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.

Figure 1

Expected 10‐year evolution of the number of carotid plaques (A) for typical patients with SLE and healthy controls (HCs), (B) for typical individuals with SLE with varying numbers of cardiovascular risk factor (CVRF) targets sustainedly attained, and (C) for typical individuals with SLE with versus without DORIS remission for ≥75% of follow‐up. (A) Typical individuals are patients with SLE or HCs with baseline characteristic values (included in multivariate model 4A of plaque progression in patients with SLE vs HCs) set at the median for quantitative and at the mode for qualitative variables: no use of antihypertensives, lipid‐lowering agents or antiplatelets, Systemic Coronary Risk Evaluation 0.1, estimated glomerular filtration rate 111 mL/minutes/1.73 m², and no carotid plaques. (B) Typical individuals with SLE are patients with baseline characteristic values (included in multivariate model 5A of plaque progression in patients with SLE) set at the median for quantitative and at the mode for qualitative variables: 43 years old; no reception of antihypertensives, lipid‐lowering agents, or antiplatelets; and no DORIS remission ≥75% of follow‐up. (C) Typical individuals with SLE are patients with baseline characteristic values (included in multivariate model 5A) set at the median for quantitative and at the mode for qualitative variables: 43 years old; no reception of antihypertensives, lipid‐lowering agents, or antiplatelets; and two CVRF targets sustainedly attained during the follow‐up. DORIS, Definition of Remission in SLE; SLE, systemic lupus erythematosus.