β₂-glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: The Honolulu Heart Program

Background - It has been hypothesized that immunoreactivity to β₂-glycoprotein I (β₂GPI)-dependent anticardiolipin antibody (aCL), but not ,B2GP1-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 i schemic 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.