A real-world study has found that high percentages of patients with primary antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE)-related APS have poorly controlled cardiovascular (CV) risk factors despite current guidelines and acknowledged that while those with SLE-related APS may have a higher CV disease burden than those with primary APS, the latter are more likely to have poorly controlled CV risk factors.

“Attainment of cardiovascular risk factor targets in accordance with established guidelines has not previously been evaluated in large, multicenter APS cohorts,” said senior study author Maria Tektonidou, MD, PhD, head of Rheumatology at Laiko Hospital and the School of Medicine at National and Kapodistrian University of Athens in Athens,Greece.

“Additionally, the present findings provide novel evidence of a differential gap in risk factor management across APS subtypes, underscoring a distinct and unmet care need in primary APS,” she added.

The study, conducted by the Survey of Cardiovascular Risk Factors-SLE and APS collaborators and published online in The Lancet Rheumatology, enrolled 1003 patients from 11 countries. It claimed to be the first study to compare CV risks between patients with primary APS and SLE-related APS.

“To my knowledge, this is the largest multicenter cross-sectional evaluation of cardiovascular risk among patients with APS,” said Yu “Ray” Zuo, MD, associate director of the APS program at the University of Michigan in Ann Arbor, Michigan, who was not involved with the study.

The study was unique, Zuo said, because it used “unusually comprehensive assessments” of clinical and laboratory cardiovascular risk factors, such as A1c, full lipid panels and detailed medication data.

Study Results

Tektonidou noted while the 2022 European Alliance of Associations for Rheumatology (EULAR) recommendations for managing CV risks in patients with rheumatic and musculoskeletal diseases, including APS and SLE, highlighted the importance of screening and rigorous management of CV risk factors, “accumulating evidence indicates that risk factor management remains suboptimal in these populations.”

In the overall study population, the rates of several CV risk factors were considered high: hypertension, 41%; hyperlipidemia, 34%; obesity, 32% (of 919 patients); and current smoking, 19% (of 963).

The study found the SLE-related APS group had a higher prevalence of hypertension (50% vs 33%; P < .0001) and hyperlipidemia (40% vs 30%; P = .0009) than the primary APS group but a lower rate of current smoking (16% vs 22%; P = .012).

Patients with primary APS had worse rates for smoking cessation (78% vs 84%; P = .012), reaching target blood pressure < 130/80 mm Hg (48% vs 57%; P = .0067), and having two or more cardiovascular risk factor targets (smoking, BMI, blood pressure, low-density lipoprotein [LDL]) than those with SLE-related APS.

Among patients with high and very high CV disease risks, the patients with primary APS had worse results achieving targets for BMI (26% vs 39%; P = .013), LDL (16% vs 26%; P = .049), and triglycerides (56% vs 72%; P = .0083), and for achieving two or three or more targets for control.

The overall study population also had high rates of thrombosis: 41% had arterial thrombosis (P = .024)and 53% venous thrombosis (P = .019). Seventy percent (P < .0001) were on anticoagulation therapy.

The study used multivariable regression analysis to identify vulnerable groups, Tektonidou said. “Our findings demonstrated that older age, male sex, a history of arterial thrombosis, and current glucocorticoid use were inversely associated with cardiovascular risk factor control,” she said. In one of the researchers’ models, ethnicity emerged as an independent predictor of CV risk factor target attainment, she added, with better control observed in Asian patients than in White patients and worse control in Black patients than in White patients.

There is little research into why people with primary APS have poorer control of their CV risk factors than those with SLE-related APS, Tektonidou said. “Primary APS often sits across various medical specialties — rheumatology, hematology, obstetrics, cardiology and primary care — which may explain weaker risk factor management compared with SLE patients who are routinely followed by rheumatologists,” she said. “Although this doesn’t prove fewer visits or emergency-guided follow-up, it points to under-structured preventive care in primary APS.”

Commentary

“This paper provides timely and important data,” said Zuo of the University of Michigan. “Rheumatologists should regard APS as a high cardiovascular risk condition and incorporate structured CV prevention into routine care.”

It’s a call for rheumatologists and cardiologists to actively monitor and treat blood pressure, lipids, smoking, and BMI in patients with APS “rather than assuming another provider is addressing these issues.”

The study also indicated that primary APS warrants more proactive management, he said.

“The key finding is not which risk factors are present, but rather that SLE-related APS appears more aggressively managed despite high risk, whereas primary APS remains comparatively under-treated despite also being at substantial risk,” Zuo said.

He said CV risk control is poor in patients with APS because their doctors may typically focus on thrombosis and anticoagulation rather than preventive cardiology.

“Primary APS patients tend to be younger and appear otherwise healthy, which may reduce the urgency to check lipid profiles, screen for diabetes or prehypertension, or initiate aggressive CV prevention,” Zuo said.

He added that standard risk calculators may also underestimate autoimmune-associated risk, making clinicians less inclined to intensify treatment. “Moreover,” Zuo said, “unlike in rheumatoid arthritis or SLE, where CV risk is well recognized and integrated into routine management, there is limited evidence and no established framework for incorporating comprehensive CV risk stratification into APS care.” 

The study also highlighted limited access to clinicians with APS expertise, Zuo said. His APS program in Michigan frequently receives referrals from across the country.

Zuo noted that the study did not address additional risk conferred by specific antiphospholipid antibodies. “Many patients with APS or SLE-related APS have IgA [immunoglobulin A] anti-beta-2-GPI [glycoprotein i] or IgA anticardiolipin antibodies, which are not routinely measured,” he said.

His own group’s work has shown IgA antiphospholipid antibodies are independently associated with future atherosclerotic cardiovascular disease events. Other studies by his group, presented at the American College of Rheumatology 2024 and 2025 meetings, have shown that IgA anti-beta-2-GPI impairs function of high-density lipoprotein, promotes oxidative LDL changes, and damages vascular endothelium in mouse models.

“These antibodies therefore represent an additional, independent source of cardiovascular risk in both primary and secondary APS, underscoring the need for routine, comprehensive CV risk stratification in this population,” Zuo said.

This study was independently funded. Tektonidou reported financial relationships with AbbVie, Boehringer Ingelheim, DEMO Pharmaceuticals, Eli Lilly, Faran Pharmaceuticals, GlaxoSmithKline, and UCB. Zuo reported no relevant financial relationships.

Richard Mark Kirkner is a medical journalist based in Philadelphia.