Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

Key Points Question At a single time point without confirmatory testing, what is the prevalence of antiphospholipid antibodies (aPL), and are they associated with future atherosclerotic cardiovascular disease (ASCVD) risk? Findings In this population-based cohort study including 2427 participants, the prevalence of any aPL tested by solid-phase assays at a single time point was 14.5%, with approximately one-third of those detected at a moderate or high titer. The IgA isotypes of anticardiolipin and anti-beta-2 glycoprotein I were associated with future ASCVD events. Meaning These results suggest that some aPL are associated with increased ASCVD risk in the general population; longitudinal studies with serial laboratory assessments will be needed to further explore these associations. This cohort study examines the association between measurements of antiphospholipid antibodies (aPL) at a single time point and atherosclerotic cardiovascular disease risk in a diverse population. Importance The prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated. Objective To determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population. Design, Setting, and Participants This cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti-beta-2 glycoprotein I [a beta 2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023. Main Outcomes and Measures Associations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons. Results Among the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), a beta 2GPI IgM (63 [2.6%]), and a beta 2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and a beta 2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; a beta 2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of a beta 2GPI IgA negatively correlated with cholesterol efflux capacity (r=-0.055; P=.009) and positively correlated with circulating oxidized LDL (r=0.055; P=.007). a beta 2GPI IgA-positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Conclusions and Relevance In this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and a beta 2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

Automated summary

This population-based cohort study found that the prevalence of antiphospholipid antibodies (aPL) tested at a single time point was 14.5%, with approximately one-third at a moderate or high titer. The IgA isotypes of anticardiolipin and anti-beta-2 glycoprotein I were associated with future atherosclerotic cardiovascular disease (ASCVD) events.