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. 2025 Jan 2;25(1):10.
doi: 10.1186/s12889-024-21131-2.

Joint association of the inflammatory marker and cardiovascular-kidney-metabolic syndrome stages with all-cause and cardiovascular disease mortality: a national prospective study

Yifei Cao #  1 , Wenfeng Wang #  1   2   3   4 , Shidong Xie  1   2   3   4 , Yanfang Xu  5   6   7   8   9 , Zishan Lin  10   11   12   13   14
Affiliations

Joint association of the inflammatory marker and cardiovascular-kidney-metabolic syndrome stages with all-cause and cardiovascular disease mortality: a national prospective study

Yifei Cao et al. BMC Public Health. .

Abstract

Background: Cardiovascular-kidney-metabolic (CKM) syndrome and systemic inflammation significantly contribute to mortality. However, the joint associations of CKM stages and systemic inflammation with all-cause and cardiovascular disease (CVD) mortality remain unclear. This study aimed to evaluate the independent and joint associations of CKM stages and systemic inflammation with all-cause and CVD mortality in a representative cohort of United States adults.

Methods: We analyzed data from 29,459 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (1999-2018). CKM stages were classified based on metabolic risk factors, CVD, and chronic kidney disease. Systemic inflammation was assessed using multiple indicators, and time-dependent ROC analysis identified the systemic inflammatory response index (SIRI) as the most effective inflammatory marker. The associations of CKM stages and SIRI with mortality were evaluated.

Results: Over a median follow-up of 109 months, 5,583 all-cause deaths and 1,843 CVD-specific deaths occurred. Both advanced CKM stages and elevated SIRI were associated with higher risks of all-cause and CVD mortality. Individuals with advanced CKM stages (Stages 3-4) and elevated SIRI (> 0.81) had the highest risks of all-cause (HR: 1.84, 95% CI: 1.65-2.05) and CVD mortality (HR: 2.50, 95% CI: 2.00-3.12). These associations were particularly pronounced in adults aged < 60 years (P for interaction < 0.001).

Conclusions: Advanced CKM stages and elevated SIRI are associated with increased risks of all-cause and CVD mortality, particularly in younger adults. These findings highlight the significance of targeted interventions to address systemic inflammation and CKM progression, potentially improving long-term outcomes in high-risk populations.

Keywords: Cardiovascular disease; Cardiovascular-kidney-metabolic syndrome; Chronic kidney disease; Obesity; Systemic inflammatory response index.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethics approval and consent to participate The National Center for Health Statistics and Ethics Review Board approved the protocol for NHANES, and all participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart detailing the selection process for eligible participants. CKM, cardiovascular-kidney-metabolic syndrome, MEC, Mobile Examination Center, PIR, family income-to-poverty ratio, HEI2015, Healthy eating index-2015
Fig. 2
Fig. 2
Kaplan-Meier curves displayed for all-cause mortality (A) and CVD mortality (B) across five CKM stages
Fig. 3
Fig. 3
The time-dependent ROC of inflammation markers for diagnosing all-cause mortality (A) and CVD mortality (B). Association between SIRI and all-cause (C) and CVD mortality (D). Adjusted for age, sex, race, marital, family income-to-poverty ratio, education, physical activity, smoke, drinking, and Healthy eating index-2015. SII, systemic immune-inflammation index; PIV, pan-immune-inflammation value; SIRI, systemic inflammatory response index; NPAR, neutrophil-percentage-to-albumin ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; AGR, albumin-to-globulin ratio
Fig. 4
Fig. 4
Joint association of CKM stages and SIRI value with all-cause mortality and CVD mortality
See this image and copyright information in PMC

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