ArticleArquivos brasileiros de cardiologia2026
Investigating the Causal Role of Inflammatory Cytokines in the Development of Cardiovascular, Kidney, and Metabolic Diseases.
Article in Arquivos brasileiros de cardiologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundObservational studies have linked inflammatory cytokines to cardiometabolic disorders; however, whether these associations reflect causal effects across interconnected organ systems remains unclear.
objectivesThis Mendelian randomization (MR) study investigates causality between 91 inflammatory cytokines and multiorgan dysfunction across cardiovascular, kidney, and metabolic systems in the cardiovascular-kidney-metabolic (CKM) syndrome era.
methodsGenetic instruments associated with 91 inflammatory cytokines were obtained from the Olink Target Inflammation panel across 11 European-ancestry cohorts. The inverse variance weighting (IVW) method was considered as the main analysis, complemented by sensitivity analyses including MR-Egger and weighted median methods.
resultsGenetically predicted levels of inflammatory cytokines showed widespread causal associations across CKM-related traits. Specifically, 31 cytokines were associated with cardiovascular outcomes, 26 with kidney traits, 10 with obesity-related traits, and 21 with diabetes-related traits, yielding a total of 60 cytokines with at least one significant association. Notably, FGF5 and IL6 emerged as paradoxical regulators, exerting opposing effects across different organ systems, while MCSF was consistently identified as a pan-vascular risk amplifier for cardiovascular diseases.
conclusionsThis comprehensive MR analysis reveals substantial causal heterogeneity in inflammatory cytokine effects across cardiovascular, kidney, and metabolic systems. These findings highlight the clinical importance of tissue- and context-specific inflammatory modulation, supporting the development of precision therapeutic strategies for CKM syndrome.
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