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

Background/Objectives: Irreversible organ damage is a central determinant of long-term outcomes in systemic lupus erythematosus (SLE). We aimed to define patterns of long-term damage accrual and identify dominant predictors of damage severity and mortality in a contemporary SLE cohort. Methods: This retrospective single-center study (2014-2023) included adult patients fulfilling 2019 EULAR/ACR SLE classification criteria. Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), at last follow-up and categorized as none (0), mild–moderate (1–2), or severe (≥3). Various variables were assessed, including sociodemographic, disease-related characteristics, comorbidities, hospitalizations, emergency department visits, and all-cause mortality. Multivariable logistic regression and Cox models were applied. 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. Conclusion: 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.