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113 results on '"Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use"'

1. Temporal trends in abdominal aortic aneurysmal disease: a nationwide cohort study on cardiovascular morbidity and medical cardioprotective therapy

Author: Chalotte W Nicolajsen, Mette Søgaard, Nikolaj Eldrup, Martin Jensen, Torben B Larsen, Samuel Z Goldhaber, and Peter B Nielsen
Subjects: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Epidemiology, Cardiovascular disease, Cohort Studies, Stroke, myocardial infarction, Cardiovascular Diseases, Aortic Aneurysm, Abdominal/epidemiology, Risk Factors, Disease Progression, Humans, Abdominal aortic aneurysm, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Medical cardioprotective treatment, Cardiology and Cardiovascular Medicine, Cardiovascular Diseases/diagnosis, Aortic Aneurysm, Abdominal, Aged
Abstract: Aims Abdominal aortic aneurysmal disease is associated with increased risk of cardiovascular morbidity and death, which potentially can be reduced with cardioprotective medical therapy. The aim of this study was to observe temporal trends in prevalence and incidence of cardiovascular comorbidity as well as use of medical cardioprotective treatment in patients diagnosed with abdominal aortic aneurysmal disease. Methods and results This was a population-based cohort study based on data from national health registries, including all patients diagnosed with abdominal aortic aneurysms between 1998 and 2018. Data were stratified into four time periods (1999–2003, 2004–2008, 2009–2013, and 2014–2018) to illustrate trends over time. Outcome measures were (i) cardiovascular comorbidity and medical cardioprotective therapy at time of diagnosis, (ii) new admissions for atherosclerotic cardiovascular disease, and (iii) all-cause mortality after 2-year follow-up. The study cohort included 33 296 individuals. Mean age was 74 years. Prevalence of atherosclerotic cardiovascular comorbidity at diagnosis decreased from 41.5 to 32.6%. Use of statins increased from 17.9 to 66.9%, antiplatelets from 45.6 to 63.3%, and combined therapy with both antiplatelets and statins from 11.3 to 44.8%, and from 12.1 to 50.7% when anticoagulant therapy was included. Developments in medication use plateaued after 2013. Prevalence and incidence of atherosclerotic cardiovascular disease decreased through all four time periods. The same applied to all-cause mortality, which decreased from 24.3 to 12.4 deaths (per 100 person-years). Conclusion In patients diagnosed with abdominal aortic aneurysm, cardiovascular comorbidity at diagnosis, risk of future cardiovascular events, and all-cause mortality is decreasing. Nevertheless, cardiovascular burden and mortality rates remain substantial, and medical cardioprotective therapy can be further improved.
Published: 2022

2. Re-analysis of ventilator-free days (VFD) in acute respiratory distress syndrome (ARDS) studies

Author: Rejina Mariam Verghis, Cliona McDowell, Bronagh Blackwood, Bohee Lee, Daniel F. McAuley, and Mike Clarke
Subjects: Simvastatin, Respiratory Distress Syndrome, Acute respiratory distress syndrome, Critical Care, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Methodology, Medicine (miscellaneous), Hurdle Mode, Respiration, Artificial/methods, Respiratory Distress Syndrome/therapy, Ventilator-free days, Respiration, Artificial, Clinical trials, Simvastatin/therapeutic use, Humans, Pharmacology (medical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lung
Abstract: Background Over recent decades, improvements in healthcare have reduced mortality and morbidity rates in many conditions. This has resulted, in part, from the identification of effective interventions in randomised trials, and in conducting such trials, a composite outcome measure (COM) with multiple components will increase event rates, which allows study completion with a smaller sample size. In critical care research, the COM “ventilator-free days” (VFD) combines mortality and duration of mechanical ventilation (MV) into a single continuous measure, which can be analysed in a variety of ways. This study investigates the usefulness of Poisson and two-part Poisson models compared to t-distribution for the analysis of VFD. Methods Data from four studies (ALbuterol for the Treatment of ALI (ALTA), Early vs. Delayed Enteral Nutrition (EDEN), Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute Lung Injury (ALI) to reduce pulmonary dysfunction (HARP-2), Statins for Acutely Injured Lungs from Sepsis (SAILS)) were used for analysis, with the VFD results summarised using mean, standard deviation (SD), median, interquartile range (25th and 75th percentiles) and minimum and maximum values. The statistical analyses that are compared used the t-test, Poisson, zero-inflated Poisson (ZIP) and two-part Logit-Poisson hurdle models. The analyses were exploratory in nature, and the significance level for differences in the estimates was set to 0.05. Results In HARP-2, which compared simvastatin and placebo, the mean (SD) VFD for all patients was 12.0 (10.2), but this mean value did not represent the data distribution as it falls in a zone between two peaks, with the lowest frequency of occurrence. The mean (SD) VFD after excluding patients who died before day 28 and patients who did not achieve unassisted breathing were 15.9 (8.7) and 18.2 (6.6), respectively. The mean difference (95% CI) between the two groups was 1.1 (95% CI: 0.7 to 2.8; p = 0.20) based on an independent t-test. However, when the two-part hurdle model was used, the simvastatin arm had a significantly higher number of non-zero values compared to the placebo group, which indicated that more patients were alive and free of mechanical ventilation in the simvastatin group. Similarly, in ALTA, this model found that significantly more patients were alive and free of MV in the control group. In EDEN and SAILS, there was no significant difference between the control and intervention groups. Conclusion Our analyses show that the t-test and Poisson model are not appropriate for bi-modal data (such as VFD) where there is a large number of zero events. The two-part hurdle model was the most promising approach. There is a need for future research to investigate other analysis techniques, such as two-part quantile regression and to determine the impact on sample size requirements for comparative effectiveness trials.
Published: 2023

3. Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis

Author: Solenne, Vigne, Donovan, Duc, Benjamin, Peter, Jessica, Rebeaud, Yannick, Yersin, Florian, Ruiz, Valentine, Bressoud, Tinh-Hai, Collet, and Caroline, Pot
Subjects: Encephalomyelitis, Autoimmune, Experimental, EAE, Hypercholesterolemia, Autoimmunity, Multiple sclerosis, Mice, Cholesterol, Animals, Encephalomyelitis, Autoimmune, Experimental/drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Hypercholesterolemia/metabolism, Multiple Sclerosis, Neuroinflammatory Diseases, Alirocumab, LDL receptor, Neuroinflammation, PCSK9, lipids (amino acids, peptides, and proteins), Neurology. Diseases of the nervous system, Hydroxymethylglutaryl-CoA Reductase Inhibitors, RC346-429
Abstract: Background Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) commonly affecting young adults. There is increasing evidence that environmental factors are important in the development and course of MS. The metabolic syndrome (MetS) which comprises dyslipidemia has been associated with a worse outcome in MS disease. Furthermore, the lipid-lowering drug class of statins has been proposed to improve MS disease course. However, cholesterol is also rate-limiting for myelin biogenesis and promotes remyelination in MS animal models. Thus, the impact of circulating blood cholesterol levels during the disease remains debated and controversial. Methods We assessed the role of circulating cholesterol on the murine model of MS, the experimental autoimmune encephalomyelitis (EAE) disease using two different approaches: (1) the mouse model of familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, and (2) the use of the monoclonal anti-PCSK9 neutralizing antibody alirocumab, which reduces LDLr degradation and consequently lowers blood levels of cholesterol. Results Elevated blood cholesterol levels induced by LDLr deficiency did not worsen clinical symptoms of mice during EAE. In addition, we observed that the anti-PCSK9 antibody alirocumab did not influence EAE disease course, nor modulate the immune response in EAE. Conclusions These findings suggest that blood cholesterol level has no direct role in neuro-inflammatory diseases and that the previously shown protective effects of statins in MS are not related to circulating cholesterol.
Published: 2022

4. The Way to a Woman's Heart: Assessing, Personalizing, and Reclassifying Atherosclerotic Cardiovascular Disease Risk in Female Patients.

Author: Liu, Jing, Saeed, Anum, Hussain, Aliza, and Virani, Salim S.
Subjects: *PREMATURE menopause, *CARDIOVASCULAR diseases, *WOMEN patients, *PREMATURE ovarian failure, *HEART, *RISK assessment
Abstract: The article informs about assessing, personalizing, and reclassifying atherosclerotic cardiovascular disease risk in female patients. Topics discussed include risk enhancers specific to women, the value of evaluating coronary artery calcium (CAC); and female-specific risk enhancers are preeclampsia, gestational hypertension, preterm delivery, and delivery of infants small for their gestational age.
Published: 2020
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5. Association of Prior Intracerebral Hemorrhage With Major Adverse Cardiovascular Events

Author: David Gaist, Stine Munk Hald, Luis Alberto García Rodríguez, Anne Clausen, Sören Möller, Jesper Hallas, and Rustam Al-Shahi Salman
Subjects: Stroke/etiology, Male, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Fibrinolytic Agents/therapeutic use, Myocardial Infarction/complications, Myocardial Infarction, General Medicine, Cerebral Hemorrhage/epidemiology, Cohort Studies, Stroke, Fibrinolytic Agents, Case-Control Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Aged, Cerebral Hemorrhage, Ischemic Stroke
Abstract: ImportancePatients with stroke due to nontraumatic (spontaneous) intracerebral hemorrhage (ICH) often harbor vascular risk factors and comorbidities, but it is unclear which major adverse cardiovascular events (MACEs) occur more frequently among patients with a prior ICH than the general population.ObjectiveTo evaluate the risk of a MACE for patients with a prior ICH compared with the general population.Design, Setting, and ParticipantsThis cohort study identified 8991 patients with a first ICH in the Danish Stroke Registry from January 1, 2005, to June 30, 2018, who were aged 45 years or older and survived more than 30 days after an ICH. Patients in this ICH cohort were matched 1:40 on age, sex, and ICH-onset date with a comparison cohort of 359 185 individuals from the general population without a prior ICH. Both cohorts were followed up for 6 months or more until December 31, 2018, for outcomes using registry data. Data were analyzed from October 1, 2021, to July 19, 2022.ExposuresIntracerebral hemorrhage identified by a nationwide clinical database.Main Outcomes and MeasuresThe main outcomes were ICH, ischemic stroke, myocardial infarction, and a composite of MACEs. For each outcome, a case-control study nested within the cohorts was also performed, adjusting for time-varying exposures and potential confounders. Crude absolute event rates per 100 person-years, adjusted hazard ratios (aHRs) and 95% CIs and, in the nested case-control analyses, crude and adjusted odds ratios and 95% CIs were calculated.ResultsThe ICH cohort (n = 8991; 4814 men [53.5%]; mean [SD] age, 70.7 [11.5] years) had higher event rates than the comparison cohort (n = 359 185; 192 256 men [53.5%]; mean [SD] age, 70.7 [11.5] years) for MACEs (4.16 [95% CI, 3.96-4.37] per 100 person-years vs 1.35 [95% CI, 1.33-1.36] per 100 person-years; aHR, 3.13 [95% CI, 2.97-3.30]), ischemic stroke (1.52 [95% CI, 1.40-1.65] per 100 person-years vs 0.56 [95% CI, 0.55-0.57] per 100 person-years; aHR, 2.64 [95% CI, 2.43-2.88]), and ICH (1.44 [95% CI, 1.32-1.56] per 100 person-years vs 0.06 [95% CI, 0.06-0.07] per 100 person-years; aHR, 23.49 [95% CI, 21.12-26.13]) but not myocardial infarction (0.52 [95% CI, 0.45-0.60] per 100 person-years vs 0.48 [95% CI, 0.47-0.49] per 100 person-years; aHR, 1.12 [95% CI, 0.97-1.29]). Nested case-control analyses returned risk estimates of similar magnitude as the cohort analyses.Conclusions and RelevanceThe findings of this cohort study suggest that Danish patients with a prior ICH had statistically significantly higher rates of MACEs than the general population, indicating a need for attention to optimal secondary prevention with blood pressure lowering and antithrombotic and statin therapies after an ICH in clinical research and practice.
Published: 2022

6. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab

Author: Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Pablo Carlos, Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H. Asita de Silva, Ulf Landmesser, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B Schiavi, Marcelo Garrido, Andrés F Alvarisqueta, Sonia A Sassone, Anselmo P Bordonava, Alberto E Alves De Lima, Jorge M Schmidberg, Ernesto A Duronto, Orlando C Caruso, Leonardo P Novaretto, Miguel Angel Hominal, Oscar R Montaña, Alberto Caccavo, Oscar A Gomez Vilamajo, Alberto J Lorenzatti, Luis R Cartasegna, Gustavo A Paterlini, Ignacio J Mackinnon, Guillermo D Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R Codutti, Horacio O Jure, Julio OE Bono, Adrian D Hrabar, Julio A Vallejos, Rodolfo A Ahuad Guerrero, Federico Novoa, Cristian A Patocchi, Cesar J Zaidman, Maria E Giuliano, Ricardo D Dran, Marisa L Vico, Gabriela S Carnero, Pablo N Guzman, Juan C Medrano Allende, Daniela F Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto F Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva- Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi’An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian’An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Ph. Gabriel Steg, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun- Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Pablo Carlos Montenegro Valdovinos, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan PY Yan, David CW Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Dr. Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter AM Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J Wiersma, Dirk Basart, Ruud MA Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus JE Verdel, Bart RG Brueren, Roland PTh Troquay, Eric P Viergever, Nadea YY Al-Windy, Gerard L Bartels, Jan H Cornel, Walter RM Hermans, Johannes PR Herrman, Robert J Bos, Reginald GEJ Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Eelko Ronner, Bjorn E Groenemeijer, Patrick NA Bronzwaer, Anho AH Liem, Bernard JWM Rensing, Marcel JJA Bokern, Remco Nijmeijer, Ferry MRJ Hersbach, Frank F Willems, Antonius TM Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R Calderon Ticona, Julio R Durand Velasquez, Sandra A Negron Miguel, Enrique S Sanabria Perez, Jesus M Carrion Chambilla, Carlos A Chavez Ayala, Reynaldo P Castillo Leon, Rolando J Vargas GonzalesC, Jose D Hernandez Zuniga, Luis A Camacho Cosavalente, Jorge E Bravo Mannucci, Javier Heredia Landeo, Nassip C Llerena Navarro, Yudy M Roldan Concha, Víctor E Rodriguez Chavez, Henry A Anchante Hernandez, Carlos A Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H Pereira, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian GC Podoleanu, Mircea CA Constantinescu, Cristina M Bengus, Constantin Militaru, Doina Rosu, Irinel R Parepa, Adrian V Matei, Tom M Alexandru, Mihaela Malis, Ioan Coman, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I Voevoda, Tatyana V Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V Tyrenko, Igor G Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E Kapp, Matthys M de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J Van Zyl, Peter J Sebastian, Thayabran Pillay, Jan A Saaiman, Patrick J Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O Ebrahim, Mahomed Sarvan, Joseph H Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, Jose R Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J Alonso Martin, Jose Maria Serrano Antolin, José R De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei- Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey- Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K Aggarwal, Piers Clifford, Yuk- Ki Wong, Syed MR Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahma, Ayyaz Sultan, Timothy Reynolds, David Sharman, david Spriging, Rob Butler, Peter Wilkinson, Gregory YH Lip, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure II, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D’Urso, Fadi El- Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K Devarapalli, Michael Koren, Harish Chandna, George Dodds III, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl III, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun (Tom) Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O’Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Jean- Francois Tamby, Melanie Verrier, Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Roe, Matthew T., Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Raczak, Grzegorz, Vogel, Robert, Szwed, Hanna, Monteiro, Pedro, Mesquita Bastos, Jose, Pereira, Helder H., Morais, Joao, Seixo, Filipe, Mendonça, Carlos, Botelho, Ana, Caetano, Francisca, Minescu, Bogdan, Chaitman, Bernard, Istratoaie, Octavian, Tesloianu, Dan N., Dorobantu, Maria, Cristian, Gabriel, Dumitrescu, Silviu, Podoleanu, Cristian Gc, Constantinescu, Mircea Ca, Bengus, Cristina M., Militaru, Constantin, Rosu, Doina, Kelsey, Sheryl F., Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Malis, Mihaela, Coman, Ioan, Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Olsson, Anders G., Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Khlevchuk, Tatiana, Shalaev, Sergey, Rouleau, Jean-Lucien, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Shchekotov, Vladimir, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Simoons, Maarten L., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Alexander, Karen, Baranova, Elena, Kosmachova, Elena, Karpov, Yuriy, Karpov, Yuri, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Ilya, Masterov, Kanorsky, Sergey, Meloni, Chiara, Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Tosic, Biljana Putnikovic, Stankovic, Aleksandar, Rosenson, Robert, Arandjelovic, Aleksandra, Radovanovic, Slavica, Todic, Branislava, Ristic, Arsen D., Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Karadzic, Ana, Dodic, Slobodan, Dimkovic, Sinisa, Sijbrands, Eric J. G., Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Tricoci, Pierluigi, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Alexander, John H., Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P., Ranjith, Naresh, Armaganijan, Luciana, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E., de V Basson, Matthys M., Lottering, Hanlie, Van Aswegen, Dina, Van Zyl, Louis J., Sebastian, Peter J., Bagai, Akshay, Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Dalby, Anthony J., Reuter, Helmuth, Bahit, Maria Cecilia, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. Cequier, Peris, Vicente Bodí, Jimenez, Francisco Fuentes, Marín, Francisco, Cruz Fernández, Jose M., Hidalgo Urbano, Rafael Jesus, Gil-Extremera, Blas, Toledo, Pablo, Brennan, J. Matthew, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R., Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Clifton, Shaun, Alonso Martin, Joaquin J., Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R., Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, DeVore, Adam D., Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M., Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Deloatch, Shalonda, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Dickey, Sheila, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Dombrowski, Keith, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Ducrocq, Grégory, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Eapen, Zubin, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I.-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Endsley, Patricia, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Eppinger, Arleen, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Harrison, Robert W., Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Hess, Connie Ng, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Hlatky, Mark A., Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Jordan, Joseph Dedrick, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-ki, Iqbal, Syed Mr, Subkovas, Eduardas, Knowles, Joshua W., Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kolls, Bradley J., Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Kong, David F., Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Yh, Ossei-Gerning, Nicholas, Vardi, Gil, Leonardi, Sergio, Baldari, Duccio, Brabham, David, Treasure Ii, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Lillis, Linda, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Lopes, Renato D., Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Maron, David J., Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, Mouhamad, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Moriarty, Katie, Mahaffey, Kenneth W., Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Marcus, Jill, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds Iii, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Mathews, Robin, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Fenton, Sarah, Singh, Narendra, Mehta, Rajendra H., Shah, Anil V., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Mentz, Robert J., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Moreira, Humberto Graner, Link, Chad, Bortnick, Anna, Kinzfogl Iii, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Patel, Chetan B., Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Pereira, Sabrina Bernardez, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Perkins, Lynn, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Povsic, Thomas J., Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Puymirat, Etienne, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun Tom, Vidovich, Mladen, Knutson, Thomas, Jones, William Schuyler, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Shah, Bimal R., Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T., Massey, Clara, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Sherwood, Matthew W., Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Stringfellow, Kenya, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Sujjavanich, Darin, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Toma, Mustafa, Pollock, Stewart, French, William J., Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Trotter, Charlene, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, van Diepen, Sean F. P., Nager, Paul, Vohra, Rakesh, Sharma, Mukesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Wilson, Matthew D., Sporn, Daniel, Stapleton, Dwight, Eisenberg, Steven, Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. 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Wouter, Vrolix, Mathias Cm, De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Dilic, Mirza, Durak-Nalbantic, Azra, Kulić, Mehmed, Vulic, Dusko, Muslibegovic, Adis, Goronja, Boris, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Zeiher, Andreas M., Rech, Rafael, Rossi, Paulo Rf, Cerqueira, Maria José Ag, Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, José Antonio M., Filho, Pedro Pimentel, Soggia, Ana Priscila, de Santos, Mayler On, Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Manenti, Euler Roberto F. Fernandes, Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro, Silveira, Jose A., Saporito, Wladmir, Neto, Jose A. Marin, Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar Ksb, Reis, Helder Jl, Machado, Leandro, Aidar Ayoub, José Carlos, Todorov, Georgi V., Nikolov, Fedya P., Velcheva, Elena S., Tzekova, Maria L., Benov, Haralambi O., Petranov, Stanislav L., Edelberg, Jay M., Tumbev, Haralin S., Shehova-Yankova, Nina S., Markov, Dimitar T., Raev, Dimitar H., Mollov, Mihail N., Kichukov, Kostadin N., Ilieva-Pandeva, Katya A., Gotcheva, Nina N., Ivanova, Raya, Gospodinov, Maryana, Hanotin, Corinne, Mincheva, Valentina M., Lazov, Petar V., Dimov, Bojidar I., Senaratne, Manohara, Stone, James, Kornder, Jan, Pearce, Stephen, Dion, Danielle, Savard, Daniel, Pesant, Yves, Pandey, Amritanshu, Robinson, Simon, Gosselin, Gilbert, Vizel, Saul, Hoag, Gordon, Bourgeois, Ronald, Morisset, Anne, Sabbah, Eric, Sussex, Bruce, Kouz, Simon, Moryusef, Angèle, MacDonald, Paul, Diaz, Ariel, Michaud, Nicolas, Fell, David, Leung, Raymond, Vuurmans, Tycho, Lai, Christopher, Nigro, Frank, Davies, Richard, Nogareda, Gustavo, Pordy, Robert, Vijayaraghavan, Ram, Ducas, John, Lepage, Serge, Mehta, Shamir, Cha, James, Dupuis, Robert, Fong, Peter, Lutchmedial, Sohrab, Rodes-Cabau, Josep, Fadlallah, Hussein, Sasiela, William J., Cleveland, David, Huynh, Thao, Bata, Iqbal, Hameed, Adnan, Pincetti, Cristian, Potthoff, Sergio, Prieto, Juan C., Acevedo, Monica, Aguirre, Arnoldo, Vejar, Margarita, Tamby, Jean-François, Yañez, Mario, Araneda, Guillermo, Fernandez, Mauricio, Perez, Luis, Varleta, Paola, Florenzano, Fernando, Huidobro, Laura, Raffo, Carlos A., Olivares, Claudia, Nahuelpan, Leonardo, Montecinos, Humberto, Chen, Jiyan, Dong, Yugang, Huang, Weijian, Wang, Jianzhong, Huang, Shi'An, Yao, Zhuhua, Li, Xiang, Cui, Lan, Lin, Wenhua, Sun, Yuemin, Wang, Jingfeng, Li, Jianping, Zhang, Xuelian, Zhu, Hong, Chen, Dandan, Huang, Lan, Dong, Shaohong, Su, Guohai, Xu, Biao, Su, Xi, Cheng, Xiaoshu, Lin, Jinxiu, Zong, Wenxia, Li, Huanming, Feng, Yi, Xu, Dingli, Yang, Xinchun, Ke, Yuannan, Lin, Xuefeng, Zhang, Zheng, Zheng, Zeqi, Luo, Zhurong, Chen, Yundai, Ding, Chunhua, Zhong, Yi, Zheng, Yang, Li, Xiaodong, Peng, Daoquan, Zhao, Shuiping, Li, Ying, Liu, Xuebo, Wei, Meng, Liu, Shaowen, Yu, Yihua, Qu, Baiming, Jiang, Weihong, Zhou, Yujie, Zhao, Xingsheng, Yuan, Zuyi, Guo, Ying, Xu, Xiping, Shi, Xubo, Ge, Junbo, Fu, Guosheng, Bai, Feng, Fang, Weiyi, Shou, Xiling, Yang, Xiangjun, Wang, Jian'An, Xiang, Meixiang, Sun, Yingxian, Lu, Qinghua, Zhang, Ruiyan, Zhu, Jianhua, Xu, Yizhou, Fan, Zhongcai, Li, Tianchang, Wu, Chun, Jaramillo, Nicolas, Vallejo, Gregorio Sanchez, Luna Botia, Diana C., Lopez, Rodrigo Botero, De Salazar, Dora I. Molina, Bonfanti, Alberto J. Cadena, Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I., Garcia Lozada, Henry J., Prieto, Juan-Carlos, Coronel Arroyo, Julian A., Accini Mendoza, Jose L., Fernandez Ruiz, Ricardo L., Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G., Sotomayor Herazo, Aristides, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A., Trujillo, Angela M. Fernandez, Yong, Huo, Strozzi, Maja, Car, Siniša, Miličić, Davor, Lovrić Benčić, Martina, Pintarić, Hrvoje, Prvulović, Đeiti, Šikić, Jozica, Peršić, Viktor, Mileta, Dean, Štambuk, Kresimir, López-Jaramillo, Patricio, Babić, Zdravko, Tomulic, Vjekoslav, Lukenda, Josip, Mejic-Krstulovic, Stanka, Starcevic, Boris, Spinar, Jindrich, Horak, David, Velicka, Zdenek, Alan, David, Machova, Vilma, Pećin, Ivan, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Reiner, Zeljko, Marusincova, Ivana, Ostadal, Petr, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Matuska, Jiri, Poulsen, Steen H., Raungaard, Bent, Clemmensen, Peter, Bang, Lia E., May, Ole, Bøttcher, Morten, Hove, Jens D., Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Johansen, Peter, Jeppesen, Jørgen, Poulsen, Steen Hvitfeldt, Nielsen, Tonny, Kristensen, Kjeld S., Walichiewicz, Piotr Maria, Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Viigimaa, Margus, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Nieminen, Markku S., Vikman, Saila, Huikuri, Heikki, Airaksinen, Juhani, Coste, Pierre, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Steg, Ph Gabriel, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Chumburidze, Vakhtang, Lefèvre, Thierry, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Marx, Nikolaus, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Liberopoulos, Evangelos, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Carlos, Pablo, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun-Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Valdovinos, Montenegro, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Tse, Hung-Fat, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Kiss, Robert Gabor, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Hahalis, Georgios, Lekakis, John, Hatzitolios, Apostolos, Fausto Ovando, Sergio R., Montenegro Valdovinos, Pablo Carlos, Arango Benecke, Juan L., Xavier, Denis, Rodriguez De Leon, Edgar R., Yan, Bryan Py, Siu, David Cw, Turi, Tibor, Merkely, Bela, Gabor Kiss, Robert, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, András, Zahger, Doron, Édes, István, Müller, Gábor, Horvath, Iván, Kapin, Tibor, Szigeti, Zsolt, Faluközy, József, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Reddy Proddutur, Naveen, Valgimigli, Marco, Regella, Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Pawar, Sudhir, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N., Kimura, Takeshi, Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B., Monteiro, Minguel R., Kim, Hyo Soo, Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Dr Aparna, Sachin, Patil, Chopra, Vijay K., Goyal, Naresh K., Shinde, Rituparna, Kim, Sang-Hyun, Manakshe, Gajendra V., Patki, Nitin, Sethi, Sumeet, Munusamy, Vengatesh, Sunil Thanvi, Sunil Karnaand, Adhyapak, Srilakshmi, Patil, Chandrakant, Pandurangi, Ulhas, Mathur, Rishabh, Gupta, Jugal, Erglis, Andrejs, Kalashetti, Suhas, Bhagwat, Ajit, Raghuraman, Bagirath, Kumar Yerra, Shiv, Bhansali, Prasant, Borse, Rohidas, Rahul, Patil, Das, Srihari, Kumar, Vinay, Abdullakutty, Jabir, Laucevicius, Aleksandras, Saathe, Shireesh, Palimkar, Priya, Abdullkutty, Jabir, Sathe, Shireesh, Atar, Shaul, Shechter, Michael, Mosseri, Morris, Arbel, Yaron, Ehud, Chorin, Ofer, Havakuk, Kedev, Sasko, Lotan, Chaim, Rosenschein, Uri, Katz, Amos, Henkin, Yaakov, Francis, Adi, Klutstein, Marc, Nikolsky, Eugenia, Zukermann, Robert, Turgeman, Yoav, Halabi, Majdi, Yusoff, Khalid, Marmor, Alon, Kornowski, Ran, Jonas, Michael, Amir, Offer, Hasin, Yonathan, Rozenman, Yoseph, Fuchs, Shmuel, Zvi, Vered, Hussein, Osamah, Gavish, Dov, Ramos López, Gabriel Arturo, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Wolfovitz, Efrat, Lishner, Michael, Elias, Nizar, Piovaccari, Giancarlo, De Pellegrin, Annamaria, Garbelotto, Raffaella, Alings, Marco, Guardigli, Gabriele, Marco, Valgimigli, Licciardello, Giovanni, Auguadro, Carla, Scalise, Filippo, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Senni, Michelle, Calabrò, Paolo, Novo, Salvatore, Faggiano, Pompilio, Metra, Marco, De Cesare, Nicoletta B., Berti, Sergio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, PierMarco, Palvarini, Michela, Halvorsen, Sigrun, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, Olivari, Zoran, Filardi, Pasquale Perrone, Ferratini, Maurizio, Racca, Vittorio, Dai, Kazuoki, Shimatani, Yuji, Kamiya, Haruo, Correa Flores, Roger M., Ando, Kenji, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Sy, Rody G., Hirooka, Keiji, Doi, Yasuji, Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Budaj, Andrzej, Shimizu, Masatoshi, Katsuda, Yousuke, Wada, Atsuyuki, Shinke, Toshiro, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Nakao, Koichi, Furukawa, Yutaka, Sugino, Hiroshi, Tamura, Ritsu, Mano, Toshiaki, Uematsu, Masaaki, Utsu, Noriaki, Ito, Kashima, Haraguchi, Takuya, Sato, Katsuhiko, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Masutani, Motomaru, Yoon, Jung Han, Kim, Hack-Lyoung, Sik Park, Hun, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Kim, Hyo-Soo, Kim, Hae Young, Hong, Taekjong, Tahk, Seung-Jea, Kim, Youngkwon, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Chua, Terrance, Kibarskis, Aleksandras, Kubilius, Raimondas, Bojovski, Stojko, Lozance, Nensi, Kjovkaroski, Aleksandar, Doncovska, Snezana, Ong, Tiong Kiam, Kasim, Sazzli, Maskon, Oteh, Kandasamy, Balachandran, Liew, Houng B., Wan Mohamed, Wan Mohd Izani, Castillo, Armando García, Calvillo, Jorge Carrillo, Campos, Pedro Fajardo, Núñez Fragoso, Juan Carlos, Bayram Llamas, Edmundo Alfredo, Alcocer Gamba, Marco Antonio, Madrigal, Jaime Carranza, González Salas, Luis Gerardo, Rosas, Enrique López, González Díaz, Belinda, Vázquez, Eduardo Salcido, Nacoud Ackar, Alfredo, Llamas Esperón, Guillermo Antonio, Martínez Sánchez, Carlos Rodolfo, De Leon, María Guerrero, Suarez Otero, Rodrigo, Salmón, Guillermo Fanghänel, Pérez Ríos, Jesús Antonio, Garza Ruíz, José Angel, Breedveld, Robert W., Feenema-Aardema, Margriet, Borger-Van Der Burg, Alida, Hoogslag, Pieter Am, Suryapranata, Harry, Tuñón, José, Oomen, Antonius, Van Haelst, Paulus, Feenema-Aradema, Margriet, Wiersma, Jacobijne J., Basart, Dirk, Van Der Wal, Ruud Ma, Zwart, Peter, Monraats, Pascalle, Van Kesteren, Henricus, Karalis, Ioannis, de Silva, H. Asita, Jukema, Johan, Verdel, Gerardus Je, Brueren, Bart Rg, Troquay, Roland P. Th, Viergever, Eric P., Al-Windy, Nadea Yy, Bartels, Gerard L., Cornel, Jan H., Hermans, Walter Rm, Herrman, Johannes Pr, Bos, Robert J., Groutars, Reginald Gej, Van Der Zwaan, Coenraad C., Kaplan, Refik, Ronner, Eelko, Groenemeijer, Bjorn E., Bronzwaer, Patrick Na, Liem, Anho Ah, Rensing, Bernard Jwm, Bokern, Marcel Jja, Nijmeijer, Remco, Hersbach, Ferry Mrj, Willems, Frank F., Gosselink, Antonius Tm, Rasoul, Saman, Elliott, John, Wilkins, Gerard, Fisher, Raewyn, Scott, Douglas, Hart, Hamish, Stewart, Ralph, Harding, Scott, Ternouth, Ian, Fisher, Nicholas, Wilson, Samuel, Aitken, Denise, Anscombe, Russell, Davidson, Laura, Tomala, Tadeusz, Nygård, Ottar, Sparby, Jon Arne, Andersen, Kjell, Gullestad, Lars, Jortveit, Jarle, Munk, Peter S., Singsaas, Erlend Gyllensten, Hurtig, Ulf, Calderon Ticona, Jorge R., Durand Velasquez, Julio R., Negron Miguel, Sandra A., Sanabria Perez, Enrique S., Carrion Chambilla, Jesus M., Chavez Ayala, Carlos A., Castillo Leon, Reynaldo P., Vargas GonzalesC, Rolando J., Hernandez Zuniga, Jose D., Camacho Cosavalente, Luis A., Bravo Mannucci, Jorge E., Landeo, Javier Heredia, Llerena Navarro, Nassip C., Roldan Concha, Yudy M., Rodriguez Chavez, Víctor E., Anchante Hernandez, Henry A., Zea Nunez, Carlos A., Ramos, Walter Mogrovejo, Ferrolino, Arthur, Sy, Rosa Allyn G., Tirador, Louie, Matiga, Generoso, Coching, Raul Martin, Bernan, Alisa, Rogelio, Gregorio, Morales, Dante D., Tan, Edgar, Sulit, Dennis Jose, Wlodarczak, Adrian, Skonieczny, Grzegorz, Ray, Kausik K., Pawlowicz, Lidia, Wojewoda, Pawel, Busz-Papiez, Benita, Bednarski, Janusz, Goch, Aleksander, Staneta, Pawel, Dulak, Elzbieta, Saminski, Krzysztof, Krasowski, Wlodzimierz, Sudnik, Wanda, Zurakowski, Aleksander, Skorski, Marcin, Lysek, Roman, Miklaszewicz, Beata, Lipko, Jan Andrzej, Kostarska-Srokosz, Edyta, Piepiorka, Marek, Drzewiecka, Anna, Stasiewski, Arkadiusz, Bhatt, Deepak L, Bittner, Vera A, Goodman, Shaun G, Harrington, Robert A, Jukema, J Wouter, White, Harvey D, Zeiher, Andreas M, Roe, Matthew T, Mahaffey, Kenneth W, Edelberg, Jay M, Sasiela, William J, Aylward, Philip E, Lopes, Renato D, Gotcheva, Nina N, Nieminen, Markku S, Laucevičius, Aleksandras, Correa Flores, Roger M, Sy, Rody G, Ristic, Arsen D, Dalby, Anthony J, de Silva, H Asita, Ray, Kausik K, Moriarty, Patrick M, Kelsey, Sheryl F, Olsson, Anders G, Simoons, Maarten L, Sijbrands, Eric J G, Alexander, John H, Brennan, J Matthew, DeVore, Adam D, Harrison, Robert W, Hlatky, Mark A, Knowles, Joshua W, Kolls, Bradley J, Kong, David F, Maron, David J, Mehta, Rajendra H, Mentz, Robert J, Patel, Chetan B, Povsic, Thomas J, Shah, Bimal R, Sherwood, Matthew W, van Diepen, Sean F P, Wilson, Matthew D, Schiavi, Lilia B, Alvarisqueta, Andrés F, Sassone, Sonia A, Bordonava, Anselmo P, Alves De Lima, Alberto E, Schmidberg, Jorge M, Duronto, Ernesto A, Caruso, Orlando C, Novaretto, Leonardo P, Montaña, Oscar R, Gomez Vilamajo, Oscar A, Lorenzatti, Alberto J, Cartasegna, Luis R, Paterlini, Gustavo A, Mackinnon, Ignacio J, Caime, Guillermo D, Codutti, Oscar R, Jure, Horacio O, Hrabar, Adrian D, Vallejos, Julio A, Ahuad Guerrero, Rodolfo A, Patocchi, Cristian A, Zaidman, Cesar J, Giuliano, Maria E, Dran, Ricardo D, Vico, Marisa L, Carnero, Gabriela S, Guzman, Pablo N, Medrano Allende, Juan C, Garcia Brasca, Daniela F, Bustamante Labarta, Miguel H, Colombo, Hugo R, Luciardi, Hector L, Waisman, Gabriel D, Berli, Mario A, Garcia Duran, Ruben O, Cestari, Horacio G, Luquez, Hugo A, Giordano, Jorge A, Saavedra, Silvia S, Waites, Jonathon H, Arstall, Margaret A, Rogers, James F, Oqueli Flores, Romulo E, Lehman, Sam J, Garrahy, Paul J, Carroll, Patrick A, Wolf, Luc De, Nicolau, Jose C, Giorgeto, Flavio E, Silva, Ricardo P, Abrantes, José Antonio M, Bodanese, Luiz C, Michalaros, Yorghos L, Eliaschewitz, Freddy G, Vidotti, Maria H, Leaes, Paulo E, Botelho, Roberto V, Manenti, Euler Roberto F Fernandes, Precoma, Dalton B, Moura Jorge, Jose C, Silveira, Jose A, Neto, Jose A Marin, Feitosa, Gilson S, Ritt, Luiz Eduardo F, de Souza, Juliana A, Todorov, Georgi V, Nikolov, Fedya P, Velcheva, Elena S, Tzekova, Maria L, Benov, Haralambi O, Petranov, Stanislav L, Tumbev, Haralin S, Shehova-Yankova, Nina S, Markov, Dimitar T, Raev, Dimitar H, Mollov, Mihail N, Kichukov, Kostadin N, Ilieva-Pandeva, Katya A, Mincheva, Valentina M, Lazov, Petar V, Dimov, Bojidar I, Prieto, Juan C, Raffo, Carlos A, Luna Botia, Diana C, De Salazar, Dora I Molina, Bonfanti, Alberto J Cadena, Barrera Silva, Sandra I, Garcia Lozada, Henry J, Coronel Arroyo, Julian A, Accini Mendoza, Jose L, Fernandez Ruiz, Ricardo L, Quintero Ossa, Alvaro M, Manzur Jatin, Fernando G, Urina Triana, Miguel A, Trujillo, Angela M Fernandez, Poulsen, Steen H, Bang, Lia E, Hove, Jens D, Kristensen, Kjeld S, Lomholdt, Jens D, Klausen, Ib C, Fausto Ovando, Sergio R, Arango Benecke, Juan L, Rodriguez De Leon, Edgar R, Premchand, Rajendra K, Abhyanakar, Atul D, Govinda, Ravishankar A, Patil, Sachin N, Joshi, Abhijeet B, Pothineni, Ramesh B, Monteiro, Minguel R, Iyengar, Shamanna S, Fulwani, Mahesh C, Chopra, Vijay K, Goyal, Naresh K, Manakshe, Gajendra V, Pellegrin, Annamaria De, De Cesare, Nicoletta B, Piatti, Piermarco, Luca, Giuseppe De, Leo, Alessandro De, Petrulionienė, Žaneta, Šakalytė, Gintarė, Šlapikas, Rimvydas, Liew, Houng B, Breedveld, Robert W, Wiersma, Jacobijne J, Troquay, Roland PTh, Viergever, Eric P, Bartels, Gerard L, Cornel, Jan H, Bos, Robert J, Van Der Zwaan, Coenraad C, Groenemeijer, Bjorn E, Willems, Frank F, Munk, Peter S, Calderon Ticona, Jorge R, Durand Velasquez, Julio R, Negron Miguel, Sandra A, Sanabria Perez, Enrique S, Carrion Chambilla, Jesus M, Chavez Ayala, Carlos A, Castillo Leon, Reynaldo P, Vargas GonzalesC, Rolando J, Hernandez Zuniga, Jose D, Camacho Cosavalente, Luis A, Bravo Mannucci, Jorge E, Llerena Navarro, Nassip C, Roldan Concha, Yudy M, Rodriguez Chavez, Víctor E, Anchante Hernandez, Henry A, Zea Nunez, Carlos A, Sy, Rosa Allyn G, Morales, Dante D, Pereira, Helder H, Tesloianu, Dan N, Bengus, Cristina M, Parepa, Irinel R, Matei, Adrian V, Alexandru, Tom M, Barbarash, Olga L, Vishnevsky, Alexander Y, Lomakin, Nikita V, Voevoda, Mikhail I, Tretyakova, Tatyana V, Tyrenko, Vadim V, Ivanov, Igor G, Asanin, Milika R, Apostolovic, Svetlana R, Dincic, Dragan V, Cyster, Henry P, Kapp, Ilse E, de V Basson, Matthys M, Aswegen, Dina Van, Van Zyl, Louis J, Sebastian, Peter J, Saaiman, Jan A, Commerford, Patrick J, Ebrahim, Iftikhar O, Mynhardt, Joseph H, Fillat, Angel R Cequier, Cruz Fernández, Jose M, Gonzalez-Juanatey, Jose R, Alonso Martin, Joaquin J, De Berrazueta Fernández, José R, Escudier, Juan M, Herath, Jagath I, Hsieh, I-Chang, Barna, Olga M, Aggarwal, Rajesh K, Wong, Yuk-Ki, Devarapalli, Sai K, Shah, Anil V, Kondo, Nicholas I, Azizad, Masoud M, Jong, Geert T, O'Donnell, Philip J, Marais, H John, Khaira, Ajit S, French, William J, Lester, F Martin, Sundram, P Sandy, Gilbert, John M, Schmedtje, John F, Colhoun, Helen M, Dempsey, Michael A, and McClanahan, Mark A
Subjects: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Anticholesteremic Agents/adverse effects, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], prevention & control, heart disease risk factors, diagnosis [Cardiovascular Diseases], Antibodies, Monoclonal, Humanized, PCSK9 inhibitors, acute coronary syndrome, apolipoproteins B, LDL cholesterol, Antibodies, acute coronary syndrome, LDL, drug therapy [Atherosclerosis], Risk Factors, Physiology (medical), therapeutic use [Hydroxymethylglutaryl-CoA Reductase Inhibitors], Monoclonal, Humans, Cardiac and Cardiovascular Systems, Humanized, Cardiovascular Diseases/diagnosis, Apolipoproteins B, Kardiologi, diagnosis [Acute Coronary Syndrome], Anticholesteremic Agents, PCSK9 inhibitors, apolipoproteins B, cholesterol, LDL, cholesterol, Atherosclerosis/drug therapy, Cholesterol, LDL, Atherosclerosis, Acute Coronary Syndrome/diagnosis, drug therapy, Cholesterol, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, epidemiology, adverse effects [Anticholesteremic Agents], Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract: Circulation : an official journal of the American Heart Association / ed.-in-chief Ephraim Donosco 146(9), 657-672 (2022). doi:10.1161/CIRCULATIONAHA.121.057807, Published by Ovid, [Erscheinungsort nicht ermittelbar]
Published: 2022

7. Dose-dependent impact of statin therapy intensity on circulating progenitor cells in patients undergoing percutaneous coronary intervention for the treatment of acute versus chronic coronary syndrome

Author: Roberta Florescu, Elisa Liehn, Nicole Schaaps, Jörg Schröder, Mohammad Almalla, Sebastian Mause, Anne Cornelissen, and Felix Vogt
Subjects: Multidisciplinary, Acute Coronary Syndrome/drug therapy, Percutaneous Coronary Intervention, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Stem Cells, Leukocytes, Mononuclear, Humans, Prospective Studies, Acute Coronary Syndrome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Percutaneous Coronary Intervention/adverse effects
Abstract: PLOS ONE 17(5), e0267433 (2022). doi:10.1371/journal.pone.0267433, Published by PLOS, San Francisco, California, US
Published: 2022
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8. Patient-oriented risk score for predicting death 1 year after myocardial infarction : the SweDen risk score

Author: Rylance, Rebecca Tremain, Wagner, Philippe, Olesen, Kevin K. W., Carlson, Jonas, Alfredsson, Joakim, Jernberg, Tomas, Leosdottir, Margret, Johansson, Pelle, Vasko, Peter, Maeng, Michael, Mohammed, Moman Aladdin, and Erlinge, David
Subjects: Heart Failure, Sweden/epidemiology, myocardial infarction, Kardiologi, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, acute coronary syndrome, biostatistics, Risk Factors, Humans, Cardiac and Cardiovascular Systems, Myocardial Infarction/diagnosis
Abstract: ObjectivesOur aim was to derive, based on the SWEDEHEART registry, and validate, using the Western Denmark Heart registry, a patient-oriented risk score, the SweDen score, which could calculate the risk of 1-year mortality following a myocardial infarction (MI).MethodsThe factors included in the SweDen score were age, sex, smoking, diabetes, heart failure and statin use. These were chosen a priori by the SWEDEHEART steering group based on the premise that the factors were information known by the patients themselves. The score was evaluated using various statistical methods such as time-dependent receiver operating characteristics curves of the linear predictor, area under the curve metrics, Kaplan-Meier survivor curves and the calibration slope.ResultsThe area under the curve values were 0.81 in the derivation data and 0.76 in the validation data. The Kaplan-Meier curves showed similar patient profiles across datasets. The calibration slope was 1.03 (95% CI 0.99 to 1.08) in the validation data using the linear predictor from the derivation data.ConclusionsThe SweDen risk score is a novel tool created for patient use. The risk score calculator will be available online and presents mortality risk on a colour scale to simplify interpretation and to avoid exact life span expectancies. It provides a validated patient-oriented risk score predicting the risk of death within 1 year after suffering an MI, which visualises the benefit of statin use and smoking cessation in a simple way. Funding Agencies|Swedish Research Council; Swedish Heart and Lung Foundation
Published: 2022

9. Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials

Author: Frederik Kraglund, Diana H. Christensen, Andreas H. Eiset, Gerda E. Villadsen, Joe West, and Peter Jepsen
Subjects: Liver Neoplasms/epidemiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Liver Cirrhosis/complications, Hepatology, Liver Cirrhosis, Alcoholic, Aspirin/therapeutic use, Humans, Fibrosis, Carcinoma, Hepatocellular/epidemiology
Abstract: BACKGROUND AND AIMS: Observational studies have shown an association between statin or aspirin use and a decreased risk of HCC, but the effects of a well-defined treatment strategy remain unknown. We emulated trials of the effects of continuous statin or aspirin use on HCC risk in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis).APPROACH AND RESULTS: We specified target trials for statins and, separately, aspirin and emulated them using Danish health care registries. All eligible patients with ALD cirrhosis diagnosed in 2000-2018 were included in either an exposed or an unexposed arm. Patients were followed until HCC or death without HCC. The 5-year risk of HCC was estimated using marginal structural models with inverse probability weighting. Using statins continuously for 5 years compared with not using statins resulted in a relative risk (RR) of HCC of 0.67 (95% CI: 0.45-0.91). The RR of death without HCC was 0.69 (95% CI: 0.65-0.77). For aspirin, the RR was 1.05 (95% CI: 0.60-1.42) for HCC and 1.02 (95% CI: 0.95-1.09) for death without HCC.CONCLUSIONS: In patients with ALD cirrhosis, 5 years of continuous statin use resulted in a 33% RR reduction of HCC (number needed to treat = 94) and a 31% RR reduction of death without HCC (number needed to treat = 7). Such strong causal effects are implausible and best explained by uncontrollable confounding, highlighting the need for randomized trials. Aspirin use likely does not affect the risk of HCC or death without HCC.
Published: 2023

10. Statin use and patterns of breast cancer recurrence in the Malmö Diet and Cancer Study

Author: Maria Inasu, Maria Feldt, Helena Jernström, Signe Borgquist, and Sixten Harborg
Subjects: Neoplasm Recurrence, Local/epidemiology, recurrence, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Breast Neoplasms/epidemiology, Statins, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cholesterol, Breast Neoplasms, General Medicine, Diet, Cholesterol, Breast cancer, Recurrence, distant metastases, cohort study, Humans, Surgery, Female, Original Article, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Neoplasm Recurrence, Local, RC254-282, Distant recurrences, Proportional Hazards Models
Abstract: Background Accumulating evidence suggests that statins have a beneficial effect on breast cancer prognosis. Previous studies have reported a positive association between statin use and breast cancer survival; however, the relationship between statin use and patterns of breast cancer recurrence remains unclear. Patients and methods We identified all Malmö Diet and Cancer Study (MDCS) participants diagnosed with incident invasive breast cancer between 2005 and 2014. The follow-up period began at breast cancer diagnosis and continued until the first invasive breast cancer recurrence event, death, emigration or the end of the follow-up (June 8, 2020). We estimated incidence rates (IRs) of recurrence and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for disease recurrence to compare post-diagnosis statin users with non-users. Results The final study cohort consisted of 360 eligible patients with a median follow-up of 8.6 years. Overall, there were 71 recurrences in 2932 total person-years. According to statin use, there were 14 recurrences in 595 person-years among statin users, and 57 recurrences in 2337 person-years in non-users. Statin use was associated with a reduced risk of breast cancer recurrence (HRadj = 0.88 [95% CI: 0.82–0.96]). Regarding the pattern of recurrence, statin use was associated with a reduced risk of distant recurrence (HRadj = 0.86 [95% CI: 0.80–0.94]) but not loco-regional recurrence (HRadj = 0.97 [95% CI: 0.87–1.08]). Conclusion In the MDCS, statin use was associated with a reduced risk of distant breast cancer recurrence, whereas no association between statin use and loco-regional breast cancer recurrence was found. This site-based difference in disease recurrence may be explained by statin's inhibition of epithelial-mesenchymal transition., Highlights • Breast cancer patients using statins have fewer recurrences. • Post-diagnosis statin use specifically reduced the risk of distant recurrence. • No protection against loco-regional recurrences was observed.
Published: 2021

11. Observational study of the medical management of patients with peripheral artery disease

Author: David Sidloff, Jannick A N Dorresteijn, V Htun, Ruth A. Benson, Z Mera, Athanasios Saratzis, Brenig L. Gwilym, R Lefroy, David C. Bosanquet, Toby Richards, Frank L.J. Visseren, A Tsui, A Thatcher, George Dovell, Nikesh Dattani, M Parks, N E M Jaspers, Rachael O. Forsythe, O Thomas, Joseph Shalhoub, and Tristan R A Lane
Subjects: Male, medicine.medical_specialty, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Platelet Aggregation Inhibitors/therapeutic use, Blood Pressure, 030204 cardiovascular system & hematology, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Journal Article, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Cardiovascular Diseases/etiology, Risk factor, Prospective cohort study, 11 Medical and Health Sciences, Aged, Aspirin, Lipids/blood, business.industry, Absolute risk reduction, Guideline, Middle Aged, Guideline Adherence/statistics & numerical data, Lipids, United Kingdom, Blood pressure, Cardiovascular Diseases, Cohort, Peripheral Arterial Disease/complications, Female, Smoking Cessation, Surgery, Guideline Adherence, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Vascular and Endovascular Research Network (VERN) Collaborators, business, Risk Reduction Behavior, Platelet Aggregation Inhibitors, Fibrinolytic agent, medicine.drug
Abstract: Background Previous research has suggested that patients with peripheral artery disease (PAD) are not offered adequate risk factor modification, despite their high cardiovascular risk. The aim of this study was to assess the cardiovascular profiles of patients with PAD and quantify the survival benefits of target-based risk factor modification. Methods The Vascular and Endovascular Research Network (VERN) prospectively collected cardiovascular profiles of patients with PAD from ten UK vascular centres (April to June 2018) to assess practice against UK and European goal-directed best medical therapy guidelines. Risk and benefits of risk factor control were estimated using the SMART-REACH model, a validated cardiovascular prediction tool for patients with PAD. Results Some 440 patients (mean(s.d.) age 70(11) years, 24·8 per cent women) were included in the study. Mean(s.d.) cholesterol (4·3(1·2) mmol/l) and LDL-cholesterol (2·7(1·1) mmol/l) levels were above recommended targets; 319 patients (72·5 per cent) were hypertensive and 343 (78·0 per cent) were active smokers. Only 11·1 per cent of patients were prescribed high-dose statin therapy and 39·1 per cent an antithrombotic agent. The median calculated risk of a major cardiovascular event over 10 years was 53 (i.q.r. 44–62) per cent. Controlling all modifiable cardiovascular risk factors based on UK and European guidance targets (LDL-cholesterol less than 2 mmol/l, systolic BP under 140 mmHg, smoking cessation, antiplatelet therapy) would lead to an absolute risk reduction of the median 10-year cardiovascular risk by 29 (20–38) per cent with 6·3 (4·0–9·3) cardiovascular disease-free years gained. Conclusion The medical management of patients with PAD in this secondary care cohort was suboptimal. Controlling modifiable risk factors to guideline-based targets would confer significant patient benefit.
Published: 2019

12. Association of Statin Use and Oncological Outcomes After Neoadjuvant Radiotherapy in Patients With Rectal Cancer

Author: Tina Fransgaard, Jesper Hallas, Lau Caspar Thygesen, and Ismail Gögenur
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Colorectal cancer, medicine.drug_class, medicine.medical_treatment, statins, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Rectal cancer, Neoadjuvant therapy, Aged, Aged, 80 and over, Rectal Neoplasms, business.industry, Hazard ratio, Chemoradiotherapy, General Medicine, Middle Aged, medicine.disease, Rectal Neoplasms/mortality, Neoadjuvant Therapy, Radiation therapy, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Propensity score matching, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract: AIM: The aim of the study was to examine if statin exposure during neoadjuvant chemoradiotherapy improves oncological outcomes in patients with rectal cancer. PATIENTS AND METHODS: The study cohort consisted of patients who were undergoing neoadjuvant chemoradiotherapy and resection for rectal cancer. The statin users were matched 1:1 with non-users using propensity score-based matching. The primary outcome of the study was disease-free survival; secondary outcomes were recurrence-free survival and all-cause mortality. RESULTS: A total of 704 patients were included in the study. Disease-free survival was not different between the two groups [hazard ratio (HR)=0.98, 95% confidence intervaI (CI)=0.77-1.25, p=0.88]. Both recurrence-free survival (HR=1.02, 95% CI=0.74-1.39, p=0.92) and all-cause mortality (HR=0.92, 95% CI=0.68-1.23, p=0.56) were similar for the two groups. CONCLUSION: The study does not support that statin use is associated with response to neoadjuvant chemoradiotherapy in terms of disease-free survival, recurrence-free survival or all-cause mortality.
Published: 2019

13. Controverses sur le dépistage et la prise en charge des dyslipidémies familiales en 2020 [Controversies concerning screening and treatment of primary dyslipidemias in 2020]

Author: Bretagne, L., Aubert, C., Nanchen, D., and Rodondi, N.
Subjects: Cholesterol, LDL/blood, Dyslipidemias/blood, Dyslipidemias/diagnosis, Dyslipidemias/genetics, Dyslipidemias/therapy, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Quality of Life, Risk Factors
Abstract: Familial dyslipidemia is rare compared to polygenetic causes. Nevertheless, it is important not to miss this diagnosis, as it is more strongly associated with an increased risk of early cardiovascular disease and scores for calculating cardiovascular risk are not valid in this population. Early detection and management based on lifestyle optimization and treatment of cardiovascular risk factors can delay the onset of cardiovascular complications and thus improve patients' quality of life. A LDL-Cholesterol of 4,9 mmol/l has recently been suggested as the cut-off for starting lipid lowering therapy, but remains controversial because the majority of people above this threshold do not have primary monogenic dyslipidemia. The age at which therapy should be initiated as well as the targets for treatment are also controversial.
Published: 2020

14. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials

Author: Terje R. Pedersen, Gregory G. Schwartz, Andrew Tonkin, Anastasia Lesogor, Helen M. Colhoun, Christiane Drechsler, Florian Kronenberg, Peter Willeit, John Simes, Paul M. Ridker, Sotirios Tsimikas, Anders G. Olsson, Samia Mora, Paul J. Nestel, and Christoph Wanner
Subjects: Male, medicine.medical_specialty, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, Hypercholesterolemia, Population, Cardiovascular Diseases/blood, Lipoprotein(a)/blood, Hypercholesterolemia/drug therapy, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, 030212 general & internal medicine, education, Stroke, Aged, Randomized Controlled Trials as Topic, Cholesterol, HDL/blood, education.field_of_study, biology, business.industry, Cholesterol, Cholesterol, HDL, Hazard ratio, Cholesterol, LDL, General Medicine, Lipoprotein(a), Middle Aged, medicine.disease, Cholesterol, LDL/blood, chemistry, Cardiovascular Diseases, Meta-analysis, biology.protein, Female, lipids (amino acids, peptides, and proteins), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Biomarkers, Biomarkers/blood, Lipoprotein
Abstract: BACKGROUND: Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established cardiovascular disease or on statin therapy is uncertain.METHODS: Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures. HRs for cardiovascular events were estimated within each trial across predefined lipoprotein(a) groups (15 to FINDINGS: Analyses included data for 29 069 patients with repeat lipoprotein(a) measurements (mean age 62 years [SD 8]; 8064 [28%] women; 5751 events during 95 576 person-years at risk). Initiation of statin therapy reduced LDL cholesterol (mean change -39% [95% CI -43 to -35]) without a significant change in lipoprotein(a). Associations of baseline and on-statin treatment lipoprotein(a) with cardiovascular disease risk were approximately linear, with increased risk at lipoprotein(a) values of 30 mg/dL or greater for baseline lipoprotein(a) and 50 mg/dL or greater for on-statin lipoprotein(a). For baseline lipoprotein(a), HRs adjusted for age and sex (vs INTERPRETATION: In this individual-patient data meta-analysis of statin-treated patients, elevated baseline and on-statin lipoprotein(a) showed an independent approximately linear relation with cardiovascular disease risk. This study provides a rationale for testing the lipoprotein(a) lowering hypothesis in cardiovascular disease outcomes trials.FUNDING: Novartis Pharma AG.
Published: 2018

15. Role of Experience With Preventive Medication and Personal Risk Attitude in Non-Attendance at Triple Vascular Screening

Author: Jes S. Lindholt, Rikke Søgaard, and Tina Birgitte Hansen
Subjects: Male, Health Knowledge, Attitudes, Practice, Denmark, Psychological intervention, Disease, 030230 surgery, Logistic regression, 0302 clinical medicine, Risk Factors, Odds Ratio, Mass Screening, Registries, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Aortic aneurysm, Secondary prevention, Attendance, Primary Prevention/methods, Primary Prevention, Treatment Outcome, Peripheral Arterial Disease/diagnosis, Hypertension, Hypertension/diagnosis, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Health literacy, Vascular disease, Risk Assessment, Peripheral Arterial Disease, 03 medical and health sciences, Fibrinolytic Agents, Mass Screening/methods, Predictive Value of Tests, Peripheral arterial disease, medicine, Humans, Antihypertensive Agents, Aged, Antihypertensive Agents/therapeutic use, Fibrinolytic Agents/therapeutic use, business.industry, Case-control study, Mass screening, Odds ratio, medicine.disease, Comorbidity, Denmark/epidemiology, Logistic Models, Case-Control Studies, Emergency medicine, Patient Compliance, Surgery, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Aortic Aneurysm, Abdominal, Aortic Aneurysm, Abdominal/diagnostic imaging
Abstract: BACKGROUND: Non-attendance for vascular screening potentially restricts the overall benefit of screening at population level, but may be the result of rational judgment on the part of invitees who might not consider their risk to be relevant. The aim of this study was to investigate the role of current use of preventive medication and personal risk attitude as potential factors explaining non-attendance at triple vascular screening.METHODS: This was a case control study across 25,078 men offered screening and intervention for abdominal aortic aneurysm, peripheral artery disease, and hypertension in the Viborg Vascular (VIVA) screening trial. Data on socio-demographic and socio-economic characteristics, diagnoses, and use of preventive medication were extracted from national registries. A proxy for personal risk attitude was constructed. Logistic regression was used to estimate odds ratios with 95% confidence intervals.RESULTS: Use of statins (0.78; 95% CI 0.71-0.85), antihypertensives (1.26, 95% CI 1.13-1.41), or antithrombotics (1.13, 95% CI 1.04-1.23) were all associated with non-attendance. With regards to personal risk attitude, a statistically significant association was found between users of preventive medication with no recent diagnosis of cardiovascular disease and non-attendance (0.82, 95% CI 0.72-0.94). The role of traditional factors explaining non-attendance at vascular screening, such as low socio-economic status and comorbidity, was confirmed.CONCLUSION: Non-attendance at triple vascular screening is influenced by use of preventive medications and traditional explanatory factors of non-attendance at vascular screening, including existing CVD comorbidity. Attendance rates might benefit from rethinking risk communication alongside screening invitations according to varying invitee profiles and clinical risk scenarios, and from providing interventions targeted at individuals with lower levels of health literacy.
Published: 2018

16. Preventive drug therapy and contralateral breast cancer:summary of the evidence of clinical trials and observational studies

Author: Rikke Langballe, Annet Bens, Deirdre Cronin-Fenton, Lene Mellemkjær, Jonine L. Bernstein, and Søren Friis
Subjects: Oncology, Retinoids/therapeutic use, Antineoplastic Agents, Hormonal/therapeutic use, Estrogen receptor, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Breast Neoplasms/prevention & control, skin and connective tissue diseases, media_common, Randomized Controlled Trials as Topic, Diphosphonates, Aromatase Inhibitors, Anti-Inflammatory Agents, Non-Steroidal, Neoplasms, Second Primary, Hematology, General Medicine, Metformin, Observational Studies as Topic, 030220 oncology & carcinogenesis, Female, Anti-Inflammatory Agents, Non-Steroidal/therapeutic use, Diphosphonates/therapeutic use, medicine.drug, Drug, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, media_common.quotation_subject, Antineoplastic Agents, Breast Neoplasms, Article, 03 medical and health sciences, Retinoids, Pharmacotherapy, Breast cancer, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Metformin/therapeutic use, Antihypertensive Agents, Antihypertensive Agents/therapeutic use, business.industry, Antineoplastic Agents/therapeutic use, medicine.disease, Neoplasms, Second Primary/prevention & control, Clinical trial, Tamoxifen, Tamoxifen/therapeutic use, Relative risk, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Aromatase Inhibitors/therapeutic use
Abstract: Background: Breast cancer patients have a lifelong 2–4-fold increased risk of developing a second primary tumor in the contralateral breast compared with the risk for a first primary breast cancer in the general female population. Prevention of contralateral breast cancer (CBC) has received increased attention during recent decades. Here, we summarize and discuss the available literature on drug preventive therapy and CBC. Results: The endocrine-targetting drugs, tamoxifen and aromatase inhibitors are used as standard adjuvant treatment for estrogen receptor (ER)-positive breast cancer. Both are associated with relative risk reductions of CBC of up to 50%, but incur serious side effects. Several prescription drugs originally developed for other purposes, including bisphosphonates, statins, non-steroidal anti-inflammatory drugs, metformin, anti-hypertensives and retinoids, have shown anti-cancer activity in preclinical models. However, results of observational studies on CBC are sparse and inconsistent, with only statins demonstrating promise as preventive agents and a potential treatment option for ER-negative breast cancer patients. Conclusion: Future studies are needed to assess the effect of statins in risk reduction and to identify other drugs with chemopreventive potential against CBC. Eventually, efforts must be directed towards identifying those breast cancer patients likely to benefit most from specific preventive therapies.
Published: 2019

17. Limited adherence to peripheral arterial disease guidelines and suboptimal ankle brachial index reliability in Dutch primary care

Author: Marc R.H.M. van Sambeek, Joep A.W. Teijink, Marc R. Scheltinga, Ellen Huijbers, Lindy N.M. Gommans, Edith M. Willigendael, Niels Pesser, Aafke Snoeijen, David Hageman, RS: CAPHRI - R5 - Optimising Patient Care, Epidemiologie, Promovendi PHPC, and Cardiovascular Biomechanics
Subjects: Male, Cross-sectional study, Platelet Aggregation Inhibitors/therapeutic use, Exercise Therapy/standards, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Ankle Brachial Index/standards, Medicine, 030212 general & internal medicine, LOWER-EXTREMITY, Supervised exercise therapy, Netherlands, Secondary prevention, GENERAL-PRACTITIONERS, Primary care, Peripheral, Exercise Therapy, RANDOMIZED CLINICAL-TRIAL, medicine.anatomical_structure, Practice Guidelines as Topic, Female, Guideline Adherence/standards, medicine.symptom, Cardiology and Cardiovascular Medicine, General practice, medicine.medical_specialty, Referral, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, PRESSURE, DIAGNOSIS, Intermittent claudication, 03 medical and health sciences, General Practice/standards, Peripheral arterial disease, MANAGEMENT, Humans, cardiovascular diseases, Ankle brachial index, Medical prescription, Primary Health Care/standards, Aged, Primary Health Care, BARRIERS, business.industry, Guideline adherence, Reproducibility of Results, Guideline, body regions, Cross-Sectional Studies, SUPERVISED EXERCISE, Physical therapy, Surgery, Ankle, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, human activities, Platelet Aggregation Inhibitors, TASK-FORCE, Peripheral Arterial Disease/prevention & control
Abstract: Objective/Background: The Dutch College of General Practitioners' guideline on peripheral arterial disease (PAD) provides clear recommendations on the management of PAD. An ankle brachial index (ABI) measurement, prescription of antiplatelet drugs and statins, and supervised exercise therapy (SET) for intermittent claudication (IC) are advised. The aims of this study were to determine the adherence of general practitioners (GPs) to their own guideline on PAD and to evaluate the reliability of primary care ABI measurements. Methods: This was a cross-sectional study. All patients suspected of having symptomatic PAD who were referred by GPs to a large hospital in 2015 were evaluated regarding three of the guideline criteria: (i) ABI measurement; (ii) prescription of secondary prevention; (iii) initiation of SET. ABI values obtained in primary care and the hospital's vascular laboratory were compared using correlation coefficients and regression analysis. An abnormal ABI was defined as a value =.9). Results: Of 308 potential patients with new onset PAD, 58% (n = 178) had undergone ABI measurement prior to referral. A modest correlation between ABI values obtained in primary care and the vascular laboratory was found (r = .63, p < .001). Furthermore, a moderate reliability was calculated (intraclass correlation coefficient 0.60, 95% confidence interval 0.49-0.69, p < .001). Of the new patients with an abnormal ABI, 59% used antiplatelet drugs and 55% used statins. A referral for SET was initiated by a GP in 10% of new PAD patients with IC symptoms. Conclusions: Adherence by Dutch GPs to their own society's PAD guideline has room for improvement. The reliability of ABI measurements is suboptimal, whereas rates of prescription of secondary prevention and initiation of SET as primary treatment for IC need upgrading. (C) 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Published: 2018

18. Statin Therapy May Influence the Incidence of Postoperative Atrial Fibrillation.

Author: Saso, Srdjan, Vecht, Joshua A., Rao, Christopher, Protopapas, Aristotle, Ashrafian, Hutan, Leff, Daniel, Darzi, Ara, and Athanasiou, Thanos
Subjects: *STATINS (Cardiovascular agents), *ATRIAL fibrillation, *SURGICAL complications, *ARRHYTHMIA, *RANDOMIZED controlled trials, *DISEASE risk factors, CARDIAC surgery patients
Abstract: Atrial fibrillation is the most common postoperative arrhythmia in patients who undergo cardiac surgery. We sought to determine whether the administration of statins reduces the incidence of postoperative atrial fibrillation in cardiac surgery patients. We performed a meta-analysis on all studies published between 2004 and 2008 that reported comparisons between statin treatment or nontreatment in these patients. Our primary focus was the incidence of postoperative atrial fibrillation. Random-effects modeling and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. Ten qualifying studies generated a total of 4,459 patients. The incidence of postoperative atrial fibrillation was 22.6% (622/2,758) in the statin-treated group and 29.8% (507/1,701) in the untreated group. Using the random-effects model, we calculated an odds ratio (OR) of 0.60 (95% confidence interval [CI], 0.48-0.76). When we considered only the 4 randomized studies (919 patients) in order to reduce the effects of heterogeneity, this significant reduction in the incidence of postoperative atrial fibrillation in the statin group was maintained (OR, 0.55; 95% CI, 0.41-0.73) with no heterogeneity (X² of heterogeneity, 2.96; P=0.4). In studies wherein only coronary artery bypass grafting was performed, statin treatment decreased postoperative atrial fibrillation (OR, 0.64; 95% CI, 0.43-0.95). We conclude that statin administration results in a reduction in the incidence of atrial fibrillation in patients who undergo cardiac surgery. Further research into the underlying mechanism can elucidate possible relationships between the dosage and type of statin used. [ABSTRACT FROM AUTHOR]
Published: 2009

19. Statins Improve Human Coronary Atherosclerotic Plaque Morphology.

Author: Reilly, Stephanie D., Litovsky, Silvio H., Steinkampf, Michael P., and Caulfield, James B.
Subjects: *STATINS (Cardiovascular agents), *CORONARY disease, *ATHEROSCLEROTIC plaque, *HEART transplantation, *MYOCARDIAL infarction, *DIABETES, *LOW density lipoproteins
Abstract: Statin treatment markedly reduces the incidence of acute coronary events in patients with coronary atherosclerosis. Although imaging studies have indirectly shown the beneficial effects of statins on plaque morphology, there has to our knowledge been no reported histologic comparison of the morphology of coronary plaque in statin-treated versus untreated patients who had substantial coronary artery atherosclerosis. We retrospectively studied arterial sections from the native hearts of patients who had experienced end-stage ischemic heart disease and subsequent cardiac transplantation. Of 44 qualified patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not. Pathologic examination of each explanted heart confirmed coronary artery disease and previous myocardial infarction in all patients. Diabetes mellitus was more prevalent in the study group. The groups were similar in levels of total and low-density lipoprotein cholesterol, and in the available number of arterial cross-sections per patient. All patients had plaques. High-grade lesions were found in 66.3% of cross-sections in the control group, and in 34.6% in the study group (P=0.011). Conversely, the degree of inflammation was markedly lower in the study group: low-grade fibrous plaques occurred in 45.7% of cross-sections in the study group, versus 11.3% in the control group (P=0.006).The study group had significantly fewer high-grade plaques and more fibrous plaques than did the control group at the time of transplantation. Our findings show that statin therapy substantially enhances plaque stabilization. We further suggest that reduction of plaque inflammation is an important aspect of this stabilization. [ABSTRACT FROM AUTHOR]
Published: 2008

20. WHO study on Prevention of REcurrences of Myocardial Infarction and StrokE (WHO-PREMISE).

Author: Mendis, Shanthi, Abegunde, Dele, Yusuf, Salim, Ebrahim, Shah, Shaper, Gerry, Ghannem, Hassen, and Shengelia, Bakuti
Subjects: *PREVENTION of heart diseases, *MYOCARDIAL infarction, *CORONARY disease, *SURVEYS, *SMOKING, *CIGARETTE smokers, *EXERCISE, *FOOD habits, *CHOLESTEROL, *BLOOD sugar
Abstract: Objective To determine the extent of secondary prevention of coronary heart disease (CHD) and cerebrovascular disease (CVD) in low- and middle-income countries. Methods A descriptive cross-sectional survey of a sample of 10 000 CHD (85.2%) and CVD (14.8%) patients (6252 men; 3748 women) was conducted over 6 months in geographically defined areas. The mean age was 59.2 years (standard deviation (SD), 10.8). Consecutive patients were recruited from a stratified random sample of primary, secondary and tertiary care facilities in defined areas in 10 countries (Brazil, Egypt, India, Indonesia, Islamic Republic of Iran, Pakistan, Russian Federation, Sri Lanka, Tunisia and Turkey). The main outcome measures were levels of lifestyle and physiological risk factors, and the use of drugs for secondary prevention of CHD and CVD. Findings Approximately 82%, 89% and 77% of patients were aware of the cardiovascular benefits of quitting smoking, a heart-healthy diet and regular physical activity, respectively. About half (52.5%) engaged in less than 30 minutes of physical activity per day, 35% did not follow a heart-healthy diet and 12.5 % were current tobacco users. Blood pressure had been measured in 93.8% (range 71-100%), blood cholesterol in 85.5% (range 29-97%) and blood sugar in 75.5% (range 65-99%) in the preceding 12 months. The proportions who had received medications among CHD and CVD patients were: aspirin, 81.2%, 70.6%; beta-blockers, 48.1%, 22.8%; angiotensin-converting enzyme inhibitor, 39.8%, 37.8%; statins, 29.8%, 14.1%, respectively. About one-fifth of patients with CHD had undergone revascularization. Conclusion A significant proportion of patients did not receive appropriate medications. About 47% of patients had at least two or more modifiable risk factors (smoking, physical inactivity, hypertension, diabetes or hypercholesterolaemia). There are considerable missed opportunities for prevention of recurrences in those with established CVD in low- and middle-income countries. [ABSTRACT FROM AUTHOR]
Published: 2005

21. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

Subjects: Causality, Hyperlipidemias/drug therapy, Cholesterol, LDL/blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Research Support, Non-U.S. Gov't, Hypolipidemic Agents/therapeutic use, Clinical Neurology, Journal Article, Humans, Brain Ischemia/epidemiology, Mendelian Randomization Analysis, Stroke/epidemiology, Coronary Disease/epidemiology
Abstract: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.MethodsWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.ResultsA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10 -8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10 -3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 -3) when compared with that for CHD.ConclusionsIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
Published: 2019

22. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

Author: METASTROKE Collaboration of the International Stroke Genetics Consortium
Subjects: Causality, Hyperlipidemias/drug therapy, Cholesterol, LDL/blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Research Support, Non-U.S. Gov't, Hypolipidemic Agents/therapeutic use, Clinical Neurology, Journal Article, Humans, Brain Ischemia/epidemiology, Mendelian Randomization Analysis, Stroke/epidemiology, Coronary Disease/epidemiology
Abstract: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.MethodsWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.ResultsA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10 -8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10 -3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 -3) when compared with that for CHD.ConclusionsIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
Published: 2019

23. Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events The ODYSSEY OUTCOMES Trial

Author: Szarek, Michael, White, Harvey D., Schwartz, Gregory G., Alings, Marco, Bhatt, Deepak L., Bittner, Vera A., Diaz, Rafael, Edelberg, Jay M., Goodman, Shaun G., Hanotin, Corinne, Harrington, Robert A., Jukema, J. Wouter, Kimura, Takeshi, Kiss, Robert Gabor, Lecorps, Guillaume, Mahaffey, Kenneth W., Moryusef, Angele, Pordy, Robert, Roe, Matthew T., Tricoci, Pierluigi, Xavier, Denis, Zeiher, Andreas M., Steg, Gabriel, Clemmensen, Peter, Gislason, Gunnar, Larsen, John, Davidsen, Flemming, Videbaek, Lars, and Andersen, Dorthe
Subjects: total events, Male, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, food and beverages, alirocumab, Antibodies, Monoclonal/therapeutic use, Middle Aged, Antibodies, Monoclonal, Humanized, acute coronary syndrome, Acute Coronary Syndrome/drug therapy, Humans, Female, Drug Therapy, Combination, Follow-Up Studies, Aged
Abstract: Background: The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. Objectives: This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. Methods: Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. Results: With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. Conclusions: In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS.
Published: 2019

24. Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project

Author: Emma H. Allott, Jeannette T. Bensen, James L. Mohler, L. Joseph Su, Elizabeth T.H. Fontham, Lenore Arab, Susan E. Steck, Merle H. Mishel, and Laura Farnan
Subjects: Male, 0301 basic medicine, Oncology, Prostate Cancer Aggressiveness, medicine.medical_specialty, Inverse Association, Pathology, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Epidemiology, Prostatic Neoplasms/prevention & control, Logistic regression, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, North Carolina, medicine, Humans, business.industry, Prostatic Neoplasms, Cancer, Middle Aged, Statin treatment, Louisiana, medicine.disease, United States, Confidence interval, Treatment Outcome, 030104 developmental biology, Prostate cancer screening, 030220 oncology & carcinogenesis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract: Background: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use. Methods: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association. Results: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56–0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45–1.39), men screened at low/recommended frequency (≤once/year; OR, 0.66; 95% CI, 0.41–1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53–1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25–0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59–1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70–2.64). Conclusions: Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers. Impact: Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670–7. ©2016 AACR.
Published: 2016

25. Comparison of Five Major Guidelines for Statin Use in Primary Prevention in a Contemporary General Population

Author: Mortensen, Martin Bødtker, Nordestgaard, Børge Grønne, Mortensen, Martin Bødtker, and Nordestgaard, Børge Grønne
Abstract: Background: Five major organizations recently published guidelines for using statins to prevent atherosclerotic cardiovascular disease (ASCVD): in 2013, the American College of Cardiology/American Heart Association (ACC/AHA); in 2014, the United Kingdom's National Institute for Health and Care Excellence (NICE); and in 2016, the Canadian Cardiovascular Society (CCS), the U.S. Preventive Services Task Force (USPSTF), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS).Objective: To compare the utility of these guidelines for primary prevention of ASCVD.Design: Observational study of actual ASCVD events during 10 years, followed by a modeling study to estimate the effectiveness of different guidelines.Setting: The Copenhagen General Population Study.Participants: 45 750 Danish persons aged 40 to 75 years who did not use statins and did not have ASCVD at baseline.Measurements: The number of participants eligible to use statins according to each guideline and the estimated number of ASCVD events that statins could have prevented.Results: The percentage of participants eligible for statins was 44% by the CCS guideline, 42% by ACC/AHA, 40% by NICE, 31% by USPSTF, and 15% by ESC/EAS. The estimated percentage of ASCVD events that could have been prevented by using statins for 10 years was 34% for CCS, 34% for ACC/AHA, 32% for NICE, 27% for USPSTF, and 13% for ESC/EAS.Limitation: This study was limited to primary prevention in white Europeans.Conclusion: Guidelines recommending that more persons use statins for primary prevention of ASCVD should prevent more events than guidelines recommending use by fewer persons.Primary Funding Source: Copenhagen University Hospital.
Published: 2018

26. Update on statin-mediated anti-inflammatory activities in atherosclerosis

Author: François Mach and Fabrizio Montecucco
Subjects: Statin, medicine.drug_class, Immunology, Anti-Inflammatory Agents, Inflammation, 030204 cardiovascular system & hematology, Biology, Pharmacology, Signal Transduction/drug effects/immunology, Antioxidants, Anti-Inflammatory Agents/*immunology/therapeutic use, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Immunology and Allergy, Animals, Humans, Inflammation/drug therapy/immunology, cardiovascular diseases, 030304 developmental biology, ddc:616, 0303 health sciences, Cholesterol/immunology, Kinase, Cholesterol, nutritional and metabolic diseases, Atherosclerosis, Hydroxymethylglutaryl-CoA reductase, 3. Good health, Disease Models, Animal, chemistry, Hydroxymethylglutaryl-CoA Reductase Inhibitors/*immunology/therapeutic use, Atherosclerosis/drug therapy/*immunology, Protein prenylation, lipids (amino acids, peptides, and proteins), Signal transduction, medicine.symptom, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Intracellular, Signal Transduction
Abstract: Anti-inflammatory activities of statins in atherosclerosis have been well documented by both basic research and clinical studies. Statins have been introduced in the 1980s as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to block cholesterol synthesis and lower cholesterol serum levels. In the last three decades, statins have been shown to possess several anti-inflammatory and antioxidant activities resulting in the beneficial reduction of atherosclerotic processes and cardiovascular risk in both humans and animal models. Inflammatory intracellular pathways involving kinase phosphorylation and protein prenylation are modulated by statins. The same intracellular mechanisms might also cause statin-induced myotoxicity. In the present review, we will update evidence on statin-mediated regulation of inflammatory pathways in atherogenesis.
Published: 2018

27. Concurrent new drug prescriptions and prognosis of early breast cancer:studies using the Danish Breast Cancer Group clinical database

Author: Cronin-Fenton, Deirdre, Lash, Timothy L, Ahern, Thomas P, Damkier, Per, Christiansen, Peer, Ejlertsen, Bent, and Sørensen, Henrik T
Subjects: Estrogen Antagonists/therapeutic use, Glucocorticoids/therapeutic use, Analgesics, Opioid/therapeutic use, Breast Neoplasms/pathology, Databases, Factual, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Platelet Aggregation Inhibitors/therapeutic use, Denmark, Adrenergic beta-Antagonists/therapeutic use, Prognosis, Cardiotonic Agents/therapeutic use, Digoxin/therapeutic use, Angiotensin-Converting Enzyme Inhibitors/therapeutic use, Cyclooxygenase 2 Inhibitors/therapeutic use, Tamoxifen/therapeutic use, Simvastatin/therapeutic use, Aspirin/therapeutic use, Disease Progression, Humans, Female, Anti-Inflammatory Agents, Non-Steroidal/therapeutic use, Neoplasm Recurrence, Local, skin and connective tissue diseases, Serotonin Uptake Inhibitors/therapeutic use
Abstract: BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter the viability of breast cancer cells in pre-clinical studies. Routine use of these drugs, therefore, may impact breast cancer prognosis, and could have important implications for public health.METHODS: The Danish Breast Cancer Group (DBCG) clinical database provides high-quality prospectively collected data on breast cancer diagnosis, treatment, and routine follow-up for breast cancer recurrence. Individual-level linkage of DBCG data to other population-based and medical registries in Denmark, including the Danish National Prescription Registry, has facilitated large population-based pharmacoepidemiology studies. A unique advantage of using DBCG data for such studies is the ability to investigate the association of drugs with breast cancer recurrence rather than breast cancer mortality - which may be misclassified - or all-cause mortality. Here we summarize findings from pharmacoepidemiological studies, based on DBCG data, on the association between routinely used prescription drugs and risk of breast cancer recurrence.RESULTS: Our findings suggest that concurrent use of glucocorticoids, ACE inhibitors, aspirin, NSAIDs, selective COX-2 inhibitors, digoxin, and opioids has little impact on breast cancer recurrence. Similarly, patients who use SSRIs concurrently with tamoxifen treatment are not at increased risk of recurrence. In contrast, post-diagnostic use of simvastatin, a lipophilic statin, correlates with a decreased risk of breast cancer recurrence, providing a rationale for a prospective randomized clinical trial investigating simvastatin as an adjuvant therapy for breast cancer.CONCLUSION: As a whole, findings of pharmacoepidemiological studies based on DBCG data provide reassurance to physicians and healthcare personnel who provide supportive care during and after cancer (including prescriptions for comedications) and to breast cancer survivors for whom the risk of breast cancer recurrence is a major concern.
Published: 2018

28. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

Abstract: BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, o
Published: 2017

29. Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks:Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial

Author: Ganz, Peter, Amarenco, Pierre, Goldstein, Larry B, Sillesen, Henrik, Bao, Weihang, Preston, Gregory M, Welch, K Michael A, Ganz, Peter, Amarenco, Pierre, Goldstein, Larry B, Sillesen, Henrik, Bao, Weihang, Preston, Gregory M, and Welch, K Michael A
Abstract: BACKGROUND AND PURPOSE: Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes.METHODS: We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models.RESULTS: There was no association between time to stroke and lipoprotein-associated phospholipase A2, monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P<0.0001), neopterin (hazard ratio, 1.137; P=0.0107), myeloperoxidase (hazard ratio, 1.177; P=0.0022), and adiponectin (hazard ratio, 1.207; P=0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 (P=0.015) and yielded a continuous net reclassification improvement (29.1%; P<0.0001) and an integrated discrimination improvement (42.3%; P<0.0001).CONCLUSIONS: Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk
Published: 2017

30. Statin Therapy in ARAS: Beyond Cholesterol Lowering

Author: Pascal Meier
Subjects: medicine.medical_specialty, Cholesterol, business.industry, Atherosclerosis/blood, Atherosclerosis/complications, Cholesterol/blood, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Renal Artery Obstruction/blood, Renal Artery Obstruction/drug therapy, Treatment Outcome, Treatment outcome, Urology, Renal Artery Obstruction, Cholesterol lowering, Atherosclerosis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, chemistry.chemical_compound, chemistry, Internal Medicine, medicine, Statin therapy, business
Published: 2017

31. Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes

Author: David Nanchen, Christian Schmied, Giulio G. Stefanini, Reto Auer, Jacques Cornuz, Baris Gencer, Lorenz Räber, Stephan Windecker, Olivier Muller, Christian M. Matter, Peter Jüni, Roland Klingenberg, François Mach, Thomas F. Lüscher, Pierre Vogt, Nicolas Rodondi, University of Zurich, and Nanchen, David
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Network algorithms, 610 Medicine & health, Familial hypercholesterolemia, Disease, 030204 cardiovascular system & hematology, 2705 Cardiology and Cardiovascular Medicine, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, 360 Social problems & social services, Internal medicine, medicine, Prevalence, Humans, In patient, 030212 general & internal medicine, Acute Coronary Syndrome, Acute Coronary Syndrome/complications, Acute Coronary Syndrome/epidemiology, Analysis of Variance, Atherosclerosis/epidemiology, Atherosclerosis/prevention & control, Cholesterol, LDL/drug effects, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Hyperlipoproteinemia Type II/complications, Hyperlipoproteinemia Type II/drug therapy, Middle Aged, Proprotein Convertases/antagonists & inhibitors, Quality of Health Care, Serine Endopeptidases, Switzerland, Lipid clinic, business.industry, Cholesterol, LDL, medicine.disease, Atherosclerosis, Confidence interval, 3. Good health, Endocrinology, 10209 Clinic for Cardiology, Proprotein Convertases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Proprotein Convertase 9, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: AIMS: We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION: A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required.
Published: 2017

32. Statin use, Candidate Mevalonate Pathway Biomarkers, and Colon Cancer Survival in a Population-Based Cohort Study

Author: Helen G. Coleman, Liam J. Murray, Roisin O'Neill, Maurice B Loughrey, Peter Bankhead, Anna Gavin, Christopher Cardwell, Jacqueline James, Claire McGready, Kenneth Arthur, Ronan T. Gray, Victoria Bingham, Peter W. Hamilton, Manuel Salto-Tellez, and Stephen McQuaid
Subjects: 0301 basic medicine, Oncology, Colonic Neoplasms/chemistry, Male, Cancer Research, Epidemiology, Colorectal cancer, Pharmacology, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, HMGCR protein, Aged, 80 and over, education.field_of_study, Tissue microarray, Hazard ratio, Gastroenterology, colonic neoplasms, Middle Aged, tumour suppressor protein p53, Survival Rate, 030220 oncology & carcinogenesis, Cohort, lipids (amino acids, peptides, and proteins), Female, KRAS, Mevalonic Acid/metabolism, Metabolic Networks and Pathways, Cohort study, medicine.medical_specialty, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Population, Mevalonic Acid, Biology, survival, Proto-Oncogene Proteins p21(ras), Biomarkers, Tumor/analysis, Proto-Oncogene Proteins p21(ras)/genetics, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Biomarkers, Tumor, medicine, Humans, education, Survival rate, Aged, Hepatology, Proportional hazards model, business.industry, Hydroxymethylglutaryl CoA Reductases/analysis, medicine.disease, Tumor Suppressor Protein p53/analysis, 030104 developmental biology, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Tumor Suppressor Protein p53, business
Abstract: BACKGROUND: Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed.METHODS: The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004 and 2008. Statin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical expression of p53 and HMGCR in tissue microarrays and the presence of KRAS mutations in extracted DNA. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer-specific and overall survival.RESULTS: Statin use was not associated with improved cancer-specific survival in this cohort (HR=0.91, 95% CI 0.64-1.28). Statin use was also not associated with improved survival when the analyses were stratified by tumour p53 (wild-type HR=1.31, 95% CI 0.67-2.56 vs aberrant HR=0.80, 95% CI 0.52-1.24), HMGCR (HMGCR-high HR=0.69, 95% CI 0.40-1.18 vs HMGCR-low HR=1.10, 95% CI 0.66-1.84), and KRAS (wild-type HR=0.73, 95% CI 0.44-1.19 vs mutant HR=1.21, 95% CI 0.70-2.21) status.CONCLUSIONS: Statin use was not associated with improved survival either independently or when stratified by potential mevalonate pathway biomarkers in this population-based cohort of colon cancer patients.
Published: 2017

33. Statin Use, Serum Lipids, and Prostate Inflammation in Men with a Negative Prostate Biopsy: Results from the REDUCE Trial

Author: Lauren E. Howard, Ramiro Castro-Santamaria, Adriana C. Vidal, Stephen J. Freedland, Daniel M. Moreira, Emma H. Allott, and Gerald L. Andriole
Subjects: Male, Cancer Research, medicine.medical_specialty, Prostate/pathology, Statin, Prostate biopsy, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, Biopsy, Prostate-Specific Antigen/blood, Prostatitis, Blood lipids, Gastroenterology, Article, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, medicine.diagnostic_test, business.industry, Lipids/blood, Prostatic Neoplasms, Cancer, Prostatic Neoplasms/blood, Prostate-Specific Antigen, Middle Aged, medicine.disease, Lipids, Prostate-specific antigen, Endocrinology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, lipids (amino acids, peptides, and proteins), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Prostatitis/blood, business
Abstract: Statin use is associated with lower advanced prostate cancer risk. In addition to cholesterol lowering, statins have systemic anti-inflammatory properties. However, their effect on histologic prostate inflammation is not well understood, particularly among men at increased prostate cancer risk but with a negative prostate biopsy. We examined associations between serum lipid levels, statin use, and histologic prostate inflammation using data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Statin use and lipid levels [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] were assessed at baseline. Inflammation was assessed by central review. Logistic regression was used to examine the effects of lipids and statin use on presence and extent of chronic and acute prostate inflammation [none, moderate (
Published: 2017

34. No benefits of statins for sudden cardiac death prevention in patients with heart failure and reduced ejection fraction: A meta-analysis of randomized controlled trials

Author: H. Le, Bernard Burnand, M. Fall, Muaamar Al-Gobari, François Gueyffier, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)
Subjects: [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Sudden Cardiac Death, law.invention, Sudden cardiac death, Mathematical and Statistical Techniques, 0302 clinical medicine, Randomized controlled trial, law, Cause of Death, Odds Ratio, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, Cause of death, Multidisciplinary, Ejection fraction, Drugs, Research Assessment, 3. Good health, Treatment Outcome, Meta-analysis, Physical Sciences, Cardiology, Statistics (Mathematics), Research Article, medicine.medical_specialty, Drug Research and Development, Systematic Reviews, Death Rates, Science, Research and Analysis Methods, 03 medical and health sciences, Internal medicine, Humans, Clinical Trials, Statistical Methods, Demography, Heart Failure, Pharmacology, Death, Sudden, Cardiac/epidemiology, Death, Sudden, Cardiac/etiology, Death, Sudden, Cardiac/prevention & control, Heart Failure/complications, Heart Failure/physiopathology, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Publication Bias, Stroke Volume, business.industry, Statins, Publication bias, medicine.disease, Randomized Controlled Trials, Death, Sudden, Cardiac, Relative risk, Heart failure, People and Places, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Clinical Medicine, business, Mathematics, Meta-Analysis, Ejection Fraction
Abstract: Background and objectivesStatins showed mixed results in heart failure (HF) patients. The benefits in major HF outcomes, including all-cause mortality and sudden cardiac death (SCD), have always been discordant across systematic reviews and meta-analyses. We intended to systematically identify and appraise the available evidence that evaluated the effectiveness of statins in clinical outcomes for HF patients.DesignSystematic review and meta-analysis.Data sourcesWe searched, until April 28, 2016: Medline, Embase, ISI Web of Science and EBM reviews (Cochrane DSR, ACP journal club, DARE, CCTR, CMR, HTA, and NHSEED), checked clinicaltrials.gov for ongoing trials and manually searched references of included studies.Eligibility criteria for selecting studiesWe identified 24 randomized clinical trials that evaluated the efficacy of statins for HF patients. All randomized clinical trials were assessed for risk of bias and pooled together in a meta-analysis. Pre-specified outcomes were sudden cardiac death, all-cause mortality, and hospitalization for worsening heart failure.ResultsStatins did not reduce sudden cardiac death (SCD) events in HF patients [relative risk (RR) 0.92, 95% confidence interval (CI) 0.70 to 1.21], all-cause mortality [RR 0.88, 95% CI 0.75 to 1.02] but significantly reduced hospitalization for worsening heart failure (HWHF) although modestly [RR 0.79, 95% CI 0.66 to 0.94]. Nevertheless, estimated predictive intervals were insignificant in SCD, all-cause mortality and HWHF [RR, 0.54 to 1.63, 0.64 to 1.19, and 0.54 to 1.15], respectively. An important finding was the possible presence of publication bias, small-study effects and heterogeneity of the trials conducted in HF patients.ConclusionsStatins do not reduce sudden cardiac death, all-cause mortality, but may slightly decrease hospitalization for worsening heart failure in HF patients. The evaluation of the risk of biases suggested moderate quality of the published results. Until new evidence is available, this study supports the 2013 ACCF/AHA guidelines to not systematically prescribe statins in "only" HF patients, which should help avoid unnecessary polypharmacy.
Published: 2017

35. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease

Author: Jørgen Vestbo, Truls Sylvan Ingebrigtsen, Jesper Hallas, Peter Lange, Børge G. Nordestgaard, and Jacob Louis Marott
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Time Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Population, Disease, law.invention, Pulmonary Disease, Chronic Obstructive, Randomized controlled trial, Recurrence, law, Internal medicine, medicine, Humans, education, Aged, Retrospective Studies, education.field_of_study, COPD, biology, business.industry, C-reactive protein, Retrospective cohort study, medicine.disease, Comorbidity, Pulmonary Disease, Chronic Obstructive/drug therapy, Treatment Outcome, Disease Progression, Physical therapy, biology.protein, Population study, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Follow-Up Studies
Abstract: BACKGROUND: We tested the hypothesis that statin use in individuals with COPD is associated with a reduced risk of exacerbations.METHODS: We identified 5794 individuals with COPD and a measurement of C reactive protein (CRP) in the Copenhagen General Population Study (2003-2008). During 3 years of follow-up we recorded exacerbations with hospital admissions or oral corticosteroid treatment. In a nested case-control design, matching on age, gender, smoking, COPD severity and comorbidity, we estimated the association between statin use and exacerbations. In addition, we examined the association between statin use and high CRP (>3 mg/L), and the association between high CRP and exacerbations during follow-up.RESULTS: Statin use was associated with reduced odds of exacerbations in crude analysis, OR=0.68 (95% CI 0.51 to 0.91, p=0.01), as well as in multivariable conditional logistic regression analysis, OR=0.67 (0.48 to 0.92, p=0.01). However, in the subgroup with the most severe COPD and without cardiovascular comorbidity, we observed a null association between statin use and exacerbations, OR=1.1 (0.5 to 2.1, p=0.83). Furthermore, statin use was associated with reduced odds of a high CRP, OR=0.69 (0.56 to 0.85, pCONCLUSIONS: Statin use was associated with reduced odds of exacerbations in individuals with COPD from the general population, although this was not apparent in those with the most severe COPD without cardiovascular comorbidity. Statins may thus only associate with reduced risk of exacerbations in patients with COPD with coexisting cardiovascular disease.
Published: 2014

36. Comparison of Application of the ACC/AHA Guidelines, Adult Treatment Panel III Guidelines, and European Society of Cardiology Guidelines for Cardiovascular Disease Prevention in a European Cohort

Author: Maryam Kavousi, M. Arfan Ikram, Ewout W. Steyerberg, Albert Hofman, David Nanchen, Maarten J.G. Leening, Bruno H. Stricker, Oscar H. Franco, Philip Greenland, Ian D. Graham, Epidemiology, Cardiology, Public Health, Radiology & Nuclear Medicine, and Internal Medicine
Subjects: Male, medicine.medical_specialty, Pediatrics, Cardiology, Risk Assessment, Cohort Studies, Rotterdam Study, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, medicine, Humans, Cumulative incidence, Myocardial infarction, Stroke, Societies, Medical, Aged, Netherlands, business.industry, General Medicine, Guideline, American Heart Association, Cardiovascular Diseases/epidemiology, Cardiovascular Diseases/prevention & control, Europe, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Middle Aged, Models, Theoretical, Practice Guidelines as Topic, Risk Assessment/methods, Stroke/epidemiology, United States, medicine.disease, Coronary heart disease, Cardiovascular Diseases, Cohort, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Cohort study
Abstract: Importance The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines introduced a prediction model and lowered the threshold for treatment with statins to a 7.5% 10-year hard atherosclerotic cardiovascular disease (ASCVD) risk. Implications of the new guideline’s threshold and model have not been addressed in non-US populations or compared with previous guidelines. Objective To determine population-wide implications of the ACC/AHA, the Adult Treatment Panel III (ATP-III), and the European Society of Cardiology (ESC) guidelines using a cohort of Dutch individuals aged 55 years or older. Design, Setting, and Participants We included 4854 Rotterdam Study participants recruited in 1997-2001. We calculated 10-year risks for “hard” ASCVD events (including fatal and nonfatal coronary heart disease [CHD] and stroke) (ACC/AHA), hard CHD events (fatal and nonfatal myocardial infarction, CHD mortality) (ATP-III), and atherosclerotic CVD mortality (ESC). Main Outcomes and Measures Events were assessed until January 1, 2012. Per guideline, we calculated proportions of individuals for whom statins would be recommended and determined calibration and discrimination of risk models. Results The mean age was 65.5 (SD, 5.2) years. Statins would be recommended for 96.4% (95% CI, 95.4%-97.1%; n = 1825) of men and 65.8% (95% CI, 63.8%-67.7%; n = 1523) of women by the ACC/AHA, 52.0% (95% CI, 49.8%-54.3%; n = 985) of men and 35.5% (95% CI, 33.5%-37.5%; n = 821) of women by the ATP-III, and 66.1% (95% CI, 64.0%-68.3%; n = 1253) of men and 39.1% (95% CI, 37.1%-41.2%; n = 906) of women by ESC guidelines. With the ACC/AHA model, average predicted risk vs observed cumulative incidence of hard ASCVD events was 21.5% (95% CI, 20.9%-22.1%) vs 12.7% (95% CI, 11.1%-14.5%) for men (192 events) and 11.6% (95% CI, 11.2%-12.0%) vs 7.9% (95% CI, 6.7%-9.2%) for women (151 events). Similar overestimation occurred with the ATP-III model (98 events in men and 62 events in women) and ESC model (50 events in men and 37 events in women). The C statistic was 0.67 (95% CI, 0.63-0.71) in men and 0.68 (95% CI, 0.64-0.73) in women for hard ASCVD (ACC/AHA), 0.67 (95% CI, 0.62-0.72) in men and 0.69 (95% CI, 0.63-0.75) in women for hard CHD (ATP-III), and 0.76 (95% CI, 0.70-0.82) in men and 0.77 (95% CI, 0.71-0.83) in women for CVD mortality (ESC). Conclusions and Relevance In this European population aged 55 years or older, proportions of individuals eligible for statins differed substantially among the guidelines. The ACC/AHA guideline would recommend statins for nearly all men and two-thirds of women, proportions exceeding those with the ATP-III or ESC guidelines. All 3 risk models provided poor calibration and moderate to good discrimination. Improving risk predictions and setting appropriate population-wide thresholds are necessary to facilitate better clinical decision making.
Published: 2014

37. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

Subjects: Hyperlipidemias/drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Clinical Neurology, Mendelian Randomization Analysis, Research Support, Stroke/epidemiology, LDL/blood, Causality, Cholesterol, Hypolipidemic Agents/therapeutic use, Journal Article, Humans, Brain Ischemia/epidemiology, Non-U.S. Gov't, Coronary Disease/epidemiology
Abstract: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.MethodsWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.ResultsA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10 -8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10 -3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 -3) when compared with that for CHD.ConclusionsIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
Published: 2019

38. Lipid-Lowering Therapies: Risks in Women and Evidence-Based Options.

Author: Shah, Tina and Virani, Salim S.
Subjects: *LIPIDS in the body, *ATHEROSCLEROTIC plaque, *CARDIOVASCULAR disease diagnosis, *STATINS (Cardiovascular agents), *WOMEN'S health
Abstract: The article discusses several lipid-lowering therapies for women. Topics discussed include identifying the prevalence of atherosclerotic cardiovascular disease risk factors, the use of statins for lowering low-density lipoprotein cholesterol in women, and the risk of developing diabetes mellitus post-consumption of statin.
Published: 2018
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39. Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible Diabetes (ATTEMPT): A Prospective-Randomized Study in Middle Aged Men and Women

Author: Vassilios G, Athyros, Emmanouel, Ganotakis, Genovefa D, Kolovou, Vassilios, Nicolaou, Apostolos, Achimastos, Eleni, Bilianou, Theodore, Alexandrides, Asterios, Karagiannis, Konstantinos, Paletas, Evangelos N, Liberopoulos, Konstantinos, Tziomalos, Dimitrios, Petridis, Anna, Kakafika, Moses S, Elisaf, Dimitri P, Mikhailidis, and N, Tsakoudakis
Subjects: Male, medicine.medical_specialty, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Atorvastatin, Disease, Group B, law.invention, Treatment and control groups, Sex Factors, Randomized controlled trial, Risk Factors, law, Cholesterol, LDL/blood/*drug effects, Diabetes mellitus, Internal medicine, Humans, Medicine, Outpatient clinic, Pyrroles, Treatment effect, Prospective Studies, Prospective cohort study, Aged, Metabolic Syndrome, Pharmacology, medicine.diagnostic_test, business.industry, Pyrroles/*therapeutic use, Cholesterol, LDL, Middle Aged, medicine.disease, Heptanoic Acids/*therapeutic use, Metabolic Syndrome X/complications/*drug therapy, Cardiovascular Diseases, Heptanoic Acids, Cardiovascular Diseases/etiology/*prevention & control, Physical therapy, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Metabolic syndrome, Cardiology and Cardiovascular Medicine, business, Lipid profile, Follow-Up Studies, medicine.drug
Abstract: AIM: To assess the reduction in estimated cardiovascular disease (e-CVD) risk after multifactorial treatment for 6 months and follow this change during the next 3-years. PATIENTS-METHODS: This prospective, randomized, target driven study included 1,123 subjects (512/611 men/women, aged 45-65 years) with metabolic syndrome (MetS) without diabetes or CVD referred to specialist outpatient clinics. Patients were randomized to two treatment groups: group A with low density lipoprotein cholesterol (LDL-C) target of < 100 mg/dl and group B with a target of < 130 mg/dl. Atorvastatin was used in both groups on top of optimal multifactorial treatment, (quinapril, amlodipine, hydrochlorothiazide for hypertension, metformin for impaired fasting glucose, and orlistat for obesity). The e-CVD risk was calculated using the Framingham, the PROCAM and Reynold's equations. RESULTS: Reductions in e-CVD risk at 6 months were > 50%in all patients, but were superior in group A and in women. Reductions were even greater during the next 3-years and were mainly attributed to changes in lipid profile. Actual CVD events were 1 in group A and 13 in group B; p=0.0012. CONCLUSIONS: Attaining the treatment target of LDL-C < 100 mg/dl within multifactorial treatment of MetS by expert clinics, is achievable and beneficial even in patients without diabetes or known CVD. This induces a considerable e-CVD risk reduction in MetS patients. Actual CVD events were negligible, suggesting that e-CVD risk overestimates actual CVD risk in MetS, at least in patients achieving LDL-C < 100 mg/dl [ClinicalTrials.gov ID: NCT00416741]. Curr Vasc Pharmacol
Published: 2011

40. Effect of HMG-CoA reductase inhibitors on vascular cell apoptosis: Beneficial or detrimental?

Author: Yiannis S. Chatzizisis, Niki Katsiki, Apostolos I. Hatzitolios, Moses Elisaf, and Konstantinos Tziomalos
Subjects: Programmed cell death, medicine.medical_specialty, Statin, Vascular smooth muscle, medicine.drug_class, Apoptosis, Restenosis, Internal medicine, Humans, Medicine, Rosuvastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/therapeutic use, cardiovascular diseases, Graft Occlusion, Vascular/prevention & control, biology, business.industry, Vascular disease, Graft Occlusion, Vascular, nutritional and metabolic diseases, Apoptosis/*drug effects, Atherosclerosis, medicine.disease, Endocrinology, Atherosclerosis/pathology/*prevention & control, HMG-CoA reductase, Cancer research, biology.protein, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Pravastatin, medicine.drug
Abstract: Vascular cell apoptosis, an active form of programmed cell death, plays an integral role in atherosclerosis and in-stent restenosis after angioplasty, thus promoting the precipitation of acute cardiovascular events. Beyond their cholesterol-lowering effects, HMG-CoA reductase inhibitors, or statins, have been persistently reported to influence the apoptotic process. In this review we discuss the effect of statin treatment on vascular cell apoptosis, and therefore on atherosclerosis development, plaque rupture and in-stent restenosis, based on the results of up-to-date experimental and clinical studies. Lipophilic statins have been shown to induce apoptosis in a variety of cell types, including vascular smooth muscle cells and endothelial cells, whereas hydrophilic statins (rosuvastatin and pravastatin) have not. The clinical importance of statin induced apoptosis remains controversial, as it may blunt vascular wall thickening in the early stages of atherosclerosis or reduce the neointimal response to injury on the one hand, but on the other hand it may also promote destabilization of vulnerable plaques precipitating acute cardiovascular events. Current data support the initiation of statin treatment early enough to inhibit both the formation of atherosclerotic plaques (primary prevention) and in-stent restenosis (secondary prevention). Atherosclerosis
Published: 2010

41. Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome

Author: Thomas F. Lüscher, Nicolas Rodondi, Roland Klingenberg, Stephan Windecker, François Mach, Lorenz Räber, Silvia Canivell, Dik Heg, Christian M. Matter, David Carballo, David Nanchen, Baris Gencer, Olivier Muller, University of Zurich, and Nanchen, David
Subjects: Male, Myocardial Infarction, lcsh:Medicine, Blood Pressure, 030204 cardiovascular system & hematology, Vascular Medicine, 0302 clinical medicine, Recurrence, Risk Factors, Medicine and Health Sciences, Coronary Heart Disease, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Family history, lcsh:Science, Prospective cohort study, Stroke, Aged, 80 and over, 2. Zero hunger, Cardiac Rehabilitation, Multidisciplinary, Hazard ratio, Drugs, Middle Aged, Angina, Prognosis, 3. Good health, Hospitalization, Treatment Outcome, Cardiovascular Diseases, 10209 Clinic for Cardiology, Cardiology, Female, Research Article, Acute coronary syndrome, medicine.medical_specialty, 610 Medicine & health, Rehabilitation Medicine, 03 medical and health sciences, Diagnostic Medicine, 360 Social problems & social services, Internal medicine, medicine, Humans, Acute Coronary Syndrome, Acute Coronary Syndrome/complications, Acute Coronary Syndrome/diagnosis, Acute Coronary Syndrome/mortality, Aged, Cardiovascular Diseases/complications, Cardiovascular Diseases/mortality, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Multimorbidity, Multivariate Analysis, Proportional Hazards Models, Pharmacology, 1000 Multidisciplinary, business.industry, Proportional hazards model, lcsh:R, Statins, medicine.disease, lcsh:Q, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Body mass index
Abstract: OBJECTIVE To examine the prognosis of patients with cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome compared to patients without prior multimorbidity. METHODS This multicenter prospective cohort study in Switzerland included 5,635 patients hospitalized with acute coronary syndrome between 2009 and 2014, with a one-year follow-up period. We defined cardiovascular and non-cardiovascular multimorbidity as having at least two prior comorbidities before the index hospitalization. Multivariable adjusted Cox proportional models were built to assess the one-year risk of recurrent cardiovascular events, defined as cardiovascular mortality and non-fatal myocardial infarction or stroke. The final model was adjusted for age, gender, body mass index, tobacco consumption, education, and family history of cardiovascular disease, prescription of high-dose statinsat discharge and use of cardiac rehabilitation after discharge. RESULTS Overall, 3,664 patients (65%) had no multimorbidity, 1,839 (33%) had cardiovascular multimorbidity, 62 (1%) had non-cardiovascular multimorbidity, and 70 (1%) had both cardiovascular and non-cardiovascular multimorbidity. The multivariate risk of recurrent cardiovascular events was increased among patients with cardiovascular multimorbidity (hazard ratio (HR) 2.05, 95% CI: 1.54-2.73, p
Published: 2018

42. Statin therapy after first stroke reduces 10-year stroke recurrence and improves survival

Author: H. J. Milionis, Athanasios P. Kyritsis, M. S. Elisaf, Konstantinos Vemmos, Efstathios Manios, Sotirios Giannopoulos, Maria Kosmidou, and Vasileios F. Panoulas
Subjects: Male, medicine.medical_specialty, Neurology, Kaplan-Meier Estimate, Brain Ischemia, Cohort Studies, Internal medicine, Confidence Intervals, Secondary Prevention, medicine, Humans, Registries, cardiovascular diseases, Stroke, Aged, Proportional Hazards Models, Retrospective Studies, Proportional hazards model, business.industry, Hazard ratio, Retrospective cohort study, medicine.disease, Recurrence/prevention & control, Confidence interval, Surgery, Treatment Outcome, Stroke/*drug therapy/mortality/*prevention & control, Brain Ischemia/*drug therapy/mortality/*prevention & control, Multivariate Analysis, Cohort, Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use, Regression Analysis, Female, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Follow-Up Studies, Forecasting, Cohort study
Abstract: OBJECTIVE: To determine whether statin therapy after hospital discharge affects ischemic stroke recurrence and long-term mortality in patients admitted for a first-ever occurrence of ischemic stroke. METHODS: This was a retrospective observational study involving linked hospitalization and death records. The cohort comprised a series of 794 consecutive, first-ever acute ischemic stroke patients from the Athenian Stroke Registry, admitted to the acute stroke unit and the general medicine and neurology ward of our institutions since January 1997 for whom there was available information covering a 10-year follow-up period. Cox proportional hazards model was used to identify risk factors for stroke recurrence and death. RESULTS: The recurrence rate was 16.3% among stroke patients not receiving a statin after hospital discharge compared with 7.5% among those who received statin therapy (p = 0.002). Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio [HR], 0.65, 95% confidence interval [CI] 0.39 to 0.97, p < 0.01). Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event (adjusted HR, 0.43; 95% CI 0.29 to 0.61, p < 0.01). CONCLUSIONS: Prescribing statin therapy upon hospital discharge to patients with first-ever acute stroke lowers the risk of 10-year stroke recurrence and improves survival. Neurology
Published: 2009

43. Poor Adherence to Statin and Antihypertensive Therapies as Risk Factors for Fatal Stroke

Author: G. David Batty, Pekka Martikainen, Kimmo Herttua, Mika Kivimäki, Department of Social Research (2010-2017), Clinicum, Department of Public Health, Center for Population, Health and Society, and Population Research Unit (PRU)
Subjects: Male, Finland/epidemiology, Disease, 030204 cardiovascular system & hematology, Stroke/mortality, law.invention, Poor adherence, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, DISEASE METAANALYSIS, Medicine, 030212 general & internal medicine, Registries, Stroke, Finland, Hypertension/drug therapy, Follow up studies, DEATH, ICD-10, Middle Aged, 3142 Public health care science, environmental and occupational health, 3. Good health, Cardiovascular Diseases, Medication Adherence/statistics & numerical data, Hypertension, Female, Cardiology and Cardiovascular Medicine, BURDEN, statin and antihypertensive therapy, medicine.medical_specialty, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, Hypercholesterolemia, Hypercholesterolemia/drug therapy, Article, Medication Adherence, 03 medical and health sciences, MEDICATION, Internal medicine, Humans, cardiovascular diseases, Antihypertensive Agents, Aged, Antihypertensive Agents/therapeutic use, business.industry, MORTALITY, Case-control study, medicine.disease, RANDOMIZED-TRIALS, PREVENTION, Case-Control Studies, Physical therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Follow-Up Studies
Abstract: BACKGROUND Poor adherence to medication regimens is common, potentially contributing to the occurrence of related disease. OBJECTIVES The authors sought to assess the risk of fatal stroke associated with nonadherence to statin and/ or antihypertensive therapy. METHODS We conducted a population-based study using electronic medical and prescription records from Finnish national registers in 1995 to 2007. Of the 58,266 hypercholesterolemia patients age 30+ years without pre-existing stroke or cardiovascular disease, 532 patients died of stroke (cases), and 57,734 remained free of incident stroke (controls) during the mean follow-up of 5.5 years. We captured year-by-year adherence to statin and antihypertensive therapy in both study groups and estimated the excess risk of stroke death associated with nonadherence. RESULTS In all hypercholesterolemia patients, the adjusted odds ratio for stroke death for nonadherent compared with adherent statin users was 1.35 (95% confidence interval [CI] 1.04 to 1.74) 4 years before and 2.04 (95% CI: 1.72 to 2.43) at the year of stroke death or the end of the follow-up. In hypercholesterolemia patients with hypertension, relative to those who adhered to statins and antihypertensive therapy, the odds ratio at the year of stroke death was 7.43 (95% CI: 5.22 to 10.59) for those nonadherent both to statin and antihypertensive therapy, 1.82 (95% CI: 1.43 to 2.33) for those non-adherent to statin but adherent to antihypertensive therapy, and 1.30 (95% CI: 0.53 to 3.20) for those adherent to statin, but nonadherent to antihypertensive, therapy. CONCLUSIONS Individuals with hypercholesterolemia and hypertension who fail to take their prescribed statin and antihypertensive medication experience a substantially increased risk of fatal stroke. The risk is lower if the patient is adherent to either one of these therapies. (C) 2016 by the American College of Cardiology Foundation.
Published: 2015

44. Impact of hypertension on the outcome of patients admitted with acute coronary syndrome

Author: Paul Erne, Andreas W. Schoenenberger, Manfred Essig, Thomas Kaeslin, Jean-Michel Gaspoz, Osmund Bertel, Dragana Radovanovic, University of Zurich, and Erne, Paul
Subjects: Male, Acute coronary syndrome, medicine.medical_specialty, Hypertension/complications/drug therapy/mortality, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Physiology, Angiotensin-Converting Enzyme Inhibitors, 610 Medicine & health, Comorbidity, Logistic regression, 2705 Cardiology and Cardiovascular Medicine, Switzerland/epidemiology, Internal medicine, Internal Medicine, Clinical endpoint, Odds Ratio, Medicine, Humans, Myocardial infarction, Hospital Mortality, Registries, Acute Coronary Syndrome, Killip class, ddc:613, Aged, Aged, 80 and over, business.industry, Odds ratio, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 1314 Physiology, Middle Aged, medicine.disease, Prognosis, Acute Coronary Syndrome/complications/mortality, Confidence interval, Surgery, Hospitalization, Institutional repository, Angiotensin-Converting Enzyme Inhibitors/therapeutic use, Logistic Models, 2724 Internal Medicine, Hypertension, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Switzerland
Abstract: OBJECTIVE The role of hypertension and its impact on outcome in patients with acute coronary syndrome (ACS) is still debated. This study aimed to compare the outcomes of hypertensive and nonhypertensive ACS patients. METHODS Using data of ACS patients enrolled in the Acute Myocardial Infarction in Switzerland Plus Registry from 1997 to 2013, characteristics at presentation and outcomes in hospital and after 1 year were analyzed. Hypertension was defined as previously diagnosed and treated by a physician. The primary endpoint was mortality. Data were analyzed using multiple logistic regressions. RESULTS Among 41 771 ACS patients, 16 855 (40.4%) were without and 24 916 (59.6%) with preexisting hypertension. Patients with preexisting hypertension had a more favorable in-hospital outcome [odds ratio (OR) in-hospital mortality 0.82, 95% confidence interval (CI) 0.73-0.93; P = 0.022]. The independent predictors of in-hospital mortality for patients with preexisting hypertension were age, Killip class greater than 2, Charlson Comorbidity Index greater than 1, no pretreatment with statins and lower admission systemic blood pressure. Preexisting hypertension was not an independent predictor of 1-year mortality in the subgroup of patients (n = 7801) followed: OR 1.07, 95% CI 0.78-1.47; P = 0.68. Independent predictors of mortality 1 year after discharge for the 4796 patients with preexisting hypertension were age, male sex and comorbidities. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists and statins prescribed at discharge improved the outcomes. CONCLUSION Outcome of ACS patients with preexisting hypertension was associated with an improved in-hospital prognosis after adjustment for their higher baseline risk. However, this effect was not long-lasting and does not necessarily mean a causal relationship exists. Short-term and long-term management of patients with hypertension admitted with ACS could be further improved.
Published: 2015

45. Visualization of Coronary Artery Calcification: Influence on Risk Modification

Author: Jesper M. Jensen, Hans Erik Bøtker, Bjarne L. Nørgaard, Niels Peter Rønnow Sand, Lene H. Nielsen, Døne Bagdat, Charlotte Fuglesang, Rikke Elmose Mols, and Peter Vedsted
Subjects: Male, medicine.medical_specialty, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, Angina pectoris, Hypercholesterolemia, Coronary Disease, Coronary artery calcification, Hypercholesterolemia/drug therapy, Calcinosis/diagnostic imaging, Coronary Angiography, Adherence preventive therapy, law.invention, Medication Adherence, Coronary artery disease, chemistry.chemical_compound, Randomized controlled trial, Patient Education as Topic, law, Risk Factors, Internal medicine, Hyperlipidemia, medicine, Clinical endpoint, Humans, Prospective Studies, Risk factor modification, Cholesterol, business.industry, Lifestyle behavior, Coronary Disease/diagnostic imaging, Calcinosis, General Medicine, Middle Aged, Atherosclerosis, medicine.disease, chemistry, Cardiology, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Agatston score, business, Risk Reduction Behavior
Abstract: Objectives Direct health provider to patient presentation of coronary computed tomography angiography findings may increase adherence to preventive therapy and risk modification. The purpose of this study was to assess the influence of visualization of coronary artery calcification and lifestyle recommendations on cholesterol concentrations and other risk variables in symptomatic patients with nonobstructive coronary artery disease and hyperlipidemia. Methods We performed a prospective 2-center randomized controlled trial. Patients were randomized 1:1 to intervention or standard follow-up in general practice. The primary end point was change in plasma total cholesterol concentration at 6 months follow-up. Results We included 189 patients (mean [± standard deviation] age 61 [12] years, 57% were male). Median (range) Agatston score was 166 (70-2054). The reduction in plasma total cholesterol concentrations tended to be higher in the intervention group than in the control group, 51.04 mg/dL versus 45.63 mg/dL ( P = .181). In a subgroup including patients continuing statin therapy during follow-up (n = 147), the reduction in plasma total cholesterol concentrations was more pronounced in the intervention group than in the control group, 66.13 mg/dL versus 55.68 mg/dL ( P = .027). In the intervention group, there was a higher degree of statin adherence and a higher proportion of patients who stopped smoking and commenced healthier dietary behavior than in the control group. Conclusions Visualization of coronary artery calcification and brief recommendations about risk modification after coronary computed tomography angiography in symptomatic patients with nonobstructive coronary artery disease and hyperlipidemia may have a favorable influence on plasma total cholesterol concentration, adherence to statin therapy, and risk behavior. Further investigations are needed.
Published: 2015

46. Ezetimibe added to statin therapy after acute coronary syndromes

Author: Cannon, Christopher P., Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, Califf, Musliner T, Robert M., Tershakovec, A, Gurfinkel, E, Aylward, P, Tonkin, A, Maurer, G, Van de Werf, F, Nicolau, Jc, Theroux, P, Genest, J, Armstrong, P, Corbalan, R, Isaza, D, Spinar, J, Grande, P, Voitk, J, Kesaniemi, A, Bassand, Jp, Farnier, M, Darius, H, Keltai, M, Mathur, A, Mittal, S, Reddy, K, Lewis, B, De Ferrari GM, Ophuis, To, Jukema, J, White, H, Pedersen, T, Britto, F, Ruzyllo, W, Carrageta, M, Duris, T, Dalby, A, Seung, Kb, Lopez-Sendon, J, Dellborg, M, Mach, F, Guneri, S, Parkhomenko, A, Brady, A, Cannon, C, Blazing, M, Ballantyne, C, de Lemos, J, Kleiman, N, Mcguire, Dk, Centeno, E, Casalins, M, Cartasegna, L, Beltrano, Mc, Guerrero, R, Fanuele, M, Berra, F, Egido, J, Colombo, H, Dellatorre, M, Terns, P, Blumberg, E, Reges, P, Azize, G, Ramos, H, Fernandez, R, Carlessi, C, Milesi, R, Schmuck, R, Duronto, E, Procopio, G, Carlevaro, O, Maffeo, H, Beloscar, J, Viso, M, Hominal, M, Castoldi, M, Bluguermann, J, Mauro, D, Macin, S, Cocco, N, Ruiz, N, Ricart, J, Lozada, A, Nani, S, Turri, D, Fernandez, H, Caruso, O, Zarandon, R, Bono, J, Arias, V, Allall, O, Marino, J, Cusimano, S, Schygiel, P, Buzetti, C, Penaloza, N, Berli, M, Worthley, S, Roach, A, Chew, D, Wright, T, Leitch, J, Hicks, E, Rankin, J, Venn-Edmonds, C, Lehman, R, Morrison, H, Shaw, J, Mak, V, Hii, C, Smith, K, Cross, D, Lilwall, L, Nelson, G, Loxton, A, Horowitz, J, Rose, J, Steinwender, C, Leisch, F, Kammler, J, Brussee, H, Zweiker, R, Niederl, E, Weihs, W, Giorgio, G, Lang, I, Drexel, H, Zanolin, D, Hoppe, U, Atzenhofer-Baumgartner, K, Pichler, M, Hainzer, D, Eber, B, Pichler, F, Foeger, B, Wechselberger, T, Mayr, H, Hofer, J, Stockenhuber, F, Warlits, B, Huber, K, Egger, F, Weidinger, F, Ziegler, B, Jirak, P, Metzler, B, Pachinger, O, Wanitschek, M, Auer, J, Grabscheit, G, Podczeck-Schweighofer, A, Priesnitz, T, Frank, H, El Allaf, D, Marechal, P, Roosen, J, Joly, E, Lefebvre, P, Arend, C, Sinnaeve, P, De Velder, L, Hellemans, S, Vanhauwaert, B, Van Dorpe, A, Heyse, A, Vantomme, C, Striekwold, H, Van Den Broeck, D, Lancellotti, P, Schoors, D, Lemoine, I, Taeymans, Y, De Wolf, L, Brike, C, Vercauteren, S, Tahon, S, Vervoort, G, Mestdagh, I, Pirenne, B, Cardinal, F, Lips, S, Dujardin, K, Debrouwer, K, Dhooghe, G, Holvoet, G, van de Borne, P, Renard, M, De Clippel, M, Lesseliers, H, Van Miert, N, Saraiva, J, Vicente, C, Rossi, P, Dos Santos LB, Duda, N, Tognon, Ap, Serrano, C, Gomes, Fl, Manenti, Er, Silveira, Ds, Maia, L, Mouco, Om, Paiva, M, Antonangelo, A, de Souza, J, Lino, Ea, Leães, P, Blacher, Mg, Kormann, A, Ultramari, Ft, Dutra, O, Mendelski, Am, Morgado, S, Ardito, W, Greque, G, Ardito, Rv, Pimentel Filho, P, Zucchetti, C, Alves, A, Seabra, Am, Mattos, M, Miranda, Lf, Silva, D, Uehara, Rm, Marin Neto, J, Schmidt, A, Braga, J, Rodrigues, A, 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D., Atkinson, C., Adgey, A., McKeag, N., Bishop, A., Glover, J., Barbir, M., Breen, J., Robson, H., Townend, J., Dwenger, E., Ekpo, E., Shakespeare, C., Barr, C., McClements, B., McAllister, A., De Belder, M., Cooke, J., Williams, S., Daniel, D., Pye, M., Griffith, K., Wright, L., Trevelyan, J., Doughty, A., Hughes, E., Phillips, C., Penny, W., Groves, P., Kardos, A., Purvis, J., McNeill, A., Jones, A., Brown, J., Saeed, B., Sprigings, D., Herity, N., Brown, C., Unks, M., Cauthren, T., Bertolet, B., Jones, M., Decker, S., Chambers, J., Stahlberg, J., Varma, S., Gencheff, N., Price, A., McElroy, D., Chu, A., Crutchfield, B., Eaton, G., Looney, A., Qureshi, M., Wilks, J., Drenning, D., Overman, A., Andreou, C., Russo, P., Stuckey, T., Pruitt, H., D'Urso, M., DeRaad, R., Rogers, W., Thorington, S., Pasquini, J., Iwaoka, R., Tannenbaum, M., Prouty, D., Wiseman, A., Sharow, A., Graham, B., Ali, M.I., Dale, H., Tarsi, D., Picone, M., Juarez, S., Hamroff, G., Hollenweger, L., Scirica, B., Sabatine, M., Marti, J., Perlman, R., Pavlides, A., Joffe, I., Albirini, A., Campbell, T., Puri, S., Lopez, C., Pearce, D., Shah, D., McPherson, J., Donegan, R., Murdock, D., Block, D., Malik, A., Musina, R., Dauber, I., Varner, C., Bach, R., Palazzolo, M., Bhalla, H., Thompson, M., Pollock, S., Johnson, S., Lipson, L., Brunk, S., Karas, S., Vicari, R., Kuvin, J., Mooney, P., Aycock, G., Lane, B., Sharma, M., Gibson, T., Chang, G., DiVito, P., Mehta, R., Watkins, K., Chiu, A., Gunderson, J., Tedder, B., Williams, P., Hage-Korban, E., Childs, A., Banerjee, S., Kazi, F., Bennett, J., Barnes, D., Wohns, D., Noorman, C., Aggarwal, K., Lau-Sickman, A., Paulowski, J., Amos, M., Rider, J., Fenton, S., Schantz, M., Hakas, J., Mcsorley, J., Felten, W., Bitzer, V., Russell, J., Loyo, J., Adjei, A., Mehta, K., Uretsky, B., Hale, M., Shaikh, S., Miller, M., Hollenbaugh, D., Crawford, K., Fortuin, D., Galindo, A., Del Core, M., Butkus, E., Collins, J., Prior, J., Hahn, R., Greene-Nashold, J., Alexander, J., Genova, E., MacDonell, A., Broadwater, S., Kereiakes, D., White, D., Lopez, M., Schenks, R., Lui, H., Gibbons, P., Davis, B., Thornton, K., Daley, P., Budzon, S., McCullum, K., Delio-Cox, B., Nadar, V., Keim, S., McLaurin, B., Davis, C., Betzu, R., Al-Jumaily, J., Bolli, R., Alshaher, M., Leesar, M., Collins, T., Akkad, H., Bilazarian, S., Marsters, M., Kennett, J., Melegrito, K., Mostel, E., Harris, R., Chang, M., Hatfield, G., Makam, S., Garvey, M., Levite, H., White, J., Abdel-Latief, A., Pelletier, L., Carr, K., Mckenna, K., De Lemos, J., Soto, G., Kozina, J., Harris, D., Vlastaris, A., Bittel, B., Riba, A., Gugudis, J., Singh, N., Qureshi, I., Doty, W., Lehmann, J., Lieber, I., Martin, S., Nicu, M., Bhalodkar, N., Ravi, P., Canto, J., Bass, M., Campbell, C., Steinhubl, S., Moles, K., Harjai, K., Stapleton, D.D., Hoey, K., Erwin, J., Fikes, W., Stein, B., Sabatino, K., Teklinski, A., Colfer, H., Ward, P., Langevin, E., Faucett, S., Mamdani, S., DeSimone, L., Tuohy, E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., Peacock, G., Kieval, J., Barron, M., Lewis, D., Grice, R., Bobek, M., Moore, C., Nygaard, T., Fischell, T., Salman, W., Schneider, C., Muhlestein, B., Peeler, D., Chang, D., Todd, A., Chilakamarri, V., Hanley, P., Gelormini, J., Iacona, M.A., Effron, B., Mazzurco, S., Mazzella, M., Wyman, P., Orchard, R., Battin, D., Rezkalla, S., Bishop, C., Sharp, S., Gredler, F., Knap, P., Fadel, M., Saucedo, J., Keng, A., Imburgia, M., Blank, E., Effat, M., Khoury, S., Mardis, R., Baldari, D., Tafuri, L., Mascolo, R., Taylor, D., Mandviwala, M., Khan, W., Mumford, T., Mayer, N., Mitchell, B., Oliver, T., Lombardi, W., Zimmerman, T., Rohrbeck, S., Cooke, L., Craig, M., Mego, D., Griffin, B., Perez, J., LeClerc, K., Addington, J., Aboufakher, R., Ahmed, A., Westecott, B., Steel, K., Hawkins, K., Shah, A., Ward, U., McGreevy, M., Goldberg, R., Prashad, R., McDonough, C., Silver, K., Josephson, R., Witsaman, S., Labib, S., Woodhead, G., Schrank, J., Bell, K., Chandna, H., Holly, D., Bethea, C., Fife, B., Gruberg, L., Singer, A., Ramgadoo, M., Lalonde, T., Morin, R., French, W., Barillas, O., Gradner, G., Kahn, Z., Gress, J., Rocco, D., Thew, S., Stifter, W., Fisher, M., McNamara, J., Kupfer, J., Agocha, A., Cush, S., Jones, S., Whitaker, T., Stover, T., Kumkumian, G., Kent, K., Greenberg, A., Pandey, P., Pytlewski, G., Matsumura, M., Kai, W., Sameshima, S., Thomas, J., MacNicholas, D., Pillai, K., Jones, D., Navas, J.P., Laskoe, B., Patel, P., Fini, G., Minor, S., Shipwash, T., Cabrera-Santamaria, A., Rivera, E., Mincher, L., Jafar, M., Yen, M., Finkle, C., Rahimtoola, A., Severson, L., Labroo, A., Jinich, D., Tam, K., Vogel, C., Aggarwal, R., Zakhary, B., Curtis, S., Lyster, M., Humphrey, K., Lavine, P., Fujise, K., Birnbaum, Y., Allen, J., Kesselbrenner, M., Michel, K., Staniloae, C., Liu, M., Sonel, A., Macioce-Caffas, A., Amidon, T., Leggett, J., Yedinak, S., Gudmundsson, G., Sabharwal, J., Dagefoerde, N., Wu, W., Meyerrose, G., Roongsritong, C., Jenkins, L., Lieberman, S., Sokol, S., Gutierrez, C., Nelson, C., Barrett, J., Hotchkiss, D., Farley, A., Atassi, K., Christy, L., Baig, M., Di Fazio, J., Meengs, M., Thomas, K., Surmitis, J., DeVault, S., Farhat, N., Hulyalkar, A., Riddell, L., Rivera, W., Sheynberg, B., Kobayashi, J., Katsaropoulos, J., Jan, M., Krucoff, M., Paterno, C., Chandrasekaran, S., Curry, R., Cassavar, D., Wheeler, M., McGarvey, J., Schwarz, L., Miller, E., Andrea, B., Carswell, B.S., Lurie, M., Patti, J., Bowden, W., Vasiliauskas, T., Latham, R., Schwartz, B., Bradford, L., Mattleman, S., Wertheimer, J., Goulden, D., Khan, M., Hawkins, B., Ostfeld, R., Mueller, H., Ash, Y., Wilson, V., Bayer, M., Marshall, J., Dobies, D., Dawson, G., Osman, A., Saba, F., Costello, T., Fuentes, F., Underwood, C., Vijay, N., Washam, M., Dietz, W., Glasgow, B., Mukherjee, S., Hinchion, N., Speirs, S., Thornley, A., Lee, K., Movahed, M., Strootman, D., Chernick, R., Parrott, C., Flock, C., Marques, V., Syzmanski, E., Rama, P., Domingo, D., Wu, L., Bauer, B., Dionisopoulos, P., Aggarwal, A., Holcomb, R., Foster, R., Hancock, T., Hargrove, J., Fletcher, A., Stine, R., Bullivant, M., Adams, K., Lohman, J., Klepper, V., Kabour, A., Neidhardt, J., Phillips, W., Tardiff, S., Aji, J., Corut, S., Foster, G., Firek, C., St Goar, F., Sumner, R., Davis, T., Schneider, R., Schneider, W., Villa, A., Desai, V., Chhabra, A., Banks, K., Herzog, W., Burley, T., Quyyumi, A., Smiley, W., Manocha, P., Fishbein, G., Weller, C., Coffman, A., Kim, C., Kedia, A., Firth, B., Rizvi, M., Dahiya, R., Foster, B., Balcells, E., Metzger, D.C., Lester, J., Bissett, J., Fahdi, I., Sides, E.A., Azrin, M., Martin, C., Quick, A., Conaway, D., Garg, M., Schallert, G., Lancaster, L., Mckissick, S., Atieh, M., Garbarino, J., Eisenberg, D., Uusinarkaus, K., Wirtemburg, P., Ellis, J., Cristaldi, J., Berglund, R., Negus, B., Pappas, J., Rocha, R., Nguyen, T., Stone, J., Janosik, D., Labovitz, A., Elmore, N., Dave, R., Loffredo, K., Gabriel, G., Snyder, C., Ahmed, O., Stone, H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, Cp, Blazing, Ma, Giugliano, Rp, Mccagg, A, White, Ja, Theroux, P, Darius, H, Lewis, B, Ophuis, To, Jukema, Jw, De Ferrari, Gm, Ruzyllo, W, De Lucca, P, Im, K, Bohula, Ea, Reist, C, Wiviott, Sd, Tershakovec, Am, Musliner, Ta, Braunwald, E, Califf, Rm, for the IMPROVE-IT, Investigator, Cianflone, D, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], College of Information Science and Engineering, Ritsumeikan University, Montreal Heart Institute (MONTREAL HEART INSTITUTE), Laboratoire des Micro-algues toxiques, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD), Interuniversity Cardiology Institute Netherlands, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Merck Sharp & Dohme Corp., Merck & Co. Inc, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Cannon, C.P., Blazing, M.A., Giugliano, R.P., Mccagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., for the IMPROVE-IT Investigators [.., C. Rapezzi, ], Other departments, Cannon, Christopher P, Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, and Califf, Robert M.
Subjects: Male, Simvastatin, acute coronary syndrome, aged, anticholesteremic agents, azetidines, cardiovascular diseases, cholesterol, ldl, double-blind method, drug therapy, combination, ezetimibe, female, humans, hydroxymethylglutaryl-coa reductase inhibitors, kaplan-meier estimate, male, middle aged, simvastatin, triglycerides, medicine (all, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Bococizumab, Triglyceride, chemistry.chemical_compound, 0302 clinical medicine, Azetidine, Cardiovascular Disease, Anticholesteremic Agent, Acute Coronary Syndrome, Aged, Anticholesteremic Agents, Azetidines, Cardiovascular Diseases, Cholesterol, LDL, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Middle Aged, Triglycerides, 030212 general & internal medicine, Medicine (all), Research Support, Non-U.S. Gov't, Hazard ratio, General Medicine, Acute Coronary Syndrome, Aged, Anticholesteremic Agents, Azetidines, Cardiovascular Diseases, Ezetimibe, Female, Humans, Male, Middle Aged, 3. Good health, Multicenter Study, Editorial, Cholesterol, Randomized Controlled Trial, Combination, Ezetimibe, lipids (amino acids, peptides, and proteins), Human, medicine.drug, medicine.medical_specialty, Acute Coronary Syndroms, Urology, Acute Coronary Syndrome/drug therapy, Anticholesteremic Agents/adverse effects, Anticholesteremic Agents/therapeutic use, Azetidines/adverse effects, Azetidines/therapeutic use, Cardiovascular Diseases/epidemiology, Cardiovascular Diseases/mortality, Cardiovascular Diseases/prevention & control, Cholesterol, LDL/blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Simvastatin/therapeutic use, Triglycerides/blood, NO, LDL, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Drug Therapy, Internal medicine, Journal Article, medicine, Comparative Study, Alirocumab, business.industry, PCSK9, ta3121, Lomitapide, DOENÇAS CARDIOVASCULARES, Endocrinology, chemistry, Statin Therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitor, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (PCONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
Published: 2015

47. Increased Systemic and Plaque Inflammation in ABCA1 Mutation Carriers With Attenuation by Statins

Author: Fleur M. van der Valk, Sonia Tolani, Erik S.G. Stroes, Andrea E. Bochem, Marit Westerterp, Alan R. Tall, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Center for Liver, Digestive and Metabolic Diseases (CLDM), and Translational Immunology Groningen (TRIGR)
Subjects: medicine.medical_specialty, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, ATP-Binding Cassette Transporters/genetics, Lipoproteins, Inflammation, Biology, medicine.disease_cause, Cholesterol/blood, Cytokines/blood, Proinflammatory cytokine, chemistry.chemical_compound, Internal medicine, Macrophages/metabolism, Inflammation/genetics, medicine, Lipoproteins/blood, polycyclic compounds, Humans, Plaque, Apolipoproteins B, Mutation, Atherosclerotic/genetics, medicine.diagnostic_test, Cholesterol, Macrophages, Reverse cholesterol transport, Biological Transport, Plaque, Atherosclerotic/genetics, medicine.disease, Plaque, Atherosclerotic, Apolipoproteins B/blood, Endocrinology, chemistry, Positron emission tomography, ABCA1, Immunology, biology.protein, Cytokines, ATP-Binding Cassette Transporters, lipids (amino acids, peptides, and proteins), medicine.symptom, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, Dyslipidemia
Abstract: Objective— We previously demonstrated that subjects with functional ATP-binding cassette ( ABC ) A1 mutations have increased atherosclerosis, which has been attributed to the role of ABCA1 in reverse cholesterol transport. More recently, a proinflammatory effect of Abca1 deficiency was shown in mice, potentially contributing to atherogenesis. In this study, we investigated whether ABCA1 deficiency was associated with proinflammatory changes in humans. Approach and Results— Thirty-one heterozygous, 5 homozygous ABCA1 mutation carriers, and 21 matched controls were studied. 18 Fluorodeoxyglucose positron emission tomography with computed tomographic scanning was performed in a subset of carriers and controls to assess arterial wall inflammation (target:background ratio). Heterozygous ABCA1 mutation carriers had a 20% higher target:background ratio than in controls (target:background ratio; P =0.008). In carriers using statins (n=7), target:background ratio was 21% reduced than in nonstatin users (n=7; P =0.03). We then measured plasma cytokine levels. Tumor necrosis factor α, monocyte chemoattractant protein-1, and interleukin-6 levels were increased in heterozygous and homozygous ABCA1 mutation carriers. We isolated monocytes from carriers and controls and measured inflammatory gene expression. Only TNFα mRNA was increased in monocytes from heterozygous ABCA1 mutation carriers. Additional studies in THP-1 macrophages showed that both ABCA1 deficiency and lipoprotein-deficient plasma from ABCA1 mutation carriers increased inflammatory gene expression. Conclusions— Our data suggest a proinflammatory state in ABCA1 mutation carriers as reflected by an increased positron emission tomography–MRI signal in nonstatin using subjects, and increased circulating cytokines. The increased inflammation in ABCA1 mutation carriers seems to be attenuated by statins.
Published: 2015

48. Ivabradine in stable coronary artery disease without clinical heart failure

Author: Arintaya Phrommintikul, Oleksii Korzh, Jaromir Hradec, Thomas Muenzel, Vincent Maher, Aldo Pietro Maggioni, Olga Moiseeva, Aleksandar Neskovic, ELENA BOBESCU, WILLIAM HEDDLE, Catalina Arsenescu Georgescu, Marcelo Sanmartin-Fernandez, Yaroslav Malynovsky, Philippe Gabriel STEG, Vladimir Zadionchenko, Ben Freedman, Sergey Nedogoda, Roberto Ferrari, Vyacheslav Yurievich Mareev, Eduardo Costa Duarte Barbosa, Philippe Gosse, Andriy Bazylevych, Michal Tendera, Alfonso Varela-Román, Sergiy Kolomiets, Institute of Cardiovascular Medicine and Science (ICMS), Royal Brompton Hospital, Robertson Centre for Biostatistics, University of Glasgow, Hôpital Bichat - Claude Bernard, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Montreal Heart Institute Coordinating Centre (MHICC), Université de Montréal (UdeM), Third Division of Cardiology, Medical University of Silesia, Department of Cardiology and Laboratory for Technologies of Advanced Therapies Center (DCLTATC), University Hospital of Ferrara and Maria Cecilia Hospital, University of Zurich, Fox, Kim, and Medical University of Silesia (SUM)
Subjects: Male, drug ther/apy/physiopathology, [SDV]Life Sciences [q-bio], adverse effects/pharmacology/therapeutic use, Angiotensin-Converting Enzyme Inhibitors, 2700 General Medicine, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Cardiovascular Diseases/mortality/prevention & control, Angina, Coronary artery disease, 0302 clinical medicine, Intention to Treat Analysis Kaplan-Meier Estimate, Heart Rate, Ivabradine, Angiotensin-Converting Enzyme Inhibitors/therapeutic useBenzazepines/adverse effects/pharmacology/*therapeutic use, 030212 general & internal medicine, Myocardial infarction, Stable/drug therapy, Coronary Artery Disease/*drug therapy/physiopathology, General Medicine, Canadian Cardiovascular Society, Middle Aged, mortality/prevention /&/ control, Adrenergic beta-Antagonists/therapeutic use, Stable, 3. Good health, Intention to Treat Analysis, Heart Rate/*drug effects, Cardiovascular Diseases, Combination, Cardiology, Drug Therapy, Combination, Female, medicine.symptom, medicine.drug, Bradycardia, Risk, medicine.medical_specialty, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Adrenergic beta-Antagonists, 610 Medicine & health, therapeutic use, Aged, Angina, drug therapy, Angiotensin-Converting Enzyme Inhibitors, therapeutic use, Benzazepines, adverse effects/pharmacology/therapeutic use, Cardiovascular Diseases, mortality/prevention /&/ control, Coronary Artery Disease, drug ther/apy/physiopathology, Double-Blind Method, Drug Therapy, Combination, Female, Heart Failure, Heart Rate, drug effects, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, therapeutic use, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Risk, 11171 Cardiocentro Ticino, NO, 03 medical and health sciences, Drug Therapy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Double-Blind Method, Internal medicine, Heart rate, medicine, Humans, Angina, Stable, Aged, Heart Failure, business.industry, Benzazepines, medicine.disease, therapeutic use, drug effects, Heart failure, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BACKGROUND: An elevated heart rate is an established marker of cardiovascular risk. Previous analyses have suggested that ivabradine, a heart-rate-reducing agent, may improve outcomes in patients with stable coronary artery disease, left ventricular dysfunction, and a heart rate of 70 beats per minute or more.METHODS: We conducted a randomized, double-blind, placebo-controlled trial of ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction.RESULTS: At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the ivabradine group versus 70.6±10.1 beats per minute in the placebo group. After a median follow-up of 27.8 months, there was no significant difference between the ivabradine group and the placebo group in the incidence of the primary end point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval, 0.96 to 1.20; P=0.20), nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction. Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina (P=0.02 for interaction). The incidence of bradycardia was higher with ivabradine than with placebo (18.0% vs. 2.3%, PCONCLUSIONS: Among patients who had stable coronary artery disease without clinical heart failure, the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes. (Funded by Servier; SIGNIFY Current Controlled Trials number, ISRCTN61576291.).
Published: 2014

49. Carotid atherosclerotic plaque stenosis: the stabilizing role of statins

Author: Fabrizio Montecucco, Aldo Pende, Franco Dallegri, and Nathan Artom
Subjects: medicine.medical_specialty, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, Clinical Biochemistry, Coronary Artery Disease/prevention & control, Coronary Artery Disease, 030204 cardiovascular system & hematology, Biochemistry, Carotid Intima-Media Thickness, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Carotid Stenosis, cardiovascular diseases, Stroke, Subclinical infection, Randomized Controlled Trials as Topic, ddc:616, Tomography, Emission-Computed, Single-Photon, Carotid Stenosis/diagnosis/drug therapy/etiology, medicine.diagnostic_test, business.industry, Plaque, Atherosclerotic/diagnosis/drug therapy/etiology, General Medicine, Statin treatment, medicine.disease, Magnetic Resonance Imaging, Plaque, Atherosclerotic, 3. Good health, Surgery, Stenosis, Search terms, Cardiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipid profile, business, 030217 neurology & neurosurgery, Plaque inflammation
Abstract: BACKGROUND:Both pathophysiology and treatments of carotid atherosclerotic plaque stenosis represent two interesting fields of strong scientific investigation. Among different drugs, safety and efficacy of statin treatment have been widely investigated and proved. MATERIALS AND METHODS:This narrative review is based on the material searched for and obtained via MEDLINE and PubMed up to March 2014. The search terms we used were: 'carotid plaque, intima-media thickness, plaque burden, stroke' in combination with 'statins, pleiotropic effects, HMG-CoA reductase inhibitors, lipid-lowering drugs'. RESULTS:Carotid stenosis represents both a useful parameter to evaluate the atherosclerotic burden and a target for therapeutic (medical or surgical) decisions. Statins do not only improve the lipid profile, but also induce some 'pleiotropic' anti-inflammatory activities that contribute to carotid plaque stabilization. Statin-mediated protective activities are under active investigation at subclinical levels with the potential benefit of advanced imaging techniques. However, considering that some new techniques (excepted B-mode ultrasound) remain quite expensive, they can have for the moment an important role in research, but not in the clinical field. CONCLUSIONS:Emerging evidence suggests that statin treatment improves carotid atherosclerosis, inducing a partial regression of plaque inflammation and size. Innovative imaging techniques might also ameliorate the identification of patients at high risk of cerebrovascular and coronary events, for which preventive statin treatments might be essential.
Published: 2014

50. The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Author: Richard Ceska, Naveed Sattar, Elena Bilianou, Shun Ishibashi, Tamio Teramoto, Vincent Maher, Paul Valensi, Luis Masana, Kausik K. Ray, Paul D. Flynn, Henry N. Ginsberg, John J.P. Kastelein, Xavier Garcia-Moll, Selim Jambart, Ibrahim Salti, D. John Betteridge, Carlo Maria Rotella, Raimund Erbel, Deepak Bhatnagar, Terje R. Pedersen, Peter P. Toth, Lale Tokgozoglu, Masato Odawara, Bruno Vergès, Marcello Arca, Rafael Carmena, Alberto Corsini, Janusz Gumprecht, M. John Chapman, Maurizio Averna, Pedro Marques da Silva, Medicina i Cirurgia, Universitat Rovira i Virgili., Amsterdam Cardiovascular Sciences, Vascular Medicine, Sattar, N, Ginsberg, H, Ray, K, Chapman, M, Arca, M, Averna, M, Betteridge, D, Bhatnagar, D, Bilianou, E, Carmena, R, Češka, R, Corsini, A, Erbel, R, Flynn, P, Garcia-Moll, X, Gumprecht, J, Ishibashi, S, Jambart, S, Kastelein, J, Maher, V, Marques da Silva, P, Masana, L, Odawara, M, Pedersen, T, Rotella, C, Salti, I, Teramoto, T, Tokgozoglu, L, Toth, P, Valensi, P, and Vergès, B
Subjects: Male, Settore MED/09 - Medicina Interna, endocrine system diseases, HSM MED, Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects, Anticholesteremic Agents/adverse effects, Medizin, 1567-5688, Comorbidity, Type 2 diabetes, Pharmacology, Diabete, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, Cardiovascular, Fasting/blood, Cohort Studies, Risk Factors, Anticholesteremic Agents/administration & dosage, Diabetes Mellitus, Type 2/prevention & control, Multicenter Studies as Topic, Medicine, T2D, Diabetis, Anticholesteremic Agents, Diabetes, Hemoglobin A, Glycosylated/analysis, Fasting, General Medicine, Middle Aged, Diabetogenicity, CVD, Clinical Practice, Observational Studies as Topic, Cholesterol, LDL/blood, Cardiovascular Diseases, Practice Guidelines as Topic, lipids (amino acids, peptides, and proteins), Disease Susceptibility, Cardiology and Cardiovascular Medicine, Risk assessment, Cardiovascular Diseases/prevention & control, Cohort study, Adult, medicine.medical_specialty, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, Anticholesteremic Agents/therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology, Diabetes Mellitus, Type 2/etiology, Risk Assessment, Multicenter Studies as Topic/statistics & numerical data, Prediabetic State, Meta-Analysis as Topic, Diabetes mellitus, Internal Medicine, Humans, Intensive care medicine, Prediabetic State/epidemiology, Glycated Hemoglobin, Statins, business.industry, Cardiovascular Diseases/epidemiology, nutritional and metabolic diseases, Cholesterol, LDL, medicine.disease, Anticholesteremic Agents/pharmacology, Diabetes Mellitus, Type 2/epidemiology, Diabetes Mellitus, Type 2, Estatines (Medicaments cardiovasculars), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Observational Study as Topic, Forecasting
Abstract: Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines. (C) 2014 Published by Elsevier Ireland Ltd.
Published: 2014
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