Study: Reducing Cardiovascular Risks Helps Lupus Patients

Patients with systemic lupus erythematosus (SLE) have a 2.3-fold higher risk of atherosclerotic plaque progression over 10 years than healthy people, but controlling traditional cardiovascular disease (CVD) risk factors and achieving long-term remission can reduce that risk, a recent paper reports.¹

Testing positive for three antiphospholipid antibodies (APLs) is associated with increased incidence of CVD events over 10 years, according to researchers from the National and Kapodistrian University of Athens (NKUA), Greece. APLs can mistakenly target the body’s own phospholipids and proteins bound to them and make blood clots more likely.

“Cardiovascular disease in lupus is driven by the cumulative burden of both disease-related and traditional cardiovascular risk factors,” notes senior author Maria Tektonidou, MD, PhD, professor of medicine and head of the Rheumatology Unit at NKUA. Disease-related risk factors include disease activity, disease duration, lupus nephritis, glucocorticoid use and the presence of antiphospholipid antibodies. Traditional risk factors include hypertension, smoking, hyperlipidemia, diabetes, obesity and sedentary lifestyles.

For patients with SLE, “it’s not enough to assess the presence of cardiovascular risk factors. We must persistently control them,” she emphasizes.

The Study

Dr. Maria Tektonidou

Dr. Tektonidou notes that when she and her co-authors began their study in 2012, it was well known that patients with lupus have greater cardiovascular risk than healthy people, but no one had studied the presence and progression of subclinical atherosclerotic plaque in patients over a long period of time. The researchers aimed not only to examine the presence of traditional CVD risk factors, such as hypertension, dyslipidemia and smoking, but also how controlling them consistently over 10 years affects the progression of atherosclerosis and incident cardiovascular events.

The researchers assessed the pro­gres­sion of atherosclerotic plaque in lupus patients over a 10-year period. They also examined the sustained achievement of treat-to-target states in SLE, including lupus low disease activity state and remission according to the Definition of Remission in SLE (DORIS), plus the persistent positivity of APLs throughout the 10-year follow-up period rather than in single point-of-time assessments, says Dr. Tektonidou.

Overall, the researchers analyzed a total of 738 carotid ultrasound measurements from 413 lupus patients and 325 age- and sex-matched controls.

All participants were white, and over 90% were women. Their median blood pressure at baseline was 116/71 mmHg among patients and 120/76 mmHg for controls. About 40% of patients and 33% of controls were current smokers. Slightly more patients had a family history of coronary artery disease (roughly 14% of patients vs. 11.7% of controls). At baseline, median low-density lipoprotein (LDL) cholesterol values measured 107.5 mg/dL for patients and 121 mg/dL for controls. Median body mass index was 24.6 for patients and 24.2 for controls.

Multivariate regression models examined potential predictors of plaque progression, including patient characteristics, systemic coronary risk evaluation and attaining traditional CVD risk factor targets. These traditional CVD targets included blood pressure below 140/90 mmHg, BMI of 25 or less, not smoking, healthy levels of blood lipids and physical activity. In addition to DORIS, other predictors studied included medications and persistent triple APL positivity during follow-up. The researchers recorded cardiovascular events over 10 years and assessed potential associations.

Findings

Lupus patients’ plaque progression was lowered by 32% with each sustainably achieved traditional cardiovascular risk-factor target. Achieving DORIS-defined remission for 75% or more of the follow-up period was associated with a 43% decrease in atherosclerosis progression risk.

Triple APL positivity—which includes lupus anti-coagulant, anti-cardiolipin and anti-beta2 glycoprotein I antibodies—increased the risk for incident cardiovascular events over the 10-year follow-up period, Dr. Tektonidou notes. This finding shows the need for early identification of APLs and managing them appropriately, the paper states.

“Among disease-related features, persistent antiphospholipid antibody positivity, particularly triple positivity, emerged as an important risk predictor for incident CVD events in our SLE cohort, recognizing a subgroup of patients at even higher risk,” she adds.

Dr. Tektonidou was surprised that seven of eight lupus patients who developed cardiovascular events during the 10-year follow-up were considered at low or moderate risk for cardiovascular disease by commonly used prediction tools. “This finding suggests carotid atherosclerotic plaque presence can improve cardiovascular risk stratification,” she says.

Dr. Tektonidou was also surprised that cumulative glucocorticoid dose, a well-established predictor of CVD events, was not correlated with plaque progression or incident CVD events. This finding may result from low disease activity and subsequently low glucocorticoid doses (a median of 0.3 mg) administered daily during follow-up, she says.

Although long-term hydroxychloroquine use has been previously associated with reduced CVD risk in individuals with SLE, “our results could not show that consistent hydroxychloroquine use throughout the 10-year follow-up protected against athero­sclerosis progression or incident CVD events,” Dr. Tektonidou says. “A possible explanation is that most of our patients used hydroxychloroquine consistently throughout follow-up.”

The small number of incident CVD events in the cohort limited the statistical power for multivariate analysis and robust associations with incident CVD events, Dr. Tektonidou says.

She plans to confirm her findings in larger, more diverse groups of SLE patients. In the meantime, Dr. Tektonidou encourages other research teams “to use longitudinal and trajectory-based analysis instead of relying on cross-sectional evaluations when assessing CVD risk in auto­immune diseases, including SLE.” Additionally, Dr. Tektonidou points to a need for reliable biomarkers to accompany clinical and imaging parameters to enhance CVD risk stratification and refine existing risk prediction tools.

Because cardiovascular disease in lupus is driven by the cumulative, long-term burden of both traditional and disease-specific factors, rheumatologists “should prioritize sustained disease remission, strict control of traditional CVD risk factors, consistent lifestyle modifications, early identification of persistent antiphospholipid antibody positivity, long-term hydroxychloroquine use and reduced glucocorticoid exposure,” Dr. Tektonidou suggests.

Deborah Levenson is a writer and editor based in College Park, Md.

Reference

1. Papazoglou N, Sfikakis PP, Tektonidou MG. Atherosclerotic plaque progression and incident cardiovascular events in a 10-year prospective study of patients with systemic lupus erythematosus: The impact of persistent cardiovascular risk factor target attainment and sustained DORIS remission. Arthritis Rheumatol. 2025 Jun;77(6):716–726.