Due to the progress of early diagnosis and cancer treatment, more and more cancer patients have survived. As of 2014, there were about 14.5 million cancer survivors in the United States, and this number is expected to increase to 19million by 2024. Cardiovascular disease (CVD) is the second leading cause of death among cancer survivors. In some cancers, CVD mortality has been shown to increase gradually during follow-up, and cancer mortality has stabilized or decreased. Therefore, the prevention of cardiovascular disease is an important part of cancer survival. Despite its relevance, this issue has not received enough attention.

Triglyceride glucose (TYG) index has been introduced as an alternative marker of insulin resistance. Fasting blood glucose and triglyceride levels can be easily calculated without sampling serum insulin. Previous studies have shown that TYG index is associated with metabolic diseases, subclinical atherosclerosis and CVD. However, the association between TYG index and CVD in cancer survivors is still unknown, and these survivors have a higher risk of subsequent CVD. Therefore, the purpose of this study was to determine the relationship between TYG index and the development of CVD in the future. These cancer patients survived for more than 5 years in a large population-based cohort of cancer patients, and initially did not have CVD.

Baseline characteristics of the study population

A total of 155167 cancer survivors (mean age 59.9 years ± 12.0 years, female 59.1%) were included in this study. The baseline demographic and biochemical profiles are shown in Table 1. In this cohort, gastric cancer (18.8%), thyroid cancer (15.6%), breast cancer (13.9%) and colorectal cancer (11.7%) were the most common types of cancer. With the increase of TYG index, systolic blood pressure, BMI and total cholesterol gradually increased, while high-density lipoprotein cholesterol gradually decreased. Similarly, high TYG means that the array shows more alcohol consumption, a higher proportion of smokers and less physical activity. During the median follow-up of 10 years (mean 9.6 years), 13279 cases of CVD were hospitalized.

Relationship between TYG index and cardiovascular events

For primary cardiovascular events, a gradual increase in risk was observed at the TYG index level. Compared with TYG index <8, the HR with TYG index of 8.0-8.4 was 1.08 (95% CI 1.01-1.14); TYG index is 1.10 of 8.5-8.9 (95% CI 1.03-1.17); TYG index is 1.23 (95% CI 1.15-1.31) of 9.0-9.4; TYG index is 1.34 (95% CI 1.23-1.47) of 9.5-9.9; After controlling for age, gender, behavioral factors and other laboratory findings, the TYG index ≥ 10 was 1.55 (95% CI 1.35-1.79) (Table 2). Subgroup analysis by age and sex also revealed a similar positive correlation. As a sensitivity test, the same analysis was carried out after excluding people who died in the previous 3 years of follow-up, and similar results were found.

When analyzing the association between TYG index and CVD subtypes, the graded positive association between TYG index and clinical outcomes is particularly significant for atherosclerotic cardiovascular disease (ASCVD), such as IHD (including AMI) and ischemic stroke, rather than hemorrhagic stroke or heart failure. For example, when the TYG index is 8.0-8.4, the AMI adjusted HR is 1.23 (95% CI 0.97-1.55); TYG index is 1.40 (95% CI 1.11-1.77) of 8.5-8.9; 1.75 (95% CI 1.36-2.23), TYG index is 9.0-9.4; TYG index is 9.5-9.9, 2.07 (95% CI 1.53-2.80); TYG index ≥ 10 was 2.58 (95% CI 1.65-4.02). The adjusted hr for ischemic stroke was 1.13 (95% CI 1.02-1.25) when the TYG index was 8.0-8.4, 1.15 (95% CI 1.04-1.28) when the TYG index was 8.5-8.9, 1.34 (95% CI 1.20-1.51) when the TYG index was 9.0-9.4, 1.56 (95% CI 1.35-1.82) when the TYG index was 9.5-9.9, and 1.92 (95% CI 1.53-2.41) when the TYG index was ≥ 10. In contrast, for hemorrhagic stroke and heart failure, most TYG categories have p values >0.05, indicating a non significant association.

The restricted cubic spline curve of primary cardiovascular events shows a positive correlation with similar grades observed in the classification analysis (Fig. 1). Compared with non ASCVD subtypes, the correlation slope of ASCVD subtypes (including AMI and ischemic stroke) is steeper, and the linear correlation is more obvious (nonlinear >p value is 0.05).

When linear correlation is assumed, primary cardiovascular events increase by 16% for every 1 unit increase in TYG index (HR 1.16; 95%ci 1.12-1.19). For AMI, this connection is the strongest. For each unit increase in TYG index, the risk of AMI hospitalization increased by 45% (HR, 1.45; 95%ci 1.30-1.62), ischemic stroke increased by 23% (HR 1.23; 95%ci 1.17-1.30), IHD increased by 20% (HR 1.20; 95%ci 1.14-1.26), and overall stroke increased by 13% (HR 1.13, 95%ci 1.08-1.19), after adjusting for baseline covariates. The correlation between TYG index and primary cardiovascular events did not differ between subgroups (P interaction >0.05), except for blood glucose status, where a stronger association was found in the hyperglycemic group (P interaction =0.003) (Figure 2).

Exploratory analysis: the relationship between individual fasting blood glucose and triglyceride levels and primary cardiovascular events

With regard to fasting blood glucose, compared with the reference group with fasting blood glucose levels <100 mg/dl, the risk of fasting blood glucose levels ≥ 140 mg/dl after baseline covariate adjustment was significantly higher. For triglyceride levels, triglyceride levels ≥ 500 mg / dL were associated with a 59% increased risk of primary cardiovascular events (HR 1.59, 95%ci 1.26-2.01) compared with the group with triglyceride levels <50 mg / dl. When analyzing six fasting blood glucose triglyceride combination categories, the group with fasting blood glucose ≥ 140 mg / dl and tg<100 mg / dl was not associated with higher risk, while the group with fasting blood glucose ≥ 140 mg / dl and TG ≥ 500 mg / dl was associated with 2.63 times the risk.

Current research shows that in a large national cohort involving more than 150000 cancer survivors, TYG index is positively correlated with cardiovascular events in a dose-dependent manner. Similar results were also observed in subgroups of different ages and sexes. It is worth noting that the classification of ASCVD subtypes (such as IHD, AMI and ischemic stroke) is positively correlated, but not hemorrhagic stroke or heart failure. In addition, the slope of association between AMI and ischemic stroke is higher. This study is also the first study to prove the risk of CVD based on the baseline TYG index of cancer survivors. TYG index can be used as a simple alternative marker for risk stratification of future CVD events in cancer survivors.

Source of original text: Jung MH, Yi SW, An SJ, et al. Associations between the triglyceride-glucose index and cardiovascular disease in over 150,000 cancer survivors: a population-based cohort study. Cardiovasc Diabetol. 2022;21(1):52. Published 2022 Apr 16. doi:10.1186/s12933-022-01490-z


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