Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study
Abstract
Background Arterial thrombosis is a major clinical manifestation of the antiphospholipid syndrome, which is an autoimmune disease found mostly in young women. Although the presence of circulating antiphospholipid antibodies in individuals who have a thrombotic event is a prerequisite for the diagnosis of the antiphospholipid syndrome, the risk of arterial thrombosis associated with antiphospholipid antibodies in the general population is unclear.Methods In RATIO (Risk of Arterial Thrombosis In relation to Oral contraceptives), a large multicentre population-based case-control study, we enrolled women aged under 50 years who were admitted to hospital at 16 centres with first ischaemic stroke or myocardial infarction between January, 1990, and October, 1995. An additional 59 women who presented with ischaemic stroke at the University Medical Centre Utrecht between 1996 and 2001 were also enrolled. Information on cardiovascular risk factors (such as oral contraceptive use, smoking, and hypertension) were assessed with a standard questionnaire. During the second phase (1998-2002), blood samples were taken to measure antiphospholipid antibody profiles (lupus anticoagulant, anticardiolipin IgG, anti-beta(2)-glycoprotein I IgG, and antiprothrombin IgG) and to determine genetic prothrombotic risk factors (factor V G1691A variant, prothrombin G20210A variant, and factor XIII 204Phe allele).Findings 175 patients with ischaemic stroke, 203 patients with myocardial infarction, and 628 healthy controls were included. Patients were frequency matched with controls for age, residence area, and index year. Lupus anticoagulant was found in 30 (17%) patients with ischaemic stroke, six (3%) patients with myocardial infarction, and four (0.7%) in the control group. The odds ratio for myocardial infarction was 5.3 (95% CI 1.4-20.8), which increased to 21.6 (1.9-242.0) in women who used oral contraceptives and 33.7 (6.0-189.0) in those who smoked. The odds ratio for ischaemic stroke was 43.1 (12.2-152.0), which increased to 201.0 (22.1-1828.0) in women who used oral contraceptives and 87.0 (14.5-523.0) in those who smoked. In women who had anti-beta(2)-glycoprotein I antibodies, the risk of ischaemic stroke was 2.3 (1.4-3.7), but the risk of myocardial infarction was not increased (0.9, 0.5-1.6). Neither anticardiolipin nor antiprothrombin antibodies affected the risk of myocardial infarction or ischaemic stroke.Interpretation Our results suggest that lupus anticoagulant is a major risk factor for arterial thrombotic events in young women, and the presence of other cardiovascular risk factors increases the risk even further.Funding Netherlands Heart Foundation and Leducq Foundation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In most studies, in SLE, LA is the main predictor of thrombosis.
“In most studies, it has been shown that in SLE, LA is the main predictor of thrombosis [9, 27–29].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [28]
An isolated LAC is an independent risk factor for myocardial infarction and ischemic stroke.
“Moreover,anisolated LAC is an independent risk factor for myocardial infarction and ischemic stroke. 14”
From Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome (2021) · cites this paper as [14]
Cites
MIYAKIS, S., LOCKSHIN, M. D., ATSUMI, T., BRANCH, D. W., BREY, R. L., CERVERA, R., DERKSEN, R. H. W. M., DE GROOT, P. G., KOIKE, T., MERONI, P. L., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01753.x · Cited by 7,203 · see citing works
Mutation in blood coagulation factor V associated with resistance to activated protein C
Bertina, R. M., Koeleman, B. P. C., Koster, T., Rosendaal, F. R., Dirven, R. J., de Ronde, H., van der Velden, P. A., & Reitsma, P. H. (1994) · Nature · doi:10.1038/369064a0 · Cited by 3,769 · see citing works
Self-citationPoort, S., Rosendaal, F. R., Reitsma, P. H., & Bertina, R. M. (1996) · Blood · doi:10.1182/blood.v88.10.3698.bloodjournal88103698 · Cited by 3,064 · see citing works
Self-citationThe pathophysiology of cigarette smoking and cardiovascular disease
Ambrose, J. A., & Barua, R. S. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.12.047 · Cited by 2,394 · see citing works
Cervera, R., Piette, J., Font, J., Khamashta, M. A., Shoenfeld, Y., Camps, M. T., Jacobsen, S., Lakos, G., Tincani, A., Kontopoulou‐Griva, I., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10187 · Cited by 2,156 · see citing works
Galli, M., Luciani, D., Bertolini, G., & Barbui, T. (2003) · Blood · doi:10.1182/blood-2002-02-0441 · Cited by 974 · see citing works
Rothwell, P., Coull, A., Silver, L., Fairhead, J., Giles, M., Lovelock, C., Redgrave, J., Bull, L. M., Welch, S. J. V., Cuthbertson, F. C., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67702-1 · Cited by 938 · see citing works
Patrono, C., Baigent, C., Hirsh, J., & Roth, G. J. (2008) · CHEST Journal · doi:10.1378/chest.08-0672 · Cited by 749 · see citing works
The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants
Thiagarajan, P., Pengo, V., & Shapiro, S. (1986) · Blood · doi:10.1182/blood.v68.4.869.869 · Cited by 422 · see citing works
Rosendaal, F. R., Siscovick, D. S., Schwartz, S. M., Beverly, R. K., Psaty, B. M., Longstreth, W. T., Raghunathan, T. E., Koepsell, T. D., & Reitsma, P. H. (1997) · Blood · doi:10.1182/blood.v89.8.2817 · Cited by 371 · see citing works
Self-citationOral Contraceptives and the Risk of Myocardial Infarction
Tanis, B. C., van den Bosch, M. A. A. J., Kemmeren, J. M., Cats, V. M., Helmerhorst, F. M., Algra, A., van der Graaf, Y., & Rosendaal, F. R. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa003216 · Cited by 367 · see citing works
Self-citationRosendaal, F. R., Siscovick, D. S., Schwartz, S. M., Psaty, B. M., Raghunathan, T. E., & Vos, H. L. (1997) · Blood · doi:10.1182/blood.v90.5.1747 · Cited by 348 · see citing works
Self-citationAttributable risk percent in case-control studies.
Cole, P. T., & MacMahon, B. (1971) · Journal of Epidemiology & Community Health · doi:10.1136/jech.25.4.242 · Cited by 344 · see citing works
Antithrombotic and Thrombolytic Therapy for Ischemic Stroke
Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., & Teal, P. A. (2008) · CHEST Journal · doi:10.1378/chest.08-0720 · Cited by 318 · see citing works
Vaarala, O., Mänttäri, M., Manninen, V., Tenkanen, L., Puurunen, M., Aho, K., & Palosuo, T. (1995) · Circulation · doi:10.1161/01.cir.91.1.23 · Cited by 317 · see citing works
OutiVaarala, MattiMänttäri, VesaManninen, LeenaTenkanen, MarjaPuurunen, KimmoAho, & TimoPalosuo (1995) · Circulation · Cited by 305 · see citing works
Rosing, J., Middeldorp, S., Curvers, J., Thomassen, S., Nicolaes, G. A. F., Meijers, J. C. M., Bouma, B. N., Buller, H. R., Prins, M. H., & Tans, G. (1999) · The Lancet · doi:10.1016/s0140-6736(99)06092-4 · Cited by 257 · see citing works
Horbach, D. A., van Oort, E., Donders, R. C. J. M., Derksen, R. H. W. M., & de Groot, P. G. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650686 · Cited by 246 · see citing works
Stefano, V. D., Chiusolo, P., Paciaroni, K., Casorelli, I., Rossi, E., Molinari, M., Servidei, S., Tonali, P. A., & Leone, G. G. M. (1998) · Blood · doi:10.1182/blood.v91.10.3562 · Cited by 231 · see citing works
Oral Contraceptives and the Risk of Myocardial Infarction
Tanis, B. C., van den Bosch, M. A. A. J., Kemmeren, J. M., Cats, V. M., Helmerhorst, F. M., Algra, A., van der Graaf, Y., & Rosendaal, F. R. (2002) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-200205000-00021 · Cited by 225 · see citing works
Self-citationRisk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) Study
Kemmeren, J. M., Tanis, B. C., van den Bosch, M. A. A. J., Bollen, E. L. E. M., Helmerhorst, F. M., van der Graaf, Y., Rosendaal, F. R., & Algra, A. (2002) · Stroke · doi:10.1161/01.str.0000015345.61324.3f · Cited by 220 · see citing works
Self-citationde Laat, H. B., Derksen, R. H. W. M., Urbanus, R. T., Roest, M., & de Groot, P. G. (2004) · Blood · doi:10.1182/blood-2004-03-1107 · Cited by 219 · see citing works
Self-citationLupus anticoagulants and the risk of a first episode of deep venous thrombosis
DE GROOT, P. G., LUTTERS, B., DERKSEN, R. H. W. M., LISMAN, T., MEIJERS, J. C. M., & ROSENDAAL, F. R. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01485.x · Cited by 205 · see citing works
Self-citationContraceptivos orales y riesgo de infarto de miocardio
Tanis, B. C. (2001) · New England Journal of Medicine · Cited by 192 · see citing works
Longstreth, W. T., Jr., Rosendaal, F. R., Siscovick, D. S., Vos, H. L., Schwartz, S. M., Psaty, B. M., Raghunathan, T. E., Koepsell, T. D., & Reitsma, P. H. (1998) · Stroke · doi:10.1161/01.str.29.3.577 · Cited by 169 · see citing works
Self-citationAntiphospholipid Antibodies and Stroke in Young Women
Brey, R. L., Stallworth, C. L., McGlasson, D. L., Wozniak, M. A., Wityk, R. J., Stern, B. J., Sloan, M. A., Sherwin, R. W., Price, T. R., Macko, R. F., et al. (2002) · Stroke · doi:10.1161/01.str.0000031927.25510.d1 · Cited by 141 · see citing works
Sarti, C., Stegmayr, B., Tolonen, H., Mähönen, M., Tuomilehto, J., & Asplund, K. (2003) · Stroke · doi:10.1161/01.str.0000081224.15480.52 · Cited by 138 · see citing works
Antibodies to Prothrombin Imply a Risk of Myocardial Infarction in Middle-Aged Men
Vaarala, O., Puurunen, M. K., Mänttäri, M., Manninen, V., Aho, K., & Palosuo, T. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650296 · Cited by 130 · see citing works
Janardhan, V., Wolf, P. A., Kase, C. S., Massaro, J. M., D’Agostino, R. B., Franzblau, C., & Wilson, P. W. F. (2004) · Stroke · doi:10.1161/01.str.0000117575.48205.2d · Cited by 116 · see citing works
Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke
Slooter, A. J. C., Rosendaal, F. R., Tanis, B. C., Kemmeren, J. M., van der Graaf, Y., & Algra, A. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01442.x · Cited by 112 · see citing works
Self-citationInvitation to a debate on the serological criteria that define the antiphospholipid syndrome
GALLI, M., REBER, G., DE MOERLOOSE, P., & DE GROOT, P. G. (2008) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2008.02862.x · Cited by 85 · see citing works
Self-citationMeroni, P. L., Peyvandi, F., Foco, L., Bernardinelli, L., Fetiveau, R., Mannucci, P. M., & Tincani, A. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02763.x · Cited by 77 · see citing works
Current insight into diagnostics and pathophysiology of the antiphospolipid syndrome
Urbanus, R. T., Derksen, R. H. W. M., & de Groot, P. G. (2007) · Blood Reviews · doi:10.1016/j.blre.2007.09.001 · Cited by 76 · see citing works
Self-citationRunchey, S. S., Folsom, A. R., Tsai, M. Y., Cushman, M., & McGovern, P. D. (2002) · British Journal of Haematology · doi:10.1046/j.1365-2141.2002.03949.x · Cited by 72 · see citing works
Coagulation factor XIII gene variation, oral contraceptives, and risk of ischemic stroke
Pruissen, D. M. O., Slooter, A. J. C., Rosendaal, F. R., van der Graaf, Y., & Algra, A. (2007) · Blood · doi:10.1182/blood-2007-08-110254 · Cited by 65 · see citing works
Self-citationThe Frequency of Phospholipid Antibodies in an Unselected Stroke Population
Metz, L., Edworthy, S. M., Mydlarski, R., & Fritzler, M. J. (1998) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100033515 · Cited by 59 · see citing works
Anticardiolipin antibodies in acute non-hemorrhagic stroke seen within six hours after onset
Camerlingo, M., Casto, L., Censori, B., Drago, G., Frigeni, A., Ferraro, B., Servalli, M. C., Radice, E., & Mamoli, A. (2009) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1995.tb00469.x · Cited by 51 · see citing works
Anderson, R. E., Pfeffer, M. A., Thune, J. J., et al. (2008) · American Heart Journal · doi:10.1016/j.ahj.2007.11.016 · Cited by 39 · see citing works
Safa, O., Esmon, C. T., & Esmon, N. L. (2005) · Blood · doi:10.1182/blood-2005-01-0404 · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kernan, W. N., Ovbiagele, B., Black, H. R., Bravata, D. M., Chimowitz, M. I., Ezekowitz, M. D., Fang, M. C., Fisher, M., Furie, K. L., Heck, D. V., et al. (2014) · Stroke · doi:10.1161/str.0000000000000024 · Cited by 5,170 · see citing works
Bushnell, C., McCullough, L. D., Awad, I. A., Chireau, M. V., Fedder, W. N., Furie, K. L., Howard, V. J., Lichtman, J. H., Lisabeth, L. D., Piña, I. L., et al. (2014) · Stroke · doi:10.1161/01.str.0000442009.06663.48 · Cited by 941 · see citing works
Diagnosis and management of the antiphospholipid syndrome
Garcia, D., & Erkan, D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1705454 · Cited by 819 · see citing works
Guidelines on the investigation and management of antiphospholipid syndrome
Keeling, D., Mackie, I., Moore, G. W., Greer, I. A., Greaves, M., & British Committee for Standards in Haematology (2012) · British Journal of Haematology · doi:10.1111/j.1365-2141.2012.09037.x · Cited by 740 · see citing works
Ruiz-Irastorza, G., Cuadrado, M., Ruiz-Arruza, I., Brey, R., Crowther, M., Derksen, R., Erkan, D., Krilis, S., Machin, S., Pengo, V, et al. (2011) · Lupus · doi:10.1177/0961203310395803 · Cited by 506 · see citing works
Ischaemic stroke in young adults: risk factors and long-term consequences
Maaijwee, N. A. M. M., Rutten-Jacobs, L. C. A., Schaapsmeerders, P., van Dijk, E. J., & de Leeuw, F.-E. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.72 · Cited by 377 · see citing works
Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke
Roach, R. E. J., Helmerhorst, F. M., Lijfering, W. M., Stijnen, T., Algra, A., & Dekkers, O. M. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011054.pub2 · Cited by 299 · see citing works
Self-citationLaboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH
Devreese, K. M. J., Ortel, T. L., Pengo, V., & de Laat, B. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13976 · Cited by 269 · see citing works
Otomo, K., Atsumi, T., Amengual, O., Fujieda, Y., Kato, M., Oku, K., Horita, T., Yasuda, S., & Koike, T. (2012) · Arthritis & Rheumatism · doi:10.1002/art.33340 · Cited by 254 · see citing works
Arnaud, L., Mathian, A., Ruffatti, A., Erkan, D., Tektonidou, M., Cervera, R., Forastiero, R., Pengo, V., Lambert, M., Martinez-Zamora, M. A., et al. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.10.014 · Cited by 215 · see citing works
Ruffatti, A., Del Ross, T., Ciprian, M., Bertero, M. T., Salvatore, S., Scarpato, S., Montecucco, C., Rossi, S., Caramaschi, P., Biasi, D., et al. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2010.142042 · Cited by 184 · see citing works
Reynaud, Q., Lega, J.-C., Mismetti, P., Chapelle, C., Wahl, D., Cathébras, P., & Laporte, S. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.11.004 · Cited by 179 · see citing works
Arnaud, L., Mathian, A., Devilliers, H., Ruffatti, A., Tektonidou, M., Forastiero, R., Pengo, V., Lambert, M., Lefevre, G., Martinez-Zamora, M. A., et al. (2015) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.10.019 · Cited by 146 · see citing works
Devreese, K. M. J., Bertolaccini, M. L., Branch, D. W., de Laat, B., Erkan, D., Favaloro, E. J., Pengo, V., Ortel, T. L., Wahl, D., & Cohen, H. (2025) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2024.10.022 · Cited by 92 · see citing works
Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant
Pengo, V., Testa, S., Martinelli, I., Ghirarduzzi, A., Legnani, C., Gresele, P., Passamonti, S. M., Bison, E., Denas, G., Jose, S. P., et al. (2015) · Thrombosis Research · doi:10.1016/j.thromres.2014.10.013 · Cited by 89 · see citing works
The antiphospholipid syndrome: still an enigma
Chaturvedi, S., & McCrae, K. R. (2015) · Hematology · doi:10.1182/asheducation-2015.1.53 · Cited by 51 · see citing works
Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus
Demir, S., Li, J., Magder, L. S., & Petri, M. (2021) · Rheumatology · doi:10.1093/rheumatology/keaa857 · Cited by 38 · see citing works
Domingues, V., Magder, L. S., & Petri, M. (2016) · Lupus Science & Medicine · doi:10.1136/lupus-2015-000107 · Cited by 36 · see citing works
Yin, D., de Groot, P. G., Ninivaggi, M., Devreese, K. M. J., & de Laat, B. (2021) · Thrombosis and Haemostasis · doi:10.1055/a-1344-4271 · Cited by 36 · see citing works
Self-citationPosch, F., Gebhart, J., Rand, J. H., Koder, S., Quehenberger, P., Pengo, V., Ay, C., & Pabinger, I. (2017) · BMC Medicine · doi:10.1186/s12916-017-0807-7 · Cited by 25 · see citing works
- Authors
- Urbanus, R. T., Siegerink, B., Roest, M., Rosendaal, F. R., de Groot, P. G., & Algra, A.
- Affiliations
- University Medical Center Utrecht (NL)
- Leiden University (NL)
- Leiden University Medical Center (NL)
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 8
- Issue
- 11
- Pages
- 998-1005
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2101727819
- Cited by
- 429
- References
- 39
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 31 · 2023: 14 · 2022: 21 · 2021: 23 · 2020: 20 · 2019: 34 · 2018: 22 · 2017: 28 · 2016: 27 · 2015: 22 · 2014: 31 · 2013: 21 · 2012: 42
- FWCI
- 24.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation Leducq
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- antiphospholipid antibodies, antiphospholipid syndrome, arterial thrombosis, myocardial infarction, ischemic stroke, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, anti-prothrombin antibodies, oral contraceptives, young women
- MeSH terms
- Adolescent, Adult, Brain Ischemia, Contraceptives, Oral, Hormonal, Diabetes Mellitus, Factor V, Factor XIII, Female, Humans, Hyperlipidemias, Immunoglobulin G, Middle Aged, Myocardial Infarction, Smoking, Thrombosis, Case-Control Studies, Lupus Coagulation Inhibitor, Antibodies, Antiphospholipid, Antibodies, Anticardiolipin, Risk Assessment, Stroke, beta 2-Glycoprotein I, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
