0245: Predictors of Arterial Stiffness in Connective Tissue Diseases: Insights from the Lupus Extended Autoimmune Phenotype (LEAP) Cohort Study

Background/Purpose: Connective tissue diseases (CTDs), including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren’s disease (SjD), are associated with an increased risk of cardiovascular disease (CVD), driven by chronic inflammation and immune dysregulation. Arterial stiffness, measured by carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx), serves as a reliable marker of cardiovascular health and a predictor of adverse cardiovascular events. However, factors associated with arterial stiffness in CTD populations remain poorly defined.

This study aimed to assess arterial stiffness, measured by pulse wave velocity (PWV) and augmentation index (AIx), in individuals with CTDs including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren's disease (SjD), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease (MCTD), and/or overlap and idiopathic inflammatory myositis (IIM), compared to healthy controls (HC) and to identify factors associated with arterial stiffness in this population.

Methods: Participants from the Lupus Extended Autoimmune Phenotype (LEAP) cohort were enrolled in the study, which included patients with a diagnosis of a CTD and age- and gender-matched healthy controls. Sociodemographic data, CVD risk factors, and treatment details were collected for each participant. To identify independent associations with carotid-femoral pulse wave velocity (cfPWV) and brachial and aortic augmentation index (Aix), multivariate linear regression models were used.

Results: We enrolled 382 CTD patients (167 with SLE, 75 with SjD, 53 with UCTD, 25 with SSc, 17 with overlap/MCTD, and 17 with myositis) and 28 healthy controls. Median age was 51 ± 21 years old. 357 (93%) patients were female. SLE patients were prescribed immunosuppressive treatment, antimalarial and oral steroids treatment significantly more often (p < 0.0001) than those with other diagnoses.

Patients with SSc diagnosis had a higher cfPWV compared with other CTDs (β = 0.40, p = 0.04). Across all CTDs, increased cfPWV was associated with age (β = 0.04, p = 0.002), systolic blood pressure (SBP) (β = 0.01, p = 0.001), diastolic blood pressure (DBP) (β = 0.09, p = 0.002), and aortic AIx (β = 0.09, p < 0.0001). Aortic Aix was associated with male gender (β = 6.73, p < 0.0001), age (β = 0.32, p < 0.0001), DBP (β = 0.39, p = 0.01) and mean arterial pressure (MAP) (β = 0.73, p < 0.0001). In addition, AIx brachial (β = 0.08, p < 0.0001), cfPWV (β = 0.15, p = 0.03), and central blood pressure (β = 0.49, p < 0.0001) were positively correlated with aortic AIx. Conversely, heart rate (β = -0.44, p < 0.0001) and diastolic reflection area (β = -0.13, p < 0.0001) showed significant negative associations. Brachial AIx was associated with age (β = 0.46, p = 0.02) as was a diagnosis of SSc SSc was (β = 12.67, p = 0.03). Of note, anti-Scl70 antibodies across all CTDs had a negative association with brachial AIx (β = -1.64, p = 0.08).

Conclusion: Arterial stiffness in patients with CTDs are particularly associated with blood pressure parameters, heart rate, and a diagnosis of SSc diagnosis.