Age-dependent prognostic significance of metabolic markers and comorbidities in sarcoidosis: a cohort study of 707 patients

Background Sarcoidosis is a multisystem granulomatous disorder with heterogeneous clinical expression and unpredictable outcomes. Approximately one-third of patients develop chronic or progressive disease. The absence of validated prognostic biomarkers limits early risk stratification and individualized therapeutic strategies. Emerging data suggest that metabolic dysregulation may influence disease progression and survival. Objective To assess the age-stratified prognostic value of baseline uric acid, homocysteine, cardiac involvement, hypertension, and diabetes mellitus (DM) in a large sarcoidosis cohort. Methods This longitudinal study included 707 patients (mean age 53.0 ± 11.9 years; 434 men) with histologically confirmed sarcoidosis. Baseline uric acid and homocysteine were classified as elevated or normal according to laboratory reference ranges. Cardiac involvement and comorbidities were documented at initial evaluation. Patients were stratified by age (≤59 years, n=491; ≥60 years, n=216). Survival was analyzed using Kaplan–Meier curves and log-rank testing. Age-stratified logistic regression models were applied to identify independent predictors of mortality. Results Prognostic patterns differed markedly by age. In patients ≥60 years, metabolic markers were dominant survival discriminators. Elevated uric acid was the strongest predictor (p=0.001), followed by homocysteine (p=0.045) and DM (p=0.013). Uric acid showed a strong trend toward independent mortality prediction. In patients ≤59 years, clinical phenotypes and comorbidities were more influential. DM was the most significant predictor (p<0.001) and an independent determinant of mortality. Elevated homocysteine, cardiac involvement, and hypertension were also associated with reduced survival, whereas uric acid was not significant in this group. Homocysteine demonstrated consistent prognostic relevance across both age strata. Conclusions Baseline metabolic and clinical parameters exhibit significant, age-dependent prognostic value in sarcoidosis. Uric acid appears particularly relevant in older patients, while diabetes and cardiac involvement predominate in younger individuals. Homocysteine represents a robust cross-age prognostic biomarker, supporting integration of metabolic profiling into routine risk assessment.