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March 31, 2026Cardiovascular Diabetology3 citationsOpen Access

Associations of cumulative exposure and dynamic trajectories of the triglyceride–total cholesterol–body weight index with new-onset cardiometabolic multimorbidity in middle-aged and older Chinese adults: evidence from a nationwide prospective cohort study

XCXiao ChenCWC. K. A. WangQHQi Huang

Key Result

The highest tertile of cumulative triglyceride-total cholesterol-body weight index exposure was associated with a 90% increased risk of incident cardiometabolic multimorbidity compared to the lowest tertile (HR 1.90).

Key Points

  • To explore the relationship between cumulative exposure to the triglyceride–total cholesterol–body weight index and the risk of cardiometabolic multimorbidity in older adults.
  • Utilized data from the China Health and Retirement Longitudinal Study (CHARLS)
  • Employed Cox proportional hazards models for risk assessment
  • Used K-means clustering for trajectory analysis
  • Conducted sensitivity analyses including lag analysis and interval-censored survival analysis
  • Developed a nomogram prediction model based on Cox regression
  • 424 participants developed incident CMM during follow-up (8.4%)
  • Each 1-SD increase in CumTCBI was linked to an 18% higher risk of CMM (HR = 1.18)
  • Participants in the highest TCBI tertile had a 90% increased risk of CMM (HR = 1.90)
  • Identified three TCBI trajectories; high-stable group faced a 61% higher risk (HR = 1.61)
  • Nomogram demonstrated acceptable discrimination with AUC values of 0.715 and 0.694 for training and validation cohorts, respectively

Study Design

Type

Cohort (n=5,068)

Multicenter

Yes

Structured PICO

Does higher cumulative exposure to the triglyceride-total cholesterol-body weight index (TCBI) increase the risk of incident cardiometabolic multimorbidity in middle-aged and older adults?

P
Population
Middle-aged and older Chinese adults (aged 45 years and older) without pre-existing cardiometabolic multimorbidity, median age 58.00 years, 44.4% male.
I
Intervention
Higher cumulative exposure to the triglyceride-total cholesterol-body weight index (CumTCBI) and high-stable TCBI trajectories.
C
Comparator
Lowest tertile of CumTCBI or low-stable TCBI trajectory.
O
Outcome
New-onset cardiometabolic multimorbidity (CMM), defined as the first diagnosis of a second cardiometabolic disease (diabetes, heart disease, or stroke).composite

Higher cumulative exposure to the triglyceride-total cholesterol-body weight index (TCBI) and unfavorable TCBI trajectories are independently associated with an increased risk of cardiometabolic multimorbidity, providing a practical tool for early risk stratification.

Main Result

Effect estimate: HR 1.90 (95% CI 1.43-2.52)

Limitations

  • Exact dates of CMM diagnosis were not available due to the interval-censored nature of the data
  • Non-CMM mortality and loss to follow-up may act as competing events
  • Exact dates of CMM diagnosis were not available due to the interval-censored nature of the CHARLS data
  • TCBI-related laboratory measurements were only available at two time points (wave 1 and wave 3), which constrains GBTM estimates to linear trajectories

Abstract

The global prevalence of cardiometabolic multimorbidity (CMM) has created a substantial health burden. The triglyceride–total cholesterol–body weight index (TCBI), a novel and easily computed metabolic indicator, has shown a robust association with stroke and cardiovascular disease (CVD). However, research on the risk assessment of CMM remains limited. This study aims to investigate the relationships between cumulative exposure to the TCBI (CumTCBI) and its longitudinal trajectories with the risk of incident CMM in middle-aged and older adults, as well as to develop a survival-based risk prediction model. Data from the China Health and Retirement Longitudinal Study (CHARLS) were utilized. Cox proportional hazards models and restricted cubic spline (RCS) analyses were applied to evaluate the associations between CumTCBI and the risk of CMM. Trajectory patterns of TCBI were discerned through K-means clustering. Subgroup and interaction analyses were conducted. Extensive sensitivity analyses were performed, including lag analysis, complete-case analysis, trimmed RCS analysis, interval-censored survival analysis, and Fine-Gray competing risk models. The proportional hazards assumption was verified using Schoenfeld residuals test. Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were calculated to assess incremental predictive value. A survival nomogram prediction model based on Cox regression was developed, with discrimination assessed using the time-dependent area under the receiver operating characteristic curve (ROC) and clinical utility evaluated through decision curve analysis (DCA). Among 5068 participants, 424 individuals (8.4%) developed incident CMM during the follow-up period. Following multivariable adjustment, each 1-SD increase in CumTCBI was associated with an 18% higher risk of CMM (HR = 1.18, 95%CI 1.09-1.28), and the highest tertile was linked to an increased risk of CMM compared to the lowest tertile (HR = 1.90, 95% CI 1.43-2.52). A significant nonlinear dose-response relationship between CumTCBI and the riks of CMM (P for nonlinearity < 0.001). Three distinct trajectories are identified (low-stable, moderate-stable, and high-stable), with participants in the high-stable group facing a 61% greater risk of CMM than those with consistently low TCBI (HR = 1.61, 95% CI 1.10-2.36). These associations remained consistent across subgroups and were robust in all sensitivity. The proportional hazards assumption was satisfied (global P = 0.86). NRI and IDI analyses confirmed that TCBI provided incremental predictive value beyond its individual components (NRI = 0.158, P < 0.001). The nomogram prediction model exhibited acceptable discrimination (AUC: 0.715 in the training cohort and 0.694 in the validation cohort), and DCA indicated a favorable clinical net benefit. Higher cumulative TCBI exposure and unfavorable TCBI trajectories are independently associated with increased CMM risk in middle-aged and older Chinese adults. The Cox-based nomogram provides a practical tool for early risk stratification, supporting targeted preventino and personalized management of CMM.

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Cite This Study

Chen et al. (2026) conducted a cohort in Cardiometabolic multimorbidity (CMM) (n=5,068). Cumulative triglyceride-total cholesterol-body weight index (CumTCBI) vs. Lowest tertile of CumTCBI was evaluated on Incident cardiometabolic multimorbidity (CMM) (HR 1.90, 95% CI 1.43-2.52). The highest tertile of cumulative triglyceride-total cholesterol-body weight index exposure was associated with a 90% increased risk of incident cardiometabolic multimorbidity compared to the lowest tertile (HR 1.90).

synapsesocial.com/papers/69cb6556e6a8c024954b97c7https://doi.org/10.1186/s12933-026-03155-7
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