Fast track — ArticlesAntiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study
Introduction
Arterial thrombosis is the second most common cause of death in developed countries. Although the incidence of arterial thrombosis in individuals younger than 50 years is low, the burden of disease in young people is large. Arterial thrombosis is usually associated with several risk factors for cardiovascular disease, such as smoking, hypertension, diabetes, obesity, hyperlipidaemia, or a family history of cardiovascular disease. The antiphospholipid syndrome is an acquired risk factor for arterial thrombosis. The antiphospholipid syndrome is more prevalent in young women than in the general population.1 It is characterised by vascular thrombosis or complications during pregnancy and a repeatedly positive test for antiphospholipid antibodies.2 There are several subpopulations of antiphospholipid antibodies; the coagulation inhibitor lupus anticoagulant and antibodies against the phospholipid cardiolipin or the plasma proteins β2-glycoprotein I and prothrombin are the antibody subpopulations most commonly tested for.
Owing to its non-specific clinical symptoms, diagnosis of the antiphospholipid syndrome is dependent on the detection of antiphospholipid antibodies. Data on the risk of a first thrombotic event in the presence of antiphospholipid antibodies are inconclusive3 because most studies are done in selected populations of patients. Several studies have been done to assess the thrombotic risk associated with antiphospholipid antibodies in the general population.4, 5, 6, 7, 8, 9, 10 Although there is a general consensus from the results of these studies that the presence of antiphospholipid antibodies is independently associated with increased risk of arterial thrombosis, there is still debate on the value of measuring the concentrations of different antiphospholipid antibody subpopulations in the general population.11
We investigated whether the presence of specific antiphospholipid antibody subpopulations (lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein I and antiprothrombin antibodies) affects the risk of myocardial infarction or ischaemic stroke in young women. Furthermore, we studied the effect of smoking, hyperlipidaemia, diabetes, use of oral contraceptives,12, 13 the factor V G1691A mutation (factor V Leiden),14, 15 the prothrombin G20210A mutation,15, 16, 17 and the factor XIII 204Phe allele18 on the relation between antiphospholipid antibodies and arterial thrombosis.
Section snippets
Participants
Eligible patients were women aged 18–49 years who were admitted to hospital for a first myocardial infarction or ischaemic stroke at 16 centres (eight academic centres and eight large, non-academic hospitals) between January, 1990, and October, 1995. Exclusion criteria were transient ischaemic attack that lasted less than 24 h, haemorrhagic stroke, cerebral sinus venous thrombosis, carotid artery dissection, history of cardiovascular or cerebrovascular disease, aphasia or cognitive impairment
Results
During the first phase (1990–95), 248 patients with myocardial infarction, 203 patients with ischaemic stroke, and 925 controls were enrolled (figure 1). 218 of 248 patients with myocardial infarction included during the first phase of the study agreed to participate in the second phase. Samples of venous blood were collected from 203 women with myocardial infarction and buccal swabs were taken from 15 women. Blood samples were collected from 638 of the 925 controls included during the first
Discussion
We found that lupus anticoagulants were associated with an increased risk of myocardial infarction (OR 5·3) and ischaemic stroke (OR 43·1) in women younger than 50 years. Increased concentrations of anti-β2-glycoprotein I antibodies were associated with an increased risk of ischaemic stroke (OR 2·3). Neither anticardiolipin nor antiprothrombin antibodies alone increased the risk of myocardial infarction or ischaemic stroke. There were no indications that the presence of more than one
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