Associations between the C-reactive protein-triglyceride-glucose index and its derived indices and the incidence and progression of cardiometabolic multimorbidity in participants with metabolic dysfunction-associated steatotic liver disease: a large-scale prospective cohort study

Tian, Z; Yan, X; Xue, F; Yang, J; Li, N

doi:10.1186/s12933-026-03260-7

Lipids & metabolic liver disease

Associations between the C-reactive protein-triglyceride-glucose index and its derived indices and the incidence and progression of cardiometabolic multimorbidity in participants with metabolic dysfunction-associated steatotic liver disease: a large-scale prospective cohort study

Cardiovasc DiabetolPublished 20 Jun 2026Prospective cohort study

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Authors' conclusion

CTI-related indices, particularly CTI-WHtR and CTI-WC, were significantly associated with the incidence and progression of CMM in individuals with MASLD. These indices provided modest incremental predictive value and may serve as complementary markers for risk stratification. Further external validation and clinical utility assessment are needed before their routine use in clinical practice.

Study context

Population: UK Biobank participants with MASLD and without cardiometabolic diseases (T2D, ischemic heart disease, stroke) at baseline4,219 developed cardiometabolic multimorbidity (CMM)
Participants: 109,181 participants

Exposure: CTI-related indices per 1-SD increase
Outcome: Incident cardiometabolic multimorbidity (CMM): coexistence of ≥ 2 cardiometabolic diseases (T2D, ischemic heart disease, stroke)
Follow-up: Median 16 years

Methodological detailslarge-scale, UK Biobank, multistate models, exploratory mediation analyses

Large-scale
UK Biobank
Multistate models
Exploratory mediation analyses

Main finding

As reported in the abstract

Incident CMM, HR per 1-SD increase

Hazard ratio per 1-SD increase (95% CI)P value

CTI-WHtR

1.62(1.58–1.66)

P < 0.001

CTI-WC

1.57(1.53–1.61)

P < 0.001

CTI-BMI

1.53(1.49–1.57)

P < 0.001

CTI

1.50(1.45–1.54)

P < 0.001

Per 1-SD increase, as printed

Observational data: associations, not effects.

Further findings

CMM progression (multistate transitions)

Baseline to first CMD, hazard ratios (HRs): 1.41-1.53
First CMD to CMM, HRs: 1.17-1.24
CMM to death, HRs: 1.07-1.21
Associations particularly for CTI-waist-to-height ratio (CTI-WHtR) and CTI-waist circumference (CTI-WC); subtype analyses notable for T2D incidence and ischemic heart disease (IHD)-to-CMM progression

Incremental predictive value (C-index, net reclassification improvement (NRI), integrated discrimination improvement (IDI))

Modest but statistically significant improvement over conventional model; greatest with CTI-WC and CTI-WHtR

Exploratory mediation

Glycemic, lipid, inflammatory and organ dysfunction biomarkers may partly account for associations with incident CMM

Exploratory

Original publication

Associations between the C-reactive protein-triglyceride-glucose index and its derived indices and the incidence and progression of cardiometabolic multimorbidity in participants with metabolic dysfunction-associated steatotic liver disease: a large-scale prospective cohort study. Cardiovasc Diabetol. Published 20 June 2026. doi:10.1186/s12933-026-03260-7

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