The presence of lupus anticoagulant, an antiphospholipid antibody, increased the risk of stroke by 40-fold and of heart attack by 5-fold in a Dutch study that compared young women who had survived these conditions with a healthy control group.
Smoking and use of oral contraceptives drove the risk of these arterial thrombosis events yet higher in the survivors who tested positive for lupus anticoagulant, according to a report posted online in the Lancet Neurology.
“Our data suggest that lupus anticoagulant is a major risk factor for arterial thrombotic disease…. Screening for lupus anticoagulant in young women with ischemic stroke seems to be warranted,” wrote Rolf T. Urbanus, Ph.D., of University Medical Centre Utrecht (the Netherlands) and associates (Lancet Neurol. 2009 [doi:10.1016/S1474-4422(09)70239-X]).
Most important is the elucidation that young women with antiphospholipid antibodies should be informed “about the serious risks of cigarette smoking and use of oral contraceptives,” according to an accompanying editorial by Dr. Kathryn F. Kirchoff-Torres and Dr. Steven R. Levine, both of the Stroke Center at Mount Sinai School of Medicine, New York (Lancet Neurol. 2009 [DOI:10.1016/S1474-4422(09)70263-7]).
Lupus anticoagulant is one of several antibodies implicated in antiphospholipid syndrome, an autoimmune disease that is an acquired risk factor for arterial thrombosis. The syndrome is known to be more prevalent in young women. Diagnosis is based on thrombotic events and repeated positive tests for antiphospholipid antibodies, such as those against the phospholipid cardiolipin or the plasma protein beta2-glycoprotein I, as well as the lupus anticoagulant.
For this analysis, the investigators drew participants from the multicenter RATIO (Risk of Arterial Thrombosis In relation to Oral contraceptives) study, which enrolled women aged 49 years and younger who had been hospitalized with their first ischemic stroke or MI between January 1990 and October 1995. Dr. Urbanus and colleagues also included 50 women who presented with ischemic stroke between 1996 and 2001 at the Utrecht center.
All told, the population comprised 175 women with ischemic stroke, 203 women with MI, and 628 healthy controls who were identified by random-digit dialing of telephone numbers and invited to participate. The average age was 42 years for the MI group and 39 years for the stroke patients and healthy controls.
More than a quarter of the MI and stroke groups but only 6% of the controls had hypertension. Use of oral contraceptives was higher in the stroke group (53%) than in the MI (39%) and control (33%) groups. The MI patients were most likely to be current smokers (82%), followed by those in the stroke (60%) and control (42%) groups.
Analysis of blood samples found lupus anticoagulant in 6 (3%) MI patients and 30 (17%) stroke patients, but only 4 (0.6%) healthy controls. Comparing the women with lupus anticoagulant to those who did not have the antibody produced odds ratios of 5.3 (95% confidence interval, 1.4-20.8) for MI and 43.1 (12.2-152.0) for ischemic stroke, Dr. Urbanus and his associates reported.
In women who used oral contraceptives and carried the lupus anticoagulant risk factor, the odds ratios became 21.6 (1.9-242.0) for MI and 201.0 (22.1-1,828.0) for stroke. Similarly, smoking increased the odds of MI to 337 (6.0-189.0) and of stroke to 87.0 (14.5-523.0), the investigators said.
The authors did not find increased risks with anticardiolipin or antiprothrombin antibodies. Presence of beta2-glycoprotein I antibodies doubled the risk of stroke (OR 2.3) but did not add to the risk of MI. In women with lupus anticoagulant, the presence of a second antiphospholipid antibody did not increase risk.
The investigators noted that the study had limitations, and the editorial emphasizes that “a few methodological issues … deserve attention.” The odds ratios are much higher than previously reported by other researchers who found increased risk with antiphospholipid antibodies (Stroke 2002;33:2396-400 and Stroke 2004;35:736-41). This may have been a reflection of the low prevalence of lupus anticoagulant in the healthy controls compared with historic data.
Other issues include the timing of the testing for antiphospholipid antibodies, which occurred as long as 10 years after the thrombotic events. “Some aPL [antiphospholipid antibody]-positive patients in the study by Urbanus and colleagues might not, therefore, have been aPL-positive at the time of the thrombotic event, and vice versa, making any claims of causality speculative,” wrote Dr. Kirchoff-Torres, a senior vascular neurology fellow and postdoctoral researcher, and Dr. Levine, professor of neurology and director of the cerebrovascular research training program at Mount Sinai.
Dr. Kirchoff-Torres also cited the wide confidence intervals and noted during an interview that the original study on oral contraceptive risk was not designed to look at antiphospholipid antibodies. In addition, there is no information on young women with fatal MIs or fatal ischemic strokes. It also is not reported how many women with stroke or MI had only the lupus anticoagulant as a risk factor and nothing else.