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1. Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial

Author

Lamy, André, Sirota, Dmitry A., Jacques, Frederic, Poostizadeh, Ahmad, Noiseux, Nicolas, Efremov, Sergey, Demers, Philippe, Akselrod, Boris, Wang, Chew Yin, Arora, Rakesh C., Branny, Piotr, McGuinness, Shay P., Brown, Craig D., Jeanmart, Hugues, Zhao, Qiang, Zhang, Haibo, Belley-Côté, Emilie P., Whitlock, Richard P., Browne, Austin, Copland, Ingrid, Vincent, Jessica, Khatun, Rutaba, Balasubramanian, Kumar, Bangdiwala, Shrikant I., McGillion, Michael H., Fox-Robichaud, Alison E., Spence, Jessica, Yusuf, Salim, and Devereaux, P.J.

Published
2024
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3. Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement From the American Heart Association

Author

Criqui, Michael H, Matsushita, Kunihiro, Aboyans, Victor, Hess, Connie N, Hicks, Caitlin W, Kwan, Tak W, McDermott, Mary M, Misra, Sanjay, Ujueta, Francisco, and Council, on behalf of the American Heart Association Council on Epidemiology and Prevention Council on Arteriosclerosis Thrombosis and Vascular Biology Council on Cardiovascular Radiology and Intervention Council on Lifestyle and Cardiometabolic Health Council on Peripheral Vascular Disease and Stroke

Subjects
Clinical Research, Health Services, Heart Disease, Prevention, Cardiovascular, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, American Heart Association, Atherosclerosis, Combined Modality Therapy, Diagnostic Tests, Routine, Disease Management, Disease Susceptibility, Female, Humans, Lower Extremity, Male, Mass Screening, Peripheral Arterial Disease, Prevalence, Prognosis, Public Health Surveillance, Risk Assessment, Risk Factors, Socioeconomic Factors, Treatment Outcome, United States, AHA Scientific Statements, diagnosis, epidemiology, peripheral artery disease, prognosis, risk factors, American Heart Association Council on Epidemiology and Prevention, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiovascular Radiology and Intervention, Council on Lifestyle and Cardiometabolic Health, Council on Peripheral Vascular Disease, and Stroke Council, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

Lower extremity peripheral artery disease (PAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other cardiovascular diseases such as coronary heart disease and stroke and leg outcomes such as amputation). Despite its prevalence and clinical importance, PAD has been historically underappreciated by health care professionals and patients. This underappreciation seems multifactorial (eg, limited availability of the first-line diagnostic test, the ankle-brachial index, in clinics; incorrect perceptions that a leg vascular disease is not fatal and that the diagnosis of PAD would not necessarily change clinical practice). In the past several years, a body of evidence has indicated that these perceptions are incorrect. Several studies have consistently demonstrated that many patients with PAD are not receiving evidence-based therapies. Thus, this scientific statement provides an update for health care professionals regarding contemporary epidemiology (eg, prevalence, temporal trends, risk factors, and complications) of PAD, the present status of diagnosis (physiological tests and imaging modalities), and the major gaps in the management of PAD (eg, medications, exercise therapy, and revascularization). The statement also lists key gaps in research, clinical practice, and implementation related to PAD. Orchestrated efforts among different parties (eg, health care providers, researchers, expert organizations, and health care organizations) will be needed to increase the awareness and understanding of PAD and improve the diagnostic approaches, management, and prognosis of PAD.

Published
2021

4. Abstract 17500: A Crisis of the Heart

Author

Njoroge, Joyce and Crawford, Michael H

Subjects
Heart Disease, Cardiovascular, Heart Disease - Coronary Heart Disease, Clinical Research, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

A 59 year old female with past medical history of metastatic neuroendocrine tumor without cardiac involvement was admitted for transarterial catheter embolization (TACE) procedure of liver lesions. During the TACE procedure, she developed hypertensive urgency treated with intravenous beta blocker therapy and continuous octreotide for carcinoid reaction. The following day she developed acute pulmonary edema and labile blood pressures requiring low dose norepinephrine. Octreotide infusion was up-titrated to 500 mcg/hour with concern for carcinoid crisis. On physical exam, she was tachycardic and regular without notable murmurs or extra cardiac sounds, no elevated jugular venous distension, and no lower extremity edema. She had bilateral crackles on pulmonary exam and was diaphoretic and delirious. There were sub-millimeter lateral ST- segment elevations on her electrocardiogram but her troponin levels were elevated to 14 ng/dL. Point of care cardiac ultrasound demonstrated severely impaired left ventricular systolic function without regional wall motion abnormalities. Coronary angiogram revealed diffuse coronary vasospasm and elevated left ventricular end-diastolic pressure. On right heart catheterization, she had elevated filling pressures, pulmonary arterial oxygen saturation of 25%, and cardiac index of 1.42 L/min/m2. Our patient was diagnosed with cardiogenic shock secondary to octreotide mediated coronary vasospasm causing diffuse myocardial injury. Continued multidisciplinary discussions were needed to determine appropriate vasopressor and inotropic agent use to support cardiac function without triggering further hormonal dysregulation during carcinoid crisis. Her cardiac function eventually improved with left ventricular Impella support and gradual down-titration of octreotide dose. Norepinephrine, epinephrine, and phenylephrine were avoided in favor of vasopressin, and dobutamine was switched to milrinone to prevent further sympathetic activation. She was able to wean off Impella and pressor support and had improvement of her left ventricular function on repeat echocardiography one month later. She has not had recurrence of heart failure symptoms and continues to follow up with oncology via tele-visits.

Published
2020

5. An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of CASQ2-Catecholaminergic Polymorphic Ventricular Tachycardia

Author

Ng, Kevin, Titus, Erron W, Lieve, Krystien V, Roston, Thomas M, Mazzanti, Andrea, Deiter, Frederick H, Denjoy, Isabelle, Ingles, Jodie, Till, Jan, Robyns, Tomas, Connors, Sean P, Steinberg, Christian, Abrams, Dominic J, Pang, Benjamin, Scheinman, Melvin M, Bos, J Martijn, Duffett, Stephen A, van der Werf, Christian, Maltret, Alice, Green, Martin S, Rutberg, Julie, Balaji, Seshadri, Cadrin-Tourigny, Julia, Orland, Kate M, Knight, Linda M, Brateng, Caitlin, Wu, Jeremy, Tang, Anthony S, Skanes, Allan C, Manlucu, Jaimie, Healey, Jeff S, January, Craig T, Krahn, Andrew D, Collins, Kathryn K, Maginot, Kathleen R, Fischbach, Peter, Etheridge, Susan P, Eckhardt, Lee L, Hamilton, Robert M, Ackerman, Michael J, Noguer, Ferran Rosés I, Semsarian, Christopher, Jura, Natalia, Leenhardt, Antoine, Gollob, Michael H, Priori, Silvia G, Sanatani, Shubhayan, Wilde, Arthur AM, Deo, Rahul C, and Roberts, Jason D

Subjects
Clinical Research, Cardiovascular, Genetics, Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Calsequestrin, Female, Heterozygote, Homozygote, Humans, Male, Mutation, Missense, Risk Factors, Tachycardia, Ventricular, arrhythmias, cardiac, catecholaminergic polymorphic ventricular tachycardia, death, sudden, genetics, arrhythmias, cardiac, death, sudden, cardiac, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundGenetic variants in calsequestrin-2 (CASQ2) cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of CASQ2-CPVT was sought through an international multicenter collaboration.MethodsGenotype-phenotype segregation in CASQ2-CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models. Putative dominant CASQ2 missense variants and the established recessive CASQ2-p.R33Q variant were evaluated using oligomerization assays and their locations mapped to a recent CASQ2 filament structure.ResultsA total of 112 individuals, including 36 CPVT probands (24 homozygotes/compound heterozygotes and 12 heterozygotes) and 76 family members possessing at least 1 presumed pathogenic CASQ2 variant, were identified. Among CASQ2 homozygotes and compound heterozygotes, clinical penetrance was 97.1% and 26 of 34 (76.5%) individuals had experienced a potentially fatal arrhythmic event with a median age of onset of 7 years (95% CI, 6-11). Fifty-one of 66 CASQ2 heterozygous family members had undergone clinical evaluation, and 17 of 51 (33.3%) met diagnostic criteria for CPVT. Relative to CASQ2 heterozygotes, CASQ2 homozygote/compound heterozygote genotype status in probands was associated with a 3.2-fold (95% CI, 1.3-8.0; P=0.013) increased hazard of a composite of cardiac syncope, aborted cardiac arrest, and sudden cardiac death, but a 38.8-fold (95% CI, 5.6-269.1; P

Published
2020

6. An International Multicenter Evaluation of Type 5 Long QT Syndrome

Author

Roberts, Jason D, Asaki, S Yukiko, Mazzanti, Andrea, Bos, J Martijn, Tuleta, Izabela, Muir, Alison R, Crotti, Lia, Krahn, Andrew D, Kutyifa, Valentina, Shoemaker, M Benjamin, Johnsrude, Christopher L, Aiba, Takeshi, Marcondes, Luciana, Baban, Anwar, Udupa, Sharmila, Dechert, Brynn, Fischbach, Peter, Knight, Linda M, Vittinghoff, Eric, Kukavica, Deni, Stallmeyer, Birgit, Giudicessi, John R, Spazzolini, Carla, Shimamoto, Keiko, Tadros, Rafik, Cadrin-Tourigny, Julia, Duff, Henry J, Simpson, Christopher S, Roston, Thomas M, Wijeyeratne, Yanushi D, El Hajjaji, Imane, Yousif, Maisoon D, Gula, Lorne J, Leong-Sit, Peter, Chavali, Nikhil, Landstrom, Andrew P, Marcus, Gregory M, Dittmann, Sven, Wilde, Arthur AM, Behr, Elijah R, Tfelt-Hansen, Jacob, Scheinman, Melvin M, Perez, Marco V, Kaski, Juan Pablo, Gow, Robert M, Drago, Fabrizio, Aziz, Peter F, Abrams, Dominic J, Gollob, Michael H, Skinner, Jonathan R, Shimizu, Wataru, Kaufman, Elizabeth S, Roden, Dan M, Zareba, Wojciech, Schwartz, Peter J, Schulze-Bahr, Eric, Etheridge, Susan P, Priori, Silvia G, and Ackerman, Michael J

Subjects
Genetics, Cardiovascular, Clinical Trials and Supportive Activities, Heart Disease, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Death, Sudden, Cardiac, Electric Countershock, Electrocardiography, Female, Heart Arrest, Humans, Long QT Syndrome, Male, Middle Aged, Penetrance, Potassium Channels, Voltage-Gated, Registries, arrhythmia, genetics, long QT syndrome, penetrance, sudden cardiac death, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundInsight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration.MethodsPatients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death.ResultsA total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P

Published
2020

11. Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain

Author

Hoffmann, Udo, Ferencik, Maros, Udelson, James E, Picard, Michael H, Truong, Quynh A, Patel, Manesh R, Huang, Megan, Pencina, Michael, Mark, Daniel B, Heitner, John F, Fordyce, Christopher B, Pellikka, Patricia A, Tardif, Jean-Claude, Budoff, Matthew, Nahhas, George, Chow, Benjamin, Kosinski, Andrzej S, Lee, Kerry L, and Douglas, Pamela S

Subjects
Clinical Trials and Supportive Activities, Clinical Research, Cardiovascular, Atherosclerosis, Biomedical Imaging, Heart Disease - Coronary Heart Disease, Pain Research, Heart Disease, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Aged, Chest Pain, Coronary Angiography, Coronary Artery Disease, Echocardiography, Stress, Exercise Test, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Tomography, X-Ray Computed, coronary artery disease, diagnostic tests, routine, prognosis, PROMISE Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundOptimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing.MethodsIn the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months.ResultsBoth the prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomly assigned to CTA in comparison with 4602 patients randomly assigned to functional testing (33.4% versus 78.0%, and 0.9% versus 2.1%, respectively; both P10%) who had a normal functional test were reclassified as being mildly abnormal, the discriminatory capacity improved to 0.69 (95% CI, 0.64-0.74).ConclusionsCoronary CTA, by identifying patients at risk because of nonobstructive CAD, provides better prognostic information than functional testing in contemporary patients who have stable chest pain with a low burden of obstructive CAD, myocardial ischemia, and events.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Published
2017

25. Survival After Invasive or Conservative Management of Stable Coronary Disease

Author

Judith S. Hochman, Rebecca Anthopolos, Harmony R. Reynolds, Sripal Bangalore, Yifan Xu, Sean M. O’Brien, Stavroula Mavromichalis, Michelle Chang, Aira Contreras, Yves Rosenberg, Ruth Kirby, Balram Bhargava, Roxy Senior, Ann Banfield, Shaun G. Goodman, Renato D. Lopes, Radosław Pracoń, José López-Sendón, Aldo Pietro Maggioni, Jonathan D. Newman, Jeffrey S. Berger, Mandeep S. Sidhu, Harvey D. White, Andrea B. Troxel, Robert A. Harrington, William E. Boden, Gregg W. Stone, Daniel B. Mark, John A. Spertus, David J. Maron, Shari Esquenazi-Karonika, Margaret Gilsenan, Ewelina Gwiszcz, Patenne Mathews, Samaa Mohamed, Anna Naumova, Arline Roberts, Kerrie VanLoo, Ying Lu, Zhen Huang, Samuel Broderick, Luis Guzmán, Joseph Selvanayagam, Gabriel Steg, Jean-Michel Juliard, Rolf Doerr, Matyas Keltai, Boban Thomas, Tali Sharir, Eugenia Nikolsky, Aldo P. Maggioni, Shun Kohsaka, Jorge Escobedo, Olga Bockeria, Claes Held, Leslee J. Shaw, Lawrence Phillips, Daniel Berman, Raymond Y. Kwong, Michael H. Picard, Bernard R. Chaitman, Ziad Ali, James Min, G.B. John Mancini, Jonathon Leipsic, Graham Hillis, Suku Thambar, Majo Joseph, John Beltrame, Irene Lang, Herwig Schuchlenz, Kurt Huber, Kaatje Goetschalckx, Whady Hueb, Paulo Ricardo Caramori, Alexandre de Quadros, Paola Smanio, Claudio Mesquita, João Vitola, José Marin-Neto, Expedito Ribeiro da Silva, Rogério Tumelero, Marianna Andrade, Alvaro Rabelo Alves, Frederico Dall’Orto, Carisi Polanczyk, Estevão Figueiredo, Andrew Howarth, Gilbert Gosselin, Asim Cheema, Kevin Bainey, Denis Phaneuf, Ariel Diaz, Pallav Garg, Shamir Mehta, Graham Wong, Andy Lam, James Cha, Paul Galiwango, Amar Uxa, Benjamin (Ben) Chow, Adnan Hameed, Jacob Udell, Magdy Hamid, Marie Hauguel-Moreau, Alain Furber, Pascal Goube, Philippe-Gabriel Steg, Gilles Barone-Rochette, Christophe Thuaire, Michel Slama, Georg Nickenig, Raffi Bekeredjian, P. Christian Schulze, Bela Merkely, Geza Fontos, András Vértes, Albert Varga, Ajit Kumar, Rajesh G. Nair, Purvez Grant, Cholenahally Manjunath, Nagaraja Moorthy, Santhosh Satheesh, Ranjit Kumar Nath, Gurpreet Wander, Johann Christopher, Sudhanshu Dwivedi, Abraham Oomman, Atul Mathur, Milind Gadkari, Sudhir Naik, Eapen Punnoose, Ranjan Kachru, Upendra Kaul, Arthur Kerner, Giuseppe Tarantini, Gian Piero Perna, Emanuela Racca, Andrea Mortara, Lorenzo Monti, Carlo Briguori, Gianpiero Leone, Roberto Amati, Mauro Salvatori, Antonio Di Chiara, Paolo Calabro, Marcello Galvani, Stefano Provasoli, Keiichi Fukuda, Shintaro Nakano, Aleksandras Laucevicius, Sasko Kedev, Ahmad Khairuddin, Robert Riezebos, Jorik Timmer, Spencer Heald, Ralph Stewart, Walter Mogrovejo Ramos, Marcin Demkow, Tomasz Mazurek, Jarozlaw Drozdz, Hanna Szwed, Adam Witkowski, Nuno Ferreira, Fausto Pinto, Ruben Ramos, Bogdan Popescu, Calin Pop, Leo Bockeria, Elena Demchenko, Alexander Romanov, Leonid Bershtein, Ahmed Jizeeri, Goran Stankovic, Svetlana Apostolovic, Nada Cemerlic Adjic, Marija Zdravkovic, Branko Beleslin, Milica Dekleva, Goran Davidovic, Terrance Chua, David Foo, Kian Keong Poh, Mpiko Ntsekhe, Alessandro Sionis, Francisco Marin, Vicente Miró, Montserrat Gracida Blancas, José González-Juanatey, Francisco Fernández-Avilés, Jesús Peteiro, Jose Enrique Castillo Luena, Johannes Aspberg, Mariagrazia Rossi, Srun Kuanprasert, Sukit Yamwong, Nicola Johnston, Patrick Donnelly, Andrew Moriarty, Ahmed Elghamaz, Sothinathan Gurunathan, Nikolaos Karogiannis, Benoy N. Shah, Richard H.J. Trimlett, Michael B. Rubens, Edward D. Nicol, Tarun K. Mittal, Reinette Hampson, Reto Gamma, Mark De Belder, Thuraia Nageh, Steven Lindsay, Kreton Mavromatis, Todd Miller, Subhash Banerjee, Harmony Reynolds, Khaled Nour, and Peter Stone

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85–1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63–0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08–1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04894877.

Published
2023
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26. Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT

Author

Erin A. Bohula, David D. Berg, Mathew S. Lopes, Jean M. Connors, Ijlal Babar, Christopher F. Barnett, Sunit-Preet Chaudhry, Amit Chopra, Wilson Ginete, Michael H. Ieong, Jason N. Katz, Edy Y. Kim, Julia F. Kuder, Emilio Mazza, Dalton McLean, Jarrod M. Mosier, Ari Moskowitz, Sabina A. Murphy, Michelle L. O’Donoghue, Jeong-Gun Park, Rajnish Prasad, Christian T. Ruff, Mohamad N. Shahrour, Shashank S. Sinha, Stephen D. Wiviott, Sean Van Diepen, Mark Zainea, Vivian Baird-Zars, Marc S. Sabatine, David A. Morrow, Kyung Ah Im, Retu Saxena, Brandon Wiley, Carina Benson, Roman Delamed, Nedaa Skeik, Ami Chopra, Marc Judson, Scott Beegle, Boris Shkolnik, Anupama Tiwari, Gregory Wu, Abhijit Raval, Emerald Branch, Franz Rischard, Cameron Hypes, Billie Bixby, Christian Bime, Madhan Sundaram, Nancy Sweitzer, Alfredo Vazquez Sandoval, Heath White, Katherine Berg, Shahzad Shaefi, Michael Donnino, Brett Carroll, Michael Ieong, Kimberly Ackerbauer, Jaime Murphy, Ankeet Bhatt, Alexander Blood, Siddharth Patel, Victor Luu, Shraddha Narechania, Austin Lorganger, Robert Plambeck, Ali Nayfeh, Michael Sanley, Michel Del Cor, AJ Hegg, Winston Nara, Michael Snyder, Faisal Khan, Imad Shawa, Joshua Larned, Elias Collado, Mohammed Al Faiyumi, Rajeev Mehta, Sudarshan Komanapalli, Vijayadershan Muppidi, Mehul Desai, Casey Flanagan, Leonard Genovese, Tariq Haddad, Christopher King, Amber Peterson, Thane Htun, Elizabeth Pionk, Nicolas Mouawad, Chintalapudi Kumar, Kevin Nguyen, Majid Mughal, Ryan Malek, Akarsh Parekh, Christopher Provenzano, Melissa Ianitelli, Nicole Prentice-Gaytan, Adam Bykowski, Don Tait, Shelley Schendel, Varun Yalamanchili, Vasim Lala, Victor Hunyadi, Alexander Papolos, Benjamin Kenigsberg, Aarthi Shenoy, Thomas Stuckey, Douglas McQuaid, Praveen Mannam, Jeffrey McClung, Kent Nilsson, Andrew McKown, Jason Wells, David Hotchkin, Marc Jacobs, Wayne Strauss, Rick Balestra, Vikram Sahni, R. Jeffrey Snell, Hussam Suradi, Sarah Sungurlu, Jessica Kuppy, Eileen Gajo, Foster Adams, Abbas Shehadeh, Addi Suleiman, Harish Nandigam, Jihad Slim, Sardar Ijlal Babar, Dipti Baral, Talha Nawaz, Syed Abdullah Waheed, Randy Roth, Subhas Sitaula, Shahid Hayat, Jooby Babu, Jason Caberto, Victor Hsu, Robert Chang, Markian Bochan, Rafael Garcia-Cortes, Hal Skopicki, On Chen, Lauren Pilato, Paul Richman, Alexander Adler, Praveen Sudhindra, Jamie Beversdorf, Ravindra Kashyap, Parth Mehta, Borna Mehrad, Ali Ataya, Jorge Lascano, Mark Brantly, Adam Austin, Eduard Koman, Thomas Galski, Vijaya Kumar, Ayman Soubani, Nicolas Harrison, Vineet Reddy, and Audrey Fonkam

Subjects
Venous Thrombosis, Treatment Outcome, Critical Illness, Physiology (medical), Humans, COVID-19, Anticoagulants, Thrombosis, Hemorrhage, Cardiology and Cardiovascular Medicine, Platelet Aggregation Inhibitors, Clopidogrel
Abstract

Background: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. Methods: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit–level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit–level COVID-19 rates. Results: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08–3.55]; P =0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32–0.99]; P =0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose ( P =0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P =0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56–1.48]; P =0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. Conclusions: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04409834.

Published
2022
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34. An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome

Author

Adler, Arnon, Novelli, Valeria, Amin, Ahmad S., Abiusi, Emanuela, Care, Melanie, Nannenberg, Eline A., Feilotter, Harriet, Amenta, Simona, Mazza, Daniela, Bikker, Hennie, Sturm, Amy C., Garcia, John, Ackerman, Michael J., Hershberger, Raymond E., Perez, Marco V., Zareba, Wojciech, Ware, James S., Wilde, Arthur A.M., and Gollob, Michael H.

Published
2020
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35. Reappraisal of Reported Genes for Sudden Arrhythmic Death: An Evidence-Based Evaluation of Gene Validity for Brugada Syndrome

Author

Hosseini, S. Mohsen, Kim, Raymond, Udupa, Sharmila, Costain, Gregory, Jobling, Rebekah, Liston, Eriskay, Jamal, Seema M., Szybowska, Marta, Morel, Chantal F., Bowdin, Sarah, Garcia, John, Care, Melanie, Sturm, Amy C., Novelli, Valeria, Ackerman, Michael J., Ware, James S., Hershberger, Ray E., Wilde, Arthur A. M., and Gollob, Michael H.

Published
2018
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39. Medical Misinformation: Vet the Message!

Author

Hill, Joseph A., Agewall, Stefan, Baranchuk, Adrian, Booz, George W., Borer, Jeffrey S., Camici, Paolo G., Chen, Peng-Sheng, Dominiczak, Anna F., Erol, Çetin, Grines, Cindy L., Gropler, Robert, Guzik, Tomasz J., Heinemann, Markus K., Iskandrian, Ami E., Knight, Bradley P., London, Barry, Lüscher, Thomas F., Metra, Marco, Musunuru, Kiran, Nallamothu, Brahmajee K., Natale, Andrea, Saksena, Sanjeev, Picard, Michael H., Rao, Sunil V., Remme, Willem J., Rosenson, Robert S., Sweitzer, Nancy K., Timmis, Adam, and Vrints, Christiaan

Published
2019
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43. Abstract P665: Thoracic Aorta Calcification and Left Ventricular Structure and Function Relevant to Heart Failure: The Multi-Ethnic Study of Atherosclerosis (MESA)

Author

Watanabe, Kelly A, primary, Shrout Allen, Tara, additional, Andrews, Leah I, additional, Brumback, Lyndia C, additional, Cornelissen Guillaume, Germaine G, additional, Duprez, Daniel A, additional, Jacobs, David R, additional, Criqui, Michael H, additional, and Allison, Matthew A, additional

Published
2023
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44. Abstract P367: Automated Outreach to Improve Statin Initiation and Follow-Up of Lipid Panels Among Patients With High LDL-C

Author

Mefford, Matthew T, primary, Zhou, Hui, additional, Zhou, Mengnan, additional, Derakhshan, Hananeh, additional, Harrison, Teresa N, additional, Rojas, Mara, additional, Kanter, Michael H, additional, Scott, Ronald D, additional, Imley, Tracy, additional, Sanders, Mark, additional, Timmins, Royann, additional, and Reynolds, Kristi, additional

Published
2023
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45. Survival After Invasive or Conservative Management of Stable Coronary Disease

Author

Hochman, Judith S., primary, Anthopolos, Rebecca, additional, Reynolds, Harmony R., additional, Bangalore, Sripal, additional, Xu, Yifan, additional, O’Brien, Sean M., additional, Mavromichalis, Stavroula, additional, Chang, Michelle, additional, Contreras, Aira, additional, Rosenberg, Yves, additional, Kirby, Ruth, additional, Bhargava, Balram, additional, Senior, Roxy, additional, Banfield, Ann, additional, Goodman, Shaun G., additional, Lopes, Renato D., additional, Pracoń, Radosław, additional, López-Sendón, José, additional, Maggioni, Aldo Pietro, additional, Newman, Jonathan D., additional, Berger, Jeffrey S., additional, Sidhu, Mandeep S., additional, White, Harvey D., additional, Troxel, Andrea B., additional, Harrington, Robert A., additional, Boden, William E., additional, Stone, Gregg W., additional, Mark, Daniel B., additional, Spertus, John A., additional, Maron, David J., additional, Hochman, Judith S., additional, Esquenazi-Karonika, Shari, additional, Gilsenan, Margaret, additional, Gwiszcz, Ewelina, additional, Mathews, Patenne, additional, Mohamed, Samaa, additional, Naumova, Anna, additional, Roberts, Arline, additional, VanLoo, Kerrie, additional, Lu, Ying, additional, Huang, Zhen, additional, Broderick, Samuel, additional, Guzmán, Luis, additional, Selvanayagam, Joseph, additional, Steg, Gabriel, additional, Juliard, Jean-Michel, additional, Doerr, Rolf, additional, Keltai, Matyas, additional, Thomas, Boban, additional, Sharir, Tali, additional, Nikolsky, Eugenia, additional, Maggioni, Aldo P., additional, Kohsaka, Shun, additional, Escobedo, Jorge, additional, Bockeria, Olga, additional, Held, Claes, additional, Shaw, Leslee J., additional, Phillips, Lawrence, additional, Berman, Daniel, additional, Kwong, Raymond Y., additional, Picard, Michael H., additional, Chaitman, Bernard R., additional, Ali, Ziad, additional, Min, James, additional, Mancini, G.B. John, additional, Leipsic, Jonathon, additional, Hillis, Graham, additional, Thambar, Suku, additional, Joseph, Majo, additional, Beltrame, John, additional, Lang, Irene, additional, Schuchlenz, Herwig, additional, Huber, Kurt, additional, Goetschalckx, Kaatje, additional, Hueb, Whady, additional, Caramori, Paulo Ricardo, additional, de Quadros, Alexandre, additional, Smanio, Paola, additional, Mesquita, Claudio, additional, Vitola, João, additional, Marin-Neto, José, additional, da Silva, Expedito Ribeiro, additional, Tumelero, Rogério, additional, Andrade, Marianna, additional, Alves, Alvaro Rabelo, additional, Dall’Orto, Frederico, additional, Polanczyk, Carisi, additional, Figueiredo, Estevão, additional, Howarth, Andrew, additional, Gosselin, Gilbert, additional, Cheema, Asim, additional, Bainey, Kevin, additional, Phaneuf, Denis, additional, Diaz, Ariel, additional, Garg, Pallav, additional, Mehta, Shamir, additional, Wong, Graham, additional, Lam, Andy, additional, Cha, James, additional, Galiwango, Paul, additional, Uxa, Amar, additional, Chow, Benjamin (Ben), additional, Hameed, Adnan, additional, Udell, Jacob, additional, Hamid, Magdy, additional, Hauguel-Moreau, Marie, additional, Furber, Alain, additional, Goube, Pascal, additional, Steg, Philippe-Gabriel, additional, Barone-Rochette, Gilles, additional, Thuaire, Christophe, additional, Slama, Michel, additional, Nickenig, Georg, additional, Bekeredjian, Raffi, additional, Schulze, P. Christian, additional, Merkely, Bela, additional, Fontos, Geza, additional, Vértes, András, additional, Varga, Albert, additional, Kumar, Ajit, additional, Nair, Rajesh G., additional, Grant, Purvez, additional, Manjunath, Cholenahally, additional, Moorthy, Nagaraja, additional, Satheesh, Santhosh, additional, Nath, Ranjit Kumar, additional, Wander, Gurpreet, additional, Christopher, Johann, additional, Dwivedi, Sudhanshu, additional, Oomman, Abraham, additional, Mathur, Atul, additional, Gadkari, Milind, additional, Naik, Sudhir, additional, Punnoose, Eapen, additional, Kachru, Ranjan, additional, Kaul, Upendra, additional, Kerner, Arthur, additional, Tarantini, Giuseppe, additional, Perna, Gian Piero, additional, Racca, Emanuela, additional, Mortara, Andrea, additional, Monti, Lorenzo, additional, Briguori, Carlo, additional, Leone, Gianpiero, additional, Amati, Roberto, additional, Salvatori, Mauro, additional, Di Chiara, Antonio, additional, Calabro, Paolo, additional, Galvani, Marcello, additional, Provasoli, Stefano, additional, Fukuda, Keiichi, additional, Nakano, Shintaro, additional, Laucevicius, Aleksandras, additional, Kedev, Sasko, additional, Khairuddin, Ahmad, additional, Riezebos, Robert, additional, Timmer, Jorik, additional, Heald, Spencer, additional, Stewart, Ralph, additional, Ramos, Walter Mogrovejo, additional, Demkow, Marcin, additional, Mazurek, Tomasz, additional, Drozdz, Jarozlaw, additional, Szwed, Hanna, additional, Witkowski, Adam, additional, Ferreira, Nuno, additional, Pinto, Fausto, additional, Ramos, Ruben, additional, Popescu, Bogdan, additional, Pop, Calin, additional, Bockeria, Leo, additional, Demchenko, Elena, additional, Romanov, Alexander, additional, Bershtein, Leonid, additional, Jizeeri, Ahmed, additional, Stankovic, Goran, additional, Apostolovic, Svetlana, additional, Adjic, Nada Cemerlic, additional, Zdravkovic, Marija, additional, Beleslin, Branko, additional, Dekleva, Milica, additional, Davidovic, Goran, additional, Chua, Terrance, additional, Foo, David, additional, Poh, Kian Keong, additional, Ntsekhe, Mpiko, additional, Sionis, Alessandro, additional, Marin, Francisco, additional, Miró, Vicente, additional, Blancas, Montserrat Gracida, additional, González-Juanatey, José, additional, Fernández-Avilés, Francisco, additional, Peteiro, Jesús, additional, Luena, Jose Enrique Castillo, additional, Aspberg, Johannes, additional, Rossi, Mariagrazia, additional, Kuanprasert, Srun, additional, Yamwong, Sukit, additional, Johnston, Nicola, additional, Donnelly, Patrick, additional, Moriarty, Andrew, additional, Elghamaz, Ahmed, additional, Gurunathan, Sothinathan, additional, Karogiannis, Nikolaos, additional, Shah, Benoy N., additional, Trimlett, Richard H.J., additional, Rubens, Michael B., additional, Nicol, Edward D., additional, Mittal, Tarun K., additional, Hampson, Reinette, additional, Gamma, Reto, additional, De Belder, Mark, additional, Nageh, Thuraia, additional, Lindsay, Steven, additional, Mavromatis, Kreton, additional, Miller, Todd, additional, Banerjee, Subhash, additional, Reynolds, Harmony, additional, Nour, Khaled, additional, and Stone, Peter, additional

Published
2023
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46. Abstract P667: Association of Number of Calcified Coronary Arteries and Cardiovascular Outcomes Stratified by Calcification Volume: The Multi-Ethnic Study of Atherosclerosis (MESA)

Author

Mikaila P Reyes, Tara S Allen, Michael H Criqui, Jonathan M Kermanshahchi, Julie O Denenberg, and Harpreet S Bhatia

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Coronary artery calcium (CAC) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). Data suggests number of vessels with CAC independently improves risk prediction but impact by CAC volume remains unknown. Methods: Using data from 3256 MESA participants with CAC>0 and clinical follow-up, we evaluated the association between number of arteries with CAC and risk for coronary heart disease (CHD), myocardial infarction (MI), and CVD events stratified by CAC volume (above/below median) using multivariable-adjusted Cox proportional hazards models. Results: Mean age was 63.3 years (SD 9.5) with 1363 (41.9%) women. There were 1079 (33%) with single-vessel, 822 (25%) with 2-vessel, and 1355 (42%) with 3-4 vessel CAC. Median CAC volume was 84.7 [IQR 24.5, 267.2] mm 3 . CAC in 3-4 vessels was independently associated with higher CHD risk ( Figure ) compared to 1-vessel (HR 2.01, 95% CI 1.1-3.6; p=0.018) and 2-vessels (HR 1.69, 95% CI 1.0-2.8; p=0.04) for lower CAC volumes, with similar findings for MI and CVD outcomes ( Table ). Conclusions: Number of arteries with CAC independently increases risk for ASCVD events only for those with lower CAC volumes.

Published
2023
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47. Abstract P665: Thoracic Aorta Calcification and Left Ventricular Structure and Function Relevant to Heart Failure: The Multi-Ethnic Study of Atherosclerosis (MESA)

Author

Kelly A Watanabe, Tara Shrout Allen, Leah I Andrews, Lyndia C Brumback, Germaine G Cornelissen Guillaume, Daniel A Duprez, David R Jacobs, Michael H Criqui, and Matthew A Allison

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Aortic stiffness promotes left ventricular (LV) remodeling and dysfunction. Thoracic aorta calcification (TAC) contributes to aortic stiffness, but it remains unclear how TAC presence, volume, and density impact LV structure and function. We tested the hypothesis that TAC presence and higher volume is associated with increased LV mass index, decreased LV end-diastolic volume (LVEDV) index, and impaired mid-wall circumferential strain (Ecc). Methods: We evaluated 1,693 participants from the MESA who underwent chest CT and cardiac MRI from 2010 to 2012. We used linear regression models to determine cross-sectional associations between the presence, volume, and density of TAC with LV mass index, LVEDV index, and Ecc. Each pair of predictor and outcome variables underwent three model adjustments: (1) age, gender, and race/ethnicity; (2) Model 1 plus education level, height, weight, physical activity, sedentary behavior, smoking status, eGFR, SBP, DBP, anti-HTN medication use, total cholesterol/HDL ratio, statin use, and diabetes; (3) Model 2 plus coronary artery calcium (CAC) presence and volume. TAC volume and density were evaluated separately, then jointly in the same models. Results: The mean age was 69 years (SD 9) and 53% were female, while 39% were White, 26% Black, 21% Hispanic/Latino, 15% Chinese. TAC was present in 1,518 (90%) participants. TAC volume and density were highly correlated (r=0.75) with respective median 213 (25%ile, 75%ile: 36, 800) mm 3 and mean 350 (SD 110) Hounsfield Units. LV mass index, LVEDV index, and Ecc had respective means of 65 g/m 2 (SD 14), 120 mL/m 2 (SD 31), and -18.2% (SD 2.8). After full adjustment (Model 3 without density), a 10% increase in TAC volume was associated with a 1.8% multiplicative higher Ecc (i.e., less negative Ecc) (95% CI 0.2-3.4%, p=0.04) reflecting reduced LV systolic and diastolic function. Higher TAC volume was marginally associated with higher LV mass index: a 10% increase in TAC volume was associated with a 5.6% increase (-0.6-11.7%, p=0.08) in Model 2 without density, 13.9% (2.1-25.7%, p=0.03) in Model 2 with density, 3.9% (-2.5-10.4%, p=0.23) in Model 3 without density, and 11.3% (-1.0-23.7%, p=0.08) in Model 3 with density. After adjustments in Models 2 or 3, there were no other significant associations between TAC presence, volume, or density with the outcomes. Conclusions: Higher TAC volume is associated with impaired Ecc independent of CAC and marginally associated with higher LV mass index. These results suggest that the extent of TAC may influence LV remodeling and thus reduced function.

Published
2023
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48. Abstract P367: Automated Outreach to Improve Statin Initiation and Follow-Up of Lipid Panels Among Patients With High LDL-C

Author

Matthew T Mefford, Hui Zhou, Mengnan Zhou, Hananeh Derakhshan, Teresa N Harrison, Mara Rojas, Michael H Kanter, Ronald D Scott, Tracy Imley, Mark Sanders, Royann Timmins, and Kristi Reynolds

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Despite their effectiveness in reducing low-density lipoprotein-cholesterol (LDL-C) and cardiovascular disease (CVD) risk, high-intensity statins are underutilized among patients with LDL-C ≥ 190 mg/dL. We aimed to determine if a patient outreach program (KP Sure Net) automating high-intensity statin orders and lipid panels improved statin initiation and lab completions. Methods: Kaiser Permanente Southern California adults 20-60 years of age with LDL-C ≥ 190 mg/dL and no recent statin use were compared pre- (January 2016-September 2018, n=3,534) and post- (April 2019-July 2021, n=3,555) program implementation to examine statin prescriptions and fills, lab completions, and improved LDL-C ( Results: Among adults identified during pre- and post-implementation, 759 (21.5%) and 976 (27.5%), respectively, received a statin prescription. Adults with a prescription post- versus pre-implementation were more likely to be younger, identify as Black or Asian ethnicity, be English-speaking and have higher income, but were similar by sex, education, insurance, and comorbidity burden. (Table) After multivariable adjustment, adults post- versus pre-implementation had a higher likelihood of receiving a statin prescription (RR 1.36, 95% CI 1.25, 1.48), filling their statin (RR 1.32, 95% CI 1.26, 1.38), completing their lipid panel (RR 1.60, 95% CI 1.44, 1.78), and improving LDL-C (RR 1.36, 95% CI 1.20, 1.53). Conclusion: Automating statin orders and lipid panels for high-risk adults improved prescription rates, fills and LDL-C. Understanding facilitators and barriers to adherence is an important next step in improving patients’ health.

Published
2023
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49. Abstract P677: Association of Antibodies to Citrullinated Protein Antigens (ACPA) With Coronary Artery Calcium and Abdominal Aorta Calcium in a Multi-Ethnic Community-Dwelling Population

Author

Jan M Hughes-Austin, Ronit Katz, Gary Firestein, William Robinson, Michael H Criqui, and Joachim H Ix

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Patients with rheumatoid arthritis (RA) have double the risk of cardiovascular (CV) events and greater extent of coronary artery calcium (CAC) compared to the general population. Antibodies to citrullinated protein antigens (ACPA) have been linked to CAC in patients with RA; and RA-related autoimmunity has been associated with CAC in Black women without RA. ACPA are detectable years before RA onset and in some individuals who do not develop RA. Given the association between vascular calcification and CV events in the general population, we investigated associations between ACPA and coronary and abdominal aorta calcification (AAC). Methods: In a randomly selected subset of 1968 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), we measured ACPA using a multiplex array of 28 different ACPA. Each ACPA was defined as positive if >95 th percentile cut-off in MESA. The number of (+) ACPA were summed for each participant (range 0-28). We measured AAC and CAC using computed tomography scans. We evaluated associations between number of ACPA, individual ACPA and AAC and CAC using multivariable linear regression, adjusting for covariates and testing for interactions with gender and race/ethnicity. Results: Among 1828 MESA participants with complete data, average age was 65(10); were 50% female, 40% White, 13% Chinese, 21% Black, 26% Hispanic/Latino and 27% positive (+) for at least one ACPA. Among ACPA(+) participants, median number of ACPA was 1 (1, 6) and ranged from 1-28 ACPA. Number of ACPA was neither significantly associated with CAC severity (p=0.06) nor AAC severity (p=0.48). These associations did not differ by gender or race. However, several individual ACPA were associated with CAC and AAC. In particular, for every SD higher citrullinated ApoA antibody concentration (anti-cit-ApoA), CAC severity was 0.15 (0.07)% higher (p=0.03); and AAC severity was 0.07 (0.04) % lower (p=0.08) in fully adjusted analysis. Associations between anti-cit-ApoA and AAC severity were modified by gender (p interaction =0.02), where in women for every SD higher anti-cit-ApoA, AAC severity was 0.15 (0.06)% lower (p=0.007); and in men, AAC severity was 0.03 (0.05)% higher, although this association was not statistically significant (p=0.55). For every SD higher citrullinated Fibrinogen antibody (anti-cit-Fibrinogen) concentration, CAC severity was 0.14 (0.07) % higher (p=0.05); and AAC severity was 0.10 (0.04) % lower (p=0.01) in fully adjusted analysis. There was no significant interaction between anti-cit-Fibrinogen and gender or race. Conclusion: In a community-dwelling population without RA, ACPA were associated with higher CAC severity and lower AAC severity, independent of traditional CV risk factors. Because we did not expect the inverse association between ACPA and AAC severity, continued research is needed to better understand mechanisms explaining this association.

Published
2023
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50. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Author

Subodh Verma, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Nitish K. Dhingra, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, R. Preston Mason, Jean-Claude Tardif, Christie M. Ballantyne, Fabrice M.A.C. Martens, Astrid Schut, Brian Olshansky, Mina Chung, Al Hallstrom, Lesly Pearce, Cyrus Mehta, Rajat Mukherjee, Anjan K. Chakrabarti, Eli V. Gelfand, Megan Carroll Leary, Duane S. Pinto, Yuri B. Pride, Steven Ketchum, Ramakrishna Bhavanthula, Gertrude Chester, Christina Copland, Katelyn Diffin, Ralph Doyle, Kurt Erz, Alex Giaquinto, Paula Glanton, Angela Granger, Richard H. Iroudayassamy, Rebecca Juliano, James Jin, Dimitry Klevak, Hardik Panchal, Robert Wang, Shin-Ru Wang, Gerard Abate, Peggy J. Berry, Rene Braeckman, Declan Doogan, Anne Elson, Amy HauptmannBaker, Isabel Lamela, Catherine Lubeck, Mehar Manku, Sabina Murphy, Monica Sanford, William Stirtan, Paresh Soni, Arnaud Bastien, Demetria Foster, Evangelito Gascon, Judith Johnson, Lasbert Latona, Gang Liu, Sandra Palleja, Nelly Sanjuan, Jimmy Shi, William Stager, Mukund Venkatakrishnan, Ahmed Youssef-Agha, Julie Zhu, Leela Aertker, Suresh Ankolekar, Lisa Goldberg, Natasa Rajicic, Jianfen Shu, Heng Zou, Magdy Mikhail, Gamil Dawood, N. Mathew Koshy, Sandip K. Mukherjee, Rafik Abadier, Andrea L. Lawless, William P. McGuinn, Howard Weintraub, Kathryn Rohr, Edmund Claxton, Robert J. Weiss, Terry D. Klein, Mani Nallasivan, Stephen Crowley, Marilyn King, Anthony D. Alfieri, David Fitz-Patrick, Irving Loh, Nolan J. Mayer, Rakesh Prashad, Samuel Lederman, Debra Weinstein, Harold E. Bays, Keith Chu, Alireza Maghsoudi, Paul D. Thompson, Jeff Carstens, Anna Chang, Kenneth R. Cohen, Julius Dean, Howard S. Ellison, Bernard Erickson, Enrique A. Flores, Daniel W. Gottlieb, Paul Grena, John R. Guyton, Peter H. Jones, John M. Joseph, Norman E. Lepor, Sam Lerman, Robert D. Matheney, Theodore R. Pacheco, Michael B. Russo, John Rubino, Edward S. Pereira, Albert A. Seals, Eduardo Viera, Alan D. Steljes, Jason Thompson, Shaival Kapadia, Michael McIvor, Jorge E. Salazar, Jose O. Santiago, Ralph Vicari, Martin R. Berk, William A. Kaye, Marcus McKenzie, David Podlecki, Brian D. Snyder, Stephen Nash, David M. Herrington, Wallace Johnson, Joseph R. Lee, Ronald Blonder, Alpa M. Patel, Ramon Castello, Susan Greco, Dean J. Kereiakes, Venkatesh K. Nadar, Mark Nathan, Ranganatha P. Potu, Robert Sangrigoli, Richard Smalling, Mitchell Davis, Robert Braastad, James McCriskin, Kunal Bodiwala, Joe L. Hargrove, Mark W. Graves, George Emlein, Raegan W. Durant, James W. Clower, Rohit Arora, Narendra Singh, Lisa Warsinger Martin, W Herbert Haught, Marc P. Litt, Michael D. Klein, Peter Hoagland, Michael Goldstein, Marco S. Mazzella, Daniel H. Dunker, Brian H. Kahn, Carlos S. Ince, Frank A. McGrew, Jay Lee, David Pan, Salman A. Khan, Uri Elkayam, Wasim Deeb, Anne C. Goldberg, Christopher S. Brown, Wayne N. Leimbach, Thomas S. Backer, David R. Sutton, Joel Gellman, Anu R. George, Alan S. Hoffman, Mark Kates, Kishlay Anand, Robert Bear, Brendan J. Cavanaugh, Ramon G. Reyes, Rodolfo Sotolongo, Kenneth Sabatino, Kevin Gallagher, Ehab Sorial, Chris Geohas, Kathleen E. Magness, Bernard P. Grunstra, Frederik A. Martin, William S. Knapp, Mel E. Lucas, John J. Champlin, Jason Demattia, Patrick H. Peters, Judith Kirstein, William J. Randall, Cezar S. Staniloae, Jennifer G. Robinson, Alexander Adler, Christopher Case, Andrew J. Kaplan, Gregory F. Lakin, Krishan K. Goyle, Michael J. DiGiovanna, Chester L. Fisher, Michael Lillestol, Michael Robinson, Robert G. Perry, Lawrence S. Levinson, Brian G. Everhart, Robert D. Madder, Earl F. Martin, Earl E. Martin, Imtiaz Alam, Jose Mari L. Elacion, Robina Poonawala, Taddese T. Desta, Jerome A. Robinson, Gilbert J. Martinez, Jakkidi S. Reddy, Jeffrey D. Wayne, Samuel Mujica Trenche, Westbrook I. Kaplan, Rubin H. Saavedra, Michael D. DiGregorio, Barry D. Bertolet, Neil J. Fraser, Terence T. Hart, Ronald J. Graf, David A. Jasper, Michael Dunn, Dan A. Streja, David J. Strobl, Nan Jiang, Vicki Kalen, Richard Mascolo, Mercedes B. Samson, Michael Stephens, Bret M. Bellard, Mario Juarez, Patrick J. McCarthy, John B. Checton, Michael Stillabower, Edward Goldenberg, Amin H. Karim, Naseem Jaffrani, Robert C. Touchon, Erich R. Fruehling, Clayton J. Friesen, Pradipta Chaudhuri, Frank H. Morris, Robert E. Broker, Rajesh J. Patel, Susan Hole, Randall P. Miller, Francisco G. Miranda, Sadia Dar, Shawn N. Gentry, Paul Hermany, Charles B. Treasure, Miguel E. Trevino, Raimundo Acosta, Anthony Japour, Samuel J. Durr, Thomas Wang, Om P. Ganda, Perry Krichmar, James L. Arter, Douglas Jacoby, Michael A. Schwartz, Amer Al-Karadsheh, Nelson E. Gencheff, John A. Pasquini, Richard Dunbar, Sarah Kohnstamm, Hector F. Lozano, Francine K. Welty, Thomas L. Pitts, Brian Zehnder, Salah El Hafi, Mark A. King, Arnold Ghitis, Marwan M. Bahu, Hooman Ranjbaran Jahromi, Ronald P. Caputo, Robert S. Busch, Michael D. Shapiro, Suhail Zavaro, Munib Daudjee, Shahram Jacobs, Vipul B. Shah, Frank Rubalcava, Mohsin T. Alhaddad, Henry Lui, Raj T. Rajan, Fadi E. Saba, Mahendra Pai N Gunapooti, Tshiswaka B. Kayembe, Timothy Jennings, Robert A. Strzinek, Michael H. Shanik, Pradeep K. Singh, Alastair C. Kennedy, Howard Rubenstein, Ramin Manshadi, Joanne Ladner, Lily Kakish, Ashley Kakish, Amy L. Little, Jaime Gerber, Nancy J. Hinchion, Janet Guarino, Denise Raychok, Susan Budzinski, Kathleen Kelley-Garvin, April Beckord, Jessica Schlinder, Arthur Schwartzbard, Stanley Cobos, Deborah Freeman, David Abisalih, Dervilla McCann, Kylie Guy, Jennifer Chase, Stacey Samuelson, Madeline Cassidy, Marissa Tardif, Jaime Smith, Brenna Sprout, Nanette Riedeman, Julie Goza, Lori Johnson, Chad Kraske, Sheila Hastings, Chris Dutka, Stephanie Smith, Toni McCabe, Kathleen Maloney, Paul Alfieri, Vinay Hosemane, Chanhsamone Syravanh, Cindy Pau, April Limcoiloc, Tabitha Carreira, Taryn S. Kurosawa, Razmig Krumian, Krista Preston, Ashraf Nashed, Daria Schneidman-Fernandez, Jack Patterson, John Tsakonas, Jennifer Esaki, Lynn Sprafka, Porous Patel, Brian Mitchell, Erin M. Ross, Donna Miller, Akash Prashad, Kristina M. Feyler, Natasha Juarbe, Sandra Herrera, Sarah M. Keiran, Becky Whitehead, Whitney Asher, Coury Hobbs, Abbey Elie, Jean Brooks, Amanda L. Zaleski, Brenda Foxen, Barb Lapke, Philippa Wright, Bristol Pavol, Gwen Carangi, Marla Turner, Katharine W. Sanders, Rikita S. Delamar, Virginia L. Wilson, Sarah M. Harvel, Alison M. Cartledge, Kaitlyn R. Bailey, Kathleen Mahon, Timothy Schuchard, Jen Humbert, Mark C. Hanson, Michael P. Cecil, James S. Abraham, Lorie Benedict, Claudia Slayton, Curtis S. Burnett, Rachel W. Ono-Lim, Sharon Budzinski, Shubi A. Khan, Sharon Goss, Terry Techmanski, Farida Valliani, Rimla Joseph, Edith Flores, Laurn Contreras, Ana Aguillon, Carrie-Ann Silvia, Maria Martin, Edmund K. Kerut, Leslie W. Levenson, Louis B. Glade, Brian J. Cospolich, Maureen W. Stein, Stephen P. LaGuardia, Thelma L. Sonza, Tracy M. Fife, Melissa Forschler, Jasmyne Watts, Judy Fritsch, Emese Futchko, Sarah Utech, Scott B. Baker, Miguel F. Roura, Scott A. Segel, James S. Magee, Cathy Jackson, Rebecca F. Goldfaden, Liudmila Quas, Elizabeth C. Ortiz, Michael Simpson, Robert Foster, Christopher Brian, James Trimm, Michael Bailey, Brian Snoddy, Van Reeder, Rachel Wilkinson, Harold Settle, Cynthia Massey, Angela Maiola, Michele Hall, Shelly Hall, Wanda Hall, Mark Xenakis, Janet Barrett, Giovanni Campanile, David Anthou, Susan F. Neill, Steven Karas, Enrique Polanco, Norberto Schechtman, Grace Tischner, Kay Warren, Cynthia St Cyr, Menna Kuczinski, Latrina Alexander, Maricruz Ibarra, Barry S. Horowitz, Jaime Steinsapir, Jeanette Mangual-Coughlin, Brittany Mooney, Precilia Vasquez, Kathleen Rodkey, Alexandria Biberstein, Christine Ignacio, Irina Robinson, Marcia Hibberd, Lisa B. Hoffman, Daniel J. Murak, Raghupathy Varavenkataraman, Theresa M. Ohlson Elliott, Linda A. Cunningham, Heather L. Palmerton, Sheri Poole, Jeannine Moore, Helene Wallace, Ted Chandler, Robert Riley, Farah Dawood, Amir Azeem, Michael Cammarata, Ashleigh Owen, Shivani Aggarwal, Waqas Qureshi, Mohamed Almahmoud, Abdullahi Oseni, Adam Leigh, Erin Barnes, Adam Pflum, Amer Aladin, Karen Blinson, Vickie Wayne, Lynda Doomy, Michele Wall, Valerie Bitterman, Cindi Young, Rachel Grice, Lioubov Poliakova, Jorge Davalos, David Rosenbaum, Mark Boulware, Heather Mazzola, J. Russell Strader, Russell Linsky, David Schwartz, Elizabeth Graf, Alicia Gneiting, Melissa Palmblad, Ashley Donlin, Emily Ensminger, Hillary Garcia, Dawn Robinson, Carolyn Tran, Jeffrey Jacqmein, Darlene Bartilucci, Michael Koren, Barbara Maluchnik, Melissa Parks, Jennifer Miller, Cynthia DeFosse, Albert B. Knouse, Amy Delancey, Stephanie Chin, Thomas Stephens, Mag Sohal, Juana Ingram, Swarooparani Kumar, Heather Foley, Nina Smith, Vera McKinney, Linda Schwarz, Judith Moore, Hildreth Vernon Anderson, Stefano Sdringola-Maranga, Ali Denktas, Elizabeth Turrentine, Rhonda Patterson, John Marshall, Terri Tolar, Donna Patrick, Pamela Schwartzkopf, Anthony M. Fletcher, Frances R. Harris, Sherry Clements, Tiffany Brown, William Smith, Stacey J. Baehl, Robin Fluty, Daniel VanHamersveld, Dennis Breen, Nancy Bender, Beverly Stafford, Tamika Washington, Margaret N. Pike, Mark A. Stich, Evyan Jawad, Amin Nadeem, Jill Nyland, Rhonda Hamer, Kendra Calhoun, Charlotte Mall, Samuel Cadogan, Kati Raynes, Richard Katz, Lorraine Marshall, Rashida Abbas, Jay L. Dinerman, John T. Hartley, Beth Lamb, Lisa Eskridge, Donna Raymond, Kristy Clemmer, Denise M. Fine, Paula Beardsley, Janet Werner, Bette Mahan, Courtney VanTol, Robert Herman, Christine Raiser-Vignola, Felicia McShan, Stefanie A. Neill, David R. Blick, Michael J. Liston, Denetta K. Nelson, Sandra K. Dorrell, Patricia Wyman, Ambereen Quraishi, Fernando Ferro, Frank Morris, Vicki J. Coombs, Autumn M. Mains, Austin A. Campbell, Jeanne Phelps, Cheryl A. Geary, Ellen G. Sheridan, Jean M. Downing, Arie Swatkowski, Tish Redden, Brian Dragutsky, Susan Thomas, Candace Mitchell, Diana Barker, Elanie Turcotte, Deborah Segerson, Jill Guy, Karena De La Mora, Jennifer Hong, Dennis Do, Rose Norris, Faisal Khan, Hector Montero, Stacy Kelly-White, Alan Cleland, Rosalyn Alcalde-Crawford, Melissa Morgan, Brijmohan Sarabu, Megan Minor, Shweta Kamat, Stephanie M. Estes, Nancee Harless, Alicia Disney, Jodi L. Pagano, Chad M. Alford, Noel W. Bedwell, Warren D. Hardy, Kevin DeAndrade, Jessica G. Elmore, Eric Auerbach, Anthony W. Haney, Miriam H. Brooks, Jose Torres, Lois Roper, Terry Backer, Katie Backer, John G. Evans, Ricardo A. Silva, Lorraine H. Dajani, Veronica Yousif, Tammy Ross, Sion K. Roy, Ronald Oudiz, Sajad Hamal, Ferdinand Flores, Amor Leahy, Debra Ayer, Swapna George, Chrisi Carine Stewart, Elvira Orellana, Cristina Boccalandro, Mary Rangel, Suzanne Hennings, Carl Vanselow, Teri Victor, Darlene Birdwell, Paul Haas, Anthony Sandoval, Gina Ciavarella, Caroline Saglam, Amy Bird, Keith Beck, Brian Poliquin, David Dominguez, Brittany Tenorio, Harvonya Perkins, Esther San Roman, Paris Bransford, Christy Lowrance, Marcy Broussard, Mary Ellis, Bobbi Skiles, Jessica Hamilton, Kathryn Hall, Diego Olvera, Julee A. Hartwell, Nevien Sorial, Mary Rickman, Kevin Berman, Nirav Mehta, Annie Laborin, Rodger Rothenberger, Sarah Beauvilliers, Kathy Morrell, Michael P. Schachter, Cindy L. Perkins, Elizabeth A. Gordon, Jennifer Lauer, Kim Bichsel, Kelly Oliver, Leslie J. Mellor, Candice Demattia, Jennifer Schomburg, Yenniffer Moreno, Eduardo Mansur-Garza, Lena Rippstein, Lorie Chacon, Andrea Pena, Michelle King, Susan Richardson, Annette Jessop, Nicole Tucker, Whitney Royer, Gilbert Templeton, Ann Moell, Christine Weller, Melissa J. Botts, Gretel Hollon, Elsa Homberg-Pinassi, Paula Forest, Aref Bin Abhulhak, Devona Chun-Furlong, Deborah Harrington, Emily Harlynn, Marjorie Schmitt, Constance Shelsky, Patricia Feldick, Mary Cherrico, Courtney Jagle, Nicholas Warnecke, Debra Myer, Deanna J. Ruder, Albina Underwood, Alan Rauba, George Carr, Barbara Oberhaus, Jessica Vanderfeltz, Mary Jo Stucky-Heil, Dale R. Gibson, Vonnie Fuentes, Kimberly L. Talbot, William C. Simon, Katlyn J. Grimes, Christina R. Wheeler, Cassaundra Shultz, Rhonda A. Metcalf, Jennifer L. Hill, Michelle R. Oliver, Basharat Ahmad, Fouzal Azeem, Abdul Rahim, George H. Freeman, Dawn Bloch, Heather Freeman, Jamie Brown, Sarah Rosbach, Pamela Melander, Nick Taralson, Alex Liu, Katlyn Harms, Mahfouz Michale, Jose Lopez, Maria Revoredo, Shari Edevane, Sarah Shawley, Timothy L. Jackson, Michael J. Oliver, Dina DeSalle, Patricia J. Matlock, Ionna M. Beraun, Heather Hendrix, Garrett Bromley, Ashley Niemerski, Gabby Teran, Sonia Guerrero, Murtaza Marvi, Zehra Palanpurwala, Andrea Torres, Patty Gloyd, Michelle Conger, Aziz Laurent, Olia Nayor, Catalina S. Villanueva, Munira Khambati, Tabetha J. Mumford, Melanie J. Castillo, Taddese Desta, Jerome Robinson, La Shawn Woods, Anita Bahri, Nancy Herrera, Cecilia Casaclang, Jeffrey R. Unger, Geraldine Martinez, Mia K. Moon, Stephen M. Mohaupt, Larry Sandoval, Louisito Valenzuela, Victora Ramirez, Nelly Mata, Veronica Avila, Marisol Patino, Cynthia Montano-Pereira, Omar Barnett, William M. Webster, Lorraine M. Christensen, Leighna Bofman, Melanie Livingston, Stacey Adams, Joseph Hobbs, Leesa Koskela, Mia Katz, Samuel Mujica-Trenche, Franklin Cala, Noreen T. Rana, Jennifer Scarlett, Milagros Cala Anaya, Marsha R. Jones, Kelly D. Hollis, Debbie Roth, Kristin Eads, Tina Watts, Judy Perkins, Alice Arnold, Daniel C. Ginsberg, Denise Quinn, Nicole Cureton, David B. Fittingoff, Mohammed I. Iqbal, Stephen R. White, Edith Sisneros, Michelle Ducca, David Streja, Danny Campos, Jennifer L. Boak, Farzeen Amir, Felice Anderson, James J. Kmetzo, Mary O. Bongarzone, Dawn Scott, Mary Grace De Leon, Cynthia Buda, William Graettinger, Michelle Alex, Erika Hess, James Govoni, Melissa Bartel, Travis L. Monchamp, Julie S. Roach, Sara Gibson, Amy M. Allfrey, Kristen Timpy, Kathy Bott, Karin A. Soucy, Jean Willis, Cecilia A. Valerio, Anusha Chunduri, Rebecca Coker, Nicole Vidrine, Ellen A. Thompson, Mark A. Studeny, Melissa K. Marcum, Tammy S. Monway, Douglas L. Kosmicki, Melissa J. Kelley, Corey M. Godfrey, Susan L. Krenk, Randy R. Holcomb, Deb K. Baehr, Mary K. Trauernicht, David Rowland Lowry, Betty Bondy Herts, Jeanne E Phelps, Jean-Marie Downing, Carol Gamer Dignon, Elisabeth S. Cockrill, Pravinchandra G. Chapla, Diane Fera, Margaret Chang, Patricia Fredette, Tamie Ashby, Renee Bergin, Zebediah A. Stearns, David B. Ware, Rachael M. Boudreaux, Joanna Rodriguez, Robert McKenzie, Amanda Huber, Rebecca Sommers, Heather Rowe, Stacy McLallen, Michale Haynes, Ashley Adamson, Janice Henderson, Lori McClure, Beverly A. Harris, Laura Ference, Sue Meissner-Dengler, Lisa Treasure, Doreen Nicely, Timothy L. Light, Tracey A. Osborn, Kimberly J. Mai, Pablo Vivas, Jose Rios, Dunia Rodriguez, Roger DeRaad, James Walder, Oscar Bailon, Denice Hockett, Debbie Anderson, Kelli McIntosh, Amber Odegard, Andrew Shepherd, Mary Seifert, Laurence Kelley, Rajendra Shetty, Michael Castine, David Brill, Gregory Fisher, Nicole Richmond, Kathleen Gray, Patricia Miller, Charlene Coneys, Yarixa Chanza, Monica Sumoza, Victoria M. Caudill, Kelly D. Harris, Courtney A. Manion, Melody J. Lineberger-Moore, Julie J. Wolfe, Barbara J. Rosen, Patricia DiVito, Janet L. Moffat, Christina Michaelis, Prashant Koshy, Diana Perea, Ghaith Al Yacoub, Stephanie Sadeghi, Thomas D. LeGalley, Rudolph F. Evonich, William J. Jean, Gary M. Friesen, John M. Pap, David A. Pesola, Mark D. Cowan, Kristofer M. Dosh, Dianna Larson, Adele M. Price, Jodi A. Nease, Jane E. Anderson, Lori A. Piggott, Robert Iwaoka, Kevin Sharkey, Edward McMillan, Laurie Lowder, Latisha Morgan, Kyle Davis, Tara Caldwell, Erica Breglio, Jasmine Summers, Rachel Poulimas, Muhammad Zahid, Hamid Syed, Maria Escobar, Jacob Levy, Rahma Warsi, Carol Ma, Puxiao Cen, Kimberly A. Cawthon, Delores B. Barnes, Deanna G. Allen, Margaret L. Warrington, Carol R. Stastny, Robin J. Michaels, Mohamad Saleh, John Sorin, Sunny Rathod, Urakay Juett, Steven Spencer, Aziza Keval, Jill McBride, Shane Young, Catherine Baxter, Carol Rasmussen, Shari L. Coxe, Luis Campos, Shahin Tavackoli, Diana Beckham, Darlynee Sanchez, Karanjit Basrai, Dorian Helms, Erica Clinton, Kasie Smith, Henry Cusnir, Mary Klaus Clark, Madhavagopal V. Cherukuri, Ameta Scarfaru, Stephen D. Nash, Loretta C. Grimm, Anna Grace, Kylie McElheran, Dino Subasic, Zedrick Buhay, Janet Litvinoff, Deepak Shah, Shannon Cervantes, Freda Usher, Farra Yasser, Theodore Trusevich, Ronnie L. Garcia, Jamison Wyatt, Rahul Bose, Holllilyn Miska, Traci Spivey, Amy B. Wren, Katie E. Vance, Lani L. Holman, Pam Gibbons, Elaine Eby, Sandra Shepard, Soratree Charoenthongtrakul, Brett Snodgrass, Mohammed Nazem, Shelly Keteenburg, Prathima Murthy, Frederic Prater, Ashley Rumfelt, Christina Eizensmits, Lisa Iannuzzi, Pourus R. Patel, Clellia Bergamino, Elizabeth McFeaters, Botros Rizk, Emiljia Pflaum, Danny Kalish, Rex Ambatali, Mona Ameli, Delaina Sanguinetti, Rakesh Vaidya, Martinus A.W. Broeders, Dorman Henrikus, Adrianus F.M. Kuijper, Nadea Al-Windy, Michael Magro, Karim Hamraoui, Ismail Aksoy, Guy L.J. Vermeiren, H.W.O. Roeters van Lennep, Gerard Hoedemaker, Johannes Jacobus Remmen, Kjell Bogaard, Dirk van der Heijden, Nicole MJ Knufman, Joost Frederiks, Johannes Willem Louwerenburg, Piet van Rossum, Johannes Milhous, Peter van der Meer, Arno van der Weerdt, Rob Breedveld, Mitran Keijzers, Walter Hermans, Ruud van de Wal, Peter A.G. Zwart, Marc M.J.M. van der Linden, Gerardus Zwiers, Dirk J. Boswijk, Jan Geert Tans, Jacob van Eck, Maarten V. Hessen, Barnabas J.B. Hamer, Stieneke Zoet-Nugteren, Lucien Theunissen, E.A. van Beek, Remco Nijmeijer, Pieter R. Nierop, Gerard Linssen, H.P. Swart, Timo Lenderink, Gerard L. Bartels, Frank den Hartog, Brian J. Berg van den, Wouter van Kempen, Susanne Kentgens, Gloria M. Rojas Lingan, Martinus M. Peeters, Hilligje Keterberg, Melchior Nierman, Annemieke K. den Hollander, Jacqueline Hoogendijk, Christine Voors-Pette, Vicdan Kose, Peter Viergever, Larysa Yena, Viktor Syvolap, Mykola P. Kopytsya, Olga Barna, Svitlana S. Panina, Mykhailo I. Lutai, Oxana V. Shershnyova, Iryna Luzkiv, Larysa S. Bula, Sergii Zotov, Ivan Vyjhovaniuk, Olena Lysunets, Volodymyr I. Koshlia, Nataliya Sydor, Myroslava F. Vayda, Olexiy Ushakov, Mykola Rishko, Viktor P. Shcherbak, Yevgeniya Svyshchenko, Vira Tseluyko, Andriy Yagensky, Viktoriia I. Zolotaikina, Olga Godlevska, Larysa Ivanova, Olena Koval, Olena I. Mitchenko, Galyna Y. Kardash, Yurii S. Rudyk, Mykola Stanislavchuk, Volodymyr Ivanovych Volkov, Olena G. Karlinskaya, Susanna A. Tykhonova, Nikolay Vatutin, Ganna Smirnova, Volodymyr M. Kovalenko, Viktor Lizogub, Denys Sebov, Oleksandr Dyadyk, Svetlana Andrievskaya, Mykola P. Krasko, Alexander N. Parkhomenko, Lidiya Horbach, Iryna G. Kupnovytska, Tetyana Pertseva, Oleksandr Karpenko, Dmytro Reshotko, Svitlana V. Zhurba, Leonid Rudenko, Viktoriia Yu Zharinova, Valerii B. Shatylo, Yuriy I. Karpenko, Mariya A. Orynchak, Tatiana R. Kameneva, Elena Zherlitsina, Diana N. Alpenidze, Grigoriy P. Arutyunov, Elena Baranova, Boris Bart, Dmitriy I. Belenkiy, Svetlana A. Boldueva, Elena A. Demchenko, Vera V. Eltishcheva, Alexander M. Gofman, Boris M. Goloshchekin, Ivan Gennadyevich Gordeev, Nikolay Gratsianskiy, Gadel Kamalov, Niyaz R. Khasanov, Irina M. Kholina, Zhanna D. Kobalava, Elena V. Kobeleva, Alexandra O. Konradi, Victor A. Kostenko, Andrey Dmitrievich Kuimov, Polina Y. Ermakova, Sofia K. Malyutina, Alexey V. Panov, Natalia V. Polezhaeva, Olga Reshetko, Nataliya P. Shilkina, Sergey B. Shustov, Elena A. Smolyarchuk, Raisa I. Stryuk, Elena Yurievnar Solovieva, Andrey V. Susekov, Natalia Vezikova, Svetlana N. Ivanova, Alexander A. Petrov, Vladimir O. Konstantinov, Alina S. Agafina, Victor Gurevich, Konstantin N. Zrazhevskiy, Tatiana V. Supryadkina, Nikita B. Perepech, Vadim L. Arkhipovskiy, Dmitry Yu Butko, Irina A. Zobenko, Olga V. Orlikova, Viktor Mordovin, Olga L. Barbarash, Anastasiya Lebedeva, Vladimir Nosov, Oleg V. Averkov, Elena P. Pavlikova, Yuri B. Karpov, Marina Lvovna Giorgadze, Oleg A. Khrustalev, Mikhail Arkhipov, Tatiana A. Raskina, Julia V. Shilko, Yulia Samoilova, Elena D. Kosmacheva, Sergey V. Nedogoda, Kathleen Coetzee, Lesley J. Burgess, F.C.R. Theron, Iftikhar O. Ebrahim, Gerbrand A. Haasbroek, Maria Pretorius, Julien S. Trokis, Dorothea V. Urbach, Mark J. Abelson, Adrian R. Horak, Aysha E. Badat, Ellen M. Makotoko, Hendrik Du Toit Theron, Padaruth Ramlachan, Clive H. Corbett, Ismail H. Mitha, Hendrik F.M. Nortje, Dirkie J. Jansen van Rensburg, Peter J. Sebastian, F.C.J. Bester, Louis J. van Zyl, Brian L. Rayner, Elżbieta Błach, Magda Dąbrowska, Grzegorz Kania, Agata E. Kelm-Warchol, Leszek P. Kinasz, Janusz Korecki, Mariusz Kruk, Ewa Laskowska-Derlaga, Andrzej Madej, Krzysztof Saminski, Katarzyna Wasilewska, Katarzyna Szymkowiak, Małgorzata Wojciechowska, Natalia Piorowska, Andrzej Dyczek, Rajpal K. Abhaichand, Ramesh B. Byrapaneni, Basavanagowdappa Hattur, Malipeddi Bhaskara Rao, Nitin Ghaisas, Sujit Shankar Kadam, Jugal B. Gupta, Santhosh M. Jayadev, V.A. Kothiwale, Atul Mathur, Vijay Bhaskar, Ravi K. Aluri, Udaya P. Ponangi, Mukesh K. Sarna, Sunil Sathe, Manish K. Sharma, Jilendra Pal Singh Sawhney, Chakrabhavi B. Keshavamurthy, Arun Srinivas, Hemant P. Thacker, A. Sharda, Johny Joseph, Sunil Dwivedi, Viswanathan Mohan, Rajendra K. Premchand, Jacques Bedard, Jean Bergeron, Ronald Collette, David Crowley, Richard Dumas, Sam Henein, Geoff Moran, William F. O’Mahony, Michael O’Mahony, Sammy Chan, Mark H. Sherman, Graham C. Wong, Brian D. Carlson, Milan K. Gupta, David Borts, Sean R. Peterson, Martyn Chilvers, Allan J. Kelly, Jean C. Gregoire, Simon Kouz, Josep Rodés Cabau, Minodora Andor, Mircea Cinteza, Radu Ciudin, Radu I. Cojan, Roxana O. Darabont, Dan-Lucian Dumitrascu, Carmen Fierbinteanu-Braticievici, Ana Gabriela Fruntelata, Constantin Militaru, Bogdon E. Minescu, Doina Luminita Serban, Florin Mitu, Dorel Nastase Melicovici, Ovidiu Petrascu, Octavian M. Pirvu, Cristian Podoleanu, Calin Pop, Rodica-Valentina V. Stanescu-Cioranu, Adrian Tase, Cristina Voiculet, Constantine N. Aroney, Anthony M. Dart, Timothy Davis, Karam Kostner, David N. O’Neal, Peter W. Purnell, Bhuwanendu B. Singh, David R. Sullivan, Peter Thompson, Gerald F. Watts, Adam F. Blenkhorn, John V. Amerena, Rafeeq Samie, Randall Hendriks, Joseph Proietto, Nikolai Petrovsky, Alan Whelan, David Colquhoun, Russell S. Scott, Simon C. Young, Tammy Pegg, Samuel JS Wilson, Andrew W. Hamer, Richard A. Luke, Hamish H. Hart, Gerard P. Devlin, Gerard T. Wilkins, Ian F. Ternouth, Samraj Nandra, Bruno S. Loeprich, Nicole McGrath, Stuart L. Tie, Rob J. Bos, Alexandra Wils, Tamara Jacobs, Erik A. Badings, Lillian A. Ebels-Tuinbeek, Mayke L. Scholten, Esther Bayraktar-Verver, Debby Zweers, Manoek Schiks, Carolien Kalkman, Tineke Tiemes, Jeanette Mulderij, Katarzyna Dabrowska, Wilma Wijnakker, Riny Van de Loo, Jeanne de Graauw, Giny Reijnierse, Mirjam van der Zeijst, Mariska Scholten, Henk R. Hofmeijer, Antoinette van Dijk-van der Zanden, Dineke J. van Belle, Jan Van Es, Gera Van Buchem, Wendy Zijda, Harald Verheij, Linnea Oldenhof-Janssen, Martina Bader, Marije Löwik, Sandra Stuij, Pascal Vantrimpont, Krista van Aken, Karen Hamilton, Han Blömer, Gabriela van Laerhoven, Raymond Tukkie, Maarten Janssen, Gerard Verdel, Jon Funke Küpper, Bob van Vlies, Caroline Kalkman, Joke Vooges, Marinella Vermaas, Rachel Langenberg, Niek Haenen, Frans Smeets, Arko Scheepmaker, Marcel Grosfeld, Ilvy Van Lieshout, Marleen van den Berg, Marian Wittekoek, Petra Mol, Antionette Stapel, Margaretha Sierevogel, Nancy van der Ven, Annemiek Berkelmans, Eric Viergever, Hanneke Kramer, Wilma Engelen, Karen V. Houwelingen, Thierry X. Wildbergh, Arend Mosterd, Coriet Hobé-Rap, Marjan van Doorn, Petra Bunschoten, Michel Freericks, Mireille Emans, Petra Den Boer-Penning, Els Verlek, Christine Freericks, Cornelis de Nooijer, Christina Welten, Ingrid Groenenberg, Claudia van der Horst, Esther Vonk, Geert Tjeerdsma, Gerard M. Jochemsen, Corinne van Daalen, Ingrid Y. Danse, Lucy Kuipers, Anke Pieterse, Antonius Oomen, Daan de Waard, Willem Jan Flu, Zusan Kromhout, Petra Van der Bij, Rob Feld, Brigitta Hessels-Linnemeijer, Rob Lardinois, Jan L. Posma, Zwanette R. Aukema-Wouda, Marjolijn Hendriks-van Woerden, Desiree van Wijk, Driek P. Beelen, Ingrid H. Hendriks, Jan J. Jonker, Stefanie Schipperen, Vicdan Köse, Gloria Rojas, Linda Goedhart, Hanneke van Meurs, Jacqueline Rijssemus, Lindy Swinkels-Diepenmaat, Marloes de Louw-Jansen, Dominique Bierens-Peters, Willem W. van Kempen, Marianne E. Wittekoek, Irmaina Agous, Geert Schenk, Janneke Wittekoek, Kevin Cox, Deborah F. Julia, Jan J.C. Jonker, Roel Janssen, Melchor Nierman, Hilligje Katerberg, Irene van der Haar, Willem W. Van Kempen, Taco van Mesdag, Leyda M. Alvarez Costa, Manon Schensema, Salomé Zweekhorst, Deborah Font Julia, Lauri Hanewinckel, Joyce Olsthoorn, Johan C. Berends, Arie C. van der Spek, Roy van der Berg, Rob J. Timmermann, Ingrid Boerema, Iryna Mudruk, Anna Khrystoforova, Serhii Kyselov, Yaroslava V. Hilova, Pavlo Logoida, Nataliia A. Sanina, Ilona P. Golikova, Olena O. Nemchyna, Ivan I. Isaichikov, Olga B. Potapova, Iurii V. Gura, Larysa Berestetska, Olena O. Kulianda, Oleksandr Tantsura, Oleksandr S. Kulbachuk, Volodymyr Petsentiy, Ihor Biskub, Tetyana Handych, Oleg Lagkuti, Alyna Gagarina, Taras Chendey, Oksana F. Bilonko, Olena Matova, Larysa Bezrodna, Olena Yarynkina, Tetiana Ovdiienko, Volodymyr Randchenko, Maryna Mospan, Olena Butko, Olga Romanenko, Mykhailo Pavelko, Iryna Sichkaruk, Svitlana O. Lazareva, Olena A. Kudryk, Inessa M. Koltsun, Tetiana Magdalits, Sergei Zadorozhniy, Kira Kompaniiets, Andrii Ivanov, Sergiy Romanenko, Pavlo Kaplan, Vadym Y. Romanov, Oksana P. Mykytyuk, Nataliia S. Zaitseva, Sergiy N. Pyvovar, Lyudmyla Burdeuna, Emerita Serdobinska, Tatiana I. Shevchenko, Igor I. Ivanytskyi, Olena V. Khyzhnyak, Nataliya Kalinkina, Olena Keting, Olena Sklyanna, Olga Kashanska, Anna Shevelok, Marina Khristichenko, Ievgenii Y. Titov, Danilenko O. Oleksander, Nataliia S. Polenova, Nataliia Altunina, Viktoriia Kororaieva, Stanislav Zborovskiy, Leonid Kholopov, Iurii Suliman, Lanna Lukashenko, Stanislav Shvaykin, Olexandr M. Glavatskiy, Roman O. Sychov, Roman L. Kulynych, Oleksandr A. Skarzhevskyi, Nataliia V. Dovgan, Marta Horbach, Olga Cherkasova, Iryna Tyshchenko, Liudmyla Todoriuk, Svitlana Kizim, Nataliia Brodi, Oleksandr Ivanko, Olga Garbarchuk, Liudmyla Alieksieieva, Tetiana L. Shandra, Olena Beregova, Larisa An Bodretska, Svitlana S. Naskalova, Ivanna A. Antoniuk-Shcheglova, Olena V. Bondarenko, Natalia G. Andreeva, Iryna I. Vakalyuk, Olha S. Chovganyuk, Nataliya R. Artemenko, Kiril A. Maltsev, Natalia Kalishevich, Natalia G. Kondratyeva, Svetlana A. Nikitina, Maria V. Martjanova, Anna V. Sokolova, Dmitrii O. Dragunov, Olga Kolesnik, Vera Larina, Oxana V. Tsygankova, Maria Ivanova, Illia A. Karpov, Elena M. Aronova, Ekaterina S. Vedernikova, Ekaterina I. Lubinskaya, Taras Y. Burak, Sergey I. Skichko, Farhad Rasulev, Ekaterina B. Soldatova, Alexander L. Fenin, Ilya I. Laptev, Elena E. Luchinkina, Alexandr Akatov, Natalia V. Polenova, Natalia N. Slavina, Irina N. Korovnika, Marina Yu Prochorova, Regina Shakirova, Elena N. Andreicheva, Olga A. Krasnova, Tinatin V. Lobzhanidze, Tatiana B. Dmitrova, Viktoriya V. Stakhiv, Maria I. Pechatnikova, Alexandra V. Panova, Maria Y. Tipikina, Oxana P. Rotar, Nikolay A. Bokovin, Saule K. Karabalieva, Farid Y. Tumarov, Elena V. Vasileva, Natalya Gennadevna Lozhkina, Ekaterina V. Filippova, Alisa I. Sharkaeva, Ekanerina V. Filippova Deilik, Natalia Yu Tolkacheva, Elena N. Domracheva, Andrey N. Ryabikov, Inga T. Abesadze, Marianna Z. Alugishvili, Elena P. Nikolaeva, Nadezda V. Smirnova, Valentina I. Rodionova, Polina V. Dolovstaya, Igor E. Yunonin, Sergey V. Kadin, Tatyana S. Sveklina, Anna V. Bushmanova, Elena L. Barkova, Irina S. Gomova, Yana V. Brytkova, Tatiana B. Ivanova, Marina Y. Zubareva, Inga Skopets, Lybov A. Galashevskaya, Emilia D. Butinskaya, Olga G. Gusarova, Natalia B. Kalishevich, Yana R. Pavlova, Marianna P Serebrenitskaya, Vitalina F. Grygorieva, Gulnara R. Kuchaeva, Inna A. Vasileva, Gulnara I. Ospanova, Yulia V. Vahrusheva, Irina A. Semenova, Irina E.E. Mikhailova, Olga O. Kvasova, Valeria D. Shurygina, Alexey E. Rivin, Alexey O. Savelyev, Alexey A. Savelyev, Olesya O. Milyaeva, Nadezhda N. Lapshina, Ninel A. Lantsova, Pavel V. Alexandrov, Evgeniy A. Orlikov, Alla Falkovskaya, Tatiana Ripp, Sergei Triss, Stanislav Pekarskiy, Sitkova Ekaterina, Evgeniya N. Zhuravleva, Olga Perova, Galina Kovaleva, Liubov Koroleva, Lydia Mishchenko, Boris P. Garshin, Svetlana A. Kutuzova, Lyudmila I. Provotorova, Igor P. Zadvorny, Olga V. Okhapkina, Anatoly O. Khrustalev, Tatiana Suvorova, Elena S. Shaf, Varvara A. Vershinina, Andrey A. Kozulin, Oxana A. Oleynik, Irina Y. Martynova, Natalia V. Kizhvatova, Alla S. Salasyuk, Vera V. Tsoma, Alla A. Ledyaeva, Elena V. Chumachek, S.C. Blignaut, Tersia Y. Alexander, Chano Du Plessis, Thirumani Govender, Samatha M. Du Toit, Leya Motala, Areesh Gassiep, Christina Naude (Smit), Marli Terblanche, Marlien Snoer (Kruger), Berenice Pillay, De Vries Basson, Marisa E. Theron, Bianca Fouche, Mareli E. Coetzee, Pieter Odendall, Frederik H. Van Wijk, Anna-Mari Conradie, Trudie Van der Westhuizen, Carine Tredoux, Mohamed S. Mookdam, Andie J. Van der Merwe, Karin Snyman, Gerda Smal, Yvonne De Jager, Thomas A. Mabin, Annusca King, Lindy L. Henley, Brenda M. Zwane, Jane Robinson, Marinda Karsten, Andonia M. 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Kinasz, Stefan Samborski, Ilona Bartuś, Gramzyna Latocha Korecka, Ewa Gulaj, Jolanta Sopa, Bogusław Derlaga, Marcin Baisiak, Allicia Kowalisko, Edyta Stainszewska-Marasazlek, Bartosz Szafran, Malgorzata Swiatkiewicz, Artur Racewicz, Sławomir Grycel, Jerzy Supronik, Sylwia Walendziuk, Magdalena Tarantowicz, Agata Stasiak, Anna Sidorowicz-Białynicka, Marek Dwojak, Ewa Jaźwińska-Tarnawska, Katarzyna Kupczyk, Kamila Martowska, Kamila Kulon, Katarzyna Gajda, Bivin Wilson, Krithika Velusamy, Swaidha S. Sadhiq, Bhavani Siddeshi, M. Bhanukumar, Abhishek Srivatsav, Madhan Ramesh, Sri Harsha Chalasani, Mini Johnson, Prashanth Gopu, Jeesa George, Sowmya Reddy, Swetha Tessy Thara Eleena, Damodara Rao Kodem, Haritha N. Nakkella, Padma Kumari Mandula, Anjan Kumar Vuriya, Syamala Rajana, Aruna Kale, Tiwari Rajeev, Raina Jain, Vipin Jain, Srilakshmi Mandayam Adhyapak, Lumin Sheeba, Uma C R, Ramya R, Aditya V. Kulkarni, M.S. Ganachari, Ruma Sambrekar, Mohammad Bilal, Kalyan Chakravarthy, Ravi Badhavath, Sravan Kumar, Meenakshi Simhadri, Farooque Salamuddin, Venkat Prasad, Vivek Dwivedi, Sudha Sarna, Tilak Arora, Deepak Chawla, Archana Sathe, Chaware Gayatree, Ajeet Nanda, Ram Avtar, Jyoti Sharma, Vaibhavi P S, Sasirekha D, Deepthi Kobbajji, Ramya Ningappa, Shwetha Shree, Chandrashekar K, Nandini M R, Sowjanya S, Devika I G, Yashaswini N, Sonika G, Rathna L, Priyanka R, Rupal J. Shrimanker, Lakshmi Vinutha Reddy, K. Sumathi, Babitha Devi, Bina N. Naik, Rohini Manjunath, Rajeshwari Ashok, Tony V. Kunjumon, Jesline Thomas, Shaik Samdhani, Kasthuri Selvam, Poongothai Subramani, Nandakumar Parthasarathy, Nirmal K. Bohra, Anvesh K. Gatla, Cheryl Horbatuk, Julie Sills, E B. Davey, Liz Paramonczyk, Olga Racanelli, Sandy Strybosch, Andre Belanger, Jean Palardy, Alicia Schiffrin, Sylvie Gauthier, Norman Kalyniuk, Shawn D. Whatley, Heather Lappala, Grishma Patel, Matthew Reeve, Catherine Moran, Jody Everitt, Teresa Ferrari, Christine Bouffard, Jirir Frohlich, Gordon Francis, John Mancini, Gregory Bondy, Debbie DeAngelis, Patricia Fulton, David W. Blank, Angela Lombardo, Mylène Roy, Jackie Chow, Hyman Fox, William J. Grootendorst, Angela Hutchinson, Sharon M. Chan, Christie Fitzgerald, Lynn Wilkins, Rebecca L. Raymond, Arlene Reyes, Lavoie Marc André, Denis Fortin, Hélène Ouimet, Thanh-Thao Tôn-Nu, Martine Dussureault, Marie-Hélène Blain, Madeleine Roy, Nathalie Kopajko, Chantal Fleury, Karine Maheux, Gabriela Valentina Ciobotaru, Maria C. Constantinescu, Carmen-Lucia Gherghinescu, Ana-Maria Avram, Ioan Manitiu, Aura Sinpetrean, Lucian Pop, Delia Lupu, Radu Usvat, Ana Petrisor, Nicoleta Dumitru, Camelia Moruju, Adelina Gheorghita, Magda V. Mitu, Cosmin Macarie, Ana Maria Pop, Maria-Catalina Diaconu, Iulia Grancea, Mihaela Cosma, Mihaela Crisan, Elizabeth Herron, Paul Nestel, Sally B. Kay, Kaye S. Carter, Imran Badshah, Ashley Makepeace, Jocelyn Drinkwater, Michelle England, Azette Rafei, Kylie Patterson, Alicia Jenkins, Sybil McAuley, Sue M. Kent, Joy E. Vibert, Leonie Perrett, Thomas David, Samantha L. Kaye, Monika O’Connor, Nimalie J. Perera, Nicole T. Lai, Kerry A. Kearins, Christinia Dicamillo, Heather Anderson, Louise Ferguson, Sharon D. Radtke, Charles T. Thamarappillil, Janice M. Boys, Anita K. Long, Toni Shanahan, Michael Nyguyen, Nicole Forrest, Gill Tulloch, Della Greenwell, Sarah L. Price, Aye N. Tint, Priya K. Sumithran, Tamara L. Debreceni, Lisa Walker, Mary Caruana, Kira Edwards, Maria Stathopoulos, Cilla Haywood, Dimitar Sajkov, Sharen Pringle, Anne Tabner, Kathrina Bartolay, Chamindi Abeyratne, Kylie Bragg, Patrick Mulhern, Peter Purnell, Lyn Williams, Jane Hamlyn, Aurelia Connelly, Jan Hoffman, Samantha Bailey, Jane Kerr, Zarnia Morrison, Sarah Maeder, Roberta McEwan, Prasanna Kunasekera, Patrice McGregor, Jo Young, Sharon Berry, Rick Cutfield, Michelle Choe, Catherine McNamara, Narrinder K. Shergill, Petra Crone, Miles G. Williams, Keith Dyson, Diana H. Schmid, Audrey C. Doak, Melissa Spooner, Colin Edwards, Anne Turner, Grainne M. McAnnalley, Raewyn A. Fisher, Fraser B. Hamilton, Denis H. Friedlander, Melissa R. Kirk, Jayne E. Scales, Marguerite A. McLelland, Neelam A. Dalman, Cathy E. Vickers, Carolyn Jackson, Wendy Coleman, Phillip I. Garden, and Wendy F. Arnold

Subjects
Male, medicine.medical_specialty, Rate ratio, Double-Blind Method, Ischemia, Risk Factors, Physiology (medical), Internal medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Coronary Artery Bypass, Stroke, Aged, business.industry, Unstable angina, Hazard ratio, Absolute risk reduction, Middle Aged, medicine.disease, Eicosapentaenoic Acid, Number needed to treat, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Published
2021
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