Acute aortic dissection (AAD) represents one of the most catastrophic cardiovascular emergencies, characterized by a tear in the intimal layer of the aorta that allows blood to dissect through the layers of the aortic wall (1). Despite advances in diagnostic imaging and surgical techniques, AAD remains associated with devastating outcomes, with mortality rates increasing by 1%–2% per hour if left untreated (2). The in-hospital mortality rate for surgically managed type A dissections ranges from 15% to 30%, while long-term survival remains suboptimal, with 5-year survival rates of approximately 70%–80% and 10-year survival rates declining to 50%–60% (3). These sobering statistics underscore the critical need for improved risk stratification tools to identify patients at higher risk of adverse outcomes. Several risk factors for AAD have been well established, including advanced age, male gender, hypertension, atherosclerosis, and connective tissue disorders such as Marfan syndrome (4, 5). Recent epidemiological studies have identified additional metabolic risk factors, with smoking habit, elevated systolic and diastolic blood pressure, higher non-HDL cholesterol, and lower HDL cholesterol levels demonstrating strong associations with mortality from aortic diseases. However, the relationship between metabolic dysfunction and AAD outcomes remains incompletely understood. Interestingly, while traditional cardiovascular risk factors predict AAD occurrence, their role in determining post-dissection prognosis is less well characterized, particularly for metabolic parameters.

Insulin resistance (IR), a fundamental feature of metabolic syndrome and type 2 diabetes mellitus, has emerged as a critical regulator in the development and progression of cardiovascular diseases (6, 7). IR is intrinsically linked to multiple cardiovascular risk factors, including hypertension, dyslipidemia, and hyperglycemia, collectively contributing to endothelial dysfunction, oxidative stress, and chronic inflammation (8). Recent experimental evidence suggests that IR may promote aortic dissection formation through phenotypic switching of vascular smooth muscle cells, with the majority of patients with acute thoracic aortic dissection exhibiting elevated markers of IR (9). However, the prognostic significance of IR in patients who have already developed AAD remains poorly defined, representing a significant gap in current knowledge. Traditional assessment of IR, such as the hyperinsulinemic-euglycemic clamp technique or homeostasis model assessment (HOMA-IR), requires insulin measurements that are often unavailable in emergency settings or resource-limited environments (10). Consequently, surrogate markers of IR that can be calculated from routine laboratory tests have gained considerable attention. Among these, the triglyceride-glucose (TyG) index has demonstrated superior performance as a simple, cost-effective, and reliable biomarker of IR (11). Accumulating evidence has established strong associations between elevated TyG index and adverse cardiovascular outcomes across diverse populations and disease states, including coronary artery disease, heart failure, and stroke (11–13).

Recent meta-analyses have confirmed that elevated TyG index independently predicts major adverse cardiovascular events (MACEs) in patients with coronary artery disease, with individuals in higher TyG index quartiles exhibiting a 2.14-fold increased risk compared to those with lower values (14). Beyond the TyG index, other IR surrogates have been proposed, including the TyG-BMI index (TyG index multiplied by body mass index), the TG/HDL-C ratio, and the Metabolic Score for Insulin Resistance (METS-IR) (15, 16). These indices incorporate anthropometric and lipid parameters to provide enhanced assessment of metabolic dysfunction. However, their comparative prognostic value in predicting outcomes following AAD has not been systematically evaluated. Despite the established role of IR surrogates in predicting cardiovascular events in various clinical contexts, their utility in risk stratifying patients with AAD remains unexplored. Given the high mortality associated with AAD and the routine availability of triglycerides and glucose measurements, investigating whether simple IR indices can identify patients at increased risk of major adverse cardiac and cerebrovascular events (MACCEs) following AAD would have important clinical implications. Such tools could facilitate early identification of high-risk individuals requiring intensive monitoring and aggressive therapeutic interventions.

Therefore, this study aimed to investigate the associations between four IR indices (TyG index, TyG-BMI index, TG/HDL-C ratio, and METS-IR) and MACCEs in patients with AAD. Additionally, we performed subgroup analyses in clinically relevant populations, including male patients and those with hypertension, diabetes mellitus, or smoking history, to identify patient subgroups in whom IR indices might have enhanced prognostic value. We hypothesized that elevated IR indices, particularly the TyG index, would be independently associated with increased risk of MACCEs following AAD.

This study provides novel evidence that elevated insulin resistance indices, particularly the TyG index, independently predict MACCEs in patients with acute aortic dissection. To our knowledge, this represents the first comprehensive investigation evaluating multiple IR surrogates for prognostic stratification in AAD patients. Our principal findings demonstrate that the TyG index maintained a significant association with MACCEs even after adjustment for traditional cardiovascular risk factors and laboratory parameters, with ORs ranging from 2.18 to 2.46 across different models. Importantly, subgroup analyses revealed that this association was particularly robust in male patients and current smokers, suggesting potential population-specific applications for risk stratification. These findings align with extensive evidence demonstrating the prognostic utility of the TyG index across diverse cardiovascular conditions. Previous meta-analyses have consistently shown that elevated TyG index predicts adverse outcomes in patients with coronary artery disease, with individuals in higher TyG quartiles exhibiting more than twofold increased risk of major adverse cardiovascular events (14, 17). The magnitude of association observed in our AAD cohort is comparable to that reported for established biomarkers such as D-dimer and inflammatory markers, suggesting that the TyG index could serve as a complementary risk stratification tool in clinical practice (18).

Several interconnected pathophysiological mechanisms may explain the association between IR and adverse outcomes in AAD patients. First, IR induces endothelial dysfunction through multiple pathways, including reduced nitric oxide bioavailability, enhanced oxidative stress, and increased production of reactive oxygen species (8, 19). These processes compromise vascular integrity and promote inflammatory cascades that may exacerbate aortic wall injury following dissection. Studies have demonstrated that IR-related endothelial dysfunction disrupts the balance between the PI3K-NO vasodilatory pathway and the MAPK-endothelin-1 vasoconstrictive pathway, leading to impaired vascular homeostasis (20). Second, IR is intimately linked with systemic inflammation, as evidenced by elevated levels of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha (21). Recent investigations have shown that inflammation partially mediates the relationship between IR and cardiovascular events, suggesting a synergistic detrimental effect (22). In the context of AAD, heightened inflammatory responses may accelerate complications such as organ malperfusion, cardiac tamponade, and thrombotic events. Third, IR promotes activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, resulting in persistent hemodynamic stress on the already compromised aortic wall (23). This increased hemodynamic burden, coupled with metabolic dysfunction, may predispose patients to extension of dissection, false lumen expansion, or even aortic rupture. The convergence of these mechanisms creates a pathophysiological milieu that substantially increases the risk of adverse cardiovascular outcomes in AAD patients with elevated insulin resistance.

The differential associations observed across subgroups provide important insights into risk stratification. The particularly strong association between TyG index and MACCEs in male patients deserves careful consideration. These findings are consistent with established sex differences in insulin resistance and cardiovascular risk. Although females generally maintain better insulin sensitivity during reproductive years, the relationship between IR and cardiovascular events appears attenuated in women compared to men (24, 25). This “female advantage” has been attributed to protective effects of estrogen, which enhances insulin signaling, reduces oxidative stress, and improves endothelial function (26). Conversely, males demonstrate stronger associations between metabolic dysfunction and cardiovascular outcomes, potentially due to greater visceral adiposity, higher inflammatory burden, and absence of estrogen's cardioprotective effects (27). Similarly, the robust association observed in smoking patients (ORs exceeding 3.0) is biologically plausible, as tobacco exposure induces insulin resistance through increased oxidative stress, chronic inflammation, and altered adipokine secretion, synergizing with IR to accelerate thrombotic complications (28). Interestingly, none of the IR indices showed significant associations with MACCEs in hypertensive patients after multivariate adjustment. This paradoxical finding may reflect the complex interplay between hypertension, IR, and aortic pathology, where the overwhelming hemodynamic burden imposed by elevated blood pressure may overshadow the additional risk conferred by metabolic dysfunction (29). Alternatively, intensive blood pressure management in hypertensive AAD patients may have effectively mitigated IR-related risks. Finally, the coexistence of hypertension and insulin resistance may introduce collinearity and risk saturation effects, limiting the ability of IR indices to further discriminate prognosis within this subgroup. These subgroup-specific findings emphasize that male AAD patients and smokers with elevated TyG index represent particularly high-risk populations warranting intensive surveillance and aggressive risk factor modification.

From a clinical perspective, the identification of a Youden index–derived TyG threshold enables translation of our findings into practical management strategies. Patients with elevated TyG index (≥8.64), particularly males and current smokers, may benefit from intensified metabolic surveillance, including more frequent monitoring of fasting glucose and triglycerides during follow-up, alongside optimization of lipid-lowering and glucose-lowering therapies according to high-risk cardiovascular targets. In these high-risk subgroups, closer imaging surveillance of the aorta and structured lifestyle interventions-especially smoking cessation-may be warranted. Importantly, the fully adjusted effect size observed for the TyG index (OR = 2.46) is comparable to that reported in meta-analyses of TyG index in other cardiovascular diseases, such as acute coronary syndrome and ischemic stroke, and is of similar magnitude to established biomarkers used in acute aortic syndromes, including D-dimer. These findings suggest that the TyG index provides clinically meaningful and complementary prognostic information rather than a marginal incremental signal.

This study highlights the TyG index as a simple, readily available, and cost-effective prognostic marker for patients with acute aortic dissection. Unlike insulin-based indices, the TyG index relies solely on routine fasting glucose and triglyceride measurements, enabling rapid risk stratification without additional testing burden, particularly in acute or resource-limited settings. Importantly, its prognostic value remained consistent across multiple multivariable models, underscoring its robustness. The key innovation of this study lies in demonstrating, for the first time, the independent and stable prognostic utility of the TyG index in AAD, supporting its potential integration into existing risk assessment frameworks to improve early identification of high-risk patients and guide individualized management strategies. Several limitations should be acknowledged. First, the retrospective single-center design may limit generalizability, and multicenter prospective studies are warranted. Second, insulin resistance indices were assessed only at baseline, and dynamic changes over time were not evaluated. Third, our relatively modest sample size of 114 patients precluded detailed analyses of specific MACCE components individually and may have limited statistical power for subgroup analyses. Future work will focus on increasing the sample size to enhance the robustness of our findings. In addition, information on medication adherence and lifestyle factors during follow-up was unavailable.

In conclusion, an elevated TyG index independently predicts MACCEs in patients with acute aortic dissection, with particularly pronounced associations in male patients and current smokers. Given its derivation from routinely available laboratory parameters, the TyG index provides a practical tool for early risk stratification and may help identify AAD survivors who warrant intensified metabolic monitoring, closer imaging surveillance, and aggressive modification of cardiometabolic risk factors. Future research should prioritize prospective multicenter validation, evaluation of TyG-guided management strategies, and investigation of whether interventions targeting insulin resistance can translate into improved long-term outcomes in high-risk AAD populations.