Association of baseline non-severe anemia with clinical outcomes following the first recorded diagnosis of systemic sclerosis

Systemic sclerosis (SSc) carries the highest mortality among systemic autoimmune diseases, yet the prognostic significance of anemia around the time of the first recorded SSc diagnosis is unclear. We examined whether baseline anemia is associated with early mortality and complications. This retrospective matched cohort study identified female adults with a first recorded SSc diagnosis between January 2010 and December 2024 from the TriNetX Research Network. Patients were required to have at least 5 years of pre-index observation without a documented SSc diagnosis. The network comprised 140 healthcare organizations, with approximately 70% of patients in the United States across all 9 census regions and 30% at international sites. Anemia was defined as hemoglobin (Hb) ≥8.0 and <12.0 g/dL and non-anemia as ≥12.0 g/dL, measured within ±30 days of diagnosis. For the Hb-stratified analysis, the anemia cohort was categorized as Hb ≥10.0 to <12.0 g/dL or ≥8.0 to <10.0 g/dL. One-to-one propensity score matching balanced baseline characteristics, and Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). The primary outcome was all-cause mortality during days 31 to 365 among patients surviving the 30-day landmark period; secondary outcomes were sepsis, acute kidney injury, intensive care unit admission, pulmonary fibrosis, and elevated C-reactive protein (≥10 mg/L). After matching, 5410 patients remained in each cohort. Baseline anemia was significantly associated with higher 1-year mortality (HR, 2.54; 95% CI, 1.99-3.22; P < .001) and with increased risks of sepsis (HR, 3.20; 95% CI, 2.38-4.30), acute kidney injury (HR, 2.24; 95% CI, 1.80-2.78), intensive care unit admission (HR, 1.92; 95% CI, 1.47-2.51), and elevated C-reactive protein (HR, 1.55; 95% CI, 1.37-1.74; all P < .001); no significant association was observed for pulmonary fibrosis (HR, 1.06; 95% CI, 0.96-1.17; P = .229). Associations persisted in sensitivity analyses and over 3-year follow-up. Mortality risk showed a graded pattern across Hb strata (Hb ≥10.0-<12.0 g/dL: HR, 1.66; Hb ≥8.0-<10.0 g/dL: HR, 3.33). Baseline anemia was associated with increased mortality and acute systemic complications following the first recorded SSc diagnosis; these observational findings warrant prospective validation.