β 2 -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

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Abstract
Background— It has been hypothesized that immunoreactivity to β2-glycoprotein 1 (β2GP1)-dependent anticardiolipin antibody (aCL), but not β2GP1-independent aCL, is associated with increased risk of ischemic stroke and myocardial infarction (MI). Methods— We performed a nested case-control study examining aCL as a risk factor for ischemic stroke and MI by using stored frozen sera obtained from subjects enrolled in the Honolulu Heart Program and followed for up for 20 years. We measured β2GP1-dependent and β2GP1-independent aCL and anti-β2GP1 immunoreactivity in 259 men who developed an ischemic stroke, in 374 men who developed an MI, and in a control group of 1360 men who remained free of both conditions. Results— Only β2GP1-dependent aCL of the IgG class was significantly associated with both incident ischemic stroke and MI. This association was attenuated in the last 5 years of the 20-year follow-up. For stroke, the risk factor–adjusted relative odds for men with a positive versus a negative β2GP1-dependent aCL of the IgG class were 2.2 (95% CI 1.5 to 3.4) at 15 years and 1.5 (95% CI 1.0 to 2.3) at 20 years. For MI, the adjusted relative odds were 1.8 (95% CI 1.2 to 2.6) at 15 years and 1.5 (95% CI 1.1 to 2.1) at 20 years. Conclusions— These data suggest that aCL IgG, particularly the β2GP1-dependent variety, is an important predictor of future stroke and MI in men.