C-Reactive Protein as a Prognostic Marker After Lacunar Stroke
Authors: Elkind Mitchell S.V. , Luna Jorge M. , McClure Leslie A. , Zhang Yu , Coffey Christopher S. , Roldan Ana , Del Brutto Oscar H. , Pretell Edwin Javier , Pettigrew L. Creed , Meyer Brett C. , Tapia Jorge , White Carole , Benavente Oscar R. ,   The LIMITS Investigators,   Clinical Sites in Order of Number of Participants (n) Enrolled,   United States, 31 sites (n=639),   University of Kentucky, Lexington, KY, Pettigrew Creed , Vaishnav Anand , Sawaya Peter , Fowler Anna , Hughes Nedda , Rice Johnya , Vanderpool Kathy ,   University of California San Diego, San Diego, CA, Meyer Brett , Jackson Christy , Gamble Paul , Kelly Nancy , Warner Janet , Bell Jo ,   Rochester Stroke Center, Rochester, MN, Meissner Irene , Graves John , Herzig Deb , Covalt Jody ,   St Louis University, St Louis, MO, Cruz-Flores Salvador , Walden H. Douglas , Holzemer Eve ,   University of Arizona, Tucson, AZ, Coull Bruce , Howard Lien , Malekniazi Mina , VanSkiver Melissa , Bruck Denise , Redman Stacey ,   Metrohealth Medical Center, Cleveland, OH, Hanna Joseph , Zipp Thomas , Bailey Scott , Cook Dana , Liskay Alice , Simcox Dana , Kappler Joan ,   Mayo Clinic Scottsdale, Scottsdale, AZ, Demaerschalk Bart , Hogan Michael , Wochos Daniel , Wieser Judith , Cleary Barbara , Wood Lori ,   Henry Ford Hospital, Detroit, MI, Katramados Angelo , Silver Brian , Yee Jerry , Aiello Krisy , Wilson Kathleen , McCarthy Sharon ,   Boston University, Boston, MA, Kase Carlos , Gavras Irene , Lau Helena , Ogrodnik Matt , Allen Nancy ,   Berman Center for Clinical Research, Minneapolis, MN, Anderson David , Grimm Richard , Brauer Donna ,   University of South Alabama, Mobile, AL, Naritoku Dean , Zweifler Richard , Culpepper Michael , Parnell Mel , Yunker Robin , Boots Kelly , Drinkard Renay , Backlin Rachel ,   Columbia University Medical Center, New York, NY, Elkind Mitch , Crew Russell John , Radhakrishan Jai , Corporan Tania E. , Diaz Julisa , Aragon Rebeca ,   University of Texas Health Science Center at San Antonio, San Antonio, TX, Benavente Oscar , Hart Robert , Pergola Pablo , Palacio Santiago , Castro Irma , Farias Arlene , Roldan Ana ,   Cooper Health System Department of Medicine, Camden, NJ, Mirsen Tom , McAllister Susan , Bastien Arnaud , Niblack Patricia ,   University Hospitals Case Medical Center, Cleveland, OH, Sundararajan Sophia , Rahman Mahboob , Horvath Tom , Korosec David , Murphy Chris ,   Oregon Health and Science University, Portland, OR, Lutsep Helmi , Girard Don , Seisler Kali , Cingel Megan , Ross Megan , Stone Rachel , Larsen Darren , Doherty Ann ,   Medical College of Wisconsin, Milwaukee, WI, Book Diane , Eapen Sunu , Grimm Clarence , Blaney Barbara , Rozman Stephanie , Gaertner Linda , Bradenburg Erin , Loomis Laura , Monarch-Cotton Jolene , Ravavelli-Meyer Jean , Golembieski Anna ,   University of Miami, Miller School, Miami, FL, Romano José , Ortiz Gustavo , del Carmen Lichtenberger Maria ,   University of Texas Southwestern, Dallas, TX, Johnson Mark , Liu Yinghui , Goldsteen Robert , Blair April , Wright Gregg , Gathua Naomie ,   Ruan Neurology Clinic and Research Center, Des Moines, IA, Jacoby Michael , Jones David , DeFrancisco Jeffrey , Hamm Theresa ,   University of Rochester Medical Center, Rochester, NY, Burgin Scott W. , Hollander Joshua , Polashenski Walter , Wallace Patricia , Weber Cheryl ,   Helen Hayes Hospital, West Haverstraw, NY, Greenberg Jason , Lennihan Laura , King Marjorie , Tenteromano Laura ,   Research Foundation of SUNY, Buffalo, NY, Pereira Lorainne , Ching Marilou , Sawyer Robert , Parkes Kathy , Conover Cheryl ,   North General Hospital, New York, NY, Weinberger Jesse , Wright Lewis , Burch Dorothy ,   University of Rochester, Rochester, NY, Benesch Curtis , Bisognano John , Leonhardt Ann , Zentner Justine , Hildreth Molly ,   Marshfield Clinic Department of Neurology, Marshfield, WI, Karanjia Percy , Murali Narayana , Dart Richard , Mancl Kathleen ,   Wake Forest University, Winston-Salem, NC, Lefkowitz David , Pavel Levy , Buchheimer Nancy , Vaughn Sara , Smith Emily , Satterfield Jean ,   University of Washington at St Louis, St Louis, MO, Van Stavern Renee , Brown Angela , Serna Jannie , Newgent Jill , Naylor Julie , Carpenter Laura ,   University of Alberta Stroke Research NACTRC, Edmonton, AB, Shuab Ashfaq , Khan Khurshid , Dean Naeen , Herbert Frederika , Kastelic Karen ,   Sutter Neuroscience Institute, Sacramento, CA, Atkinson Richard , Lieberman Roger , Carter Teresa , Zrelak Pat , Kenney Nola ,   St John’s Mercy Medical Center, St Louis, MO, Logan William , Carpenter David , Schroer Sally ,   Canada, 2 sites (n=52),   Charles LeMoyne Hospital, Greenfield Park, QC, Berger Leo , Brunet Sylvain , Pontbriand Johanne , Mainville Martine , Racicot Denise ,   McGill University Montreal General, Montreal, QC, Côté Robert , Green Laurence , Wadup Lisa , Fontaine Anne-Marie ,   Chile, 2 sites (n=90),   Hospital Clinico Universidad Católica de Chile, Santiago, Tapia Jorge , Godoy Ivan Esteban , Valdes Marcela ,   Universidad Católica, Santiago, and Hospital Naval, Viña del Mar, Matamala Gonzalo , Goecke Helmut , Parra Marcela , Pozo Jessica ,   Ecuador, 1 site (n=171),   Hospital-Clínica-Kennedy, Guayaquil, del Brutto Oscar , Santibáñez Rocio , Lara Joffre , Zambrano Mauricio ,   Mexico, 2 sites (n=18),   Hospital Civil/México, Guadalajara, Jalisco, Ruiz Sandoval José Luis , Vásquez Eduardo Salcido , Ruiz Carmen ,   Instituto Nacional de Neurología y Neurocirugía, México City, Arauz Antonio , Cervantes G. Amin , Leyva Adolfo , Camacho Itzel ,   Peru, 1 site (n=151),   Hospital Sabogal, Lima, Perú, Pretell Edwin Javier , Valdivia José , Pretell Marissa ,   Spain, 6 sites (n=137),   Hospital de Girona Dr Josep Trueta, Girona, Leal Joaquín Serena , Castellanos Mar , Cruz Verónica , Cepeda Mercè ,   Hospital Del Sagrat Cor, Barcelona, Arboix Adrià , Pelegrí Antoni , Blanco Lorena ,   Hospital del Bellvitge, Barcelona, Borrego Francisco Rubio , Gudiol Francisco ,   Hospital Universitario German Trias i Pujol, Barcelona, Gomis Meritxell , Arenillas Juan , Dávalos Antonio , Suñol Ana , Reverté Silvia ,   Hospital del Mar, Barcelona, Roquer Jaume , Serrano Ana Oliveras , Conde Jordi Jiménez , Rodríguez Ana , Romeral Gemma ,   Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Sánchez José Castillo , González Miguel Blanco , Rodríguez Manuel , Jiménez Isabel , Rodríguez Jaime ,   Statistical and Data Management Center,   University of Alabama at Birmingham, AL, McClure Leslie , Coffey Christopher , Szychowski Jeff , Howard George , Katholi Charles , Zhang Yu , Peri Kalyani , Allcorn Charles , Mailhot Richard , Irby Lisa , Guyton Fekisha , Sewell Mary Jo ,   SPS3 Coordinating Center,   University of British Columbia, Vancouver, BC, Canada, and University of Texas Health Science Center at San Antonio, TX, Benavente Oscar , Hart Robert , Pergola Pablo , Roldan Ana , Benavente Marie-France , White Carole , Robu Camilla , Kelly Che , Talbert Robert , Martinez Eduardo ,   Neuroradiology Core, Bazan Carlos , Pergola Gabriela ,   Neuropsychology Core, Pearce Lesly , Costello Raymond , Jacova Claudia , Camelia Luisa , Mendoza Crystal , Pratt Brandy , Holliday Steve ,   LIMITS Coordinating Center,   Columbia University, NY, Elkind Mitchell S.V. , Luna Jorge 
Published: February 2014

Background and Purpose—
Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke.

Methods—
Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use.

Results—
Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP >4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30–4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15–4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14–3.67). There was no interaction with randomized antiplatelet treatment.

Conclusions—
Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00059306.