Search

Your search keyword '"Leitersdorf E"' showing total 362 results
Start Over Author "Leitersdorf E"
362 results on '"Leitersdorf E"'

3. Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve.

Author

Tessler, I., Albuisson, J., Piñeiro-Sabarís, R., Verstraeten, A., Kamber Kaya, H.E., Siguero-Álvarez, M., Goudot, G., MacGrogan, D., Luyckx, I., Shpitzen, S., Levin, G., Kelman, G., Reshef, N., Mananet, H., Holdcraft, J., Muehlschlegel, J.D., Peloso, G.M., Oppenheim, O., Cheng, C., Mazzella, J.M., Andelfinger, G., Mital, S., Eriksson, P., Billon, C., Heydarpour, M., Dietz, H.C., Jeunemaitre, X., Leitersdorf, E., Sprinzak, D., Blacklow, S.C., Body, S.C., Carmi, S., Loeys, B.L., Pompa, J.L. de la, Gilon, D., Messas, E., Durst, R., Tessler, I., Albuisson, J., Piñeiro-Sabarís, R., Verstraeten, A., Kamber Kaya, H.E., Siguero-Álvarez, M., Goudot, G., MacGrogan, D., Luyckx, I., Shpitzen, S., Levin, G., Kelman, G., Reshef, N., Mananet, H., Holdcraft, J., Muehlschlegel, J.D., Peloso, G.M., Oppenheim, O., Cheng, C., Mazzella, J.M., Andelfinger, G., Mital, S., Eriksson, P., Billon, C., Heydarpour, M., Dietz, H.C., Jeunemaitre, X., Leitersdorf, E., Sprinzak, D., Blacklow, S.C., Body, S.C., Carmi, S., Loeys, B.L., Pompa, J.L. de la, Gilon, D., Messas, E., and Durst, R.

Abstract

Contains fulltext : 295944.pdf (Publisher’s version ) (Closed access), IMPORTANCE: Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart valve malformation. BAV has a heritable component, yet only a few causative genes have been identified; understanding BAV genetics is a key point in developing personalized medicine. OBJECTIVE: To identify a new gene for nsBAV. DESIGN, SETTING, AND PARTICIPANTS: This was a comprehensive, multicenter, genetic association study based on candidate gene prioritization in a familial cohort followed by rare and common association studies in replication cohorts. Further validation was done using in vivo mice models. Study data were analyzed from October 2019 to October 2022. Three cohorts of patients with BAV were included in the study: (1) the discovery cohort was a large cohort of inherited cases from 29 pedigrees of French and Israeli origin; (2) the replication cohort 1 for rare variants included unrelated sporadic cases from various European ancestries; and (3) replication cohort 2 was a second validation cohort for common variants in unrelated sporadic cases from Europe and the US. MAIN OUTCOMES AND MEASURES: To identify a candidate gene for nsBAV through analysis of familial cases exome sequencing and gene prioritization tools. Replication cohort 1 was searched for rare and predicted deleterious variants and genetic association. Replication cohort 2 was used to investigate the association of common variants with BAV. RESULTS: A total of 938 patients with BAV were included in this study: 69 (7.4%) in the discovery cohort, 417 (44.5%) in replication cohort 1, and 452 (48.2%) in replication cohort 2. A novel human nsBAV gene, MINDBOMB1 homologue MIB1, was identified. MINDBOMB1 homologue (MIB1) is an E3-ubiquitin ligase essential for NOTCH-signal activation during heart development. In approximately 2% of nsBAV index cases from the discovery and replication 1 cohorts, rare MIB1 variants were detected, predicted to be damaging, and were significantly enriched compared with populati

Published
2023

4. Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial

Author

Gerstman, M., Howes, L., Kostner, K., Nestel, P., Sullivan, D., Brath, H., Patsch, J., Paulweber, B., Toplak, H., Constance, C.M., Howlett, E., Mymin, D., Pliamm, L., Saunders, K.K., Tardif, J.-C., Tytus, R., Aschner, P., Keinänen-Klukaanniemi, S., Strandberg, T., Taskinen, M.-R., Luc, G., Richter, D., Schlienger, J.L., Zaïr, Y., Appel, K.-F., Baar, M., Luley, C., Overhoff, U., Pomykaj, T., Schaefer, T., Lau, S.T., Lee, K.L.F., Tan, K., Tomlinson, B., Tsang, M.W., Badacsonyi, K., Kalina, Á., Kanakaridisz, N., Márk, L., Péterfai, É., Regos, L., Reiber, I., Takács, J., Vértes, A., Elis, A., Gavish, D., Harats, D., Hussein, O., Hayek, T., Leitersdorf, E., Bin Abdul Ghapar, A.K., Chee, K.H., Ismail, S.B., Ling, K.H., Ramanathan, G.R.L., Sim, K.H., Alvarado, R., Benavides, M., Cardona, G.E., Gonzalez, G., Verdejo, J., Basart, D.C.G., Imholz, B.P.M., Jonker, J.J.C., Nierop, P.R., Posma, J.L., Twickler, Th.B., Barrington-Ward, E., Cutfield, R., Friedlander, D.H., Scott, R.S., Istad, H., Langslet, G., Skjelvan, G.K., Campodónico Hoyos, S.J., Coloma Araniya, R., Gallegos C., A., Pino Morales, C.A., Watanabe, L., Arutyunov, G.P., Blokhin, A.B., Bubnova, M.G., Marcevich, S.Y., Álvarez Sánchez, C., Álvarez-Sala Walther, L.A., Gil Extremera, B., Perez Jimenez, F., de Teresa Parreño, L., Anderberg, C.-P., Hedin, U., Hellberg, A., Höök, P., Kjellström, T., Nilsson, P., Olsson, A.G., Rosenqvist, U., Tolagen, K., Wolff, T., Baskin, A., Bays, H.E., Bernstein, R.I., Bittar, N., Brinton, E.A., Chee, L.H.K., Cottiero, R.A., D'Agostino, R.D., Davidson, M.H., Denker, P.S., Garcia, R.K., Hippert, R.K., Isakov, T., Kaster, S.R., Kerzner, B., Klein, E.J., Koren, M.J., Kutner, M.E., Liljenquist, D., Lorch, D.G., Jr., Lorraine, R., Lubin, B.C., Lunde, N.M., Majchrzak, T.J., McKenney, J.M., Mukherjee, S., Muse, D.D., Otruba, M.S., Pappas, J.E., Patrick, K., Powell, S.J., Riffer, E., Rink, L.D., Rohlf, J.L., Rosen, J.B., Rosenbilt, P.D., Roth, E.M., Rubenstein, C.J., Rubino, J., Rudolph, L.A., Schneider, A., Short, W.G., Silverfield, J.C., Suresh, D.P., Tarshis, G.A., Toth, P.D., Townsend, R.W., Wahl, T.O., Brinton, Eliot A., Kher, Uma, Shah, Sukrut, Cannon, Christopher P., Davidson, Michael, Gotto, Antonio M., Ashraf, Tanya B., McCrary Sisk, Christine, Dansky, Hayes, Mitchel, Yale, and Barter, Philip

Published
2015
Full Text
View/download PDF

16. Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author

Vallejo-Vaz, A.J. Marco, M.D. Stevens, C.A.T. Akram, A. Freiberger, T. Hovingh, G.K. Kastelein, J.J.P. Mata, P. Raal, F.J. Santos, R.D. Soran, H. Watts, G.F. Abifadel, M. Aguilar-Salinas, C.A. Al-Khnifsawi, M. Alkindi, F.A. Alnouri, F. Alonso, R. Al-Rasadi, K. Al-Sarraf, A. Ashavaid, T.F. Binder, C.J. Bogsrud, M.P. Bourbon, M. Bruckert, E. Chlebus, K. Corral, P. Descamps, O. Durst, R. Ezhov, M. Fras, Z. Genest, J. Groselj, U. Harada-Shiba, M. Kayikcioglu, M. Lalic, K. Lam, C.S.P. Latkovskis, G. Laufs, U. Liberopoulos, E. Lin, J. Maher, V. Majano, N. Marais, A.D. März, W. Mirrakhimov, E. Miserez, A.R. Mitchenko, O. Nawawi, H.M. Nordestgaard, B.G. Paragh, G. Petrulioniene, Z. Pojskic, B. Postadzhiyan, A. Reda, A. Reiner, Ž. Sadoh, W.E. Sahebkar, A. Shehab, A. Shek, A.B. Stoll, M. Su, T.-C. Subramaniam, T. Susekov, A.V. Symeonides, P. Tilney, M. Tomlinson, B. Truong, T.-H. Tselepis, A.D. Tybjærg-Hansen, A. Vázquez-Cárdenas, A. Viigimaa, M. Vohnout, B. Widén, E. Yamashita, S. Banach, M. Gaita, D. Jiang, L. Nilsson, L. Santos, L.E. Schunkert, H. Tokgözoğlu, L. Car, J. Catapano, A.L. Ray, K.K. Schreier, L. Pang, J. Dieplinger, H. Hanauer-Mader, G. Desutter, J. Langlois, M. Mertens, A. Rietzschel, E. Wallemacq, C. Isakovic, D. Dzankovic, A.M. Obralija, J. Pojskic, L. Sisic, I. Stimjanin, E. Torlak, V.A. Jannes, C.E. Krieger, J.E. Pereira, A.C. Ruel, I. Asenjo, S. Cuevas, A. Pećin, I. Miltiadous, G. Panayiotou, A.G. Vrablik, M. Benn, M. Heinsar, S. Béliard, S. Gouni-Berthold, I. Hengstenberg, W. Julius, U. Kassner, U. Klose, G. König, C. König, W. Otte, B. Parhofer, K. Schatz, U. Schmidt, N. Steinhagen-Thiessen, E. Vogt, A. Antza, C. Athyros, V. Bilianou, E. Boufidou, A. Chrousos, G. Elisaf, M. Garoufi, A. Katsiki, N. Kolovou, G. Kotsis, V. Rallidis, L. Rizos, C. Skalidis, E. Skoumas, I. Tziomalos, K. Shawney, J.P.S. Abbaszadegan, M.R. Aminzadeh, M. Hosseini, S. Mobini, M. Vakili, R. Zaeri, H. Agar, R. Boran, G. Colwell, N. Crowley, V. Durkin, M. Griffin, D. Kelly, M. Rakovac-Tisdall, A. Bitzur, R. Cohen, H. Eliav, O. Ellis, A. Gavish, D. Harats, D. Henkin, Y. Knobler, H. Leavit, L. Leitersdorf, E. Schurr, D. Shpitzen, S. Szalat, A. Arca, M. Averna, M. Bertolini, S. Calandra, S. Tarugi, P. Erglis, A. Gilis, D. Nesterovics, G. Saripo, V. Upena-Roze, A. Elbitar, S. Jambart, S. Khoury, P.E. Gargalskaite, U. Kutkiene, S. Al-Khateeb, A. An, C.Y. Ismail, Z. Kasim, S. Ibrahim, K.S. Radzi, A.B.M. Kasim, N.A. Nor, N.S.M. Ramli, A.S. Razak, S.A. Muid, S. Rosman, A. Sanusi, A.R. Razman, A.Z. Nazli, S.A. Kek, T.L. Azzopardi, C. Aguilar Salinas, C.A. Galán, G. Rubinstein, A. Magaña-Torres, M.T. Martagon, A. Mehta, R. Wittekoek, M.E. Isara, A.R. Obaseki, D.E. Ohenhen, O.A. Holven, K.B. Gruchała, M. Baranowska, M. Borowiec-Wolny, J. Gilis-Malinowska, N. Michalska-Grzonkowska, A. Pajkowski, M. Parczewska, A. Romanowska-Kocejko, M. Stróżyk, A. Żarczyńska-Buchowiecka, M. Kleinschmidt, M. Alves, A.C. Medeiros, A.M. Ershova, A. Korneva, V. Kuznetsova, T. Malyshev, P. Meshkov, A. Rozhkova, T. Popovic, L. Lukac, S.S. Stosic, L. Rasulic, I. Lalic, N.M. Chua, T.S.J. Ting, S.P.L. Raslova, K. Battelino, T. Cevc, M. Jug, B. Kovac, J. Podkrajsek, K.T. Sustar, U. Trontelj, K.J. Marais, D. Isla, L.P. Martin, F.J. Charng, M.-J. Chen, P.-L. Kayikçioglu, M. Dell’oca, N. Fernández, G. Ressia, A. Reyes, X. Zelarayan, M. Alieva, R.B. Hoshimov, S.U. Nizamov, U.I. Kurbanov, R.D. Lima-Martínez, M.M. Nguyen, M.-N.T. Do, D.-L. Kim, N.-T. Le, T.-T. Le, H.-A.

Abstract

Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed. © 2018 Elsevier B.V.

Published
2018

17. P6193Dalcetrapib reduces incident diabetes in patients with recent acute coronary syndrome

Author

Schwartz, G, primary, Leiter, L A, additional, Ballantyne, C M, additional, Barter, P J, additional, Black, D M, additional, Kallend, D, additional, Leitersdorf, E, additional, McMurray, J J V, additional, Nicholls, S J, additional, Olsson, A G, additional, Preiss, D, additional, Shah, P K, additional, Tardif, J C, additional, and Kittelson, J, additional

Published
2019
Full Text
View/download PDF

20. The New HIT: Human Health Information Technology

Author

Leung, T.I., Goldstein, M.K., Musen, M.A., Cronkite, R., Chen, J.H., Gottlieb, A., Leitersdorf, E., RS: CAPHRI - R2 - Creating Value-Based Health Care, and Faculteit FHML Centraal

Subjects
INTERPERSONAL CONTINUITY, User-Computer Interface, MEDICINE, DISEASES, SAFETY, Humanism, MANAGEMENT, Electronic Health Records, TELEHEALTH, RECORD, QUALITY-OF-CARE, PATIENT-CARE, TIME
Abstract

Humanism in medicine is defined as health care providers' attitudes and actions that demonstrate respect for patients' values and concerns in relation to their social, psychological and spiritual life domains. Specifically, humanistic clinical medicine involves showing respect for the patient, building a personal connection, and eliciting and addressing a patient's emotional response to illness. Health information technology (IT) often interferes with humanistic clinical practice, potentially disabling these core aspects of the therapeutic patient-physician relationship. Health IT has evolved rapidly in recent years - and the imperative to maintain humanism in practice has never been greater. In this vision paper, we aim to discuss why preserving humanism is imperative in the design and implementation of health IT systems.

Published
2017

24. Aldosterone does not predict cardiovascular events following acute coronary syndrome in patients initially without heart failure

Author

Pitts, R, Gunzburger, E, Ballantyne, CM, Barter, PJ, Kallend, D, Leiter, LA, Leitersdorf, E, Nicholls, SJ, Shah, PK, Tardif, JC, Olsson, AG, McMurray, JJV, Kittelson, J, Schwartz, GG, Pitts, R, Gunzburger, E, Ballantyne, CM, Barter, PJ, Kallend, D, Leiter, LA, Leitersdorf, E, Nicholls, SJ, Shah, PK, Tardif, JC, Olsson, AG, McMurray, JJV, Kittelson, J, and Schwartz, GG

Abstract

© 2017 The Authors. Background-Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. Methods and Results-To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF <40%), III, or IV HF were excluded. Aldosterone was measured at randomization in 4073 patients. The primary outcome was a composite of coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. Conclusions-In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events.

Published
2017

25. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus

Author

Scirica, B, Bhatt, D, Braunwald, E, Steg, P, Davidson, J, Hirshberg, B, Ohman, P, Frederich, R, Wiviott, S, Hoffman, E, Cavender, M, Udell, J, Desai, N, Mosenzon, O, Mcguire, D, Ray, K, Leiter, L, Raz, I, Abrahamsen, T, Grossman, M, Morin, S, Im, K, Gabovitch, D, Pricken, A, Buskila, A, Stahre, C, Price, D, Billing-Clason, S, Sabel, K, Monyak, J, Sjostrand, M, Wei, C, Lu, J, Miller, E, Raichlen, J, Fitt, S, Iqbal, N, Donovan, M, Aguilar-Salinas, C, Alvarsson, M, Amerena, J, Ardissino, D, Averkov, O, Avogaro, A, Barnett, A, Bretzel, R, Chiang, C, Codoceo, V, Corbalan, R, Dalby, A, Darius, H, Deerochanawong, C, Dellborg, M, Eliaschewitz, F, Garcia-Castillo, A, Gomis, R, Henry, P, Hoekstra, J, Jermendy, G, Kastelein, J, Keech, A, Kiss, R, Krempf, M, Laakso, M, Leitersdorf, E, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Medina, F, Moses, R, Nicolau, J, Opolski, G, Ophuis, T, Paolasso, E, Ruda, M, Kumar, K, Shestakova, M, Sheu, W, Smahelova, A, Bhupathiraju, B, Spinar, J, Sritata, P, Strojeck, K, Villena-Chavez, J, Jia, W, Huo, Y, Lowe, C, Awtry, E, Berger, C, Desai, A, Gelfand, E, Leeman, D, Link, M, Ruberg, F, Vita, J, Rost, N, Silverman, S, Greenberger, N, Lerch, M, Gersh, B, Nesto, R, Del Prato, S, Tuomilehto, J, Kelsey, S, Alvarisqueta, A, Cuadrado, J, Rista, L, Hermida, S, Baccaro, C, Luquez, C, Lagrutta, M, Maffei, L, Bartolacci, I, Montana, O, Cutuli, H, Berli, M, Lorenzatti, A, Frechtel, G, La Greca, R, Fretes, O, Diaz, M, Papini, N, Farias, E, Issa, C, Elbert, A, Lehman, R, Arya, M, Singh, B, Colquhoun, D, Jayasinghe, R, de Looze, F, Blombery, P, Ward, G, Szto, G, Abhayaratna, W, Borges, J, Russo, L, Felicio, J, Santos, F, Guimaraes, F, Castro, M, Rossi, P, Armaganijan, D, Leaes, P, Bandeira, F, Franken, M, Rassi, N, Rea, R, Zanella, M, Amodeo, C, Cesar, L, Betti, R, Chacra, A, Schmid, H, Bell, A, Syan, G, Zadra, R, Conter, H, Dumas, R, Borts, D, Dattani, I, Poirier, P, Cha, J, Dzongowski, P, Labonte, R, St Pierre, B, Gaudet, D, Kouz, S, Lamy, A, Tishler, S, Chehayeb, R, Bedard, J, Hramiak, I, Teitelbaum, I, Fortin, C, Woo, V, Conway, J, Mehta, P, Robinson, S, Sussex, B, Chiasson, J, Muirhead, N, Bose, S, Ouellet, A, Yale, J, Bhargava, R, Lau, D, Tobe, S, Perron, P, Sigalas, J, Bilodeau, L, Tytus, R, Achyuthan, G, Pearce, M, Steele, A, Bailey, G, Ma, P, St-Maurice, F, Rupka, D, Houlden, R, Bailey, A, Rewa, G, Sohal, P, Ting, R, Prieto, J, Rodriguez, M, Godoy, G, Larenas, G, Pincetti, C, Cobos, L, Saavedra, V, Varleta, P, Lucero, F, Kuzmanic, O, Acevedo, M, Aguirre, M, Florenzano, F, Ma, J, Bao, Y, Jiang, M, Xu, W, Shi, Y, Zheng, M, Li, Y, Dong, Y, Zhao, W, Sun, M, Lei, M, Wang, J, Pistek, Z, Rihacek, I, Kucera, D, Brada, M, Naplava, R, Karasova, J, Vlasicova, H, Skopecek, J, Spinarova, L, Raclavska, L, Sarbochova, R, Okenka, L, Racicka, E, Urbancova, K, Oznerova, M, Lorenc, Z, Wasserburger, B, Zahumensky, E, Grunfeldova, H, Hradec, J, Lukac, M, Svacina, S, Podzimek, J, Hemzsky, L, Mikulkova, I, Pavlickova, J, Brychta, T, Chochola, J, Couffinhal, T, Elbaz, M, Petit, C, Faller, B, Marechaud, R, Moulin, P, Fendri, S, Nazeyrollas, P, Wendisch, U, Busch, K, Klausmann, G, Duengen, H, Appel, K, Toursarkissian, N, Jung, T, Ott, P, Schenkenberger, I, Kuesters, D, Landers, B, Nischik, R, Fischer, H, Tschoepe, D, Paschen, B, Krause, K, Derwahl, K, Wenzl-Bauer, V, Hamann, A, Strotmann, H, Milek, K, Mueller, S, Chu, D, Tan, K, Kung, K, Tsang, C, Tomlinson, B, Koranyi, L, Kerenyi, Z, Benczur, B, Illyes, L, Hidvegi, T, Somogyi, A, Valco, J, Ferenczi, S, Rapi, J, Voros, P, Winkler, G, Sydo, T, Hetey, M, Simon, K, Penzes, J, Kempler, P, Bako, B, Lengyel, Z, Witmann, I, Dudas, M, Vandorfi, G, Takacs, J, Matoltsy, A, Ladanyi, E, Gyimesi, A, Sadikot, S, Parikh, K, Jain, S, Yajnik, C, Sosale, A, Shamanna, P, Srikanta, S, Shah, S, Srinivas, A, Banker, D, Shah, P, Sharda, A, Makkar, B, Rais, N, Mardikar, H, Mishra, A, Bhupati, S, Menon, J, Sathe, S, Gupta, R, Sharma, V, Darawsha, M, Herskovits, T, Hamoud, S, Nikolsky, E, Adawi, F, Zimlichman, R, Tsalihin, D, Wainstein, J, Klainman, E, Mosseri, M, Yerushalmi, Y, Karnieli, E, Knobler, H, Benchetrit, S, Tsur, A, Yagil, Y, Atar, S, Beberashvili, I, Fuchs, S, Stern, N, Pollak, A, Chajek-Shaul, T, Rozenman, Y, Biton, A, Bramucci, E, Fiscella, A, Grassia, V, Piatti, P, De Cosmo, S, Di Lorenzo, L, Merlini, P, Mannucci, E, Frontoni, S, Trevisan, R, Zenari, L, Lambiase, C, Salvioni, A, Silvestri, O, Ambrosio, G, Di Bartolo, P, Fattore, L, Presbitero, P, Calabrese, M, Evola, R, Gamba, M, Ibarra, M, Munoz, E, Sanchez, D, Herrera, C, Rios, J, Llamas, E, Esperon, G, Cantu, E, Fragoso, J, Gonzalez, J, Martinez, G, Padilla, F, Mier, G, Marmolejo, D, Ruiz, J, Portilla, N, Rosas, E, Machado, G, Ramos, J, Briones, I, van Hessen, M, Strikwerda, S, The, S, Kooy, A, Ronner, E, Nierop, P, Remmen, J, Groenemeijer, B, Hamer, B, Basart, D, van Lennep, H, Nieuwdorp, M, van Dijk, M, Kentgens, S, van Kempen, W, Hoogendijk, J, Spiering, W, Voors-Pette, C, Kose, V, de Waard, D, Gonkel, F, Kaasjager, H, Lingan, G, Agous, I, Kruik, H, Imholz, B, Pieterse, M, Manrique, H, Villena, J, Leon, L, Kundert, K, Minchola, J, Pinto, M, Heredia, J, Rodriguez, A, Guerreros, C, Berrospi, P, Zubiate, C, Allemant, A, Arbanil, H, Ponciano, W, Calderon, J, Lisson, R, Segura, L, Sidorowicz-Bialynicka, A, Sciborski, R, Fares, I, Mader, P, Skierkowska, J, Stasinska, T, Pomiecko, W, Skorski, M, Krzyzagorska, E, Polaszewska-Muszynska, M, Sowinski, D, Strojek, K, Rosinska-Migda, J, Romanczuk, P, Golebiowski, G, Kubica, J, Mazurek, T, Wojnowski, L, Pasternak, D, Stachlewski, P, Trzepla, E, Bogdanowicz, G, Uzunow, A, Potakowska, I, Miszczyszyn, Z, Waszyrowski, T, Smolenskaya, O, Lukyanov, Y, Vorokhobina, N, Khalimov, Y, Orlikova, O, Rebrov, A, Kukharchuk, V, Boldueva, S, Arkhipov, M, Zhelninova, T, Pavlysh, E, Antsiferov, M, Panov, A, Pavlova, M, Shustov, S, Demchenko, E, Galyavich, A, Malakhina, E, Semenova, O, Kobalava, Z, Kotova, S, Gavrisheva, I, Oschepkova, E, Karpov, Y, Sidorenko, B, Kislyak, O, Ametov, A, Dreval, A, Grineva, E, Mkrtumyan, A, Tyurina, T, Sazonova, O, Bonnici, F, Ranjith, N, Burgess, L, Nortje, H, Distiller, L, Mitha, I, Moore, R, Conradie, M, Horak, A, Pillay, S, Wellmann, H, Berg, E, Pillai, P, Padayachee, T, Corbett, C, Makan, H, Wing, J, Vawda, Z, Ebrahim, I, Mitha, E, Bhorat, A, Fernandez, J, Munoz, C, Cortada, J, Conde, A, Calvo, C, Extremera, B, Delgado, E, Masmiquel, L, Puig, J, Parreno, L, Mauricio, D, Redon, J, Brito, M, Lopez, C, de la Morera, J, Linderfalk, C, Larnefeldt, H, Olsson, A, Lonneborg, L, Ekelund, M, Samad, B, Borgencrantz, B, Nilsson, J, Berglund, O, Svensson, M, Mooe, T, Curiac, D, Albin, J, Angesjo, E, Lannemyr, O, Chen, J, Tien, K, Ueng, K, Lai, W, Yin, W, Hung, Y, Shyu, K, Hou, J, Lam, H, Laothavorn, P, Kuanprasert, S, Khovidhunkit, W, Benjasuratwong, Y, Chotinaiwattarakul, C, Mamanasiri, S, Suraamornkul, S, Pratipanawatr, T, Nitiyanant, W, Heller, S, Pieters, R, Strang, C, Bodalia, B, Middleton, A, Hall, T, Chapman, G, Calvert, J, Reed, R, Tam, D, Butcher, G, Jones, N, Takhar, A, Turner, W, Mcnally, D, Corey, O, Chapman, J, Mohr, S, Edwards, S, Ocampo, A, Kandath, D, Aude, Y, Ervin, W, Savin, V, Anderson, R, Littlefield, R, Oberoi, M, Platt, G, Yazdani, S, Mangoo-Karim, R, Walder, J, Gogia, H, Chandrashekhar, Y, Boccalandro, F, Rogers, W, Bilazarian, S, Zieve, F, Siage, Y, O'Connor, T, Mudaliar, S, Nikas, A, Giusti, R, Glover, R, Chilka, S, French, W, Roth, E, Singh, N, Christofferson, R, Stich, M, Dagogo-Jack, S, Allison, J, Zengotita, G, Ison, R, Iteld, B, Sulistio, M, Gonzalez, E, Gorman, T, Hage-Korban, E, Reddy, R, Byars, W, Antonishen, M, Benjamin, S, First, B, Rosado, J, Bruschetta, H, Poling, T, Rosendorff, C, Kerstein, H, Saba, F, Willis, J, Adams, K, Vazquez, E, Ellison, H, Kahn, B, Kereiakes, D, Powell, S, Raskin, P, Smith, K, Varma, S, Whittier, F, Casanova, R, Isserman, S, Kaye, W, Mcguinn, W, Bartkowiak, A, Dworkin, L, Labrador, C, Podlecki, D, Popovtzer, M, Aronoff, S, Ballantyne, C, Ortiz, E, Mora, A, Pitts, T, Reinhardt, S, Soucie, G, Wainwright, W, Henson, B, Sklaver, N, Arakaki, R, Brown, J, Chalavarya, G, Chochinov, R, Dixon, T, Kutner, M, Perlman, R, Raisinghani, A, Salacata, A, Awasty, V, Elinoff, V, George, W, LaRochelle-Gryseels, A, Mercado, A, Miller, G, Qureshi, M, Steljes, A, Wefald, F, Wilson, J, Chinn, J, Chuang, R, Comulada-Rivera, A, Hartman, I, Narayan, P, Pacheco, T, Weiss, R, Beavins, J, Creevy, J, Hamroff, G, Hodson, R, Kosinski, E, Krichmar, P, Patel, R, Schneider, R, Shapiro, J, Sharp, D, Speer, J, Stegemoller, R, Waxman, F, Chang, F, Braun, E, Eder, F, Minor, S, Albert, M, Carr, K, Diaczok, B, Gastman, I, Gupta, V, Longshaw, K, Gonzalez-Campoy, J, Raikhel, M, Thomas, J, Wood, K, Diab, I, Furda, J, Gelernt, M, Halter, M, House, B, Kaster, S, Raad, G, Stamatin, R, Barker, B, Blonder, R, Bloomberg, R, Calderon, R, Carrol, A, Comerota, A, Feinglos, M, Henderson, D, Kastelic, R, Stonesifer, L, Talano, J, Lee, P, Brosseau, J, Clark, W, Cohen, E, Fialkow, J, Horton, K, Kozman, H, Mcgill, J, Mihills, C, Poonawala, R, Shore, K, Tejada, L, Torres, R, Wright, W, Calatayud, G, Chandna, H, Drozdiak, R, Fink, R, Gill, R, Glandt, M, Gottlieb, D, Hack, T, Kay, J, Mansouri, V, Mcknight, T, Mostel, E, Schmidt, L, Seide, H, Sonel, E, Taylor, R, Velasquez, M, Bretton, E, Feldman, R, Hartman, A, Hershon, K, Leach, C, Martin, E, Mohiuddin, F, Naygandhi, Y, Riske, T, Schima, S, Uzoaga, E, Ward, H, Weinstock, R, Williams, T, Altschuller, A, Aoki, T, Blumenthal, S, Cash, A, Eisner, G, Gutmann, J, Hagan, M, Kabour, A, Markus, T, Mckenzie, W, Moursi, M, Mystkowski, P, Ovalle, F, Perkins, R, Popeil, L, Saniuk, R, Sierra, Y, Alvarado, O, Anderson, J, Bajaj, M, Blank, R, Chu, A, Levinsky, L, Levy, P, Osborne, J, Pavon, H, Sanderlin, D, Schaer, G, Zarich, S, Atassi, K, Bayron, C, Casagrande, M, Das, D, Gimness, M, Handel, F, Kinstrey, T, Leu, S, Osei, K, Nouel, J, Soltani, Z, Sussman, H, Chiu, K, Duda, R, Farnsworth, K, Lano, M, Lee, F, Levin, P, Pratt, S, Richwine, R, Ruiz-Rivera, L, Turner, J, Wood, J, Zigrang, W, Baquerizo, H, Colon, C, Demattia, J, Desai, V, Fitz-Patrick, D, Goral, S, Odhav, A, Prentiss, A, Ruff, C, Wu, W, Wyne, K, Abbott, L, Applegate, R, Cabral, J, Kotha, P, Ortega, P, Simmons, D, Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, Desai N, Abrahamsen T, Grossman M, Morin S, Im K, Hoffman E, Gabovitch D, Pricken A, Buskila A, Stahre C, Price D, Billing-Clason S, Sabel K, Monyak J, Sjostrand M, Wei C, Lu J, Miller E, Raichlen J, Fitt S, Iqbal N, Donovan M, Davidson JA, Aguilar-Salinas C, Alvarsson M, Amerena J, Ardissino D, Averkov O, Avogaro A, Barnett A, Bretzel R, Chiang CE, Codoceo V, Corbalan R, Dalby A, Darius H, Deerochanawong C, Dellborg M, Eliaschewitz F, Garcia-Castillo A, Gomis R, Henry P, Hoekstra J, Jermendy G, Kastelein J, Keech A, Kiss R, Krempf M, Laakso M, Leiter L, Leitersdorf E, Lewis B, Litwak L, Lopez-Sendon J, Ma R, McGuire D, Medina F, Moses R, Nicolau JC, Opolski G, Ophuis TO, Paolasso E, Ruda M, Kumar KMP, Shestakova M, Sheu WHH, Smahelova A, Bhupathiraju BSR, Spinar J, Sritata P, Strojeck K, Villena-Chavez JE, Jia WP, Huo Y, Lowe C, Awtry E, Berger C, Desai AS, Gelfand E, Leeman D, Link M, Ruberg F, Vita J, Rost N, Silverman S, Greenberger NJ, Lerch MM, Gersh B, Nesto R, Del Prato S, Tuomilehto J, Kelsey S, Alvarisqueta A, Cuadrado J, Rista L, Hermida S, Baccaro C, Luquez C, Lagrutta M, Maffei L, Bartolacci I, Montana O, Cutuli H, Berli M, Lorenzatti A, Frechtel G, La Greca R, Fretes O, Diaz M, Papini NR, Farias E, Issa C, Elbert A, Lehman R, Arya M, Singh B, Colquhoun D, Jayasinghe R, de Looze F, Blombery P, Ward G, Szto G, Abhayaratna W, Borges J, Russo L, Felicio J, Santos F, Guimaraes F, Castro ML, Rossi P, Armaganijan D, Leaes P, Bandeira F, Franken M, Rassi N, Rea R, Zanella M, Amodeo C, Cesar L, Betti R, Chacra A, Schmid H, Bell A, Syan G, Zadra R, Conter H, Dumas R, Borts D, Dattani I, Poirier P, Cha J, Dzongowski P, Labonte R, St Pierre B, Gaudet D, Kouz S, Lamy A, Tishler S, Chehayeb R, Bedard J, Hramiak I, Teitelbaum I, Fortin C, Woo V, Conway J, Mehta P, Robinson S, Sussex B, Chiasson J, Muirhead N, Bose S, Ouellet A, Yale J, Bhargava R, Lau D, Tobe S, Perron P, Sigalas J, Bilodeau L, Tytus R, Achyuthan G, Pearce M, Steele A, Bailey G, Ma P, St-Maurice F, Rupka D, Houlden R, Bailey A, Rewa G, Sohal P, Ting R, Prieto J, Rodriguez M, Godoy G, Larenas G, Pincetti C, Cobos L, Saavedra V, Varleta P, Lucero F, Kuzmanic O, Acevedo M, Aguirre M, Florenzano F, Ma J, Bao Y, Jiang M, Xu W, Shi Y, Zheng M, Li Y, Dong Y, Zhao W, Sun M, Lei M, Wang J, Pistek Z, Rihacek I, Kucera D, Brada M, Naplava R, Karasova J, Vlasicova H, Skopecek J, Spinarova L, Raclavska L, Sarbochova R, Okenka L, Racicka E, Urbancova K, Oznerova M, Lorenc Z, Wasserburger B, Zahumensky E, Grunfeldova H, Hradec J, Lukac M, Svacina S, Podzimek J, Hemzsky L, Mikulkova I, Pavlickova J, Brychta T, Chochola J, Couffinhal T, Elbaz M, Petit C, Faller B, Marechaud R, Moulin P, Fendri S, Nazeyrollas P, Wendisch U, Busch K, Klausmann G, Duengen H, Appel K, Toursarkissian N, Jung T, Ott P, Schenkenberger I, Kuesters D, Landers B, Nischik R, Fischer H, Tschoepe D, Paschen B, Krause K, Derwahl K, Wenzl-Bauer V, Hamann A, Strotmann H, Milek K, Mueller S, Chu D, Tan K, Kung K, Tsang C, Tomlinson B, Koranyi L, Kerenyi Z, Benczur B, Illyes L, Hidvegi T, Somogyi A, Valco J, Ferenczi S, Rapi J, Voros P, Winkler G, Sydo T, Hetey M, Simon K, Penzes J, Kempler P, Bako B, Lengyel Z, Witmann I, Dudas M, Vandorfi G, Takacs J, Matoltsy A, Ladanyi E, Gyimesi A, Sadikot S, Parikh K, Jain S, Yajnik C, Sosale A, Shamanna P, Srikanta S, Shah S, Srinivas A, Banker D, Shah P, Sharda A, Makkar B, Rais N, Mardikar H, Mishra A, Bhupati S, Menon J, Sathe S, Gupta R, Sharma V, Darawsha M, Herskovits T, Hamoud S, Nikolsky E, Adawi F, Zimlichman R, Tsalihin D, Wainstein J, Klainman E, Mosseri M, Yerushalmi Y, Karnieli E, Knobler H, Benchetrit S, Tsur A, Yagil Y, Atar S, Beberashvili I, Fuchs S, Stern N, Pollak A, Chajek-Shaul T, Rozenman Y, Biton A, Bramucci E, Fiscella A, Grassia V, Piatti P, De Cosmo S, Di Lorenzo L, Merlini P, Mannucci E, Frontoni S, Trevisan R, Zenari L, Lambiase C, Salvioni A, Silvestri O, Ambrosio G, Di Bartolo P, Fattore L, Presbitero P, Calabrese M, Evola R, Gamba MA, Ibarra MOD, Munoz EC, Sanchez DR, Herrera CH, Rios JP, Llamas EB, Esperon GL, Cantu EG, Fragoso JN, Gonzalez JG, Martinez GR, Padilla FP, Mier GM, Marmolejo DH, Ruiz JG, Portilla NC, Rosas EL, Machado GM, Ramos JC, Briones IR, van Hessen MWJ, Strikwerda S, The SHK, Kooy A, Ronner E, Nierop PR, Remmen JJ, Groenemeijer BE, Hamer BJB, Basart DCG, van Lennep HWOR, Nieuwdorp M, van Dijk MPM, Kentgens S, van Kempen WW, Hoogendijk J, Spiering W, Voors-Pette C, Kose V, de Waard DEP, Gonkel F, Kaasjager HAH, Lingan GMR, Agous I, Kruik HJ, Imholz BPM, Pieterse M, Manrique H, Villena J, Leon L, Kundert K, Minchola J, Pinto M, Heredia J, Rodriguez A, Guerreros C, Berrospi P, Zubiate C, Allemant A, Arbanil H, Ponciano W, Calderon J, Lisson R, Segura L, Sidorowicz-Bialynicka A, Sciborski R, Fares I, Mader P, Skierkowska J, Stasinska T, Pomiecko W, Skorski M, Krzyzagorska E, Polaszewska-Muszynska M, Sowinski D, Strojek K, Rosinska-Migda J, Romanczuk P, Golebiowski G, Kubica J, Mazurek T, Wojnowski L, Pasternak D, Stachlewski P, Trzepla E, Bogdanowicz G, Uzunow A, Potakowska I, Miszczyszyn Z, Waszyrowski T, Smolenskaya O, Lukyanov Y, Vorokhobina N, Khalimov Y, Orlikova O, Rebrov A, Kukharchuk V, Boldueva S, Arkhipov M, Zhelninova T, Pavlysh E, Antsiferov M, Panov A, Pavlova M, Shustov S, Demchenko E, Galyavich A, Malakhina E, Semenova O, Kobalava Z, Kotova S, Gavrisheva I, Oschepkova E, Karpov Y, Sidorenko B, Kislyak O, Ametov A, Dreval A, Grineva E, Mkrtumyan A, Tyurina T, Sazonova O, Bonnici F, Ranjith N, Burgess L, Nortje H, Distiller L, Mitha I, Moore R, Conradie M, Horak A, Pillay S, Wellmann H, Berg E, Pillai P, Padayachee T, Corbett C, Makan H, Wing J, Vawda Z, Ebrahim I, Mitha E, Bhorat A, Fernandez JC, Munoz C, Cortada JB, Conde AC, Calvo C, Extremera BG, Delgado E, Masmiquel L, Puig JG, Parreno LD, Mauricio D, Redon J, Brito M, Lopez C, de la Morera JS, Linderfalk C, Larnefeldt H, Olsson A, Lonneborg L, Ekelund M, Samad B, Borgencrantz B, Nilsson J, Berglund O, Svensson M, Mooe T, Curiac D, Albin J, Angesjo E, Lannemyr O, Chiang C, Sheu W, Chen J, Tien K, Ueng K, Lai W, Yin W, Hung Y, Shyu K, Hou J, Lam H, Laothavorn P, Kuanprasert S, Khovidhunkit W, Benjasuratwong Y, Chotinaiwattarakul C, Mamanasiri S, Suraamornkul S, Pratipanawatr T, Nitiyanant W, Heller S, Ray K, Pieters R, Strang C, Bodalia B, Middleton A, Hall T, Chapman G, Calvert J, Reed R, Tam D, Butcher G, Jones N, Takhar A, Turner W, McNally D, Corey O, Chapman J, Mohr S, Edwards S, Bhatt D, Ocampo A, Kandath D, Aude Y, Ervin W, Savin V, Anderson R, Littlefield R, Oberoi M, Platt GE, Yazdani S, Mangoo-Karim R, Walder J, Gogia H, Chandrashekhar Y, Boccalandro F, Rogers W, Bilazarian S, Zieve F, Siage Y, O'Connor T, Mudaliar S, Nikas A, Giusti R, Glover R, Chilka S, French W, Roth E, Singh N, Christofferson R, Stich M, Dagogo-Jack S, Allison J, Zengotita GA, Ison R, Iteld B, Sulistio M, Gonzalez E, Gorman T, Hage-Korban E, Reddy R, Byars W, Antonishen M, Benjamin S, First B, Rosado J, Bruschetta H, Poling T, Rosendorff C, Kerstein HJ, Saba F, Willis J, Adams K, Vazquez EC, Ellison H, Kahn B, Kereiakes D, Powell S, Raskin P, Smith K, Varma S, Whittier F, Casanova R, Isserman S, Kaye W, McGuinn W, Bartkowiak A, Dworkin L, Labrador CA, Podlecki D, Popovtzer M, Aronoff S, Ballantyne C, Ortiz EG, Mora A, Pitts T, Reinhardt S, Soucie G, Wainwright W, Henson B, Sklaver N, Arakaki R, Brown J, Chalavarya G, Chochinov R, Dixon T, Kutner M, Perlman R, Raisinghani A, Salacata A, Awasty V, Elinoff V, George W, LaRochelle-Gryseels A, Mercado A, Miller G, Qureshi M, Steljes A, Wefald F, Wilson J, Chinn J, Chuang RB, Comulada-Rivera A, Hartman I, Narayan P, Pacheco T, Weiss R, Beavins J, Creevy J, Hamroff G, Hodson R, Kosinski E, Krichmar P, Patel R, Schneider R, Shapiro J, Sharp D, Speer J, Stegemoller R, Waxman F, Chang FY, Braun E, Eder F, Minor S, Albert M, Carr KW, Diaczok B, Gastman I, Gupta V, Longshaw K, Gonzalez-Campoy JM, Raikhel M, Thomas J, Wood K, Diab I, Furda J, Gelernt M, Halter M, House B, Kaster S, Raad G, Stamatin R, Barker B, Blonder R, Bloomberg RJ, Calderon RB, Carrol A, Comerota A, Feinglos M, Henderson D, Kastelic R, Stonesifer LD, Talano J, Lee PV, Brosseau J, Clark W, Cohen E, Fialkow J, Horton K, Kozman H, McGill J, Mihills C, Poonawala R, Shore K, Tejada L, Torres R, Wright W, Calatayud G, Chandna H, Drozdiak R, Fink R, Gill R, Glandt M, Gottlieb DW, Hack T, Kay J, Mansouri V, McKnight T, Mostel E, Schmidt L, Seide H, Sonel E, Taylor R, Velasquez M, Bretton E, Feldman R, Hartman A, Hershon K, Leach CR, Martin E, Mohiuddin F, Naygandhi Y, Riske T, Schima S, Uzoaga ER, Ward H, Weinstock R, Williams T, Altschuller A, Aoki T, Blumenthal S, Cash A, Eisner G, Gutmann J, Hagan M, Kabour A, Markus T, McKenzie W, Moursi M, Mystkowski P, Ovalle F, Perkins R, Popeil L, Saniuk R, Sierra Y, Alvarado O, Anderson J, Bajaj M, Blank R, Chu A, Levinsky L, Levy P, Osborne J, Pavon H, Sanderlin D, Schaer G, Zarich S, Atassi K, Bayron C, Casagrande M, Das D, Gimness M, Handel F, Kinstrey T, Leu S, Osei K, Nouel JS, Soltani Z, Sussman H, Chiu K, Duda R, Farnsworth K, Lano M, Lee F, Levin P, Pratt S, Richwine R, Ruiz-Rivera L, Turner J, Wood J, Zigrang WD, Baquerizo HR, Colon CB, Demattia J, Desai V, Fitz-Patrick D, Goral S, Odhav A, Prentiss A, Ruff C, Wu W, Wyne K, Abbott LG, Applegate R, Cabral J, Kotha P, Ortega P, Simmons D, Scirica, B, Bhatt, D, Braunwald, E, Steg, P, Davidson, J, Hirshberg, B, Ohman, P, Frederich, R, Wiviott, S, Hoffman, E, Cavender, M, Udell, J, Desai, N, Mosenzon, O, Mcguire, D, Ray, K, Leiter, L, Raz, I, Abrahamsen, T, Grossman, M, Morin, S, Im, K, Gabovitch, D, Pricken, A, Buskila, A, Stahre, C, Price, D, Billing-Clason, S, Sabel, K, Monyak, J, Sjostrand, M, Wei, C, Lu, J, Miller, E, Raichlen, J, Fitt, S, Iqbal, N, Donovan, M, Aguilar-Salinas, C, Alvarsson, M, Amerena, J, Ardissino, D, Averkov, O, Avogaro, A, Barnett, A, Bretzel, R, Chiang, C, Codoceo, V, Corbalan, R, Dalby, A, Darius, H, Deerochanawong, C, Dellborg, M, Eliaschewitz, F, Garcia-Castillo, A, Gomis, R, Henry, P, Hoekstra, J, Jermendy, G, Kastelein, J, Keech, A, Kiss, R, Krempf, M, Laakso, M, Leitersdorf, E, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Medina, F, Moses, R, Nicolau, J, Opolski, G, Ophuis, T, Paolasso, E, Ruda, M, Kumar, K, Shestakova, M, Sheu, W, Smahelova, A, Bhupathiraju, B, Spinar, J, Sritata, P, Strojeck, K, Villena-Chavez, J, Jia, W, Huo, Y, Lowe, C, Awtry, E, Berger, C, Desai, A, Gelfand, E, Leeman, D, Link, M, Ruberg, F, Vita, J, Rost, N, Silverman, S, Greenberger, N, Lerch, M, Gersh, B, Nesto, R, Del Prato, S, Tuomilehto, J, Kelsey, S, Alvarisqueta, A, Cuadrado, J, Rista, L, Hermida, S, Baccaro, C, Luquez, C, Lagrutta, M, Maffei, L, Bartolacci, I, Montana, O, Cutuli, H, Berli, M, Lorenzatti, A, Frechtel, G, La Greca, R, Fretes, O, Diaz, M, Papini, N, Farias, E, Issa, C, Elbert, A, Lehman, R, Arya, M, Singh, B, Colquhoun, D, Jayasinghe, R, de Looze, F, Blombery, P, Ward, G, Szto, G, Abhayaratna, W, Borges, J, Russo, L, Felicio, J, Santos, F, Guimaraes, F, Castro, M, Rossi, P, Armaganijan, D, Leaes, P, Bandeira, F, Franken, M, Rassi, N, Rea, R, Zanella, M, Amodeo, C, Cesar, L, Betti, R, Chacra, A, Schmid, H, Bell, A, Syan, G, Zadra, R, Conter, H, Dumas, R, Borts, D, Dattani, I, Poirier, P, Cha, J, Dzongowski, P, Labonte, R, St Pierre, B, Gaudet, D, Kouz, S, Lamy, A, Tishler, S, Chehayeb, R, Bedard, J, Hramiak, I, Teitelbaum, I, Fortin, C, Woo, V, Conway, J, Mehta, P, Robinson, S, Sussex, B, Chiasson, J, Muirhead, N, Bose, S, Ouellet, A, Yale, J, Bhargava, R, Lau, D, Tobe, S, Perron, P, Sigalas, J, Bilodeau, L, Tytus, R, Achyuthan, G, Pearce, M, Steele, A, Bailey, G, Ma, P, St-Maurice, F, Rupka, D, Houlden, R, Bailey, A, Rewa, G, Sohal, P, Ting, R, Prieto, J, Rodriguez, M, Godoy, G, Larenas, G, Pincetti, C, Cobos, L, Saavedra, V, Varleta, P, Lucero, F, Kuzmanic, O, Acevedo, M, Aguirre, M, Florenzano, F, Ma, J, Bao, Y, Jiang, M, Xu, W, Shi, Y, Zheng, M, Li, Y, Dong, Y, Zhao, W, Sun, M, Lei, M, Wang, J, Pistek, Z, Rihacek, I, Kucera, D, Brada, M, Naplava, R, Karasova, J, Vlasicova, H, Skopecek, J, Spinarova, L, Raclavska, L, Sarbochova, R, Okenka, L, Racicka, E, Urbancova, K, Oznerova, M, Lorenc, Z, Wasserburger, B, Zahumensky, E, Grunfeldova, H, Hradec, J, Lukac, M, Svacina, S, Podzimek, J, Hemzsky, L, Mikulkova, I, Pavlickova, J, Brychta, T, Chochola, J, Couffinhal, T, Elbaz, M, Petit, C, Faller, B, Marechaud, R, Moulin, P, Fendri, S, Nazeyrollas, P, Wendisch, U, Busch, K, Klausmann, G, Duengen, H, Appel, K, Toursarkissian, N, Jung, T, Ott, P, Schenkenberger, I, Kuesters, D, Landers, B, Nischik, R, Fischer, H, Tschoepe, D, Paschen, B, Krause, K, Derwahl, K, Wenzl-Bauer, V, Hamann, A, Strotmann, H, Milek, K, Mueller, S, Chu, D, Tan, K, Kung, K, Tsang, C, Tomlinson, B, Koranyi, L, Kerenyi, Z, Benczur, B, Illyes, L, Hidvegi, T, Somogyi, A, Valco, J, Ferenczi, S, Rapi, J, Voros, P, Winkler, G, Sydo, T, Hetey, M, Simon, K, Penzes, J, Kempler, P, Bako, B, Lengyel, Z, Witmann, I, Dudas, M, Vandorfi, G, Takacs, J, Matoltsy, A, Ladanyi, E, Gyimesi, A, Sadikot, S, Parikh, K, Jain, S, Yajnik, C, Sosale, A, Shamanna, P, Srikanta, S, Shah, S, Srinivas, A, Banker, D, Shah, P, Sharda, A, Makkar, B, Rais, N, Mardikar, H, Mishra, A, Bhupati, S, Menon, J, Sathe, S, Gupta, R, Sharma, V, Darawsha, M, Herskovits, T, Hamoud, S, Nikolsky, E, Adawi, F, Zimlichman, R, Tsalihin, D, Wainstein, J, Klainman, E, Mosseri, M, Yerushalmi, Y, Karnieli, E, Knobler, H, Benchetrit, S, Tsur, A, Yagil, Y, Atar, S, Beberashvili, I, Fuchs, S, Stern, N, Pollak, A, Chajek-Shaul, T, Rozenman, Y, Biton, A, Bramucci, E, Fiscella, A, Grassia, V, Piatti, P, De Cosmo, S, Di Lorenzo, L, Merlini, P, Mannucci, E, Frontoni, S, Trevisan, R, Zenari, L, Lambiase, C, Salvioni, A, Silvestri, O, Ambrosio, G, Di Bartolo, P, Fattore, L, Presbitero, P, Calabrese, M, Evola, R, Gamba, M, Ibarra, M, Munoz, E, Sanchez, D, Herrera, C, Rios, J, Llamas, E, Esperon, G, Cantu, E, Fragoso, J, Gonzalez, J, Martinez, G, Padilla, F, Mier, G, Marmolejo, D, Ruiz, J, Portilla, N, Rosas, E, Machado, G, Ramos, J, Briones, I, van Hessen, M, Strikwerda, S, The, S, Kooy, A, Ronner, E, Nierop, P, Remmen, J, Groenemeijer, B, Hamer, B, Basart, D, van Lennep, H, Nieuwdorp, M, van Dijk, M, Kentgens, S, van Kempen, W, Hoogendijk, J, Spiering, W, Voors-Pette, C, Kose, V, de Waard, D, Gonkel, F, Kaasjager, H, Lingan, G, Agous, I, Kruik, H, Imholz, B, Pieterse, M, Manrique, H, Villena, J, Leon, L, Kundert, K, Minchola, J, Pinto, M, Heredia, J, Rodriguez, A, Guerreros, C, Berrospi, P, Zubiate, C, Allemant, A, Arbanil, H, Ponciano, W, Calderon, J, Lisson, R, Segura, L, Sidorowicz-Bialynicka, A, Sciborski, R, Fares, I, Mader, P, Skierkowska, J, Stasinska, T, Pomiecko, W, Skorski, M, Krzyzagorska, E, Polaszewska-Muszynska, M, Sowinski, D, Strojek, K, Rosinska-Migda, J, Romanczuk, P, Golebiowski, G, Kubica, J, Mazurek, T, Wojnowski, L, Pasternak, D, Stachlewski, P, Trzepla, E, Bogdanowicz, G, Uzunow, A, Potakowska, I, Miszczyszyn, Z, Waszyrowski, T, Smolenskaya, O, Lukyanov, Y, Vorokhobina, N, Khalimov, Y, Orlikova, O, Rebrov, A, Kukharchuk, V, Boldueva, S, Arkhipov, M, Zhelninova, T, Pavlysh, E, Antsiferov, M, Panov, A, Pavlova, M, Shustov, S, Demchenko, E, Galyavich, A, Malakhina, E, Semenova, O, Kobalava, Z, Kotova, S, Gavrisheva, I, Oschepkova, E, Karpov, Y, Sidorenko, B, Kislyak, O, Ametov, A, Dreval, A, Grineva, E, Mkrtumyan, A, Tyurina, T, Sazonova, O, Bonnici, F, Ranjith, N, Burgess, L, Nortje, H, Distiller, L, Mitha, I, Moore, R, Conradie, M, Horak, A, Pillay, S, Wellmann, H, Berg, E, Pillai, P, Padayachee, T, Corbett, C, Makan, H, Wing, J, Vawda, Z, Ebrahim, I, Mitha, E, Bhorat, A, Fernandez, J, Munoz, C, Cortada, J, Conde, A, Calvo, C, Extremera, B, Delgado, E, Masmiquel, L, Puig, J, Parreno, L, Mauricio, D, Redon, J, Brito, M, Lopez, C, de la Morera, J, Linderfalk, C, Larnefeldt, H, Olsson, A, Lonneborg, L, Ekelund, M, Samad, B, Borgencrantz, B, Nilsson, J, Berglund, O, Svensson, M, Mooe, T, Curiac, D, Albin, J, Angesjo, E, Lannemyr, O, Chen, J, Tien, K, Ueng, K, Lai, W, Yin, W, Hung, Y, Shyu, K, Hou, J, Lam, H, Laothavorn, P, Kuanprasert, S, Khovidhunkit, W, Benjasuratwong, Y, Chotinaiwattarakul, C, Mamanasiri, S, Suraamornkul, S, Pratipanawatr, T, Nitiyanant, W, Heller, S, Pieters, R, Strang, C, Bodalia, B, Middleton, A, Hall, T, Chapman, G, Calvert, J, Reed, R, Tam, D, Butcher, G, Jones, N, Takhar, A, Turner, W, Mcnally, D, Corey, O, Chapman, J, Mohr, S, Edwards, S, Ocampo, A, Kandath, D, Aude, Y, Ervin, W, Savin, V, Anderson, R, Littlefield, R, Oberoi, M, Platt, G, Yazdani, S, Mangoo-Karim, R, Walder, J, Gogia, H, Chandrashekhar, Y, Boccalandro, F, Rogers, W, Bilazarian, S, Zieve, F, Siage, Y, O'Connor, T, Mudaliar, S, Nikas, A, Giusti, R, Glover, R, Chilka, S, French, W, Roth, E, Singh, N, Christofferson, R, Stich, M, Dagogo-Jack, S, Allison, J, Zengotita, G, Ison, R, Iteld, B, Sulistio, M, Gonzalez, E, Gorman, T, Hage-Korban, E, Reddy, R, Byars, W, Antonishen, M, Benjamin, S, First, B, Rosado, J, Bruschetta, H, Poling, T, Rosendorff, C, Kerstein, H, Saba, F, Willis, J, Adams, K, Vazquez, E, Ellison, H, Kahn, B, Kereiakes, D, Powell, S, Raskin, P, Smith, K, Varma, S, Whittier, F, Casanova, R, Isserman, S, Kaye, W, Mcguinn, W, Bartkowiak, A, Dworkin, L, Labrador, C, Podlecki, D, Popovtzer, M, Aronoff, S, Ballantyne, C, Ortiz, E, Mora, A, Pitts, T, Reinhardt, S, Soucie, G, Wainwright, W, Henson, B, Sklaver, N, Arakaki, R, Brown, J, Chalavarya, G, Chochinov, R, Dixon, T, Kutner, M, Perlman, R, Raisinghani, A, Salacata, A, Awasty, V, Elinoff, V, George, W, LaRochelle-Gryseels, A, Mercado, A, Miller, G, Qureshi, M, Steljes, A, Wefald, F, Wilson, J, Chinn, J, Chuang, R, Comulada-Rivera, A, Hartman, I, Narayan, P, Pacheco, T, Weiss, R, Beavins, J, Creevy, J, Hamroff, G, Hodson, R, Kosinski, E, Krichmar, P, Patel, R, Schneider, R, Shapiro, J, Sharp, D, Speer, J, Stegemoller, R, Waxman, F, Chang, F, Braun, E, Eder, F, Minor, S, Albert, M, Carr, K, Diaczok, B, Gastman, I, Gupta, V, Longshaw, K, Gonzalez-Campoy, J, Raikhel, M, Thomas, J, Wood, K, Diab, I, Furda, J, Gelernt, M, Halter, M, House, B, Kaster, S, Raad, G, Stamatin, R, Barker, B, Blonder, R, Bloomberg, R, Calderon, R, Carrol, A, Comerota, A, Feinglos, M, Henderson, D, Kastelic, R, Stonesifer, L, Talano, J, Lee, P, Brosseau, J, Clark, W, Cohen, E, Fialkow, J, Horton, K, Kozman, H, Mcgill, J, Mihills, C, Poonawala, R, Shore, K, Tejada, L, Torres, R, Wright, W, Calatayud, G, Chandna, H, Drozdiak, R, Fink, R, Gill, R, Glandt, M, Gottlieb, D, Hack, T, Kay, J, Mansouri, V, Mcknight, T, Mostel, E, Schmidt, L, Seide, H, Sonel, E, Taylor, R, Velasquez, M, Bretton, E, Feldman, R, Hartman, A, Hershon, K, Leach, C, Martin, E, Mohiuddin, F, Naygandhi, Y, Riske, T, Schima, S, Uzoaga, E, Ward, H, Weinstock, R, Williams, T, Altschuller, A, Aoki, T, Blumenthal, S, Cash, A, Eisner, G, Gutmann, J, Hagan, M, Kabour, A, Markus, T, Mckenzie, W, Moursi, M, Mystkowski, P, Ovalle, F, Perkins, R, Popeil, L, Saniuk, R, Sierra, Y, Alvarado, O, Anderson, J, Bajaj, M, Blank, R, Chu, A, Levinsky, L, Levy, P, Osborne, J, Pavon, H, Sanderlin, D, Schaer, G, Zarich, S, Atassi, K, Bayron, C, Casagrande, M, Das, D, Gimness, M, Handel, F, Kinstrey, T, Leu, S, Osei, K, Nouel, J, Soltani, Z, Sussman, H, Chiu, K, Duda, R, Farnsworth, K, Lano, M, Lee, F, Levin, P, Pratt, S, Richwine, R, Ruiz-Rivera, L, Turner, J, Wood, J, Zigrang, W, Baquerizo, H, Colon, C, Demattia, J, Desai, V, Fitz-Patrick, D, Goral, S, Odhav, A, Prentiss, A, Ruff, C, Wu, W, Wyne, K, Abbott, L, Applegate, R, Cabral, J, Kotha, P, Ortega, P, Simmons, D, Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, Desai N, Abrahamsen T, Grossman M, Morin S, Im K, Hoffman E, Gabovitch D, Pricken A, Buskila A, Stahre C, Price D, Billing-Clason S, Sabel K, Monyak J, Sjostrand M, Wei C, Lu J, Miller E, Raichlen J, Fitt S, Iqbal N, Donovan M, Davidson JA, Aguilar-Salinas C, Alvarsson M, Amerena J, Ardissino D, Averkov O, Avogaro A, Barnett A, Bretzel R, Chiang CE, Codoceo V, Corbalan R, Dalby A, Darius H, Deerochanawong C, Dellborg M, Eliaschewitz F, Garcia-Castillo A, Gomis R, Henry P, Hoekstra J, Jermendy G, Kastelein J, Keech A, Kiss R, Krempf M, Laakso M, Leiter L, Leitersdorf E, Lewis B, Litwak L, Lopez-Sendon J, Ma R, McGuire D, Medina F, Moses R, Nicolau JC, Opolski G, Ophuis TO, Paolasso E, Ruda M, Kumar KMP, Shestakova M, Sheu WHH, Smahelova A, Bhupathiraju BSR, Spinar J, Sritata P, Strojeck K, Villena-Chavez JE, Jia WP, Huo Y, Lowe C, Awtry E, Berger C, Desai AS, Gelfand E, Leeman D, Link M, Ruberg F, Vita J, Rost N, Silverman S, Greenberger NJ, Lerch MM, Gersh B, Nesto R, Del Prato S, Tuomilehto J, Kelsey S, Alvarisqueta A, Cuadrado J, Rista L, Hermida S, Baccaro C, Luquez C, Lagrutta M, Maffei L, Bartolacci I, Montana O, Cutuli H, Berli M, Lorenzatti A, Frechtel G, La Greca R, Fretes O, Diaz M, Papini NR, Farias E, Issa C, Elbert A, Lehman R, Arya M, Singh B, Colquhoun D, Jayasinghe R, de Looze F, Blombery P, Ward G, Szto G, Abhayaratna W, Borges J, Russo L, Felicio J, Santos F, Guimaraes F, Castro ML, Rossi P, Armaganijan D, Leaes P, Bandeira F, Franken M, Rassi N, Rea R, Zanella M, Amodeo C, Cesar L, Betti R, Chacra A, Schmid H, Bell A, Syan G, Zadra R, Conter H, Dumas R, Borts D, Dattani I, Poirier P, Cha J, Dzongowski P, Labonte R, St Pierre B, Gaudet D, Kouz S, Lamy A, Tishler S, Chehayeb R, Bedard J, Hramiak I, Teitelbaum I, Fortin C, Woo V, Conway J, Mehta P, Robinson S, Sussex B, Chiasson J, Muirhead N, Bose S, Ouellet A, Yale J, Bhargava R, Lau D, Tobe S, Perron P, Sigalas J, Bilodeau L, Tytus R, Achyuthan G, Pearce M, Steele A, Bailey G, Ma P, St-Maurice F, Rupka D, Houlden R, Bailey A, Rewa G, Sohal P, Ting R, Prieto J, Rodriguez M, Godoy G, Larenas G, Pincetti C, Cobos L, Saavedra V, Varleta P, Lucero F, Kuzmanic O, Acevedo M, Aguirre M, Florenzano F, Ma J, Bao Y, Jiang M, Xu W, Shi Y, Zheng M, Li Y, Dong Y, Zhao W, Sun M, Lei M, Wang J, Pistek Z, Rihacek I, Kucera D, Brada M, Naplava R, Karasova J, Vlasicova H, Skopecek J, Spinarova L, Raclavska L, Sarbochova R, Okenka L, Racicka E, Urbancova K, Oznerova M, Lorenc Z, Wasserburger B, Zahumensky E, Grunfeldova H, Hradec J, Lukac M, Svacina S, Podzimek J, Hemzsky L, Mikulkova I, Pavlickova J, Brychta T, Chochola J, Couffinhal T, Elbaz M, Petit C, Faller B, Marechaud R, Moulin P, Fendri S, Nazeyrollas P, Wendisch U, Busch K, Klausmann G, Duengen H, Appel K, Toursarkissian N, Jung T, Ott P, Schenkenberger I, Kuesters D, Landers B, Nischik R, Fischer H, Tschoepe D, Paschen B, Krause K, Derwahl K, Wenzl-Bauer V, Hamann A, Strotmann H, Milek K, Mueller S, Chu D, Tan K, Kung K, Tsang C, Tomlinson B, Koranyi L, Kerenyi Z, Benczur B, Illyes L, Hidvegi T, Somogyi A, Valco J, Ferenczi S, Rapi J, Voros P, Winkler G, Sydo T, Hetey M, Simon K, Penzes J, Kempler P, Bako B, Lengyel Z, Witmann I, Dudas M, Vandorfi G, Takacs J, Matoltsy A, Ladanyi E, Gyimesi A, Sadikot S, Parikh K, Jain S, Yajnik C, Sosale A, Shamanna P, Srikanta S, Shah S, Srinivas A, Banker D, Shah P, Sharda A, Makkar B, Rais N, Mardikar H, Mishra A, Bhupati S, Menon J, Sathe S, Gupta R, Sharma V, Darawsha M, Herskovits T, Hamoud S, Nikolsky E, Adawi F, Zimlichman R, Tsalihin D, Wainstein J, Klainman E, Mosseri M, Yerushalmi Y, Karnieli E, Knobler H, Benchetrit S, Tsur A, Yagil Y, Atar S, Beberashvili I, Fuchs S, Stern N, Pollak A, Chajek-Shaul T, Rozenman Y, Biton A, Bramucci E, Fiscella A, Grassia V, Piatti P, De Cosmo S, Di Lorenzo L, Merlini P, Mannucci E, Frontoni S, Trevisan R, Zenari L, Lambiase C, Salvioni A, Silvestri O, Ambrosio G, Di Bartolo P, Fattore L, Presbitero P, Calabrese M, Evola R, Gamba MA, Ibarra MOD, Munoz EC, Sanchez DR, Herrera CH, Rios JP, Llamas EB, Esperon GL, Cantu EG, Fragoso JN, Gonzalez JG, Martinez GR, Padilla FP, Mier GM, Marmolejo DH, Ruiz JG, Portilla NC, Rosas EL, Machado GM, Ramos JC, Briones IR, van Hessen MWJ, Strikwerda S, The SHK, Kooy A, Ronner E, Nierop PR, Remmen JJ, Groenemeijer BE, Hamer BJB, Basart DCG, van Lennep HWOR, Nieuwdorp M, van Dijk MPM, Kentgens S, van Kempen WW, Hoogendijk J, Spiering W, Voors-Pette C, Kose V, de Waard DEP, Gonkel F, Kaasjager HAH, Lingan GMR, Agous I, Kruik HJ, Imholz BPM, Pieterse M, Manrique H, Villena J, Leon L, Kundert K, Minchola J, Pinto M, Heredia J, Rodriguez A, Guerreros C, Berrospi P, Zubiate C, Allemant A, Arbanil H, Ponciano W, Calderon J, Lisson R, Segura L, Sidorowicz-Bialynicka A, Sciborski R, Fares I, Mader P, Skierkowska J, Stasinska T, Pomiecko W, Skorski M, Krzyzagorska E, Polaszewska-Muszynska M, Sowinski D, Strojek K, Rosinska-Migda J, Romanczuk P, Golebiowski G, Kubica J, Mazurek T, Wojnowski L, Pasternak D, Stachlewski P, Trzepla E, Bogdanowicz G, Uzunow A, Potakowska I, Miszczyszyn Z, Waszyrowski T, Smolenskaya O, Lukyanov Y, Vorokhobina N, Khalimov Y, Orlikova O, Rebrov A, Kukharchuk V, Boldueva S, Arkhipov M, Zhelninova T, Pavlysh E, Antsiferov M, Panov A, Pavlova M, Shustov S, Demchenko E, Galyavich A, Malakhina E, Semenova O, Kobalava Z, Kotova S, Gavrisheva I, Oschepkova E, Karpov Y, Sidorenko B, Kislyak O, Ametov A, Dreval A, Grineva E, Mkrtumyan A, Tyurina T, Sazonova O, Bonnici F, Ranjith N, Burgess L, Nortje H, Distiller L, Mitha I, Moore R, Conradie M, Horak A, Pillay S, Wellmann H, Berg E, Pillai P, Padayachee T, Corbett C, Makan H, Wing J, Vawda Z, Ebrahim I, Mitha E, Bhorat A, Fernandez JC, Munoz C, Cortada JB, Conde AC, Calvo C, Extremera BG, Delgado E, Masmiquel L, Puig JG, Parreno LD, Mauricio D, Redon J, Brito M, Lopez C, de la Morera JS, Linderfalk C, Larnefeldt H, Olsson A, Lonneborg L, Ekelund M, Samad B, Borgencrantz B, Nilsson J, Berglund O, Svensson M, Mooe T, Curiac D, Albin J, Angesjo E, Lannemyr O, Chiang C, Sheu W, Chen J, Tien K, Ueng K, Lai W, Yin W, Hung Y, Shyu K, Hou J, Lam H, Laothavorn P, Kuanprasert S, Khovidhunkit W, Benjasuratwong Y, Chotinaiwattarakul C, Mamanasiri S, Suraamornkul S, Pratipanawatr T, Nitiyanant W, Heller S, Ray K, Pieters R, Strang C, Bodalia B, Middleton A, Hall T, Chapman G, Calvert J, Reed R, Tam D, Butcher G, Jones N, Takhar A, Turner W, McNally D, Corey O, Chapman J, Mohr S, Edwards S, Bhatt D, Ocampo A, Kandath D, Aude Y, Ervin W, Savin V, Anderson R, Littlefield R, Oberoi M, Platt GE, Yazdani S, Mangoo-Karim R, Walder J, Gogia H, Chandrashekhar Y, Boccalandro F, Rogers W, Bilazarian S, Zieve F, Siage Y, O'Connor T, Mudaliar S, Nikas A, Giusti R, Glover R, Chilka S, French W, Roth E, Singh N, Christofferson R, Stich M, Dagogo-Jack S, Allison J, Zengotita GA, Ison R, Iteld B, Sulistio M, Gonzalez E, Gorman T, Hage-Korban E, Reddy R, Byars W, Antonishen M, Benjamin S, First B, Rosado J, Bruschetta H, Poling T, Rosendorff C, Kerstein HJ, Saba F, Willis J, Adams K, Vazquez EC, Ellison H, Kahn B, Kereiakes D, Powell S, Raskin P, Smith K, Varma S, Whittier F, Casanova R, Isserman S, Kaye W, McGuinn W, Bartkowiak A, Dworkin L, Labrador CA, Podlecki D, Popovtzer M, Aronoff S, Ballantyne C, Ortiz EG, Mora A, Pitts T, Reinhardt S, Soucie G, Wainwright W, Henson B, Sklaver N, Arakaki R, Brown J, Chalavarya G, Chochinov R, Dixon T, Kutner M, Perlman R, Raisinghani A, Salacata A, Awasty V, Elinoff V, George W, LaRochelle-Gryseels A, Mercado A, Miller G, Qureshi M, Steljes A, Wefald F, Wilson J, Chinn J, Chuang RB, Comulada-Rivera A, Hartman I, Narayan P, Pacheco T, Weiss R, Beavins J, Creevy J, Hamroff G, Hodson R, Kosinski E, Krichmar P, Patel R, Schneider R, Shapiro J, Sharp D, Speer J, Stegemoller R, Waxman F, Chang FY, Braun E, Eder F, Minor S, Albert M, Carr KW, Diaczok B, Gastman I, Gupta V, Longshaw K, Gonzalez-Campoy JM, Raikhel M, Thomas J, Wood K, Diab I, Furda J, Gelernt M, Halter M, House B, Kaster S, Raad G, Stamatin R, Barker B, Blonder R, Bloomberg RJ, Calderon RB, Carrol A, Comerota A, Feinglos M, Henderson D, Kastelic R, Stonesifer LD, Talano J, Lee PV, Brosseau J, Clark W, Cohen E, Fialkow J, Horton K, Kozman H, McGill J, Mihills C, Poonawala R, Shore K, Tejada L, Torres R, Wright W, Calatayud G, Chandna H, Drozdiak R, Fink R, Gill R, Glandt M, Gottlieb DW, Hack T, Kay J, Mansouri V, McKnight T, Mostel E, Schmidt L, Seide H, Sonel E, Taylor R, Velasquez M, Bretton E, Feldman R, Hartman A, Hershon K, Leach CR, Martin E, Mohiuddin F, Naygandhi Y, Riske T, Schima S, Uzoaga ER, Ward H, Weinstock R, Williams T, Altschuller A, Aoki T, Blumenthal S, Cash A, Eisner G, Gutmann J, Hagan M, Kabour A, Markus T, McKenzie W, Moursi M, Mystkowski P, Ovalle F, Perkins R, Popeil L, Saniuk R, Sierra Y, Alvarado O, Anderson J, Bajaj M, Blank R, Chu A, Levinsky L, Levy P, Osborne J, Pavon H, Sanderlin D, Schaer G, Zarich S, Atassi K, Bayron C, Casagrande M, Das D, Gimness M, Handel F, Kinstrey T, Leu S, Osei K, Nouel JS, Soltani Z, Sussman H, Chiu K, Duda R, Farnsworth K, Lano M, Lee F, Levin P, Pratt S, Richwine R, Ruiz-Rivera L, Turner J, Wood J, Zigrang WD, Baquerizo HR, Colon CB, Demattia J, Desai V, Fitz-Patrick D, Goral S, Odhav A, Prentiss A, Ruff C, Wu W, Wyne K, Abbott LG, Applegate R, Cabral J, Kotha P, Ortega P, and Simmons D

Abstract

BACKGROUND: The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. METHODS: We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS: A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). CONCLUSIONS: DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was

Published
2013

26. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus

Author

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, Desai N, Abrahamsen T, Grossman M, Morin S, Im K, Hoffman E, Gabovitch D, Pricken A, Buskila A, Stahre C, Price D, Billing-Clason S, Sabel K, Monyak J, Sjostrand M, Wei C, Lu J, Miller E, Raichlen J, Fitt S, Iqbal N, Donovan M, Davidson JA, Aguilar-Salinas C, Alvarsson M, Amerena J, Ardissino D, Averkov O, Avogaro A, Barnett A, Bretzel R, Chiang CE, Codoceo V, Corbalan R, Dalby A, Darius H, Deerochanawong C, Dellborg M, Eliaschewitz F, Garcia-Castillo A, Gomis R, Henry P, Hoekstra J, Jermendy G, Kastelein J, Keech A, Kiss R, Krempf M, Laakso M, Leiter L, Leitersdorf E, Lewis B, Litwak L, Lopez-Sendon J, Ma R, McGuire D, Medina F, Moses R, Nicolau JC, Opolski G, Ophuis TO, Paolasso E, Ruda M, Kumar KMP, Shestakova M, Sheu WHH, Smahelova A, Bhupathiraju BSR, Spinar J, Sritata P, Strojeck K, Villena-Chavez JE, Jia WP, Huo Y, Lowe C, Awtry E, Berger C, Desai AS, Gelfand E, Leeman D, Link M, Ruberg F, Vita J, Rost N, Silverman S, Greenberger NJ, Lerch MM, Gersh B, Nesto R, Del Prato S, Tuomilehto J, Kelsey S, Alvarisqueta A, Cuadrado J, Rista L, Hermida S, Baccaro C, Luquez C, Lagrutta M, Maffei L, Bartolacci I, Montana O, Cutuli H, Berli M, Lorenzatti A, Frechtel G, La Greca R, Fretes O, Diaz M, Papini NR, Farias E, Issa C, Elbert A, Lehman R, Arya M, Singh B, Colquhoun D, Jayasinghe R, de Looze F, Blombery P, Ward G, Szto G, Abhayaratna W, Borges J, Russo L, Felicio J, Santos F, Guimaraes F, Castro ML, Rossi P, Armaganijan D, Leaes P, Bandeira F, Franken M, Rassi N, Rea R, Zanella M, Amodeo C, Cesar L, Betti R, Chacra A, Schmid H, Bell A, Syan G, Zadra R, Conter H, Dumas R, Borts D, Dattani I, Poirier P, Cha J, Dzongowski P, Labonte R, St Pierre B, Gaudet D, Kouz S, Lamy A, Tishler S, Chehayeb R, Bedard J, Hramiak I, Teitelbaum I, Fortin C, Woo V, Conway J, Mehta P, Robinson S, Sussex B, Chiasson J, Muirhead N, Bose S, Ouellet A, Yale J, Bhargava R, Lau D, Tobe S, Perron P, Sigalas J, Bilodeau L, Tytus R, Achyuthan G, Pearce M, Steele A, Bailey G, Ma P, St-Maurice F, Rupka D, Houlden R, Bailey A, Rewa G, Sohal P, Ting R, Prieto J, Rodriguez M, Godoy G, Larenas G, Pincetti C, Cobos L, Saavedra V, Varleta P, Lucero F, Kuzmanic O, Acevedo M, Aguirre M, Florenzano F, Ma J, Bao Y, Jiang M, Xu W, Shi Y, Zheng M, Li Y, Dong Y, Zhao W, Sun M, Lei M, Wang J, Pistek Z, Rihacek I, Kucera D, Brada M, Naplava R, Karasova J, Vlasicova H, Skopecek J, Spinarova L, Raclavska L, Sarbochova R, Okenka L, Racicka E, Urbancova K, Oznerova M, Lorenc Z, Wasserburger B, Zahumensky E, Grunfeldova H, Hradec J, Lukac M, Svacina S, Podzimek J, Hemzsky L, Mikulkova I, Pavlickova J, Brychta T, Chochola J, Couffinhal T, Elbaz M, Petit C, Faller B, Marechaud R, Moulin P, Fendri S, Nazeyrollas P, Wendisch U, Busch K, Klausmann G, Duengen H, Appel K, Toursarkissian N, Jung T, Ott P, Schenkenberger I, Kuesters D, Landers B, Nischik R, Fischer H, Tschoepe D, Paschen B, Krause K, Derwahl K, Wenzl-Bauer V, Hamann A, Strotmann H, Milek K, Mueller S, Chu D, Tan K, Kung K, Tsang C, Tomlinson B, Koranyi L, Kerenyi Z, Benczur B, Illyes L, Hidvegi T, Somogyi A, Valco J, Ferenczi S, Rapi J, Voros P, Winkler G, Sydo T, Hetey M, Simon K, Penzes J, Kempler P, Bako B, Lengyel Z, Witmann I, Dudas M, Vandorfi G, Takacs J, Matoltsy A, Ladanyi E, Gyimesi A, Sadikot S, Parikh K, Jain S, Yajnik C, Sosale A, Shamanna P, Srikanta S, Shah S, Srinivas A, Banker D, Shah P, Sharda A, Makkar B, Rais N, Mardikar H, Mishra A, Bhupati S, Menon J, Sathe S, Gupta R, Sharma V, Darawsha M, Herskovits T, Hamoud S, Nikolsky E, Adawi F, Zimlichman R, Tsalihin D, Wainstein J, Klainman E, Mosseri M, Yerushalmi Y, Karnieli E, Knobler H, Benchetrit S, Tsur A, Yagil Y, Atar S, Beberashvili I, Fuchs S, Stern N, Pollak A, Chajek-Shaul T, Rozenman Y, Biton A, Bramucci E, Fiscella A, Grassia V, Piatti P, De Cosmo S, Di Lorenzo L, Merlini P, Mannucci E, Frontoni S, Trevisan R, Zenari L, Lambiase C, Salvioni A, Silvestri O, Ambrosio G, Di Bartolo P, Fattore L, Presbitero P, Calabrese M, Evola R, Gamba MA, Ibarra MOD, Munoz EC, Sanchez DR, Herrera CH, Rios JP, Llamas EB, Esperon GL, Cantu EG, Fragoso JN, Gonzalez JG, Martinez GR, Padilla FP, Mier GM, Marmolejo DH, Ruiz JG, Portilla NC, Rosas EL, Machado GM, Ramos JC, Briones IR, van Hessen MWJ, Strikwerda S, The SHK, Kooy A, Ronner E, Nierop PR, Remmen JJ, Groenemeijer BE, Hamer BJB, Basart DCG, van Lennep HWOR, Nieuwdorp M, van Dijk MPM, Kentgens S, van Kempen WW, Hoogendijk J, Spiering W, Voors-Pette C, Kose V, de Waard DEP, Gonkel F, Kaasjager HAH, Lingan GMR, Agous I, Kruik HJ, Imholz BPM, Pieterse M, Manrique H, Villena J, Leon L, Kundert K, Minchola J, Pinto M, Heredia J, Rodriguez A, Guerreros C, Berrospi P, Zubiate C, Allemant A, Arbanil H, Ponciano W, Calderon J, Lisson R, Segura L, Sidorowicz-Bialynicka A, Sciborski R, Fares I, Mader P, Skierkowska J, Stasinska T, Pomiecko W, Skorski M, Krzyzagorska E, Polaszewska-Muszynska M, Sowinski D, Strojek K, Rosinska-Migda J, Romanczuk P, Golebiowski G, Kubica J, Mazurek T, Wojnowski L, Pasternak D, Stachlewski P, Trzepla E, Bogdanowicz G, Uzunow A, Potakowska I, Miszczyszyn Z, Waszyrowski T, Smolenskaya O, Lukyanov Y, Vorokhobina N, Khalimov Y, Orlikova O, Rebrov A, Kukharchuk V, Boldueva S, Arkhipov M, Zhelninova T, Pavlysh E, Antsiferov M, Panov A, Pavlova M, Shustov S, Demchenko E, Galyavich A, Malakhina E, Semenova O, Kobalava Z, Kotova S, Gavrisheva I, Oschepkova E, Karpov Y, Sidorenko B, Kislyak O, Ametov A, Dreval A, Grineva E, Mkrtumyan A, Tyurina T, Sazonova O, Bonnici F, Ranjith N, Burgess L, Nortje H, Distiller L, Mitha I, Moore R, Conradie M, Horak A, Pillay S, Wellmann H, Berg E, Pillai P, Padayachee T, Corbett C, Makan H, Wing J, Vawda Z, Ebrahim I, Mitha E, Bhorat A, Fernandez JC, Munoz C, Cortada JB, Conde AC, Calvo C, Extremera BG, Delgado E, Masmiquel L, Puig JG, Parreno LD, Mauricio D, Redon J, Brito M, Lopez C, de la Morera JS, Linderfalk C, Larnefeldt H, Olsson A, Lonneborg L, Ekelund M, Samad B, Borgencrantz B, Nilsson J, Berglund O, Svensson M, Mooe T, Curiac D, Albin J, Angesjo E, Lannemyr O, Chiang C, Sheu W, Chen J, Tien K, Ueng K, Lai W, Yin W, Hung Y, Shyu K, Hou J, Lam H, Laothavorn P, Kuanprasert S, Khovidhunkit W, Benjasuratwong Y, Chotinaiwattarakul C, Mamanasiri S, Suraamornkul S, Pratipanawatr T, Nitiyanant W, Heller S, Ray K, Pieters R, Strang C, Bodalia B, Middleton A, Hall T, Chapman G, Calvert J, Reed R, Tam D, Butcher G, Jones N, Takhar A, Turner W, McNally D, Corey O, Chapman J, Mohr S, Edwards S, Bhatt D, Ocampo A, Kandath D, Aude Y, Ervin W, Savin V, Anderson R, Littlefield R, Oberoi M, Platt GE, Yazdani S, Mangoo-Karim R, Walder J, Gogia H, Chandrashekhar Y, Boccalandro F, Rogers W, Bilazarian S, Zieve F, Siage Y, O'Connor T, Mudaliar S, Nikas A, Giusti R, Glover R, Chilka S, French W, Roth E, Singh N, Christofferson R, Stich M, Dagogo-Jack S, Allison J, Zengotita GA, Ison R, Iteld B, Sulistio M, Gonzalez E, Gorman T, Hage-Korban E, Reddy R, Byars W, Antonishen M, Benjamin S, First B, Rosado J, Bruschetta H, Poling T, Rosendorff C, Kerstein HJ, Saba F, Willis J, Adams K, Vazquez EC, Ellison H, Kahn B, Kereiakes D, Powell S, Raskin P, Smith K, Varma S, Whittier F, Casanova R, Isserman S, Kaye W, McGuinn W, Bartkowiak A, Dworkin L, Labrador CA, Podlecki D, Popovtzer M, Aronoff S, Ballantyne C, Ortiz EG, Mora A, Pitts T, Reinhardt S, Soucie G, Wainwright W, Henson B, Sklaver N, Arakaki R, Brown J, Chalavarya G, Chochinov R, Dixon T, Kutner M, Perlman R, Raisinghani A, Salacata A, Awasty V, Elinoff V, George W, LaRochelle-Gryseels A, Mercado A, Miller G, Qureshi M, Steljes A, Wefald F, Wilson J, Chinn J, Chuang RB, Comulada-Rivera A, Hartman I, Narayan P, Pacheco T, Weiss R, Beavins J, Creevy J, Hamroff G, Hodson R, Kosinski E, Krichmar P, Patel R, Schneider R, Shapiro J, Sharp D, Speer J, Stegemoller R, Waxman F, Chang FY, Braun E, Eder F, Minor S, Albert M, Carr KW, Diaczok B, Gastman I, Gupta V, Longshaw K, Gonzalez-Campoy JM, Raikhel M, Thomas J, Wood K, Diab I, Furda J, Gelernt M, Halter M, House B, Kaster S, Raad G, Stamatin R, Barker B, Blonder R, Bloomberg RJ, Calderon RB, Carrol A, Comerota A, Feinglos M, Henderson D, Kastelic R, Stonesifer LD, Talano J, Lee PV, Brosseau J, Clark W, Cohen E, Fialkow J, Horton K, Kozman H, McGill J, Mihills C, Poonawala R, Shore K, Tejada L, Torres R, Wright W, Calatayud G, Chandna H, Drozdiak R, Fink R, Gill R, Glandt M, Gottlieb DW, Hack T, Kay J, Mansouri V, McKnight T, Mostel E, Schmidt L, Seide H, Sonel E, Taylor R, Velasquez M, Bretton E, Feldman R, Hartman A, Hershon K, Leach CR, Martin E, Mohiuddin F, Naygandhi Y, Riske T, Schima S, Uzoaga ER, Ward H, Weinstock R, Williams T, Altschuller A, Aoki T, Blumenthal S, Cash A, Eisner G, Gutmann J, Hagan M, Kabour A, Markus T, McKenzie W, Moursi M, Mystkowski P, Ovalle F, Perkins R, Popeil L, Saniuk R, Sierra Y, Alvarado O, Anderson J, Bajaj M, Blank R, Chu A, Levinsky L, Levy P, Osborne J, Pavon H, Sanderlin D, Schaer G, Zarich S, Atassi K, Bayron C, Casagrande M, Das D, Gimness M, Handel F, Kinstrey T, Leu S, Osei K, Nouel JS, Soltani Z, Sussman H, Chiu K, Duda R, Farnsworth K, Lano M, Lee F, Levin P, Pratt S, Richwine R, Ruiz-Rivera L, Turner J, Wood J, Zigrang WD, Baquerizo HR, Colon CB, Demattia J, Desai V, Fitz-Patrick D, Goral S, Odhav A, Prentiss A, Ruff C, Wu W, Wyne K, Abbott LG, Applegate R, Cabral J, Kotha P, Ortega P, Simmons D, General Internal Medicine, Vascular Medicine, Other departments, Scirica, B, Bhatt, D, Braunwald, E, Steg, P, Davidson, J, Hirshberg, B, Ohman, P, Frederich, R, Wiviott, S, Hoffman, E, Cavender, M, Udell, J, Desai, N, Mosenzon, O, Mcguire, D, Ray, K, Leiter, L, Raz, I, Abrahamsen, T, Grossman, M, Morin, S, Im, K, Gabovitch, D, Pricken, A, Buskila, A, Stahre, C, Price, D, Billing-Clason, S, Sabel, K, Monyak, J, Sjostrand, M, Wei, C, Lu, J, Miller, E, Raichlen, J, Fitt, S, Iqbal, N, Donovan, M, Aguilar-Salinas, C, Alvarsson, M, Amerena, J, Ardissino, D, Averkov, O, Avogaro, A, Barnett, A, Bretzel, R, Chiang, C, Codoceo, V, Corbalan, R, Dalby, A, Darius, H, Deerochanawong, C, Dellborg, M, Eliaschewitz, F, Garcia-Castillo, A, Gomis, R, Henry, P, Hoekstra, J, Jermendy, G, Kastelein, J, Keech, A, Kiss, R, Krempf, M, Laakso, M, Leitersdorf, E, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Medina, F, Moses, R, Nicolau, J, Opolski, G, Ophuis, T, Paolasso, E, Ruda, M, Kumar, K, Shestakova, M, Sheu, W, Smahelova, A, Bhupathiraju, B, Spinar, J, Sritata, P, Strojeck, K, Villena-Chavez, J, Jia, W, Huo, Y, Lowe, C, Awtry, E, Berger, C, Desai, A, Gelfand, E, Leeman, D, Link, M, Ruberg, F, Vita, J, Rost, N, Silverman, S, Greenberger, N, Lerch, M, Gersh, B, Nesto, R, Del Prato, S, Tuomilehto, J, Kelsey, S, Alvarisqueta, A, Cuadrado, J, Rista, L, Hermida, S, Baccaro, C, Luquez, C, Lagrutta, M, Maffei, L, Bartolacci, I, Montana, O, Cutuli, H, Berli, M, Lorenzatti, A, Frechtel, G, La Greca, R, Fretes, O, Diaz, M, Papini, N, Farias, E, Issa, C, Elbert, A, Lehman, R, Arya, M, Singh, B, Colquhoun, D, Jayasinghe, R, de Looze, F, Blombery, P, Ward, G, Szto, G, Abhayaratna, W, Borges, J, Russo, L, Felicio, J, Santos, F, Guimaraes, F, Castro, M, Rossi, P, Armaganijan, D, Leaes, P, Bandeira, F, Franken, M, Rassi, N, Rea, R, Zanella, M, Amodeo, C, Cesar, L, Betti, R, Chacra, A, Schmid, H, Bell, A, Syan, G, Zadra, R, Conter, H, Dumas, R, Borts, D, Dattani, I, Poirier, P, Cha, J, Dzongowski, P, Labonte, R, St Pierre, B, Gaudet, D, Kouz, S, Lamy, A, Tishler, S, Chehayeb, R, Bedard, J, Hramiak, I, Teitelbaum, I, Fortin, C, Woo, V, Conway, J, Mehta, P, Robinson, S, Sussex, B, Chiasson, J, Muirhead, N, Bose, S, Ouellet, A, Yale, J, Bhargava, R, Lau, D, Tobe, S, Perron, P, Sigalas, J, Bilodeau, L, Tytus, R, Achyuthan, G, Pearce, M, Steele, A, Bailey, G, Ma, P, St-Maurice, F, Rupka, D, Houlden, R, Bailey, A, Rewa, G, Sohal, P, Ting, R, Prieto, J, Rodriguez, M, Godoy, G, Larenas, G, Pincetti, C, Cobos, L, Saavedra, V, Varleta, P, Lucero, F, Kuzmanic, O, Acevedo, M, Aguirre, M, Florenzano, F, Ma, J, Bao, Y, Jiang, M, Xu, W, Shi, Y, Zheng, M, Li, Y, Dong, Y, Zhao, W, Sun, M, Lei, M, Wang, J, Pistek, Z, Rihacek, I, Kucera, D, Brada, M, Naplava, R, Karasova, J, Vlasicova, H, Skopecek, J, Spinarova, L, Raclavska, L, Sarbochova, R, Okenka, L, Racicka, E, Urbancova, K, Oznerova, M, Lorenc, Z, Wasserburger, B, Zahumensky, E, Grunfeldova, H, Hradec, J, Lukac, M, Svacina, S, Podzimek, J, Hemzsky, L, Mikulkova, I, Pavlickova, J, Brychta, T, Chochola, J, Couffinhal, T, Elbaz, M, Petit, C, Faller, B, Marechaud, R, Moulin, P, Fendri, S, Nazeyrollas, P, Wendisch, U, Busch, K, Klausmann, G, Duengen, H, Appel, K, Toursarkissian, N, Jung, T, Ott, P, Schenkenberger, I, Kuesters, D, Landers, B, Nischik, R, Fischer, H, Tschoepe, D, Paschen, B, Krause, K, Derwahl, K, Wenzl-Bauer, V, Hamann, A, Strotmann, H, Milek, K, Mueller, S, Chu, D, Tan, K, Kung, K, Tsang, C, Tomlinson, B, Koranyi, L, Kerenyi, Z, Benczur, B, Illyes, L, Hidvegi, T, Somogyi, A, Valco, J, Ferenczi, S, Rapi, J, Voros, P, Winkler, G, Sydo, T, Hetey, M, Simon, K, Penzes, J, Kempler, P, Bako, B, Lengyel, Z, Witmann, I, Dudas, M, Vandorfi, G, Takacs, J, Matoltsy, A, Ladanyi, E, Gyimesi, A, Sadikot, S, Parikh, K, Jain, S, Yajnik, C, Sosale, A, Shamanna, P, Srikanta, S, Shah, S, Srinivas, A, Banker, D, Shah, P, Sharda, A, Makkar, B, Rais, N, Mardikar, H, Mishra, A, Bhupati, S, Menon, J, Sathe, S, Gupta, R, Sharma, V, Darawsha, M, Herskovits, T, Hamoud, S, Nikolsky, E, Adawi, F, Zimlichman, R, Tsalihin, D, Wainstein, J, Klainman, E, Mosseri, M, Yerushalmi, Y, Karnieli, E, Knobler, H, Benchetrit, S, Tsur, A, Yagil, Y, Atar, S, Beberashvili, I, Fuchs, S, Stern, N, Pollak, A, Chajek-Shaul, T, Rozenman, Y, Biton, A, Bramucci, E, Fiscella, A, Grassia, V, Piatti, P, De Cosmo, S, Di Lorenzo, L, Merlini, P, Mannucci, E, Frontoni, S, Trevisan, R, Zenari, L, Lambiase, C, Salvioni, A, Silvestri, O, Ambrosio, G, Di Bartolo, P, Fattore, L, Presbitero, P, Calabrese, M, Evola, R, Gamba, M, Ibarra, M, Munoz, E, Sanchez, D, Herrera, C, Rios, J, Llamas, E, Esperon, G, Cantu, E, Fragoso, J, Gonzalez, J, Martinez, G, Padilla, F, Mier, G, Marmolejo, D, Ruiz, J, Portilla, N, Rosas, E, Machado, G, Ramos, J, Briones, I, van Hessen, M, Strikwerda, S, The, S, Kooy, A, Ronner, E, Nierop, P, Remmen, J, Groenemeijer, B, Hamer, B, Basart, D, van Lennep, H, Nieuwdorp, M, van Dijk, M, Kentgens, S, van Kempen, W, Hoogendijk, J, Spiering, W, Voors-Pette, C, Kose, V, de Waard, D, Gonkel, F, Kaasjager, H, Lingan, G, Agous, I, Kruik, H, Imholz, B, Pieterse, M, Manrique, H, Villena, J, Leon, L, Kundert, K, Minchola, J, Pinto, M, Heredia, J, Rodriguez, A, Guerreros, C, Berrospi, P, Zubiate, C, Allemant, A, Arbanil, H, Ponciano, W, Calderon, J, Lisson, R, Segura, L, Sidorowicz-Bialynicka, A, Sciborski, R, Fares, I, Mader, P, Skierkowska, J, Stasinska, T, Pomiecko, W, Skorski, M, Krzyzagorska, E, Polaszewska-Muszynska, M, Sowinski, D, Strojek, K, Rosinska-Migda, J, Romanczuk, P, Golebiowski, G, Kubica, J, Mazurek, T, Wojnowski, L, Pasternak, D, Stachlewski, P, Trzepla, E, Bogdanowicz, G, Uzunow, A, Potakowska, I, Miszczyszyn, Z, Waszyrowski, T, Smolenskaya, O, Lukyanov, Y, Vorokhobina, N, Khalimov, Y, Orlikova, O, Rebrov, A, Kukharchuk, V, Boldueva, S, Arkhipov, M, Zhelninova, T, Pavlysh, E, Antsiferov, M, Panov, A, Pavlova, M, Shustov, S, Demchenko, E, Galyavich, A, Malakhina, E, Semenova, O, Kobalava, Z, Kotova, S, Gavrisheva, I, Oschepkova, E, Karpov, Y, Sidorenko, B, Kislyak, O, Ametov, A, Dreval, A, Grineva, E, Mkrtumyan, A, Tyurina, T, Sazonova, O, Bonnici, F, Ranjith, N, Burgess, L, Nortje, H, Distiller, L, Mitha, I, Moore, R, Conradie, M, Horak, A, Pillay, S, Wellmann, H, Berg, E, Pillai, P, Padayachee, T, Corbett, C, Makan, H, Wing, J, Vawda, Z, Ebrahim, I, Mitha, E, Bhorat, A, Fernandez, J, Munoz, C, Cortada, J, Conde, A, Calvo, C, Extremera, B, Delgado, E, Masmiquel, L, Puig, J, Parreno, L, Mauricio, D, Redon, J, Brito, M, Lopez, C, de la Morera, J, Linderfalk, C, Larnefeldt, H, Olsson, A, Lonneborg, L, Ekelund, M, Samad, B, Borgencrantz, B, Nilsson, J, Berglund, O, Svensson, M, Mooe, T, Curiac, D, Albin, J, Angesjo, E, Lannemyr, O, Chen, J, Tien, K, Ueng, K, Lai, W, Yin, W, Hung, Y, Shyu, K, Hou, J, Lam, H, Laothavorn, P, Kuanprasert, S, Khovidhunkit, W, Benjasuratwong, Y, Chotinaiwattarakul, C, Mamanasiri, S, Suraamornkul, S, Pratipanawatr, T, Nitiyanant, W, Heller, S, Pieters, R, Strang, C, Bodalia, B, Middleton, A, Hall, T, Chapman, G, Calvert, J, Reed, R, Tam, D, Butcher, G, Jones, N, Takhar, A, Turner, W, Mcnally, D, Corey, O, Chapman, J, Mohr, S, Edwards, S, Ocampo, A, Kandath, D, Aude, Y, Ervin, W, Savin, V, Anderson, R, Littlefield, R, Oberoi, M, Platt, G, Yazdani, S, Mangoo-Karim, R, Walder, J, Gogia, H, Chandrashekhar, Y, Boccalandro, F, Rogers, W, Bilazarian, S, Zieve, F, Siage, Y, O'Connor, T, Mudaliar, S, Nikas, A, Giusti, R, Glover, R, Chilka, S, French, W, Roth, E, Singh, N, Christofferson, R, Stich, M, Dagogo-Jack, S, Allison, J, Zengotita, G, Ison, R, Iteld, B, Sulistio, M, Gonzalez, E, Gorman, T, Hage-Korban, E, Reddy, R, Byars, W, Antonishen, M, Benjamin, S, First, B, Rosado, J, Bruschetta, H, Poling, T, Rosendorff, C, Kerstein, H, Saba, F, Willis, J, Adams, K, Vazquez, E, Ellison, H, Kahn, B, Kereiakes, D, Powell, S, Raskin, P, Smith, K, Varma, S, Whittier, F, Casanova, R, Isserman, S, Kaye, W, Mcguinn, W, Bartkowiak, A, Dworkin, L, Labrador, C, Podlecki, D, Popovtzer, M, Aronoff, S, Ballantyne, C, Ortiz, E, Mora, A, Pitts, T, Reinhardt, S, Soucie, G, Wainwright, W, Henson, B, Sklaver, N, Arakaki, R, Brown, J, Chalavarya, G, Chochinov, R, Dixon, T, Kutner, M, Perlman, R, Raisinghani, A, Salacata, A, Awasty, V, Elinoff, V, George, W, LaRochelle-Gryseels, A, Mercado, A, Miller, G, Qureshi, M, Steljes, A, Wefald, F, Wilson, J, Chinn, J, Chuang, R, Comulada-Rivera, A, Hartman, I, Narayan, P, Pacheco, T, Weiss, R, Beavins, J, Creevy, J, Hamroff, G, Hodson, R, Kosinski, E, Krichmar, P, Patel, R, Schneider, R, Shapiro, J, Sharp, D, Speer, J, Stegemoller, R, Waxman, F, Chang, F, Braun, E, Eder, F, Minor, S, Albert, M, Carr, K, Diaczok, B, Gastman, I, Gupta, V, Longshaw, K, Gonzalez-Campoy, J, Raikhel, M, Thomas, J, Wood, K, Diab, I, Furda, J, Gelernt, M, Halter, M, House, B, Kaster, S, Raad, G, Stamatin, R, Barker, B, Blonder, R, Bloomberg, R, Calderon, R, Carrol, A, Comerota, A, Feinglos, M, Henderson, D, Kastelic, R, Stonesifer, L, Talano, J, Lee, P, Brosseau, J, Clark, W, Cohen, E, Fialkow, J, Horton, K, Kozman, H, Mcgill, J, Mihills, C, Poonawala, R, Shore, K, Tejada, L, Torres, R, Wright, W, Calatayud, G, Chandna, H, Drozdiak, R, Fink, R, Gill, R, Glandt, M, Gottlieb, D, Hack, T, Kay, J, Mansouri, V, Mcknight, T, Mostel, E, Schmidt, L, Seide, H, Sonel, E, Taylor, R, Velasquez, M, Bretton, E, Feldman, R, Hartman, A, Hershon, K, Leach, C, Martin, E, Mohiuddin, F, Naygandhi, Y, Riske, T, Schima, S, Uzoaga, E, Ward, H, Weinstock, R, Williams, T, Altschuller, A, Aoki, T, Blumenthal, S, Cash, A, Eisner, G, Gutmann, J, Hagan, M, Kabour, A, Markus, T, Mckenzie, W, Moursi, M, Mystkowski, P, Ovalle, F, Perkins, R, Popeil, L, Saniuk, R, Sierra, Y, Alvarado, O, Anderson, J, Bajaj, M, Blank, R, Chu, A, Levinsky, L, Levy, P, Osborne, J, Pavon, H, Sanderlin, D, Schaer, G, Zarich, S, Atassi, K, Bayron, C, Casagrande, M, Das, D, Gimness, M, Handel, F, Kinstrey, T, Leu, S, Osei, K, Nouel, J, Soltani, Z, Sussman, H, Chiu, K, Duda, R, Farnsworth, K, Lano, M, Lee, F, Levin, P, Pratt, S, Richwine, R, Ruiz-Rivera, L, Turner, J, Wood, J, Zigrang, W, Baquerizo, H, Colon, C, Demattia, J, Desai, V, Fitz-Patrick, D, Goral, S, Odhav, A, Prentiss, A, Ruff, C, Wu, W, Wyne, K, Abbott, L, Applegate, R, Cabral, J, Kotha, P, Ortega, P, and Simmons, D

Subjects
Male, Adamantane, Dipeptidyl peptidase-4 inhibitor, Type 2 diabetes, Kaplan-Meier Estimate, Saxagliptin, chemistry.chemical_compound, 80 and over, glucose, saxagliptin, Aged, 80 and over, Medicine (all), Hazard ratio, 11 Medical And Health Sciences, General Medicine, Dipeptides, Middle Aged, Hospitalization, Cardiovascular Diseases, Female, Aged, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Double-Blind Method, Heart Failure, Humans, Hypoglycemia, Hypoglycemic Agents, Pancreatitis, Alogliptin, Type 2, medicine.drug, insulin, medicine.medical_specialty, General & Internal Medicine, Internal medicine, Diabetes mellitus, medicine, Empagliflozin, Diabetes Mellitus, Intensive care medicine, glycosylated hemoglobin, business.industry, Semaglutide, SAVOR-TIMI 53 Steering Committee and Investigators, medicine.disease, chemistry, placebo, business
Abstract

BACKGROUND: The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. METHODS: We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS: A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P

Published
2013

30. Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries

Author

Futema, M. (Marta), Shah, S. (Sonia), Cooper, J.A. (Jackie A.), Li, K. (Kawah), Whittall, R.A. (Ros A.), Sharifi, M. (Mahtab), Goldberg, O. (Olivia), Drogari, E. (Euridiki), Mollaki, V. (Vasiliki), Wiegman, A. (Albert), Defesche, J.C. (Joep), D'Agostino, M.N. (Maria N.), D'Angelo, A. (Antonietta), Rubba, P. (Paolo), Fortunato, G. (Giuliana), Walus̈-Miarka, M. (Małgorzata), Hegele, R.A. (Robert), Bamimore, M.A. (Mary Aderayo), Durst, R. (Ronen), Leitersdorf, E. (Eran), Mulder, M.T. (Monique), Roeters van Lennep, J.E. (Jeanine), Sijbrands, E.J.G. (Eric), Whittaker, J.C. (John C.), Talmud, P.J., Humphries, S.E. (Steve), Futema, M. (Marta), Shah, S. (Sonia), Cooper, J.A. (Jackie A.), Li, K. (Kawah), Whittall, R.A. (Ros A.), Sharifi, M. (Mahtab), Goldberg, O. (Olivia), Drogari, E. (Euridiki), Mollaki, V. (Vasiliki), Wiegman, A. (Albert), Defesche, J.C. (Joep), D'Agostino, M.N. (Maria N.), D'Angelo, A. (Antonietta), Rubba, P. (Paolo), Fortunato, G. (Giuliana), Walus̈-Miarka, M. (Małgorzata), Hegele, R.A. (Robert), Bamimore, M.A. (Mary Aderayo), Durst, R. (Ronen), Leitersdorf, E. (Eran), Mulder, M.T. (Monique), Roeters van Lennep, J.E. (Jeanine), Sijbrands, E.J.G. (Eric), Whittaker, J.C. (John C.), Talmud, P.J., and Humphries, S.E. (Steve)

Abstract

Background: Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in 1 of 3 genes. In the60%of patients who are mutation negative, we have recently shown that the clinical phenotype can be associated with an accumulation of common small-effect LDL cholesterol (LDL-C)-raising alleles by use of a 12-single nucleotide polymorphism (12-SNP) score. The aims of the study were to improve the selection of SNPs and replicate the results in additional samples.Methods: We used ROC curves to determine the optimum number of LDL-C SNPs. For replication analysis, we genotyped patients with a clinical diagnosis of FH from 6 countries for 6 LDL-C-associated alleles. We compared the weighted SNP score among patients with no confirmed mutation (FH/M-), those with amutation(FH/M-), and controls from aUK population sample (WHII).Results: Increasing the number of SNPs to 33 did not improve the ability of the score to discriminate between FH/M-and controls, whereas sequential removal of SNPs with smaller effects/lower frequency showed that a weighted score of 6 SNPs performed as well as the 12-SNP score. Metaanalysis of the weighted 6-SNP score, on the basis of polymorphisms in CELSR2 (cadherin, EGF LAG 7-pass G-type receptor 2), APOB (apolipoprotein B), ABCG5/8 [ATP-binding cassette, sub-family G (WHITE), member 5/8], LDLR (low density lipoprotein receptor), and APOE (apolipoprotein E) loci, in the independent FH/M-cohorts showed a consistently higher score in comparison to the WHII population (P<2.2× 10-16). Modeling in individuals with a 6-SNP score in the top three-fourths of the score distribution indicated a >95% likelihood of a polygenic explanation of their increased LDL-C.Conclusions: A 6-SNP LDL-C score consistently distinguishes FH/M-patients from healthy individuals. The hypercholesterolemia in 88% of mutation-negative patients is likely to have a polygenic basis.

Published
2015
Full Text
View/download PDF

31. Hematopoietic overexpression of Cyp27a1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr(-/-) mice

Author

Hendrikx, Tim, Hendrikx, Tim, Jeurissen, Mike L.J., Bieghs, V., Walenbergh, Sofie M.A., van Gorp, Patrick J., Verheyen, F., Houben, Tom, Guichot, Y. D., Gijbels, M.J., Leitersdorf, E., Hofker, M.H., Luetjohann, D., Shiri-Sverdlov, Ronit, Hendrikx, Tim, Hendrikx, Tim, Jeurissen, Mike L.J., Bieghs, V., Walenbergh, Sofie M.A., van Gorp, Patrick J., Verheyen, F., Houben, Tom, Guichot, Y. D., Gijbels, M.J., Leitersdorf, E., Hofker, M.H., Luetjohann, D., and Shiri-Sverdlov, Ronit

Abstract

Background & Aims: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic lipid accumulation and inflammation. Currently, the underlying mechanisms, leading to hepatic inflammation, are still unknown. The breakdown of free cholesterol inside Kupffer cells (KCs) by the mitochondrial enzyme CYP27A1 produces 27-hydroxycholesterol (27HC). We recently demonstrated that administration of 27HC to hyperlipidemic mice reduced hepatic inflammation. In line, hematopoietic deletion of Cyp27a1 resulted in increased hepatic inflammation. In the current manuscript, the effect of hematopoietic overexpression of Cyp27a1 on the development of NASH and cholesterol trafficking was investigated. We hypothesized that Cyp27a1 overexpression in KCs will lead to reduced hepatic inflammation.Methods: Irradiated Ldlr(-/-) mice were transplanted (tp) with bone marrow from mice overexpressing Cyp27a1 (Cyp27a1(over)) and wild type (Wt) mice and fed either chow or a high-fat, high-cholesterol (HFC) diet for 3 months. Additionally, gene expression was assessed in bone marrow-derived macrophages (BMDM) from Cyp27a1(over) and Wt mice.Results: In line with our hypothesis, hepatic inflammation in HFC-fed Cyp27a1(over)-tp mice was reduced and KCs were less foamy compared to Wt-tp mice. Remarkably, these changes occurred even though plasma and liver levels of 27HC did not differ between both groups. BMDM from Cyp27a1(over) mice revealed reduced inflammatory gene expression and increased expression of cholesterol transporters compared to Wt BMDM after lipopolysaccharide (LPS) stimulation.Conclusions: Our data suggest that overexpression of Cyp27a1 in KCs reduces hepatic inflammation independently of 27HC levels in plasma and liver, further pointing towards KCs as specific target for improving the therapy of NASH. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Published
2015

33. Effects of dalcetrapib in patients with a recent acute coronary syndrome

Author

Schwartz, G.G., Olsson, A.G., Abt, M., Ballantyne, C.M., Barter, P.J., Brumm, J., Chaitman, B.R., Holme, I.M., Kallend, D., Leiter, L.A., Leitersdorf, E., McMurray, J.J.V., Mundl, H., Nicholls, S.J., Shah, P.K., Tardif, J., and Wright, R.S.

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes.

Published
2012

35. O067 : Hematopoietic overexpression of CYP27A1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr-/- mice via NPC-modulated cholesterol transport

Author

Hendrikx, T., primary, Jeurissen, M.L., additional, Walenbergh, S.M., additional, Houben, T., additional, van Gorp, P.J., additional, Verheyen, F., additional, Gijbels, M.J., additional, Leitersdorf, E., additional, Hofker, M., additional, Lütjohann, D., additional, and Shiri-Sverdlov, R., additional

Published
2015
Full Text
View/download PDF

36. Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial

Author

Brinton, Eliot A., primary, Kher, Uma, additional, Shah, Sukrut, additional, Cannon, Christopher P., additional, Davidson, Michael, additional, Gotto, Antonio M., additional, Ashraf, Tanya B., additional, McCrary Sisk, Christine, additional, Dansky, Hayes, additional, Mitchel, Yale, additional, Barter, Philip, additional, Gerstman, M., additional, Howes, L., additional, Kostner, K., additional, Nestel, P., additional, Sullivan, D., additional, Brath, H., additional, Patsch, J., additional, Paulweber, B., additional, Toplak, H., additional, Constance, C.M., additional, Howlett, E., additional, Mymin, D., additional, Pliamm, L., additional, Saunders, K.K., additional, Tardif, J.-C., additional, Tytus, R., additional, Aschner, P., additional, Keinänen-Klukaanniemi, S., additional, Strandberg, T., additional, Taskinen, M.-R., additional, Luc, G., additional, Richter, D., additional, Schlienger, J.L., additional, Zaïr, Y., additional, Appel, K.-F., additional, Baar, M., additional, Luley, C., additional, Overhoff, U., additional, Pomykaj, T., additional, Schaefer, T., additional, Lau, S.T., additional, Lee, K.L.F., additional, Tan, K., additional, Tomlinson, B., additional, Tsang, M.W., additional, Badacsonyi, K., additional, Kalina, Á., additional, Kanakaridisz, N., additional, Márk, L., additional, Péterfai, É., additional, Regos, L., additional, Reiber, I., additional, Takács, J., additional, Vértes, A., additional, Elis, A., additional, Gavish, D., additional, Harats, D., additional, Hussein, O., additional, Hayek, T., additional, Leitersdorf, E., additional, Bin Abdul Ghapar, A.K., additional, Chee, K.H., additional, Ismail, S.B., additional, Ling, K.H., additional, Ramanathan, G.R.L., additional, Sim, K.H., additional, Alvarado, R., additional, Benavides, M., additional, Cardona, G.E., additional, Gonzalez, G., additional, Verdejo, J., additional, Basart, D.C.G., additional, Imholz, B.P.M., additional, Jonker, J.J.C., additional, Nierop, P.R., additional, Posma, J.L., additional, Twickler, Th.B., additional, Barrington-Ward, E., additional, Cutfield, R., additional, Friedlander, D.H., additional, Scott, R.S., additional, Istad, H., additional, Langslet, G., additional, Skjelvan, G.K., additional, Campodónico Hoyos, S.J., additional, Coloma Araniya, R., additional, Gallegos C., A., additional, Pino Morales, C.A., additional, Watanabe, L., additional, Arutyunov, G.P., additional, Blokhin, A.B., additional, Bubnova, M.G., additional, Marcevich, S.Y., additional, Álvarez Sánchez, C., additional, Álvarez-Sala Walther, L.A., additional, Gil Extremera, B., additional, Perez Jimenez, F., additional, de Teresa Parreño, L., additional, Anderberg, C.-P., additional, Hedin, U., additional, Hellberg, A., additional, Höök, P., additional, Kjellström, T., additional, Nilsson, P., additional, Olsson, A.G., additional, Rosenqvist, U., additional, Tolagen, K., additional, Wolff, T., additional, Baskin, A., additional, Bays, H.E., additional, Bernstein, R.I., additional, Bittar, N., additional, Brinton, E.A., additional, Chee, L.H.K., additional, Cottiero, R.A., additional, D'Agostino, R.D., additional, Davidson, M.H., additional, Denker, P.S., additional, Garcia, R.K., additional, Hippert, R.K., additional, Isakov, T., additional, Kaster, S.R., additional, Kerzner, B., additional, Klein, E.J., additional, Koren, M.J., additional, Kutner, M.E., additional, Liljenquist, D., additional, Lorch, D.G., additional, Lorraine, R., additional, Lubin, B.C., additional, Lunde, N.M., additional, Majchrzak, T.J., additional, McKenney, J.M., additional, Mukherjee, S., additional, Muse, D.D., additional, Otruba, M.S., additional, Pappas, J.E., additional, Patrick, K., additional, Powell, S.J., additional, Riffer, E., additional, Rink, L.D., additional, Rohlf, J.L., additional, Rosen, J.B., additional, Rosenbilt, P.D., additional, Roth, E.M., additional, Rubenstein, C.J., additional, Rubino, J., additional, Rudolph, L.A., additional, Schneider, A., additional, Short, W.G., additional, Silverfield, J.C., additional, Suresh, D.P., additional, Tarshis, G.A., additional, Toth, P.D., additional, Townsend, R.W., additional, and Wahl, T.O., additional

Published
2015
Full Text
View/download PDF

39. Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients

Author

Bruckert, E., Lièvre, M., Giral, P., Crepaldi, G., Masana, L., Vrolix, M., Leitersdorf, E., Dejager, S., Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]
Published
2003

40. The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice.

Author

Bieghs, V., Bieghs, V., Hendrikx, T., van Gorp, P.J.J., Verheyen, F., Guichot, Y. D., Walenbergh, S.M., Gijbels, M.J.J., Rensen, S.S.M., Bast, A., Plat, J., Kalhan, S. C., Leitersdorf, E., Hofker, M.H., Lutjohann, D., Shiri-Sverdlov, R., Bieghs, V., Bieghs, V., Hendrikx, T., van Gorp, P.J.J., Verheyen, F., Guichot, Y. D., Walenbergh, S.M., Gijbels, M.J.J., Rensen, S.S.M., Bast, A., Plat, J., Kalhan, S. C., Leitersdorf, E., Hofker, M.H., Lutjohann, D., and Shiri-Sverdlov, R.

Abstract

BACKGROUND & AIMS:: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation. Although steatosis is benign and reversible, inflammation can increase liver damage. Hepatic inflammation has been associated with accumulation of cholesterol in lysosomes of Kupffer cells. 27-hydroxycholesterol (27HC), a derivative of cholesterol formed by CYP27A1, can mobilize cholesterol from the lysosomes to the cytoplasm. We investigated whether 27HC can change the intracellular distribution cholesterol and reduce hepatic inflammation in mice. METHODS:: We transplanted bone marrow from irradiated wild-type or Cyp27a1-/-mice to mice that do not express the low density lipoprotein receptor ( Ldlr-/-), which are hyperlipidemic; 9 weeks later, mice were fed either regular chow or a high-fat, high-cholesterol (HFC) diet for 3 months. In a separate experiment, Ldlr-/- mice were given subcutaneous injections of 27HC and placed on regular chow or HFC diets for 3 weeks. Blood and liver tissues samples were collected and analyzed for intracellular cholesterol distribution and inflammation. RESULTS:: In Ldlr-/-mice that received bone marrow transplants from Cyp27a1-/-mice, lysosomes of Kupfer cells had a greater accumulation of cholesterol than those of mice that received bone marrow from wild-type mice, after the HFC diet. Liver histology and gene expression analyses showed increased inflammation and liver damage in mice given bone marrow transplants from Cyp27a1-/-mice and placed on the HFC diet. Administration of 27HC to Ldlr-/-mice, following the HFC diet, reduced the accumulation of lysosomal cholesterol and hepatic inflammation, compared with mice that were not given 27HC. CONCLUSIONS:: Accumulation of cholesterol in lysosomes of Kupfer cells promotes hepatic inflammation in mice. The cholesterol derivative 27HC reduces accumulation of cholesterol in lysosomes and might be used to treat NASH.

Published
2013

42. The alpha-defensins stimulate proteoglycan-dependent catabolism of low-density lipoprotein by vascular cells: a new class of inflammatory apolipoprotein and a possible contributor to atherogenesis

Author

Aa, Higazi, Nassar T, Ganz T, Dj, Rader, Udassin R, Bdeir K, Hiss E, Bs, Sachais, Kevin Jon Williams, Leitersdorf E, and Db, Cines

Subjects
Dose-Response Relationship, Drug, Arteriosclerosis, Neutrophils, Proteins, Blood Proteins, CHO Cells, Muscle, Smooth, Vascular, Defensins, Lipoproteins, LDL, Receptors, LDL, Cricetinae, Animals, Humans, Proteoglycans, Endothelium, Vascular
Abstract

Inflammation may contribute to the pathogenesis of atherosclerosis. On the basis of previous reports that human atherosclerotic lesions contain alpha-defensins, a class of cationic proteins released by activated neutrophils, the study was designed to ask whether defensins modulate the binding and catabolism of low-density lipoprotein (LDL) by human vascular cells. The results of the study demonstrated that defensin stimulated the binding of (125)I-LDL to cultured human umbilical vein endothelial cells, smooth muscle cells, and fibroblasts approximately 5-fold in a dose-dependent and saturable manner. Defensin and LDL formed stable complexes in solution and on cell surfaces. Stimulation of LDL binding by defensin was not inhibited by antibodies against the LDL-receptor (LDL-R), or by recombinant receptor-associated protein, which blocks binding of ligands to the alpha(2)-macroglobulin receptor/LDL-R-related protein and other LDL-R family members. Furthermore, defensin stimulated the binding, endocytosis, and degradation of LDL by fibroblasts lacking LDL-R. Stimulation of LDL degradation by defensin was inhibited approximately 75% by low concentrations of heparin (0.2 units/mL) and was similarly reduced in CHO cells lacking heparan-sulfate-containing proteoglycans. The effect of defensin was substantially increased in cells overexpressing the core protein of the syndecan-1 heparan sulfate proteoglycan. The alpha-defensins released from activated neutrophils may provide a link between inflammation and atherosclerosis by changing the pattern of LDL catabolism from LDL-R to the less efficient LDL-R-independent, proteoglycan-dependent pathway. (Blood. 2000;96:1393-1398)

Published
2000

43. Mechanism of action of fibrates on lipid and lipoprotein metabolism

Author

Staels, B., Dallongeville, J., Auwerx, J., Schoonjans, K., Leitersdorf, E., Fruchart, J. C., Staels, B., Dallongeville, J., Auwerx, J., Schoonjans, K., Leitersdorf, E., and Fruchart, J. C.

Abstract

Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations. Recent investigations indicate that the effects of fibrates are mediated, at least in part, through alterations in transcription of genes encoding for proteins that control lipoprotein metabolism. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). The PPAR-alpha form mediates fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II. Fibrates lower hepatic apoC-III production and increase lipoprotein lipase--mediated lipolysis via PPAR. Fibrates stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the beta-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production. In summary, both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results