PARIS — Migraine is an independent risk factor for stroke and other arterial thrombotic events in patients with lupus, but Raynaud's phenomenon is not.
The increased thrombotic risk conferred by migraine in patients with systemic lupus erythematosus (SLE) is of similar magnitude in migraineurs with and without aura, said Dr. Simone Appenzeller, a rheumatologist at McGill University, Montreal.
Speaking at the annual European Congress of Rheumatology, she reported on 327 patients prospectively followed for an average of 5 years since being diagnosed with SLE. One hundred of the 327 met International Headache Society diagnostic SLE criteria for migraine, including 38 who had migraine with aura.
When they were diagnosed with SLE, 5.5% of patients had a history of stroke or other arterial thrombotic events. During follow-up, 11.9% of participants experienced such events. Migraine proved to be independently associated with 4.3-fold increased odds of arterial vascular thrombotic events in a multivariate analysis adjusted for known thrombotic risk factors, including hypertension and diabetes, as well as for the presence of lupus anticoagulant, antiphospholipid antibodies, family history of cardiovascular events, and the use of aspirin or oral anticoagulants.
In addition, migraine was independently associated with a 9.8-fold rise in the odds of antiphospholipid antibodies being present. More frequent migraine with aura was linked to a higher risk of thrombotic events. However, duration of migraines was not.
The Raynaud's study involved 748 SLE patients, including the 327 from the migraine study. Their median age was 25 years, and 690 were women. Two hundred and fifty subjects (33%) had Raynaud's phenomenon. During a median 7 years of follow-up, 16% of the SLE patients developed arterial vascular thrombotic events. Another 6% had a history of such an event at baseline, when they were diagnosed with SLE.
In a multivariate model adjusted for common thrombotic risk factors, neither the presence nor duration of Raynaud's phenomenon independently predicted arterial thrombotic events. This finding is of particular interest because Raynaud's phenomenon is the result of small-artery ischemia. If Raynaud's doesn't predispose to arterial thrombotic events in patients with SLE, it suggests that the pathophysiologic basis of such events lies chiefly elsewhere.
The presence of the antiphospholipid syndrome was associated with an adjusted 9.8-fold increased rate of a history of arterial thrombotic events at the time SLE was diagnosed, and with a 5.7-fold greater rate of such events during the follow-up period than in unaffected patients with SLE.
Dr. Appenzeller noted that the mechanism by which migraine leads to stroke and other ischemic vascular events is likely to prove complex. She offered some hypotheses: Migraine and ischemic vascular events could be linked by genetic factors; drugs prescribed for migraine might predispose to such events; migraine might directly cause ischemic events; the headaches might adversely effect endothelial function in ways predisposing to vascular events even during migraine-free periods; and/or migraine may be associated with an increased prevalence of the major risk factors for stroke and other vascular events.
With regard to this last possibility, she noted that in several studies of the migraine/stroke association in individuals without SLE, the link tends to be strongest in the absence of traditional cardiovascular risk factors, and the association diminishes with advancing age. These findings suggest that the mechanism by which migraine increases thrombotic risk is independent of the standard major cardiovascular risk factors, which become more potent in older populations.