Triglyceride-glucose body mass index predicts prognosis in patients with ST-elevation myocardial infarction

Triglyceride glycemic-body mass index (TyG-BMI) is a simple and reliable surrogate for insulin resistance (IR). However, it is still unclear if TyG-BMI has any predictive value in patients having percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). The purpose of this study was to examine the TyG-BMI index's prognostic significance and predictive power in patients with STEMI. The study comprised a total of 2648 consecutive STEMI patients who underwent PCI. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE), defined as the combination of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization. The TyG-BMI index was formulated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2] × BMI. 193 patients in all experienced MACE over a median follow-up of 14.7 months. There was a statistically significant difference between the Kaplan–Meier survival curves for the TyG-BMI index tertiles (log-rank test, p = 0.019) for the cumulative incidence of MACE. The adjusted HRs for the incidence of MACE in the middle and highest quartiles of the TyG-BMI index compared with the lowest quartile were 1.37 (95% CI 0.92, 2.03) and 1.53 (95% CI 1.02, 2.29), respectively, in the fully adjusted Cox regression model. At six months, one year, and three years, the TyG-BMI area under the curve (AUC) for predicting MACE was 0.691, 0.666, and 0.637, respectively. Additionally, adding the TyG-BMI index to the risk prediction model enhanced outcome prediction. In STEMI patients undergoing PCI, TyG-BMI was independently linked to MACE. TyG-BMI could be a simple and solid way to assess MACE risk and prognosis.


Data collection and definitions
At the time of admission, we gathered from patients general clinical data (age, sex, height, and weight), medical history data (previous acute myocardial infarction, previous stroke, previous PCI, previous arrhythmia, family history of coronary artery disease, hypertension, diabetes mellitus, smoking, and alcohol consumption), and diagnostic data.Following a 12-h fast, patients were subjected to normal laboratory testing for blood sugar, creatinine, blood urea nitrogen (BUN), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), troponin T (TnT), and D-dimer.Angiographic data and procedure information were extracted from the medical record, including whether stenting, multivessel disease, thrombolysis, and timely PCI were performed.Moreover, we obtained echocardiographic data and information on medications at discharge (calcium channel blockers (CCB), angiotensin II receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEI), and beta-blockers.The TyG-BMI index was calculated as ln[TG(mg/dL) × FBG(mg/dL)/2] × BMI.
Patients were considered to have hypertension if they self-reported it, were taking an antihypertensive drug, or had systolic and/or diastolic blood pressure readings above 140/90 mm Hg.Patients were considered to have diabetes mellitus if they self-reported having the disease, were using insulin or oral hypoglycemic medicine, or were confirmed to fit the criteria during an examination after being admitted to the hospital.Age, Killip classification, heart rate, the presence of cardiac arrest during the visit, ST-segment deviation, serum creatinine, systolic blood pressure, and positive cardiac biomarkers were the eight factors used to create a Global Registry of Acute Coronary Events (GRACE) risk score for each patient 24 .Timely PCI was defined as coronary interventions carried out on STEMI patients within 90 min of the initial medical examination 25 .All information was gathered retroactively with the aid of standardized data collection forms.Through outpatient, readmission, or telephone contact, follow-up data was gathered.

Endpoints
Major adverse cardiovascular events, which include all-cause mortality, target vessel revascularization, nonfatal myocardial infarction, and nonfatal stroke, served as the study's main endpoint.Target vessel revascularization, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality were secondary endpoints.Fatalities

The TyG-BMI index and cardiovascular incidents
In this study, the average follow-up was 14.70 (6.00-32.43)months.Table 3 summarizes the incidence of MACE and specific incidents.A total of 193 patients (7.3%) experienced at least one MACE throughout the follow-up period.With rising the TyG-BMI index, the risk of compound MACE and nonfatal stroke rose (both p < 0.05).There were no significant differences in all-cause mortality, revascularization rate, or nonfatal myocardial infarction rate across the three groups.The incidence of composite MACE and individual events per 1000 person-years is illustrated in Fig. 2. For the cumulative incidence of MACE events, we constructed Kaplan-Meier survival curves (Fig. 3).With a higher TyG-BMI index, the cumulative incidence of MACE tended to increase (log-rank p = 0.019).
To identify characteristics connected to MACE, we utilized univariate Cox regression analysis (Supplementary Table S2).Body mass index, high blood pressure, diabetes, prior strokes, LVEF, LVEDD, BUN, LDL-C, CKMB, FPG, CCB usage, and the TyG-BMI index were discovered to be risk factors for MACE.After controlling for covariates, multivariate Cox proportional risk regression analysis revealed that the TyG-BMI index was still strongly linked with MACE occurrences (Table 4).The adjusted HRs for the incidence of MACE events in the middle and highest quartiles of the TyG-BMI index compared with the lowest quartile were 1.37 (95% CI 0.92, 2.03) and 1.53 (95% CI 1.02, 2.29), respectively, in the fully adjusted model.With the TyG-BMI index rising, the incidence of MACE rose statistically significantly (p for trend = 0.038).We also investigated the relationships between the TyG-BMI index and coronary revascularization, nonfatal myocardial infarction, nonfatal stroke, and overall mortality.The TyG-BMI index was discovered to represent an independent risk factor for nonfatal stroke.

Subgroup analysis
The value of the TyG-BMI index in predicting adverse cardiovascular events was further evaluated in different subgroups of the study population, including gender, age, smoking, alcohol consumption, timely PCI, www.nature.com/scientificreports/PCI.Furthermore, no significant interactions between these major stratification factors and the TyG-BMI index were discovered (all p interaction > 0.05).

Assessment of the prognostic effect of the TyG-BMI index
To further evaluate the TyG-BMI index's prognostic significance and predictive capability, we performed a ROC analysis, and the area under the curve at six months, one year, and three years achieved values of 0.691 (95% CI 0.622,0.759),0.666 (95% CI 0.609,0.723),and 0.637 (95% CI 0.591,0.683),respectively (Fig. 5).Table 5 presents the TyG-BMI incremental predictive values for MACE.The TyG-BMI index dramatically improved the risk classification for MACE by significantly raising the C-statistic, NRI, and IDI (all p < 0.05).

Discussion
This study is the first that we are aware of that looks at the connection between the TyG-BMI index and MACE events in STEMI patients undergoing PCI.The following was the study's main findings: (1) Independent of conventional cardiovascular risk variables, the TyG-BMI index was associated with the incidence of MACE in STEMI patients.(2) The majority of individuals who had an association between the TyG-BMI index and MACE were male, under the age of 55, smokers, abstainers from alcohol, non-hypertensives, and non-diabetics.(3) The TyG-BMI index's incorporation into prediction models improved prognostic forecasting in STEMI patients.In conclusion, our research demonstrated the TyG-BMI index's predictive significance for MACE in STEMI patients.The risk of MACE and all-cause mortality is still high in patients with STEMI, despite considerable advancements in PCI therapy over the last few decades, which have resulted in a large drop in mortality.However, prior research has concentrated on conventional cardiovascular risk variables, leaving a gap in the optimization of risk categorization for STEMI patients 26 .Metabolic syndrome, dyslipidemia, obesity, and type 2 diabetes have all been linked to insulin resistance as a significant risk factor [27][28][29] .Impaired insulin sensitivity is regarded as a key factor in the development of disorders linked to atherosclerosis, such as oxidative stress, endothelial dysfunction, inflammation, metabolic abnormalities, and hypertension [30][31][32] .Earlier research has demonstrated that IR is a significant risk factor for cardiovascular disease 33 .Obesity has a substantial correlation with IR, and the TyG index is a valid indicator of it.The TyG-BMI index has been demonstrated to be superior to other IR parameters evaluated by HOMA-IR in recent investigations 19 .As a simple replacement for IR, the TyG-BMI index has been proven to have predictive significance in coronary heart disease 34 .The TyG-BMI index's predictive significance in patients with STEMI, however, remained unknown.
Our findings in the current study demonstrated a relationship between the TyG-BMI index and other risk variables.The TyG-BMI index has been linked to prehypertension and hypertension in other research 35,36 , which is congruent with our findings.The association between the TyG-BMI index and the prognosis of STEMI patients with PCI was also revealed for the first time, which is more significant.We discovered a positive relationship between the TyG-BMI index and MACE in the study's participant group.Even though we made adjustments for all study-related risk variables, the outcome remained unchanged.However, recent research that included 2533 people who had drug-eluting stent implantation and percutaneous coronary intervention at the same time revealed no correlation between TyG-BMI and MACE 37 .Differences in the research populations and the incidence of MACE may account for this variance.According to data from a different study of 1092 acute coronary syndrome patients who underwent PCI 7 , greater TyG index values are associated with a higher risk of MACE in patients with STEMI, and the TyG index might be a reliable indicator of clinical outcomes in STEMI patients who had PCI.In terms of IR prediction, the TyG-BMI index is superior to the TyG index 19 .We demonstrated that in STEMI patients undergoing PCI, the TyG-BMI index may be a reliable predictor of MACE.By our findings, the TyG-BMI index has also been demonstrated to have an independent linear connection with ischemic stroke without a threshold or saturation effect 38 .The prediction of MACE in patients following PCI and patients with early-onset coronary artery disease was improved by the addition of the TyG index to baseline risk models, according to prior research 39 .According to our study, the TyG-BMI index added considerable additive prognostic value to predicting MACE in STEMI patients undergoing PCI.
Although the precise molecular processes behind the relationship between the TyG-BMI index and MACE are unclear, important pathways may be connected to IR in STEMI patients undergoing PCI.The traditional CVD risk factors of lipids, glucose, and obesity are included in the TyG-BMI index, which is an accurate predictor of IR.Insulin resistance tended to cause a variety of metabolic disorders, such as hyperglycemia, dyslipidemia, and hypertension, which were closely correlated with a poor prognosis of cardiovascular disease.Insulin resistance-related glycemic and dyslipidemic abnormalities can inhibit nitric oxide production, produce excessive reactive oxidative stress, and cause the deposition of matrix proteins and fibrosis, all of which exacerbate the inflammatory response, encourage the formation of foam cells, impair endothelial function, and encourage the www.nature.com/scientificreports/proliferation of smooth muscle cells 8,40 .By raising levels of tissue factor and fibrinogen activator inhibition, IR can also reduce fibrinolysis.This may enhance thrombosis in the cardiovascular system and encourage platelet aggregation 41 .Furthermore, IR increases excessive glycosylation, which promotes the proliferation of vascular smooth muscle cells as well as cross-linking and deposition of collagen, all of which contribute to cardiac fibrosis and stiffening of the diastolic left ventricle 42 .Finally, IR-induced ectopic angiotensinogen production and incorrect renin-angiotensin-aldosterone system activation result in fluid retention and hypertension, which in turn cause cardiovascular events 43 .
A large number of STEMI patients undergoing PCI were included in this research.As far as we are aware, this is the first study to look at the impact of the TyG-BMI index on the prevalence of MACE in patients with STEMI.In STEMI patients undergoing PCI, this study's findings implied that the TyG-BMI index may be a reliable indicator of clinical outcomes.This research did have certain restrictions, though.First of all, because this investigation was a single-center retrospective analysis, it is challenging to rule out the influence of some residual and unmeasured confounders, particularly the management of metabolic syndrome 44 , dietary practices, and physical activity.The study was limited in its relevance to other populations because it was restricted to Chinese patients.Therefore, more research is required to confirm these findings.Third, we only recorded baseline values for FPG, BMI, and triglyceride levels.The follow-up might have affected these indexes.It is unclear, therefore, whether variations in the TyG-BMI index can forecast cardiovascular outcomes.Fourth, it was unable to determine HOMA-IR values since the majority of the patients in this trial did not have their insulin levels assessed.Further research is required to evaluate the TyG-BMI index's predictive value with HOMA-IR since we were unable to compare the values of the two indices.Fifth, the TyG-BMI index requires access to the patient's FPG, BMI, and triglycerides, and the absence of one is not sufficient to predict MACE.Last but not least, patients' www.nature.com/scientificreports/laboratory indices were only evaluated once, which might have resulted in bias owing to measurement error.Additional multicenter, large, prospective investigations may support our findings.

Conclusion
In conclusion, STEMI patients undergoing PCI who had a high TyG-BMI index had an elevated risk of MACE.TyG-BMI index inclusion in the model exhibited an additional predictive value for MACE prediction.As a result, the TyG-BMI index may be a simple and reliable way to assess MACE risk and prognosis.

Figure 1 .
Figure 1.Flowchart of selecting patients for inclusion in the study.

Figure 2 .
Figure 2. Incidence rates per 1000 person-years of MACE, all-cause death, revascularization, non-fatal myocardial infarction, and non-fatal stroke in the study population by the TyG-BMI index.

Figure 3 .
Figure 3. Kaplan-Meier survival curve for MACE by the TyG-BMI index.

Figure 4 .
Figure 4. Subgroup analysis between MACE and the TyG-BMI index (Per SD) in various subgroups.

Figure 5 . 7 Table 5 .
Figure 5.The receiver operating characteristic curves of the TyG-BMI index to predict MACE.

Table 1 .
Baseline characteristics of the study population according to the TyG-BMI index.LVEF left ventricle ejection fraction, LVEDD left ventricular end-diastolic dimension, ACEI angiotensin II coenzyme inhibitor, ARB angiotensin II receptor blocker, CCB calcium channel blocker.
diabetes, and hypertension (Fig.4).Differences were statistically significant in the subgroup of patients who were men under 55 years of age, smokers, non-drinkers, non-hypertensive, non-diabetic, and who had timely

Table 2 .
The correlation between TyG-BMI index and baseline clinical risk factors.LVEF left ventricle ejection fraction, LVEDD left ventricular end-diastolic dimension, HDL-C high density lipoprotein cholesterol, LDL-C low density lipoprotein cholesterol, TC total cholesterol, TG triglyceride, BMI body mass index, Ccr creatinine clearance rate, SBP systolic blood pressure, DBP diastolic blood pressure, FPG Fasting plasma glucose, TnT Troponin T, CK creatine kinase.