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1. Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis

Author

Reith, Christina, Preiss, David, Blackwell, Lisa, Emberson, Jonathan, Spata, Enti, Davies, Kelly, Halls, Heather, Harper, Charlie, Holland, Lisa, Wilson, Kate, Roddick, Alistair J, Cannon, Christopher P, Clarke, Robert, Colhoun, Helen M, Durrington, Paul N, Goto, Shinya, Hitman, Graham A, Hovingh, G Kees, Jukema, J Wouter, Koenig, Wolfgang, Marschner, Ian, Mihaylova, Borislava, Newman, Connie, Probsfield, Jeffrey L, Ridker, Paul M, Sabatine, Marc S, Sattar, Naveed, Schwartz, Gregory G, Tavazzi, Luigi, Tonkin, Andrew, Trompet, Stella, White, Harvey, Yusuf, Salim, Armitage, Jane, Keech, Anthony, Simes, John, Collins, Rory, Baigent, Colin, Barnes, Elizabeth, Fulcher, Jordan, Herrington, William G, Kirby, Adrienne, O'Connell, Rachel, Amarenco, Pierre, Arashi, Hiroyuki, Barter, Philip, Betteridge, D John, Blazing, Michael, Blauw, Gerard J, Bosch, Jackie, Bowman, Louise, Braunwald, Eugene, Bulbulia, Richard, Byington, Robert, Clearfield, Michael, Cobbe, Stuart, Dahlöf, Björn, Davis, Barry, de Lemos, James, Downs, John R, Fellström, Bengt, Flather, Marcus, Ford, Ian, Franzosi, Maria Grazia, Fuller, John, Furberg, Curt, Glynn, Robert, Goldbourt, Uri, Gordon, David, Gotto, Jr, Antonio, Grimm, Richard, Gupta, Ajay, Hawkins, C Morton, Haynes, Richard, Holdaas, Hallvard, Hopewell, Jemma, Jardine, Alan, Kastelein, John JP, Kean, Sharon, Kearney, Patricia, Kitas, George, Kjekshus, John, Knatterud, Genell, Knopp, Robert H, Koren, Michael, Krane, Vera, Landray, Martin, LaRosa, John, Latini, Roberto, Lonn, Eva, Lucci, Donata, MacFadyen, Jean, Macfarlane, Peter, MacMahon, Stephen, Maggioni, Aldo, Marchioli, Roberto, Moyé, Lemuel, Murphy, Sabina, Neil, Andrew, Nicolis, Enrico B, Packard, Chris, Parish, Sarah, Pedersen, Terje R, Peto, Richard, Pfeffer, Marc, Poulter, Neil, Pressel, Sara, Probstfield, Jeffrey, Rahman, Mahboob, Robertson, Michele, Sacks, Frank, Schmieder, Roland, Serruys, Patrick, Sever, Peter, Shaw, John, Shepherd, James, Simpson, Lara, Sleight, Peter, Smeeth, Liam, Tobert, Jonathan, Tognoni, Gianni, Varigos, John, Wanner, Christoph, Wedel, Hans, Weis, Stephen, Welch, K Michael, Wikstrand, John, Wilhelmsen, Lars, Wiviott, Stephen, Yamaguchi, Junichi, Young, Robin, and Zannad, Faiez

Published
2024
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2. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials

Author

Reith, Christina, Baigent, Colin, Blackwell, Lisa, Emberson, Jonathan, Spata, Enti, Davies, Kelly, Halls, Heather, Holland, Lisa, Wilson, Kate, Armitage, Jane, Harper, Charlie, Preiss, David, Roddick, Alistair, Keech, Anthony, Simes, John, Collins, Rory, Barnes, Elizabeth, Fulcher, Jordan, Herrington, William G, Kirby, Adrienne, Mihaylova, Borislava, O'Connell, Rachel, Amarenco, Pierre, Barter, Philip, Betteridge (deceased), D John, Blazing, Michael, Bosch, Jackie, Bowman, Louise, Braunwald, Eugene, Cannon, Christopher P, Clearfield, Michael, Cobbe, Stuart, Colhoun, Helen M, Dahlöf, Björn, Davis, Barry, de Lemos, James, Downs, John R, Durrington, Paul N, Fellström, Bengt, Ford, Ian, Franzosi, Maria Grazia, Fuller (deceased), John, Furberg, Curt, Glynn, Robert, Gordon, David, Gotto Jr, Antonio, Grimm, Richard, Gupta, Ajay, Hawkins, C Morton, Hitman, Graham A, Holdaas (deceased), Hallvard, Jardine, Alan, Jukema, J Wouter, Kastelein, John JP, Kean, Sharon, Kjekshus, John, Knatterud (deceased), Genell, Knopp (deceased), Robert H, Koenig, Wolfgang, Koren, Michael, Krane, Vera, Landray, Martin, LaRosa, John, Latini, Roberto, Lonn, Eva, Lucci, Donata, MacFadyen, Jean, Macfarlane, Peter, MacMahon, Stephen, Maggioni, Aldo, Marchioli, Roberto, Marschner, Ian, Moyé, Lemuel, Murphy, Sabina, Neil, Andrew, Nicolis, Enrico B, Packard, Chris, Parish, Sarah, Pedersen, Terje R, Peto, Richard, Pfeffer, Marc, Poulter, Neil, Pressel, Sara, Probstfield, Jeffrey, Rahman, Mahboob, Ridker, Paul M, Robertson, Michele, Sacks, Frank, Sattar, Naveed, Schmieder, Roland, Serruys, Patrick W, Sever, Peter, Shaw (deceased), John, Shepherd (deceased), James, Simpson, Lara, Sleight (deceased), Peter, Tavazzi, Luigi, Tognoni, Gianni, Tonkin, Andrew, Trompet, Stella, Wanner, Christoph, Wedel, Hans, Weis, Stephen, Welch, K Michael, White, Harvey, Wikstrand, John, Wilhelmsen, Lars, Wiviott, Stephen, Young, Robin, Yusuf, Salim, Zannad, Faiez, Arashi, Hiroyuki, Byington, Robert, Clarke, Robert, Flather, Marcus, Goldbourt, Uri, Goto, Shinya, Hopewell, Jemma, Hovingh, Kees, Kearney, Patricia, Kitas, George, Newman, Connie, Sabatine, Marc S, Schwartz, Greg, Smeeth, Liam, Tobert, Jonathan, Varigos, John, and Yamaguchi, Junichi

Published
2022
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5. Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients

Author

Sirimarco, Gaia, Labreuche, Julien, Bruckert, Eric, Goldstein, Larry B., Fox, Kim M., Rothwell, Peter M., Amarenco, Pierre, Bousser, Marie-Germaine, Chamorro, Angel, Ford, Ian, Fox, Kim, Fisher, Marc, Hennerici, Michael G., Mattle, Heinrich, Rothwell, Peter M., Callahan, Fred, III, Goldstein, Larry B., Sillesen, Henrik, Welch, K. Michael A., and Zivin, Justin A.

Published
2014
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6. Atorvastatin Reduces First and Subsequent Vascular Events Across Vascular Territories:The SPARCL Trial

Author

Szarek, Michael, Amarenco, Pierre, Callahan, Alfred, DeMicco, David, Fayyad, Rana, Goldstein, Larry B., Laskey, Rachel, Sillesen, Henrik, and Welch, K. Michael

Subjects
total events, transient ischemic attack, cardiovascular diseases, atorvastatin, stroke
Abstract

Background: In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, atorvastatin was compared with placebo in 4,731 participants with recent stroke or transient ischemic attack and no known coronary heart disease. Atorvastatin reduced the first occurrence of stroke and the first occurrence of a composite of vascular events. Objectives: The aim of this post hoc analysis was to assess the occurrence of all (first and subsequent) vascular events and the effect of atorvastatin to reduce these events by vascular territory (cerebrovascular, coronary, or peripheral) in SPARCL. Methods: Treatment effects on total adjudicated vascular events, overall and by vascular territory, were summarized by marginal proportional hazards models. Vascular event rates were estimated for each treatment group with cumulative incidence functions. Results: The placebo group had an estimated 41.2 first and 62.7 total vascular events per 100 participants over 6 years. There were 164 fewer first and 390 fewer total vascular events in the atorvastatin group (total events hazard ratio: 0.68; 95% confidence interval: 0.60 to 0.77). The total events reduction included 177 fewer cerebrovascular, 170 fewer coronary, and 43 fewer peripheral events. Over 6 years, an estimated 20 vascular events per 100 participants were avoided with atorvastatin treatment. Conclusions: In participants with recent stroke or transient ischemic attack, the total number of vascular events prevented with atorvastatin was more than twice the number of first events prevented. Total event reduction provides a comprehensive metric to capture the totality of atorvastatin clinical efficacy in reducing disease burden after stroke or transient ischemic attack. (Lipitor in the Prevention of Stroke, for Patients Who Have Had a Previous Stroke [SPARCL]; NCT00147602)

Published
2020

8. Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke–Enhanced Regimen Stroke Trial

Author

Pancioli, Arthur M., Adeoye, Opeolu, Schmit, Pamela A., Khoury, Jane, Levine, Steven R., Tomsick, Thomas A., Sucharew, Heidi, Brooks, Claudette E., Crocco, Todd J., Gutmann, Laurie, Hemmen, Thomas M., Kasner, Scott E., Kleindorfer, Dawn, Knight, William A., Martini, Sharyl, McKinney, James S., Meurer, William J., Meyer, Brett C., Schneider, Alexander, Scott, Phillip A., Starkman, Sidney, Warach, Steven, Broderick, Joseph P., Pancioli, Arthur M., Adeoye, Opeolu, Broderick, Joseph, Schmit, Pamela A., Khoury, Jane, Sucharew, Heidi, Janis, Scott, Tomsick, Thomas, Brooks, Claudette E., Crocco, Todd, Hemmen, Thomas, Kasner, Scott E., McKinney, James S., Meurer, William J., Schneider, Alex, Starkman, Sidney, Warach, Steven, Levine, Steven, Moy, Claudia, Welch, K. Michael, Tietjen, Gretchen, Clarke, William R., Bonomo, Jordan, McDonough, Erin, Ferioli, Simona, De la Rosa, Felipe de los Rios, Martini, Sharyl, Woo, Daniel, Garvin, Rachel, Kleindorfer, Dawn, Khatri, Pooja, Gensic, Anna, Flaherty, Matthew, Kanter, Daniel, Kissela, Brett, Stettler, Brian, Mackey, Jason, Cadena, Rhonda, Kohake, Shannon, Heitsch, Laura, Belagaje, Samir, Vagal, Achala, Hallenbeck, John, Benson, Richard, Hsia, Amie, Jaitly, Rakesh, Latour, Lawrence, Lynch, John, Merino, Jose, Menon, Ravi, Freeman, Jason, Magadan, Alejandro, Magaraja, Nandakumar, Jothen, Jennifer, Famakin, Bonanle, Song, Shlee, Katcheves, Alex, Nadareishvili, Zurab, Ritter, Carsen, Barsan, William, Brown, Devin, Morgenstern, Lewis, Silbergleit, Robert, Rajajee, Venkatakrishna, Rusche-Skolarus, Lesli, Burke, Jim, Fletcher, Jeffrey, Adelman, Eric, Wang, Michael, Zahuranec, Darin, Cucchiara, Brett, Messe, Steven, Wilson, Christina, Ishida, Koto, Mullen, Michael, Raser, Jonathan, Pawar, Swaroop, Rose, David, Shafi, Neelofer, Rybinnik, Igor, McGavery, Michael, Beslow, Lauren, Sansing, Lauren, Ali, Latisha, Abcede, Hermelinda, Adamczyk, Peter, Buxton, William, Froehler, Michael, Kim, Doojin, Liebeskind, David, Ovbiagele, Bruce, Porter, Verna, Rajajee, Venkatakrishna, Rao, Neal, Raychev, Radoslav, Song, Sarah, Saver, Jeffrey, Tenser, Matthew, Velani, Shamsha, Yallapragada, Anil, Meyer, Brett, Guzik, Any, Loc, Kiet, Meyer, Dawn, Tafreshi, Gilda, Choe, Jessica, Sodhi, Ajeet, Delaney, Patrick, Evans, Sean, Ghausi, Omar A., Bruce, Nhu, Neil, Will, Huisa, Brank, Stemer, Andrew, Taylor, Reid, Larson, Jeanette, Larson, Seth, Leacock, Rodney, Dash, Subasisni, Eisenstein, Robert, Kapitanyan, Raffi, Paolucci, Ugo, Shah, Chirag, Toe, Win, Brick, John, Lander, Owen, Larrabee, Hollynn, Gutmann, Laurie, Minardi, Joseph, Tadros, Allison, Tillotson, Roger, Whiteman, Charles, Paulson, Debra, Sikora, Rosanna, Cummings, Christopher, Foster, John, Carrozzella, Janice, Doellman, Traci, Ewing, Irene, Frasure, Jamey, Goodall, Emily, Kimmel, Pamela, Spilker, Judith, Tamer, Robert, Waymeyer, Peggy, Zeigler, Joyce, Davis, Lisa, Farsad, Saman, Morella, Teresa, Kade, Allison, Frederiksen, Shirley, Liz, Mary, Luciano, Jean, Guzy, Judy, Grunberg, Ileana, Rzesiewicz, Teresa, Rapp, Karen, Nanney, Tracy, Shell, Leslie, Perkins, Margaret, Benton, Cindy, Jones, Robin, Hampton, Lynne, Cuento, Claudine, Alosky, Rachel, Shepard, Stephanie, Moccio, Michelle, Albrecht, Catherine, Rosario, Yaritza, Caputo, Deborah, Davis, Stephen, Altemus, Patricia, Power, Martha, VanGilder, Reyna, Sherman, Jay, and Barr, Taura

Published
2013
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11. Risk of Stroke and Cardiovascular Events After Ischemic Stroke or Transient Ischemic Attack in Patients With Type 2 Diabetes or Metabolic Syndrome: Secondary Analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial

Author

Callahan, Alfred, Amarenco, Pierre, Goldstein, Larry B., Sillesen, Henrik, Messig, Mike, Samsa, Gregory P., Altafullah, Irfan, Ledbetter, Lucy Y., MacLeod, Mary J., Scott, Russell, Hennerici, Michael, Zivin, Justin A., and Welch, K. Michael

Published
2011
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12. Reply

Author

Szarek, Michael, primary, Amarenco, Pierre, additional, Callahan, Alfred, additional, Goldstein, Larry B., additional, Sillesen, Henrik, additional, and Welch, K. Michael, additional

Published
2020
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26. Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks:Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial

Author

Ganz, Peter, Amarenco, Pierre, Goldstein, Larry B, Sillesen, Henrik, Bao, Weihang, Preston, Gregory M, Welch, K Michael A, Ganz, Peter, Amarenco, Pierre, Goldstein, Larry B, Sillesen, Henrik, Bao, Weihang, Preston, Gregory M, and Welch, K Michael A

Abstract

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

Published
2017

27. Long-term disability after lacunar stroke

Author

Dhamoon, Mandip S., primary, McClure, Leslie A., additional, White, Carole L., additional, Lakshminarayan, Kamakshi, additional, Benavente, Oscar R., additional, Elkind, Mitchell S.V., additional, Benavente, Oscar, additional, Hart, Robert, additional, Pergola, Pablo, additional, Palacio, Santiago, additional, Castro, Irma, additional, Farias, Arlene, additional, Roldan, Ana, additional, Kase, Carlos, additional, Gavras, Irene, additional, Lau, Helena, additional, Ogrodnik, Matt, additional, Allen, Nancy, additional, Meissner, Irene, additional, Graves, John, additional, Herzig, Deb, additional, Covalt, Jody, additional, Meyer, Brett, additional, Jackson, Christy, additional, Gamble, Paul, additional, Kelly, Nancy, additional, Warner, Janet, additional, Bell, Jo, additional, Demaerschalk, Bart, additional, Hogan, Michael, additional, Wochos, Daniel, additional, Wieser, Judith, additional, Cleary, Barbara, additional, Wood, Lori, additional, Hanna, Joseph, additional, Zipp, Thomas, additional, Bailey, Scott, additional, Cook, Dana, additional, Liskay, Alice, additional, Simcox, Dana, additional, Kappler, Joan, additional, Anderson, David, additional, Grimm, Richard, additional, Brauer, Donna, additional, Pettigrew, Creed, additional, Vaishnov, Anand, additional, Sawaya, Peter, additional, Fowler, Anna, additional, Hughes, Nedda, additional, Rice, Johnya, additional, Vanderpool, Kathy, additional, Cruz-Flores, Salvador, additional, Walden, H Douglas, additional, Holzemer, Eve, additional, Santhakumar, Sunitha, additional, Van Stavern, Renee, additional, Chatuverdi, Seemant, additional, Flack, John, additional, Mada, Flicia, additional, Wiseman, David, additional, Berlow, Elizabeth, additional, Klinker, Julie, additional, Chiu, David, additional, Taylor, Addison, additional, Katz, Larry, additional, Coull, Bruce, additional, Howard, Lien, additional, Malekniazi, Mina, additional, VanSkiver, Melissa, additional, Bruck, Denise, additional, Redman, Stacey, additional, Logan, William, additional, Carpenter, David, additional, Schroer, Sally, additional, Katramados, Angelo, additional, Silver, Brian, additional, Yee, Jerry, additional, Aiello, Krisy, additional, Wilson, Kathleen, additional, McCarthy, Sharon, additional, Dandapani, Bhuvaneswari, additional, Spies, C Peter, additional, Vasile, Carole, additional, Anthony, Betty, additional, Ferguson, Jennifer, additional, Krubel, Sharon, additional, Synman, Amanda, additional, Andrews, Natalie, additional, Kirshner, Howard, additional, Sussman, Craig, additional, Brown, Diane, additional, Elkind, Mitch, additional, Crew, Russell John, additional, Radhakrishan, Jai, additional, Corporan, Tania E., additional, Diaz, Julisa, additional, Aragon, Rebeca, additional, Slivka, Andrew, additional, Spetie, Dan, additional, Agriesti, Julie, additional, Notstein, Peggy, additional, Naritoku, Dean, additional, Zweifler, Richard, additional, Culpepper, Michael, additional, Parnell, Mel, additional, Yunker, Robin, additional, Boots, Kelly, additional, Drinkard, Renay, additional, Backlin, Rachel, additional, Benesch, Curtis, additional, Bisognano, John, additional, Leonhardt, Ann, additional, Zentner, Justine, additional, Hildreth, Molly, additional, Johnson, Mark, additional, Liu, Yinghui, additional, Goldsteen, Robert, additional, Blair, April, additional, Wright, Gregg, additional, Gathua, Naomie, additional, Book, Diane, additional, Eapen, Sunu, additional, Grimm, Clarence, additional, Blaney, Barbara, additional, Rozman, Stephanie, additional, Gaertner, Linda, additional, Bradenburg, Erin, additional, Loomis, Laura, additional, Cotton, Jolene Monarch-, additional, Ravavelli-Meyer, Jean, additional, Golembieski, Anna, additional, Burgin, Scott W., additional, Hollander, Joshua, additional, Polashenski, Walter, additional, Wallace, Patricia, additional, Weber, Cheryl, additional, Lutsep, Helmi, additional, Girard, Don, additional, Seisler, Kali, additional, Cingel, Megan, additional, Ross, Megan, additional, Stone, Rachel, additional, Larsen, Darren, additional, Doherty, Ann, additional, Lefkowitz, David, additional, Pavel, Levy, additional, Buchheimer, Nancy, additional, Vaughn, Sara, additional, Smith, Emily, additional, Satterfield, Jean, additional, Tirschwell, David, additional, Logar, Christine, additional, Ryan, Michael, additional, Schubert, Glenn, additional, Tanzai, Patricia, additional, Mirsen, Tom, additional, McAllister, Susan, additional, Bastien, Arnaud, additional, Niblack, Patricia, additional, Frey, James, additional, Darbonne, Carol, additional, Karanjia, Percy, additional, Murali, Narayana, additional, Dart, Richard, additional, Mancl, Kathleen, additional, Atkinson, Richard, additional, Lieberman, Roger, additional, Carter, Teresa, additional, Zrelak, Pat, additional, Kenney, Nola, additional, Jacoby, Michael, additional, Jones, David, additional, DeFrancisco, Jeffrey, additional, Hamm, Theresa, additional, Romano, José, additional, Ortiz, Gustavo, additional, Carmen Lichtenberger, Maria del, additional, Linas, Rafael, additional, Kravet, Steven, additional, Alt, Janice, additional, Sundararajan, Sophia, additional, Rahman, Mahboob, additional, Horvath, Tom, additional, Korosec, David, additional, Murphy, Chris, additional, Greenberg, Jason, additional, Lennihan, Laura, additional, King, Marjorie, additional, Tenteromano, Laura, additional, Frankel, Michael, additional, Doyle, Joyce, additional, Braimah, Janet, additional, Pereira, Lorainne, additional, Ching, Marilou, additional, Sawyer, Robert, additional, Parkes, Kathy, additional, Conover, Cheryl, additional, Albakri, Erfan, additional, Ramirez, German, additional, Segal, Stephenie, additional, Taylor, Kathy, additional, Jackson, Judy, additional, Helgason, Kathy, additional, Hillmann, Maureen, additional, Ringel, Robert, additional, Fleming, Nicholas, additional, Mckown, Bunny, additional, Cohen, Stanley, additional, Jenders, Robert, additional, Singh, Ravinder, additional, La, Minh-Thu, additional, Trinh, Khanhphong, additional, Weinberger, Jesse, additional, Wright, Lewis, additional, Burch, Dorothy, additional, Horowitz, Ronnie, additional, Atlas, Steven, additional, Augustine, Sandra, additional, Brown, Angela, additional, Serna, Jannie, additional, Newgent, Jill, additional, Naylor, Julie, additional, Carpenter, Laura, additional, Warwick, Tanya, additional, Stoltz, Steven, additional, Garcia, Rebekah, additional, Scheck, Michael, additional, Chadwick, Linda, additional, Fleck, James, additional, Weinberger, Myron, additional, Sears, Alison, additional, Fanale, Chris, additional, Neeper, Lenden, additional, Fisk, Paula, additional, Sabry, Daniel, additional, Phoenix, Ron, additional, Tong, David, additional, Garcia, Madelleine, additional, Mackey, Ariane, additional, Morin, Jovette, additional, Haché, Annette, additional, Lessard, Claudette, additional, Côté, Robert, additional, Green, Laurence, additional, Wadup, Lisa, additional, Fontaine, Anne-Marie, additional, Gubitz, Gordon, additional, Rebello, Rosario, additional, Dean, Tim, additional, Reidy, Yvette, additional, Sharma, Mukul, additional, Stotts, Grant, additional, Clark, Heather, additional, Mortensen, Melodie, additional, Sauve, Jenniffer, additional, Sharma, Doris, additional, Savage, Michelle, additional, Minuk, Jeffrey, additional, Trudeau, Luc, additional, Schanz, Claudia, additional, Berger, Leo, additional, Brunet, Sylvain, additional, Pontbriand, Johanne, additional, Mainville, Martine, additional, Racicot, Denise, additional, Hill, Michael, additional, Fischer, Karyn, additional, Cole-Kaskayne, Andrea, additional, Keeney, Carol, additional, Shuab, Ashfaq, additional, Khan, Khurshid, additional, Dean, Naeen, additional, Herbert, Frederika, additional, Kastelic, Karen, additional, Pretell, Edwin Javier, additional, Valdivia, José, additional, Pretell, Marissa, additional, Brutto, Oscar del, additional, Santibáñez, Rocio, additional, Lara, Joffre, additional, Zambrano, Mauricio, additional, Arauz, Antonio, additional, Cervantes, G Amin, additional, Leyva, Adolfo, additional, Camacho, Itzel, additional, Ruiz Sandoval, José Luis, additional, Vásquez, Eduardo Salcido, additional, Ruiz, Carmen, additional, Brito, Carlos Cantú, additional, Fernández, Margarita, additional, Góngora-Rivera, Juan Fernándo, additional, Escamilla, Juan Manuel, additional, Moxica, Joaquín, additional, Arciniega, Genny, additional, Gonzalez, Wendy Joana, additional, Matamala, Gonzalo, additional, Goecke, Helmut, additional, Parra, Marcela, additional, Pozo, Jessica, additional, Tapia, Jorge, additional, Godoy, Ivan Esteban, additional, Valdes, Marcela, additional, Estol, Conrado, additional, Peralta, Cecilia, additional, Ellenberg, Adriana, additional, Chezzio, Daniela, additional, Fernández Pardal, Manuel M., additional, Trimachi, Hernan, additional, Bonardo, Pablo, additional, Mazziotti, Julieta, additional, Rey, Raul Carlos, additional, Caruso, Gustavo, additional, Melamud, Luciana, additional, Lepera, Sandra, additional, Stilman, Ana Paula, additional, Ameriso, Sebastian, additional, Sánchez, Ramiro, additional, Bruera, Guadalupe, additional, Moschini, Javier, additional, Ramírez, Maria J., additional, Bueri, José A., additional, Sevilla, Sebastián, additional, de Ambrosi, Bruno, additional, Marinsalta, Gabriela, additional, Rubio, Francisco, additional, Krupinski, Yurek, additional, Carvajal, Ana, additional, Roquer, Jaume, additional, Serrano, Ana Oliveras, additional, Conde, Jordi Jiménez, additional, Rodríguez, Ana, additional, Romeral, Gemma, additional, Arboix, Adrià, additional, Pelegrí, Antoni, additional, Blanco, Lorena, additional, Vergé, David Cánovas, additional, Herrero, Jordi Estela, additional, Gómez, Ana, additional, Leal, Joaquín Serena, additional, Castellanos, Mar, additional, Cruz, Verónica, additional, Cepeda, Mercè, additional, Gomis, Meritxell, additional, Arenillas, Juan, additional, Dávalos, Antonio, additional, Suñol, Ana, additional, Reverté, Silvia, additional, Martí-Villalta, José Lluis, additional, Martínez, Sergio, additional, Marín, Rebeca, additional, Sánchez, José Castillo, additional, González, Miguel Blanco, additional, Rodríguez, Manuel, additional, Jiménez, Isabel, additional, Rodríguez, Jaime, additional, Tejedor, Exuperio Díez, additional, Martínez, Patricia, additional, Fuentes, Blanca, additional, Singla, Lluis Soler, additional, Balaguer, Ernest, additional, Izquierdo, Joan, additional, Soler, Cristina, additional, Armenteros, Maria, additional, Shepherd, Alexander, additional, Benavente, Marie-France, additional, White, Carole, additional, Robu, Camilla, additional, Kelly, Che, additional, Talbert, Robert, additional, Martinez, Eduardo, additional, Bazan, Carlos, additional, Pergola, Gabriela, additional, Pearce, Lesly, additional, Costello, Raymond, additional, Jacova, Claudia, additional, Camelia, Luisa, additional, Mendoza, Crystal, additional, Pratt, Brandy, additional, Kin, B., additional, Holliday, Steve, additional, McClure, Leslie, additional, Coffey, Christopher, additional, Szychowski, Jeff, additional, Howard, George, additional, Katholi, Charles, additional, Zhang, Yu, additional, Peri, Kalyani, additional, Allcorn, Charles, additional, Mailhot, Richard, additional, Irby, Lisa, additional, Guyton, Fekisha, additional, Sewell, Mary Jo, additional, Ringer, Robert, additional, Raisch, Dennis, additional, Hunt, Dave, additional, Rosso, Clara M., additional, Martin, Ariadna, additional, Sanllorente, Mireia, additional, Arabetti, Celso, additional, Fernández, José Luis, additional, Cremona, Maria Julia, additional, Capece, Ana, additional, Benavente, Marie, additional, Conwit, Robin, additional, Elkind, Mitchell, additional, Moy, Claudia, additional, Aguilar, Maria, additional, Sherman, David, additional, Nasco, Elaine, additional, Blackshear, Joe, additional, Chung, Mina, additional, Fayad, Pierre, additional, Gage, Brian, additional, Johnston, Clay, additional, Kernan, Walter, additional, Leira, Enrique, additional, Merino, Jose, additional, Roman, Gustavo, additional, Sila, Cathy, additional, Sung, Gene, additional, van Walraven, Carl, additional, Stern, Barney, additional, Welch, K. Michael, additional, Clarke, William, additional, Cutler, Jeffrey, additional, Furie, Karen, additional, Johnston, Karen, additional, and Mayo, Matthew, additional

Published
2015
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30. KEY NOTE LECTUREAPPeriaqueductal gray matter dysfunction in migraine and chronic daily headache may be due to free radical damage

Author

Welch, K. Michael A., Nagesh, Vijaya, Aurora, Sheena K., and Gelman, Neil

Subjects
Free radicals (Chemistry) -- Health aspects, Migraine -- Physiological aspects, Brain -- Physiological aspects, Magnetic resonance imaging -- Usage, Health
Abstract

Byline: K. Michael A. Welch (1), Vijaya Nagesh (2), Sheena K. Aurora (2), Neil Gelman (2) Abstract: The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG in episodic migraine patients between attacks and in chronic daily headache patients during headache using high-resolution magnetic resonance imaging (MRI) techniques to map the transverse relaxation rates R2, R2* and R2' in the PAG, red nucleus (RN) and substantia nigra (SN). R2' is a measure of non-heme iron in tissues. We hypothesized that repeated hyperoxia of brainstem structures observed during migraine may generate free radical damage over time, resulting in iron deposition in vulnerable tissue. Seventeen patients diagnosed with episodic migraine with and without aura (EM), 17 with chronic daily headache (CDH) and medication overuse, and 17 normal adults (N) were imaged with a 3 tesla MRI system. In the PAG, there was a significant increase in mean R2' and R2* values in both the EM and CDH groups (p&lt 0.05) compared to normal, but no significant difference in these values between the EM and CDH groups, or between migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2' in the EM and CDH groups. Duration of the episodic migraine stage in the CDH group did not correlate significantly with R2', although the total duration of the episodic migraine plus daily headache stages of the CDH group strongly correlated with R2'. No effect of age was noted on R2'. Decrease in mean R2' and R2* values also was observed in the RN and SN of the CDH compared to N and EM groups (p&lt 0.05), explained best by flow activation due head pain. Iron homeostasis in the PAG was selectively, persistently and progressively impaired in the EM and CDH groups, possibly caused by free radicals generated during repeated migraine attacks. These results support and emphasize the role of the PAG in migraine, potentially by dysfunctional control of the trigeminovascular nociceptive system. Development of CDH out of EM may be associated with a critical threshold of iron deposition and drug withdrawal excitation of the dysfunctional PAG. Author Affiliation: (1) University of Kansas Medical Center, 3901 Rainbow Blvd., Room 6002 Wescoe, Kansas City, Kansas 66160-7702, USA, e-mail: kwelch2@kumc.edu, Tel.: +1-913-588-5448, Fax: +1-913-588-5444, US (2) Department of Neurology, Henry Ford Health Sciences Center and NMR Research Center, Detroit, Michigan, USA, US

Published
2001

36. Assessing the Effects of Antihypertensive Medication on Cerebral Blood Flow: Demonstration in Internal Carotid Artery Occlusion

Author

Fagan, Susan C., Ewing, James R., Levine, Steven R., Tietjen, Gretchen E., Ramadan, Nabih M., and Welch, K. Michael A.

Abstract

Dynamic cerebral blood flow (CBF) studies using acetazolamide or hypercapnia as a vasodilatory challenge have attempted to evaluate intracranial hemodynamics. We report two patients with asymptomatic internal carotid artery occlusion in whom the vasodilatory stimulus was a single oral dose of antihypertensive medication (prazosin hydrochloride or enalapril maléate). In both patients, changes in regional CBF occurred that were larger than those seen in nine normal controls. One patient experienced an improvement in regional CBF with a reduction in probe pair asymmetry. In the other patient, who had bilateral carotid artery disease, a decrease in regional CBF in all 16 probes (mean decrease 12 percent) and an accentuation of the predose asymmetry were observed. Both patients remained asymptomatic throughout the study. Assessing these effects on cerebral circulation may help identify patients at risk for iatrogenic focal cerebral ischemia and provide information regarding the functional status of the cerebral vasculature.

Published
1991
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39. Response of the brain to oligemia: gene expression, c-Fos, and Nrf2 localization

Author

Liverman, Christopher S., Cui, Lisa, Yong, Chi, Choudhuri, Rajani, Klein, Robert M., Welch, K. Michael A., and Berman, Nancy E.J.

Subjects
*GENE expression, *BLOOD flow, *PROTEINS, *IMMUNOHISTOCHEMISTRY
Abstract

Oligemia is blood flow reduction without acute tissue damage that occurs in shock, migraine, and stroke penumbra. We developed a mouse model of oligemia by lowering mean arterial pressure to 30–40 mm Hg, resulting in a 50% reduction in cerebral blood flow as measured by laser Doppler, and reperfusing the blood after 30 min. Control experiments included anesthesia-only and surgery without blood withdrawal. Using immunohistochemistry, we localized the transcription factors Nrf2, which regulates expression of antioxidant and detoxification protein, and c-Fos, a marker of neuronal activation. Nrf2 was found only in oligemia mice and was localized in neurons of the cingulate cortex and cerebellar Purkinje cells. By contrast, c-Fos was found widely expressed in both groups and was localized in neurons in regions associated with response to stress, immunomodulation, and fluid homeostasis, including the periaqueductal gray and periventricular nucleus. These data indicate that c-Fos expression occurs as a result of surgical stress, but Nrf-2 upregulation is specific to oligemia. The CLONTECH Atlas 1.2 Mouse Array was used to assess genes that were up or down-regulated in oligemia versus surgery controls. Of 1176 genes, 29 differed between oligemia and surgery groups. Upregulation of oxidative stress induced (OSI) protein, heat shock protein (HSP) 84 and transthyretin (TTR) precursor in the oligemia group was confirmed with RT-PCR. The expression of HSP 84, transthyretin precursor, and OSI genes adds further evidence that oligemia induces an oxidative stress response in the brain. [Copyright &y& Elsevier]

Published
2004
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44. Prediction of major vascular events after stroke: the stroke prevention by aggressive reduction in cholesterol levels trial.

Author

Ovbiagele B, Goldstein LB, Amarenco P, Messig M, Sillesen H, Callahan A 3rd, Hennerici MG, Zivin J, and Welch KM

Subjects
Aged, Atorvastatin, Coronary Disease complications, Coronary Disease prevention & control, Female, Follow-Up Studies, Heptanoic Acids therapeutic use, Humans, Ischemic Attack, Transient complications, Ischemic Attack, Transient prevention & control, Male, Middle Aged, Prognosis, Pyrroles therapeutic use, Risk Assessment, Treatment Outcome, Vascular Diseases epidemiology, Anticholesteremic Agents therapeutic use, Stroke complications, Stroke prevention & control, Vascular Diseases etiology, Vascular Diseases prevention & control
Abstract

Background: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial., Methods: Data from the 4731 subjects enrolled in the SPARCL study were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination (c-statistics) was assessed using the areas under the receiver operating characteristic curves., Results: Of 3969 subjects with complete data, 27% had a baseline FCRS of 20% or more. In multivariable analysis, an FCRS of 20% or more was associated with twice the risk of subsequent MVEs (HR = 1.92, 95% confidence interval [CI]: 1.63-2.27). The novel model based on a multivariable analysis included age (HR = 1.37, 95% CI: 1.25-1.51 per 10 years), diabetes (HR = 1.82, 95% CI: 1.51-2.18), male sex (HR = 1.35, 95% CI: 1.12-1.61), and an apolipoprotein (APO)-B/APO-A1 ratio (HR = 1.56, 95% CI: 1.16-2.11). The c-statistic was .58 (95% CI: .55-.60) for the FCRS of 20% or more and .65 (95% CI: .63-.67) for the novel model., Conclusions: Both a baseline FCRS of 20% or more and a novel predictive model were associated with future MVEs in SPARCL trial subjects. The novel model needs to be validated, and the benefits of using either the FCRS or the novel model in clinical practice needs to be assessed., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Published
2014
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46. "Ottorino Rossi" Award 2003.

Author

Welch KM

Subjects
Central Nervous System Diseases history, History, 20th Century, History, 21st Century, Italy, Societies, Scientific, United States, Awards and Prizes, Cerebrovascular Disorders history, Neurobiology history
Published
2003

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