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Coronary Artery Disease: HELP
Articles by Ulf Landmesser
Based on 31 articles published since 2008
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Between 2008 and 2019, Ulf Landmesser wrote the following 31 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial A new look at HDL in coronary disease: can we escape natural history? 2011

Gielen, Stephan / Landmesser, Ulf. · ·Heart · Pubmed #21835756.

ABSTRACT: -- No abstract --

2 Review Algorithmic Approach for Optical Coherence Tomography-Guided Stent Implantation During Percutaneous Coronary Intervention. 2018

Shlofmitz, Evan / Shlofmitz, Richard A / Galougahi, Keyvan Karimi / Rahim, Hussein M / Virmani, Renu / Hill, Jonathan M / Matsumura, Mitsuaki / Mintz, Gary S / Maehara, Akiko / Landmesser, Ulf / Stone, Gregg W / Ali, Ziad A. ·Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA; Department of Cardiology, St. Francis Hospital, 100 Port Washington Boulevard, Suite 105, Roslyn, NY 11576, USA; Clinical Trials Center, Cardiovascular Research Foundation, 1700 Broadway 9th Floor, New York, NY 10019, USA. · Department of Cardiology, St. Francis Hospital, 100 Port Washington Boulevard, Suite 105, Roslyn, NY 11576, USA. · Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. · CVPath Institute, 19 Firstfield Road, Gaithersburg, MD 20878, USA. · London Bridge Hospital, 2nd Floor, St Olaf House, London SE1 2PR, UK; Department of Cardiology, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. · Clinical Trials Center, Cardiovascular Research Foundation, 1700 Broadway 9th Floor, New York, NY 10019, USA. · Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA; Clinical Trials Center, Cardiovascular Research Foundation, 1700 Broadway 9th Floor, New York, NY 10019, USA. · Department of Cardiology, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin 12200, Germany. · Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA; Department of Cardiology, St. Francis Hospital, 100 Port Washington Boulevard, Suite 105, Roslyn, NY 11576, USA; Clinical Trials Center, Cardiovascular Research Foundation, 1700 Broadway 9th Floor, New York, NY 10019, USA. Electronic address: zaa2112@columbia.edu. ·Interv Cardiol Clin · Pubmed #29983145.

ABSTRACT: Intravascular imaging plays a key role in optimizing outcomes for percutaneous coronary intervention (PCI). Optical coherence tomography (OCT) utilizes a user-friendly interface and provides high-resolution images. OCT can be used as part of daily practice in all stages of a coronary intervention: baseline lesion assessment, stent selection, and stent optimization. Incorporating a standardized, algorithmic approach when using OCT allows for precision PCI.

3 Review High-Density Lipoproteins: Effects on Vascular Function and Role in the Immune Response. 2018

Haghikia, Arash / Landmesser, Ulf. ·Department of Cardiology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin 12203, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Postfach 65 21 33, Berlin 13316, Germany. Electronic address: arash.haghikia@charite.de. · Department of Cardiology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin 12203, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Postfach 65 21 33, Berlin 13316, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, Berlin 10178, Germany. ·Cardiol Clin · Pubmed #29609761.

ABSTRACT: The focus in studies of high-density lipoproteins was on their capacity to remove excess cholesterol and deliver it to the liver. Other functions and vascular effects have been described. Clinical trials and translational/genetic studies have led to a refined understanding of the role of high-density lipoprotein; it is likely not a causal cardiovascular risk factor. In healthy subjects, it limits lipid oxidation, protects endothelial cell functions/integrity, and exerts antiinflammatory/antiapoptotic effects. In patients with coronary disease or diabetes, it undergoes modifications/remodeling, resulting in dysfunctional high-density lipoprotein. We summarize recent findings about the regulation of its function and discuss the clinical implications.

4 Review Intracoronary optical coherence tomography: Clinical and research applications and intravascular imaging software overview. 2017

Tenekecioglu, Erhan / Albuquerque, Felipe N / Sotomi, Yohei / Zeng, Yaping / Suwannasom, Pannipa / Tateishi, Hiroki / Cavalcante, Rafael / Ishibashi, Yuki / Nakatani, Shimpei / Abdelghani, Mohammad / Dijkstra, Jouke / Bourantas, Christos / Collet, Carlos / Karanasos, Antonios / Radu, Maria / Wang, Ancong / Muramatsu, Takashi / Landmesser, Ulf / Okamura, Takayuki / Regar, Evelyn / Räber, Lorenz / Guagliumi, Giulio / Pyo, Robert T / Onuma, Yoshinobu / Serruys, Patrick W. ·Erasmus University Medical Centre, Thoraxcenter, Rotterdam, The Netherlands. · Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, United States. · Academic Medical Center-University of Amsterdam, Amsterdam, The Netherlands. · Leiden University Medical Center, Leiden, The Netherlands. · University College of London Hospitals, London, United Kingdom. · Copenhagen University Hospital, Copenhagen, Denmark. · Fujita Health University Hospital, Toyoake, Japan. · Charite Universitätsmedizin Berlin, Berlin, Germany. · Yamaguchi University, Yamaguchi, Japan. · Department of Cardiovascular Surgery, University Hospital Zürich, Switzerland. · Bern University Hospital, Bern, Switzerland. · Ospedali Riuniti di Bergamo, Bergamo, Italy. · Albert Einstein College of Medicine, Montefiore Medical Center, NY. · International Centre for Circulatory Health, Imperial College, London, United Kingdom. ·Catheter Cardiovasc Interv · Pubmed #28109054.

ABSTRACT: By providing valuable information about the coronary artery wall and lumen, intravascular imaging may aid in optimizing interventional procedure results and thereby could improve clinical outcomes following percutaneous coronary intervention (PCI). Intravascular optical coherence tomography (OCT) is a light-based technology with a tissue penetration of approximately 1 to 3 mm and provides near histological resolution. It has emerged as a technological breakthrough in intravascular imaging with multiple clinical and research applications. OCT provides detailed visualization of the vessel following PCI and provides accurate assessment of post-procedural stent performance including detection of edge dissection, stent struts apposition, tissue prolapse, and healing parameters. Additionally, it can provide accurate characterization of plaque morphology and provides key information to optimize post-procedural outcomes. This manuscript aims to review the current clinical and research applications of intracoronary OCT and summarize the analytic OCT imaging software packages currently available. © 2017 Wiley Periodicals, Inc.

5 Review Platelets and coronary artery disease: Interactions with the blood vessel wall and cardiovascular devices. 2016

Reinthaler, Markus / Braune, Steffen / Lendlein, Andreas / Landmesser, Ulf / Jung, Friedrich. ·Department for Cardiology, Charité Universitätsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Helmholtz Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany; and Joint Laboratory HZG/Charité-FUB, Kantstr. 55, 14513 Teltow, Germany. · Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Helmholtz Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany. · Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Helmholtz Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany and Joint Laboratory HZG/Charité-FUB, Kantstr. 55, 14513 Teltow, Germany. · Department for Cardiology, Charité Universitätsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany and Joint Laboratory HZG/Charité-FUB, Kantstr. 55, 14513 Teltow, Germany. ·Biointerphases · Pubmed #27277200.

ABSTRACT: In view of the rare presence of studies concerning platelet function as risk factor in atherosclerotic patients, processes underlying thromboembolic events are reviewed in this paper. The morphology and the structural organization-membrane receptors, the open canalicular and dense tubular systems, the cytoskeleton, mitochondria, granules, lysosomes, and peroxisomes-of platelets are described. Platelet function under physiological conditions in atherosclerosis and after implantation of cardiovascular devices is summarized.

6 Review LDL, HDL, VLDL, and CVD Prevention: Lessons from Genetics? 2015

Hewing, Bernd / Landmesser, Ulf. ·Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany. ·Curr Cardiol Rep · Pubmed #26031673.

ABSTRACT: Over the past years, genetic studies on lipid traits have substantially extended our understanding of the relationship between lipid metabolism and coronary artery disease (CAD). Thereby, novel pathways and interactions in lipid metabolism unraveled by genetic studies have led to promising novel treatment strategies that are currently evaluated for prevention and treatment of CAD, such as low-density lipoprotein cholesterol (LDL-C) lowering by inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9). This review article discusses findings from recent genetic studies and their implications for the understanding of the relation between lipid metabolism and CAD as well as the development of novel therapeutic strategies supported by these studies.

7 Review High-density lipoproteins as modulators of endothelial cell functions: alterations in patients with coronary artery disease. 2014

Kratzer, Adelheid / Giral, Hector / Landmesser, Ulf. ·Division of Cardiology, University Heart Center, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland Center of Molecular Cardiology, University of Zurich, Zurich, Switzerland. · Division of Cardiology, University Heart Center, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland Center of Molecular Cardiology, University of Zurich, Zurich, Switzerland ulf.landmesser@usz.ch. ·Cardiovasc Res · Pubmed #24935432.

ABSTRACT: Alteration of endothelial cell functions, including reduced endothelial nitric oxide (NO) availability, increased endothelial cell apoptosis, adhesion molecule/chemokine expression and pro-thrombotic activation are thought to contribute to the pathophysiology of atherosclerosis and coronary-artery-disease (CAD) with its clinical complications, such as acute coronary syndromes. High-density lipoproteins (HDL) from healthy subjects or reconstituted HDL have been observed to exert potential direct anti-atherogenic effects by modulating these endothelial cell functions. Importantly, endothelial effects of HDL have now been reported to be highly heterogeneous, and are modulated as part of immune responses. More recently, this has also been observed for HDL of patients with CAD, where HDL becomes potentially pro-inflammatory and endothelial-protective properties are markedly altered. Several mechanisms may lead to these altered endothelial effects of HDL in patients with CAD, including oxidative modification of HDL-associated lipids and proteins, such as apoA-I and paraoxonase-1, and alterations of HDL-proteome. These findings have to be considered with respect to interpretation of recent clinical studies failing to demonstrate reduced cardiovascular events by HDL-cholesterol raising strategies in patients with CAD. Both clinical and genetic studies suggest that HDL-cholesterol levels alone are not a sufficient therapeutic target in patients with CAD. The focus of this review is to summarize the role of HDL onto endothelial homeostasis and to describe recently characterized molecular pathways involved. We highlight how structural and functional modifications of HDL particles in patients with CAD may perturb the physiological homeostasis and lead to a loss of endothelial-protective properties of HDL in patients with CAD.

8 Clinical Trial Non-invasive assessment of coronary artery disease with CT coronary angiography and SPECT: a novel dose-saving fast-track algorithm. 2010

Pazhenkottil, Aju P / Herzog, Bernhard A / Husmann, Lars / Buechel, Ronny R / Burger, Irene A / Valenta, Ines / Landmesser, Ulf / Wyss, Christophe A / Kaufmann, Philipp A. ·Cardiac Imaging, University Hospital Zurich, Ramistrasse 100, CH-8091, Zurich, Switzerland. ·Eur J Nucl Med Mol Imaging · Pubmed #19789871.

ABSTRACT: PURPOSE: To validate a new low-dose and rapid stepwise individualized algorithm for non-invasive assessment of ischemic coronary artery disease by sequential use of prospectively ECG-triggered low-dose CT coronary angiography (CTCA) and low-dose single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). METHODS: Forty patients referred for elective invasive coronary angiography (CA) were prospectively enrolled to undergo a comprehensive non-invasive evaluation with low-dose CTCA and a dose-reduced stress/rest SPECT-MPI scan (using dedicated reconstruction algorithms for low count scans). The following algorithm was reviewed: CTCA first, followed by a stress-only MPI if a coronary stenosis (> or = 50% diameter narrowing) or equivocal findings were observed. Only abnormal stress MPI scans were followed by rest MPI. The accuracy of the individualized algorithm to predict coronary revascularization and its mean effective radiation dose were assessed. RESULTS: CTCA documented CAD in 18 and equivocal findings in two patients, thus, requiring additional stress MPI scans. Of these, 16 were abnormal, therefore requiring a rest MPI scan, revealing ischemia in 15 patients. Sensitivity, specificity, negative and positive predictive value, and accuracy of the individualized algorithm for predicting coronary revascularization was 93.3%, 96.0%, 96.0%, 93.3% and 95.0% on a per-patient base. The mean effective radiation dose was significantly lower for the individualized (4.8 +/- 3.4 mSv) versus the comprehensive method (8.1 +/- 1.5 mSv) resulting in a total population radiation dose reduction of 132.6 mSv. CONCLUSION: This new individualized low-dose algorithm allows rapid and accurate prediction of invasive CA findings and of treatment decision with minimized radiation dose.

9 Article Prognostic impact of Interleukin-1 receptor antagonist in patients with documented coronary artery disease. 2018

Schofer, Niklas / Ludwig, Sebastian / Rübsamen, Nicole / Schnabel, Renate / Lackner, Karl J / Ruprecht, Hans J / Bickel, Christoph / Landmesser, Ulf / Blankenberg, Stefan / Zeller, Tanja. ·Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany. Electronic address: n.schofer@uke.de. · Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany. · Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; German Center of Cardiovascular Research (DZHK), partner site Hamburg/Lübeck/Kiel, Hamburg, Germany. · Department of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany. · Department of Medicine II, GPR Klinikum Ruesselsheim, Ruesselsheim, Germany. · Department of Internal Medicine, Federal Armed Forces Hospital Koblenz, Koblenz, Germany. · Department of Cardiology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany. ·Int J Cardiol · Pubmed #29395365.

ABSTRACT: BACKGROUND: IL-1β-mediated inflammation contributes to development and progression of coronary artery disease (CAD). We aimed to assess the prognostic impact of the inflammatory marker Interleukin-1 receptor antagonist (IL1-Ra), reflecting high IL-1β activity, in patients with documented CAD. METHODS: IL-1Ra levels were determined in 1337 subjects of the AtheroGene study, a prospective cardiovascular registry comprising patients with CAD as detected by coronary angiography presenting with acute coronary syndrome (ACS) or stable angina. Median follow-up was 6.4 years. RESULTS: Patients with IL1-Ra levels in the highest tertile presented more often with ACS (55% vs. 40% vs. 34%, p < 0.001), were more commonly treated with PCI (47% vs. 39% vs. 34%, p < 0.001), had lower left ventricular ejection fraction (LVEF) (61 ± 15% vs. 62 ± 15% vs. 65 ± 14%, p = 0.001) and higher hs-CRP levels (10.0 vs. 4.2 vs. 2.5 mg/L, p < 0.001). IL1-Ra levels at baseline were predictive for all-cause mortality in the total study cohort after adjustment for conventional cardiovascular risk factors, LVEF, hs-CRP and Troponin T (adjusted HR 1.45 (95% CI 1.16-1.82), p < 0.001). In a subgroup of patients with ACS, but not in those with stable angina, IL1-Ra was an independent predictor for cardiovascular mortality (ACS: adjusted HR 1.93 (95% CI 1.33-2.80), p < 0.001; stable angina: adjusted HR: 1.26 (95% CI 0.92-1.73), p = 0.16). CONCLUSION: IL1-Ra is an independent predictor for adverse outcome in patients with documented CAD, beyond the prognostic value of hs-CRP and Troponin T in particular in the setting of ACS. For CAD patients our finding might improve both, risk assessment in secondary prevention and patient selection for anti-inflammatory treatment.

10 Article Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes. 2017

Klingenberg, Roland / Aghlmandi, Soheila / Liebetrau, Christoph / Räber, Lorenz / Gencer, Baris / Nanchen, David / Carballo, David / Akhmedov, Alexander / Montecucco, Fabrizio / Zoller, Stefan / Brokopp, Chad / Heg, Dik / Jüni, Peter / Marti Soler, Helena / Marques-Vidal, Pedro-Manuel / Vollenweider, Peter / Dörr, Oliver / Rodondi, Nicolas / Mach, François / Windecker, Stephan / Landmesser, Ulf / von Eckardstein, Arnold / Hamm, Christian W / Matter, Christian M / Lüscher, Thomas F. ·Department of Cardiology, University Heart Center, University Hospital of Zurich and Center for Molecular Cardiology, University of Zurich, Rämistr. 100, CH-8091 Zurich, Switzerland and Wagistr. 12, CH-8952 Schlieren, Switzerland. · Department of Cardiology, Kerckhoff Heart and Thorax Center, Kerckhoff-Klinik, Benekestr. 2-8, D-61231 Bad Nauheim, Germany. · DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Benekestr. 2-8, D-61231 Bad Nauheim, Germany. · Institute of Social and Preventive Medicine (ISPM), University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland. · CTU Bern, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland. · Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Spitalstr. 12, CH-4056 Basel, Switzerland. · Department of Cardiology, Cardiovascular Center, University Hospital of Bern, Freiburgstr. 18, CH-3010 Bern, Switzerland. · Department of Cardiology, Cardiovascular Center, University Hospital of Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva 14, Switzerland. · Department of Ambulatory Care and Community Medicine, University of Lausanne, Rue du Bugnon 44, CH-1011 Lausanne, Switzerland. · First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6, Viale Benedetto XV, IT-16132 Genoa, Italy. · Bioinformatics, Genetic Diversity Center, Federal Institute of Technology (ETH), Universitätsstr. 16, CH-8092 Zurich, Switzerland. · Department of Cardiothoracic Surgery, Regenerative Medicine Center, Department of Cardiothoracic Surgery, University Hospital of Zurich, Wagistr. 12, CH-8952 Schlieren, Switzerland. · Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, 209 Victoria St, Toronto, ON M5B 1T8, Canada. · Department of General Internal Medicine, University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. · Department of Cardiology, University Hospital of Giessen, Klinikstr. 33; D-35392 Giessen, Germany. · Institute of Primary Health Care (BIHAM), University of Bern, Gesellschaftsstr. 49, CH-3012 Bern, Switzerland. · Department of General Internal Medicine, University Hospital of Bern, Freiburgstr. 18, CH-3010 Bern, Switzerland. · Department of Cardiology, Charité Campus Benjamin-Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany. · Institute of Clinical Chemistry, University Hospital of Zurich, Rämistr. 100, CH-8091 Zurich, Switzerland. ·Eur Heart J · Pubmed #29155984.

ABSTRACT: Aims: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. Methods and results: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. Conclusion: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.

11 Article PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. 2017

Thiele, Holger / Akin, Ibrahim / Sandri, Marcus / Fuernau, Georg / de Waha, Suzanne / Meyer-Saraei, Roza / Nordbeck, Peter / Geisler, Tobias / Landmesser, Ulf / Skurk, Carsten / Fach, Andreas / Lapp, Harald / Piek, Jan J / Noc, Marko / Goslar, Tomaž / Felix, Stephan B / Maier, Lars S / Stepinska, Janina / Oldroyd, Keith / Serpytis, Pranas / Montalescot, Gilles / Barthelemy, Olivier / Huber, Kurt / Windecker, Stephan / Savonitto, Stefano / Torremante, Patrizia / Vrints, Christiaan / Schneider, Steffen / Desch, Steffen / Zeymer, Uwe / Anonymous351213. ·From Heart Center Leipzig, University Hospital, Leipzig (H.T., M.S., S.D.), Universitätsmedizin Mannheim, Mannheim (I.A.), University Heart Center Lübeck, Lübeck (G.F., S. de Waha, R.M.-S.), German Center for Cardiovascular Research (DZHK) (G.F., S. de Waha, R.M.-S., U.L., C.S., S.B.F., S.D.) and Universitätsklinikum Charité, Campus Benjamin Franklin (U.L., C.S.), Berlin, Universitätsklinikum Würzburg, Würzburg (P.N.), Klinikum der Eberhard-Karls-Universität Tübingen, Tübingen (T. Geisler), Klinikum Links der Weser, Bremen (A.F.), Helios Klinik Erfurt, Erfurt (H.L.), Ernst-Moritz-Arndt-Universität, Greifswald (S.B.F.), Universitäres Herzzentrum Regensburg, Regensburg (L.S.M.), and Institut für Herzinfarktforschung (S. Schneider, U.Z.) and Klinikum Ludwigshafen (U.Z.), Ludwigshafen - all in Germany · Academic Medical Center, Amsterdam (J.J.P.) · University Medical Center Ljubljana, Ljubljana, Slovenia (M.N., T. Goslar) · Institute of Cardiology, Warsaw, Poland (J.S.) · Golden Jubilee National Hospital, Glasgow, United Kingdom (K.O.) · Vilnius University Hospital Santaros Klinikos and Faculty of Medicine, Vilnius University, Vilnius, Lithuania (P.S.) · Sorbonne Université Paris 6, ACTION Study Group, Centre Hospitalier Universitaire Pitié-Salpêtrière (G.M., O.B.), and Applied Research, Technology Transfer, Industrial Collaboration, Société Par Actions Simplifiée (P.T.), Paris · Wilhelminenspital, Department of Cardiology, and Sigmund Freud University, Medical School, Vienna (K.H.) · University of Bern, Inselspital, Bern, Switzerland (S. Windecker) · Manzoni Hospital, Lecco, Italy (S. Savonitto) · and Universitair Ziekenhuis Antwerp, Antwerp, Belgium (C.V.). ·N Engl J Med · Pubmed #29083953.

ABSTRACT: BACKGROUND: In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial. METHODS: In this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke. RESULTS: At 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07). The time to hemodynamic stabilization, the risk of catecholamine therapy and the duration of such therapy, the levels of troponin T and creatine kinase, and the rates of bleeding and stroke did not differ significantly between the two groups. CONCLUSIONS: Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI. (Funded by the European Union 7th Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).

12 Article High incidence of cardiac dysfunction and response to antiviral treatment in patients with chronic hepatitis C virus infection. 2017

Poller, Wolfgang / Kaya, Ziya / Muche, Marion / Kasner, Mario / Skurk, Carsten / Kappert, Kai / Tauber, Rudolf / Escher, Felicitas / Schultheiss, Heinz-Peter / Epple, Hans-Jörg / Landmesser, Ulf. ·Department of Cardiology, Campus Benjamin Franklin, CC11, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. wolfgang.poller@charite.de. · German Centre for Cardiovascular Research (DZHK), Site Berlin, Germany. wolfgang.poller@charite.de. · German Centre for Cardiovascular Research (DZHK), Site Heidelberg, Germany. · Department of Cardiology, University of Heidelberg, Heidelberg, Germany. · Department of Gastroenterology, Infectiology and Rheumatology, CC 13, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Department of Cardiology, Campus Benjamin Franklin, CC11, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. · Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany. · German Centre for Cardiovascular Research (DZHK), Site Berlin, Germany. · Institute for Clinical Diagnostics and Therapy (IKDT), Berlin, Germany. · Department of Cardiology, CVK, Charité-Universitätsmedizin Berlin, Berlin, Germany. ·Clin Res Cardiol · Pubmed #28236021.

ABSTRACT: AIMS: Hepatitis C virus (HCV) has been associated with cardiomyopathies. Former anti-HCV therapies employing interferon could have serious side effects in patients with advanced heart failure since interferon may adversely impact upon cardiac function. We, therefore, examined whether the novel, interferon-free and highly virus-selective anti-HCV combination therapy might be applicable even in advanced or end-stage heart failure. METHODS AND RESULTS: In a retrospective series of HCV-positive patients admitted to our institution with suspected cardiac disease, coronary, valvular or hypertensive heart disease was diagnosed in 70/146 (47.9%). Among the others, 36/76 (47.4%) had myocardial disease: LV (32.9%)/RV (13.2%) hypertrophy, RV dysfunction (13.2%)/dilation (6.6%), severe diastolic dysfunction (7.9%), pulmonary hypertension (22.4%). One critically ill patient listed for heart transplantation (HTX) had previously not tolerated an interferon-based protocol. To still improve her chance of enduring transplant survival, we attempted an interferon-free virus-selective antiviral combination drug protocol under careful monitoring of possible side effects. Regarding clinical status she tolerated this treatment well, with the exception of transient severe hyponatremia requiring substitution. Her NYHA functional class improved from II-IV before to class II immediately after successful complete HCV elimination. CONCLUSIONS: Whereas prevalence of cardiac dysfunction and potential benefit from antiviral treatment was reported previously, there is lack of data regarding the response of patients with advanced heart failure. Since the highly HCV-selective drugs used above do not eliminate other cardiotropic viruses and have no direct effect on inflammation, massive improvement in such critically ill patients indicates a causal role of HCV in their cardiac failure, and of HCV elimination in their functional recovery.

13 Article Decreased phosphatidylcholine plasmalogens--A putative novel lipid signature in patients with stable coronary artery disease and acute myocardial infarction. 2016

Sutter, Iryna / Klingenberg, Roland / Othman, Alaa / Rohrer, Lucia / Landmesser, Ulf / Heg, Dierik / Rodondi, Nicolas / Mach, Francois / Windecker, Stephan / Matter, Christian M / Lüscher, Thomas F / von Eckardstein, Arnold / Hornemann, Thorsten. ·Institute of Clinical Chemistry, University and University Hospital of Zurich, Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Zurich, Switzerland. · Department of Cardiology and Cardiovascular Research, University Heart Center, University Hospital Zurich, Zurich, University of Zurich, Switzerland. · Institute of Clinical Chemistry, University and University Hospital of Zurich, Zurich, Switzerland; Institute of Social and Preventive Medicine, Clinical Trials Unit, University of Bern, Bern, Switzerland. · Institute of Clinical Chemistry, University and University Hospital of Zurich, Zurich, Switzerland. · Competence Center for Integrated Human Physiology, University of Zurich, Zurich, Switzerland; Department of Cardiology and Cardiovascular Research, University Heart Center, University Hospital Zurich, Zurich, University of Zurich, Switzerland; Department of Cardiology, Charité Universitätsmedizin Berlin, Berlin, Germany. · Institute of Social and Preventive Medicine, Clinical Trials Unit, University of Bern, Bern, Switzerland. · Department of Internal Medicine, University Hospital Bern, Bern, Switzerland. · Cardiology, University Hospital Geneva, Switzerland. · Cardiovascular Center, University Hospital Bern, Switzerland. · Competence Center for Integrated Human Physiology, University of Zurich, Zurich, Switzerland; Department of Cardiology and Cardiovascular Research, University Heart Center, University Hospital Zurich, Zurich, University of Zurich, Switzerland. · Institute of Clinical Chemistry, University and University Hospital of Zurich, Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Zurich, Switzerland; Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich and University of Zurich, Zurich, Switzerland. · Institute of Clinical Chemistry, University and University Hospital of Zurich, Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Zurich, Switzerland; Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich and University of Zurich, Zurich, Switzerland. Electronic address: thorsten.hornemann@usz.ch. ·Atherosclerosis · Pubmed #26773473.

ABSTRACT: OBJECTIVE: Glycerophospholipids and sphingolipids are structurally heterogeneous due to differences in the O- and N-linked fatty acids and head groups. Sphingolipids also show a heterogeneity in their sphingoid base composition which up to now has been little appreciated. The aim of this study was to investigate the association of certain glycerophospholipid and sphingolipid species with stable coronary artery disease (CAD) and acute myocardial infarction (AMI). METHODS: The lipid profile in plasma from patients with stable CAD (n = 18) or AMI (n = 17) was compared to healthy subjects (n = 14). Sixty five glycerophospholipid and sphingolipid species were quantified by LC-MS. The relative distribution of these lipids into lipoprotein fractions was analyzed. RESULTS: In the CAD cohort, 45 glycerophospholipid and sphingolipid species were significantly lower compared to healthy controls. In the AMI group, 42 glycerophospholipid and sphingolipid species were reduced. Four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) showed the most significant difference. Out of eleven analyzed sphingoid bases, four were lower in the CAD and six in the AMI group. Sphingosine-1-phosphate (S1P) levels were reduced in the AMI group whereas an atypical C16:1 S1P was lower in both groups. Phosphatidylcholine and sphingomyelin species were exclusively present in lipoprotein particles, whereas lysophosphatidylcholines were mainly found in the lipoprotein-free fraction. The observed differences were not explained by the use of statins as confirmed in a second, independent cohort. CONCLUSIONS: Reduced levels of four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) were identified as a putatively novel lipid signature for CAD and AMI.

14 Article Plasmalogens of high-density lipoproteins (HDL) are associated with coronary artery disease and anti-apoptotic activity of HDL. 2015

Sutter, Iryna / Velagapudi, Srividya / Othman, Alaa / Riwanto, Meliana / Manz, Jasmin / Rohrer, Lucia / Rentsch, Katharina / Hornemann, Thorsten / Landmesser, Ulf / von Eckardstein, Arnold. ·Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland. · Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Personalized Medicine, ETH Zurich and University of Zurich, Switzerland. · Division of Nephrology, Institute of Physiology, University of Zurich, Switzerland. · Divison of Cardiology, University Hospital Zurich, Switzerland; Cardiovascular Research, Institute of Physiology, University of Zurich, Switzerland. · Competence Center for Integrated Human Physiology, University of Zurich, Switzerland; Divison of Cardiology, University Hospital Zurich, Switzerland; Cardiovascular Research, Institute of Physiology, University of Zurich, Switzerland. · Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland; Competence Center for Personalized Medicine, ETH Zurich and University of Zurich, Switzerland. Electronic address: arnold.voneckardstein@usz.ch. ·Atherosclerosis · Pubmed #26093887.

ABSTRACT: OBJECTIVE: Low high-density lipoprotein (HDL) cholesterol and loss of atheroprotective functions of HDL are associated with coronary artery disease (CAD). Here, we investigated the associations of HDL phospholipids with acute and stable CAD as well as with the anti-apoptotic activity of HDL. METHODS: 49 species of phosphatidylcholines (PCs), lysophosphatidylcholines and sphingomyelins (SMs) as well as three species of sphingosine-1-phosphate (S1P) were quantified by liquid chromatography - mass spectrometry in HDL isolated from 22 healthy subjects as well as 23 and 22 patients with stable CAD and acute coronary syndrome (ACS), respectively. Native HDL and artificially reconstituted HDL (rHDL) were tested for their capacity to inhibit apoptosis of endothelial cells (ECs) induced by serum deprivation. RESULTS: HDL of CAD or ACS patients differed from HDL of healthy controls by the content in nine of the 52 quantified phospholipid species as well as reduced anti-apoptotic activity. The capacity of HDL to inhibit EC apoptosis correlated significantly with five of eleven odd-chain PC's (= plasmalogens), two S1P's, SM42:2, PC34:2, and PC32:0. An orthogonal partial least square - discriminant analysis revealed independent associations of stable CAD with HDL-associated PC34:2, PC33:3 and PC35:2 as well as anti-apoptotic activity of HDL and of ACS with HDL-associated PC33:3, PC35:2, SM42:1, PC34:2 and PC36:2. rHDL reconstituted with apoA-I, PC34:1, and PC35:2 inhibited apoptosis of EC's more effectively than rHDL containing only apoA-I and PC34:1. CONCLUSIONS: The inverse association of HDL-plasmalogen levels with both stable and acute CAD may reflect direct anti-apoptotic effects of plasmologens on ECs.

15 Article Circulating FABP4 is a prognostic biomarker in patients with acute coronary syndrome but not in asymptomatic individuals. 2015

Reiser, Hans / Klingenberg, Roland / Hof, Danielle / Cooksley-Decasper, Seraina / Fuchs, Nina / Akhmedov, Alexander / Zoller, Stefan / Marques-Vidal, Pedro / Marti Soler, Helena / Heg, Dik / Landmesser, Ulf / Rodondi, Nicolas / Mach, Francois / Windecker, Stephan / Vollenweider, Peter / Matter, Christian M / Lüscher, Thomas F / von Eckardstein, Arnold / Gawinecka, Joanna. ·From the Institute of Clinical Chemistry (H.R., D.H., S.C.-D., A.v.E., J.G.), Department of Cardiology, University Heart Center (R.K., N.F., A.A., U.L., C.M.M.), University Hospital Zurich, Zurich, Switzerland · Competence Center for Systems Physiology and Metabolic Diseases (CC-SPMD), Zurich, Switzerland (H.R., A.v.E.) · Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland (S.C.-D., U.L., C.M.M., T.F.L., A.v.E.) · Bioinformatics, Genetic Diversity Center, Federal Institute of Technology (ETH), Zurich, Switzerland (S.Z.) · Department of Internal Medicine (P.M.-V., P.V.), Institute of Social and Preventive Medicine, Department of Community Medicine and Public Health (H.M.S.), University of Lausanne, Lausanne, Switzerland · Institute of Social and Preventive Medicine, and Clinical Trials Unit, Department of Clinical Research (D.H.), Department of General Internal Medicine (N.R.), Department of Cardiology, Swiss Cardiovascular Center Bern (S.W.), University Hospital Bern, Bern, Switzerland · and Department of Cardiology, University Hospital Geneva, Geneva, Switzerland (F.M.). ·Arterioscler Thromb Vasc Biol · Pubmed #26069234.

ABSTRACT: OBJECTIVE: Blood-borne biomarkers reflecting atherosclerotic plaque burden have great potential to improve clinical management of atherosclerotic coronary artery disease and acute coronary syndrome (ACS). APPROACH AND RESULTS: Using data integration from gene expression profiling of coronary thrombi versus peripheral blood mononuclear cells and proteomic analysis of atherosclerotic plaque-derived secretomes versus healthy tissue secretomes, we identified fatty acid-binding protein 4 (FABP4) as a biomarker candidate for coronary artery disease. Its diagnostic and prognostic performance was validated in 3 different clinical settings: (1) in a cross-sectional cohort of patients with stable coronary artery disease, ACS, and healthy individuals (n=820), (2) in a nested case-control cohort of patients with ACS with 30-day follow-up (n=200), and (3) in a population-based nested case-control cohort of asymptomatic individuals with 5-year follow-up (n=414). Circulating FABP4 was marginally higher in patients with ST-segment-elevation myocardial infarction (24.9 ng/mL) compared with controls (23.4 ng/mL; P=0.01). However, elevated FABP4 was associated with adverse secondary cerebrovascular or cardiovascular events during 30-day follow-up after index ACS, independent of age, sex, renal function, and body mass index (odds ratio, 1.7; 95% confidence interval, 1.1-2.5; P=0.02). Circulating FABP4 predicted adverse events with similar prognostic performance as the GRACE in-hospital risk score or N-terminal pro-brain natriuretic peptide. Finally, no significant difference between baseline FABP4 was found in asymptomatic individuals with or without coronary events during 5-year follow-up. CONCLUSIONS: Circulating FABP4 may prove useful as a prognostic biomarker in risk stratification of patients with ACS.

16 Article Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis. 2014

Windecker, Stephan / Stortecky, Stefan / Stefanini, Giulio G / da Costa, Bruno R / Rutjes, Anne Wilhelmina / Di Nisio, Marcello / Silletta, Maria G / Maione, Ausilia / Alfonso, Fernando / Clemmensen, Peter M / Collet, Jean-Philippe / Cremer, Jochen / Falk, Volkmar / Filippatos, Gerasimos / Hamm, Christian / Head, Stuart / Kappetein, Arie Pieter / Kastrati, Adnan / Knuuti, Juhani / Landmesser, Ulf / Laufer, Günther / Neumann, Franz-Joseph / Richter, Dimitri / Schauerte, Patrick / Sousa Uva, Miguel / Taggart, David P / Torracca, Lucia / Valgimigli, Marco / Wijns, William / Witkowski, Adam / Kolh, Philippe / Jüni, Peter. · ·BMJ · Pubmed #24958153.

ABSTRACT: OBJECTIVE: To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN: Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES: Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: 100 trials in 93,553 patients with 262,090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION: Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.

17 Article High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular mortality. 2013

Silbernagel, Guenther / Schöttker, Ben / Appelbaum, Sebastian / Scharnagl, Hubert / Kleber, Marcus E / Grammer, Tanja B / Ritsch, Andreas / Mons, Ute / Holleczek, Bernd / Goliasch, Georg / Niessner, Alexander / Boehm, Bernhard O / Schnabel, Renate B / Brenner, Hermann / Blankenberg, Stefan / Landmesser, Ulf / März, Winfried. ·Department of Angiology, Swiss Cardiovascular Center, Inselspital, University of Bern, Bern, Switzerland. ·Eur Heart J · Pubmed #24014391.

ABSTRACT: AIMS: High-density lipoprotein (HDL) cholesterol is a strong predictor of cardiovascular mortality. This work aimed to investigate whether the presence of coronary artery disease (CAD) impacts on its predictive value. METHODS AND RESULTS: We studied 3141 participants (2191 males, 950 females) of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean ± standard deviation age of 62.6 ± 10.6 years, body mass index of 27.5 ± 4.1 kg/m², and HDL cholesterol of 38.9 ± 10.8 mg/dL. The cohort consisted of 699 people without CAD, 1515 patients with stable CAD, and 927 patients with unstable CAD. The participants were prospectively followed for cardiovascular mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A total of 590 participants died from cardiovascular diseases. High-density lipoprotein cholesterol by tertiles was inversely related to cardiovascular mortality in the entire cohort (P = 0.009). There was significant interaction between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In stratified analyses, HDL cholesterol was strongly associated with cardiovascular mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18-0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95% CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI) = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in 3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER cohort, and by a meta-analysis comprising all three cohorts. CONCLUSION: The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patients.

18 Article Lack of protective role of HDL-C in patients with coronary artery disease undergoing elective coronary artery bypass grafting. 2013

Angeloni, Emiliano / Paneni, Francesco / Landmesser, Ulf / Benedetto, Umberto / Melina, Giovanni / Lüscher, Thomas Felix / Volpe, Massimo / Sinatra, Riccardo / Cosentino, Francesco. ·Department of Cardiac Surgery, University of Rome 'Sapienza', Ospedale Sant'Andrea, Rome, Italy. ·Eur Heart J · Pubmed #23704708.

ABSTRACT: AIMS: Primary prevention studies have confirmed that high-density lipoprotein cholesterol (HDL-C) levels are strongly associated with reduced cardiovascular events. However, recent evidence suggests that HDL-C functionality may be impaired under certain conditions. In the present study, we hypothesize that HDL-C may lose their protective role in the secondary prevention of coronary artery disease (CAD). METHODS AND RESULTS: A consecutive series of 1548 patients undergoing isolated first-time elective CABG at one institution between 2004 and 2009 was studied. According to the ATPIII criteria, pre-operative HDL-C values were used to identify patients with high (Group A) vs. low HDL-C (Group B). To eliminate biased estimates, a propensity score model was built and two cohorts of 1:1 optimally matched patients were obtained. Cumulative survival and major adverse cardiovascular events (MACE) were analysed by means of Kaplan-Meier method. Cox proportional-hazards regression models were used to identify independent predictors of MACE and death. Propensity matching identified two cohorts of 502 patients each. At a median follow-up time of 32 months, there were 44 out of 502 (8.8%) deaths in Group A and 36 out of 502 deaths in Group B (7.2%, HR 1.19; P = 0.42). MACE occurred in 165 out of 502 (32.9%) in Group A and 120 out of 502 (23.9%) in Group B (P = 0.04). Regression analysis showed that pre-operative HDL-C levels were not associated with reduced but rather increased MACE occurrence during follow-up (HR 1.43, P = 0.11). CONCLUSION: Higher HDL-C levels are not associated with reduced risk of vascular events in CAD patients undergoing CABG. Our findings may support efforts to improve HDL-C functionality instead of increasing their levels.

19 Article Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs. 2013

Wagner, Jasmin / Riwanto, Meliana / Besler, Christian / Knau, Andrea / Fichtlscherer, Stephan / Röxe, Tino / Zeiher, Andreas M / Landmesser, Ulf / Dimmeler, Stefanie. ·Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Frankfurt, Germany. ·Arterioscler Thromb Vasc Biol · Pubmed #23559634.

ABSTRACT: OBJECTIVE: MicroRNAs are important intracellular regulators of gene expression, but also circulate in the blood being protected by extracellular vesicles, proteins, or high-density lipoprotein (HDL). Here, we evaluate the regulation and potential function of HDL- and low-density lipoprotein-bound miRs isolated from healthy subjects and patients with coronary artery disease. APPROACH AND RESULTS: HDL-bound miRs with known effects in the cardiovascular system were analyzed in HDL isolated from healthy subjects (n=10), patients with stable coronary artery disease (n=10), and patients with an acute coronary syndrome (n=10). In HDL from healthy subjects, miR-223 was detected at concentrations >10 000 copies/µg HDL, and miR-126 and miR-92a at about 3000 copies/µg HDL. Concentrations of most miRs were substantially higher in HDL as compared with low-density lipoprotein. However, HDL-bound miR-223 contributed to only 8% of the total circulating miRs. The signatures of miRs varied only slightly in HDL derived from patients with coronary artery disease. We did not observe a significant uptake of HDL-bound miRs into endothelial cells, smooth muscle cells, or peripheral blood mononuclear cells. However, patient-derived HDL transiently reduced miR expression particularly when incubated with smooth muscle and peripheral blood mononuclear cells. CONCLUSIONS: Circulating miRs are detected in HDL and to a lesser extent in low-density lipoprotein, and the miR-signatures are only slightly altered in patients with coronary artery disease. Lipoprotein-bound miRs were not efficiently delivered to endothelial, smooth muscle, and peripheral blood mononuclear cells suggesting that the lipoprotein-associated pool of miRs is not regulating the function of the studied cells in vitro.

20 Article Peripheral blood monocyte Sirt1 expression is reduced in patients with coronary artery disease. 2013

Breitenstein, Alexander / Wyss, Christophe A / Spescha, Remo D / Franzeck, Fabian C / Hof, Danielle / Riwanto, Meliana / Hasun, Matthias / Akhmedov, Alexander / von Eckardstein, Arnold / Maier, Willibald / Landmesser, Ulf / Lüscher, Thomas F / Camici, Giovanni G. ·Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland. ·PLoS One · Pubmed #23382833.

ABSTRACT: BACKGROUND: Inflammation plays a key role in atherosclerosis. Sirt1 regulates transcription factors involved in inflammatory processes and blunts atherosclerosis in mice. However, its role in humans remains to be defined. This study was therefore designed to investigate the role of Sirt1 in the development of atherosclerosis. METHODS AND RESULTS: 48 male subjects admitted for cardiac catheterization were subdivided into healthy subjects, patients with stable coronary artery disease (CAD), and with acute coronary syndromes (ACS). Monocytes were isolated and Sirt1 mRNA levels were determined. Sirt1 gene expression was higher in healthy subjects as compared to patients with CAD or ACS (P<0.05), respectively. Interestingly, HDL levels correlated positively with Sirt1 expression. Thus, HDL from the three groups was isolated and incubated with THP-1 monocytes to determine the effects of HDL on Sirt1 protein in controlled experimental conditions. HDL from healthy subjects stimulated Sirt1 expression in THP-1 monocytes to a higher degree than HDL from CAD and ACS patients (P<0.05). Paraoxonase-1 (PON-1), a HDL-associated enzyme, showed a reduced activity in HDL isolated from CAD and ACS patients as compared to the controls (P<0.001). CONCLUSIONS: Monocytic Sirt1 expression is reduced in patients with stable CAD and ACS. Experiments on THP-1 monocytes suggest that this effect is HDL-dependent and is mediated by a reduced activity of HDL-associated enzyme PON1.

21 Article Altered activation of endothelial anti- and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein-proteome remodeling. 2013

Riwanto, Meliana / Rohrer, Lucia / Roschitzki, Bernd / Besler, Christian / Mocharla, Pavani / Mueller, Maja / Perisa, Damir / Heinrich, Kathrin / Altwegg, Lukas / von Eckardstein, Arnold / Lüscher, Thomas F / Landmesser, Ulf. ·Cardiology, Cardiovascular Center, University Hospital Zurich, Switzerland. ·Circulation · Pubmed #23349247.

ABSTRACT: BACKGROUND: Endothelial dysfunction and injury are thought to play an important role in the progression of coronary artery disease (CAD). High-density lipoprotein from healthy subjects (HDL(Healthy)) has been proposed to exert endothelial antiapoptotic effects that may represent an important antiatherogenic property of the lipoprotein. The present study therefore aimed to compare effects of HDL(CAD) and HDL(Healthy) on the activation of endothelial anti- and proapoptotic pathways and to determine which changes of the lipoprotein are relevant for these processes. METHODS AND RESULTS: HDL was isolated from patients with stable CAD (HDL(sCAD)), an acute coronary syndrome (HDL(ACS)), and healthy subjects. HDL(Healthy) induced expression of the endothelial antiapoptotic Bcl-2 protein Bcl-xL and reduced endothelial cell apoptosis in vitro and in apolipoprotein E-deficient mice in vivo. In contrast, HDL(sCAD) and HDL(ACS) did not inhibit endothelial apoptosis, failed to activate endothelial Bcl-xL, and stimulated endothelial proapoptotic pathways, in particular, p38-mitogen-activated protein kinase-mediated activation of the proapoptotic Bcl-2 protein tBid. Endothelial antiapoptotic effects of HDL(Healthy) were observed after inhibition of endothelial nitric oxide synthase and after delipidation, but not completely mimicked by apolipoprotein A-I or reconstituted HDL, suggesting an important role of the HDL proteome. HDL proteomics analyses and subsequent validations and functional characterizations suggested a reduced clusterin and increased apolipoprotein C-III content of HDL(sCAD) and HDL(ACS) as mechanisms leading to altered effects on endothelial apoptosis. CONCLUSIONS: The present study demonstrates for the first time that HDL(CAD) does not activate endothelial antiapoptotic pathways, but rather stimulates potential endothelial proapoptotic pathways. HDL-proteome remodeling plays an important role for these altered functional properties of HDL. These findings provide novel insights into mechanisms leading to altered vascular effects of HDL in coronary disease.

22 Article The impact of partial and complete loss-of-function mutations in endothelial lipase on high-density lipoprotein levels and functionality in humans. 2013

Singaraja, Roshni R / Sivapalaratnam, Suthesh / Hovingh, Kees / Dubé, Marie-Pierre / Castro-Perez, José / Collins, Heidi L / Adelman, Steven J / Riwanto, Meliana / Manz, Jasmin / Hubbard, Brian / Tietjen, Ian / Wong, Kenny / Mitnaul, Lyndon J / van Heek, Margaret / Lin, Linus / Roddy, Thomas A / McEwen, Jason / Dallinge-Thie, Geesje / van Vark-van der Zee, Leonie / Verwoert, Germaine / Winther, Michael / van Duijn, Cornelia / Hofman, Albert / Trip, Mieke D / Marais, A David / Asztalos, Bela / Landmesser, Ulf / Sijbrands, Eric / Kastelein, John J / Hayden, Michael R. ·Xenon Pharmaceuticals Inc., Burnaby, Canada. ·Circ Cardiovasc Genet · Pubmed #23243195.

ABSTRACT: BACKGROUND: Endothelial lipase is a phospholipase with activity against high-density lipoprotein. Although a small number of mutations in LIPG have been described, the role of LIPG in protection against atherosclerosis is unclear. METHODS AND RESULTS: We identified 8 loss-of-function (LOF) mutations in LIPG in individuals with high-density lipoprotein cholesterol. Functional analysis confirmed that most rare mutations abolish lipase activity in vitro, indicating complete LOF, whereas 2 more common mutations N396S and R476W reduce activity by ≈50%, indicating partial LOF and implying ≈50% and ≈75% remaining endothelial lipase function in heterozygous complete LOF and partial LOF mutation carriers, respectively. complete LOF mutation carriers had significantly higher plasma high-density lipoprotein cholesterol levels compared with partial LOF mutation carriers. Apolipoprotein B-depleted serum from complete LOF carriers showed significantly enhanced cholesterol efflux acceptor capacity, whereas only trends were observed in partial LOF carriers. Carriers of LIPG mutations exhibited trends toward reduced coronary artery disease in 4 independent cohorts (meta-analysis odds ratio, 0.7; P=0.04). CONCLUSIONS: Our data suggest that the impact of LIPG mutations is directly related to their effect on endothelial lipase function and support that antagonism of endothelial lipase function improves cardioprotection.

23 Article Dizziness and pre-syncope: an unusual clinical presentation of a spontaneous coronary artery dissection as revealed by optical coherence tomography. 2011

Hasun, Matthias / Manka, Robert / Lüscher, Thomas F / Landmesser, Ulf. ·Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland. ·J Am Coll Cardiol · Pubmed #21884960.

ABSTRACT: -- No abstract --

24 Article Cardiac hybrid imaging in a patient with a single coronary artery originating from the right sinus of Valsalva. 2011

Ghadri, Jelena R / Fiechter, Michael / Templin, Christian / Lüscher, Thomas F / Kaufmann, Philipp A / Landmesser, Ulf. ·Cardiac Imaging, University Hospital Zurich, Zurich, Switzerland. ·Eur Heart J · Pubmed #21821842.

ABSTRACT: -- No abstract --

25 Article Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. 2011

Besler, Christian / Heinrich, Kathrin / Rohrer, Lucia / Doerries, Carola / Riwanto, Meliana / Shih, Diana M / Chroni, Angeliki / Yonekawa, Keiko / Stein, Sokrates / Schaefer, Nicola / Mueller, Maja / Akhmedov, Alexander / Daniil, Georgios / Manes, Costantina / Templin, Christian / Wyss, Christophe / Maier, Willibald / Tanner, Felix C / Matter, Christian M / Corti, Roberto / Furlong, Clement / Lusis, Aldons J / von Eckardstein, Arnold / Fogelman, Alan M / Lüscher, Thomas F / Landmesser, Ulf. ·Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland. ·J Clin Invest · Pubmed #21701070.

ABSTRACT: Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1- and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair-stimulating effects of HDL.

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