Risk Factors for Cerebrovascular Events in Systemic Lupus Erythematosus: Results from an International, Inception Cohort Study

John G Hanly¹, Qiuju Li², Li Su³, Murray Urowitz⁴, Juanita Romero-Diaz⁵, Caroline Gordon⁶, Sang-Cheol Bae⁷, Sasha Bernatsky⁸, Ann E. Clarke⁹, Daniel J Wallace¹⁰, Joan T. Merrill¹¹, David A. Isenberg¹², Anisur Rahman¹³, Ellen M. Ginzler¹⁴, Paul R. Fortin¹⁵, D Gladman¹⁶, Jorge Sanchez-Guerrero¹⁷, Michelle Petri¹⁸, Ian N. Bruce¹⁹, Mary Anne Dooley²⁰, Rosalind Ramsey-Goldman²¹, Cynthia Aranow²², Graciela S. Alarcon²³, Kristján Steinsson²⁴, Gunnar K. Sturfelt²⁵, Ola Nived²⁶, Susan Manzi²⁷, M Khamashta²⁸, Ronald F. van Vollenhoven²⁹, Asad Zoma³⁰, Guillermo Ruiz-Irastorza³¹, S. Sam Lim³², Murat Inanc³³, Kenneth C. Kalunian³⁴, Diane L. Kamen³⁵, Christine A. Peschken³⁶, Søren Jacobsen³⁷, Anca Askanase³⁸, Chris Theriault³⁹, Vernon Farewell⁴⁰ and Manuel Ramos-Casals⁴¹, ¹Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada, ²MRC Biostatistics Unit, Cambridge, United Kingdom, ³Nova Scotia Rehab Site, Division of Rheumatology, Capital Health and Dalhousie University, Halifax, NS, Canada, ⁴Medicine, Toronto Western Hospital and University of Toronto, Toronto, ON, Canada, ⁵Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city, Mexico, ⁶NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, ⁷Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of, ⁸Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada, ⁹Division of Rheumatology, University of Calgary, Calgary, AB, Canada, ¹⁰Cedars-Sinai Medical Center, West Hollywood, CA, ¹¹Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹²Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom, ¹³Rayne Institute, Centre for Rheumatology Research, UCL Division of Medicine, London, United Kingdom, ¹⁴Rheumatology, SUNY Downstate Medical Center, Brooklyn, NY, ¹⁵Rheumatology, University of Laval, Quebec, QC, Canada, ¹⁶University of Toronto, Toronto, ON, Canada, ¹⁷Rheumatology, Toronto Western Hospital, Toronto, ON, Canada, ¹⁸Rheumatology Division, Johns Hopkins University School of Medicine, Baltimore, MD, ¹⁹NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom, ²⁰Dooley Rheumatology, Chapel Hill Doctors, Chapel Hill, NC, ²¹FSM, Northwestern University, Chicago, IL, ²²Molecular Medicine and Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, ²³Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ²⁴Rheumatology, Univ. Hospital, Reykjavik, Iceland, ²⁵Department of Rheumatology, Univ Hospital Lund, Lund, Sweden, ²⁶Department of Rheumatology, University Hospital, Lund, Sweden, ²⁷Lupus Center of Excellence, West Penn Allegheny Health System, Pittsburgh, PA, ²⁸Lupus Research Unit, Lupus Research Unit, The Rayne Institute, King's College London School of Medicine, St Thomas' Hospital, London, United Kingdom, ²⁹Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), The Karolinska Institute, Stockholm, Sweden, ³⁰Rheumatology, Hairmyres Hospital, East Kilbride, Great Britain, ³¹Universidad del Pais Vasco, Servicio de Medicina Interna, Hospital de Cruces, Bizkaia, Spain, ³²Medicine, Emory University School of Medicine, Atlanta, GA, ³³Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey, ³⁴Division of Rheumatology, Allergy & Immunology, UCSD School of Medicine Center for Innovative Therapy, La Jolla, CA, ³⁵Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, ³⁶RR 149G, Univ of Manitoba, Winnipeg, MB, Canada, ³⁷Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, ³⁸Rheumatology, Columbia University Medical Center, New York, NY, ³⁹Medicine, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada, ⁴⁰Medicine, Division of Rheumatology, Capital Health and Dalhousie University, Halifax, NS, Canada, ⁴¹Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Spain, Barcelona, Spain

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: neuropsychiatric disorders and systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 14, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment - Poster II: Damage Accrual and Quality of Life

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Neuropsychiatric (NP) disease in patients with SLE includes cerebrovascular events (CerVE). We determined the frequency, attribution and risk factors for CerVE in a large, multi-ethnic/racial, inception cohort of SLE patients with long-term followup.

Methods: A prospective study of new onset SLE patients was performed by an international network of 32 academic centers in 11 countries. Patients were evaluated at enrollment and annually for up to 17 years. Data were collected at each assessment on demographic and clinical manifestations, medications, SLE disease activity index-2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index (SDI). Nervous system events were recorded using the ACR case definitions for 19 NP syndromes. These included the following CerVE: (i) Stroke; (ii) Transient ischemia; (iii) Chronic multifocal ischemia; (iv) Subarachnoid and intracranial hemorrhage; (v) Sinus thrombosis. Pre-defined rules determined the attribution of NP events to SLE and non-SLE causes. Demographic variables, clinical variables, medications and NP related lupus autoantibodies were examined as potential predictors of the risk of SLE CerVE by univariate and multivariate Cox regression analyses.

Results: Of 1,826 SLE patients, 88.8% were female, 48.8% Caucasian, 16.8% African, 15.4% Hispanic, 15% Asian and 4% other. At enrollment the mean±SD age was 35.1±13.3 years, SLE duration was 5.6±4.2 months, SLEDAI-2K was 5.3±5.4 and SDI was 0.31±0.73. The mean follow-up was 6.5±4.1 years. Over the study 929 (50.9%) patients had 1,844 NP events of which 573 (31.1%) in 378/1826 (20.7%) patients were attributed to SLE. CerVE were the fourth most frequent NP event: 82/1,826 (4.5%) patients had 109 events of which 103/109 (94.5%) were attributed to SLE and 44 (40.4%) were identified at the enrollment visit. The incidence of first and recurrent CerVE was 5.8/1000 and 32.7/1000 person years respectively. The predominant events were stroke [60/109 (55.0%)] and transient ischemia [28/109 (25.7%)] followed by subarachnoid and intracranial hemorrhage [9/109 (8.3%)], chronic multifocal ischemia [9/109 (8.3%)] and sinus thrombosis [3/109 (2.8%)]. Multivariate analysis identified significant associations between CerVE and concurrent NP events attributed to SLE (HR (95% CI): (3.18; 1.72-5.88), concurrent non-SLE NP events (2.75; 1.55-4.89) (p<0.001), patients of African ancestry at US SLICC sites (2.95; 1.44-6.06) (p=0.003) and increased cumulative organ damage score (excluding NP variables) (p=0.04). There was a significant association between lupus anticoagulant at enrolment and the risk of first CerVE (4.4; 1.8-10.9) but not with recurrent events (0.87; 0.34-2.24) (p=0.012) likely due to the greater use of anticoagulants following the initial CerVE event (94%) compared to at the time of the initial events (37%).

Conclusion: CerVE are the fourth most frequent NP event in SLE, are usually attributable to lupus and occur frequently around the time of SLE diagnosis. Risk factors include other concurrent NP events, African ancestry and lupus anticoagulant.

Disclosure: J. G. Hanly, None; Q. Li, None; L. Su, None; M. Urowitz, None; J. Romero-Diaz, None; C. Gordon, None; S. C. Bae, None; S. Bernatsky, None; A. E. Clarke, None; D. J. Wallace, None; J. T. Merrill, None; D. A. Isenberg, None; A. Rahman, None; E. M. Ginzler, None; P. R. Fortin, None; D. Gladman, AbbVie, Amgen, Celgene, Janssen, Novartis, Pfizer, UCB, 2,AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, 5; J. Sanchez-Guerrero, None; M. Petri, None; I. N. Bruce, None; M. A. Dooley, None; R. Ramsey-Goldman, exagen, 2; C. Aranow, None; G. S. Alarcon, None; K. Steinsson, None; G. K. Sturfelt, None; O. Nived, None; S. Manzi, exagen, 2; M. Khamashta, None; R. F. van Vollenhoven, AbbVie, Amgen, Biotest, BMS, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex., 2,AbbVie, Amgen, Biotest, BMS, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex., 5,AbbVie, Amgen, Biotest, BMS, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex., 8; A. Zoma, None; G. Ruiz-Irastorza, None; S. S. Lim, None; M. Inanc, None; K. C. Kalunian, None; D. L. Kamen, None; C. A. Peschken, None; S. Jacobsen, None; A. Askanase, None; C. Theriault, None; V. Farewell, None; M. Ramos-Casals, None.

To cite this abstract in AMA style:

Hanly JG, Li Q, Su L, Urowitz M, Romero-Diaz J, Gordon C, Bae SC, Bernatsky S, Clarke AE, Wallace DJ, Merrill JT, Isenberg DA, Rahman A, Ginzler EM, Fortin PR, Gladman D, Sanchez-Guerrero J, Petri M, Bruce IN, Dooley MA, Ramsey-Goldman R, Aranow C, Alarcon GS, Steinsson K, Sturfelt GK, Nived O, Manzi S, Khamashta M, van Vollenhoven RF, Zoma A, Ruiz-Irastorza G, Lim SS, Inanc M, Kalunian KC, Kamen DL, Peschken CA, Jacobsen S, Askanase A, Theriault C, Farewell V, Ramos-Casals M. Risk Factors for Cerebrovascular Events in Systemic Lupus Erythematosus: Results from an International, Inception Cohort Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/risk-factors-for-cerebrovascular-events-in-systemic-lupus-erythematosus-results-from-an-international-inception-cohort-study/. Accessed .

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-for-cerebrovascular-events-in-systemic-lupus-erythematosus-results-from-an-international-inception-cohort-study/