Clinical associations and related factors of metabolic syndrome in systemic sclerosis: results from an observational multicenter study of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale).

Metabolic syndrome (MetS) has been increasingly recognised as a relevant comorbidity in systemic autoimmune diseases; however, data on its prevalence and clinical associations in systemic sclerosis (SSc) remain limited and heterogeneous. This study aimed to evaluate the prevalence of MetS in a large Italian SSc cohort and to explore its clinical, functional, and vascular associations. A cross-sectional multicenter study enrolled 613 SSc patients from 11 tertiary Rheumatology centres across Italy, fulfilling ACR/EULAR 2013 criteria. MetS was defined according to the International Harmonised 2009 Joint Interim Statement criteria. Clinical, laboratory, functional, and imaging data were collected. Comparisons were performed between MetS+ve and MetS-ve patients. Logistic regression analysis was performed to identify factors associated with MetS. Among 570 patients with complete data, MetS was identified in 8.4% (48/570). MetS+ve patients were older and more frequently had active disease according to the EScSG index (45.2% vs. 17.7%, p = 0.0001). They more commonly exhibited mild restrictive lung impairment, with a higher proportion showing FVC 70-79% (21.6% vs. 7%, p = 0.008), as well as moderately reduced DLCO. Cardiovascular involvement was more prevalent in MetS+ve patients, particularly left ventricular diastolic dysfunction (54.3% vs. 25.8%, p = 0.0001) and clinically diagnosed PAH (27.3% vs. 12.6%, p = 0.007). Moreover, advanced microvascular damage, reflected by a higher frequency of late nailfold videocapillaroscopy (NVC) pattern (38.5% vs. 23.1%, p = 0.031), was more common among MetS+ve patients. In multivariable analysis adjusted \for age and sex, active disease (OR 4.79, 95% CI 2.09-10.98; p < 0.0001) and mild lung restriction (FVC 70-79%) (OR 4.54, 95% CI 1.62-12.69; p = 0.004) remained independently associated with MetS. Systemic arterial hypertension was the most frequent component of MetS (77.1%). In this large Italian SSc cohort, MetS, although relatively infrequent, identified a distinct clinical phenotype characterised by increased disease activity, mild lung functional impairment, and more advanced microvascular damage. These findings support the clinical relevance of cardiometabolic comorbidity in SSc and highlight the importance of comprehensive metabolic assessment in routine care. Prospective studies are needed to clarify temporal relationships and underlying mechanisms.