Stroke is a vital cause of long-term disability and mortality, representing a substantial threat to global public health (1). It is classified into ischemic and hemorrhagic types, with ischemic stroke (IS) being more prevalent, accounting for approximately 87% of all stroke occurrences worldwide (2). IS is primarily caused by acute arterial occlusion. Its etiologies include thromboembolism from large artery atherosclerosis, cardioembolism, small vessel disease, other identified causes such as hypercoagulable states and arterial dissection, and undetermined factors (3, 4). Hemorrhagic stroke, resulting from cerebral vascular injury or rupture, comprises two subtypes: intracerebral and subarachnoid hemorrhage. With an aging population, the incidence of stroke may constantly rise. According to 2017 data from the European Union, there were 1.12 million stroke events, 9.53 million stroke survivors, and 460,000 stroke-related deaths. By 2047, stroke events are projected to increase by 3%, while epidemic cases are expected to rise by 27%. However, stroke-related deaths and disability-adjusted life years are forecasted to decrease by 17% and 33%, respectively (5). The treatment and rehabilitation of stroke impose substantial economic burdens on both society and patients. In 2017, global medical costs related to stroke were estimated at $315 billion, with an additional $576 billion in lost income (6). These figures underscore the critical importance of early detection, intervention, and management to mitigate stroke progression.

Insulin resistance (IR) is characterized by weakened physiological function of insulin, wherein normal insulin levels fail to elicit an adequate physiological response (7). IR impairs endothelial function, enhances platelet aggregation, and promotes thrombosis, contributing to the development of IS. Moreover, it disrupts lipid metabolism, accelerating the formation of atherosclerosis and plaque (8, 9). Previous investigations have identified IR as a risk factor for stroke onset and progression, and it was related to poor functional prognosis following acute IS (7, 10, 11). Although the hyperinsulinemic-euglycemic clamp remains the gold standard for assessing IR, its widespread use is constrained by its time-consuming, labor-intensive, and costly nature (12). The triglyceride glucose (TyG), a reliable and cost-effective marker of IR, has been associated with higher stroke incidence in individuals without prior stroke history (13). A meta-analysis further established a significant link between the TyG indicator and the risk of stroke recurrence and mortality (14). The TyG-waist height ratio (WHtR), which integrates the TyG index with the obesity-related WHtR, has demonstrated superior diagnostic efficiency and predictive power for cardiovascular disease mortality compared to TyG (15). In conclusion, monitoring changes in these markers may aid in assessing metabolic function, potentially facilitating stroke prevention and improving prognosis.

Previous studies have revealed a positive correlation between TyG and TyG-body mass index (BMI) levels and stroke prevalence (16, 17). While these studies provide valuable insights, a noticeable gap remains in our understanding of the correlation between changes in TyG-WHtR and stroke occurrence. Therefore, this research seeks to elucidate the relationship between TyG-WHtR and stroke prevalence by analyzing relevant clinical data from NHANES.

This study is the first to explore the association between TyG-WHtR and stroke occurrence among Americans. A total of 8,757 representative participants were included, and a significant positive correlation of TyG-WHtR levels and stroke prevalence was observed. This association remained robust after making adjustments for relevant covariables. Specifically, each unit increase of TyG-WHtR was associated with a 26% higher likelihood of stroke. Subgroup analyses further indicated that stratification of CHD, angina pectoris, and moderate recreational exercise may influence this relationship. Consistent with these findings, a meta-analysis revealed that elevated TyG levels were independently linked to an increased stroke incidence in people without preexisting atherosclerotic cardiovascular disease (24). For individuals with CHD or angina pectoris, the use of lipid-lowering and antiplatelet medications may attenuate the association between TyG-WHtR and stroke prevalence. Physical exercise induces beneficial changes in lipid metabolism and enhances insulin sensitivity through various adaptations in glucose transport and metabolism (25). Therefore, physical activity may mitigate the impact of TyG-WHtR-related metabolic disorders on stroke. ROC analysis further demonstrated that TyG-WHtR had superior predictive value compared to TyG. Therefore, TyG-WHtR may be considered a valuable and cost-effective marker for stroke prevention and early identification, particularly in individuals who are not engaged in moderate physical exercise and those without CHD or angina pectoris. Special attention should be given to these populations when managing stroke risk and evaluating the role of TyG-WHtR in stroke prediction.

IR can aggravate atherosclerosis and contribute to hemodynamic disorders, which are closely related to the occurrence, early neurological deterioration, recurrence, and poor prognosis of IS (10, 26, 27). TyG is an effective and simple alternative marker for identifying IR. Evidence suggests that TyG has been broadly employed in research on CVD, type 2 diabetes mellitus, depression, chest pain, and stroke (15, 28–30). A study involving 10,132 individuals from American communities found that higher TyG levels were linked to an elevated risk of stroke and IS (31). Previous investigations have further demonstrated a link between IR and CVD in non-hypertensive populations (32). Moreover, a large-scale Chinese study with an 11-year follow-up revealed the predictive value of the TyG indicator for stroke and IS, though it did not exhibit a consistent predictive effect for ICH (33).

Metabolic syndrome (MetS) is a pathological condition featured as metabolic abnormalities, encompassing IR, hypertension, atherogenic dyslipidemia, and abdominal obesity (34, 35). Obesity-related metrics are often combined with the TyG index to evaluate MetS. A national cohort study reported that TyG-BMI, TyG-WC, and TyG-WHtR have superior predictive effects for MetS compared to simple obesity- or lipid-related indicators, as well as TyG alone. A Chinese cohort study of 4,583 individuals showed that TyG-BMI levels were linked to stroke risk among individuals aged 45 and older (36). Additionally, a study revealed that TyG and related metrics were positively related to atherosclerotic cardiovascular disease (37). WHtR is an easily accessible and useful metric for evaluating abdominal obesity, with previous studies highlighting its predictive role for stroke risk and its influence on post-stroke functional recovery (38–40). However, the exploration of the relationship between TyG-WHtR level and the probability of suffering a stroke remains insufficient. Therefore, the current study fills the insufficiency and points out their positive correlation. Our research findings emphasize the importance of multidimensional stroke prevention in both clinical practice and public health. Obesity serves as a key risk factor for stroke, and effective weight management may be essential for reducing stroke incidence and slowing disease progression. A meta-analysis illustrated that bariatric surgery decreased stroke incidence, especially IS (41). Moreover, reducing obesity and improving metabolism through physical exercise, a healthy diet, and lifestyle modifications may help alleviate the substantial burden of stroke (42).

The potential mechanism linking TyG-WHtR to stroke requires further elucidation. Atherosclerosis, a long-term inflammatory disorder, is closely related to stroke occurrence (43). This process is influenced by multiple factors such as IR, hyperglycemia, inflammation, and dyslipidemia (44, 45). Abnormal insulin signaling in endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages accelerates the formation and development of arteriosclerosis. In ECs, downregulation of the insulin receptor-Akt1 signaling pathway leads to endothelial dysfunction and an increase in the entry of inflammatory cells into plaques (46). In addition, IR promotes the proliferation of VSMCs, thereby accelerating plaque growth (47). In hyperinsulinemic and obese states, the insulin receptors of macrophages are downregulated, and intimal macrophages contribute to atherosclerosis by participating in inflammation and secreting protease and procoagulant factors (46, 48). Hyperglycemia results in excessive reactive oxygen species (ROS) production, induces pro-inflammatory responses, and promotes advanced glycation end-products formation through protein glycoxidation and glycation (44, 49). Furthermore, obesity promotes ectopic lipid deposition, induces lipotoxicity, releases excessive ROS, and triggers endoplasmic reticulum stress and inflammatory responses. These metabolic disturbances lead to the development of IR and chronic low-grade inflammatory condition, both of which are considered pivotal in the pathogenesis of stroke (50, 51).

This exploration has multiple strengths. First, the extensive sample size and inclusion of representative individuals enhance the robustness and generalizability of the findings. Second, stratifying TyG-WHtR into quartiles and categorizing participants by stroke status enabled a more effective assessment of the impact of TyG-WHtR levels on population characteristics and the distinct features of stroke patients. Third, comprehensive adjustments for potential confounders minimized bias and improved the reliability of the results. Finally, subgroup analyses revealed a significant correlation between TyG-WHtR levels and stroke in individuals who did not participate in moderate exercise and in those without CHD or angina pectoris, providing valuable insights for stroke prevention and intervention strategies.

Nevertheless, we acknowledge several limitations that should be considered when interpreting these findings. First, due to the constraints of a cross-sectional design, a causal link between TyG-WHtR and stroke cannot be established. Second, the reliance on self-reported comorbidities may introduce recall bias. Additionally, the study does not differentiate between stroke subtypes. Finally, although multiple confounding factors were considered, the potential impact of unaccounted variables cannot be excluded.

This study identified an association between elevated TyG-WHtR levels and increased stroke prevalence, underscoring the importance of blood sugar and lipid management in stroke prevention. These findings suggest that TyG-WHtR may function as a valuable predictive metric for stroke, offering potential guidance for clinical prevention and early intervention. However, prospective clinical trials are needed to further validate these results and provide valuable insights for clinical practice.