Inflammation–metabolism composite (CRP–triglyceride–glucose index) predicts all-cause and cardiovascular mortality in MASLD with advanced fibrosis: Evidence from a national NHANES cohort
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.
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and associated with metabolic dysfunction, systemic inflammation, and increased cardiovascular risk. The C-reactive protein–Triglyceride–Glucose Index (CTI) is a novel composite biomarker reflecting low-grade inflammation and insulin resistance. However, its prognostic value for long-term mortality in patients with MASLD and advanced fibrosis remains unclear. Therefore, this study aimed to investigate the association between CTI and the risk of all-cause and cardiovascular mortality in individuals with MASLD using a nationally representative cohort. We used data from National Health and Nutrition Examination Survey 2001 to 2018 and included 8791 adults with MASLD. Advanced fibrosis was defined by FIB-4, NAFLD Fibrosis Score, and AST-to-Platelet Ratio Index. Survey-weighted Cox models evaluated associations between CTI (per standard deviation increase) and all-cause and cardiovascular mortality. Restricted cubic splines examined dose–response patterns. Effect modification by sex, age, and race/ethnicity was assessed in stratified analyses. Over follow-up, 1806 deaths occurred. Higher CTI was independently associated with increased all-cause (HR 1.16, 95% confidence interval [CI]: 1.12–1.20) and cardiovascular mortality (HR 1.12, 95% CI: 1.04–1.20) in MASLD. Among participants with advanced fibrosis, CTI remained associated with all-cause (HR 1.14, 95% CI: 1.07–1.23) and cardiovascular mortality (HR 1.14, 95% CI: 1.01–1.29). Splines showed a U-shaped association between CTI and mortality in MASLD (nadir CTI ~7.5–7.9) but an approximately linear positive association in advanced fibrosis. Associations were stronger in women, older adults, and racial/ethnic minorities. Our observational findings suggest that CTI is associated with long-term all-cause and cardiovascular mortality in MASLD and advanced fibrosis. As a simple, integrative biomarker, CTI may help refine early risk stratification in high-risk MASLD populations.
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
Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with coronary heart disease (CHD), but convenient and effective biomarkers for identifying CHD risk in patients with MASLD remain limited. The C-reactive protein–triglyceride–glucose index (CTI) reflects both systemic inflammation and insulin resistance, and may add value to cardiovascular risk stratification. This study examined the association of CTI with the presence and severity of CHD in patients with MASLD and developed a nomogram for individualized CHD assessment. Methods This study included 611 patients with MASLD who underwent coronary angiography. Participants were classified according to coronary angiography findings. Logistic regression was first performed to assess the association between CTI and CHD, followed by subgroup and restricted cubic spline (RCS) analyses. Among patients with CHD, the association between CTI and coronary lesion severity was assessed. Receiver operating characteristic (ROC) analysis and DeLong’s test were applied to compare the discriminative performance of CTI with other simple insulin resistance-related indices. Independent predictors of CHD were identified using the least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, and a nomogram model was subsequently established and internally validated. Results Among the 611 patients with MASLD, 387 (63.3%) had CHD. CTI was independently associated with odds of CHD (OR 2.48, 95% CI 1.69–3.63, P < 0.001) and higher CTI levels corresponded to greater coronary stenosis severity. The association between CTI and CHD was generally stable across common subgroups, but it was stronger in patients aged ≥55 years. CTI showed significantly better discriminative ability for CHD than other simple indices of insulin resistance. Smoking status, age, neutrophils (NEUT), non-high-density lipoprotein cholesterol (non-HDL-C), serum albumin (ALB), CTI, and subclinical carotid atherosclerosis (SCAS) were included in the final nomogram. The AUC was 0.845 (95% CI 0.815–0.876), indicating good discrimination for CHD. Conclusions Higher CTI was associated with CHD presence and greater coronary lesion burden among MASLD patients. The nomogram may help identify patients who warrant further cardiovascular evaluation.
Kaiyu Shen, Jiajia Zhao, Kunkun Li et al.· Frontiers in Endocrinology· 0 citations
Background: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. The C-reactive protein–triglyceride–glucose (CTI) index captures metabolic inflammation and insulin resistance, while obesity indices reflect adiposity-related cardiometabolic risk. However, the predictive value of combining CTI with obesity indices for CVD remains unclear. Objectives: To examine the prognostic utility of CTI combined with established and novel obesity indicators for CVD, and to benchmark their predictive efficacy. Design: Nationally representative prospective cohort study. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative prospective cohort, 7847 adults aged 45 years and above without baseline CVD were enrolled. CTI was calculated from C-reactive protein, fasting blood glucose, and triglycerides (TG); each obesity index was combined with CTI to form composite parameters (CTI-body mass index (CTI-BMI), CTI-waist circumference (CTI-WC), CTI-waist-to-height ratio (CTI-WHtR), CTI-body roundness index (CTI-BRI), CTI-weight-adjusted waist index (CTI-WWI), CTI-Chinese visceral adiposity index (CTI-CVAI), CTI-a body shape index (CTI-ABSI)). We employed Cox proportional hazard models, restricted cubic spline analyses, Kaplan–Meier survival plots, ROC curve evaluations, and weighted quantile sum (WQS) regression to examine the links and prognostic utility of each metric with incident CVD across baseline and cumulative exposure tiers. Results: Over a 9-year follow-up period, 1938 new-onset CVD cases were documented. Following multivariable adjustment, each CTI-obesity composite metric showed a significant positive link to CVD risk (p < 0.05). Moreover, all CTI‑obesity composite parameters showed stronger associations with CVD than CTI alone. CTI‑CVAI demonstrated the relatively best predictive accuracy among the evaluated indices, though absolute discriminatory ability remained modest (baseline area under the ROC curve (AUC): 0.596; cumulative AUC: 0.600). Trajectory clustering found that, versus the well-managed group, the poorly managed subgroup had 21%–71% higher CVD risk (max 71% for CTI-WC). WQS regression indicated that CRP and obesity indices (especially CVAI) were the major contributors in the mixed exposure; cumulative exposure WQS analysis showed that cumulative TG and cumulative obesity parameters contributed the most. Conclusion: CTI combined with obesity indices, particularly CTI-CVAI, was associated with modestly improved predictive ability for CVD risk compared with CTI alone. This parameter may offer incremental information for CVD risk stratification by integrating metabolic inflammation and visceral fat markers.
Mengjie Zhao, Xujie Wang, Xuexue Zhang et al.· Therapeutic Advances in Endo...· 0 citations
Objective Advanced cardiovascular–kidney–metabolic (CKM) syndrome corresponds to an elevated risk of mortality. The C‐reactive protein–triglyceride glucose index (CTI) reflects both insulin resistance and inflammation, processes that are crucial to CKM progression. However, it remains uncertain whether CTI is linked to mortality risk and how this relationship may vary across different CKM progression stages. Methods A total of 8314 participants were drawn from American adults. Participants were then grouped by advanced CKM stages. CTI was calculated as 0.412 × Ln (CRP [mg/L]) + Ln (TG [mg/dl] × FBG [mg/dl])/2. The endpoints focused on all‐cause and cardiovascular mortality. Associations of CTI with advanced CKM stages and mortality were examined using logistic and Cox regression models, respectively. Results The highest CTI quartile (Q4) exhibited a markedly greater prevalence of advanced CKM stages relative to Q1 (p < 0.001). During a median follow‐up of 152 months, 1606 participants died, including 475 cardiovascular deaths. Each SD increase in CTI was associated with a 35% higher risk of all‐cause mortality (95% CI: 1.24–1.48) and a 40% higher risk of cardiovascular mortality (95% CI: 1.20–1.62). Similarly, compared with Q1, participants in Q4 of CTI had higher risks of all‐cause mortality (HR = 1.82, 95% CI: 1.46–2.27) and cardiovascular mortality (HR = 2.29, 95% CI: 1.56–3.34), with homogeneous associations across different CKM stages (interaction p > 0.05). Conclusion Higher CTI levels were accompanied by a greater prevalence of advanced CKM stages and were associated with increased risks of all‐cause and cardiovascular mortality across CKM stages. CTI may provide complementary information for mortality‐risk assessment although further validation is needed.
Siqi Yi, W. Qiu, Yanchen Zhu et al.· International Journal of End...· 0 citations
Background Patients with cardiovascular-kidney-metabolic (CKM) syndrome have high mortality risk. The C-reactive protein–triglyceride glucose index (CTI) integrates inflammation and insulin resistance, yet its stage-specific prognostic value is undefined. Methods and results This retrospective cohort study included 8,632 CKM patients (2020–2025), stratified by CTI quartiles. All-cause mortality was assessed using adjusted Cox models. Among 860 deaths (10.0%), CTI was an independent mortality predictor in both stage 0–3 (HR 1.68, 95% CI 1.30–2.18) and stage 4 CKM (HR 1.54, 1.33–1.77). Compared with Q1, Q4 patients had significantly higher risk (stage 0–3: HR 4.57, 2.32–8.99; stage 4: HR 2.26, 1.64–3.13). A linear dose-response relationship was confirmed (P for nonlinear >0.05). CTI showed superior 1-year predictive performance over TyG index (AUC: stage 0–3, 0.73 vs. 0.62; stage 4, 0.69 vs. 0.51). Conclusion CTI is a potent, independent predictor of all-cause mortality in CKM, with a linear dose-response relationship. By integrating inflammatory and metabolic pathways, it provides superior risk stratification over TyG index, highlighting its clinical utility.
Jiacai Lin, Shaobin Qiu, Shuling Su et al.· Frontiers in Cardiovascular...· 0 citations
Objective The triglyceride-glucose (TyG) index has been explored as a prognostic marker in chronic kidney disease (CKD), but it does not capture the complex interplay of metabolic dysfunction and chronic inflammation inherent to CKD pathogenesis. This study aimed to explore the associations between TyG-derived inflammatory indices and the risks of all-cause and cardiovascular disease (CVD) mortality in patients with CKD. Methods This retrospective cohort study included adults with CKD from the National Health and Nutrition Examination Survey (NHANES) 1999–2018, with mortality follow-up through December 2019. The associations of the TyG index and five TyG-derived inflammatory indices (TyG-NLR, TyG-MLR, TyG-lgPLR, TyG-lgSII, and TyG-SIRI) with mortality risk were evaluated using receiver operating characteristic (ROC) curves and survey-weighted Cox proportional hazards regression models. Results A total of 3,534 patients with CKD were included. TyG-MLR showed the highest area under the ROC curve (AUC) among the evaluated indices, with an AUC of 0.66 for all-cause mortality and 0.68 for CVD mortality. After stratification by TyG-MLR quartiles (Q1–Q4), patients in the Q4 group had an estimated 3.3-year reduction in life expectancy at the age of 45 compared with the Q1 group. Conclusions This study suggests that TyG-derived inflammatory indices may hold clinical value in predicting mortality risk among patients with CKD. In the first systematic comparison of multiple such indices, TyG-MLR emerged as the best-performing indicator, although its discriminative performance was moderate. Prospective validation in independent cohorts is warranted.
Rong-Wen Lin, Hui-Juan Zhao, Bo Wu· Science in progress· 0 citations
