In this study of ACS patients from a coronary care unit, 23.2% experienced MACE during one-year follow-up. After multivariable adjustment, the TyG index wasindentified as an significant linear association with MACE risk. Notably, renal function stratification revealed differential prognostic value: significant TyG-MACE associations were observed in patients with eGFR < 60 mL/min/1.73m2, whereas no such relationship was evident in those with preserved renal function (eGFR ≥ 60 mL/min/1.73m2). These findings support the use of the TyG index as a practical indicator for cardiovascular risk stratification in ACS patients, particularly for this subgroup with renal dysfunction.
The ACS cohort had a mean TyG index(8.99 ± 0.68) exceeding that reported in population-based studies such as the PURE trial[10]. This elevation may be attributed to the high prevalence of metabolic comorbidities (obesity, diabetes, dyslipidemia) in ACS patients [11, 12], which are known to increase TyG index values. Additionally, acute physiological stress during ACS hospitalization can transiently exacerbate hyperglycemia and insulin resistance [13, 14] and triglyceride metabolism [15], further increasing TyG index levels. The study showed that FT3 concentrations were decreased in the highest TyG tertile group, which is consistent with the inflammatory activation and euthyroid sick syndrome commonly observed during acute coronary events [16, 17], suggesting that an increase in the TyG index may reflect integrated metabolic-inflammatory-endocrine dysregulation in ACS pathophysiology.
The TyG index is a reliable biomarker for assessing insulin resistance, which integrates two parameters of lipid metabolism and glucose metabolism [18, 19] and has significant predictive value in identifying the risk of metabolic disorders, including type 2 diabetes, hypertension, CVDs and their progression [20–23]. Insulin resistance and hypertriglyceridemia also contribute to the occurrence and progression of renal impairment [24]. The kidney is a key organ for insulin metabolism. In the state of insulin resistance, abnormal glucose metabolism, oxidative stress, inflammatory responses, and changes in renal hemodynamics lead to increased vascular endothelial permeability, glomerular sclerosis, and tubular epithelial damage, ultimately leading to renal dysfunction [25]. Furthermore, hypertriglyceridemia promotes the development of renal artery atherosclerosis and contributes to the development of chronic renal insufficiency, regardless of the presence of diabetes [26]. Emerging evidence positions the TyG index as a prognostic marker for predicting CKD development in diabetes patients and acute kidney injury risk during coronary artery disease hospitalization [27–30]. While numerous studies have suggested that the TyG index is linked to the severity of coronary artery stenosis, in-hospital and long-term cardiovascular outcomes in ACS patients [6, 31–33], its prognostic utility across renal function strata remains underexplored. The study explored the relationship between the TyG index and long-term prognosis in ACS patients based on eGFR grouping.
Approximately 18.8% of patients with ACS experience moderate to severe renal impairment (eGFR < 60 mL/min/1.73m2) [34]. In our study, which included ACS patients in the coronary care unit, about 23% had eGFR < 60 mL/min/1.73m2. Stratified analysis based on eGFR showed that the TyG index was an independent predictor of MACE in patients with renal impairment, whereas no significant association was observed in those with preserved renal function. These findings suggest potential renal-mediated mechanisms underlying TyG-associated cardiovascular risk.
Stress-induced hyperglycemia in ACS patients is associated with both short-term and long-term adverse outcomes, demonstrating a J-shaped relationship between stress-hyperglycemia ratio and prognosis [35–37]. Concurrently, acute physiological stress elevates triglyceride levels by activating stress hormones such as cortisol and adrenaline, which increase fat breakdown and reduce triglyceride clearance. A multicenter registry study involving 14483 participants showed that elevated triglyceride levels were associated with and increased risk of death in patients with first-time ACS and a higher risk of MACE risk in patients with recurrent ACS [38].
ACS patients with renal dysfunction have multiple risk factors, including diabetes, hypertension, and atherogenic dyslipidemia. Therapeutic limitation due to renal insufficiency, including restricted use of renin-angiotensin system (RAS) inhibitors and deferred coronary angiography or revascularization increases the cardiovascular risk in this population. Furthermore, the acute physiological stress during ACS induces oxidative stress and inflammatory, which may exacerbate renal dysfunction in these patients [39]. The study found that in the subgroup with inpaired renal function, the risk of MACE increased by 43% elevated for each one standard deviation in the TyG index, while no significant association was observed in patients with preserved renal function. Notably, the study detected lower LDL-C levels in MACE patients (2.16 mmol/L vs 2.00 mmol/L, P = 0.003). This phenomenon is known as the “lipid paradox”, which may related to factors such as age, nutritional status and inflammatory state [40, 41]. This manifestation associated with advanced age, lower hemoglobin levels, and lower statin use in the MACE patients.
Stress-induced hyperglycemia is a manifestation of severe illness, and guidelines recommend a target ranges of 140–180 mg/dL (7.8–10 mmol/L) for fasting glucose in critically ill patients, reflecting accumulated evidence on stress hyperglycemia management [42]. Current research on lipid management suggests the role of endorse eicosapentaenoic acid (EPA) supplementation for high-risk cardiovascular patients with elevated triglycerides (150–499 mg/dL) despite optimized LDL-C levels, as demonstrated in the REDUCE-IT trial [43, 44]. In a recent cohort study, approximately 20.9% of ACS patients may benefit from triglyceride-lowering therapy[38]. Nevertheless, clinical equipoise persists regarding acute-phase triglyceride modulation in ACS patients, particularly given the paucity of evidence guiding therapeutic thresholds and agent selection during the post-ACS period. Our study’s integration of triglyceride and glucose metabolism biomarkers provides a framework for pharmacological interventions and dietary recommendations particularly for renal-impaired ACS patients (eGFR < 60 mL/min/1.73m2).
Certain limitations of this study should be considered. Firstly, the absence of longitudinal TyG index measurements during hospitalization precludes analysis of acute metabolic fluctuations and their prognostic implications. Secondly, our cohort included limited representation of advanced chronic kidney disease patients (eGFR < 30 mL/min/1.73m2), restricted statistical power for subgroup analyses.