High CTI and frailty jointly associated with greater stroke risk

In a nationwide prospective cohort study of 8,755 Chinese adults without stroke at enrollment, high levels of the C-reactive protein–triglyceride-glucose index (CTI) and a high frailty index were each independently associated with greater risk of incident stroke. The highest estimate occurred among participants with both high CTI and high frailty: their fully adjusted hazard ratio was 2.42 (95% confidence interval, 1.81–3.24) compared with the group that had low CTI and low frailty. These findings describe associations and do not establish that CTI or frailty causes stroke.

The researchers used data from the China Health and Retirement Longitudinal Study, a nationwide prospective cohort of middle-aged and older adults. They classified participants according to CTI level and frailty status and applied Cox proportional hazards models to evaluate the independent and joint associations of these measures with incident stroke. During follow-up, 515 participants developed a stroke.

In the fully adjusted model, high CTI was associated with a hazard ratio of 1.62 (95% confidence interval, 1.35–1.95), while a high frailty index was associated with a hazard ratio of 1.53 (95% confidence interval, 1.25–1.87). Joint classification revealed progressively higher stroke-risk estimates across the four groups. Relative to participants with low CTI and low frailty, those with high CTI but low frailty had a hazard ratio of 1.88 (95% confidence interval, 1.51–2.35).

Participants with low CTI but high frailty had a hazard ratio of 2.05 (95% confidence interval, 1.51–2.79), and those with both high CTI and high frailty had the largest estimate, at 2.42 (95% confidence interval, 1.81–3.24). The researchers also evaluated statistical interaction between CTI and frailty. They detected no significant interaction on the additive scale but did detect a significant interaction on the multiplicative scale.

A model that combined CTI and the frailty index performed better for predicting incident stroke than a model using either indicator alone. The reported associations were also stable across subgroup and sensitivity analyses. Together, the results indicate that assessing CTI and frailty together captured more information about stroke risk than considering either measure by itself in this population.

The study does not, however, show that changing either CTI or frailty would reduce stroke incidence. Several features limit how the findings should be interpreted. The study was observational, so potential confounding and other explanations for the observed associations cannot be excluded.

Its participants came from China and were middle-aged or older, meaning the results do not by themselves establish whether the same relationships apply to younger adults or populations in other countries. The findings nevertheless support further evaluation of joint CTI and frailty assessment as a possible approach to stroke-risk stratification.

Subject of Research: Joint associations of metabolic inflammation, frailty, and incident stroke in a Chinese prospective cohort

Article Title: Joint association of the C-reactive protein-triglyceride-glucose index and frailty with incident stroke: a nationwide prospective cohort study

Article References: Zheng, C., Yuan, Y., Yu, H., Lei, X., Zhu, Y., Jian, X., Xia, S., li, Y., Lai, X., & Zhang, L. (2026). Joint association of the C-reactive protein-triglyceride-glucose index and frailty with incident stroke: a nationwide prospective cohort study. BMC Public Health. https://doi.org/10.1186/s12889-026-28962-1

Image Credits: AI Generated

DOI: 10.1186/s12889-026-28962-1

Keywords: stroke risk, frailty, C-reactive protein, triglyceride-glucose index, metabolic inflammation, prospective cohort, risk stratification, older adults, Joint, association, C-reactive, protein-triglyceride-glucose