Supplementary Material for: Cardiovascular Events in Lupus Nephritis; A Systematic Review and Meta-Analysis

Background: Systemic lupus erythematous (SLE) is known to be associated with cardiovascular events (CVE). However, the incidence of CVE has not been thoroughly investigated in lupus nephritis (LN) patients. In this meta-analysis, we aim to assess the incidence of CVE in patients with LN. Methods: We performed a literature search in PubMed, Scopus, and Web of Science database for studies reporting CVE (myocardial infarction (MI), heart failure, cerebrovascular accident (CVA) (i.e ischemic or hemorrhagic stroke, or transient ischemic attack), any cardiovascular or cerebrovascular-related disease or death) in patients with LN. In addition, subgroup analyses were conducted according to geographical locations and kidney disease status. We also separately reported the incidence rate of MI, CVA, and cardiovascular or cerebrovascular-related deaths, with CVE and MI risk in patients with LN. Results: Twenty-one records, encompassing 29489 subjects, were included. The overall CVE incidence was 9% (95% confidence interval (CI): 6%-12%). Specifically, the incidence of MI (8 studies, n= 5735), CVA (9 studies, n= 6053), and mortality attributed to any cardiovascular or cerebrovascular disease (10 studies, n= 26511) were 4% (95%CI: 2%-7%), 4% (95%CI: 2%-7%), and 5% (95%CI: 3%-7%), respectively. Geographically, patients residing in Asia exhibited a lower incidence of CVE (2.3%, 95%CI: 1.6%-3.3%) compared to those residing in North America (10.1%, 95%CI: 5.7%-17.2%) and Europe (13.3%, 95%CI: 7.6%-22.4%). Patients with LN had higher risk of CVE compared to SLE subjects (hazard ratio: 1.18, 95%CI: 1.03-1.34, P= 0.014). Conclusions: CVE occurrence among individuals with LN, is significant, and this disease entity increases CVE risk, highlighting the importance of implementing early therapeutic interventions to prevent poor outcomes.