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

1. Uso de agentes hipolipemiantes y cumplimiento de metas terapéuticas en pacientes de alto riesgo cardiovascular en la República Argentina.

Author: RODRIGO SIGAL, ALAN, ANTONIOLLI, MELISA, LÓPEZ SANTI, PILAR, AQUINO, NICOLÁS, LERECH, EZEQUIEL, and BOTTO, FERNANDO
Abstract: Copyright of Revista Argentina de Cardiología is the property of Sociedad Argentina de Cardiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Published: 2021
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2. 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

3. 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

4. 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

5. 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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6. 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

7. Linee guida ESC 2021 per la prevenzione delle malattie cardiovascolari nella pratica clinica elaborate dalla Task Force per la prevenzione delle malattie cardiovascolari nella pratica clinica costituita da rappresentanti della Società Europea di Cardiologia e di 12 società medico-scientifiche con il contributo straordinario dell’Associazione Europea di Cardiologia Preventiva (EAPC)

Author: ESC Scientific Document Group, Observerende Klinische wetenschappen, Hart- en vaatziekten, and Cardiologie
Subjects: Europe, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Prevention, primary prevention, Humans, ESC, Cardiovascular Diseases/drug therapy, Guidelines, Cardiovascular disease, Cardiology and Cardiovascular Medicine
Published: 2022

8. Oméga-3 fortement dosés pour la prévention cardiovasculaire : une fausse bonne idée ? [High-dose Omega-3 for cardiovascular prevention, a bad idea?]

Author: Berger, Christine, Gencer, Baris, and Nanchen, David
Subjects: Cardiovascular Diseases/etiology, Cardiovascular Diseases/prevention & control, Fatty Acids, Omega-3/therapeutic use, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Hypertriglyceridemia/complications, Hypertriglyceridemia/drug therapy, Triglycerides/therapeutic use
Abstract: Hypertriglyceridemia is a cardiovascular risk factor independent of LDL cholesterol. Omega-3 reduce triglycerides levels, but without proven benefit to reduce cardiovascular risk. Recently, two studies on high-dose omega-3 derivatives have shown contradictory results on the risk of cardiovascular events: REDUCE-IT (4 g/day of icosapent ethyl) showed a 25 % reduction; STRENGTH (4 g/day of a mixture of eicosapentaenoic acid and docosahexaenoic acid) showed no effect. An increased risk of atrial fibrillation was observed in both studies. The European 2021 cardiovascular prevention guidelines propose to consider high-dose ethyl icosapent on a case-by-case basis in patients with hypertriglyceridemia.
Published: 2022

9. Prescription rates for commonly used drugs before and after a prostate cancer diagnosis

Author: Signe Benzon Larsen, Christian Dehlendorff, Charlotte Skriver, Anton Pottegård, Søren Friis, Martin Andreas Røder, Klaus Brasso, and Anne Katrine Duun-Henriksen
Subjects: Male, Prostatic Neoplasms/diagnosis, Aged, 80 and over, Cancer Research, Prostate cancer, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Prostatic Neoplasms, Lag-time, Middle Aged, Surveillance bias, Prescriptions, Oncology, Pharmaceutical Preparations, Humans, Drug use, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Prescription rate, Aged
Abstract: Purpose: To investigate differences in prescription rates of commonly used drugs among prostate cancer patients and cancer-free comparisons and between patients diagnosed with localized and non-localized disease. Methods: We conducted a register-based study including all men aged 50–85 years diagnosed with prostate cancer in Denmark from 1998 to 2015 and an age-matched cancer-free comparison cohort. We calculated the number of new and total prescriptions from three years before to three years after the date of diagnosis of the case for selected drug classes divided by the number of person-months and stratified by stage at diagnosis. Results: We included 54,286 prostate cancer patients and 249,645 matched comparisons. 30,712 patients were diagnosed with localized disease and 12,884 with non-localized disease. The rates of new prescriptions increased considerably among patients within the year before the diagnosis. Hereafter the rates varied between drug classes. For most drug classes, total prescription rates for patients and comparisons increased similarly in the study period. Total prescription rates varied between men with localized and non-localized disease for all drug classes apart from statins. Conclusion: Our findings indicate that a large proportion of prostate cancer cases are likely diagnosed during medical work-up for other reasons than prostate cancer. Increased rates occur within the last year before diagnosis and future studies on the interaction between drug use and prostate cancer should at least include a one year pre-diagnostic lag-time. Post-diagnostic prescription rates demonstrated an increased use of drugs most likely associated with the consequences of the disease.
Published: 2022

10. 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 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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 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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 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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. Sandy, Jain, Diwakar, Zainea, Mark, Tze-Kay Yan, Andrew, Bayron, Carlos, Karlsberg, Ronald, Dohad, Suhail, Lui, Henry, Keen, William, Westerhausen, Donald, Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William, Schiavi, Lilia B., Chang, Mark, Murphy, Sherrill, Henry, John, Schifferdecker, Branislav, Gilbert, John M., Chalavarya, Gopal, Eaton, Charles, Schmedtje, John F., Christenson, Stuart, Dotani, Imran, Garrido, Marcelo, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Assi, Nizar, Conrad, Gary, Kotha, Purushotham, Love, Michael, Giesler, Gregory, Alvarisqueta, Andrés F., Rubenstein, Howard, Gamil, Dawood, Akright, Laura, Krawczyk, Justine, Cobler, Joanne, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Sassone, Sonia A., Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Bordonava, Anselmo P., Egydio, Flavia, Kawakami, Anelise, Oliveira, Janaina, Goodman, Shaun G., Wozniak, Julianna, Alves De Lima, Alberto E., Matthews, Alexander, Ratky, Caroline, Valiris, Janine, Berdan, Lisa, Hepditch, Anita, Quintero, Kirby, Rorick, Tyrus, Westbrook, Melissa, Danchin, Nicolas, Schmidberg, Jorge M., Bezault, Madeleine, Drouet, Elodie, Simon, Tabassome, White, Harvey D., Alsweiler, Caroline, Sinnaeve, Peter, Luyten, Anne, Aylward, Philip E., Butters, Julie, Griffith, Liddy, Duronto, Ernesto A., Shaw, Michelle, Grunberg, Lena, Szarek, Michael, Islam, Shahidul, Brégeault, Marie-France, Bougon, Nathalie, Faustino, Douglas, Fontecave, Sylvie, Murphy, Judith, Caruso, Orlando C., Tamby, Jean-Francois, Verrier, Melanie, Agnetti, Veronique, Andersen, Dorthe, Badreddine, Emmy, Bekkouche, Mhamed, Bouancheau, Cecile, Brigui, Imane, Brocklehurst, Maddy, Cianciarulo, Joseph, Novaretto, Leonardo P., Devaul, Dawn, Domokos, Szilvia, Gache, Cecile, Gobillot, Caroline, Guillou, Severine, Healy, Jan, Heath, Megan, Jaiwal, Gayatri, Javierre, Carine, Labeirie, Julien, Hominal, Miguel Angel, Monier, Myriam, Morales, Ulises, Mrabti, Asmaa, Mthombeni, Bicky, Okan, Betim, Smith, Lucile, Sheller, Jennifer, Sopena, Sebastien, Pellan, Valerie, Benbernou, Fadela, Montaña, Oscar R., Bengrait, Nafissa, Lamoureux, Maud, Kralova, Katarina, Scemama, Michel, Bejuit, Raphael, Coulange, Anthony, Berthou, Christelle, Repincay, Jérôme, Lorenzato, Christelle, Etienne, Alexis, Caccavo, Alberto, Gouet, Valerie, Lecorps, Guillaume, Loizeau, Virginie, Normand, Mickael, Ourliac, Anne, Rondel, Christelle, Adamo, Antony, Beltran, Pascale, Barraud, Pauline, Dubois-Gache, Helene, Gomez Vilamajo, Oscar A., Halle, Benjamin, Metwally, Lamia, Mourgues, Maxime, Sotty, Marc, Vincendet, Marion, Cotruta, Raluca, Chengyue, Zhu, Fournie-Lloret, Dominique, Morrello, Christine, Perthuis, Aurelie, Lorenzatti, Alberto J., Picault, Patrick, Zobouyan, Isabelle, Colhoun, Helen M., Dempsey, Michael A., McClanahan, Mark A., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R., Jure, Horacio O., Bono, Julio Oe, Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Schwartz, Gregory G., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., Nani, Sebastian, Blumberg, Eduardo Ds, Colombo, Hugo R., Bhatt, Deepak L., Liberman, Alberto, Fuentealba, Victorino, 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., Bittner, Vera A., Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris Ls, Shaw, James, Diaz, Rafael, Arstall, Margaret A., Horowitz, John, Ninio, Daniel, Rogers, James F., Colquhoun, David, Oqueli Flores, Romulo E., Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Aroney, Constantine, Coverdale, Steven Gm, Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Drexel, Heinz, Huber, Kurt, Harrington, Robert A., Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Jukema, J. 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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. 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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

11. 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
Full Text: View/download PDF

12. 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

13. 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

14. 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

15. Statin Initiation and Risk of Amyotrophic Lateral Sclerosis:A Danish Population-based Cohort Study

Author: Henrik Toft Sørensen, Erzsébet Horváth-Puhó, Timothy L. Lash, Nils Skajaa, Victor W. Henderson, and Istvan Bakos
Subjects: Male, medicine.medical_specialty, Statin, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, Epidemiology, Denmark, Population, Population-based, Cohort Studies, Internal medicine, medicine, Humans, Amyotrophic lateral sclerosis, education, Birth Year, education.field_of_study, business.industry, Incidence, Amyotrophic Lateral Sclerosis, Hazard ratio, Statins, Amyotrophic Lateral Sclerosis/chemically induced, Infant, medicine.disease, Confidence interval, Denmark/epidemiology, Child, Preschool, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Cohort study
Abstract: Background: The evidence of an association between statins and amyotrophic lateral sclerosis (ALS) is heterogeneous and inconclusive. Methods: We performed a population-based cohort study consisting of 974,304 statin initiators ≥40 years of age and 1,948,606 matched general population comparators identified from Danish, nationwide registries (1996-2016). We computed incidence rates and hazard ratios (HRs) of a first-time hospital-based diagnosis of ALS. HRs were controlled for sex, birth year, calendar year, medically diagnosed comorbidities, and concomitant medications. Results: During a median follow-up of 7.7 years, 852 ALS events occurred among statin initiators (11.3 [95% confidence interval (CI) = 10.6, 12.1] events per 100,000 person-years) and 1,679 among noninitiators (11.4 [95% CI = 10.9, 12.0] events per 100,000 person years). The overall adjusted HR indicated a slight association between statin initiation and ALS (1.11 [95% CI = 1.00, 1.23]. In the first year after initiation, the HR was 1.40 (95% CI = 1.09, 1.79) for both sexes combined, 1.00 (95% CI = 0.70, 1.42) for men, and 1.92 (95% CI = 1.30, 2.82) for women. The associations diminished to approximately null after the first year of follow-up for both sexes combined and for men, but point estimates were above 1 for women until 10 years after initiation. Conclusions: Statin initiation was largely unassociated with ALS diagnosis but was associated with an elevated risk of ALS in women, especially in the first year after initiation. The association could be explained by reverse causation, detection bias, early neurotoxic effects of statins that affect women more than men, or a combination thereof.
Published: 2021

16. Statin Medications and Development and Progression of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms.

Author: Patel, Darshan, Myers, Jeremy, Brant, William, Sarma, Aruna, and Hotaling, James
Abstract: Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) are common among aging men and impact quality of life. Recently, there has been an interest in alternative mechanisms of BPH and LUTS, specifically the role of chronic prostatic inflammation. Statin medications, known for their cholesterol-lowering properties, also possess certain anti-inflammatory effects, which may be of interest in the treatment and/or prevention of BPH and LUTS. Prior studies of statins have yielded conflicting results. These were limited by cross-sectional designs or limited follow-up, small sample sizes, and inability to control for confounding. One prior randomized control trial found no difference between atorvastatin vs. placebo in the treatment of BPH and LUTS after 6 months. Additional randomized trials with longer follow-up time evaluating the impact of statins on incident BPH and LUTS are required to assess the therapeutic potential of statins and develop a better understanding of alternative mechanisms for BPH and LUTS. [ABSTRACT FROM AUTHOR]
Published: 2016
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17. 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

18. 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

19. Letter to the editor regarding: 'The relationship between post-diagnostic statin usage and breast cancer prognosis varies by hormone receptor phenotype: a systemic review and meta-analysis'

Author: Thomas P. Ahern, Signe Borgquist, and Sixten Harborg
Subjects: Oncology, medicine.medical_specialty, Statin, Letter to the editor, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, business.industry, medicine.drug_class, MEDLINE, Obstetrics and Gynecology, General Medicine, Prognosis, medicine.disease, Phenotype, Hormones, Human genetics, Breast cancer, Hormone receptor, Neoplasms, Meta-analysis, Internal medicine, medicine, Humans, business
Published: 2021

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. Effects of a diet rich in arabinoxylan and resistant starch compared with a diet rich in refined carbohydrates on postprandial metabolism and features of the metabolic syndrome

Author: Bolette Hartmann, Hans Stødkilde-Jørgensen, Mette Bohl, Ann Bjørnshave, Kjeld Hermansen, Anne Grethe Schioldan, Søren Gregersen, Stine Hald, and Jens J. Holst
Subjects: Dietary Fiber, Male, 0301 basic medicine, Food Handling, Medicine (miscellaneous), Type 2 diabetes, Starch/metabolism, Diet, Western/adverse effects, chemistry.chemical_compound, 0302 clinical medicine, Arabinoxylan, Dyslipidemias/blood, Resistant starch, Metabolic Syndrome, Whole Grains, Cross-Over Studies, Nutrition and Dietetics, Starch, Middle Aged, Postprandial Period, Postprandial, Inflammation Mediators/blood, Digestion, Female, Xylans, lipids (amino acids, peptides, and proteins), Inflammation Mediators, Adult, medicine.medical_specialty, Statin, food.ingredient, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, medicine.drug_class, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Insulin resistance, food, Internal medicine, medicine, Humans, Aged, Dyslipidemias, Models, Statistical, 030109 nutrition & dietetics, Carbohydrate, medicine.disease, Endocrinology, chemistry, Diet, Western, Metabolic Syndrome/diet therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Insulin Resistance, Metabolic syndrome, Dietary Fiber/metabolism, Xylans/metabolism, Biomarkers
Abstract: Purpose: Low intake of dietary fibre is associated with the development of type 2 diabetes. Dyslipidaemia plays a key role in the pathogenesis of type 2 diabetes. Knowledge of the impact of dietary fibres on postprandial lipaemia is, however, sparse. This study aimed in subjects with metabolic syndrome to assess the impact on postprandial lipaemia and features of the metabolic syndrome of a healthy carbohydrate diet (HCD) rich in cereal fibre, arabinoxylan and resistant starch compared to a refined-carbohydrate western-style diet (WSD). Methods: Nineteen subjects completed the randomised, crossover study with HCD and WCD for 4-week. Postprandial metabolism was evaluated by a meal-challenge test and insulin sensitivity was assessed by HOMA-IR and Matsuda index. Furthermore, fasting cholesterols, serum-fructosamine, circulating inflammatory markers, ambulatory blood pressure and intrahepatic lipid content were measured. Results: We found no diet effects on postprandial lipaemia. However, there was a significant diet × statin interaction on total cholesterol (P = 0.02) and LDL cholesterol (P = 0.002). HCD decreased total cholesterol (−0.72 mmol/l, 95% CI (−1.29; −0.14) P = 0.03) and LDL cholesterol (−0.61 mmol/l, 95% CI (−0.86; −0.36) P = 0.002) compared with WSD in subjects on but not without statin treatment. We detected no other significant diet effects. Conclusions: In subjects with metabolic syndrome on statins a 4-week diet rich in arabinoxylan and resistant starch improved fasting LDL and total cholesterol compared to subjects not being on statins. However, we observed no diet related impact on postprandial lipaemia or features of the metabolic syndrome. The dietary fibre x statin interaction deserves further elucidation.
Published: 2017

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. 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

43. 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

44. 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

45. 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

46. 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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47. Pathophysiological role of neutrophils in acute myocardial infarction

Author: Federico Carbone, Alessio Nencioni, N. Vuilleumier, François Mach, and Fabrizio Montecucco
Subjects: 0301 basic medicine, Pathology, Myocardial Reperfusion Injury/pathology, Neutrophils, medicine.medical_treatment, Myocardial Infarction, 030204 cardiovascular system & hematology, Pathogenesis, 0302 clinical medicine, Ischemia, Neutrophils/cytology/metabolism, Myocardial infarction, ddc:616, Hematology, Plaque, Atherosclerotic, Pathophysiology, 3. Good health, Chemokines/metabolism, Neutrophil Infiltration, cardiovascular system, Chemokines, medicine.symptom, Lipoproteins, HDL, Neointima, medicine.medical_specialty, Acute Coronary Syndrome/metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Myocardial Reperfusion Injury, Inflammation, 03 medical and health sciences, Immune system, Percutaneous Coronary Intervention, Atherosclerosis/metabolism, Reactive Oxygen Species/metabolism, Angioplasty, medicine, Animals, Humans, Plaque, Atherosclerotic/metabolism, Acute Coronary Syndrome, ddc:576, Ischemia/pathology, business.industry, Lipoproteins, HDL/chemistry, Percutaneous coronary intervention, Atherosclerosis, medicine.disease, 030104 developmental biology, Multivariate Analysis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Reactive Oxygen Species, business, Myocardial Infarction/blood, Inflammation/pathology
Abstract: SummaryThe pathogenesis of acute myocardial infarction is known to be mediated by systemic, intraplaque and myocardial inflammatory processes. Among different immune cell subsets, compelling evidence now indicates a pivotal role for neutrophils in acute coronary syndromes. Neutrophils infiltrate coronary plaques and the infarcted myocardium and mediate tissue damage by releasing matrix-degrading enzymes and reactive oxygen species. In addition, neutrophils are also involved in post-infarction adverse cardiac remodelling and neointima formation after angioplasty. The promising results obtained in preclinical models with pharmacological approaches interfering with neutrophil recruitment or function have confirmed the pathophysiological relevance of these immune cells in acute coronary syndromes and prompted further studies of these therapeutic interventions. This narrative review will provide an update on the role of neutrophils in acute myocardial infarction and on the pharmacological means that were devised to prevent neutrophil-mediated tissue damage and to reduce post-ischaemic outcomes.
Published: 2013
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48. 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

49. Stabilisation of atherosclerotic plaques. Position paper of the European Society of Cardiology (ESC) Working Group on atherosclerosis and vascular biology

Author: Mat J.A.P. Daemen, Marek Naruszewicz, Erling Falk, Jacob F. Bentzon, Rob Krams, J. Wouter Jukema, Lale Tokgozoglu, Joerg Herrmann, Brenda R. Kwak, Gerard Pasterkamp, Seppo Ylä-Herttuala, Johannes Waltenberger, Christian Weber, Nikolaus Marx, Hector M. Garcia-Garcia, Andrew C. Newby, Patrick W. Serruys, Imo E. Hoefer, Cardiology, ACS - Amsterdam Cardiovascular Sciences, and Pathology
Subjects: 0301 basic medicine, Platelet Aggregation Inhibitors/therapeutic use, Anti-Inflammatory Agents, ddc:616.07, 030204 cardiovascular system & hematology, medicine.disease_cause, Anti-Inflammatory Agents/therapeutic use, Lipid Metabolism/drug effects, Renin-Angiotensin System, 0302 clinical medicine, Plaque, Atherosclerotic/pathology, Societies, Medical, treatment, Vascular biology, imaging, Hematology, Adrenergic beta-Antagonists/therapeutic use, Plaque, Atherosclerotic, 3. Good health, Lipoproteins, LDL, Europe, medicine.anatomical_structure, Cardiology, Lipoproteins, LDL/therapeutic use, Artery, medicine.medical_specialty, plaque stabilisation, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Aortic Rupture, Adrenergic beta-Antagonists, 03 medical and health sciences, Internal medicine, medicine, Humans, In patient, Pathological, business.industry, Retroperitoneal Fibrosis, Lipid Metabolism, Atherosclerosis, Vulnerable plaque, 030104 developmental biology, Clinical research, Atherosclerosis/drug therapy/pathology/physiopathology, Renin-Angiotensin System/drug effects, Vasa vasorum, Position paper, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, vulnerable plaques, Platelet Aggregation Inhibitors
Abstract: SummaryPlaque rupture and subsequent thrombotic occlusion of the coronary artery account for as many as three quarters of myocardial infarctions. The concept of plaque stabilisation emerged about 20 years ago to explain the discrepancy between the reduction of cardiovascular events in patients receiving lipid lowering therapy and the small decrease seen in angiographic evaluation of atherosclerosis. Since then, the concept of a vulnerable plaque has received a lot of attention in basic and clinical research leading to a better understanding of the pathophysiology of the vulnerable plaque and acute coronary syndromes. From pathological and clinical observations, plaques that have recently ruptured have thin fibrous caps, large lipid cores, exhibit outward remodelling and invasion by vasa vasorum. Ruptured plaques are also focally inflamed and this may be a common denominator of the other pathological features. Plaques with similar characteristics, but which have not yet ruptured, are believed to be vulnerable to rupture. Experimental studies strongly support the validity of anti-inflammatory approaches to promote plaque stability. Unfortunately, reliable non-invasive methods for imaging and detection of such plaques are not yet readily available. There is a strong biological basis and supportive clinical evidence that low-density lipoprotein lowering with statins is useful for the stabilisation of vulnerable plaques. There is also some clinical evidence for the usefulness of antiplatelet agents, beta blockers and renin-angiotensin-aldosterone system inhibitors for plaque stabilisation. Determining the causes of plaque rupture and designing diagnostics and interventions to prevent them are urgent priorities for current basic and clinical research in cardiovascular area.
Published: 2011

50. 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

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