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1. Outcomes after reperfusion therapies in patients with ACA stroke: A multicenter cohort study from the EVATRISP collaboration

Author

Filioglo, A, Simaan, N, Honig, A, Heldner, M R, von Rennenberg, R, Pezzini, A, Padjen, V, Rentzos, A, Altersberger, V L, Baumgartner, P, Zini, A, Grisendi, I, Aladdin, S, Gomori, J M, Pilgram-Pastor, S M, Scheitz, J F, Magoni, M, Berisavac, I, Nordanstig, A, Psychogios, M, Luft, A, Gentile, M, Assenza, F, Arnold, M, Nolte, C H, Gamba, M, Ercegovac, M, Jood, K, Engelter, S T, Wegener, S, Forlivesi, S, Zedde, M, Gensicke, H, Tatlisumak, T, Cohen, J E, and Leker, R R

Subjects
Endovascular Procedures, eye diseases, Brain Ischemia, Cohort Studies, Stroke, stomatognathic diseases, Treatment Outcome, Neurology, Fibrinolytic Agents, Reperfusion, Humans, Thrombolytic Therapy, Neurology (clinical), 610 Medicine & health, Thrombectomy
Abstract

BACKGROUND Patients with stroke secondary to occlusions of the anterior cerebral artery (ACA) often have poor outcomes. The optimal acute therapeutic intervention for these patients remains unknown. METHODS Patients with isolated ACA-stroke were identified from 10 centers participating in the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) prospective registry. Patients treated with endovascular thrombectomy (EVT) were compared to those treated with intravenous thrombolysis (IVT). Odds ratios with 95% confidence intervals (OR; 95%CI) were calculated using multivariate regression analysis. RESULTS Included were 92 patients with ACA-stroke. Of the 92 ACA patients, 55 (60%) were treated with IVT only and 37 (40%) with EVT (��bridging IVT). ACA patients treated with EVT had more often wake-up stroke (24% vs. 6%, p��=��0.044) and proximal ACA occlusions (43% vs. 24%, p��=��0.047) and tended to have higher stroke severity on admission [NIHSS: 10.0 vs 7.0, p��=��0.054). However, odds for favorable outcome, mortality or symptomatic intracranial hemorrhage did not differ significantly between both groups. Exploration of the effect of clot location inside the ACA showed that in patients with A1 or A2/A3 ACA occlusions the chances of favorable outcome were not influenced by treatment allocation to IVT or EVT. DISCUSSION Treatment with either IVT or EVT could be safe with similar effect in patients with ACA-strokes and these effects may be independent of clot location within the occluded ACA.

Published
2021

2. Does prior administration of rtPA influence acute ischemic stroke clot composition? Findings from the analysis of clots retrieved with mechanical thrombectomy from the RESTORE registry

Author

Rossi, R. Molina, S. Mereuta, O.M. Douglas, A. Fitzgerald, S. Tierney, C. Pandit, A. Brennan, P. Power, S. O’Hare, A. Gilvarry, M. McCarthy, R. Magoufis, G. Tsivgoulis, G. Nagy, A. Vadász, Á. Jood, K. Redfors, P. Nordanstig, A. Ceder, E. Dunker, D. Carlqvist, J. Psychogios, K. Szikora, I. Tatlisumak, T. Rentzos, A. Thornton, J. Doyle, K.M.

Abstract

Background and purpose: There is still much debate whether bridging-therapy [intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT)] might be beneficial compared to MT alone. We investigated the effect of IVT on size and histological composition of the clots retrieved from patients undergoing bridging-therapy or MT alone. Methods: We collected mechanically extracted thrombi from 1000 acute ischemic stroke (AIS) patients included in RESTORE registry. Patients were grouped according to the administration (or not) of IVT before thrombectomy. Gross photos of each clot were taken and Extracted Clot Area (ECA) was measured using ImageJ software. Martius Scarlett Blue stain was used to characterize the main histological clot components [red blood cells (RBCs), fibrin (FIB), platelets/other (PTL)] and Orbit Image Analysis was used for quantification. Additionally, we calculated the area of each main component by multiplying the component percent by ECA. Chi-squared and Kruskal–Wallis tests were used for statistical analysis. Results: 451 patients (45%) were treated with bridging-therapy while 549 (55%) underwent MT alone. When considering only percent histological composition, we did not find any difference in RBC% (P = 0.895), FIB% (P = 0.458) and PTL% (P = 0.905). However, bridging-therapy clots were significantly smaller than MT-alone clots [32.7 (14.8–64.9) versus 36.8 (20.1–79.8) mm2, N = 1000, H1 = 7.679, P = 0.006*]. A further analysis expressing components per clot area showed that clots retrieved from bridging-therapy cases contained less RBCs [13.25 (4.29–32.06) versus 14.97 (4.93–39.80) mm2, H1 = 3.637, P = 0.056] and significantly less fibrin [9.10 (4.62–17.98) versus 10.54 (5.57–22.48) mm2, H1 = 7.920, P = 0.005*] and platelets/other [5.04 (2.26–11.32) versus 6.54 (2.94–13.79) mm2, H1 = 9.380, P = 0.002*] than MT-alone clots. Conclusions: Our results suggest that previous IVT administration significantly reduces thrombus size, proportionally releasing all the main histological components. © 2021, The Author(s).

Published
2021

3. Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates

Author

Fitzgerald, S. Rossi, R. Mereuta, O.M. Molina, S. Okolo, A. Douglas, A. Jabrah, D. Pandit, A. McCarthy, R. Gilvarry, M. Ceder, E. Dehlfors, N. Dunker, D. Nordanstig, A. Redfors, P. Jood, K. Magoufis, G. Psychogios, K. Tsivgoulis, G. Alderson, J. O'Hare, A. Power, S. Brennan, P. Nagy, A. Vadász, Á. Brinjikji, W. Kallmes, D. Szikora, I. Tatlisumak, T. Rentzos, A. Thornton, J. Doyle, K.M.

Abstract

Objectives: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. Materials and Methods: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. Results: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. Conclusion: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots. © 2020 The Authors

Published
2021

4. EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: Basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry

Author

Nordanstig, A. Curtze, S. Gensicke, H. Zinkstok, S.M. Erdur, H. Karlsson, C. Karlsson, J.-E. Martinez-Majander, N. Sibolt, G. Lyrer, P. Traenka, C. Baharoglu, M.I. Scheitz, J.F. Bricout, N. Hénon, H. Leys, D. Eskandari, A. Michel, P. Hametner, C. Ringleb, P.A. Arnold, M. Fischer, U. Sarikaya, H. Seiffge, D.J. Pezzini, A. Zini, A. Padjen, V. Jovanovic, D.R. Luft, A. Wegener, S. Kellert, L. Feil, K. Kägi, G. Rentzos, A. Lappalainen, K. Leker, R.R. Cohen, J.E. Gomori, J. Brehm, A. Liman, J. Psychogios, M. Kastrup, A. Papanagiotou, P. Gralla, J. Magoni, M. Majoie, C.B.L.M. Bohner, G. Vukasinovic, I. Cvetic, V. Weber, J. Kulcsar, Z. Bendszus, M. Möhlenbruch, M. Ntaios, G. Kapsalaki, E. Jood, K. Nolte, C.H. Nederkoorn, P.J.J. Engelter, S. Strbian, D. Tatlisumak, T.

Abstract

Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements. © 2021 BMJ Publishing Group. All rights reserved.

Published
2021

5. Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

Author

van Kammen, MS, de Sousa, DA, Poli, S, Cordonnier, C, Heldner, MR, van de Munckhof, A, Krzywicka, K, van Haaps, T, Ciccone, A, Middeldorp, S, Levi, MM, Hovinga, JAK, Silvis, S, Hiltunen, S, Mansour, M, Arauz, A, Barboza, MA, Field, TS, Tsivgoulis, G, Nagel, S, Lindgren, E, Tatlisumak, T, Jood, K, Putaala, J, Ferro, JM, Arnold, M, Coutinho, JM, Guisado-Alonso D., and Cerebral Venous Sinus Thrombosis T

Abstract

Importance Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, Setting, and Participants This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main Outcomes and Measures Clinical characteristics and mortality rate. Results Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and Relevance In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination. Question What are the clinical characteristics and outcomes of patients with cerebral venous sinus thrombosis with thrombocytopenia syndrome after SARS-CoV-2 vaccination? Findings In this cohort study of 116 patients with cerebral venous sinus thrombosis after SARS-CoV-2 vaccination, 78 (67.2%) had thrombosis with thrombocytopenia syndrome. Patients with thrombosis with thrombocytopenia syndrome were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%), and 47% died during hospitalization. Meaning Patients with cerebral venous sinus thrombosis after SARS-CoV-2 vaccination who met criteria for thrombosis with thrombocytopenia syndrome had a distinct clinical profile and high mortality rate. This cohort study describes the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis after SARS-CoV-2 vaccination with and without thrombosis with thrombocytopenia syndrome.

Published
2021

6. Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

Author

Traylor, M, Zhang, Cr, Adib Samii, P, Devan, Wj, Parsons, Oe, Lanfranconi, S, Gregory, S, Cloonan, L, Falcone, Gj, Radmanesh, F, Fitzpatrick, K, Kanakis, A, Barrick, Tr, Moynihan, B, Lewis, Cm, Boncoraglio, Gb, Lemmens, R, Thijs, V, Sudlow, C, Wardlaw, J, Rothwell, Pm, Meschia, Jf, Worrall, Bb, Levi, C, Bevan, S, Furie, Kl, Dichgans, M, Rosand, J, Markus, Hs, Rost, N, Smoller, S, Sorkin, J, Wang, X, Selim, M, Pikula, A, Wolf, P, Debette, S, Seshadri, S, de Bakker, P, Chasman, D, Rexrode, K, Chen, I, Rotter, J, Luke, M, Sale, M, Lee, Th, Chang, Kc, Elkind, M, Goldstein, L, James, Ml, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez Conde, J, Cotlarcius, I, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, Kj, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Ahmadi, K, Opherk, C, Duering, M, Malik, R, Gonik, M, Staals, J, Melander, O, Burri, P, Sadr Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller Myhsok, B, Meschia, J, Brott, T, Pare, G, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Yvonne Chan, Yf, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Ke, Le, Lee, Wl, Tan, Ek, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jern, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Sheu, W, Chiou, Hy, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Martín, Jj, Klijn, K, Van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, Alessandro, Padovani, Alessandro, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Rannikmae, K, Silliman, S, Mcdonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, Mcardle, P, Chang, Yc, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Attia, J, Farrall, M, Giese, Ak, Fornage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, Jm, and Sheth, K.

Subjects
Cerebral Small Vessel Diseases, Genetic Predisposition to Disease, Genetic Testing, Humans, Polymorphism, Single Nucleotide, Risk Factors, Stroke, White Matter, Genome-Wide Association Study, Neurology (clinical), Single Nucleotide, C420 Human Genetics, Article, C431 Medical Genetics, C400 Genetics, Polymorphism, C440 Molecular Genetics
Abstract

Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.

Published
2016

7. Publisher Correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes (Nature Genetics, (2018), 50, 4, (524-537), 10.1038/s41588-018-0058-3)

Author

Malik, R., Chauhan, G., Traylor, M., Sargurupremraj, M., Okada, Y., Mishra, A., Rutten-Jacobs, L., Giese, A. -K, Laan, S. W., Gretarsdottir, S., Anderson, C. D., Chong, M., Adams, H. H. H., Ago, T., Almgren, P., Amouyel, P., Ay, H., Bartz, T. M., Benavente, O. R., Bevan, S., Boncoraglio, G. B., Brown, R. D., Butterworth, A. S., Carrera, C., Carty, C. L., Chasman, D. I., Chen, W. -M, Cole, J. W., Correa, A., Cotlarciuc, I., Cruchaga, C., Danesh, J., Bakker, P. I. W., Destefano, A. L., Den Hoed, M., Duan, Q., Engelter, S. T., Falcone, G. J., Gottesman, R. F., Grewal, R. P., Gudnason, V., Gustafsson, S., Haessler, J., Harris, T. B., Hassan, A., Havulinna, A. S., Heckbert, S. R., Holliday, E. G., Howard, G., Hsu, F. -C, Hyacinth, H. I., Ikram, M. A., Ingelsson, E., Irvin, M. R., Jian, X., Jiménez-Conde, J., Johnson, J. A., Jukema, J. W., Kanai, M., Keene, K. L., Kissela, B. M., Kleindorfer, D. O., Kooperberg, C., Kubo, M., Lange, L. A., Langefeld, C. D., Langenberg, C., Launer, L. J., Lee, J. -M, Lemmens, R., Leys, D., Lewis, C. M., Lin, W. -Y, Lindgren, A. G., Lorentzen, E., Magnusson, P. K., Maguire, J., Manichaikul, A., Mcardle, P. F., Meschia, J. F., Mitchell, B. D., Mosley, T. H., Nalls, M. A., Ninomiya, T., O’donnell, M. J., Psaty, B. M., Pulit, S. L., Rannikmäe, K., Reiner, A. P., Rexrode, K. M., Rice, K., Rich, S. S., Ridker, P. M., Rost, N. S., Rothwell, P. M., Rotter, J. I., Rundek, T., Sacco, R. L., Sakaue, S., Sale, M. M., Salomaa, V., Sapkota, B. R., Schmidt, R., Schmidt, C. O., Schminke, U., Sharma, P., Slowik, A., Sudlow, C. L. M., Tanislav, C., Tatlisumak, T., Taylor, K. D., Thijs, V. N. S., Thorleifsson, G., Thorsteinsdottir, U., Tiedt, S., Trompet, S., Tzourio, C., Duijn, C. M., Walters, M., Wareham, N. J., Wassertheil-Smoller, S., Wilson, J. G., Wiggins, K. L., Yang, Q., Yusuf, S., Bis, J. C., Pastinen, T., Ruusalepp, A., Schadt, E. E., Koplev, S., Björkegren, J. L. M., Codoni, V., Civelek, M., Smith, N. L., Trégouët, D. A., Christophersen, I. E., Roselli, C., Lubitz, S. A., Ellinor, P. T., Tai, E. S., Kooner, J. S., Kato, N., He, J., Harst, P., Elliott, P., Chambers, J. C., Takeuchi, F., Johnson, A. D., Amin, N., Aparicio, H. S., Arnett, D. K., Attia, J., Beiser, A. S., Berr, C., Buring, J. E., Bustamante, M., Caso, V., Cheng, Y. -C, Choi, S. H., Chowhan, A., Cullell, N., Dartigues, J. -F, Delavaran, H., Delgado, P., Dörr, M., Engström, G., Ford, I., Gurpreet, W. S., Hamsten, A., Heitsch, L., Hozawa, A., Ibanez, L., Ilinca, A., Ingelsson, M., Iwasaki, M., Jackson, R. D., Jood, K., Jousilahti, P., Kaffashian, S., Kalra, L., Kamouchi, M., Kitazono, T., Kjartansson, O., Kloss, M., Koudstaal, P. J., Krupinski, J., Labovitz, D. L., Laurie, C. C., Levi, C. R., Li, L., Lind, L., Lindgren, C. M., Lioutas, V., Liu, Y. M., Lopez, O. L., Makoto, H., Martinez-Majander, N., Matsuda, K., Minegishi, N., Montaner, J., Morris, A. P., Muiño, E., Müller-Nurasyid, M., Norrving, B., Ogishima, S., Parati, E. A., Peddareddygari, L. R., Pedersen, N. L., Pera, J., Perola, M., Pezzini, A., Pileggi, S., Rabionet, R., Riba-Llena, I., Ribasés, M., Romero, J. R., Roquer, J., Rudd, A. G., Sarin, A. -P, Sarju, R., Sarnowski, C., Sasaki, M., Satizabal, C. L., Satoh, M., Sattar, N., Sawada, N., Sibolt, G., Sigurdsson, Á, Smith, A., Sobue, K., Soriano-Tárraga, C., Stanne, T., Stine, O. C., Stott, D. J., Strauch, K., Takai, T., Tanaka, H., Tanno, K., Teumer, A., Tomppo, L., Nuria P Torres-Aguila, Touze, E., Tsugane, S., Uitterlinden, A. G., Valdimarsson, E. M., Lee, S. J., Völzke, H., Wakai, K., Weir, D., Williams, S. R., Wolfe, C. D. A., Wong, Q., Xu, H., Yamaji, T., Sanghera, D. K., Melander, O., Jern, C., Strbian, D., Fernandez-Cadenas, I., Longstreth, W. T., Rolfs, A., Hata, J., Woo, D., Rosand, J., Pare, G., Hopewell, J. C., Saleheen, D., Stefansson, K., Worrall, B. B., Kittner, S. J., Seshadri, S., Fornage, M., Markus, H. S., Howson, J. M. M., Kamatani, Y., Debette, S., and Dichgans, M.

9. Serum magnesium and calcium levels in relation to ischemic stroke Mendelian randomization study

Author

Susanna C. Larsson, Matthew Traylor, Stephen Burgess, Giorgio B. Boncoraglio, Christina Jern, Karl Michaëlsson, Hugh S. Markus, Rainer Malik, Ganesh Chauhan, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab HH Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, raci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Daniel I Chasman, Wei-Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul IW de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Jeffrey Haessler, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Susan R Heckbert, Elizabeth G Holliday, George Howard, Fang-Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei-Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O'Donnell, Bruce M Psaty, Sara L Pulit, Kristiina Rannikmäe, Alexander P Reiner, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Paul M Ridker, Natalia S Rost, Peter M Rothwell, Jerome I Rotter, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie LM Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent NS Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil-Smoller, James G Wilson, Kerri L Wiggins, Qiong Yang, Salim Yusuf, Najaf Amin, Hugo S Aparicio, Donna K Arnett, John Attia, Alexa S Beiser, Claudine Berr, Julie E Buring, Mariana Bustamante, Valeria Caso, Yu-Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean-François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J Koudstaal, Jerzy Krupinski, Daniel L Labovitz, Cathy C Laurie, Christopher R Levi, Linxin Li, Lars Lind, Cecilia M Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L Lopez, Hirata Makoto, Nicolas Martinez-Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P Morris, Elena Muiño, Martina Müller-Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A Parati, Leema Reddy Peddareddygari, Nancy L Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba-Llena, Marta Ribasés, Jose R Romero, Jaume Roquer, Anthony G Rudd, Antti-Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano-Tárraga, Tara Stanne, O Colin Stine, David J Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P Torres-Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G Uitterlinden, Einar M Valdimarsson, Sven J van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R Williams, Charles DA Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K Sanghera, Olle Melander, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna MM Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, Berr, Claudine, Unit of Cardiovascular and Nutritional Epidemiology [Stockholm, Sweden], Karolinska Institutet [Stockholm]-Institute of Environmental Medicine [Stockholm, Sweden], Stroke Research Group [London, UK] (Department of Brain Repair and Rehabilitation), University of London - UCL [London, UK], MRC Biostatistics Unit [Cambridge, UK], University of Cambridge [UK] (CAM), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, Department of Surgical Sciences [Uppsala, Sweden], This work was supported by the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council. Hugh Markus is supported by an NIHR Senior Investigator award. His and Matthew Traylor’s work is supported by infrastructural support from the Cambridge University Hospitals Trust NIHR Biomedical Research Centre., MEGASTROKE project of the International Stroke Genetics Consortium : Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HH, Ago T, Almgren P, Amouyel P, Ay H, Bartz RM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD Jr, Butterworth AS, Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A, Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PI, DeStefano AL, Hoed MD, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP, Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS, Heckbert SR, Holliday EG, Howard G, Hsu FC, Hyacinth HI, Ikram MA, Ingelsson E, Irvin MR, Jian X, Jiménez-Conde J, Johnson JA, Jukema JW, Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M, Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee JM, Lemmens R, Leys D, Lewis CM, Lin WY, Lindgren AG, Lorentzen E, Magnusson PK, Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley TH, Nalls MA, Ninomiya T, O'Donnell MJ, Psaty BM, Pulit SL, Rannikmäe K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V, Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A, Sudlow CL, Tanislav C, Tatlisumak T, Taylor KD, Thijs VN, Thorleifsson G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM, Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Yang Q, Yusuf S, Amin N, Aparicio HS, Arnett DK, Attia J, Beiser AS, Berr C, Buring JE, Bustamante M, Caso V, Cheng YC, Choi SH, Chowhan A, Cullell N, Dartigues JF, Delavaran H, Delgado P, Dörr M, Engström G, Ford I, Gurpreet WS, Hamsten A, Heitsch L, Hozawa A, Ibanez L, Ilinca A, Ingelsson M, Iwasaki M, Jackson RD, Jood K, Jousilahti P, Kaffashian S, Kalra L, Kamouchi M, Kitazono T, Kjartansson O, Kloss M, Koudstaal PJ, Krupinski J, Labovitz DL, Laurie CC, Levi CR, Li L, Lind L, Lindgren CM, Lioutas V, Liu YM, Lopez OL, Makoto H, Martinez-Majander N, Matsuda K, Minegishi N, Montaner J, Morris AP, Muiño E, Müller-Nurasyid M, Norrving B, Ogishima S, Parati EA, Peddareddygari LR, Pedersen NL, Pera J, Perola M, Pezzini A, Pileggi S, Rabionet R, Riba-Llena I, Ribasés M, Romero JR, Roquer J, Rudd AG, Sarin AP, Sarju R, Sarnowski C, Sasaki M, Satizabal CL, Satoh M, Sattar N, Sawada N, Sibolt G, Sigurdsson Á, Smith A, Sobue K, Soriano-Tárraga C, Stanne T, Stine OC, Stott DJ, Strauch K, Takai T, Tanaka H, Tanno K, Teumer A, Tomppo L, Torres-Aguila NP, Touze E, Tsugane S, Uitterlinden AG, Valdimarsson EM, van der Lee SJ, Völzke H, Wakai K, Weir D, Williams SR, Wolfe CD, Wong Q, Xu H, Yamaji T, Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth WT Jr, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC, Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M, Markus HS, Howson JM, Kamatani Y, Debette S, Dichgans M., Larsson, Susanna C [0000-0003-0118-0341], Apollo - University of Cambridge Repository, and Neurology

Subjects
medicine.medical_specialty, Neurology, Heredity, Neurologi, [SDV]Life Sciences [q-bio], chemistry.chemical_element, Calcium, Polymorphism, Single Nucleotide, Gastroenterology, Article, Brain Ischemia, Brain ischemia, 03 medical and health sciences, 0302 clinical medicine, Human genetics, Internal medicine, Mendelian randomization, Medicine, Humans, Magnesium, 030212 general & internal medicine, Stroke, Herència (Biologia), Genètica humana, business.industry, Neurosciences, Mendelian Randomization Analysis, Odds ratio, medicine.disease, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Intracranial Embolism, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery, Neurovetenskaper
Abstract

Comment inThe yin and yang of magnesium and calcium: New genetic insights for stroke? [Neurology. 2019]; International audience; Objective To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach. Methods Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases). Results In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10 −4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10 −4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype. Conclusions This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.

Published
2019

10. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Author

Debette, Stéphanie, Kamatani, Yoichiro, Wolf, Christiane, Agabiti Rosei, Enrico, Lanfranconi, Silvia, Ferrarese, Carlo, Susani, Emanuela, Bicocca, Milano, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Paciaroni, Maurizio, Ballabio, Elena, Dittrich, Ralf, Parati, Eugenio A, Ciusani, Emilio, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Touzé, Emmanuel, Altintas, Ayse, Martin, Juan José, Kittner, Steven, MItchell, Braxton, Stine, Colin, O'Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J, de Lau, Lonneke M L, Hofman, Albert, Southerland, Andrew M, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Samson, Yves, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Abboud, Shérine, Béjot, Yannick, Caso, Valeria, Bersano, Anna, Gschwendtner, Andreas, Metso, Tiina M, Sessa, Maria, Cole, John, Lamy, Chantal, Medeiros, Elisabeth, Beretta, Simone, Bonati, Leo H, Grau, Armin J, Michel, Patrik, Majersik, Jennifer J, Sharma, Pankaj, Kloss, Manja, Kalashnikova, Ludmila, Nazarova, Maria, Dobrynina, Larisa, Bartels, Eva, Guillon, Benoit, van den Herik, Evita G, Fernandez-Cadenas, Israel, Jood, Katarina, Nalls, Michael A, De Leeuw, Frank-Erik, Chauhan, Ganesh, Jern, Christina, Cheng, Yu-Ching, Werner, Inge, Metso, Antti J, Lichy, Christoph, Lyrer, Philippe A, Brandt, Tobias, Boncoraglio, Giorgio B, Wichmann, Heinz-Erich, Gieger, Christian, Engelter, Stefan T, Johnson, Andrew D, Böttcher, Thomas, Castellano, Maurizio, Arveiler, Dominique, Ikram, M Arfan, Breteler, Monique M B, Padovani, Alessandro, Meschia, James F, Kuhlenbäumer, Gregor, Rolfs, Arndt, Pezzini, Alessandro, Worrall, Bradford B, Consortium, International Stroke Genetics, Ringelstein, Erich-Bernd, Zelenika, Diana, Tatlisumak, Turgut, Lathrop, Mark, Leys, Didier, Amouyel, Philippe, Dallongeville, Jean, Group, CADISP, Thijs, Vincent, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Markus, Hugh S, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vullier, Fabrice, Tzourio, Christophe, Dos Santos, Michael, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Dichgans, Martin, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Lorenza Muiesan, Maria, Salvetti, Massimo, Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Helsinki University Central Hospital [Finland] (HUCH), Heidelberg University Hospital [Heidelberg], University Hospital Basel [Basel], Università degli Studi di Brescia = University of Brescia (UniBs), University Hospitals Leuven [Leuven], Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University of Cambridge [UK] (CAM), Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Virginia, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neurochirurgie Expérimentale [Brussels] (ULB 257), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Perugia = University of Perugia (UNIPG), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Ospedale San Raffaele, University of Maryland School of Medicine, University of Maryland System, Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Klinikum Ludwigshafen [Germany], Service of Neurology [CHUV, Lausanne, Switzerland], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Utah School of Medicine [Salt Lake City], Institute of Cardiovascular Research (ICR2UL), Royal Holloway [University of London] (RHUL), Ashford and St Peter's hospitals NHS foundation trust, Russian Academy of Sciences [Moscow] (RAS), Centre for Cognition and Decision Making [HSE, Moscow], Institut of Cognitive Neuroscience [HSE, Moscow] (ICN), Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE)-Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE), Zentrum für neurologische Gefäßdiagnostik - Center for Neurological Vascular Diagnostics [Munich, Germany], Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Department of Neurology [Erasmus MC, Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital Universitario Mutua de Terrassa, Vall d'Hebron University Hospital [Barcelona], Insitute of Neuroscience and Physiology, University of Gothenburg (GU), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Schmieder Klinik [Heidelberg, Germany], Helmholtz Zentrum München = German Research Center for Environmental Health, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University Hospital Rostock, Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Brescia, Mayo Clinic [Jacksonville], Institute of Experimental Medicine - Institut für Experimentelle Medizin [Kiel, Germany] (IEM), Christian-Albrechts-Universität zu Kiel (CAU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, McGill University and Genome Quebec Innovation Centre, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Pharmacologie de la mort neuronale et de la plasticité cérébrale, IFR114-Université de Lille, Droit et Santé, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, The CADISP study has been supported by INSERM, Lille 2 University, Institut Pasteur de Lille and Lille University Hospital and received funding from the European Regional Development Fund (FEDER funds) and Région Nord-Pas-de-Calais in the framework of Contrat de Projets Etat-Region 2007–2013 Région Nord-Pas-de-Calais (grant 09120030), Centre National de Génotypage, the Emil Aaltonen Foundation, the Paavo Ilmari Ahvenainen Foundation, the Helsinki University Central Hospital Research Fund, the Helsinki University Medical Foundation, the Päivikki and Sakari Sohlberg Foundation, the Aarne Koskelo Foundation, the Maire Taponen Foundation, the Aarne and Aili Turunen Foundation, the Lilly Foundation, the Alfred Kordelin Foundation, the Finnish Medical Foundation, the Orion Farmos Research Foundation, the Maud Kuistila Foundation, the Finnish Brain Foundation, the Biomedicum Helsinki Foundation, Projet Hospitalier de Recherche Clinique Régional, Fondation de France, Génopôle de Lille, Adrinord, the Basel Stroke Funds, the Käthe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences and the Swiss Heart Foundation.L.H.B., S.T.E. and P.A.L. were supported, in part, by a grant from the Swiss National Science Foundation (33CM30-124119). S.D. is supported by a Chair of Excellence from the French National Research Agency (ANR). S.D. and M.D. are supported by a grant from the Leducq Foundation. M.D. is supported by the Vascular Dementia Research Foundation. I.F.-C. is supported by the Miguel Servet programme (CP12/03298) from the Spanish Ministry of Health (Instituto de Salud Carlos III). G.K. is a member of the Deutsche Forschungsgemeinschaft Cluster of Excellence 'Inflammation at Interfaces'. P.S. is supported by a Department of Health (UK) senior fellowship. A.M.S. is supported by the American Heart Association/American Stroke Association National Clinical Research Program (AHA 3CRP14140001). V.T. is supported by Fonds Wetenschappelijk Onderzoek Flanders., CADISP Group, RIKEN Center for Integrative Medical Science, Università degli Studi di Brescia [Brescia], University of Virginia [Charlottesville], Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière]], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Neurologie Expérimentale [ULB, Brussels, Belgium] (ULB 257), Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Università degli Studi di Perugia (UNIPG), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), National Research University Higher School of Economics [Moscow] (HSE)-National Research University Higher School of Economics [Moscow] (HSE), Radboud university [Nijmegen], Helmholtz-Zentrum München (HZM), Westfälische Wilhelms-Universität Münster (WWU), The authors thank the staff and participants of all CADISP centers for their important contributions., Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Erasmus MC other, Epidemiology, Debette, S, Kamatani, Y, Metso, T, Kloss, M, Chauhan, G, Engelter, S, Pezzini, A, Thijs, V, Markus, H, Dichgans, M, Wolf, C, Dittrich, R, Touzé, E, Southerland, A, Samson, Y, Abboud, S, Béjot, Y, Caso, V, Bersano, A, Gschwendtner, A, Sessa, M, Cole, J, Lamy, C, Medeiros, E, Beretta, S, Bonati, L, Grau, A, Michel, P, Majersik, J, Sharma, P, Kalashnikova, L, Nazarova, M, Dobrynina, L, Bartels, E, Guillon, B, Van Den Herik, E, Fernandez Cadenas, I, Jood, K, Nalls, M, De Leeuw, F, Jern, C, Cheng, Y, Werner, I, Metso, A, Lichy, C, Lyrer, P, Brandt, T, Boncoraglio, G, Wichmann, H, Gieger, C, Johnson, A, Böttcher, T, Castellano, M, Arveiler, D, Ikram, M, Breteler, M, Padovani, A, Meschia, J, Kuhlenbäumer, G, Rolfs, A, Worrall, B, Ringelstein, E, Zelenika, D, Tatlisumak, T, Lathrop, M, Leys, D, Amouyel, P, Dallongeville, J, Lemmens R, P, and Ferrarese, C

Subjects
Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Myocardial Infarction, Genome-wide association study, Carotid Artery, Internal, Dissection, Gastroenterology, epidemiology [Carotid Artery, Internal, Dissection], Brain Ischemia, 0302 clinical medicine, Migraine Disorder, Odds Ratio, Finland, Vertebral Artery Dissection, 0303 health sciences, education.field_of_study, epidemiology [Hypercholesterolemia], MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Phactr-1 protein, human, MESH: Brain Ischemia, MESH: Follow-Up Studies, 3. Good health, MESH: Myocardial Infarction, Human, medicine.medical_specialty, Migraine Disorders, Hypercholesterolemia, MESH: Vertebral Artery Dissection, Lower risk, genetics [Brain Ischemia], Article, Follow-Up Studie, MESH: Carotid Artery, Internal, Dissection, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, genetics [Carotid Artery, Internal, Dissection], Genetics, Genetic predisposition, epidemiology [Brain Ischemia], Humans, epidemiology [Vertebral Artery Dissection], Polymorphism, education, Alleles, MESH: Humans, genetics [Vertebral Artery Dissection], MESH: Adult, Odds ratio, Microfilament Protein, medicine.disease, Adult, Female, Follow-Up Studies, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Hypertension, Microfilament Proteins, Middle Aged, Obesity, Risk Factors, Polymorphism, Single Nucleotide, MESH: Genome-Wide Association Study, Carotid Artery, MESH: Female, 030217 neurology & neurosurgery, epidemiology [Finland], Cervical Artery, Vertebral artery dissection, epidemiology [Hypertension], MESH: Hypertension, MESH: Risk Factors, MESH: Obesity, Stroke, Allele, Dissection, MESH: Finland, MESH: Genetic Predisposition to Disease, MESH: Hypercholesterolemia, Single Nucleotide, MESH: Migraine Disorders, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], epidemiology [Myocardial Infarction], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Population, MESH: Genetic Pleiotropy, physiology [Microfilament Proteins], Biology, MESH: Microfilament Proteins, Internal medicine, ddc:570, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, 030304 developmental biology, epidemiology [Obesity], Risk Factor, MESH: Alleles, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Internal, MESH: Odds Ratio, MESH: Male, epidemiology [Migraine Disorders], genetics [Microfilament Proteins]
Abstract

Item does not contain fulltext Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 x 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 x 10(-3); combined P = 1.00 x 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Published
2015

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