In this study, we found a relationship between the TyG index and cardiovascular risk in patients with H-type hypertension combined with CHD for the first time. The results of this study are summarized as follows: (1) the incidence of adverse cardiovascular events was significantly greater in patients with a higher TyG index than in those with a lower TyG index during the established observation period; (2) The TyG index was significantly associated with MACEs after adjusting for confounders, regardless of whether it was analyzed as a continuous or categorical variable; (3) the patient's TyG index showed a nonlinear relationship with the probability of risk of MACEs and was associated with a variety of cardiovascular risk factors; and (4) the inclusion of the TyG index in the baseline model significantly enhanced the predictive efficacy of the model for Mace risk. This study demonstrated that the TyG index, as a simple and easy-to-measure method for estimating IR, can improve the accuracy and pertinence of the risk stratification of patients with H-type hypertension undergoing PCI, thereby identifying high-risk patients among them. Our findings expand the understanding of the TyG index as a tool for risk stratification and identifying individuals at higher risk of cardiovascular disease, especially in patients with dual cardiovascular disease. Most previous studies have focused on single cardiovascular diseases. Patients with multiple comorbid cardiovascular diseases, though less common, are at particularly high risk and face complex clinical challenges. Therefore, improving diagnosis and risk stratification for these patients is especially important.

Hypertension and diabetes mellitus are important and common risk factors for cardiovascular disease and can accelerate the onset and progression of coronary heart disease [25, 26]. H-type hypertension is a special type of hypertension that substantially increases the risk of coronary artery disease compared with essential hypertension and is a new risk factor for CVD [21]. In addition, a cross-sectional study revealed that H-type hypertension was significantly associated with metabolic syndrome, including IR, but failed to explain the causal relationship [19]. It has been reported that hypertension and hyperhomocysteinemia have a synergistic detrimental effect on the prognosis of patients with coronary artery disease and that the underlying mechanisms are intricate and cover multiple levels of effects, including Hcy, including participation in and exacerbation of the process of endothelial damage in blood vessels, stimulation of vascular smooth muscle proliferation, and induction of lipid metabolism disorders, as well as contributing to the coagulation system and platelet dysfunction [21]. A study of 5724 patients in the United States reported that the interaction of hypertension and plasma Hcy increased the risk of all-cause mortality and CVD death in middle-aged and older adults. For every 1 µmol/L increase in plasma Hcy in hypertensive patients, the risk of all-cause mortality and CVD mortality increased by 8% and 7%, respectively. The corrected risk ratios for all-cause and CVD deaths were 1.08 (1.06–1.10) and 1.07 (1.04–1.10), respectively [27]. Patients with H-type hypertension combined with CHD tend to have a worse prognosis. Therefore, it is particularly important to identify such patients early and stratify their risk of adverse cardiovascular events. Given prior evidence that the TyG index predicts poor outcomes in several cardiovascular diseases, we evaluated its association with the risk of cardiovascular events in our study population to investigate its predictive role.

IR is the main feature of type 2 diabetes. It is closely related to various pathological processes such as endothelial dysfunction, glucose and lipid metabolism disorder, oxidative stress and systemic inflammation, and has been proven to be a risk factor for a variety of cardiovascular events [28,29,30]. IR has been shown to promote CVD in both diabetic and nondiabetic patients and is predictive of poor CVD prognosis [31, 32]. Therefore, accurate identification of IR is clinically important for optimizing primary and secondary prevention strategies for cardiovascular risk and implementing more precise risk stratification. The glucose-triglyceride (TyG) index was first proposed in 2008 by Simental-Mendia et al. It is used mainly to identify IR in individuals with type 2 diabetes mellitus and is superior to the traditional Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in terms of accuracy and simplicity [33, 34]. With increasing research in recent years, the TyG index has been closely associated with the prognosis of heart failure, stroke, hypertension, CHD, atrial fibrillation, CKD, metabolic syndrome, atherosclerosis, etc. [35,36,37]. A large cohort study involving 15,056 patients by Xin et al. revealed that the TyG index and the risk of hypertension were positively correlated [38]. In addition, the TyG index is significantly associated with the incidence of coronary obstructive disease in hypertensive patients, and this association is independent of differences in sex, age, diabetes status, and coronary artery calcium score [39]. Several recent studies have shown that the TyG index predicts a higher risk of MACEs within 1 year in patients with hypertension combined with CHD, and that this trend is particularly pronounced in diabetic patients [17]. In a cohort study of 2531 patients, Wang et al. reported that the TyG index predicted the 3-year incidence of mortality in patients with diabetes mellitus combined with acute coronary syndrome, even after adjusting for potential confounders [40]. In patients with H-type hypertension, the TyG index was significantly correlated with the extent of coronary artery lesions, and after adjusting for the effects of relevant confounders, the TyG index was significantly correlated with the severity of coronary artery lesions [18, 41]. In addition, a registry study revealed that the TyG index can be highly accurate in assessing the risk of arterial stiffness in patients with H-type hypertension and that maintaining a low TyG index may be a preventive measure for arterial stiffness in patients with H-type hypertension [42]. In a cross-sectional study, the TyG index in postmenopausal women was significantly associated with the risk of developing H-type hypertension, with a positive linear correlation [43], which may be due to an increase in IR as well as a decrease in estrogen levels in the body. The above studies show that the TyG index has a strong ability to predict the risk of cardiovascular events, but the effect of the TyG index on the prognosis of patients with H-type hypertension combined with CHD is not clear.

In the present study, our findings revealed significant correlations between the TyG index and traditional cardiovascular risk factors (age, blood pressure, diabetes mellitus, previous history of stroke, LDL-C level, etc.). In the Cox proportional risk regression model, we applied 3 adjusted and unadjusted models for regression analysis, and almost fully adjusted Model 3 represented the most comprehensive risk prediction model and showed the predictive value of the TyG index in relation to the incidence of MACEs in patients. To confirm the reliability and stability of the findings, we performed subgroup analyses. In the subgroup analysis, we observed a significant interaction effect of the TyG index with age and LDL-C. The TyG index can be used as a prognostic indicator in elderly (> 65 years) patients with H-type hypertension combined with CHD. Age was independently associated with H-type hypertension and coronary heart disease, which was consistent with previous studies. On the one hand, with the increase of age, the metabolic function of the human body declines, including folic acid and vitamin B12, resulting in the occurrence of hypercysteinemia; In addition, aging leads to vascular endothelial dysfunction, vascular regulation of blood pressure decline, leading to hypertension, coronary heart disease and its complications [44, 45]. In addition, the predictive value of TyG-represented IR seemed to be more favorable in patients with LDL-C > 1.5 [HR (95% CI) LDL-C > 1.5 mmol/L 1.46 (1.08 to 1.97) vs LDL-C ≤ 1.5 mmol/L 2.31 (1.09 to 4.92), P for interaction = 0.035]. The formation and deposition of LDL is an important factor in coronary artery stenosis and myocardial ischemia. When LDL is subjected to oxidative stress, its structure is changed to form oxidized low-density lipoprotein, which induces the proliferation and migration of vascular smooth muscle cells. In addition, there is an interaction between LDL and Hcy, which together promote the development of atherosclerosis [46, 47]. By adding the TyG index to the established conventional hazard model, we found a significant improvement in risk prediction ability in terms of the C statistic, NRI, and IDI. In this study, in addition to the TyG index, RBC, HbA1C%, Hb, and Alb were also significantly correlated with MACEs. The RBC reflects the oxygen-carrying capacity of blood. When there are too many RBCs, they may increase blood viscosity and promote the formation of blood clots, thereby increasing the risk of cardiovascular disease. Conversely, too few RBCs may lead to hypoxia in the heart muscle, affecting heart function. HbA1C% is primarily used to assess glycemic control in diabetics, but it is susceptible to various factors such as red blood cell lifespan, anemia, and blood transfusions. Hb, an essential component of red blood cells, is responsible for transporting oxygen. Anemia can lead to hypoxia in the heart muscle, affecting heart function and thereby increasing the risk of cardiovascular disease. In addition, anemia may also cause hemodynamic changes, increasing cardiac load and further exacerbating the development of cardiovascular disease. Albumin (Alb) is primarily used for assessing the diagnosis and treatment of liver function, malnutrition, nephrotic syndrome, and other diseases. In contrast, as a new cardiovascular disease risk assessment indicator, the TyG index has the advantages of comprehensive assessment, high sensitivity, simple calculation, and wide application range. Therefore, we use it as a predictor of adverse outcomes in patients.

Notably, the critical value of the TyG index associated with poor prognosis varied across studies, largely because of the heterogeneity of the study populations. For example, in a registry study of older adults with H-type hypertension, patients with a TyG index greater than 9 were significantly associated with the risk of first stroke. This may be related to the fact that the elderly population itself has a reduced ability to metabolize blood glucose and lipids, and a lack of attention has led to undertreatment [48]. In patients with hypertension combined with coronary artery disease, a TyG index greater than 8.69 was significantly associated with a poor prognosis. This is because IR-associated pathologies are important causes of the exacerbation of hypertension and coronary artery disease [49]. The relatively low critical value of the TyG index in the population included in this study compared with the above studies may be related to the early intensification of lipid and glucose-lowering therapy for such patients in the medical center and the fact that a portion of the patients had better control of lipids and glucose prior to referral to this cardiovascular disease center.

Although the underlying mechanism by which the TyG index is associated with poor prognostic risk in patients with H-type hypertension combined with CHD has not been clarified, we hypothesized that it may be due to IR. First, IR is associated with metabolic abnormalities such as hyperglycemia, dyslipidemia, hypertension, and obesity. IR induces the production of glycosylation products and oxygen free radicals, which further triggers inflammatory responses and oxidative stress, leading to endothelial dysfunction and vascular endothelial damage [50]; IR leads to impaired insulin-related signaling pathways, which leads to hypertension and atherosclerosis; IR affects Hcy-metabolizing enzymes and insulin levels to increase Hcy levels, and increased Hcy levels promote the development of CVD; and IR leads to abnormal platelet function, including the induction of an overactive state and abnormal adhesion, and contributes to increased levels of thromboxane a2-mediated tissue factor expression [30]. These pathological factors strongly increase the likelihood of arterial thrombosis and inflammatory activity. These findings explain why a high TyG index predicts the risk of cardiovascular events in patients with H-type hypertension combined with coronary artery disease.

However, this study has some limitations. Firstly, this is a retrospective cohort study conducted in a single center in China, and the causal relationship cannot be definitively determined. The selection of samples and the collection of data are based on the specific conditions of the center, which may introduce selection bias and geographical limitations. Therefore, the external effects of the findings should be further examined; the TyG index in our study was measured only once at baseline, and we failed to consider the changes in the TyG index during the follow-up period, which may have led to biased analysis; The sample size collected in this study was limited, and further prospective multicenter studies with larger sample sizes and more time points are needed to improve reliability in the future.