The TyG-WC index, which integrates TG, FBS, and WC, can be a promising forecasting tool for cardiovascular diseases and mortality. This meta-analysis demonstrated that elevated levels of TyG-WC are significantly associated with increased overall mortality, cardiovascular mortality, and various cardiovascular conditions, including MI, CAD, stroke, and PAD. Notably, our systematic search identified only one study on the relation between TyG-WC and HF, which suggested a positive and significant correlation.

Since the elements of this marker—TG, FBS, and waist circumference—are easy to measure and cost-effective in a hospital setting, TyG-WC could be a useful screening tool that wouldn’t significantly raise costs for patients or the overall healthcare system. To the best of our knowledge, this is the first meta-analysis evaluating the relationship between TYG-WC and cardiovascular diseases and mortality.

The impact of TyG-WC on cardiovascular diseases can be anticipated considering its two components (TyG and WC), as TyG and WC are related to cardiovascular diseases. Prior research has demonstrated that TyG is a marker with considerable sensitivity and specificity in identifying vascular diseases and metabolic disorders, and it can significantly predict insulin resistance (IR). IR is a key factor in metabolic abnormalities, systemic inflammation, endothelial dysfunction, and atherosclerosis [21,22,23]. Furthermore, TyG has been linked to hypertension, a condition that contributes to various cardiovascular diseases, including coronary artery disease, heart failure, and increased overall mortality [24, 25]. Obesity, particularly abdominal obesity indicative of visceral fat, can affect atherosclerotic processes and, together with TyG, may predict hypertension and insulin resistance [24, 26, 27]. Also, a study evaluating the codependence of TyG and obesity’s role in cardiovascular diseases suggested that TyG was significantly related to cardiovascular diseases in obese patients, in contrast this correlation was insignificant for nonobese adults [28]. This highlights the importance of considering obesity-related modalities while interpreting TyG.

Several studies have evaluated the predictive value of the TyG index when combined with obesity measurements like BMI, WtHR, and WC [29, 30]. Among these combinations, TyG-WC and TyG-WtHR are recommended as more effective tools for identifying individuals at risk for cardiovascular disease [29]. Research involving 1,145 asymptomatic participants suggested that TyG-WC is a stronger and more reliable predictor of coronary artery calcification—a marker associated with cardiovascular diseases—comparing the the HOMA-IR, TyG index, and TyG-BMI [30]. Given that TyG-WC emphasizes visceral adiposity compared to TyG-BMI, which focuses on overall obesity, it may serve as a superior predictor of metabolic and cardiovascular diseases. Additionally, previous investigations have suggested that TyG-WC correlates more strongly with cardiovascular mortality in men than in women, while it is more associated with cardiovascular diseases in women comparing men [29]. However, because of limited gender-specific studies, we couldn’t perform subgroup meta-analyses based on gender. And the need for further research on this cofounding modality should be considered.

The results regarding the effect of obesity and TYG body weight indices were always a matter of contradiction. Some studies suggested that there is an obesity paradox in terms of the severity and mortality of cardiovascular diseases [31, 32]. The increased glucose availability because of elevated endogenous glucose production and macrophage availability in high glucose status can bring pathophysiological background for lower cardiovascular mortality in obese patients [33, 34]. However, some studies suggest that some biases like higher socioeconomic status in obese patients and comorbidities that lead to medication intake protecting regarding cardiovascular death like statin can participate in this paradox [35,36,37]. Also, a meta-analysis on the effect of TyG on cardiovascular mortality suggested no significant association between these two factors [38]. However, our study draws a line on these contradictory findings by determining a significant higher cardiovascular mortality by elevated TyG-WC after systematic and meta-analysis evaluating these factors. Hence, this marker can be used instead of obesity indices for predicting cardiovascular outcome.

This study acknowledges several limitations. Firstly, the number of studies eligible for inclusion in this meta-analysis was limited. Consequently, we were not able to conduct meta-analyses on some of the cardiovascular diseases like HF considering only one study examining the impact of TyG-WC on HF. Therefore, further research exploring this relationship is necessary. Additionally, considering obesity and its various markers present distinct effects on genders, conducting subgroup analyses based on gender would be advantageous. However, the limited number of gender-specific studies prevented us from undertaking such analyses, highlighting the need for further investigations. Thirdly, the inclusion of various study designs (prospective, retrospective, and cross-sectional) may contribute to variability in our results. While subgroup analyses revealed significant findings primarily in prospective cohorts, the lack of significance for certain outcomes in the other study designs may limit the broader applicability of our conclusions. Finally, our meta-analysis did not account for various lifestyle factors, such as smoking, dietary habits, physical activity levels, age, and socioeconomic status, which can significantly influence both TyG-WC and cardiovascular outcomes.

The strength of this study primarily lies in the comprehensiveness of its findings. While previous research has addressed the relationship between TyG-WC and cardiovascular diseases, there has been a lack of systematic evaluations in this regard. By including a range of cardiovascular conditions, such as MI, PAD, CAD and stroke, this study offers insights more specific than a general assessment of cardiovascular health. Future research should focus on determining precise cut-off values for the TyG-WC index. Defining specific thresholds would improve risk stratification in clinical practice, allowing healthcare providers to identify individuals at higher risk for adverse cardiovascular outcomes more effectively. Additionally, follow-up studies should aim to evaluate the predictive value of TyG-WC in patients with various comorbidities. Understanding how TyG-WC correlates with cardiovascular risk in individuals with conditions such as diabetes, hypertension, or metabolic syndrome could provide critical insights into its clinical utility.

In conclusion, this study emphasizes the significant role of TyG-WC in cardiovascular and overall mortality, as well as its association with various cardiovascular diseases, including MI, stroke, PAD, and CAD. Additionally, it identifies a current knowledge gap regarding the relationship between TyG-WC and HF, as well as the need for gender-specific studies.