Antiphospholipid antibody positivity in early systemic lupus erythematosus is associated with subsequent vascular events

Abstract

Objective: aPL are found in the blood of 20-30% of patients with SLE. Although aPL cause vascular thrombosis in the antiphospholipid syndrome, it is not clear whether positive aPL levels in early SLE increase risk of subsequent vascular events (VE). In a previous analysis of 276 patients with SLE, we found that early positivity for ≥2 of IgG anti-cardiolipin (anti-CL), IgG anti-β2-glycoprotein I (anti-β2GPI) and anti-domain I of β2-glycoprotein I (anti-DI) showed a possible association with VE. Here we have extended that analysis.

Methods: Serum samples taken from 501 patients with SLE early in their disease had been tested for IgG anti-CL, anti-β2GPI and anti-DI by ELISA. Complete VE history was available for 423 patients of whom 23 were excluded because VE occurred before the diagnosis of SLE. For the remaining 400 patients we carried out Kaplan-Meier survival analysis to define groups at higher risk of VE.

Results: Of 400 patients, 154 (38.5%) were positive for one or more aPL, 27 (6.8%) were double/triple-positive and 127 (31.8%) were single-positive. There were 91 VE in 77 patients, of whom 42 were aPL-positive in early disease. VE were significantly increased in aPL-positive vs aPL-negative patients (P = 0.041) and in double/triple-positive vs single-positive vs aPL-negative patients (P = 0.0057). Omission of the IgG anti-DI assay would have missed 14 double/triple-positive patients of whom six had VE.

Conclusion: Double/triple-positivity for IgG anti-CL, anti-β2GPI and anti-DI in early SLE identifies a population at higher risk of subsequent VE.

Keywords: APS; SLE; cardiovascular.

Figure 1.

Kaplan–Meier survival curves comparing incidence of vascular events over time in groups stratified by serology in early disease samples. (A) Comparison of aPL-positive vs aPL-negative groups. (B) Comparison of single-positive vs double/triple positive vs negative groups. The overall P-value for difference between curves was 0.0057. Pairwise comparisons showed double/triple-positive vs aPL-negative P = 0.0026, single-positive vs aPL-negative P = 0.19 and double/triple positive vs single-positive P = 0.025

Figure 2.

Further Kaplan–Meier survival curves comparing incidence of vascular events over time in groups stratified by serology in early disease samples. (A) Comparison of single anti-β2GPI positive vs aPL-negative groups. (B) Comparison of single anti-DI positive vs aPL-negative groups. (C) Comparison of single anti-CL positive vs aPL-negative groups. (D) An analysis carried out to simulate what would have happened if only the criteria assays—IgG anti-β2GPI and anti-CL—had been carried out. There would have been 332 aPL-negative, 55 single-positive and 13 double-positive patients. The increased risk in positive vs negative patients is still present but the survival curves for double-positive and single-positive patients do not diverge. The overall P-value for difference between curves was 0.0033. Pairwise comparisons showed double-positive vs aPL-negative P = 0.0077, single-positive vs aPL-negative P = 0.015 and double positive vs single-positive P = 0.38