Prothrombotic factors do not increase the risk of recurrent ischemic events after cryptogenic stroke at young age: the FUTURE study

go back to reference Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle HP, Schroth G, Remonda L, Sturzenegger M, Fischer U, Baumgartner RW (2005) Ischaemic stroke in young adults: predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry 76(2):191–195. https://doi.org/10.1136/jnnp.2004.040543 CrossRefPubMedPubMedCentral Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle HP, Schroth G, Remonda L, Sturzenegger M, Fischer U, Baumgartner RW (2005) Ischaemic stroke in young adults: predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry 76(2):191–195. https://​doi.​org/​10.​1136/​jnnp.​2004.​040543 CrossRefPubMedPubMedCentral

go back to reference Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, Flaherty ML, Khatri P, Ferioli S, La Rosa FD, Broderick JP, Kleindorfer DO (2012) Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology 79(17):1781–1787. https://doi.org/10.1212/WNL.0b013e318270401d CrossRefPubMedPubMedCentral Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, Flaherty ML, Khatri P, Ferioli S, La Rosa FD, Broderick JP, Kleindorfer DO (2012) Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology 79(17):1781–1787. https://​doi.​org/​10.​1212/​WNL.​0b013e318270401d​ CrossRefPubMedPubMedCentral

go back to reference Griffiths D, Sturm J (2011) Epidemiology and etiology of young stroke. Stroke Res Treat 2011:209370. https://doi.org/10.4061/2011/209370 PubMedPubMedCentral Griffiths D, Sturm J (2011) Epidemiology and etiology of young stroke. Stroke Res Treat 2011:209370. https://​doi.​org/​10.​4061/​2011/​209370 PubMedPubMedCentral

go back to reference Hamedani AG, Cole JW, Mitchell BD, Kittner SJ (2010) Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment. Stroke 41(8):1599–1603. https://doi.org/10.1161/strokeaha.110.581256 CrossRefPubMedPubMedCentral Hamedani AG, Cole JW, Mitchell BD, Kittner SJ (2010) Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment. Stroke 41(8):1599–1603. https://​doi.​org/​10.​1161/​strokeaha.​110.​581256 CrossRefPubMedPubMedCentral

go back to reference Hamedani AG, Cole JW, Cheng Y, Sparks MJ, O’Connell JR, Stine OC, Wozniak MA, Stern BJ, Mitchell BD, Kittner SJ (2013) Factor V leiden and ischemic stroke risk: the Genetics of Early Onset Stroke (GEOS) study. J Stroke Cerebrovasc Dis 22(4):419–423. https://doi.org/10.1016/j.jstrokecerebrovasdis.2011.10.007 CrossRefPubMed Hamedani AG, Cole JW, Cheng Y, Sparks MJ, O’Connell JR, Stine OC, Wozniak MA, Stern BJ, Mitchell BD, Kittner SJ (2013) Factor V leiden and ischemic stroke risk: the Genetics of Early Onset Stroke (GEOS) study. J Stroke Cerebrovasc Dis 22(4):419–423. https://​doi.​org/​10.​1016/​j.​jstrokecerebrova​sdis.​2011.​10.​007 CrossRefPubMed

go back to reference Morris JG, Singh S, Fisher M (2010) Testing for inherited thrombophilias in arterial stroke: can it cause more harm than good? Stroke 41(12):2985–2990. https://doi.org/10.1161/strokeaha.110.595199 CrossRefPubMed Morris JG, Singh S, Fisher M (2010) Testing for inherited thrombophilias in arterial stroke: can it cause more harm than good? Stroke 41(12):2985–2990. https://​doi.​org/​10.​1161/​strokeaha.​110.​595199 CrossRefPubMed

go back to reference Sciascia S, Sanna G, Khamashta MA, Cuadrado MJ, Erkan D, Andreoli L, Bertolaccini ML (2015) The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann Rheum Dis 74(11):2028–2033. https://doi.org/10.1136/annrheumdis-2014-205663 CrossRefPubMed Sciascia S, Sanna G, Khamashta MA, Cuadrado MJ, Erkan D, Andreoli L, Bertolaccini ML (2015) The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann Rheum Dis 74(11):2028–2033. https://​doi.​org/​10.​1136/​annrheumdis-2014-205663 CrossRefPubMed

go back to reference Urbanus RT, Siegerink B, Roest M, Rosendaal FR, de Groot PG, Algra A (2009) Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol 8(11):998–1005. https://doi.org/10.1016/s1474-4422(09)70239-x CrossRefPubMed Urbanus RT, Siegerink B, Roest M, Rosendaal FR, de Groot PG, Algra A (2009) Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol 8(11):998–1005. https://​doi.​org/​10.​1016/​s1474-4422(09)70239-x CrossRefPubMed

go back to reference Pezzini A, Grassi M, Del Zotto E, Lodigiani C, Ferrazzi P, Spalloni A, Patella R, Giossi A, Volonghi I, Iacoviello L, Magoni M, Rota LL, Rasura M, Padovani A (2009) Common genetic markers and prediction of recurrent events after ischemic stroke in young adults. Neurology 73(9):717–723. https://doi.org/10.1212/WNL.0b013e3181b59aaf CrossRefPubMed Pezzini A, Grassi M, Del Zotto E, Lodigiani C, Ferrazzi P, Spalloni A, Patella R, Giossi A, Volonghi I, Iacoviello L, Magoni M, Rota LL, Rasura M, Padovani A (2009) Common genetic markers and prediction of recurrent events after ischemic stroke in young adults. Neurology 73(9):717–723. https://​doi.​org/​10.​1212/​WNL.​0b013e3181b59aaf​ CrossRefPubMed

go back to reference Pezzini A, Grassi M, Lodigiani C, Patella R, Gandolfo C, Zini A, Delodovici ML, Paciaroni M, Del Sette M, Toriello A, Musolino R, Calabro RS, Bovi P, Adami A, Silvestrelli G, Sessa M, Cavallini A, Marcheselli S, Bonifati DM, Checcarelli N, Tancredi L, Chiti A, Del Zotto E, Spalloni A, Giossi A, Volonghi I, Costa P, Giacalone G, Ferrazzi P, Poli L, Morotti A, Rasura M, Simone AM, Gamba M, Cerrato P, Micieli G, Melis M, Massucco D, De Giuli V, Iacoviello L, Padovani A (2014) Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults. Circulation 129(16):1668–1676. https://doi.org/10.1161/circulationaha.113.005663 CrossRefPubMed Pezzini A, Grassi M, Lodigiani C, Patella R, Gandolfo C, Zini A, Delodovici ML, Paciaroni M, Del Sette M, Toriello A, Musolino R, Calabro RS, Bovi P, Adami A, Silvestrelli G, Sessa M, Cavallini A, Marcheselli S, Bonifati DM, Checcarelli N, Tancredi L, Chiti A, Del Zotto E, Spalloni A, Giossi A, Volonghi I, Costa P, Giacalone G, Ferrazzi P, Poli L, Morotti A, Rasura M, Simone AM, Gamba M, Cerrato P, Micieli G, Melis M, Massucco D, De Giuli V, Iacoviello L, Padovani A (2014) Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults. Circulation 129(16):1668–1676. https://​doi.​org/​10.​1161/​circulationaha.​113.​005663 CrossRefPubMed

go back to reference van Goor MP, Alblas CL, Leebeek FW, Koudstaal PJ, Dippel DW (2004) Do antiphospholipid antibodies increase the long-term risk of thrombotic complications in young patients with a recent TIA or ischemic stroke? Acta Neurol Scand 109(6):410–415. https://doi.org/10.1111/j.1600-0404.2004.00241.x CrossRefPubMed van Goor MP, Alblas CL, Leebeek FW, Koudstaal PJ, Dippel DW (2004) Do antiphospholipid antibodies increase the long-term risk of thrombotic complications in young patients with a recent TIA or ischemic stroke? Acta Neurol Scand 109(6):410–415. https://​doi.​org/​10.​1111/​j.​1600-0404.​2004.​00241.​x CrossRefPubMed

go back to reference Munts AG, van Genderen PJ, Dippel DW, van Kooten F, Koudstaal PJ (1998) Coagulation disorders in young adults with acute cerebral ischaemia. J Neurol 245(1):21–25CrossRefPubMed Munts AG, van Genderen PJ, Dippel DW, van Kooten F, Koudstaal PJ (1998) Coagulation disorders in young adults with acute cerebral ischaemia. J Neurol 245(1):21–25CrossRefPubMed

go back to reference Renna R, Pilato F, Profice P, Della Marca G, Broccolini A, Morosetti R, Frisullo G, Rossi E, De Stefano V, Di Lazzaro V (2014) Risk factor and etiology analysis of ischemic stroke in young adult patients. J Stroke Cerebrovasc Dis 23(3):e221-227. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.008 CrossRef Renna R, Pilato F, Profice P, Della Marca G, Broccolini A, Morosetti R, Frisullo G, Rossi E, De Stefano V, Di Lazzaro V (2014) Risk factor and etiology analysis of ischemic stroke in young adult patients. J Stroke Cerebrovasc Dis 23(3):e221-227. https://​doi.​org/​10.​1016/​j.​jstrokecerebrova​sdis.​2013.​10.​008 CrossRef

go back to reference Nencini P, Baruffi MC, Abbate R, Massai G, Amaducci L, Inzitari D (1992) Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischemia. Stroke 23(2):189–193CrossRefPubMed Nencini P, Baruffi MC, Abbate R, Massai G, Amaducci L, Inzitari D (1992) Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischemia. Stroke 23(2):189–193CrossRefPubMed

go back to reference Rutten-Jacobs LC, Maaijwee NA, Arntz RM, Van Alebeek ME, Schaapsmeerders P, Schoonderwaldt HC, Dorresteijn LD, Overeem S, Drost G, Janssen MC, van Heerde WL, Kessels RP, Zwiers MP, Norris DG, van der Vlugt MJ, van Dijk EJ, de Leeuw FE (2011) Risk factors and prognosis of young stroke. The FUTURE study: a prospective cohort study. Study rationale and protocol. BMC Neurol 11:109. https://doi.org/10.1186/1471-2377-11-109 CrossRefPubMedPubMedCentral Rutten-Jacobs LC, Maaijwee NA, Arntz RM, Van Alebeek ME, Schaapsmeerders P, Schoonderwaldt HC, Dorresteijn LD, Overeem S, Drost G, Janssen MC, van Heerde WL, Kessels RP, Zwiers MP, Norris DG, van der Vlugt MJ, van Dijk EJ, de Leeuw FE (2011) Risk factors and prognosis of young stroke. The FUTURE study: a prospective cohort study. Study rationale and protocol. BMC Neurol 11:109. https://​doi.​org/​10.​1186/​1471-2377-11-109 CrossRefPubMedPubMedCentral

go back to reference Rutten-Jacobs LC, Maaijwee NA, Arntz RM, Schoonderwaldt HC, Dorresteijn LD, van der Vlugt MJ, van Dijk EJ, de Leeuw FE (2013) Long-term risk of recurrent vascular events after young stroke: The FUTURE study. Ann Neurol 74(4):592–601. https://doi.org/10.1002/ana.23953 CrossRefPubMed Rutten-Jacobs LC, Maaijwee NA, Arntz RM, Schoonderwaldt HC, Dorresteijn LD, van der Vlugt MJ, van Dijk EJ, de Leeuw FE (2013) Long-term risk of recurrent vascular events after young stroke: The FUTURE study. Ann Neurol 74(4):592–601. https://​doi.​org/​10.​1002/​ana.​23953 CrossRefPubMed

go back to reference Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T (1980) Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ 58(1):113–130PubMedPubMedCentral Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T (1980) Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ 58(1):113–130PubMedPubMedCentral

go back to reference Hatano S (1976) Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ 54(5):541–553PubMedPubMedCentral Hatano S (1976) Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ 54(5):541–553PubMedPubMedCentral

go back to reference Arntz RM, van Alebeek ME, Synhaeve NE, van Pamelen J, Maaijwee NA, Schoonderwaldt H, van der Vlugt MJ, van Dijk EJ, Rutten-Jacobs LC, de Leeuw F-E (2016) The very long-term risk and predictors of recurrent ischaemic events after a stroke at a young age: The FUTURE study. Eur Stroke J 1(4):337–345. https://doi.org/10.1177/2396987316673440 CrossRef Arntz RM, van Alebeek ME, Synhaeve NE, van Pamelen J, Maaijwee NA, Schoonderwaldt H, van der Vlugt MJ, van Dijk EJ, Rutten-Jacobs LC, de Leeuw F-E (2016) The very long-term risk and predictors of recurrent ischaemic events after a stroke at a young age: The FUTURE study. Eur Stroke J 1(4):337–345. https://​doi.​org/​10.​1177/​2396987316673440​ CrossRef

go back to reference Bousser MG, Amarenco P, Chamorro A, Fisher M, Ford I, Fox K, Hennerici MG, Mattle HP, Rothwell PM (2009) Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study. Cerebrovasc Dis 27(5):509–518. https://doi.org/10.1159/000212671 CrossRefPubMed Bousser MG, Amarenco P, Chamorro A, Fisher M, Ford I, Fox K, Hennerici MG, Mattle HP, Rothwell PM (2009) Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study. Cerebrovasc Dis 27(5):509–518. https://​doi.​org/​10.​1159/​000212671 CrossRefPubMed

go back to reference Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20(7):864–870CrossRefPubMed Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20(7):864–870CrossRefPubMed

go back to reference Kasner SE, Chalela JA, Luciano JM, Cucchiara BL, Raps EC, McGarvey ML, Conroy MB, Localio AR (1999) Reliability and validity of estimating the NIH stroke scale score from medical records. Stroke 30(8):1534–1537CrossRefPubMed Kasner SE, Chalela JA, Luciano JM, Cucchiara BL, Raps EC, McGarvey ML, Conroy MB, Localio AR (1999) Reliability and validity of estimating the NIH stroke scale score from medical records. Stroke 30(8):1534–1537CrossRefPubMed

go back to reference Williams LS, Yilmaz EY, Lopez-Yunez AM (2000) Retrospective assessment of initial stroke severity with the NIH Stroke Scale. Stroke 31(4):858–862CrossRefPubMed Williams LS, Yilmaz EY, Lopez-Yunez AM (2000) Retrospective assessment of initial stroke severity with the NIH Stroke Scale. Stroke 31(4):858–862CrossRefPubMed

go back to reference Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, 3rd (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24 (1):35–41CrossRefPubMed Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, 3rd (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24 (1):35–41CrossRefPubMed

go back to reference Saver JL (2016) Cryptogenic stroke. N Engl J Med 374(21):2065–2074. https://doi.org/10.1056/NEJMcp1503946 doiCrossRefPubMed Saver JL (2016) Cryptogenic stroke. N Engl J Med 374(21):2065–2074. https://​doi.​org/​10.​1056/​NEJMcp1503946 doiCrossRefPubMed

go back to reference Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, Katus HA, Newby LK, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela P, Underwood R, Bax JJ, Beller GA, Bonow R, Van der Wall EE, Bassand JP, Wijns W, Ferguson TB, Steg PG, Uretsky BF, Williams DO, Armstrong PW, Antman EM, Fox KA, Hamm CW, Ohman EM, Simoons ML, Poole-Wilson PA, Gurfinkel EP, Lopez-Sendon JL, Pais P, Mendis S, Zhu JR, Wallentin LC, Fernandez-Aviles F, Fox KM, Parkhomenko AN, Priori SG, Tendera M, Voipio-Pulkki LM, Vahanian A, Camm AJ, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Morais J, Brener S, Harrington R, Morrow D, Lim M, Martinez-Rios MA, Steinhubl S, Levine GN, Gibler WB, Goff D, Tubaro M, Dudek D, Al-Attar N (2007) Universal definition of myocardial infarction. Circulation 116(22):2634–2653. https://doi.org/10.1161/circulationaha.107.187397 CrossRefPubMed Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, Katus HA, Newby LK, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela P, Underwood R, Bax JJ, Beller GA, Bonow R, Van der Wall EE, Bassand JP, Wijns W, Ferguson TB, Steg PG, Uretsky BF, Williams DO, Armstrong PW, Antman EM, Fox KA, Hamm CW, Ohman EM, Simoons ML, Poole-Wilson PA, Gurfinkel EP, Lopez-Sendon JL, Pais P, Mendis S, Zhu JR, Wallentin LC, Fernandez-Aviles F, Fox KM, Parkhomenko AN, Priori SG, Tendera M, Voipio-Pulkki LM, Vahanian A, Camm AJ, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Morais J, Brener S, Harrington R, Morrow D, Lim M, Martinez-Rios MA, Steinhubl S, Levine GN, Gibler WB, Goff D, Tubaro M, Dudek D, Al-Attar N (2007) Universal definition of myocardial infarction. Circulation 116(22):2634–2653. https://​doi.​org/​10.​1161/​circulationaha.​107.​187397 CrossRefPubMed

go back to reference Pocock SJ, Clayton TC, Altman DG (2002) Survival plots of time-to-event outcomes in clinical trials: good practice and pitfalls. Lancet 359(9318):1686–1689. https://doi.org/10.1016/s0140-6736(02)08594-x CrossRefPubMed Pocock SJ, Clayton TC, Altman DG (2002) Survival plots of time-to-event outcomes in clinical trials: good practice and pitfalls. Lancet 359(9318):1686–1689. https://​doi.​org/​10.​1016/​s0140-6736(02)08594-x CrossRefPubMed

go back to reference Pahus SH, Hansen AT, Hvas AM (2016) Thrombophilia testing in young patients with ischemic stroke. Thromb Res 137:108–112. https://doi.org/10.1016/j.thromres.2015.11.006 CrossRefPubMed Pahus SH, Hansen AT, Hvas AM (2016) Thrombophilia testing in young patients with ischemic stroke. Thromb Res 137:108–112. https://​doi.​org/​10.​1016/​j.​thromres.​2015.​11.​006 CrossRefPubMed

go back to reference Fugate JE, Lyons JL, Thakur KT, Smith BR, Hedley-Whyte ET, Mateen FJ (2014) Infectious causes of stroke. Lancet Infect Dis 14(9):869–880. https://doi.org/10.1016/s1473-3099(14)70755-8 CrossRefPubMed Fugate JE, Lyons JL, Thakur KT, Smith BR, Hedley-Whyte ET, Mateen FJ (2014) Infectious causes of stroke. Lancet Infect Dis 14(9):869–880. https://​doi.​org/​10.​1016/​s1473-3099(14)70755-8 CrossRefPubMed

go back to reference Ferro JM, Massaro AR, Mas JL (2010) Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol 9(11):1085–1096. https://doi.org/10.1016/s1474-4422(10)70251-9 CrossRefPubMed Ferro JM, Massaro AR, Mas JL (2010) Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol 9(11):1085–1096. https://​doi.​org/​10.​1016/​s1474-4422(10)70251-9 CrossRefPubMed

go back to reference Wittwer B, Pelletier S, Ducrocq X, Maillard L, Mione G, Richard S (2015) Cerebrovascular events in Lyme Neuroborreliosis. J Stroke Cerebrovasc Dis 24(7):1671–1678. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.056 CrossRefPubMed Wittwer B, Pelletier S, Ducrocq X, Maillard L, Mione G, Richard S (2015) Cerebrovascular events in Lyme Neuroborreliosis. J Stroke Cerebrovasc Dis 24(7):1671–1678. https://​doi.​org/​10.​1016/​j.​jstrokecerebrova​sdis.​2015.​03.​056 CrossRefPubMed