Risk of Cardiovascular Disease Elevated for Certain Patients with Systemic Lupus Erythematosus

The presence of positive antiphospholipid antibodies (aPLs) is associated with future atherosclerotic cardiovascular disease (ASCVD) risk among individuals with systemic lupus erythematosus (SLE).¹

These findings were presented at the American College of Rheumatology (ACR) 2023 Convergence held in San Diego, California. The study’s investigators pointed to the fact that those with diagnoses of SLE are known to have a rising susceptibility to cardiovascular diseases, adding that the incidence is 23.3 events per 1000 patient-years.

The investigators presenting this data noted that aPLs are autoantibodies that are known to impact phospholipid-binding proteins. These phospholipid-binding proteins are known to be connected to conditions such as stroke, heart attack, pulmonary embolism, and pregnancy-related complications in antiphospholipid syndrome.²

While 30 – 40% of those with SLE have aPLs, their effects on cardiovascular disease risk was noted by the research team as having been poorly understood. Yufang Ding, a medical student from Peking Union Medical College Hospital in Beijing, and Ding’s mentors Mengtao Li and Jiuliang Zhao, carried out a prospective study that was multi-center and involved more than 1,500 subjects with diagnosed lupus.

These subjects with a lupus diagnosis had been recruited through the Chinese SLE Treatment and Research Group (CSTAR). These specific individuals from Ding and colleagues’ research had been included in the CSTAR in the time between 2006 – 2021.

The team’s research, looking predominantly at East Asian females, explored potential associations between aPLs and future atherosclerotic cardiovascular disease in those with SLE. They did this through the measurement of 7 aPL isotopes and then through the implementation of a detailed analysis of the data.

These 7 aPL isotypes, which included aβ2GPI (IgG/IgM/IgA), aCL (IgG/IgM/IgA), and LA, were looked at by the research team in accordance with international guidelines at the time of the SLE diagnosis of the study’s subjects and then throughout the follow-up period.¹

The investigators looked at data on the subjecta’ clinical manifestations, their disease activity, and any organ damage. Future events caused by atherosclerotic cardiovascular disease were considered by the research team as the existence of new nonfatal stroke, nonfatal myocardial infarction, peripheral or coronary artery revascularization, or cardiovascular death.

Overall, the investigators found that results showed a positive correlation between aPL positivity, traditional cardiovascular risk factors , and atherosclerotic cardiovascular disease. The team emphasized the independent association of specific aPLs with cardiovascular events.

Additionally, the research team reported on the potential benefit of antiplatelet and anticoagulant therapy with regard to diminishing atherosclerotic cardiovascular disease risk among those with SLE.

Ding noted that prior studies on the subject had indicated that an inflammatory cascade tends to trigger the time when aPLs bind to β2GPI. Ding noted that this will result in vasculopathy, inflammation, and thrombosis, so Ding’s team’s positive correlation found between aPLs, traditional risk factors and cardiovascular disease was seen as likely.²

“Few studies have demonstrated the role of different aPL isotopes in ACSD development,” Ding said in a statement. “In our study, we identified that aCL IgG, aCL IgM and lupus anticoagulant positivity are independently associated with ASCVD after adjusting for traditional cardiovascular disease risk factors.”

Ding and colleagues did acknowledge the limitations of their study, explaining that one statistical challenge is the “dynamic and time-varying interplay among aPL positivity.” Additionally, as the team used an observational design, they acknowledged that it can be difficult to account for confounding variables such as choices in treatment as well as patient outcomes.

Despite the noted limitations of the investigators’ research, Ding indicated that individuals with lupus, especially ones who test positive for aPLs, may see benefit in undergoing more vigilant surveillance for future heart disease based on the research’s implications.

This research summarized here received support from the Chinese National Key Research R&D Program and the CAMS Innovation fund for Medical Sciences.

1. ^{Ding Y, Huang C, zhao J, Wang Q, Tian X, Li M, Zeng x. The Impact of Antiphospholipid Antibodies on Future Atherosclerotic Cardiovascular Disease Risk in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/the-impact-of-antiphospholipid-antibodies-on-future-atherosclerotic-cardiovascular-disease-risk-in-systemic-lupus-erythematosus/. Accessed November 14, 2023.}
2. ^{Study Finds Positive Antiphospholipid Antibodies Raises Cardiovascular Disease Risk in Patients with Systemic Lupus Erythematosus. American College of Rheumatology. November 7, 2023. Date accessed: November 14, 2023. https://rheumatology.org/press-releases/study-finds-positive-antiphospholipid-antibodies-raises-cardiovascular-disease-risk-in-patients-with-systemic-lupus-erythematosus.}