Metabolic syndrome and its association with mortality in patients with sarcoidosis

Background Sarcoidosis is a chronic multisystem inflammatory disease with variable clinical course and prognosis. Beyond organ-specific involvement, systemic inflammation and cardiometabolic comorbidities may influence long-term outcomes. Metabolic syndrome (MetS), characterized by clustering of obesity, hypertension, dyslipidemia and insulin resistance, represents a pro-inflammatory and pro-atherogenic state whose prognostic significance in patients with sarcoidosis has not been adequately investigated. Purpose To evaluate the prevalence of metabolic syndrome in a large cohort of patients with sarcoidosis and to assess its association with all-cause and cardiovascular mortality. Methods We analyzed 707 consecutive patients with confirmed sarcoidosis. Patients were stratified according to the presence or absence of MetS. Baseline demographic characteristics, cardiometabolic risk factors, medical therapy, and cardiac involvement were recorded. The primary endpoint was all-cause mortality, and cardiovascular mortality was assessed as a secondary endpoint. Cox proportional hazards regression models were used to identify predictors of mortality. Results MetS was present in 35% of the cohort. Patients with MetS were significantly older (56.6±11.4 vs. 51.1±11.7 years, p<0.001) and more frequently male (44% vs. 35.5%, p=0.03). As expected, they had higher BMI (31.7±5.1 vs. 26.5±4.5 kg/m², p<0.001) and markedly increased prevalence of hypertension (53.6% vs. 6.1%), diabetes mellitus (29.4% vs. 3.9%), and dyslipidemia (44% vs. 20.8%) (all p<0.001). Cardiac involvement was more common among patients with MetS (29.9% vs. 22.7%, p=0.044). Angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists were more frequently prescribed in the MetS group. During a median follow-up of 48 (IQR 22-76) months, 31 died (4.4%). Patients with MetS exhibited significantly higher all-cause mortality compared with those without MetS (Figure 1, 9.3% vs. 1.7%; unadjusted HR 5.16, 95% CI 2.31-11.54, p<0.001). In multivariable analysis adjusting for age, sex, corticosteroid use, and other clinically relevant covariates, MetS remained an independent predictor of all-cause mortality (adjusted HR 4.38, 95% CI 1.68–11.37, p=0.002). Additional independent predictors included male sex (adjusted HR 5.20, 95% CI 2.19–12.33, p<0.001), increasing age (adjusted HR 1.08 per year, 95% CI 1.03–1.13, p<0.001), and corticosteroid use (adjusted HR 2.53, 95% CI 1.04–6.17, p=0.04). Cardiovascular mortality was markedly higher in patients with MetS (4.4% vs. 0.4%, Figure 2), corresponding to a nearly tenfold increased risk (HR 9.89, 95% CI 2.19-44.61, p<0.001). Conclusions Metabolic syndrome is highly prevalent in patients with sarcoidosis and is independently associated with substantially increased all-cause and cardiovascular mortality. These findings underscore the importance of cardiometabolic burden in sarcoidosis prognosis.Figure 1Figure 2