Jul 2026· Anatolian journal of cardiology· 0 citations
Medicine
TL;DR
RCII exhibited an independent and positive association with CKM risk in the US and Chinese populations, with consistent dose-response and nonlinear trends, and may be a practical and integrative biomarker for identifying individuals with an increased CKM risk.
BACKGROUND
Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder manifested as the interconnected dysregulation of cardiovascular disease, chronic kidney disease, and metabolic abnormalities. Systemic inflammation was identified as an important contributor to CKM syndrome. Based on data from the National Health and Nutrition Examination Survey (NHANES), this research sought to explore associations between the inflammation burden index (IBI) and the risk of CKM syndrome (specifically stages 3-4).
METHODS
This research used data from six NHANES cycles (1999-2010). CKM stages were constructed based on the American Heart Association recommendations, with stages 3-4 classified as advanced CKM syndrome. Weighted multivariable logistic regression was used to investigate associations between IBI and CKM stages 3-4. Restricted cubic splines were employed to evaluate potential nonlinear relationships. Subgroup analyses stratified by age, sex, and body mass index were performed. Moreover, sensitivity analyses were conducted.
RESULTS
In total, 13,830 participants were included. Among them, 3322 were in CKM stages 3-4. In the fully adjusted model, IBI was positively associated with the risk of CKM stages 3-4 [odds ratio (OR) = 1.026, 95% confidence interval (CI): 1.008-1.044, P = 0.005]. In the sensitivity model excluding patients with hypertension and diabetes (Model 4), the association remained significant (OR = 1.030, 95% CI: 1.014-1.047, P < 0.001). RCS analyses further indicated a significant nonlinear dose-response relationship between IBI and the risk of CKM stages 3-4 (P for nonlinearity <0.001). This association remained reliable in subgroup and sensitivity analyses.
CONCLUSIONS
Elevated IBI is independently associated with a higher risk of CKM syndrome. As a composite inflammatory index that integrates multiple inflammatory cells and acute-phase proteins, IBI holds promise for identifying individuals at high risk for advanced CKM syndrome.
Yixuan Wu, Mei Li, Zhen Fang et al.· Metabolic Syndrome and Relat...· 0 citations
Cardiovascular-kidney-metabolic (CKM) syndrome integrates metabolic abnormalities, chronic kidney disease, and cardiovascular disease (CVD), with stages 0–3 representing a critical window for primary prevention. Whether the Chinese visceral adiposity index (CVAI) adds predictive value for CVD in this population remains uncertain.
Using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationwide prospective cohort, we included 7,539 participants with CKM stages 0–3. Incident CVD (heart disease or stroke) was the primary outcome. Cox proportional hazards models and restricted cubic splines assessed the association and dose-response relationship, and discrimination was evaluated with the AUC and censoring-adjusted time-dependent AUC, with comparisons against BMI, waist circumference, VAI, and TyG.
Over a median follow-up of 8.0 years, 1,718 incident CVD events were recorded. Each SD increase in CVAI was associated with a 19.5% higher CVD risk (HR, 1.195; 95% CI, 1.135–1.259), with a graded quartile effect (Q4 vs. Q1 HR, 1.585; 95% CI, 1.359–1.848;
P
for trend < 0.001) and a continuous dose-response relationship (
P
for nonlinearity = 0.931). Adding CVAI modestly improved discrimination (AUC, 0.640 to 0.646; DeLong
P
= 0.039), but its AUC was not superior to BMI (0.647) or waist circumference (0.646). Primary CVAI findings remained consistent across subgroup and sensitivity analyses and in competing-risk models, whereas VAI showed no significant independent association.
CVAI is independently and continuously associated with incident CVD in CKM stages 0–3 and may serve as a practical adjunctive tool for early CVD risk stratification.
Long Feng, Geng Yang, He-Song Zeng et al.· Cardiovascular Diabetology· 0 citations
The observational findings suggest that CTI is associated with long-term all-cause and cardiovascular mortality in MASLD and advanced fibrosis and may help refine early risk stratification in high-risk MASLD populations.
Hao Wang, Yifeng Zhou, Xiaoyu Cui et al.· Medicine· 0 citations
Stroke pathogenesis in Cardiovascular-Kidney-Metabolic (CKM) is driven by a complex interplay of insulin resistance (IR), systemic inflammation, and adiposity. This study investigated whether integrating adiposity-related measures with the inflammation-IR axis could refine stroke risk prediction in individuals at CKM stage 0–3. A total of 3,348 participants (aged ≥ 45) at CKM stages 0–3 were included from the China Health and Retirement Longitudinal Study (CHARLS). Baseline levels, cumulative exposures, and longitudinal changes were assessed for the original C-reactive protein-triglyceride glucose index (CTI) and seven adiposity-modified CTI indices. Associations with stroke risk were evaluated using Cox proportional hazards models, and potential non-linear relationships were examined using restricted cubic splines. Predictive performance at 3 and 5 years was assessed using fixed-horizon receiver operating characteristic (ROC) analysis. Discrimination was quantified by the area under the curve (AUC) and compared using DeLong’s test, while incremental predictive value was further evaluated using the integrated discrimination improvement (IDI) index. Mediation analysis was used to evaluate the potential role of estimated pulse wave velocity (ePWV) in these associations. Subgroup and sensitivity analyses were conducted to test result robustness, and weighted quantile sum (WQS) regression was performed to determine the relative contribution of components within CTI-related indices. During follow-up, 263 new cases of stroke were observed (7.9%). In fully adjusted models, participants in the highest tertile of all CTI-related indices had significantly increased stroke risk, with hazard ratios (HRs) ranging from 1.92 (95%CI 1.35–2.73) for original CTI to 2.52 (95%CI 1.76–3.61) for CTI-WHtR. K-means clustering of longitudinal changes identified three trajectory groups; compared with the stable group, both markedly increasing and slowly increasing trajectories of CTI and its modified indices were significantly associated with higher stroke risk. In fixed-horizon ROC analyses, the 3-year AUCs for all indices exceeded 0.70. Among baseline indices, CTI-BRI, CTI-BMI, CTI-WC, and CTI-WHtR showed significantly higher AUCs than the original CTI, whereas only CTI-BMI demonstrated a small but significant improvement in IDI over CTI (IDI = 0.0021, 95% CI 0.0004–0.0038; P = 0.012). Among cumulative indices, cumCTI-BMI and cumCTI-WHtR showed significantly higher 3-year AUCs than cumCTI. CTIs-stroke associations were stronger in advanced CKM stages (2–3). Furthermore, component analysis identified CVAI (29.0% in 2012; 29.3% in 2015) as the primary driver of predictive power. ePWV partially mediated the associations between CTI-related indices and incident stroke, with mediation proportions of 12.44%–21.20%. CTI and adiposity-modified CTI indices were independently associated with incident stroke among adults at CKM stages 0–3, especially in advanced CKM stages. Incorporating adiposity-related information provided modest and inconsistent improvement in short-term prediction, with CVAI contributing most prominently and ePWV suggesting a potential arterial stiffness pathway. These findings support the relevance of combined inflammatory, IR, and adiposity burden in stroke risk assessment, but the clinical use of complex composite indices should be balanced against screening feasibility.
Dan Yang, Yan Deng, Z. Su et al.· Cardiovascular Diabetology· 0 citations
Background Inflammation plays a critical role in the onset and progression of cardiovascular–kidney–metabolic (CKM) syndrome. However, the optimal inflammatory biomarker that simultaneously reflects disease severity and predicts future progression of CKM remains unexplored. Methods This study utilized data from three nationally representative cohorts: National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKB), and China Health and Retirement Longitudinal Study (CHARLS). In NHANES, three machine learning approaches were applied to identify the inflammatory biomarker most strongly associated with CKM stages. The association between this biomarker and CKM severity was validated in UKB and CHARLS. Its predictive value for CKM progression was examined in UKB and CHARLS with Cox proportional hazard models. Multiple sensitivity analyses were conducted to ensure the robustness of the findings. Results Among 15 circulating inflammatory biomarkers, the C‐reactive protein–triglyceride glucose index (CTI) was identified as the most informative indicator of advanced CKM risk. In the cross‐sectional analyses, 8959 participants from NHANES, 208,625 from UKB, and 8550 from CHARLS were included. After adjustment for potential confounders, higher CTI levels were consistently associated with advanced CKM across the three cohorts (NHANES: odds ratio [OR] = 1.35, 95% confidence interval (CI): 1.20–1.48; UKB: OR = 1.55, 95% CI: 1.46–1.64; CHARLS: OR = 1.42, 95% CI: 1.28–1.60). In longitudinal analyses including 186,753 participants from UKB and 3673 from CHARLS, elevated CTI levels predicted an increased risk of incident advanced CKM (UKB: HR = 1.22, 95% CI: 1.17–1.30; CHARLS: HR = 1.21, 95% CI: 1.01–1.46). Conclusions CTI emerged as the most robust inflammatory biomarker for assessing disease severity and predicting CKM progression among multiple candidates. Its reproducible associations across national cohorts support its utility for early detection and risk stratification, offering a basis to refine CKM management.
Yupeng Zeng, Huhao Feng, Haiying Cheng et al.· Mediators of Inflammation· 0 citations
Cardiovascular disease (CVD) remains a leading global cause of mortality, with metabolic and inflammatory dysregulation playing pivotal roles. The C-reactive protein-triglyceride glucose index (CTI), a novel biomarker integrating inflammation (CRP) and insulin resistance (triglyceride-glucose index), has shown promise in predicting adverse outcomes, but its associations with CVD and mortality in the general population remain unclear. The aim of this study is to explore the association of the C-reactive protein-triglyceride glucose index with cardiovascular disease and mortality. This study analyzed data from 8720 adults in the National Health and Nutrition Examination Survey (NHANES) 2001–2010. CTI was calculated as CTI 0.412 × ln(CRP [mg/L]) + [ln(TG [mg/dL] × FPG [mg/dL])]/2. Multivariable logistic regression examined the association between CTI tertiles (T1–T3) and CVD, and Cox regression assessed the relationship between CTI tertiles and cardiovascular and all-cause mortality, with adjustment for demographic, lifestyle, and clinical factors. Higher CTI tertiles were correlated with worse metabolic profiles and higher prevalence of hypertension and diabetes (P < .001). After full adjustment, the highest CTI tertile (T3) was associated with increased CVD risk (odds ratio = 1.50, 95% confidence interval [CI]: 1.18–1.92, P = .004), cardiovascular mortality (hazard ratio = 1.54, 95% CI: 1.06–2.25, P = .024), and all-cause mortality (hazard ratio = 1.53, 95% CI: 1.29–1.89, P < .001). Restricted cubic spline analysis revealed a nonlinear relationship between CTI and cardiovascular mortality, as well as all-cause mortality. Higher CTI is associated with prevalent CVD and independently predicts increased cardiovascular and all-cause mortality.
Zhenze Yu, Zihan Zhao, Mingzhuang Sun et al.· Medicine· 0 citations