An article published Online First and in the November edition of The Lancet Neurology reports that women with a particular subtype of antibody called lupus anticoagulant (LA) have a more than 40-fold increased risk of stroke. Moreover, they have a 5-fold increased risk of heart attack compared with the general population of young women. The autoimmune condition antiphospholipid syndrome mostly affects young women. The use of oral contraceptive and smoking increase the risks all the more. The article is the work of Dr Rolf Urbanus and Dr Philip de Groot, University Medical Centre Utrecht, Netherlands, in cooperation with colleagues from the Leiden University Medical Centre.

An autoantibody is an antibody that is directed against one of the individual’s own proteins. Normally the immune system does not recognise the body’s own proteins and cells, but on occasion the immune system starts to recognise ‘self’-proteins, causing damage and inflammation. Antiphospholipid syndrome occurs when the autoantibodies attach to cell membranes. This interferes with the regular clotting mechanism of the blood. When young women under 50 years suffer a thrombotic event such as a stroke or heart attack, diagnosis usually occurs. This is when antiphospholipid antibodies are tested. This condition causes thrombosis, bleeding, and repeat miscarriage in women, however, before this study the level of the increased risk for stroke and heart attack was unidentified.

Data from the RATIO study (Risk of Arterial Thrombosis In relation to Oral contraceptives) was used for the analysis. Between 1990 and 2001, a total of 1,006 women aged under 50 years were enrolled. The authors used questionnaires to measure the prevalence of various risk factors, with blood samples taken to measure various phospholipid antibodies, including LA. The group of patients included 175 women who had had a stroke, 203 had had a heart attack, and 628 healthy controls.

LA was found in 17 percent (30) patients with stroke, 3 percent (6) patients with heart attack, and 0.7 percent (4) healthy controls. The researchers observed that that 4 of 628 healthy controls had LA and estimated the prevalence in women in the general population to be 7 in 1,000, or 0.7 percent. Earlier studies have made higher calculations. LA increased the risk of stroke 43-fold compared with healthy controls. In women with LA who smoked, the risk was raised 87-fold. Moreover, for women with LA who used oral contraceptives, the risk was increased more than 200-fold. In addition, LA increased with risk of heart attack 5-fold compared with healthy controls. LA added to smoking increased the risk 34-fold, and LA added to oral contraceptives increased the risk 22-fold. These increased risks are explained by the fact that smoking and oral contraceptive use augment the action of LA.

The authors explain: “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 this risk even further…Screening for lupus anticoagulant in young women with ischaemic stroke seems to be warranted.”

In an associated note, Dr Kathryn Kirchoff-Torres and Dr Steven R Levine, Stroke Center, Mount Sinai School of Medicine, New York, NY, USA, remark that the most significant characteristic of the study is its conclusion: that young women with LA need to be warned about the dangers of smoking and use of oral contraceptives.

“Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study”
Rolf T Urbanus, Bob Siegerink, Mark Roest, Frits R Rosendaal, Philip G de Groot, Ale Algra
DOI: 10.1016/S1474-4422(09)70239-X
The Lancet Neurology

Written by Stephanie Brunner (B.A.)