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

Abstract

Objective

Cardiovascular disease (CVD) is a leading cause of death in individuals with systemic lupus erythematosus (SLE). We assessed atherosclerotic plaque progression and incident cardiovascular events in patients with SLE over a 10-year follow-up.

Methods

We prospectively analyzed 738 carotid ultrasound measurements (413 in patients with SLE and 325 in age/sex-matched healthy controls [HCs]) to assess new plaque development from baseline to 3-, 7-, and 10-year follow-up. Multivariate mixed-effects Poisson regression models examined potential predictors of plaque progression, including patient characteristics, Systemic Coronary Risk Evaluation, traditional cardiovascular risk factor (CVRF) target attainment, Definition of Remission in SLE (DORIS), medications, and persistent triple anti-phospholipid antibody (aPL) positivity during follow-up. Ten-year incident cardiovascular events were recorded, and univariate Cox regression analysis assessed potential associations.

Results

Patients with SLE had a 2.3-fold higher risk of carotid plaque progression than HCs (incidence rate ratio [IRR] 2.26, P = 0.002). Plaque progression risk in patients with SLE was reduced by 32% (IRR 0.68, P = 0.004) per each sustainedly attained CVRF target during follow-up, including blood pressure, lipids, smoking, body weight, and physical activity. DORIS achievement ≥75% of follow-up was associated with a 43% decrease in atherosclerosis progression risk (IRR 0.57, P = 0.033). Ten-year risk of incident cardiovascular events was higher in individuals with SLE than HCs (eight versus one event, permutation-based log-rank P = 0.036) and was associated with persistent triple aPL positivity.

Conclusion

Patients with SLE experience a 2.3-fold higher 10-year atherosclerosis progression risk than HCs, mitigated by sustained CVRF control and prolonged clinical remission. Persistent triple aPL positivity is associated with increased incidence of CVD events.