Abstract
Background:
Triglyceride-glucose (TyG) index has been increasingly studied as a simple and reliable predictor of adverse events of some cardiovascular disorders. However, its prognostic effect on postoperative outcomes in patients with abdominal aortic aneurysm (AAA) is still unknown. The current study aimed to explore the potential role of TyG index in predicting mortality of AAA patients following endovascular aneurysm repair (EVAR).
Materials and methods:
This retrospective cohort study analyzed the preoperative TyG index in a total of 188 AAA patients who underwent EVAR with the follow-up of 5 years. Data were analyzed with SPSS software Version 23.0. Association between the TyG index and all-cause mortality was evaluated using Cox regression models and Kaplan-Meier method.
Results:
Cox regression analyses showed that per 1-unit increment of TyG index was significantly associated with an increased risk of postoperative 30-day, 1-year, 3-year, and 5-year mortality, even after adjustment for potential confounders (all P<0.05). Kaplan-Meier analysis suggested that patients with high TyG index (≥8.68) had a worse overall survival (P = 0.007).
Conclusion:
The elevated TyG index could be a promising predictive factor of postoperative mortality in AAA patients after EVAR.
Introduction
Abdominal aortic aneurysm (AAA) is an irreversible progressive widening of the abdominal aorta and endovascular aneurysm repair (EVAR) intervention is regarded as a safe and effective method of treating AAA (1). Reliable preoperative risk factor detection makes it possible to early predict poor outcomes of AAA patients after surgery in clinical practice. The triglyceride-glucose (TyG) index, a product of fasting triglyceride (TG) and fasting plasma glucose (FPG), is considered to be a simple, cost-effective, valid and reliable surrogate marker for insulin resistance (IR) (2, 3). IR plays a crucial role in the pathogenesis of cardiovascular disease and has been established as a predictor of elevated mortality (4). Recently, several investigations discovered that the high TyG index might be an independent risk factor for all-cause mortality in patients with a variety of cardiovascular disorders (5, 6). For example, acute myocardial infarction and coronary angiography patients with a high TyG index owned a higher risk of all-cause mortality (5). Survival of AAA patients following EVAR may be influenced by age, some inflammatory biomarkers such as white blood cell (WBC) and C-reactive protein (CRP), and comorbidities like diabetes, renal insufficiency and stroke (7, 8). However, the predictive value of TyG index on early and late mortality of AAA patients after EVAR surgery remains unclear.
In this research, we intended to examine whether there was an association between the TyG index and all-cause mortality in AAA patients who received EVAR treatment. Our results may provide ideas for improving AAA risk stratification and clinical decision-making.
Materials and methods
This retrospective cohort study included 188 AAA patients undergoing EVAR in the First Hospital of China Medical University between February 2015 and November 2017. All patients were diagnosed by computed tomography angiography and successfully followed up for 5 years with complete preoperative fasting TG and FPG levels obtained upon hospital admission. The TyG index was calculated with the following formula: TyG index = Ln [fasting TG (mg/dL) × FPG (mg/dL)/2] (9). The subjects with previous aortic surgery, congenital disorder, malignant tumor, hematological disease or unavailable survival time were excluded. Baseline demographics, clinical information and laboratory data were obtained from hospital electronic medical records. A clinical follow-up was performed via telephone or medical records, and the primary outcomes were all-cause mortality during the follow-up period (30 days, 1 year, 3 years, and 5 years after EVAR). We completed the last follow-up visits on November 8, 2022. The study was approved by the Ethics Committee of the First Hospital of China Medical University (Shenyang, China).
Analyses were conducted with SPSS software Version 23.0. Categorical variables were reported in numbers and percentages and continuous variables were expressed as mean ± standard deviation. The differences of TyG index between groups were analyzed using Student's t-test. Univariate Cox regression analyses were utilized to identify the factors associated with mortality and variables with univariate P < 0.10 were included in the multivariate model for adjustment. We applied the unadjusted and adjusted Cox proportional hazards model to estimate the correlation between TyG index and all-cause mortality, and results were described by hazard ratios (HRs) with 95% confidence intervals (CIs). The optimal cut-point for the TyG index was determined based upon receiver operating characteristic (ROC) analysis. Kaplan-Meier survival analysis with the log-rank test was carried out to estimate the cumulative probability of survival. The statistical significance was defined as a P-value (two-sided) < 0.05.
Results
During the follow-up period of 5 years, a total of 42 patients died with an overall mortality rate of 22.3%. Patients who died had a higher preoperative TyG index than those who survived (8.88 ± 0.80 vs. 8.56 ± 0.59, P = 0.004). As presented in Table 1, body mass index (BMI), heart rate, diabetes, WBC and CRP were possible risk factors for 30-day mortality in AAA patients after EVAR. Meanwhile, age, stroke, renal insufficiency, diabetes, WBC and CRP might be related to 1-year mortality, and age, diabetes, WBC, D-dimer and CRP were potential confounding factors for 3- and 5- year mortality.
Table 1
| Variable | AAA patients (n = 188) | 30-day mortality (n = 10) | 1-year mortality (n = 25) | 3-year mortality (n = 37) | 5-year mortality (n = 42) | ||||
|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | Pvalue | HR (95% CI) | Pvalue | HR (95% CI) | Pvalue | HR (95% CI) | Pvalue | ||
| Age, years | 67.04 ± 10.24 | 1.017 (0.953–1.085) | 0.621 | 1.051 (1.003–1.102) | 0.038 | 1.038 (0.999–1.079) | 0.058 | 1.048 (1.009–1.089) | 0.014 |
| Male, n (%) | 152 (80.9%) | 0.944 (0.192–4.649) | 0.944 | 0.939 (0.329–2.698) | 0.908 | 0.825 (0.341–1.997) | 0.670 | 0.832 (0.357–1.941) | 0.670 |
| BMI, kg/m2 | 23.73 ± 3.00 | 1.319 (1.054–1.651) | 0.016 | 1.100 (0.956–1.265) | 0.185 | 1.093 (0.969–1.232) | 0.149 | 1.067 (0.952–1.197) | 0.265 |
| Heart rate, bmp | 77.67 ± 11.42 | 1.047 (0.995–1.102) | 0.075 | 1.013 (0.977–1.050) | 0.493 | 1.002 (0.971–1.034) | 0.880 | 0.996 (0.966–1.026) | 0.771 |
| Smoking, n (%) | 71 (37.8%) | 0.905 (0.247–3.325) | 0.881 | 0.747 (0.304–1.833) | 0.524 | 1.157 (0.555–2.411) | 0.698 | 1.018 (0.502–2.065) | 0.960 |
| Drinking, n (%) | 37 (19.7%) | 1.021 (0.208–5.024) | 0.979 | 0.750 (0.241–2.336) | 0.620 | 0.749 (0.287–1.955) | 0.555 | 0.773 (0.313–1.912) | 0.578 |
| Coronary artery disease, n (%) | 42 (22.3%) | 0.863 (0.176–4.225) | 0.855 | 1.114 (0.414–2.997) | 0.831 | 0.949 (0.397–2.268) | 0.907 | 1.316 (0.595–2.912) | 0.497 |
| Stroke, n (%) | 24 (12.8%) | 3.204 (0.769–13.350) | 0.110 | 2.544 (0.899–7.200) | 0.079 | 1.430 (0.524–3.900) | 0.485 | 1.518 (0.583–3.949) | 0.393 |
| Peripheral arterial disease, n (%) | 52 (27.7%) | 0.640 (0.131–3.118) | 0.581 | 1.921 (0.802–4.602) | 0.143 | 1.556 (0.722–3.350) | 0.259 | 1.230 (0.581–2.603) | 0.589 |
| Chronic obstructive pulmonary disease, n (%) | 14 (7.4%) | 1.410 (0.166–12.007) | 0.753 | 0.481 (0.060–3.845) | 0.490 | 1.123 (0.297–4.248) | 0.864 | 0.944 (0.251–3.553) | 0.932 |
| Renal insufficiency, n (%) | 19 (10.1%) | 2.368 (0.465–12.061) | 0.299 | 2.661 (0.866–8.177) | 0.088 | 2.055 (0.724–5.829) | 0.176 | 1.705 (0.606–4.800) | 0.312 |
| Hypertension, n (%) | 135 (71.8%) | 1.606 (0.330–7.823) | 0.557 | 1.283 (0.482–3.413) | 0.618 | 1.539 (0.653–3.625) | 0.324 | 1.582 (0.698–3.582) | 0.272 |
| Diabetes, n (%) | 31 (16.5%) | 5.846 (1.581–21.613) | 0.008 | 4.508 (1.793–11.335) | 0.001 | 2.771 (1.187–6.468) | 0.018 | 2.235 (0.971–5.148) | 0.059 |
| Dyslipidemia, n (%) | 116 (61.7%) | 1.396 (0.263–7.411) | 0.695 | 0.623 (0.253–1.535) | 0.304 | 0.867 (0.401–1.875) | 0.717 | 0.981 (0.468–2.056) | 0.960 |
| WBC, × 109/L | 6.99 ± 2.60 | 1.251 (1.052–1.487) | 0.011 | 1.162 (1.012–1.333) | 0.033 | 1.215 (1.066–1.384) | 0.003 | 1.179 (1.040–1.337) | 0.010 |
| D-dimer, ug/ml | 2.77 ± 3.58 | 0.955 (0.765–1.193) | 0.687 | 1.040 (0.938–1.153) | 0.454 | 1.106 (1.014–1.207) | 0.023 | 1.100 (1.009–1.198) | 0.030 |
| CRP, mg/L | 23.54 ± 44.82 | 1.010 (1.001–1.019) | 0.027 | 1.008 (1.001–1.016) | 0.029 | 1.015 (1.006–1.023) | <0.001 | 1.013 (1.005–1.021) | 0.001 |
| Aneurysm diameter, cm | 5.55 ± 1.32 | 1.358 (0.886–2.082) | 0.160 | 0.962 (0.696–1.330) | 0.815 | 1.037 (0.792–1.359) | 0.790 | 1.041 (0.805–1.347) | 0.759 |
Univariate Cox regression analyses of factors associated with mortality following EVAR for AAA during follow-up.
EVAR, Endovascular aneurysm repair; AAA, Abdominal aortic aneurysm; HR, Hazard ratio; CI, Confidence interval; BMI, Body mass index; WBC, White blood cell; CRP, C-reactive protein.
The significant association between the TyG index and postoperative mortality was found in both univariate and adjusted regression models (Table 2). Under Cox regression with multiple adjustments, per 1-unit increment of TyG index remained to have a relationship with a 3.015-, 2.848-, 2.524-, and 2.560-fold greater risk for 30-day, 1-year, 3-year, and 5-year mortality, respectively (all P < 0.05; Table 2).
Table 2
| HR (95% CI) | P value | |
|---|---|---|
| Univariate analysis | ||
| 30-day mortality | 3.019 (1.447–6.297) | 0.003 |
| 1-year mortality | 2.379 (1.330–4.256) | 0.003 |
| 3-year mortality | 2.076 (1.223–3.524) | 0.007 |
| 5-year mortality | 2.043 (1.218–3.427) | 0.007 |
| Multivariate analysis | ||
| 30-day mortalitya | 3.015 (1.269–7.163) | 0.012 |
| 1-year mortalityb | 2.848 (1.369–5.925) | 0.005 |
| 3-year mortalityc | 2.524 (1.294–4.922) | 0.007 |
| 5-year mortalityc | 2.560 (1.381–5.083) | 0.003 |
The association between the TyG index and postoperative mortality of AAA patients.
Adjusted for BMI, heart rate, diabetes, WBC, and CRP.
Adjusted for age, stroke, renal insufficiency, diabetes, WBC, and CRP.
Adjusted for age, diabetes, WBC, D-dimer, and CRP.
TyG, Triglyceride-glucose; AAA, Abdominal aortic aneurysm; HR, Hazard ratio; CI, Confidence interval; BMI, Body mass index; WBC, White blood cell; CRP, C-reactive protein.
The ROC analysis determined that the predictive cutoff value of the TyG index for overall mortality was 8.68, yielding an area under the curve of 0.626 (95% CI = 0.529–0.723, P = 0.013). Kaplan-Meier analysis indicated that patients with high TyG index (≥8.68) suffered worse cumulative survival than those with low TyG index (<8.68; P = 0.007; Figure 1).
Figure 1
Discussion
To the best of our knowledge, this was the first analysis to assess the effect of TyG index on clinical outcomes in AAA patients following EVAR, with a focus on both short-term and long-term mortality. According to the results, we demonstrated that an increase in the TyG index was significantly correlated with a higher risk of 30-day, 1-year, 3-year, and 5-year mortality, independent of potential risk factors. The survival probability in the TyG index ≥ 8.68 group was markedly lower than that in the TyG index <8.68 group. These findings highlight the usefulness of this simple and easy-to-calculate index to early identify AAA subjects at high risk of developing severe condition after EVAR therapy.
It should be noted that about 80.9% of AAA patients in the present cohort are males, which may be ascribed to the fact that AAA is a complex condition primarily affecting older men with an approximate 6:1 prevalence in males relative to females, and various studies support the protective role of estrogen against AAA (10, 11). Currently, the differential of the TyG index has come into focus to elucidate its role in the prognosis of patients with several forms of cardiovascular disease. It has been reported that higher TyG values were linked with an enhanced risk of adverse cardiovascular events in ST-elevation myocardial infarction patients who underwent percutaneous coronary intervention (12). Zhou et al. found that a TyG index >8.7 was connected to a higher risk of all-cause mortality in individuals with ischemic stroke (6). Notably, we discovered a similar threshold value of around 8.7 for elevated risk of mortality in patients after AAA repair.
Although the exact mechanism underlying the interaction between the TyG index and poor outcomes is not fully understood, it may be explained as follows. First, TyG index is a reliable indicator to evaluate IR. Previous evidence has suggested that IR can favor AAA initiation and progression (13). Moreover, IR usually leads to increased systemic and tissue inflammation, oxidative stress, endothelial dysfunction and renin-angiotensin-aldosterone system activation, thereby resulting in cell damage and affecting the longevity of individual's life (3, 14, 15). Second, TyG is usually associated with lipid and glucose metabolism disturbance, reflecting well the fat toxicity and sugar toxicity that can adversely affect cardiovascular outcomes (16, 17). In addition, a higher TyG index is independently related to the occurrence and development of arterial stiffness, nephric microvascular damage and several diseases including hypertension, diabetes, stroke, coronary artery disease, non-alcoholic fatty liver and malignancy, which are identified as risk factors for early and late mortality in AAA patients after EVAR (4, 17–19). Therefore, it seems reasonable to propose that AAA subjects with higher TyG levels are more likely to experience a course of vascular and organ impairment, contributing to an increased risk of all-cause mortality after EVAR. In clinical practice, our findings may guide clinicians to normalize the preoperative glucose or triglyceride under a target range, which is conducive to a good prognosis for patients with AAA repair.
Some limitations should be acknowledged. First, the TyG index was only collected at baseline and its changes during follow-up were not measured. Second, some influence of selection bias could not be excluded. Third, this was a single-center study based on a relative small cohort. Larger multicenter studies are necessary to confirm our results and define the causal effects of elevated TyG with mortality following EVAR for AAA.
In summary, TyG index could serve as a novel independent predictor for all-cause mortality in AAA patients after EVAR surgery and we also determined a specific cutoff value of TyG relevant to increased mortality. The detection of the TyG index may benefit the early risk stratification and clinical intervention to prevent postoperative all-cause death events.
Statements
Data availability statement
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.
Ethics statement
The studies involving human participants were reviewed and approved by the Ethics Committee of the First Hospital of China Medical University (Shenyang, China). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
Author contributions
TL, JJ, and CM: designed the study and interpreted the findings and revised the manuscript. TL: analyzed data and wrote the manuscript. TL and CY: carried out the study. CY and JY: did clinical data collection. All authors contributed to the article and approved the submitted version.
Funding
This work was supported by grants from the National Natural Science Foundation of China (82001828), Department of Science & Technology of Liaoning Province (2021JH1/10400051), and the National Natural Science Foundation of China (U21A20387).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1.
Eldrup-JorgensenJKraissLWChaikofELNealDForbesTL. Vascular quality initiative assessment of compliance with society for vascular surgery clinical practice guidelines on the care of patients with abdominal aortic aneurysm. J Vascular Surg. (2020) 72:874–85. 10.1016/j.jvs.2019.10.097
2.
MaggeSNZemelBSPipanMEGiddingSSKellyA. Cardiometabolic risk and body composition in youth with down syndrome. Pediatrics. (2019) 144:137. 10.1542/peds.2019-0137
3.
MaoQZhouDLiYWangYXuSCZhaoXH. The triglyceride-glucose index predicts coronary artery disease severity and cardiovascular outcomes in patients with non-ST-segment elevation acute coronary syndrome. Dis Markers. (2019) 2019:6891537. 10.1155/2019/6891537
4.
KimKSHongSHwangYCAhnHYParkCY. Evaluating triglyceride and glucose index as a simple and easy-to-calculate marker for all-cause and cardiovascular mortality. J Gen Internal Med. (2022) 37:4153–9. 10.1007/s11606-022-07681-4
5.
ZhangYDingXHuaBLiuQGaoHChenHet al. Predictive effect of triglyceride-glucose index on clinical events in patients with type 2 diabetes mellitus and acute myocardial infarction: results from an observational cohort study in China. Cardiovasc Diabetol. (2021) 20:43. 10.1186/s12933-021-01236-3
6.
ZhouYPanYYanHWangYLiZZhaoXet al. Triglyceride glucose index and prognosis of patients with ischemic stroke. Front Neurol. (2020) 11:456. 10.3389/fneur.2020.00456
7.
KainthASSuraTAWilliamsMSWittgenCZakharyESmedsMRet al. Outcomes after endovascular reintervention for aortic interventions. J Vascular Surg. (2022) 75:877–83 e2. 10.1016/j.jvs.2021.08.090
8.
KingAHSchmaierAHHarthKCKuminsNHWongVLZidarDAet al. Elevated neutrophil-lymphocyte ratio predicts mortality following elective endovascular aneurysm repair. J va|Scular Surg. (2020) 72:129–37. 10.1016/j.jvs.2019.10.058
9.
Simental-MendiaLERodriguez-MoranMGuerrero-RomeroF. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndrome Related Disord. (2008) 6:299–304. 10.1089/met.2008.0034
10.
VillardCRoyJBogdanovicMErikssonPHultgrenR. Sex hormones in men with abdominal aortic aneurysm. J Vascular Surg. (2021) 74:2023–9. 10.1016/j.jvs.2021.06.020
11.
HensleySEUpchurch GRJr. Repair of abdominal aortic aneurysms: JACC focus seminar, part 1. J Am Coll Cardiol. (2022) 80:821–31. 10.1016/j.jacc.2022.04.066
12.
LuoEWangDYanGQiaoYLiuBHouJet al. High triglyceride-glucose index is associated with poor prognosis in patients with acute ST-elevation myocardial infarction after percutaneous coronary intervention. Cardiovasc Diabetol. (2019) 18:150. 10.1186/s12933-019-0957-3
13.
LareyreFMoratalCZeregECarboniJPanaia-FerrariPBayerPet al. Association of abdominal aortic aneurysm diameter with insulin resistance index. Biochem Med. (2018) 28:030702. 10.11613/BM.2018.030702
14.
SchraubenSJJepsonCHsuJYWilsonFPZhangXLashJPet al. Insulin resistance and chronic kidney disease progression, cardiovascular events, and death: findings from the chronic renal insufficiency cohort study. BMC Nephrol. (2019) 20:60. 10.1186/s12882-019-1220-6
15.
YangQVijayakumarAKahnBB. Metabolites as regulators of insulin sensitivity and metabolism. Nat Rev Mol Cell Biol. (2018) 19:654–72. 10.1038/s41580-018-0044-8
16.
SuWYChenSCHuangYTHuangJCWuPYHsuWHet al. Comparison of the effects of fasting glucose, hemoglobin A(1c), and triglyceride-glucose index on cardiovascular events in type 2 diabetes mellitus. Nutrients. (2019) 11:2838. 10.3390/nu11112838
17.
DongJYangHZhangYChenLHuQ. A high triglyceride glucose index is associated with early renal impairment in the hypertensive patients. Front Endocrinol. (2022) 13:1038758. 10.3389/fendo.2022.1038758
18.
YangYHuangXWangYLengLXuJFengLet al. The impact of triglyceride-glucose index on ischemic stroke: a systematic review and meta-analysis. Cardiovasc Diabetol. (2023) 22:2. 10.1186/s12933-022-01732-0
19.
YanYWangDSunYMaQWangKLiaoYet al. Triglyceride-glucose index trajectory and arterial stiffness: results from hanzhong adolescent hypertension cohort study. Cardiovasc Diabetol. (2022) 21:33. 10.1186/s12933-022-01453-4
Summary
Keywords
triglyceride, glucose, abdominal aortic aneurysm, biomarker, mortality
Citation
Li T, Yang C, Yang J, Jing J and Ma C (2023) Elevated triglyceride-glucose index predicts mortality following endovascular abdominal aortic aneurysm repair. Front. Nutr. 10:1116425. doi: 10.3389/fnut.2023.1116425
Received
05 December 2022
Accepted
30 January 2023
Published
13 February 2023
Volume
10 - 2023
Edited by
Qinghui Ai, Ocean University of China, China
Reviewed by
Weiwei Dai, Fudan University, China; Jingwei Liu, University of California, Riverside, United States
Updates
Copyright
© 2023 Li, Yang, Yang, Jing and Ma.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jingjing Jing ✉ hellojjjing@163.comChunyan Ma ✉ macy@cmu1h.com
†These authors have contributed equally to this work
This article was submitted to Nutrition and Metabolism, a section of the journal Frontiers in Nutrition
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.