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Start Over Author "Pella Daniel" Topic myocardial infarction
12 results on '"Pella Daniel"'

1. Pre-heart failure at 2D- and 3D-speckle tracking echocardiography: A comprehensive review.

Author

Singh RB, Sozzi FB, Fedacko J, Hristova K, Fatima G, Pella D, Cornelissen G, Isaza A, Pella D, Singh J, Carugo S, Nanda NC, and Elkilany GEN

Subjects
Diastole, Echocardiography methods, Humans, Heart Failure diagnosis, Myocardial Infarction complications, Ventricular Dysfunction, Left
Abstract

Chronic heart failure (CHF) has different stages and includes pre-HF (PHF), a state of high risk of developing myocardial dysfunction and advanced CHF. Some major behavioral risk factors of PHF might predispose to biological risk factors such as obesity, diabetes mellitus, dyslipidemia, hypertension, myocardial infarction, and cardiomyopathy. These risk factors damage the myocytes leading to fibrosis, apoptosis, cardiac hypertrophy, along with alterations in cardiomyocyte' size and shape. A condition of physiological subcellular remodeling resulting into a pathological state might be developed, conducting to PHF. Both PHF and heart failure (HF) are associated with the activation of phospholipases and protease, mitochondrial dysfunction, oxidative stress and development of intra-cellular free Ca 2+  [Ca 2+ ] i overloading to an elevation in diastolic [Ca 2+ ] i . Simultaneously, cardiac gene expression is activated leading to further molecular, structural and biochemical changes of the myocardium. The sub-cellular remodeling may be intimately involved in the transition of cardiac hypertrophy to heart failure. 2D- and 3D-speckle tracking echocardiography (STE) have been used to quantify regional alterations of longitudinal strain and area strain, through their polar projection, which permits a further assessment of both sites and degrees of myocardial damage. The examination of strain can identify sub-clinical cardiac dysfunction or cardiomyocyte remodeling. During remodeling of the myocardium cardiac strain is attenuated, therefore it is an indicator of disease assessment., (© 2022 Wiley Periodicals LLC.)

Published
2022
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2. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

Author

Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, and Glynn RJ

Subjects
Aged, Anti-Inflammatory Agents adverse effects, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Atherosclerosis blood, C-Reactive Protein metabolism, Cardiovascular Diseases epidemiology, Cardiovascular Diseases mortality, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Incidence, Infections etiology, Interleukin-1beta immunology, Lipids blood, Male, Middle Aged, Myocardial Infarction prevention & control, Neutropenia chemically induced, Secondary Prevention, Stroke prevention & control, Anti-Inflammatory Agents administration & dosage, Antibodies, Monoclonal administration & dosage, Atherosclerosis drug therapy, Interleukin-1beta antagonists & inhibitors, Myocardial Infarction drug therapy
Abstract

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved., Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death., Results: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31)., Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).

Published
2017
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4. Increased concentrations of lipoprotein(a), circadian rhythms and metabolic reactions evoked by acute myocardial infarction, associated with acute reactions in relation to large breakfasts.

Author

Singh RB, Pella D, Sharma JP, Rastogi S, Kartikey K, Goel VK, Sharma R, Neki NS, Kumar A, and Otsuka K

Subjects
Acute Disease, Blood Glucose, Cholesterol blood, Coronary Artery Disease blood, Coronary Artery Disease complications, Coronary Artery Disease diagnosis, Diet methods, Humans, India ethnology, Male, Middle Aged, Myocardial Infarction complications, Myocardial Infarction metabolism, Triglycerides blood, Biotransformation, Circadian Rhythm physiology, Diet adverse effects, Lipoproteins blood, Myocardial Infarction physiopathology
Abstract

Of 54 patients with acute coronary artery disease (CAD) that were included in this study, 41 patients had acute myocardial infarction (AMI), five patients possible MI, four patients unstable angina and the remaining four angina pectoris. The control subjects (n = 85) were randomly selected from the general population of the city of Moradabad of similar age range after exclusion for CAD (n = 9), diabetes (n = 6) and excess intake of trans fatty acids (n = 20). The incidence of lipoprotein(a) excess (> 30 mg/dl; 42.6 vs 24.7%; P < 0.05) and mean concentration of lipoprotein(a) (Lp[a], 6.4 mg/dl, 95% confidence interval: 2.8-10.5; P < 0.05) was significantly greater in the acute CAD group compared with control subjects. Mean total cholesterol and triglycerides were significantly higher and mean nitrite level lower in the study group as compared with the control group.There was a significant greater incidence of cardiac events in the second quarter of the day compared with the fourth quarter. Lp(a), triglycerides, blood glucose, plasma insulin, malondialdehyde, diene conjugates, TBARS and TNF-alpha and IL-6 levels, which were significantly greater during the acute phase, showed a significant decline and serum nitrite and coenzyme Q demonstrated an increase at 4 weeks of follow-up when the acute reactions evoked by MI had been controlled. Large breakfasts were a predisposing factor for cardiac events in the second quarter of the day and it was significantly associated with metabolic reactions. The findings indicate that acute reactions as a result or as circadian rhythms appear to be important in the pathogenesis of AMI-associated complications and that a large breakfast in association with nitrite deficiency may further trigger the circadian rhythms. However, more studies in a larger number of subjects would be necessary in order to confirm our findings.

Published
2004
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5. Mechanisms of acute myocardial infarction study (MAMIS).

Author

Singh RB, Pella D, Neki NS, Chandel JP, Rastogi S, Mori H, Otsuka K, and Gupta P

Subjects
Activity Cycles, Age Factors, Case-Control Studies, Chronobiology Disorders complications, Chronobiology Disorders physiopathology, Climate, Coronary Artery Disease complications, Coronary Artery Disease diagnosis, Coronary Artery Disease drug therapy, Eating physiology, Electrocardiography, Female, Humans, Male, Middle Aged, Myocardial Infarction blood, Myocardial Infarction diagnosis, Neurosecretory Systems chemistry, Neurosecretory Systems metabolism, Neurosecretory Systems physiopathology, Patient Selection, Physical Exertion, Sex Factors, Sleep Deprivation complications, Sleep Deprivation epidemiology, Stress, Psychological complications, Stress, Psychological epidemiology, Sympathetic Nervous System metabolism, Sympathetic Nervous System physiopathology, Myocardial Infarction complications, Precipitating Factors
Abstract

Acute myocardial infarction (AMI) is a highly dynamic event, which is associated with marked neuroendocrinological dysfunction in addition to cardiac damage. The immediate trigger for AMI is not precisely known. Studies conducted by Lown, Braunwald, Halberg, Otsuka and our group have demonstrated a marked increase in sympathetic activity, oxidative stress, and magnesium and potassium deficiency during AMI. Clinical studies have reported an increased incidence of AMI, sudden death and ischemia during first quarter of the day when there is a rapid withdrawal of vagal activity and increase in sympathetic tone. In one case-control study of 202 patients with AMI, there was a significant (P < 0.02) increase in cardiac events in the second quarter of the day compared to other quarters, respectively (16.8%, 41.0%, 13.8%, 28.2% per quarter). This characteristic remained prevalent in both men and women and among patients with and without known AMI (n = 52), diabetes (n = 53) or hypertension (n = 75). Triggers of AMI were noted among 162 (82.2%) of the patients. Neuropsychological mechanisms were observed as follows: emotional stress (45.5%), sleep deprivation (27.7%), cold climate (29.2%), hot climate (24.7%), large meals (47.5%) and physical exertion (31.2%). These triggering factors are known to enhance sympathetic activity and decrease vagal tone, resulting in an increased secretion of plasma cortisol, noradrenaline, aldosterone, angiotension-converting enzyme (ACE), interleukin (IL)-1, -2, -6, -18, and tumor necrosis factor-alpha (TNF-alpha), all of which are are proinflammatory agents. There is also a deficiency in the serum levels of vitamin A, E, and C and magnesium, potassium, melatonin, and IL-10 (an anti-inflammatory agent). In our study, we found a decrease in magnesium, potassium, vitamin A, E, C and beta carotene combined with an increase in thiobarbituric acid-reactive substances (TBARS), MDA and diene conjugates, TNF-alpha and IL-6, all of which are indicators of oxidative damage and proinflammatory activity, respectively.

Published
2004
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6. Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction.

Author

Singh RB, Neki NS, Kartikey K, Pella D, Kumar A, Niaz MA, and Thakur AS

Subjects
Adult, Antioxidants therapeutic use, Arteriosclerosis etiology, Cholesterol, HDL blood, Coenzymes, Double-Blind Method, Female, Humans, Male, Malondialdehyde blood, Middle Aged, Myocardial Infarction blood, Myocardial Infarction complications, Risk Factors, Thiobarbituric Acid Reactive Substances metabolism, Vitamin E blood, Arteriosclerosis prevention & control, Myocardial Infarction drug therapy, Ubiquinone analogs & derivatives, Ubiquinone therapeutic use
Abstract

In a randomized, double-blind, controlled trial, the effects of oral treatment with coenzyme Q10 (CoQ10, 120 mg/day), a bioenergetic and antioxidant cytoprotective agent, were compared for 1 year, on the risk factors of atherosclerosis, in 73 (CoQ, group A) and 71 (B vitamin group B) patients after acute myocardial infarction (AMI). After 1 year, total cardiac events (24.6 vs. 45.0%, p < 0.02) including non-fatal infarction (13.7 vs. 25.3%, p < 0.05) and cardiac deaths were significantly lower in the intervention group compared to control group. The extent of cardiac disease, elevation in cardiac enzymes, left ventricular enlargement, previous coronary artery disease and elapsed time from symptom onset to infarction at entry to study showed no significant differences between the two groups. Plasma level of vitamin E (32.4 +/- 4.3 vs. 22.1 +/- 3.6 umol/L) and high density lipoprotein cholesterol (1.26 +/- 0.43 vs. 1.12 +/- 0.32 mmol/L) showed significant (p < 0.05) increase whereas thiobarbituric acid reactive substances, malondialdehyde (1.9 + 0.31 vs. 3.1 + 0.32 pmol/L) and diene conjugates showed significant reduction respectively in the CoQ group compared to control group. Approximately half of the patients in each group (n = 36 vs. 31) were receiving lovastatin (10 mg/day) and both groups had a significant reduction in total and low density lipoprotein cholesterol compared to baseline levels. It is possible that treatment with CoQ10 in patients with recent MI may be beneficial in patients with high risk of atherothrombosis, despite optimal lipid lowering therapy during a follow-up of 1 year. Adverse effect of treatments showed that fatigue (40.8 vs. 6.8%, p < 0.01) was more common in the control group than CoQ group.

Published
2003

7. CoQ10 in the Treatment of Heart and Vascular Disease

Author

Singh, Ram B., Kartikey, Kumar, Moshiri, Mahmood, Neki, Narankar S., Pella, Daniel, Rastogi, Shanti S., Srivastav, Shiv S. L., Krishna, Atul, Dhalla, Naranjan S., editor, Chockalingam, Arun, editor, Berkowitz, H. Ivan, editor, and Singal, Pawan K., editor

Published
2003
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9. Effects of alirocumab on types of myocardial infarction : insights from the ODYSSEY OUTCOMES trial

Author

White, Harvey D., Steg, Ph. Gabriel, Harrington, Robert A., Endsley, Patricia, Gusi Tragant, Gabriel, Benedicto, Amparo, Gonzalez-Juanatey, Carlos, Camprubi Potau, Mercedes, Plaza Perez, Ignacio, Moris De La Tassa, Cesar, Loma-Osorio Rincon, Pablo, Balaguer Recena, Javier, M Escudier, Juan, Constantine, Godwin, Eppinger, Arleen, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Fernando, Nimali, Jayawardena, Jayanthimala, Santharaj, Wijeyasingam, Ekanayaka, Ruvan, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Hess, Connie Ng, Sirisena, Thilak, Rajapaksha, Ajantha, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagstrom, Emil, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hlatky, Mark A., Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjorn, Moccetti, Tiziano, Mueller, Christian, Mach, Francois, Jordan, Joseph Dedrick, Binder, Ronald, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I. Chang, Lin, Wei Hsiang, Knowles, Joshua W., Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Kolls, Bradley J., Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Kong, David F., Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Leonardi, Sergio, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Lillis, Linda, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Jukema, J. Wouter, Lopes, Renato D., Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-Ki, Maron, David J., Iqbal, Syed M. R., Subkovas, Eduardas, Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Kurian, John, Levy, Terry, Marcus, Jill, Barr, Craig, Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Mathur, Anthony, Brodison, Adrian, Oliver, Richard, Mudawi, Telal, Reynolds, Timothy, Mathews, Robin, Sharman, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Y. H., Halcox, Julian, Vardi, Gil, Baldari, Duccio, Brabham, David, Treasure, Charles, Dahl, Charles, Mehta, Rajendra H., Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Mentz, Robert J., Rogers, William Jr., Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Khan, Misal, Shoukfeh, Mohammad, Dagher, Georges, Lieber, Ira, Kumar, Priya, East, Cara, Moreira, Humberto Graner, Krichmar, Perry, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Suh, David, Arif, Imran, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, Patel, Chetan B., El-Ahdab, Fadi, Nelson, William, Harris, Barry, Cohen, Steven, Carter, Luther, Sabatino, Kenneth, Haddad, Tariq, Malik, Amir, Rao, Sunder, Mulkay, Angel, Pereira, Sabrina Bernardez, Jovin, Ion, Klancke, Kim, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds, George, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Perkins, Lynn, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Singh, Narendra, Shah, Anil V., Povsic, Thomas J., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Keating, Friederike, Kondo, Nicholas I., Shetty, Sanjay, Waider, Winfried, Puymirat, Etienne, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Izzo, Mark, Kumar, Anil, Hattler, Brack, Link, Chad, Bortnick, Anna, Kinzfogl, George, Jones, William Schuyler, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Abbas, Jalal, White, Matthew, Ranadive, Nandkishore, Shah, Bimal R., Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Sherwood, Matthew W., Horwitz, Phillip, Jafar, Zubair, Mcgarvey, Joseph Jr., Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Stringfellow, Kenya, Herzog, William Jr., Lindsey, Jason, Nowins, Rosemary, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, May, Wade, Galski, Thomas, Chu, Alan, Sujjavanich, Darin, Mody, Freny, Hodes, Zachary, Fairlamb, James, Lambert, Charles Jr., Raisinghani, Ajit, Abbate, Antonio, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Toma, Mustafa, Park, Hyeun (Tom, Vidovich, Mladen, Knutson, Thomas, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Kimmelstiel, Carey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Trotter, Charlene, Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Fisher, Daniel, Xenakis, Mark, van Diepen, Sean F. P., Perlmutter, Neal, Bhagwat, Ravi, Strader, James Jr., Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Claxton, Edmund Jr., Berk, Martin, Rossi, Peter, Mahaffey, Kenneth W., Wilson, Matthew D., Joshi, Parag, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Yan, Andrew Tze-Kay, Pancholy, Samir, Ray, Michael, Farrar, Michael, Pollock, Stewart, French, William J., Diamantis, Steve, Gimple, Lawrence, Schwartz, Steven, Pereira, Edward, Spriggs, Douglas, Schiavi, Lilia B., Strain, Janet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, Nager, Paul, Garrido, Marcelo, Vohra, Rakesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Sporn, Daniel, Eisenberg, Steven, Alvarisqueta, Andres F., Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. Sandy, Jain, Diwakar, Zainea, Mark, Bayron, Carlos, Karlsberg, Ronald, Lui, Henry, Sassone, Sonia A., Keen, William, Westerhausen, Donald Jr., Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William Jr., Chang, Mark, Gilbert, John M., Chalavarya, Gopal, Eaton, Charles, Bordonava, Anselmo P., Schmedtje, John F. Jr., Christenson, Stuart, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Conrad, Gary, Kotha, Purushotham, Love, Michael, Alves De Lima, Alberto E., Giesler, Gregory, Rubenstein, Howard, Akright, Laura, Schifferdecker, Branislav, Krawczyk, Justine, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Schmidberg, Jorge M., Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Duronto, Ernesto A., Moryusef, Angele, Caruso, Orlando C., Novaretto, Leonardo P., Angel Hominal, Miguel, Montana, Oscar R., Caccavo, Alberto, Gomez Vilamajo, Oscar A., Lorenzatti, Alberto J., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Pordy, Robert, Caime, Guillermo D., Amuchastegui, Marcos, Codutti, Oscar R., Jure, Horacio O., Bono, Julio O. E., Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Roe, Matthew T., 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., Nani, Sebastian, Blumberg, Eduardo D. S., Colombo, Hugo R., Liberman, Alberto, Luciardi, Hector L., Waisman, Gabriel D., Berli, Mario A., Garcia Duran, Ruben O., Cestari, Horacio G., Luquez, Hugo A., Giordano, Jorge A., Tricoci, Pierluigi, Saavedra, Silvia S., Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris L. S., Shaw, James, Arstall, Margaret A., Horowitz, John, Rogers, James F., Colquhoun, David, Zeiher, Andreas M., Flores, Romulo E. Oqueli, Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Coverdale, Steven G. M., Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Zweiker, Robert, Szarek, Michael, Schwartz, Gregory G., Hoppe, Uta, Huber, Kurt, Berger, Rudolf, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Vrolix, Mathias C. M., Aylward, Philip E., De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Drexel, Heinz, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Durak-Nalbantic, Azra, Vulic, Dusko, Muslibegovic, Adis, Sinnaeve, Peter, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Rech, Rafael, Rossi, Paulo R. F., Cerqueira, Maria Jose A. G., Duda, Norberto, Dilic, Mirza, Kalil, Renato, Kormann, Adrian, Abrantes, Jose Antonio M., Pimentel Filho, Pedro, Soggia, Ana Priscila, de Santos, Mayler O. N., Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Fernandes Manenti, Euler Roberto F., Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro G. M. de B., Silveira, Jose A., Saporito, Wladimir, Gotcheva, Nina N., Marin Neto, Jose A., Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar K. S. B., Reis, Helder J. 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W., Turi, Tibor, Merkely, Bela, Alings, Marco, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, Andras, Edes, Istvan, Muller, Gabor, Horvath, Ivan, Kapin, Tibor, Falukozy, Jozsef, Halvorsen, Sigrun, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Proddutur, Naveen Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Correa Flores, Roger M., Sinha, Dhurjati, Patil, Sachin N., Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Sy, Rody G., Pothineni, Ramesh B., Monteiro, Minguel R., Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Aparna, Chopra, Vijay K., Goyal, Naresh K., Budaj, Andrzej, Shinde, Rituparna, Manakshe, Gajendra V., Patki, Nitin, Sethi, Sumeet, Munusamy, Vengatesh, Karna, Sunil, Adhyapak, Srilakshmi, Pandurangi, Ulhas, Mathur, Rishabh, Kalashetti, Suhas, Edelberg, Jay M., Morais, Joao, Bhagwat, Ajit, Raghuraman, Bagirath, Yerra, Shiv Kumar, Bhansali, Prasant, Borse, Rohidas, Das, Srihari, Abdullakutty, Jabir, Saathe, Shireesh, Palimkar, Priya, Atar, Shaul, Dorobantu, Maria, Shechter, Michael, Mosseri, Morris, Arbel, Yaron, Lotan, Chaim, Rosenschein, Uri, Katz, Amos, Henkin, Yaakov, Francis, Adi, Klutstein, Marc, Nikolsky, Eugenia, Karpov, Yuri, Turgeman, Yoav, Halabi, Majdi, Kornowski, Ran, Jonas, Michael, Amir, Offer, Rozenman, Yoseph, Fuchs, Shmuel, Hussein, Osamah, Gavish, Dov, Vered, Zvi, Ristic, Arsen D., Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Piovaccari, Giancarlo, De Pellegrin, Annamaria, Guardigli, Gabriele, Licciardello, Giovanni, Auguadro, Carla, Cuccia, Claudio, Salvioni, Alessandro, Chua, Terrance, Musumeci, Giuseppe, Calabro, Paolo, Novo, Salvatore, Faggiano, Pompilio, De Cesare, Nicoletta B., Berti, Sergio, Cavallini, Claudio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Murin, Jan, Piatti, Piermarco, Palvarini, Michela, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, Filardi, Pasquale Perrone, Ferratini, Maurizio, Dai, Kazuoki, Kamiya, Haruo, Ando, Kenji, Fras, Zlatko, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Hirooka, Keiji, Dalby, Anthony J., Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Shimizu, Masatoshi, Katsuda, Yousuke, Tunon, Jose, Wada, Atsuyuki, Shinke, Toshiro, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Sakamoto, Tomohiro, Furukawa, Yutaka, Sugino, Hiroshi, Mano, Toshiaki, Utsu, Noriaki, de Silva, H. Asita, Ito, Kashima, Haraguchi, Takuya, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Yoon, Jung Han, Park, Hun Sik, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Hong, Taekjong, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Muller, Christian, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Kibarskis, Aleksandras, Kubilius, Raimondas, Bojovski, Stojko, Lozance, Nensi, Kjovkaroski, Aleksandar, Doncovska, Snezana, Ong, Tiong Kiam, Kasim, Sazzli, Maskon, Oteh, Kandasamy, Balachandran, Liew, Houng B., Mohamed, Wan Mohd Izani Wan, Garcia Castillo, Armando, Carrillo Calvillo, Jorge, Fajardo Campos, Pedro, Nunez Fragoso, Juan Carlos, Bayram Llamas, Edmundo Alfredo, Alcocer Gamba, Marco Antonio, Carranza Madrigal, Jaime, Gonzalez Salas, Luis Gerardo, Lopez Rosas, Enrique, Gonzalez Diaz, Belinda, Salcido Vazquez, Eduardo, Nacoud Ackar, Alfredo, Llamas Esperon, Guillermo Antonio, Martinez Sanchez, Carlos Rodolfo, Guerrero De Leon, Maria, Suarez Otero, Rodrigo, Fanghanel Salmon, Guillermo, Perez Rios, Jesus Antonio, Garza Ruiz, Jose Angel, Breedveld, Robert W., Hoogslag, Pieter A. M., Suryapranata, Harry, Oomen, Antonius, Wiersma, Jacobijne J., Van Der Wal, Ruud M. A., Van Huysduynen-Monraats, Pascalle S. Hooft, Karalis, Ioannis, Verdel, Gerardus J. E., Brueren, Bart R. G., Troquay, Roland P. Th, Viergever, Eric P., Al-Windy, Nadea Y. Y., Bartels, Gerard L., Ray, Kausik K., Cornel, Jan H., Hermans, Walter R. M., Herrman, Johannes P. R., Bos, Robert J., Groutars, Reginald G. E. J., Van Der Zwaan, Coenraad C., Kaplan, Refik, Ronner, Eelko, Groenemeijer, Bjorn E., Bronzwaer, Patrick N. A., Liem, Anho A. H., Rensing, Bernard J. W. M., Bokern, Marcel J. J. A., Nijmeijer, Remco, Hersbach, Ferry M. R. J., Willems, Frank F., Gosselink, Antonius T. M., Elliott, John, Wilkins, Gerard, Fisher, Raewyn, Vogel, Robert, Scott, Douglas, Hart, Hamish, Stewart, Ralph, Harding, Scott, Ternouth, Ian, Fisher, Nicholas, Aitken, Denise, Anscombe, Russell, Tomala, Tadeusz, Nygard, Ottar, Chaitman, Bernard, Sparby, Jon Arne, Andersen, Kjell, Gullestad, Lars, Jortveit, Jarle, Munk, Peter S., Hurtig, Ulf, Ticona, Jorge R. Calderon, Velasquez, Julio R. Durand, Miguel, Sandra A. Negron, Perez, Enrique S. Sanabria, Kelsey, Sheryl F., Chambilla, Jesus M. Carrion, Ayala, Carlos A. Chavez, Leon, Reynaldo P. Castillo, Gonzales, Rolando J. Vargas, Zuniga, Jose D. Hernandez, Cosavalente, Luis A. Camacho, Mannucci, Jorge E. Bravo, Navarro, Nassip C. Llerena, Concha, Yudy M. Roldan, Chavez, Victor E. Rodriguez, Olsson, Anders G., Hernandez, Henry A. Anchante, Nunez, Carlos A. Zea, Ferrolino, Arthur, Sy, Rosa Allyn G., Tirador, Louie, Matiga, Generoso, Coching, Raul Martin, Bernan, Alisa, Rogelio, Gregorio, Morales, Dante D., Rouleau, Jean-Lucien, Tan, Edgar, Wlodarczak, Adrian, Jaworska, Krystyna, Skonieczny, Grzegorz, Pawlowicz, Lidia, Wojewoda, Pawel, Busz-Papiez, Benita, Bednarski, Janusz, Goch, Aleksander, Staneta, Pawel, Simoons, Maarten L., Dulak, Elzbieta, Saminski, Krzysztof, Krasowski, Wlodzimierz, Sudnik, Wanda, Zurakowski, Aleksander, Skorski, Marcin, Lysek, Roman, Miklaszewicz, Beata, Kubica, Jacek, Lipko, Jan Andrzej, Alexander, Karen, Kostarska-Srokosz, Edyta, Piepiorka, Marek, Drzewiecka, Anna, Sciborski, Ryszard, Stasiewski, Arkadiusz, Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Meloni, Chiara, Mirek-Bryniarska, Ewa, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Monteiro, Pedro, Bastos, Jose Mesquita, Pereira, Helder H., Martins, Dinis, Seixo, Filipe, Rosenson, Robert, Mendonca, Carlos, Botelho, Ana, Minescu, Bogdan, Istratoaie, Octavian, Tesloianu, Dan N., Cristian, Gabriel, Podoleanu, Cristian G. C., Constantinescu, Mircea C. A., Bengus, Cristina M., Militaru, Constantin, Sijbrands, Eric J. G., Rosu, Doina, Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Lyamina, Nadezhda, Alexander, John H., Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Shalaev, Sergey, Khaisheva, Larisa, Chizhov, Petr, Armaganijan, Luciana, Viktorova, Inna, Osokina, Natalya, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Hanotin, Corinne, Bagai, Akshay, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Baranova, Elena, Shogenov, Zaur, Kosmachova, Elena, Bahit, Maria Cecilia, Karpov, Yuriy, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Brennan, J. Matthew, Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Putnikovic, Biljana, Stankovic, Aleksandar, Arandjelovic, Aleksandra, Radovanovic, Slavica, Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Clifton, Shaun, Dodic, Slobodan, Dimkovic, Sinisa, Poh, Kian-Keong, Ong, Hean Yee, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, DeVore, Adam D., Mazur, Juraj, Majercak, Ivan, Dzupina, Andrej, Fazekas, Frantisek, Gonsorcik, Jozef, Bugan, Viliam, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Smik, Rudolf, Deloatch, Shalonda, Dukat, Andrej, Zuran, Ivan, Oklukar, Janez, Suligoj, Natasa Cernic, Cevc, Matija, Lipar, Luka, Cyster, Henry P., Ranjith, Naresh, Corbett, Clive, Bayat, Junaid, Dickey, Sheila, Makotoko, Ellen Makoali, Kapp, Ilse E., Basson, Matthys M. de V., Lottering, Hanlie, Van Zyl, Louis J., Sebastian, Peter J., Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Dombrowski, Keith, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Reuter, Helmuth, Moodley, Rajendran, Vida, Manuel, Cequier Fillat, Angel R., Bodi Peris, Vicente, Fuentes Jimenez, Francisco, Ducrocq, Gregory, Marin, Francisco, Cruz Fernandez, Jose M., Gil-Extremera, Blas, Worner Diz, Fernando, Garcia-Dorado, David, Iniguez, Andres, Tunon Fernandez, Jose, Gonzalez-Juanatey, Jose R., Fernandez Portales, Javier, Civeira Murillo, Fernando, Eapen, Zubin, Matas Pericas, Laia, Luis Zamorano, Jose, De Mora Martin, Manuel, Bruguera Cortada, Jordi, Alonso Martin, Joaquin J., De Berrazueta Fernandez, Jose R., Diaz Fernandez, Jose Francisco, Garcia Lledo, Jose Alberto, Cosin Sales, Juan, Botas Rodriguez, Javier, Sinnaeve, Peter, İÜC, Ege Üniversitesi, Cardiology, Internal Medicine, and ODYSSEY OUTCOMES Investigators

Subjects
Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, Cardiac & Cardiovascular Systems, Myocardial Infarction, UNIVERSAL DEFINITION, 030204 cardiovascular system & hematology, THERAPY, DISEASE, chemistry.chemical_compound, 0302 clinical medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, 1102 Cardiorespiratory Medicine and Haematology, Oxygen supply, Kardiologi, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, CHOLESTEROL, Middle Aged, MI types, Cardiology, LDL Cholesterol Lipoproteins, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.medical_specialty, ODYSSEY OUTCOMES Investigators, Antibodies, Monoclonal, Humanized, CLASSIFICATION, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Humans, ddc:610, Alirocumab, Mortality, Prevention, METAANALYSIS, Aged, Science & Technology, Task force, Cholesterol, business.industry, EVOLOCUMAB, 1103 Clinical Sciences, Cholesterol, LDL, medicine.disease, Evolocumab, chemistry, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, Human medicine, business
Abstract

Gislason, Gunnar H/0000-0002-0548-402X; Malynovsky, Yaroslav V/0000-0002-9118-1104; Bhatt, Deepak L./0000-0002-1278-6245; Nikolaev, Konstantin/0000-0003-4601-6203; Sherwood, Matthew/0000-0002-4305-5883; Chumakova, Galina A/0000-0002-2810-6531; Raffel, Owen C/0000-0001-5470-7050; Leonardi, Sergio/0000-0002-4800-6132; Tse, Hung Fat/0000-0002-9578-7808; Reshetko, Olga/0000-0003-3107-7636; Pereira, Helder/0000-0001-8656-4883; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Ersanli, Murat/0000-0003-1847-3087; Muenzel, Thomas/0000-0001-5503-4150; Sandhu, Manjinder/0000-0003-2538-2079; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Manakshe, Gajendra/0000-0002-4983-4271; Abbate, Antonio/0000-0002-1930-785X; STEG, Philippe Gabriel/0000-0001-6896-2941; Szarek, Michael/0000-0002-0046-0264; Bittner, Vera/0000-0001-9456-850X; Goodman, Shaun/0000-0001-8068-2440, WOS: 000490154300015, PubMed: 31121022, Aims the third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (>= 1.8 mmol/L) despite intensive statin therapy. in a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI. Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. the data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types., Sanofi; Regeneron Pharmaceuticals, Supported by Sanofi and Regeneron Pharmaceuticals.

Published
2019

10. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

Author

Schwartz, G. G., Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., Harrington, R. A., Jukema, J. W., Lecorps, G., Mahaffey, K. W., Moryusef, A., Pordy, R., Quintero, K., Roe, M. T., Sasiela, W. J., Tamby, J. -F., Tricoci, P., White, H. D., Zeiher, A. M., Aylward, Philip E., Drexel, Heinz, Sinnaeve, Peter, Dilic, Mirza, Lopes, Renato D., Gotcheva, Nina N., Goodman, Shaun G., Prieto, Juan-Carlos, Yong, Huo, Lopez-Jaramillo, Patricio, Pecin, Ivan, Reiner, Zeljko, Ostadal, Petr, Poulsen, Steen Hvitfeldt, Viigimaa, Margus, Nieminen, Markku S., Danchin, Nicolas, Chumburidze, Vakhtang, Marx, Nikolaus, Liberopoulos, Evangelos, Montenegro Valdovinos, Pablo Carlos, Tse, Hung-Fat, Kiss, Robert Gabor, Xavier, Denis, Zahger, Doron, Valgimigli, Marco, Kimura, Takeshi, Kim, Hyo Soo, Kim, Sang-Hyun, Erglis, Andrejs, Laucevicius, Aleksandras, Kedev, Sasko, Yusoff, Khalid, Ramos Lopez, Gabriel Arturo, Alings, Marco, Halvorsen, Sigrun, Correa Flores, Roger M., Sy, Rody G., Budaj, Andrzej, Morais, Joao, Dorobantu, Maria, Karpov, Yuri, Ristic, Arsen D., Chua, Terrance, Murin, Jan, Fras, Zlatko, Dalby, Anthony J., Tunon, Jose, de Silva, H. 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Matthew, Clifton, Shaun, DeVore, Adam D., Deloatch, Shalonda, Dickey, Sheila, Dombrowski, Keith, Ducrocq, Gregory, Eapen, Zubin, Endsley, Patricia, Eppinger, Arleen, Hess, Connie Ng, Hlatky, Mark A., Jordan, Joseph Dedrick, Knowles, Joshua W., Kolls, Bradley J., Kong, David F., Leonardi, Sergio, Lillis, Linda, Maron, David J., Marcus, Jill, Mathews, Robin, Mehta, Rajendra H., Mentz, Robert J., Moreira, Humberto Graner, Patel, Chetan B., Pereira, Sabrina Bernardez, Perkins, Lynn, Povsic, Thomas J., Puymirat, Etienne, Jones, William Schuyler, Shah, Bimal R., Sherwood, Matthew W., Stringfellow, Kenya, Sujjavanich, Darin, Toma, Mustafa, Trotter, Charlene, van Diepen, Sean F. P., Wilson, Matthew D., Yan, Andrew Tze-Kay, Schiavi, Lilia B., Garrido, Marcelo, Alvarisqueta, Andres F., Sassone, Sonia A., Bordonava, Anselmo P., Alves De Lima, Alberto E., Schmidberg, Jorge M., Duronto, Ernesto A., Caruso, Orlando C., Novaretto, Leonardo P., Angel Hominal, Miguel, Montana, Oscar R., Caccavo, Alberto, Gomez Vilamajo, Oscar A., Lorenzatti, Alberto J., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Codutti, Oscar R., Jure, Horacio O., Bono, Julio O. E., Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, 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., Nani, Sebastian, Blumberg, Eduardo D. S., Colombo, Hugo R., Liberman, Alberto, 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., Collins, Nicholas, Soward, Allan, Hii, Chris L. S., Shaw, James, Arstall, Margaret A., Horowitz, John, Rogers, James F., Colquhoun, David, Flores, Romulo E. Oqueli, Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Coverdale, Steven G. M., Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Zweiker, Robert, Hoppe, Uta, Huber, Kurt, Berger, Rudolf, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Vrolix, Mathias C. M., De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc J., Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Durak-Nalbantic, Azra, Vulic, Dusko, Muslibegovic, Adis, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Rech, Rafael, Rossi, Paulo R. F., Cerqueira, Maria Jose A. G., Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, Jose Antonio M., Pimentel Filho, Pedro, Soggia, Ana Priscila, de Santos, Mayler O. N., Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Fernandes Manenti, Euler Roberto F., Precoma, Dalton B., Moura Jorge, Jose C., de Silva, Pedro G. M. 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Luna, Lopez, Rodrigo Botero, De Salazar, Dora I. Molina, Bonfanti, Alberto J. Cadena, Higuera, Juan Diego, Silva, Sandra I. Barrera, Lozada, Henry J. Garcia, Arroyo, Julian A. Coronel, Mendoza, Jose L. Accini, Ruiz, Ricardo L. Fernandez, Fernandez, Angela M., Jatin, Fernando G. Manzur, Herazo, Aristides Sotomayor, Parada, Jeffrey Castellanos, Triana, Miguel A. Urina, Spinar, Jindrich, Horak, David, Stasek, Josef, Alan, David, Machova, Vilma, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Marusincova, Ivana, Svab, Premysl, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Raungaard, Bent, Clemmensen, Peter, Bang, Lia E., May, Ole, Bottcher, Morten, Hove, Jens D., Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Jeppesen, Jorgen, Nielsen, Tonny, Kristensen, Kjeld S., Walichiewicz, Piotr Maria, Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopold, sllar, Martsin, Kaja, Taskinen, Marja-Riitta, Porthan, Kimmo, Airaksinen, Juhani K., Juonala, Markus, Kiviniemi, Tuomas, Vikman, Saila, Posio, Pirjo, Taurio, Jyrki, Huikuri, Heikki, Kaikkonen, Kari, Coste, Pierre, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Steg, Philippe Gabriel, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jerome, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Lefevre, Thierry, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Rauch-Kroehnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Marx, Roger, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Gielen, Stephan, Winkelmann, Bernhard, Behrens, Steffen, Sydow, Karsten, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Boecker, Dirk, Braun-Dullaeus, Ruediger, Toursarkissian, Nicole, Jeserich, Michael, Weissbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Voeller, Heinz, Waltenberger, Johannes, Natour, Mohammed, Steiner, Stephan, Heidenreich, Lothar, Gremmler, Uwe, Killat, Holger, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Skoumas, Ioannis, Athyros, Vasilios, Parthenakis, P. I. Frangkiskos, Hahalis, P. I. Georgios, Lekakis, John, Xatzitolios, Apostolos, Fausto Ovando, Sergio R., Arango Benecke, Juan L., Rodriguez De Leon, Edgar R., Yan, Bryan P. Y., Siu, David C. W., Turi, Tibor, Merkely, Bela, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, Andras, Edes, Istvan, Muller, Gabor, Horvath, Ivan, Kapin, Tibor, Falukozy, Jozsef, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Proddutur, Naveen Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N., Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B., Monteiro, Minguel R., Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Aparna, Chopra, Vijay K., Goyal, Naresh K., Shinde, Rituparna, Manakshe, Gajendra V., Patki, Nitin, Sethi, Sumeet, Munusamy, Vengatesh, Karna, Sunil, Adhyapak, Srilakshmi, Pandurangi, Ulhas, Mathur, Rishabh, Kalashetti, Suhas, Bhagwat, Ajit, Raghuraman, Bagirath, Yerra, Shiv Kumar, Bhansali, Prasant, Borse, Rohidas, Das, Srihari, Abdullakutty, Jabir, Saathe, Shireesh, Palimkar, Priya, Atar, Shaul, Shechter, Michael, Mosseri, Morris, Arbel, Yaron, Lotan, Chaim, Rosenschein, Uri, Katz, Amos, Henkin, Yaakov, Francis, Adi, Klutstein, Marc, Nikolsky, Eugenia, Turgeman, Yoav, Halabi, Majdi, Kornowski, Ran, Jonas, Michael, Amir, Offer, Rozenman, Yoseph, Fuchs, Shmuel, Hussein, Osamah, Gavish, Dov, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Piovaccari, Giancarlo, De Pellegrin, Annamaria, Guardigli, Gabriele, Licciardello, Giovanni, Auguadro, Carla, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Calabro, Paolo, Novo, Salvatore, Faggiano, Pompilio, De Cesare, Nicoletta B., Berti, Sergio, Cavallini, Claudio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, Piermarco, Palvarini, Michela, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, Filardi, Pasquale Perrone, Ferratini, Maurizio, Dai, Kazuoki, Kamiya, Haruo, Ando, Kenji, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Hirooka, Keiji, Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Shimizu, Masatoshi, Katsuda, Yousuke, Wada, Atsuyuki, Shinke, Toshiro, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Sakamoto, Tomohiro, Furukawa, Yutaka, Sugino, Hiroshi, Mano, Toshiaki, Utsu, Noriaki, Ito, Kashima, Haraguchi, Takuya, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Yoon, Jung Han, Park, Hun Sik, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Hong, Taekjong, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Kibarskis, Aleksandras, Kubilius, Raimondas, Bojovski, Stojko, Lozance, Nensi, Kjovkaroski, Aleksandar, Doncovska, Snezana, Ong, Tiong Kiam, Kasim, Sazzli, Maskon, Oteh, Kandasamy, Balachandran, Liew, Houng B., Mohamed, Wan Mohd Izani Wan, Garcia Castillo, Armando, Carrillo Calvillo, Jorge, Fajardo Campos, Pedro, Nunez Fragoso, Juan Carlos, Bayram Llamas, Edmundo Alfredo, Alcocer Gamba, Marco Antonio, Carranza Madrigal, Jaime, Gonzalez Salas, Luis Gerardo, Lopez Rosas, Enrique, Gonzalez Diaz, Belinda, Salcido Vazquez, Eduardo, Nacoud Ackar, Alfredo, Llamas Esperon, Guillermo Antonio, Martinez Sanchez, Carlos Rodolfo, Guerrero De Leon, Maria, Suarez Otero, Rodrigo, Fanghanel Salmon, Guillermo, Perez Rios, Jesus Antonio, Garza Ruiz, Jose Angel, Breedveld, Robert W., Hoogslag, Pieter A. M., Suryapranata, Harry, Oomen, Antonius, Wiersma, Jacobijne J., Van Der Wal, Ruud M. A., Van Huysduynen-Monraats, Pascalle S. Hooft, Karalis, Ioannis, Verdel, Gerardus J. E., Brueren, Bart R. G., Troquay, Roland P. Th, Viergever, Eric P., Al-Windy, Nadea Y. Y., Bartels, Gerard L., Cornel, Jan H., Hermans, Walter R. M., Herrman, Johannes P. R., Bos, Robert J., Groutars, Reginald G. E. J., Van Der Zwaan, Coenraad C., Kaplan, Refik, Ronner, Eelko, Groenemeijer, Bjorn E., Bronzwaer, Patrick N. A., Liem, Anho A. H., Rensing, Bernard J. W. M., Bokern, Marcel J. J. A., Nijmeijer, Remco, Hersbach, Ferry M. R. J., Willems, Frank F., Gosselink, Antonius T. M., Elliott, John, Wilkins, Gerard, Fisher, Raewyn, Scott, Douglas, Hart, Hamish, Stewart, Ralph, Harding, Scott, Ternouth, Ian, Fisher, Nicholas, Aitken, Denise, Anscombe, Russell, Tomala, Tadeusz, Nygard, Ottar, Sparby, Jon Arne, Andersen, Kjell, Gullestad, Lars, Jortveit, Jarle, Munk, Peter S., Hurtig, Ulf, Ticona, Jorge R. 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A., Bengus, Cristina M., Militaru, Constantin, Rosu, Doina, Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Shalaev, Sergey, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Baranova, Elena, Shogenov, Zaur, Kosmachova, Elena, Karpov, Yuriy, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Putnikovic, Biljana, Stankovic, Aleksandar, Arandjelovic, Aleksandra, Radovanovic, Slavica, Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Dodic, Slobodan, Dimkovic, Sinisa, Poh, Kian-Keong, Ong, Hean Yee, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Mazur, Juraj, Majercak, Ivan, Dzupina, Andrej, Fazekas, Frantisek, Gonsorcik, Jozef, Bugan, Viliam, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Smik, Rudolf, Dukat, Andrej, Zuran, Ivan, Oklukar, Janez, Suligoj, Natasa Cernic, Cevc, Matija, Lipar, Luka, Cyster, Henry P., Ranjith, Naresh, Corbett, Clive, Bayat, Junaid, Makotoko, Ellen Makoali, Kapp, Ilse E., de Basson, Matthys M. V., Lottering, Hanlie, Van Zyl, Louis J., Sebastian, Peter J., Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Reuter, Helmuth, Moodley, Rajendran, Vida, Manuel, Cequier Fillat, Angel R., Bodi Peris, Vicente, Fuentes Jimenez, Francisco, Marin, Francisco, Cruz Fernandez, Jose M., Gil-Extremera, Blas, Worner Diz, Fernando, Garcia-Dorado, David, Iniguez, Andres, Tunon Fernandez, Jose, Gonzalez-Juanatey, Jose R., Fernandez Portales, Javier, Civeira Murillo, Fernando, Matas Pericas, Laia, Luis Zamorano, Jose, De Mora Martin, Manuel, Bruguera Cortada, Jordi, Alonso Martin, Joaquin J., De Berrazueta Fernandez, Jose R., Diaz Fernandez, Jose Francisco, Garcia Lledo, Jose Alberto, Cosin Sales, Juan, Botas Rodriguez, Javier, Gusi Tragant, Gabriel, Benedicto, Amparo, Gonzalez-Juanatey, Carlos, Camprubi Potau, Mercedes, Plaza Perez, Ignacio, Moris De La Tassa, Cesar, Loma-Osorio Rincon, Pablo, Balaguer Recena, Javier, M Escudier, Juan, Constantine, Godwin, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Fernando, Nimali, Jayawardena, Jayanthimala, Santharaj, Wijeyasingam, Ekanayaka, Ruvan, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Sirisena, Thilak, Rajapaksha, Ajantha, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjorn, Moccetti, Tiziano, Mueller, Christian, Mach, Francois, Binder, Ronald, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I-Chang, Lin, Wei Hsiang, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Camsari, Ahmet, Kultursay, Hakan, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-Ki, Iqbal, Syed M. R., Subkovas, Eduardas, Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Kurian, John, Levy, Terry, Barr, Craig, Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Mathur, Anthony, Brodison, Adrian, Oliver, Richard, Mudawi, Telal, Reynolds, Timothy, Sharman, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Y. H., Halcox, Julian, Vardi, Gil, Baldari, Duccio, Brabham, David, Treasure, Charles, II, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Jr., Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Khan, Misal, Shoukfeh, Mohammad, Dagher, Georges, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Suh, David, Arif, Imran, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Harris, Barry, Cohen, Steven, Carter, Luther, Sabatino, Kenneth, Haddad, Tariq, Malik, Amir, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds, George, III, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Singh, Narendra, Shah, Anil V., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Keating, Friederike, Kondo, Nicholas I., Shetty, Sanjay, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Izzo, Mark, Kumar, Anil, Hattler, Brack, Link, Chad, Bortnick, Anna, Kinzfogl, George, III, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Abbas, Jalal, White, Matthew, Ranadive, Nandkishore, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Jafar, Zubair, Mcgarvey, Joseph, Jr., Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Herzog, William, Jr., Lindsey, Jason, Nowins, Rosemary, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, May, Wade, Galski, Thomas, Chu, Alan, Mody, Freny, Hodes, Zachary, Fairlamb, James, Lambert, Charles, Jr., Raisinghani, Ajit, Abbate, Antonio, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun (Tom), Vidovich, Mladen, Knutson, Thomas, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Kimmelstiel, Carey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Jr., Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Claxton, Edmund, Jr., Berk, Martin, Rossi, Peter, Joshi, Parag, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Farrar, Michael, Pollock, Stewart, French, William J., Diamantis, Steve, Gimple, Lawrence, Schwartz, Steven, Pereira, Edward, Spriggs, Douglas, Strain, Janet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, Nager, Paul, Vohra, Rakesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Sporn, Daniel, Eisenberg, Steven, Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. Sandy, Jain, Diwakar, Zainea, Mark, Bayron, Carlos, Karlsberg, Ronald, Lui, Henry, Keen, William, Westerhausen, Donald, Jr., Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William, Jr., Chang, Mark, Gilbert, John M., Chalavarya, Gopal, Eaton, Charles, Schmedtje, John F., Jr., Christenson, Stuart, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Conrad, Gary, Kotha, Purushotham, Love, Michael, Giesler, Gregory, Rubenstein, Howard, Akright, Laura, Schifferdecker, Branislav, Krawczyk, Justine, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Internal Medicine, ODYSSEY OUTCOMES Comm Inv, VA Boston Healthcare System, Department of General Surgery. Surgical Oncology Unit, Reina Sofía University Hospital, Metacohorts Consortium, Sanofi [Vitry-sur-Seine], SANOFI Recherche, CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, University of Zurich, and Schwartz, Gregory G

Subjects
Adult, Male, medicine.medical_specialty, Acute coronary syndrome, Evinacumab, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Hypercholesterolemia, 610 Medicine & health, 2700 General Medicine, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Placebo, 11171 Cardiocentro Ticino, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Humans, Medicine, 03.02. Klinikai orvostan, 030212 general & internal medicine, Myocardial infarction, Acute Coronary Syndrome, ComputingMilieux_MISCELLANEOUS, Aged, Alirocumab, business.industry, Unstable angina, Anticholesteremic Agents, PCSK9, PCSK9 Inhibitors, Hazard ratio, Antibodies, Monoclonal, Cholesterol, LDL, General Medicine, Middle Aged, ta3121, medicine.disease, 3. Good health, Cardiovascular Diseases, Cardiology, Female, Human medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

PubMed: 30403574, 2-s2.0-85057337718, BACKGROUND Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier, had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter (1.8 mmol per liter), a non-highdensity lipoprotein cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least 80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose. Patients were randomly assigned to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter). The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. RESULTS The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P

Published
2018

11. Lipoprotein‐Associated Phospholipase A 2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Author

Wallentin, Lars, Held, Claes, Armstrong, Paul W., Cannon, Christopher P., Davies, Richard Y., Granger, Christopher B., Hagström, Emil, Harrington, Robert A., Hochman, Judith S., Koenig, Wolfgang, Krug‐Gourley, Sue, Mohler, Emile R., Siegbahn, Agneta, Tarka, Elizabeth, Steg, Philippe Gabriel, Stewart, Ralph A. H., Weiss, Robert, Östlund, Ollie, White, Harvey D., Budaj, Andrzej, Ardissino, Diego, Avezum, Alvaro, Aylward, Philip E., Bryce, Alfonso, Chen, Hong, Chen, Ming‐Fong, Corbalan, Ramon, Dalby, Anthony J., Danchin, Nicolas, De Winter, Robbert J., Denchev, Stefan, Diaz, Rafael, Elisaf, Moses, Flather, Marcus D., Goudev, Assen R., Grinfeld, Liliana, Husted, Steen, Kim, Hyo‐Soo, Linhart, Ales, Lonn, Eva, López‐Sendón, José, Manolis, Athanasios J., Nicolau, José C., Pais, Prem, Parkhomenko, Alexander, Pedersen, Terje R., Pella, Daniel, Ramos‐Corrales, Marco A., Ruda, Mikhail, Sereg, Mátyás, Siddique, Saulat, Sinnaeve, Peter, Sritara, Piyamitr, Swart, Henk P., Sy, Rody G., Teramoto, Tamio, Tse, Hung‐Fat, Weaver, W. Douglas, Viigimaa, Margus, Vinereanu, Dragos, Zhu, Junren, ACS - Amsterdam Cardiovascular Sciences, and Cardiology

Subjects
Male, medicine.medical_specialty, Phospholipase A2 Inhibitors, Myocardial Infarction, Coronary Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Double-Blind Method, Risk Factors, Interquartile range, Darapladib, Internal medicine, Oximes, medicine, Coronary Heart Disease, Humans, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Stroke, Original Research, Aged, Pharmacology, business.industry, Lipoprotein-associated phospholipase A2, lipoprotein, Hazard ratio, respiratory system, Middle Aged, medicine.disease, Treatment, STABILITY Investigators, inflammation, Benzaldehydes, Heart failure, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Cardiology, Female, lipids (amino acids, peptides, and proteins), atherosclerosis, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Background We evaluated lipoprotein‐associated phospholipase A 2 (Lp‐ PLA 2 ) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐ PLA 2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results Plasma Lp‐ PLA 2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐ PLA 2 activity levels and outcomes. At baseline, the median Lp‐ PLA 2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐ PLA 2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐ PLA 2 activity. There were no associations between on‐treatment Lp‐ PLA 2 activity or changes of Lp‐ PLA 2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐ PLA 2 activity or changes in Lp‐ PLA 2 activity levels and the effects of darapladib on outcomes. Conclusions Although high Lp‐ PLA 2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐ PLA 2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐ PLA 2 activity. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00799903.

Published
2016

12. Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Author

Wallentin, Lars, Held, Claes, Armstrong, Paul W., Cannon, Christopher P., Davies, Richard Y., Granger, Christopher B., Hagström, Emil, Harrington, Robert A., Hochman, Judith S., Koenig, Wolfgang, Krug‐Gourley, Sue, Mohler, Emile R., Siegbahn, Agneta, Tarka, Elizabeth, Steg, Philippe Gabriel, Stewart, Ralph A. H., Weiss, Robert, Östlund, Ollie, White, Harvey D., Budaj, Andrzej, Ardissino, Diego, Avezum, Alvaro, Aylward, Philip E., Bryce, Alfonso, Chen, Hong, Chen, Ming‐Fong, Corbalan, Ramon, Dalby, Anthony J., Danchin, Nicolas, De Winter, Robbert J., Denchev, Stefan, Diaz, Rafael, Elisaf, Moses, Flather, Marcus D., Goudev, Assen R., Grinfeld, Liliana, Husted, Steen, Kim, Hyo‐Soo, Linhart, Ales, Lonn, Eva, López‐Sendón, José, Manolis, Athanasios J., Nicolau, José C., Pais, Prem, Parkhomenko, Alexander, Pedersen, Terje R., Pella, Daniel, Ramos‐Corrales, Marco A., Ruda, Mikhail, Sereg, Mátyás, Siddique, Saulat, Sinnaeve, Peter, Sritara, Piyamitr, Swart, Henk P., Sy, Rody G., Teramoto, Tamio, Tse, Hung‐Fat, Weaver, W. Douglas, Viigimaa, Margus, Vinereanu, Dragos, and Zhu, Junren

Subjects
atherosclerosis, coronary disease, inflammation, lipoprotein, myocardial infarction, Biomarkers, Coronary Artery Disease, Pharmacology, Treatment, Risk Factors
Abstract

Background: We evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA 2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA 2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results: Plasma Lp‐PLA 2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA 2 activity levels and outcomes. At baseline, the median Lp‐PLA 2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA 2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA 2 activity. There were no associations between on‐treatment Lp‐PLA 2 activity or changes of Lp‐PLA 2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA 2 activity or changes in Lp‐PLA 2 activity levels and the effects of darapladib on outcomes. Conclusions: Although high Lp‐PLA 2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA 2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA 2 activity. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.

Published
2016
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