The development and progression of coronary heart disease (CHD) is closely related to atherosclerosis, in which inflammation, vascular endothelial dysfunction, hypertension, dyslipidemia, and insulin resistance (IR) can increase the risk of atherosclerosis and thus affect the prevalence of CHD (1, 2). Presently, CHD and its clinical symptoms hold the record for the highest global morbidity and mortality rates, responsible for 32% of all deaths, ranking at the top in the worldwide disease burden, and exerting significant strain on national health finances (3–5). Prompt identification and prompt handling of CHD are crucial for directing medical professionals and lessening the worldwide impact of cardiovascular conditions.

IR, defined as reduced or impaired insulin sensitivity in insulin-dependent tissues or organs manifested by impaired glucose uptake and oxidation (6), is an important risk factor for the development of type 2 diabetes and CHD. It is part of a spectrum of cardiovascular metabolic abnormalities, often referred to as IR syndrome or metabolic syndrome, which accelerates atherosclerosis and thus the prognosis of patients with CHD (7). Overweight and obesity contribute to the development of cardiovascular disease (CVD), especially CHD (8). And, obesity is also recognized as an independent risk factor for CVD. Metabolic syndrome is closely related to CVD, including CHD, and centripetal obesity is an important component of metabolic syndrome (9).

In the absence of an effective method to accurately assess IR, the triglyceride-glucose (TyG) index, based on fasting triglyceride (TG) and blood glucose levels, has become a surrogate marker that is widely used in CVD (10–13). In contrast, the triglyceride glucose body mass index (TyG-BMI), which combines obesity measurements with the TyG index, has high sensitivity and specificity for recognizing IR, and both metrics have been validated in IR (14–16) However, the interaction between these two indices is largely underexplored in critically ill patients with CHD.

Therefore, the aim of our study was to investigate the relationship between TyG-BMI index and mortality outcomes in critically ill patients with CHD.

The present study is the first retrospective investigation to explore the association between TyG-BMI index and 365-day mortality in critically ill patients with CHD using the MIMIC IV database.

In our study, we found that medium TyG-BMI index favored the prognosis of patients and suggested an L-shaped relationship between TyG-BMI and 365-day mortality based on the RCS curve. In addition, Cox regression modeling (fully adjusted model) suggested that medium TyG-BMI index was significantly associated with 365-day mortality (HR 0.71, 95%CI 0.54-0.93, P= 0.012). These results may contribute to the development of clinical guidelines to reduce mortality in these patients.

In today’s society, the prevalence of CVD has reached epidemic levels, not only among the general population but also among diagnosed patients with coronary heart disease, where the prevalence has reached astonishing levels (17–19). The relationship between obesity and CVD has been the focus of many epidemiological studies. Commonly, numerous studies have tried to determine the relationship between obesity and the risk of CHD (9). Currently, increasing evidence suggests a significant association between obesity and CVD, especially in the occurrence of coronary heart disease. Zhou (20) et al. proposed that BMI is significantly related to the relative risk (RR) of coronary heart disease, indicating that for every 2-unit increase in BMI, the risk of coronary heart disease may increase by 23% (95% CI: 1.08-1.41). However, some studies have reported that the BMI-mortality curve generally exhibits a U-shape, where mortality from CVD only increases in extreme cases of obesity, highlighting the phenomenon of the obesity paradox (21). This may be due to higher BMI providing better protective effects and sufficient physiological reserves to resist related inflammatory responses in the body. Additionally, there is an incr (22)eased mobilization of endothelial progenitor cells in the obese population, which can promote the regeneration of damaged myocardium and the development of new blood vessels, thus protecting the cardiovascular system from atherosclerosis (23). Whereas IR is strongly associated with obesity (24, 25), with more than 70% of the obese population suffering from IR (26), overweight or obese individuals may be more susceptible to the effects of IR than low or normal weight individuals (27). IR is also a risk factor for the development of CHD, which can lead to increased platelet activity and elevated adhesion-induced expression of thromboxane A2-dependent tissue factor in platelets, leading to thrombosis and inflammation, which in turn may lead to myocardial ischemic events (28). Not only that, IR also causes sympathetic excitation and sodium retention, which aggravate the cardiac load (29). In addition, chronic hyperglycemia and dyslipidemia induced by IR can induce oxidative stress, aggravate inflammatory response, impair endothelial function, and promote the proliferation of smooth muscle cells and collagen deposition, and under the effect of these factors, the patient’s myocardium will be fibrotic, which will ultimately lead to heart failure (30, 31). Undoubtedly, IR poses a risk for the emergence and advancement of CHD. Given the link between IR and obesity, along with its intricate pathophysiology and possible origins, investigating the TyG-BMI index’s impact on CHD patients becomes essential.

IR is not only a core component of metabolic disorders, but also closely associated with dyslipidemia, metabolic syndrome, and the development of atherosclerosis, which together form an important biological basis for the development, progression, and prognosis of CHD. IR is associated with dyslipidemia in the form of hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) levels, and increased numbers of small, dense low-density lipoprotein (LDL) particles, which significantly contribute to the formation of atherosclerosis (32). In addition, IR is strongly associated with multiple risk factors for the metabolic syndrome (e.g., abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, glucose intolerance, and pro-inflammatory and pro-thrombotic states), further exacerbating the risk of cardiovascular disease. IR leads to endothelial dysfunction and cellular damage by exacerbating oxidative stress and inflammatory responses (33, 34). In obese patients, endothelial dysfunction is predominantly characterized by reduced nitric oxide (NO) bioavailability in response to inflammation and oxidative stress, which is a key component in the progression of atherosclerosis (35). The development of atherosclerosis and CHD involves two core processes, inflammation and oxidative stress (36), and IR and obesity are important drivers of these processes. Therefore, IR is inextricably linked to the onset, progression and prognosis of CHD (35, 37). In patients with established ischemic cardiomyopathy, reduced insulin activity limits glucose utilization by cardiomyocytes, forcing a shift to fatty acid metabolism (38). This metabolic shift not only increases myocardial oxygen consumption, but also reduces the compensatory capacity of the non-infarcted myocardium, thus further exacerbating the disease severity of coronary artery disease. The TyG-BMI index, as a comprehensive index combining the TyG index and the BMI, is able to reflect IR and obesity at the same time, and is superior to the single TyG index, the BMI, the conventional lipid levels or other metabolic indicators (14). Therefore, the TyG-BMI index may provide new ideas for risk stratification and individualized treatment of coronary heart disease.

The metabolic abnormalities most closely associated with IR are hyperinsulinemia, some degree of glucose intolerance, hypertriglyceridemia, and low HDL cholesterol concentrations (39). Numerous studies have demonstrated the usefulness and validity of the TyG-BMI index for the assessment of IR (40, 41). In recent investigations, the TyG-BMI index has been shown to be superior to the steady-state model IR index (42). It is important to emphasize that TyG-BMI may be useful as a simple and reliable index for assessing the risk of major adverse cardiovascular events. Cheng et al. found that the TyG-BMI index (per 1 SD) was significantly associated with the occurrence of adverse cardiovascular events in a female population undergoing percutaneous coronary intervention (OR=1.33, 95% CI 1.00-1.76, p = 0.047) (43). In a single-center retrospective study by Liu et al. it was mentioned that the risk of adverse cardiovascular events in patients undergoing percutaneous coronary intervention for ST-segment elevation myocardial infarction increased statistically significantly as the TyG-BMI index increased (p for trend = 0.038) (12). Hu et al. examined the association between the TyG-BMI index and the prognosis of 2509 patients with atrial fibrillation and found an L-shaped association between the TyG-BMI index and 365-day all-cause mortality in critically ill patients with atrial fibrillation (44). These findings suggest that the TyG-BMI index has great value in predicting CVD. Similar results were also found in our study. In the fully adjusted model (model 4), it was shown that critically ill patients with CHD who had a medium TyG-BMI index had a significant advantage in terms of 365-day prognosis, and in the Kaplan−Meier survival curves, it was demonstrated that patients with a medium TyG-BMI index had a better short- term and long-term prognosis. These results may be explained by the fact that the obesity status of patients with higher BMI attenuates the deleterious effects of IR, represented by TyG, in patients with CHD. Perhaps the ‘obesity paradox’ or ‘metabolically healthy obesity’ theory also applies to critically ill CHD patients. On the one hand, obese people have increased endothelial progenitor cells, which promote regeneration of damaged myocardium and formation of new blood vessels, thereby protecting the cardiovascular system from atherosclerosis. In a recent systematic review of cohort studies of patients with CHD, lower mortality from cardiovascular events was observed in moderately obese patients (21). Obese patients may have elevated levels of renin-angiotensin compared to patients with normal BMI, which may also improve long-term cardiovascular prognosis (45). On the other hand, some patients are a subgroup of metabolically healthy obese. Metabolically healthy obesity refers to a subgroup of obese individuals with high BMI associated with a healthy metabolic profile characterized by high insulin sensitivity, a favorable lipid profile and low levels of pro-inflammatory cytokines in plasma and adipose tissue (46, 47). In addition, metabolically healthy obese patients had lower amounts of visceral adipose tissue and liver fat than metabolically unhealthy obese patients (48), and they were at lower risk of cardiovascular events and death, with incidence rates similar to those of normal weight patients (49, 50). In previous studies, it has been found that metabolically healthy obese patients show lower values of intima-media thickness, with evidence in favor of a lower tendency towards an atherosclerotic phenotype (51), allowing myocardial function to be preserved independently of BMI or adiposity. This is why in our study we found that patients with medium TyG-BMI index had better outcomes compared to other patients. Considering the interaction of TG, Glucose, and BMI, the predictive value of the TyG-BMI index for the risk of adverse outcomes needs to focus on the combined effect of these three factors. In our study, the TyG-BMI index may prove to better reveal their interactions and synergistic effects, thus more accurately predicting the risk of death in patients with CHD, which proved to have a significant L-shaped relationship with 365-day mortality.

We found an L-shaped association between the TyG-BMI index and 365-day all-cause mortality in critically ill patients with CHD. As the TyG-BMI index increased, the mortality rate of patients tended to decrease linearly. The TyG-BMI index may serve as an effective tool for classifying and preventing the risk of developing CHD. In addition, given the obesity paradox, BMI should be of equal concern in patients with a definite diagnosis of CHD.