Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk

In this retrospective analysis, we verified the association between the TyG index and cardiovascular and all-cause mortality in primary prevention. We discovered that those with a TyG index ≥ 9.83 who had a high risk of CVD also had a higher risk of both cardiovascular and all-cause mortality.

The number of people at high risk of CVD is large, and it is growing year by year as the population ages and unhealthy lifestyles develop [15,16,17]. A study published in The Lancet Public Health in December 2020 by China’s National Center for Cardiovascular Diseases studied the cardiovascular health and risk factors of 980,000 people on the Chinese mainland from 2015 to 2019. The results showed that 16.6% of people had a high risk of CVD [3]. High risk individuals have a poor prognosis, a high rate of cardiovascular death, and a high prevalence of CVD [4, 5]. Therefore, primary prevention targeting people at high risk of CVD is critical, and early identification, intervention, and improved prognosis will significantly improve community health and lower the burden of illness [18,19,20,21].

Insulin resistance is a condition in which the body’s sensitivity and responsiveness to insulin are reduced [22]. IR is an independent risk factor for CVD and can promote metabolic diseases such as obesity, hypertension, hyperlipidemia, and diabetes, and these metabolic disorders are frequently observed in high risk groups for CVD [23]. The TyG index, which combines fasting blood glucose and fasting blood lipid levels, was proposed in 2008 and is regarded as a reliable and simple IR assessment indicator [14]. Existing clinical studies have shown that the TyG index is associated with a poor prognosis of CVD in several groups, including ACS, stable coronary heart disease, unstable coronary heart disease, and so on. [9] In a study of 662 patients over the age of 80 with ACS, Jiao et al. discovered that TyG index was an independent predictor of long-term all-cause mortality (HR: 1.64, 95%CI: 1.06–2.54) and MACE (HR: 1.36, 95%CI: 1.05–1.95) [10]. Gou et al. conducted a retrospective study on 546 patients with CHF and T2DM. Results showed that TyG index was positively correlated with cardiovascular death (HR: 4.42, 95%CI: 1.49–13.15) [11]. Similarly, Liu et al. conducted a prospective study in 1,467 patients with both coronary heart disease and hypertension. The results showed that for every standard deviation (SD) increase in the TyG index, the risk of all-cause death and non-fatal cardiovascular events in this population increased by 28% (HR: 1.28, 95% CI: 1.04–1.59) [24].

In conclusion, the TyG index can be a useful biomarker to identify poor prognosis and assist in further risk stratification of patients with ACS, heart failure, etc. However, current studies on the relationship between the TyG index and CVD mainly focus on secondary prevention, and there are no clinical studies to explore the relationship between the two in primary prevention. And it is unknown if the TyG index predicts poor outcomes in high risk CVD groups. Thus, our observations fill an important knowledge gap in the field. Our study confirms prior findings that the TyG index is a strong predictor of poor outcomes in people at high risk of CVD, even after controlling for any confounding factors. We observed that the TyG index ≥ 9.83 was associated with an elevated risk of all-cause death and cardiovascular death in the high risk CVD population (HR:1.86, 95%CI: 1.37–2.51,P < 0.001; HR:2.41, 95%CI: 1.47–3.96, P = 0.001). In addition, subgroup analysis was conducted, and it was found that the TyG index had a greater ability to predict all-cause mortality in the majority of subgroups. This suggests that the TyG index is a generally stable and reliable prognostic indicator in high risk CVD people, unaffected by gender, smoking, or other factors, and that it can be widely used in high risk CVD people.

It is important to note that the exact cut-off value of the TyG index associated with poor prognosis varied across studies, which we considered to be mainly due to the heterogeneity of the study population. For example, among cancer survivors, patients with a TyG index > 8 had a higher risk of primary cardiovascular events [25]. This may be related to the long-term anticancer treatment of cancer survivors, insufficient attention to and treatment of metabolic abnormalities such as blood lipids and blood glucose. For critically ill patients, a TyG index > 9.2 was significantly associated with poor prognosis, because IR related pathological states were important causes of aggravation in ICU patients [26]. Our study focused on high risk people who have not yet developed CVD, concentrating on five major risk factors that are significantly associated with cardiovascular disease: severe hypertension, diabetes, severe dyslipidemia, gender, and smoking. These risk factors have been confirmed to be closely related to endothelial dysfunction, oxidative stress, and the inflammatory response, and the above-mentioned pathological processes are just mutually reinforcing with the pathological processes of IR. Compared with critically ill patients and tumor survivors, the study included population had a higher TyG index cut-off value, which may be related to the severe metabolic abnormalities and low levels of stress and inflammation in the high risk CVD population included in this study.

Although the cause of the association between TyG index and poor prognosis in the high risk CVD group is yet unknown, the following factors could play a role: First, IR results in an imbalance between the metabolism of glucose and lipids, which in turn promotes inflammation and oxidative stress, causes atherosclerosis to appear and develop, and accelerates the evolution of coronary heart disease [27]. Second, IR can induce increased production of glycosylated products and free radicals, cause an increase in reactive oxygen species (ROS) production, and cause vascular endothelial injury [28, 29]. Third, IR can reduce platelet anti-aggregation sensitivity to prostaglandins I2 and NO, leading to overactivation of platelets, promoting thrombosis and inflammation, causing adverse cardiovascular events and leading to poor prognosis [30]. Fourth, over-glycosylation induced by insulin resistance leads to smooth muscle cell proliferation and collagen deposition, which leads to increased heart stiffness, myocardial fibrosis, and ultimately poor prognosis such as heart failure [9, 22].

The main strength of this article is that it is the first time to explore the relationship between the TyG index and adverse prognosis of cardiovascular events in high risk populations at the level of primary prevention. However, there are also several limitations to this study. First, this study only included Chinese people, and applying it to other ethnic groups with high cardiovascular risk may have different results. But this study included a large number of people, and fully considered the geographical distribution and social and economic development factors, with a certain representativeness. Second, this is a retrospective study, which cannot fully evaluate the causal relationship between the TyG index and poor prognosis. Third, although some confounding factors were adjusted, our research results would still be affected by residual confounding factors. Finally, due to the limited clinical information collected, we did not study the difference between TyG index and other indicators representing IR in predicting the prognosis of high risk people with CVD.