Damage Accrual in Patients with Systemic Lupus Erythematosus Predicts Mortality and Is Associated Primarily with Antiphospholipid Syndrome and Hypertension

Background/Objectives: Long-term outcomes in systemic lupus erythematosus (SLE) are largely driven by irreversible organ damage, yet the relative contribution of comorbid conditions remains insufficiently characterized. We aimed to characterize damage accrual and identify comorbidities associated with damage severity and mortality. Methods: A retrospective study of adult patients with SLE followed at a single-center (2014–2023). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was used to assess damage at last follow-up. Damage was categorized as none (0), mild–moderate (1–2), or severe (≥3). Demographic, clinical, laboratory, treatment, and comorbidity data were extracted from electronic medical records. Multivariable logistic regression and Cox proportional hazards models were applied to identify factors associated with damage severity and mortality. Results: Among 182 patients (84.1% female; mean follow-up 15.6 ± 11.4 years), 59.5% accrued damage, including 30.8% with severe damage. Damage predominantly involved cardiovascular, ocular, neuropsychiatric, and musculoskeletal domains. It was associated with older age, longer disease duration, hematologic and renal involvement, and corticosteroids and immunosuppressive medications. In multivariable analysis, antiphospholipid syndrome (APS) and hypertension emerged as the dominant independent predictors of damage accrual with an odds ratio of 15.70 (95% CI 4.26–57.89, p < 0.001) and 6.46 (95% CI 2.54–16.40, p < 0.001), respectively. Mortality increased with damage severity (16.1% in SDI ≥ 3, 1.9% in SDI 1–2, none in SDI = 0; p < 0.0001). Damage was also associated with increased hospitalizations. Conclusions: Damage accrual is common and strongly predicts mortality. APS and hypertension emerge as dominant, modifiable drivers, supporting integrated cardiovascular and thrombotic risk management in SLE.