Predictive value of triglyceride glucose index combined with neutrophil-to-lymphocyte ratio for major adverse cardiac … – Nature.com

The prevalence and mortality of cardiovascular disease (CVD) continue to rise, and is one of the diseases threatening the health of Chinese people for a long time, of which the number of hospitalizations for acute ST-segment elevation myocardial infarction (STEMI) accounts for 86.8% of acute myocardial infarction (AMI), characterized by rapid onset, rapid progression, many complications, high mortality, and poor prognosis, and patients suffering from STEMI are more likely to develop major adverse cardiovascular events such as heart failure,high thrombus burden causing reinfarction and coronary microcirculation disturbance16,17, cardiogenic shock, stroke, and cardiac arrest than patients with other myocardial infarction types18,19. Although the establishment of chest pain centers and the workflow have continuously improved in various regions, the main means of treating the disease, percutaneous coronary intervention (PCI) treatment techniques, continue to mature. Although most patients can restore myocardial blood perfusion earlier and more timely than before, the in-hospital mortality rate of patients remains high. A significant number of patients develop MACE during hospitalization19.

During insulin resistance, the physiological utility of insulin is reduced, which leads to metabolic disorders, including blood lipids and blood glucose, triggers metabolic syndrome, and induces the progression of atherosclerosis through a variety of mechanisms, which has a strong correlation with cardiovascular risk20,21,22 and has become one of the hotspots of concern in the cardiovascular field. Kelly et al.23 demonstrated that serum TG levels were negatively correlated with insulin sensitivity, suggesting that the homeostasis between lipid metabolism and insulin efficacy is disrupted with increasing TG levels. Sanchez-Garcia A et al.24 showed that the TyG index had a sensitivity of 96% in the diagnosis of IR in a meta-analysis of 69,922 patients in 15 studies. With the continuous deepening of TyG index studies, TyG index has been confirmed to have a strong association with the gold standard test for the diagnosis of IR. Its predictive power is higher than the IR homeostasis assessment model25,26. TyG index is a simple index to evaluate IR. Several studies have confirmed that the TyG index is significantly correlated with the occurrence and prognosis of atherosclerosis27, and its predictive value for the prognosis of patients with coronary heart disease and type 2 diabetes is higher than that of glycosylated hemoglobin28.

Several studies have confirmed that the TyG index is an independent predictor of the occurrence and prognosis of cardiovascular disease26,28,29, but there is no conclusion on the cut-off value.Triglyceride-glucose indices have also previously been associated with slow coronary flow, which may also contribute to MACE events in patients during hospitalization30.Wang et al.31 showed in a 3-year observational study of 2531 ACS patients with diabetes that the TyG index, as independent of known traditional cardiovascular risk factors, had an optimal cut-off value for predicting MACE of 9.323, a sensitivity of 46.0%, and a specificity of 63.6% (95% CI 1.2011.746, P<0.05), and its predictive efficacy was not affected by treatment modality. Jin et al.32 conducted a clinical follow-up observation study of 1282 patients with stable coronary heart disease. The results showed that the TyG index level was directly proportional to the risk of cardiovascular events. The danger of cardiovascular events increased by 21.2% for each standard deviation increase in the TyG index (HR=1.212, 95% CI 1.0751.366, P<0.05).

Studies have shown that reactive immune responses mediated by neutrophils and adaptive immune responses mediated by lymphocytes run through atherosclerotic plaque rupture. After STEMI, neutrophils infiltrate into the myocardial infarction area, produce proteolytic enzymes, and oxidize vascular endothelial cells, resulting in a hypercoagulable state of the blood; at the same time, the stress response after myocardial infarction increases cortisol hormone secretion, resulting in a decrease in the number of lymphocytes, and NLR can reflect the balance between these two inflammatory cells and more accurately reflect the inflammatory state of the body than a single cell type, with a better predictive value33.

High NLR has also been associated with adverse events in multiple long-term follow-up clinical studies34. Klein33 et al. included 1892 STEMI patients from various centers and divided NLR at admission into quartiles. The fourth quartile of NLR was found to be significantly associated with shock within 30days (OR=3.64, 95% CI 2.026.54). Park et al.35 found that patients who died within five years had a higher initial NLR (6.398 vs. 4.231, P=0.004) in 326 PCI-treated STEMI patients. By regression analysis, patients with higher NLR were more likely to have MACE (OR=1.085, 95% CI 1.0021.174). A 6-year study of 6560 STEMI patients found a significant increase in cardiovascular mortality in the high NLR (>3.9) group (P<0.0001) by dividing the NLR into three equal points, and multivariate regression analysis found an independent predictor of annual mortality in the high NLR group (OR=2.85, 95% CI 1.545.26)36. Another study of elderly patients with coronary heart disease divided the NLR into four quartiles in 345 patients who were robust, reasonable, and weak and found a positive correlation between physical condition and NLR grade (r=0.169), and multivariate logistic regression analysis also found that patients in the fourth quartile of the NLR were more likely to have adverse MACE events (OR=2.894, P=0.011)37.

In this study, we found that TyG (OR: 2.906, 95% CI 1.9064.432) and NLR (OR: 1.075, 95% CI 1.0211.132) were independent risk factors for in-hospital MACE after PCI in STEMI patients by stepwise regression screening and multivariate logistic regression analysis (P<0.05).

We further divided the study into three models, namely the Grace score model (Model A), TyG combined with the NLR model (Model B), and Grace score combined with the TyG and NLR model (Model C).Model C was found to have a higher risk of MACE than Model A and Model B by adjusting for confounding factors.It is further indicated that the new model composed of TyG and NLR, model C, can further improve the risk prediction ability of the model for in-hospital MACE after PCI in STEMI patients by adding TyG to the old model with Grace score.

We further evaluate the new model's accuracy, Model C, by the net reclassification index (NRI) and integrated discriminant improvement (IDI).The results showed that the new model, model C, was compared with the old model, model A: NRI, NRI+, NRI, and IDI values were 0.5973, 0.3036, 0.2937, and 0.3583, respectively. With 95% confidence intervals excluding 0 and P values<0.001, our study further suggests that Model C is superior to the GRACE score, Model A, for the occurrence of in-hospital MACE after PCI in STEMI patients.

The area under the curve (AUC) for predicting MACE after PCI in STEMI patients using the traditional model consisting of the Grace score, Model A, was 0.749. In the traditional diagnostic model composed of Grace integral, TyG and NLR are introduced to form a new diagnostic model, namely Model C. In the new diagnostic model, ROC results showed that the AUC of the three combinations for predicting MACE after PCI in STEMI patients was 0.839. The results showed that model C was superior to model A in predicting MACE after PCI in STEMI patients and had particular significance in guiding clinical work.

In parallel, we performed DCA to assess the performance of the diagnostic model. Model C showed a better net gain than Model A, with threshold probabilities of 0.10.78. It further illustrates that Model C is superior to Model A in predicting the occurrence of MACE after PCI in STEMI patients.

However, this study has some limitations: First, it is a single-center study with a small sample size, and it is necessary to expand the sample size and combine multi-center for further research and analysis. Second, the TyG index measured in this study was calculated within 24h after admission. Its changes were not dynamically monitored after the application of lipid-lowering drugs. If the trial conditions allowed in the future, it could be observed at multiple points to reveal its dynamic evolution level affecting the occurrence of MACE in STEMI patients in the hospital.Third, this study did not collect the medication of patients before admission, and the medication of patients before admission should be further collected in detail at a later stage to further conduct a relevant study on the prognosis of patients.

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