A multicenter prospective study has established a strong link between antiphospholipid antibodies and atherosclerotic cardiovascular disease in patients with systemic lupus erythematosus. The study also highlights aspirin’s potential to mitigate this risk in aPL-positive patients.
Published in BMC Medicine, the study followed 1,573 patients with systemic lupus erythematosus (SLE) from the CSTAR registry across seven national centers for an average of 4.51 years. All of the participants met the inclusion criteria based on the 1997 American College of Rheumatology, 2012 Systemic Lupus International Collaborating Clinics, or 2019 European Alliance of Associations for Rheumatology classification standards. Among these, 33.4% (n = 525) tested positive for antiphospholipid antibodies (aPLs), which included anticardiolipin (aCL) antibodies, anti-β2 glycoprotein I (anti-β2GPI) antibodies, and lupus anticoagulant (LA).
During the follow-up, 7.37% (n = 116) of the patients experienced atherosclerotic cardiovascular disease (ASCVD) events, such as myocardial infarction (5.2%), stroke (3.6%), artery revascularization (6.7%), or cardiovascular death (0.3%). Among aPL-positive patients, 92 of them developed ASCVD compared with 24 among aPL-negative patients. The presence of aPLs conferred a nearly eightfold increased risk of ASCVD (hazard ratio [HR] = 7.81, 95% confidence interval [CI] = 5.00–12.24, P < .001). Among the subtypes, LA carried the highest risk (HR = 7.87, 95% CI = 5.31–11.67, P < .001).
Notably, 71.8% of aPL-positive patients exhibited high-risk profiles, defined by LA positivity, double positivity (any two of LA, aCL, or anti-β2GPI), or triple positivity. The patients with triple positivity had an ASCVD incidence rate of 45.2%.
Aspirin demonstrated a significant protective effect, reducing the ASCVD incidence in aPL-positive patients to 7.3% compared with 31.4% in those who did not receive aspirin (HR = 0.57, 95% CI = 0.25–0.93, P = .026). Other therapies, such as hydroxychloroquine, showed no preventive effect as a result of high baseline usage (> 90%) in both aPL-positive and -negative groups. Colchicine, discussed for its potential cardiovascular benefits, was not formally assessed in this study but may warrant further investigation based on prior findings in reducing inflammation and thrombotic risk.
The study also highlighted the interplay between autoimmune and traditional cardiovascular risk factors. Patients with SLE and aPLs had higher rates of smoking (4.2% vs 1.8%, P = .005), diabetes (2.9% vs 1.1%, P = .014), and hyperlipidemia (5.3% vs 3.2%, P = .045) compared with aPL-negative patients. After adjusting for these factors, aPL positivity remained an independent risk factor for ASCVD.
Data were collected using standardized forms through the CSTAR registry. The investigators highlighted the potential value of stratifying patients with SLE by aPL status to guide ASCVD risk assessment and preventive strategies. They recommended prioritizing testing for aPLs—especially LA and aCL antibodies—at diagnosis to identify high-risk patients.
The authors declared no competing interests.