Abstract
AIMS: To perform a systematic review and meta-analysis assessing the association between systemic immune-mediated diseases (SIDs) and cardiovascular death. METHODS: A systematic search of PubMed, Cochrane Library, and ClinicalTrials.gov was performed from inception through September 28, 2024. Effect measures for cardiovascular death were extracted for overall SIDs and for individual subtypes. Pre-specified sensitivity analyses and meta-regression by age, sex, and follow-up duration were conducted. The study followed MOOSE guidelines (PROSPERO-ID: CRD420251033612). RESULTS: From 76,531 records, 39 observational studies comprising 171,748 patients were included. SIDs were associated with higher cardiovascular mortality (HR 1.26; 95 % CI 1.09-1.47; p = 0.002), consistent across sensitivity analyses. Female sex significantly modified the association, whereas age and follow-up duration did not. Among SIDs subtypes, only rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and granulomatosis with polyangiitis (GPA) retained a significant association with increased cardiovascular mortality. Of 1410 adjudicated cardiovascular deaths, 1292 (91.6 %) were due to acute coronary syndrome (ACS). The pooled risk of cardiovascular death from ACS was increased by 34 % (HR 1.34; 95 % CI 1.05-1.72; p = 0.019). Heterogeneity across studies was high (I(2) = 95 %). CONCLUSIONS: SIDs were associated with an increased risk of cardiovascular death. The strongest associations were observed in SLE, GPA, RA, and among females. Although causality could not be inferred due to the observational nature and the heterogeneous cohorts of available studies, these findings underscore the need for improved risk stratification in these high-risk groups.