The Role of the TyG Index in Stroke Risk Stratification Among Middle-Aged and Older Adults

Introduction

Stroke is a significant global health concern, ranking second as a cause of death and third for disability. Despite advancements in prevention and treatment, the burden of stroke continues to rise worldwide. In 2021, there were 93.8 million people living with stroke, and 11.9 million new cases were reported.¹ Research indicates that modifiable risk factors account for much of this burden, suggesting a substantial opportunity for prevention.

Insulin resistance, characterized by reduced cellular response to insulin, contributes to stroke risk by promoting atherosclerosis, altering platelet function, and causing a hypercoagulable state.⁴ The triglyceride-glucose (TyG) index, calculated using triglyceride (TG) and fasting blood glucose (FBG) levels, is a useful and easily accessible marker of insulin resistance.⁵ Studies show that a higher TyG index is associated with a greater risk of stroke.⁶⁷ This index offers a cost-effective tool for stroke risk assessment.

Metabolic syndrome, a cluster of conditions including central adiposity, hypertension, and insulin resistance, is another significant stroke risk factor.⁹ Affecting over a billion people globally, metabolic syndrome increases the risk of stroke even further.¹⁰ The TyG index primarily reflects insulin resistance and may not fully capture the vascular risk profile of metabolic syndrome patients. Thus, this study investigates how metabolic syndrome influences the association between the TyG index and stroke risk.

Study Methodology

Participants and Design

This prospective cohort study utilized data from four waves of the China Health and Retirement Longitudinal Study (CHARLS). Researchers excluded participants under 45, without fasting blood glucose or triglyceride data, and with pre-existing stroke diagnoses. The final analysis included 7,770 middle-aged and older Chinese adults.

Blood pressure, waist circumference, and blood samples were measured and analyzed following standardized protocols. The TyG index was calculated using the formula ln [TG (mg/dl) × FBG (mg/dl)/2].5 Metabolic syndrome was defined based on the International Diabetes Federation criteria, requiring at least three of the following: elevated waist circumference, high fasting triglycerides, low HDL-C, high blood pressure, or central obesity.

Statistical Analysis

Analyses included evaluating the TyG index’s association with stroke risk both continuously and categorically. Nonlinear associations were assessed using restricted cubic spline regression models, and interaction analyses were performed to examine the role of metabolic syndrome in these relationships.

Results

Baseline Characteristics

Participants had a median age of 58 years, with 46.2% being male. The median TyG index was 8.6, and 42.2% had metabolic syndrome. Those with metabolic syndrome were older, had higher BMIs, and were more likely to have heart disease, but were less likely to be male or live in urban areas.

Table 1 Baseline Characteristics of Participants by Categorized TyG Index and Metabolic Status

Stroke Incidence

Over a median follow-up of 7 years, 7.3% of participants experienced a stroke. Higher TyG indices were associated with increased stroke risk in the entire population and those without metabolic syndrome. However, this association did not hold for individuals with metabolic syndrome.

Figure 2 Kaplan-Meier analysis curve for (A) all participants, (B) participants without MetS, and (C) participants with MetS. Red line indicates participants with high TyG, and blue line indicates those with low TyG. Abbreviations: MetS, metabolic syndrome; TyG, triglyceride-glucose.

Continuous analysis confirmed that higher TyG indices were linked to increased stroke risk in those without metabolic syndrome. However, this relationship was not present in individuals with metabolic syndrome.

Figure 3 Restricted cubic spline curve adjusted for age, sex, body mass index, married status, smoking status, heart disease, and MetS for (A) all participants, (B) participants without MetS, and (C) participants with MetS. Abbreviations: MetS, metabolic syndrome; TyG, triglyceride-glucose.

Discussion

With stroke disproportionately affecting low-income and middle-income countries, the TyG index offers a promising tool for stroke risk assessment. Its affordability and simplicity make it particularly useful for resource-limited settings.

Findings indicate that individuals without metabolic syndrome benefit more from the TyG index for stroke risk stratification. In contrast, this index may not effectively identify stroke risk in individuals with metabolic syndrome. Future research should aim to develop other cost-effective methods for stroke risk assessment in metabolic syndrome patients.

Conclusion

Metabolic syndrome plays a crucial role in the association between the TyG index and stroke risk. Higher TyG indices are linked to increased stroke risk in individuals without metabolic syndrome but not in those with metabolic syndrome. The TyG index thus appears more effective for stroke risk stratification in populations without metabolic syndrome.

Data Sharing Statement

The data and study materials supporting this study are available at the CHARLS project website: http://charls.pku.edu.cn/.

Ethics Approval and Consent to Participate

All study data was deidentified and extracted from publicly available databases, exempting it from ethics approval.

Acknowledgment

The authors declare no conflicts of interest.

Funding

This study was funded by the High-Level Public Health Technical Talent Development Program.

Disclosure

The authors declare that there are no conflicts of interest.

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