Systemic inflammation plays a crucial role in the pathogenesis and prognosis of diabetes and cardiovascular diseases. System inflammation response index (SIRI), is an emerging biomarker designed to assess the extent of systemic inflammation. We aimed to delineate the prognostic significance of SIRI in patients with both AF and type 2 diabetes mellitus (T2DM). Utilizing the Medical Information Mart for Intensive Care IV (MIMIC-IV) (v2.2) repository, subjects divided into three groups based on the SIRI index. The primary endpoint of our study was all-cause mortality during hospitalization, with one-year mortality serving as the secondary endpoint. A cohort of 2054 AF and T2DM patients participated. COX regression analysis revealed elevated SIRI levels as an independent risk factor for both in-hospital and 1-year mortality. 192 patients died during hospitalization, and 265 died during the follow-up of 1 year. When treating the SIRI as a continuous variable, a higher SIRI was significantly associated with increased all-cause mortality both in-hospital [hazard ratio (HR) 1.015, 95%CI 1.010-1.020, P = 0.015] and 1-year (HR 1. 016, 95%CI 1.008-1.015, P = 0.012). Additionally, compared to patients with the lowest tertiles of SIRI, those with the highest tertiles of SIRI possessed significantly higher all-cause mortality both in-hospital and 1-year after multivariable adjustment, and this relationship remained pronounced in AF and T2DM patients [in-hospital mortality (HR: 1.863, 95% CI 1.189-2.918, P = 0.007); one-year mortality (HR: 2.143, 95% CI 1.621-2.831, P < 0.001)]. Our RCS analyses indicated a pronounced linear association between SIRI and mortality in T2DM (p-value for non-linear < 0.001). In AF patients with T2DM, high SIRI is an independent predictor of poor survival and may be helpful for patient's risk stratification.

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