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.