Non-alcoholic fatty liver disease (NAFLD), a liver disease unrelated to alcohol consumption and characterized by an abnormal accumulation of fat in liver tissue, is a significant public health challenge worldwide (1). Current estimates indicate that the prevalence of NAFLD in adults approximately 20–30%; in certain populations, such as overweight or obese individuals and patients with type 2 diabetes, this proportion increases significantly and can reach 50—75%. The developmental mechanisms of NAFLD are extremely complex and include genetic predisposition, insulin resistance, chronic mild inflammatory responses and endoplasmic reticulum stress (2–4). Recent studies show a positive correlation between the TyG index and NAFLD severity. The TyG index, reflecting insulin sensitivity through triglyceride and fasting blood glucose levels, enhances our understanding of NAFLD’s pathophysiology and may provide new approaches for early detection and intervention (5–8).

Cardiovascular disease (CVD) is the leading global cause of mortality. Percutaneous coronary intervention (PCI) effectively treats coronary artery narrowing or blockage, reducing mortality and rehospitalization in acute coronary syndrome patients. Patients undergoing PCI often have metabolic disorders such as hypertension, elevated blood sugar, and lipid metabolism issues, which are closely linked to NAFLD development and progression (9, 10).

The triglyceride-glucose index (TyG), which combines fasting glucose and triglyceride levels, is a marker for insulin resistance (IR). The TyG-BMI extends this by incorporating body mass index (BMI), further clarifying the link between IR and overweight. Recent studies show that the TyG index is significantly associated with cardiovascular risks such as hypertension, hyperlipidemia, and type 2 diabetes (11–13). However, few studies have examined the predictive ability of IR for NAFLD risk in PCI patients. Thus, this study focuses on high-risk PCI patients to analyze the relationships between the TyG index and TyG-BMI and the risk of NAFLD. This is crucial for identifying high-risk patients, developing preventive strategies, and improving patient outcomes.

A growing number of studies have shown an association between the TyG index and the TyG-BMI index and NAFLD. A cross-sectional study with 1727 participants revealed that the TyG-BMI was a reliable predictor of NAFLD and moderate to severe fibrosis in U.S. adults (14). Another prospective cohort study involving 772 participants reported that the TyG index had moderate predictive value for cardiovascular events in patients with NAFLD (15). In addition, a further study with 10,390 participants revealed that the TyG-BMI was significantly associated with all-cause mortality, cardiovascular-related mortality, and diabetes-related mortality among adults with NAFLD in the United States; a more pronounced nonlinear positive association was observed among participants without progressive fibrosis (16). Taken together, these studies revealed an association between the TyG index and the TyG-BMI index with NAFLD, but it is worth noting that most of these studies recruited the general population rather than specific high-risk groups.

Coronary artery disease (CAD), the most common cardiovascular disease and a leading cause of death worldwide, is often treated with percutaneous coronary intervention (PCI). A retrospective cohort study involving 1,353 participants revealed that the TyG index can be used as a prognostic indicator of cardiovascular events after PCI (17). Another retrospective study involving 1,158 patients who had previously undergone coronary artery bypass grafting for acute coronary syndrome revealed that a higher TyG index was independently associated with an increased risk of serious adverse cardiac events (MACCEs), with a progressively stronger predictive effect of MACCEs (18). An analysis of 1,438 participants revealed a proportional association between higher TyG-BMI and an increased incidence of MACCEs in older or female patients (19).

Given the association between NAFLD and increased CVD risk, and the predictive value of the TyG index for both NAFLD and CVD, few studies have examined the predictive power of the TyG and TyG-BMI indices for NAFLD in PCI patients. The present study aims to address this gap.

The TyG and TyG-BMI indices, as markers of insulin resistance (IR), are strongly associated with the development of CHD and PCI. While the exact mechanisms are not fully understood, these indices are linked to insulin resistance, systemic inflammation, oxidative stress, lipid metabolism disorders, visceral fat accumulation, and endoplasmic reticulum stress. The TyG and TyG-BMI indices not only reflect IR but also correlate with these mechanisms, explaining the high prevalence of NAFLD in PCI patients.

Insulin resistance (IR) is defined as a reduced response to physiological insulin levels. IR is a key driver of several modern diseases, including metabolic syndrome, NAFLD, atherosclerosis, and type 2 diabetes mellitus (T2DM), playing a crucial role in their progression. IR leads to impaired glucose metabolism and organ dysfunction, particularly in the liver and heart (20). IR impairs the PI3K-NO pathway and enhances the MAPK-ET-1 pathway, leading to endothelial dysfunction, atherosclerotic plaque formation, exacerbated inflammation, and increased thrombosis risk, thereby worsening cardiovascular disease progression (21, 22). In NAFLD patients, impaired liver function fails to suppress excess glucose and fatty acid production, leading to local lipid and glucose accumulation that initiates and worsens IR. This results in systemic metabolic disorders and vascular endothelial damage, explaining the high risk of coronary heart disease in NAFLD patients.

Systemic inflammation plays a key role in the development of CAD and NAFLD. Haukeland’s analysis of high-quality serum samples from 47 NAFLD patients found that mild systemic inflammation, involving CCL2 and MCP-1, is prevalent and plays a key role in the disease process (23). Lipid accumulation in hepatocytes triggers local inflammation and immune cell activation. Activated immune cells release proinflammatory cytokines and chemokines, causing systemic inflammation. Signals from adipose tissue also activate and recruit hepatic immune cells, promoting inflammation that leads to cell damage and death, accelerating NAFLD progression (24). Therefore, systemic inflammation-induced IR increases the risk of NAFLD in CAD patients.

Dyslipidemia plays an important role in the development of coronary heart disease and non-alcoholic fatty liver disease. Atherogenic dyslipidemia, manifested by elevated plasma triglycerides, increased numbers of small, dense low-density lipoprotein (sdLDL) particles, and reduced levels of HDL-C, is prevalent in patients with varying degrees of NAFLD. These dysregulated fat stores in the liver or other tissues are often accompanied by cardiometabolic dysfunction, which increases the risk of cardiovascular events (25).

Visceral fat accumulation plays a key role in the development of CAD and NAFLD. The accumulation of visceral fat is closely associated with the chronic release of free fatty acid (FFA) into the bloodstream, which can trigger insulin resistance in the liver. Excessively produced triglycerides, sdLDL and LDL particles tend to deposit in peripheral blood vessels, contributing to the development of atherogenic dyslipidemia (26). Studies have shown that abdominal obesity is an independent risk factor for arterial disease in the upper and lower extremities (27). In addition, elevated FFA levels can directly or indirectly activate gluconeogenesis in the liver and reduce liver insulin sensitivity. A decrease in insulin sensitivity leads to an increase in the production of very low-density lipoprotein (VLDL) and a reduction in HDL cholesterol, which further accelerates the progression of atherogenic dyslipidemias (28). The accumulation of ectopic fat and the subsequent release of metabolites as well as the activation of inflammatory pathways trigger a series of pathophysiological changes both locally and systemically, which ultimately lead to the development of NAFLD and CVD (29). Visceral adipose tissue acts as an autonomous endocrine organ that secretes various adipokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). These adipokines can not only trigger chronic inflammatory reactions, but also disrupt insulin signaling in liver cells, impair insulin sensitivity and thus promote the development of atherogenic dyslipidemia and the accumulation of free fatty acid (FFA) in liver cells (30, 31). Therefore, the accumulation of lipids in peripheral tissues and the liver leads to lipotoxic stress in mitochondria and the endoplasmic reticulum, which in turn leads to alterations in mitochondrial function and increased production of reactive oxygen species (ROS) (32). On the one hand, endoplasmic reticulum imbalance and oxidative stress have been shown to influence metabolic inflammatory responses by inducing endothelial dysfunction, increasing the susceptibility of patients with NAFLD to cardiovascular events (33); on the other hand, the resulting oxidative stress also promotes lipid peroxidation of polyunsaturated fatty acids, leading to the formation of toxic aldehyde products and causing lipid damage. These oxidatively modified lipids have an increased atherogenic effects (34).

Endoplasmic reticulum stress (ERS) plays a central role in the development of coronary artery disease (CHD) and NAFLD. ERS is profoundly pathophysiologically linked to NAFLD, CHD, and IR through the induction of apoptosis. In NAFLD, hepatocyte apoptosis exacerbates the inflammatory response and fibrosis in the liver (35). In addition, ERS disrupts insulin signaling and promotes the development of IR, which is not only a key factor in the progression of NAFLD but also an independent risk factor for CHD (36, 37). In CHD patients, cardiomyocytes undergo ERS-induced apoptosis, which further compromises myocardial function and structural integrity. Thus, ERS regulates a network of apoptotic and metabolic dysregulation that tightly links NAFLD, CHD, and IR, highlighting its central role in the development of these diseases and its potential as a therapeutic target.

In summary, IR, as a core pathophysiological process in patients with NAFLD, CHD, and those undergoing PCI (20, 38), contributes to the onset and progression of these conditions through a variety of mechanisms including systemic inflammation, oxidative stress, dyslipidemia, visceral obesity, and ERS. The TyG and TyG-BMI indices, as validated tools for assessing IR, not only reflect IR status, but also closely correlate with the aforementioned pathophysiological mechanisms, explaining the correlation between these indices and the high prevalence of NAFLD in PCI patients (5, 39, 40). Therefore, an in-depth understanding of the relationships between TyG and TyG-BMI indices and these diseases is essential for identifying at-risk individuals and optimizing preventive and therapeutic strategies.

Currently, conventional methods for assessing NAFLD risk in clinical practice have notable limitations: liver enzyme levels lack sufficient sensitivity; imaging modalities such as ultrasound and FibroScan require specialized equipment and entail relatively high costs; non-invasive fibrosis scores (e.g., FIB-4, NFS, APRI), although practical, were primarily developed for fibrosis risk assessment in the general population and their applicability and diagnostic performance in the specific context of PCI patients remain to be fully validated. Furthermore, liver biopsy, the gold standard for diagnosis, is invasive and thus unsuitable for large-scale screening. In contrast, the triglyceride-glucose (TyG) index and its derivative, TyG-BMI, offer significant clinical advantages. These indices are calculated from routinely available laboratory and anthropometric data—namely fasting triglycerides, glucose, and body mass index—making them highly feasible, cost-effective, and suitable for large-scale screening and longitudinal monitoring.

Patients undergoing percutaneous coronary intervention (PCI) are typically concerned about the risk of cardiac events, such as recurrent myocardial infarction or in-stent restenosis. However, this study highlights that this population is also at high risk for non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. The TyG index is a reliable surrogate marker of insulin resistance, a central pathophysiological mechanism in the development and progression of NAFLD, thereby providing strong biological plausibility. The use of TyG-based indices could therefore facilitate large-scale screening and regular monitoring of liver disease in post-PCI patients, promoting a paradigm shift in clinical management from a “cardio-centric” approach to a more integrated “cardiometabolic and hepatic” care model.

There are several limitations to this study. First, this was a retrospective study with a limited sample size; the single-center nature and small sample size may have led to selection bias. Although a multivariable logistic regression was conducted to account for common confounding factors, the groups were not rigorously matched, and the differences between them were not adjusted for. Second, severe PCI patients requiring coronary vein bypass surgery or rheumatic heart disease were not included in this study, which may have led to an underestimation of the predictive power of the TyG and TyG-BMI indices for NAFLD. Third, the lack of liver enzyme data means that although ultrasonography is relatively accurate in detecting moderate to severe hepatic steatosis, it is less sensitive in detecting mild steatosis, which may lead to the underdiagnosis of mild NAFLD. Finally, the cross-sectional design of this study meant that although a positive correlation was found between the TyG and TyG-BMI indices and the prevalence of NAFLD in patients with PCI, no definitive conclusions could be drawn about their predictive value. Future large-scale, multicenter prospective studies are needed to further validate the predictive efficacy of the TyG and TyG-BMI indices for the risk of NAFLD in patients undergoing PCI.

In conclusion, this study demonstrated a significant association between the TyG index and the TyG-BMI and the risk of NAFLD in patients with PCI, and a positive correlation with the degree of liver fibrosis. As innovative markers of IR, the TyG index and TyG-BMI index have promising potential for wide application in primary health care facilities and community health services because of their simplicity, cost-effectiveness, and reliability. These results support the use of the TyG index and TyG-BMI index as valid tools for assessing the risk of NAFLD in patients undergoing PCI and provide a basis for follow-up studies. Future studies could validate these results with prospective cohort studies and explore additional biomarkers to improve their predictive accuracy.