Antiphospholipid antibodies increase risk for future cardiovascular disease in lupus
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SAN DIEGO — Patients with systemic lupus erythematosus who are positive for antiphospholipid antibodies have a greater risk for future atherosclerotic cardiovascular disease, according to data presented at ACR Convergence 2023.
“Previous studies show that lupus patients suffer from an increased risk for cardiovascular disease — approximately 23 events per 1,000 patient-years,” Yufang Ding, a medical student at Peking Union Medical College Hospital, in Beijing, said at a press conference during the meeting. “So how can we predict atherosclerosis risk in lupus patients? Antiphospholipid antibodies became the center of our investigation. Antiphospholipid antibodies are not only the key serologic feature of antiphospholipid syndrome but are also found in about 30% to 40% of lupus patients. Previous studies indicated antiphospholipid antibodies can result in vasculopathy and thrombosis.”
To examine the relationship between antiphospholipid antibodies and future atherosclerotic cardiovascular disease risk in patients with SLE, Ding and colleagues recruited 1,573 participants into a multicenter prospective study. The researchers assessed seven antiphospholipid antibody isotypes — aCL IgG/IgM/IgA, a2GPI IgG/IgM/IgA and LA — at SLE diagnosis and throughout follow-up, collecting data on disease activity and organ damage.
Atherosclerotic cardiovascular disease events included in the analysis were nonfatal myocardial infarction, nonfatal stroke, coronary or peripheral artery revascularization, or cardiovascular death.
Among the 1,573 recruited patients with SLE, 525 were positive for antiphospholipid antibodies. Among those who were positive, 20% demonstrated the LA isotype, 15.8% had aCL IgG, 12.7% had a2GPI IgG, 5.8% had aCL IgM, 5.3% had a2GPI IgM, and 3.7% had aCL IgA.
Meanwhile, a total of 116 participants developed atherosclerotic cardiovascular disease during a mean follow-up of 4.51±2.32 years. Among these patients, 92 were positive for antiphospholipid antibodies. According to the researchers, in a univariate Cox regression analysis, both antiphospholipid antibodies (HR = 7.81; 95% CI, 5-12.24) and traditional cardiovascular risk factors were associated with future atherosclerotic cardiovascular disease events.
However, in multiple Cox regression analyses, aCL IgG (HR = 1.95; 95% CI, 1.25-3), aCL IgM (HR = 1.83; 95% CI, 1.03-3.2), and LA (HR = 5.13; 95% CI, 3.23-8.2) were all independently associated with atherosclerotic cardiovascular disease. Smoking, gender, age and hypertension were also independent risk factors for atherosclerotic cardiovascular disease in patients with SLE.
The researchers additionally found that anticoagulant or antiplatelet therapy can reduce atherosclerotic cardiovascular disease risk in patients with SLE who are positive for antiphospholipid antibodies (HR = 0.57; 95% CI, 0.25-0.93).
“Our study outlines the critical relationship between antiphospholipid antibodies and atherosclerotic risk in lupus patients,” Ding said. “This underscores the need for comprehensive assessment and preventive treatment to enhance the quality of care and outcomes for these patients.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Antiphospholipid syndrome is a systemic autoimmune disorder marked by the occurrence of arterial, venous or microvascular thrombosis, as well as obstetric events. It manifests in individuals with consistently positive antiphospholipid (aPL) antibodies and stands as a significant contributor to cardiovascular events among the younger population.
Although aPL antibody syndrome was initially identified in patients with systemic lupus erythematosus, it is currently widely acknowledged that there exists a subset of individuals who exhibit elevated levels of aPL antibodies, typically of the IgG class, along with thrombotic characteristics, despite the absence of clinical signs of SLE. Conversely, aPL antibodies may emerge temporarily during various infections and in conjunction with certain medications, showing no correlation with thrombotic events.
A 5-year prospective study of initially healthy young men with dyslipidemia in the Helsinki Heart Study found that participants with the highest quartile of IgG anti-cardiolipin (aCL) antibodies had a twofold increased risk for myocardial infarction (MI) or cardiac death, compared to the controls. This risk was independent of confounding factors, such as age, smoking, systolic blood pressure, low-density lipoprotein, and high-density lipoprotein.
In another study of young patients with MI, researchers observed elevated aCL antibody levels and that high titers of these antibodies were an indicator of an increased risk for recurrent cardiovascular events. Another study by different researchers also noted an association between elevated levels of aCL antibodies and ischemic heart disease. However, other studies have failed to show this association.
Positive results for at least one of the aPL tests are reported in 30% to 50% of patients with SLE. Oral estrogens and smoking in particular have been shown to pose additional risks for vascular events in patients with aPL. Among arterial occlusions, stroke is the most frequently reported. In general, associations have been more convincing among younger patients and those with SLE. A strong positive association between lupus anticoagulant (LA) positivity and previous strokes has been observed in women younger than 50 years.
Regarding strokes, it is essential to note that valvular heart disease is one of the more common “non-criteria” manifestations associated with aPL and simultaneously represents an important risk factor for thromboembolic stroke. Heart valve disease, including Libman-Sacks endocarditis, is prevalent in SLE, with compelling evidence indicating an association with aPL.
In a comprehensive meta-analysis of 23 studies, it was demonstrated that positive aPL, particularly LA positivity, was 3 to 5.5 times more prevalent in 508 patients with SLE with heart valve involvement, compared to 988 individuals without such involvement. Patients with SLE alongside positive aPLs, especially positive aCL IgG/IgM and LA, warrant careful surveillance for future atherosclerotic cardiovascular disease events.
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Ding Y. Abstract 552. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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