Background/Purpose: The antiphospholipid syndrome (APS) is present when arterial, venous or microvascular thrombosis or obstetric morbidity concur with confirmed positive tests for antiphospholipid antibodies (aPL). Long-term anticoagulation prevents new thrombotic events in most APS patients. Information on the occurrence of pro-thrombotic aPL in myocardial infarction (MI) is conflicting due to limited size, selected populations and/or non-standardized methods in previous studies.

Methods: 805 patients (age <75 years; 6-10 weeks after a first MI) and 805 age- (mean 62± 8 years), sex- (male 81%) and area-matched controls, free from MI, were examined. Associations between aPL positivity [anti-cardiolipin (aCL) and anti-β₂glycoprotein-I (anti-β₂GPI), IgG, IgM and IgA] and MI were studied by paired statistical analyses (paired Student’s t-test, McNemar´s test). Additionally, aPL positive MI patients and 6 APS patients, defined according to the Sydney criteria, were tested on a peptide ELISA regarding reactivity to specific domains of the β₂GPI protein.

Results: Positivity for IgG anti-CL and IgG anti-β₂GPI was noted in 10.9% versus 0.9% [p<0.0001 ] and in 10.4% versus 0.9% [p<0.0001) among MI patients and controls respectively, and many MI patients had high IgG titers. aPL of IgM and IgA isotypes did not differ (figure). IgG positivity for anti-CL and anti-β₂GPI was highly correlated (r_Spearman=0.85) and these antibodies were therefore evaluated combined as aPL IgG positivity (n=88). Using this definition aPL IgG positivity remained associated with MI after adjustment for traditional cardiovascular risk factors (present smoking, hypertension, diabetes and body mass index) [adjusted OR 8.9 (95%CI: 4.6-17.3)]. Anti-β₂GPI antibodies from MI patients usually recognized one domain of the β₂GPI protein, while antibodies from APS patients targeted several domains.

Conclusion: In a large representative cohort of patients with a first-time MI and matched controls, we report a strong independent association between IgG aPL positivity and MI, suggesting that IgG aPL could be an important risk factor for MI in the general population. If long-term cohort studies can confirm causality for IgG aPL, our results may alter handling, treatment and outcomes for many patients with MI.