Association between systemic inflammation response index and advanced stages in U.S. cardiovascular-kidney-metabolic...

The American Heart Association introduced cardiovascular-kidney-metabolic (CKM) syndrome, a highly prevalent multistage comorbidity in the U.S. We investigated the association between the systemic inflammation response index (SIRI), a new inflammatory marker, and advanced CKM syndrome.

Using National Health and Nutrition Examination Survey data (2015-2020), we classified U.S. adults into five CKM syndrome stages (0-4). CKM syndrome stages 3 or 4 were considered advanced. The SIRI is determined by the formula: (monocyte count×neutrophil count)/lymphocyte count. Multivariable weighted logistic regression was used to assess advanced CKM syndrome risk by SIRI quartiles. Mediation analysis evaluated contributions of other inflammatory factors.

Among 10,405 CKM syndrome patients, 1,730 had advanced stages. Patients in the highest SIRI quartile had an odds ratio of 1.61 (95% confidence interval: 1.25-2.08) for being in advanced stages compared to those in the lowest quartile, with a 14% risk increase per unit rise in SIRI. Receiver operating characteristic analysis indicated SIRI had superior discriminative ability over other inflammatory indices for predicting advanced CKM syndrome. Mediation analysis revealed that high sensitivity C-reactive protein accounted for a minor proportion (4.94%) of the association between SIRI and advanced CKM syndrome, suggesting SIRI captures distinct inflammatory pathways.

Elevated SIRI independently predicted advanced CKM syndrome in U.S. adults and outperformed established inflammatory biomarkers, highlighting its clinical utility.