostic accuracy compared with the classic CMR index tests, similar accuracy with T2 mapping and ECV, and only T1 mapping surpassed it., Conclusions: Novel CMR mapping techniques provide high diagnostic accuracies for the diagnosis of acute myocarditis and constitute promising successors of the classic elements of the LLC for routine diagnostic protocols., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker-the perivascular fat attenuation index (FAI)-captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown., Methods: In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features., Findings: Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17-89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19-87]). Median follow-up was 72 months (range 51-109) in the derivation cohort and 54 months (range 4-105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33-3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50-2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as -70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35-24·40; p<0·0001 for cardiac mortality; 2·55, 1·65-3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90-10·88; p<0·0001 for cardiac mortality; 3·69, 2·26-6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality., Interpretation: The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥-70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients., Funding: British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk., Objective: The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups., Methods: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR)., Results: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P < .001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P = .02 and P < .001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P = .05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P < .001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver., Conclusions: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Saphenous vein graft (SVG) disease and subsequent vein graft failure remain a major problem after coronary artery bypass graft operations. In an effort to mitigate loss of endothelial viability, the vein is stored, intraoperatively, in a preservation solution. However, human SVG samples demonstrate endothelial denudation and dysfunction after such storage, the severity of which varies, depending on the medium. The paucity of clinical data evaluating preservation solutions is illustrated by the absence of optimal procedural protocol. This review evaluates the potential efficacy of different storage solutions in preserving vein grafts, in relation to a mechanistic understanding of SVG pathophysiology., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. Data have reported that the genetic variability on fibrinogen chains may affect the atherosclerotic process and the risk of coronary artery disease (CAD). We examined the combined effects of the G455A and the G58A fibrinogen genetic polymorphisms on prothrombotic profile, endothelial function and the risk of CAD in a Caucasian population., Methods: We recruited 422 patients with angiographically documented CAD and 277 controls matched for age and gender. The two polymorphisms were genotyped by polymerase chain reaction and restriction endonuclease digestion. Fibrinogen and D-Dimers levels, as well as factors' (f) V, X activity were measured by standard coagulometry techniques. Endothelial function was assessed by the flow mediated dilatation (FMD) of the brachial artery., Results: The two polymorphisms had no significant effect on the risk for CAD. Although the 58AA subjects had not significantly different levels of fibrinogen compared with the 58GG+GA in both groups (p=NS), we importantly found that the 455AA homozygosity was associated with increased fibrinogen levels not only in the control group (p=0.035), but also in the CAD group (p<0.001) compared to the G allele carriers. Moreover, both the 58AA (p=0.016) and 455AA homozygotes (p=0.022) presented with higher levels of D-Dimers in the CAD group. Interestingly, the 455AA homozygotes had increased fV activity in the CAD group (p=0.048). However, no significant effects were observed on fX activity and FMD., Conclusions: Both fibrinogen polymorphisms are capable to modify the atherosclerotic process via their effects on the coagulation cascade., (© 2013.)

Background: Adiponectin is an adipokine with an important role in cardiovascular system conferring anti-inflammatory and anti-atherogenic effects. Two common single nucleotide polymorphisms (SNP) on adiponectin gene, rs2241766 and rs1501299, have been associated with insulin resistance and diabetes mellitus risk however their effects on cardiovascular risk remain unclear. We examined the impact of rs2241766 and rs1501299 on circulating adiponectin levels, endothelial function and cardiovascular disease risk., Methods: We recruited in total 594 subjects; 462 patients with angiographically confirmed coronary artery disease (CAD) and 132 controls matched for age and gender. rs2241766 and rs1501299 were genotyped by polymerase chain reaction and restriction endonuclease digestion. Serum adiponectin levels were determined by enzyme-linked immunosorbent assay. Endothelial function was assessed by the flow mediated dilatation (FMD) of the brachial artery., Results: rs2241766 had no effects on circulating adiponectin levels or FMD. In subjects without CAD, carriers of the T/T alleles at rs1501299 had lower adiponectin levels (p=0.001) and impaired endothelial function (p<0.05). After multivariate adjustment none of the SNPs had any effect on CAD risk. However, carriers of the T allele at rs1501299 were at increased myocardial infarction (MI) risk, independently of classic risk factors (OR=2.558 [95%CI=1.587-4.123], p=0.0001). The number of T alleles in both SNPs was strongly associated with MI history (p=0.0001)., Conclusions: rs1501299 polymorphism of adiponectin gene affects circulating adiponectin levels and endothelial function in subjects without CAD. Presence of the T variant at rs1501299 on adiponectin gene is independently associated with increased myocardial infarction risk., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aims: Endothelin-1 (ET-1) has been shown to increase endothelial superoxide (O(2)(-)) production in experimental animal models. It is unclear whether ET-1 increases O(2)(-) production in humans. We sought to elucidate whether ET-1 increases O(2)(-) production in human vessels and to identify the mechanism behind this effect., Main Methods: Segments of internal mammary artery (IMA) and human saphenous vein (HSV) were harvested from 90 patients undergoing elective coronary artery bypass graft surgery. Paired vessel rings were incubated in the presence and absence of ET-1 (10(-10)M), the ET(A) receptor antagonist BQ123 alone, or in combination with the ET(B) receptor antagonist BQ788 (dual BQ) and known inhibitors of sources of O(2)(-) and further analysed for O(2)(-) production using lucigenin-enhanced chemiluminescence and DHE fluorescence., Key Findings: ET-1 increased O(2)(-) production in both IMA (2.6 ± 1.5 vs. 1.4 ± 0.8 relative light units/s/mg tissue (RLU); n=33; p < 0.0001) and HSV (1.4 ± 0.8 vs. 1.1 ± 0.6 RLU; n=24; p<0.05). The increase in O(2)(-)production induced by ET-1 in IMA was inhibited by co-incubation with dual BQ (p < 0.05; n=15) and BQ123 (p<0.05; n = 17). Of known O(2)(-) inhibitors, only incubation with Tiron and diphenyleneiodonium resulted in a significant reduction in ET-mediated O(2)(-) production., Significance: ET-1 increases O(2)(-) production especially in human arteries and less so in veins from patients with coronary artery disease via a receptor-dependent pathway involving a flavin dependent enzyme which is likely to be NADPH oxidase. Production of O(2)(-) may be an important factor underlying the negative effects of ET-1 on vascular function such as impairment of endothelium-dependent vasodilatation and pro-inflammatory effects., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed countries, with an increasing prevalence due to an aging population. The pathology underpinning CVD is atherosclerosis, a chronic inflammatory state involving the arterial wall. Accumulation of low density lipoprotein (LDL) laden macrophages in the arterial wall and their subsequent transformation into foam cells lead to atherosclerotic plaque formation. Progression of atherosclerotic lesions may gradually lead to plaque related complications and clinically manifest as acute vascular syndromes including acute myocardial or cerebral ischemia. Nanotechnology offers emerging therapeutic strategies, which may have advantage overclassical treatments for atherosclerosis. In this review, we present the potential applications of nanotechnology toward prevention, identification and treatment of atherosclerosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Myocardial injury related to coronary artery bypass grafting (CABG) is poorly characterized, and understanding the characteristic release of biomarkers associated with revascularization injury might provide novel therapeutic opportunities. This study characterized early changes in biomarkers after revascularization injury during on-pump CABG., Methods: This prospective study comprised 28 patients undergoing on-pump CABG and late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMRI) who underwent measurements of cardiac troponin I (cTnI), creatine kinase-MB, and inflammatory markers (C-reactive protein, serum amyloid A, myeloperoxidase, interleukin 6, tumor necrosis factor-α, matrix metalloproteinase 9a, monocyte chemotactic protein-1, plasminogen activator inhibitor-1a) at baseline, at 1, 6, 12, and 24 hours, and at 1 week (inflammatory markers only) post-CABG. Biomarker results at 1 hour were studied for a relationship to new myocardial infarction as defined by CMRI-LGE, and the diagnostic utility of combining positive biomarkers was assessed., Results: All patients had an uneventful recovery, but 9 showed a new myocardial infarction demonstrated by new areas of hyperenhancement on CMR. Peak cTnI at 24 hours (ρ = 0.66, p < 0.001) and CK-MB (ρ = 0.66, p < 0.001) correlated with the amount of new LGE. At 1 hour, 3 biomarkers--cTnI, interleukin 6, and tumor necrosis factor-α--were significantly elevated in patients with vs those without new LGE. Receiver operating curve analysis showed cTnI was the most accurate at detecting new LGE at 1 hour: a cutoff of cTnI exceeding 5 μg/L at 1 hour had 67% sensitivity and 79% specificity for detecting new LGE., Conclusions: Unexpected CABG-related myocardial injury occurs in a significant proportion of patients. A cTnI test at 1 hour after CABG could potentially differentiate patients with significant revascularization injury., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Several prospective epidemiological studies and clinical observations provided evidence regarding fibrinogen and coronary artery disease (CAD). Many of these studies firmly correlate fibrinogen with CAD. However, it is uncertain whether this relation is causal or reflects genetic variability and residual confounding by other risk factors. Several polymorphisms on fibrinogen chain genes affect its levels, however only few of the genetic variants are associated with increased cardiovascular risk. As regards the role of fibrinogen in myocardial infarction (MI) studies indicate that genetic variations have at best a modest impact on the process resulting in MI. Therefore, the screening of fibrinogen genes might not be useful for the assessment of the risk of MI. However, the findings that specific genotypes lead to specific differences in fibrinogen levels, but may not be linked to cardiovascular risk, complicates the hypothesis of causality of fibrinogen in the pathogenesis of cardiovascular disease., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Statin treatment improves survival in patients with atherosclerosis, but their effect on the glucose-induced variations of inflammatory markers, is unknown. We examined the effect of combined therapy with atorvastatin and metformin on glucose-induced variations of inflammatory molecules in patients with newly diagnosed diabetes mellitus type 2 (DM)., Methods: Thirty five subjects with newly diagnosed DM were randomized to receive metformin 850 mg/d (M, n=17) or metformin 850 mg/d+atorvastatin 10mg (n=18). All subjects underwent glucose loading (75 g oral glucose) at baseline and after 12 weeks of treatment. Blood samples were obtained at baseline and 3h post-loading, while serum tumor necrosis factor alpha (TNF-α) levels were determined at baseline and at 3h., Results: Serum TNF-α remained unchanged in metformin at baseline (1.36±0.18 to 1.47±0.21 pg/ml p=NS) and after treatment (1.44±0.71 to 1.31±0.17 pg/ml, p=NS), while it was reduced in metformin+atorvastatin (2.3±0.3 to 2.0±0.4 pg/ml, p=NS at baseline and 1.80±0.2 to 1.65±0.2 pg/ml, p=0.03 after treatment)., Conclusions: Interestingly, the combination of metformin and atorvastatin partly prevents the glucose-loading induced elevation of glucose levels (at 1 h), suggesting a better response to glucose intake than monotherapy with metformin. In addition, combined treatment with atorvastatin and metformin reduces the post-glucose loading levels of TNF-α compared to metformin monotherapy., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: The incorporation of right-sided chest leads (V(3)R-V(5)R) into the standard exercise testing has been reported to improve its diagnostic accuracy. The purpose of this study was to evaluate the ability of exercise testing in detecting right ventricular (RV) dysfunction post myocardial infarction (MI) of the inferior wall, using additional V(3)R-V(5)R leads., Methods: We studied 133 patients (59 ± 5 years, 81 males) with a history of inferior MI due to right coronary artery obstruction (affirmed with coronary angiography). All patients underwent an echocardiographic assessment of RV function 4 weeks after discharge and an exercise treadmill test in order to detect possible RV dysfunction. Recordings during exercise were obtained with the standard 12 leads plus V(3)R-V(5)R., Results: From 133 patients, 97 (group A) presented with normal right ventricle according to the echocardiographic study while the rest 36 patients (group B) presented with RV dysfunction. Maximal exercise-induced ST-segment deviation (in mm) was similar in the standard 12 leads for the 2 groups (2.1 ± 0.4 vs 1.8 ± 0.3, p = NS) while in V(3)R-V(5)R it was greater in group B (0.7 ± 0.3 vs 1.4 ± 0.4, p<0.05). Sensitivity, positive prognostic value, negative prognostic value and accuracy of exercise testing in detecting RV dysfunction were all improved using V(3)R-V(5)R (78 vs 47%, 39 vs 29%, 87 vs 75%, 62 vs 55% respectively, p<0.05 for all) while specificity was not deteriorated (56 vs 58%, p = NS)., Conclusions: The addition of right-sided chest leads (V(3)R-V(5)R) improves the diagnostic ability of standard exercise testing in detecting and especially in excluding RV dysfunction post inferior MI., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with chronic heart failure (HF) are characterized by alterations in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) levels. However, the impact of hypolipidemic and antioxidant treatment in MMPs and TIMPs is unknown. In the present study, we sought to compare the effects of statins and xanthine oxidase inhibitors on circulating levels of MMPs and TIMPs in patients with chronic HF., Methods: Forty-two clinically stable patients with mild to moderate HF were randomized to receive rosuvastatin 10 mg or allopurinol 300 mg daily and followed up for 1 month. Serum levels of MMP-2, -9, TIMP-1, and -2 were measured before and after treatment., Results: Levels of MMP-2 and -9 were significantly decreased in the rosuvastatin group (from 251±52 ng/ml and 400±206 ng/ml to 215±47 ng/ml and 309±166 ng/ml, p<0.001 and p<0.05 respectively), but not in the allopurinol group. In the rosuvastatin group, TIMP-2 levels were significantly increased (from 85±17 ng/ml to 93±16 ng/ml, p<0.05), while TIMP-1 remained unchanged. In the allopurinol group, no significant changes were observed regarding the levels of TIMPs., Conclusions: Short-term rosuvastatin but not allopurinol administration decreases MMP-2 and -9 and increases TIMP-2 levels., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Exercise testing (ET) stands as one of the most easy, affordable, cost effective, non invasive methods for diagnosing coronary heart disease. Its sensitivity, specificity and prognostic value, especially in the prime era of its implementation in the cardiac diagnostic procedure, is relatively limited. Novel exercise criteria and indices based either on ST segment changes or ST segment independent parameters, such as "Athens QRS score", have greatly improved the diagnostic ability and accuracy of ET. Complex ECG-derived indices linked to ST changes along with the use of right-sided precordial leads have also enhanced the diagnostic accuracy of ET with respect to the extent of ischemic heart disease and the detection of specific culprit vessels. ET contains also a prognostic value, since several ET-derived parameters have been associated with adverse outcome, including ST changes, blood pressure and heart rate response to exercise and duration of exercise., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Congestive heart failure (HF) is characterised by increased proinflammatory stimulation and impaired endothelial function. Statin treatment exerts a beneficial effect on endothelial function and inflammatory process in patients with atherosclerosis. However, its effect in patients with HF is not well studied. Therefore, in the present study we compared the effect of short-term treatment with rosuvastatin or ezetimibe on endothelial function in patients with HF., Methods: In this double-blind, placebo controlled, cross-over trial, 22 patients with HF were randomised to receive ezetimibe 20 mg/d or rosuvastatin 10 mg/d for 4 weeks, with 4 weeks wash-out period between the two interventions. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery at the beginning and at the end of each treatment period., Results: There was no change in the baseline brachial diameter after treatment with either ezetimibe (p=NS) or rosuvastatin (p=NS). However, there was a significant improvement of FMD in the rosuvastatin group (p<0.05) but not in the ezetimibe group (p=NS). The changes in lipid levels were similar between groups (p=NS). The change in FMD was not significantly correlated with the decrease of serum LDL in either the ezetimibe or rosuvastatin treated groups., Conclusions: Rosuvastatin improves endothelial function in patients with congestive heart failure, by mechanisms independent of lipid-lowering. On the contrary, lipid-lowering treatment achieved by ezetimibe is unable to affect endothelial function in these patients. These findings indicate a direct beneficial effect of statins in patients with congestive heart failure, further to lipid-lowering., (Copyright 2008 Elsevier Ireland Ltd. All rights reserved.)

Major depression is a common feature of heart failure patients and possibly stems from their common biochemical background. Depression and heart failure co-morbidity has several clinical implications on the prognosis of these patients. Furthermore antidepressive drugs have known cardiovascular side effects, while their safety and efficacy in heart failure has not been fully elucidated yet. The right choice of antidepressive treatment in heart failure constitutes an issue of high importance as it can affect the clinical outcome of these patients. In this article we highlight the role of major depression in heart failure and demonstrate their common biochemical background. Moreover we review the acquired so far knowledge on the use of the various categories of antidepressants in heart failure by reference to the existing clinical studies on antidepressants efficacy and safety in heart failure. Even though certain conclusions cannot be drawn yet, evidence suggests that the use of selective serotonin reuptake inhibitors may have a beneficial effect on clinical outcome of heart failure patients., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Atrial fibrillation has been associated with increased oxidative stress, elevated inflammatory status and endothelial dysfunction. However, the underlying mechanisms regulating the expression of inflammatory markers or oxidative stress status are unclear. We searched for clinical determinants of oxidative stress status, endothelial function and inflammatory process in patients with chronic atrial fibrillation., Methods: Sixty nine patients with chronic atrial fibrillation at a stable clinical state were recruited. Ejection fraction of the left ventricle and the dimensions of the left atrium were determined echocardiographically. Flow mediated dilatation (FMD) was evaluated in the brachial artery, while serum oxidized LDL (ox-LDL), matrix metalloproteinase-9 (MMP-9), soluble CD40-ligand (sCD40L) and C-reactive protein (CRP) were measured., Results: FMD was correlated with CRP (r=-0.423, p=0.028), independently of other clinical parameters (beta(SE): -0.0039(0.00159), p=0.022). Ox-LDL was significantly correlated with left atrium diameter(r=0.358, p=0.005) independently of other clinical variables (beta(SE):1.288(0.455), p=0.007). The only independent predictors of MMP-9 were sCD40L (beta(SE):17.232(7.654), p=0.028), CRP (beta(SE):4.249(2.186), p=0.05) and gender (beta(SE):204.657(68.153), p=0.004), but not left atrium dimensions. Independent predictors of CRP were hypertension (beta(SE): 8.531(3.973), p=0.036), sCD40L (beta(SE): 0.779(0.408), p=0.06) and age (beta(SE): 0.381(0.201), p=0.063)., Conclusions: There is a strong link between inflammation and endothelial function, in patients with atrial fibrillation. The maximum diameter of left atrium is the only independent predictor of oxidized LDL, suggesting that left atrium distension may predict oxidative stress status in these patients.