Association of the triglyceride-glucose index with cardiovascular outcomes across cardiovascular-kidney-metabolic syndrome stages

Abstract

Background/Aims: Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay between metabolic dysfunction, chronic kidney disease, and cardiovascular disease. Insulin resistance (IR) is a key driver of CKM and is associated with adverse cardiovascular outcomes. The triglyceride-glucose (TyG) index is a cost-effective surrogate marker of IR; however, its prognostic value across CKM syndrome stages remains unclear. Methods: We conducted a retrospective cohort study using data of 1,497,913 adults enrolled in the Korean National Health Insurance Database between 2009 and 2012. The participants were stratified into four CKM stages (0/1, 2, 3, and 4) and further categorized into three TyG index tertiles: Group 1 (< 8.27), Group 2 (8.27-8.81), and Group 3 (> 8.81). The primary composite outcomes were all-cause mortality, heart failure, stroke, and myocardial infarction. Results: Over an average follow-up period of 12.6 +/- 1.50 years, individuals in the highest TyG tertile demonstrated a significantly higher risk of the composite primary outcome compared to those in the lowest tertile (hazard ratio, 1.116; 95% confidence interval, 1.101-1.131; p < 0.001). This dose-dependent relationship was consistent across CKM stages, with the strongest associations observed in the early CKM stages (0/1 and 2). An elevated TyG index is also associated with an increased risk of secondary outcomes, including all-cause death, heart failure, stroke, and myocardial infarction. Conclusions: The TyG index independently predicted cardiovascular risk across the CKM syndrome stages. Its integration into routine clinical assessments could enhance early risk stratification and guide preventive strategies, particularly for patients in the early stages of CKM syndrome.