To our knowledge, this is the first study to examine the relationship between TyG index and CAD in premenopausal women. It is the first time to confirm that TyG index is an independent risk factor for CAD in premenopausal women. We also find the high TyG index had a higher risk of CAD than the low TyG index and the difference was pronounced in the age group of 49 years or older.
Cardiovascular diseases, especially CAD, are one of the leading causes of death in women, and they have received extensive attention both in China and abroad [22]. However, among these risk factors, type 2 diabetes contributes importantly to cardiovascular disease, because it is highly prevalent and adjusted calculate hazard ratios (HRs) with diabetes were: 2.00 (95% CI 1.83–2.19) for CAD [23, 24]. Before type 2 diabetes is diagnosed, IR can be present for years, thereby increasing insulin and glucose concentrations [25, 26]. IR has been shown to be superior to other cardiovascular risk factors in predicting CAD risk in previous studies, such as in a standardized meta-analysis researchers found that the relative risk of cardiovascular disease was higher for an increase of one standard deviation in HOMA-IR compared to an increase of one standard deviation in fasting glucose or fasting insulin concentration [27]. In a study of type 1 diabetes, researchers study showed that decreased insulin sensitivity in these subjects is a real cardiovascular risk factor and contributes to the onset of early atherosclerosis [28]. Hanley AJ et al found a significant association between HOMA-IR and risk of CAD [29]. And a previous prospective study showed that IR per se calculated by homeostasis model assessment is an independent risk factor for major cardiovascular events [30].
In this light, IR is a crucial mechanism for CAD and is an independent risk factor for CAD [31]. ccording to some previous studies, there is an association between IR and CAD. First, IR promotes the progression of CAD by inducing glucose metabolism imbalance, altering systemic lipid metabolism, and causing endothelial dysfunction [32]. Second, IR increases sympathetic nerve activity and leads to increased catecholamine secretion, which increases myocardial oxygen consumption [33, 34]. Third, IR facilitates atherothrombosis through increased cellular synthesis of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen and reduced production of tissue plasminogen activator [35]. In the pathogenesis of atherosclerosis, IR-mediated impairment of endothelial function was earliest found. The relationship between IR and endothelial function is closely associated with metabolic actions of phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways and mitogenactivated protein kinase (MAPK)-dependent insulin signaling [36, 37]. IR is typically defined as decreased sensitivity or responsiveness to metabolic actions of insulin. Endothelial insulin resistance is typically accompanied by reduced PI3K-NO pathway and an intact or heightened MAPK-ET-1 pathway [38]. As a result, itric oxide production is reduced and enhanced production of ET-1 in endothelium [39]. The involvement of these factors leads to vulnerable and obstructive atherosclerosis in coronary vessels [40]. Recently, the TyG index, a product of fasting serum triglycerides and glucose, has been suggested as a surrogate marker for the assessment of IR [17, 18]. This index has the advantage of being applicable in clinical practice since both triglyceride and glucose concentrations are inexpensive and routinely measured [17]. Some clinical studies have shown that the TyG index is better for the prediction of IR than HOMA-IR [41]. Previous studies have shown that the TyG index has a positive correlation with IR, similar to the insulin-mediated glucose uptake or hyperinsulinemic-euglycemic clamp test [17]. The mechanism of TyG in predicting atherosclerosis may be related to IR-mediated endothelial dysfunction, systemic inflammation, oxidative stress and vascular remodeling [42–44]. Thus the TyG index may be a useful tool to predict arterial stiffness and CAD. Therefore, we believe that the predictive effect of TyG index on CAD should be interpreted as IR reflected by TyG index. A study of Iranians showed that TyG index was significantly associated with the risk of CAD, especially in younger populations [45]. A retrospective cohort study of older than 60 years showed that participants in the top quartile of TyG index had a 72% higher risk of CAD events than the rest of the population [46]. Presently, more and more premenopausal women had CAD. Traditional opinion considered that men were easily suffered from CAD and young premenopausal women never had CAD, which contribute the inadequate concern for premenopausal women with abnormal chest pain especially atypical angina symptom. The present study, which included premenopausal women, is the first to confirm that TyG index is an independent risk factor for an increased risk of CAD in premenopausal women. The TyG index can be used as a convenient and inexpensive predictor of the CAD, providing a basis for primary prevention in young women.
The present study also had several limitations. Firstly, the sample size might be not large enough. Secondly, owing to a shortage of records insulin concentration data, we could not compare the predictive value of TyG index with those of HOMA-IR and the hyperinsulinaemic euglycaemic clamp test for the development of CAD. Thirdly, we did not enrolled men or postmenopausal women in the study. Future studies are needed to evaluate the specific relation between three different population. Moreover, the TyG index seems to be significantly affected by diet and ethnic group [47, 48]. Thus, the findings from the current study are difficult to generalize to all countries and ethnic groups. Finally, although other potential cardiac risk factors were adjusted for, we still cannot exclude the possibility of residual or unassessed confusion.