ABSTRACT
Background
The triglyceride and glucose (TyG) index has been found to be significantly associated with a higher risk of mortality. However, there has been a lack of studies exploring the specific relationship between the TyG index and all-cause and cardiovascular mortality among middle-aged and elderly with hypertension.
Methods
A total of 3,614 participants with hypertension were enrolled from the National Health and Nutrition Examination Survey. The TyG index was calculated using the formula log [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2]. The Cox proportional hazard ratios were used to evaluate the association between the TyG index and the risk of mortality.
Results
Over a follow-up period of 7.87 years, 991 all-cause death and 189 cardiovascular deaths occurred. Compared with the reference quartile, the multivariate-adjusted hazard ratios and 95% confidence intervals were 1.28 (1.07–1.53; p = .006) in the fourth quartile for all-cause mortality and 0.63 (0.42–0.96; p = .031) in the second quartile for cardiovascular mortality. Dose-response analysis indicated an L-shaped relationship.
Conclusions
The TyG index exhibited an L-shaped association with the risk of all-cause mortality among middle-aged and elderly with hypertension.
Introduction
Hypertension is the leading cause of death worldwide and the most significant risk factor for cardiovascular disease morbidity and mortality (Citation1). In 2012, the global prevalence of hypertension was estimated to be approximately 55% (Citation2).
The triglyceride glucose (TyG) index has been proposed as a surrogate marker of insulin resistance (Citation3). Several studies have indicated that the TyG index is linked to arterial stiffness (Citation4,Citation5), contributing to an elevated risk of hypertension. Moreover, the TyG index has been identified as a predictor of incident hypertension (Citation6), as well as albuminuria (Citation7) and hyperuricemia (Citation8) in hypertensive patients. However, no previous studies have investigated the specific relationship between TyG index and the long-term all-cause and cardiovascular mortality in hypertension.
Therefore, our study aimed to assess the association between the TyG index and all-cause and cardiovascular mortality in a population with hypertension.
Materials and methods
Study population
The study included individuals from a nationwide survey conducted by the National Center for Health Statistics (NCHS) in the United States. Hypertension was defined as either self-reported hypertension, systolic blood pressure of 140 mmHg or higher, diastolic blood pressure of 90 mmHg or higher, or the use of antihypertensive medications. After excluding participants with missing data on fasting triglycerides and glucose, as well as missing mortality status, we enrolled 3614 hypertensive participants in our study. All participants provided written informed consent, and the protocol was approved by the Review Board of NCHS (Protocol #98–12, Protocol #2005–06, and Protocol #2011–17).
Variables and outcomes
TyG index was calculated as ln [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2]. Fasting serum triglycerides and glucose were measured enzymatically using Roche Modular P chemistry analyzer. Information on age, gender, race, education level, smoking status, and physical activity, and comorbidities were collected by using standardized questionnaires. The height and weight of each participant were obtained from the physical examinations. Multiple imputation using predictive mean matching was performed for covariates with missing values.
Mortality status was obtained by linkage to the National Death Index by 31 December 2015. Cardiovascular disease was defined as ICD-10 codes I00-I09, I11, I13, I20-I51, I60-I69 and I70–78.
Statistical analysis
Data are presented as mean ± standard deviation or number (proportions). Differences among different TyG index quartiles (Citation9) were explored by one-way analysis of variance and chi-square test or rank sum test appropriately, with post hoc multiple comparisons. Kaplan – Meier methods were used to derive the event rates at follow-up and to plot time-to-event curves. Differences among Kaplan – Meier estimates of the three groups were evaluated using the log-rank test. Multivariate Cox regression models were employed to estimate the associations between the TyG index and the risk of all-cause and cardiovascular mortality, with 95% confidence intervals. The confounding variables were chosen based on two criteria (1): significant differences observed among TyG quartiles and (2) clinical relevance to all-cause and cardiovascular mortality. Model 1 was unadjusted. Model 2 was adjusted for age, and gender. Model 3 was adjusted for age, gender, race, education, BMI, smoking and activity. Sample weights, clustering, and stratification were incorporated in all analyses. All analyses were performed using the statistical package R version 3.6. All P values were set to a significance level of <0.05.
Results
The present study included 3,614 participants with an average of 62.5 years old and 1821 (50.4%) male individuals. The baseline characteristics of the study population according to TyG quartile are shown in . The fourth quartile tended to be younger (p = .013) and had a higher level of BMI.
Table 1. The characteristics of participants according to TyG index.
During an average follow-up of 7.87 years, there were 991 deaths from any cause and 189 deaths specifically attributed to cardiovascular causes. As shown in , Kaplan–Meier analysis suggested that the lowest and highest TyG levels were associated with a higher all-cause mortality (log-rank p = .01), but not with cardiovascular mortality (log-rank p = .1). As shown in , dose–response analysis suggested that TyG index was L-shaped associated with the risk of all-cause mortality. Therefore, we set the third quartile as the reference group. As shown in , when compared with the reference quartile, the hazard ratios of the fourth quartile for all-cause mortality were 1.22 (1.03–1.45; p = .024) in unadjusted Model 1, 1.32 (1.11–1.57; p = .002) in partly-adjusted Model 2 and 1.28 (1.07–1.53; p = .006) in fully-adjusted Model 3. As shown in , the second quartile was significantly associated with cardiovascular mortality across three models: 0.65 (0.43–0.97; p = .037) in Model 1, 0.62 (0.41–0.94; p = .025) in Model 2 and 0.63 (0.42–0.96; p = .031) in Model 3.
Figure 1. The Kaplan-Meier analysis of the prognostic effect of TyG index on all-cause mortality (a) and cardiovascular mortality (b).
Figure 2. The dose–response relationship between TyG index with all-cause mortality (a) and cardiovascular mortality (b).
Table 2. Association of TyG index with all-cause cardiovascular mortality.
Table 3. Association of TyG index with cardiovascular mortality.
Discussion
In this study, we found that TyG index was L-shaped associated with the risk of all-cause mortality in hypertensive participants. A higher TyG index was independently associated with an increased risk of all-cause mortality. In addition, no significant association between TyG index and cardiovascular mortality was found. Overall, these findings suggest that the TyG index can serve as a reference value and a predictor of all-cause mortality in clinical practice, particularly for hypertensive individuals.
There have been multiple publications reporting an increased risk of hypertension (Citation10) and stroke (Citation11) associated with TyG. Furthermore, some studies found that TyG was positively related to all-cause mortality in general population (Citation12), diabetes (Citation13) and critically ill (Citation14). In consistent with these, our results also showed that a higher TyG index increased the risk of all-cause mortality in middle-aged and elderly with hypertension. However, no significant association between TyG index and cardiovascular mortality was found. This could be explained that middle-aged and elderly were at the risk of cardiovascular diseases. Besides, a lower TyG index was not related to lower risk of mortality, which may be related to a poor nutrition status. Xia et al. found that lower triglycerides were associated with chronic illness (Citation15). This makes a strong case for target ranges for triglycerides and glucose rather than target levels.
It was reported that TyG index was an independent predictor for cardiovascular mortality in patients with diabetes (Citation16), acute coronary syndrome (Citation17), obesity (Citation18) and hypercholesterolemia (Citation19). In general population, TyG index increased the risk of death from cardiovascular diseases (Citation20,Citation21). However, our study did not observe a significant association between TyG index and cardiovascular mortality in middle-aged and elderly with hypertension. It appeared that in the population of elderly individuals or those with hypertension, the effect of triglycerides (TG) or glucose on cardiovascular mortality was eliminated.
It is important to acknowledge these limitations as they may impact the interpretation of the findings. Firstly, data on triglycerides and glucose were only collected once at baseline without follow-up measurements to track any changes over time. The second limitation was that the presence of hypertension was self-reported based on questionnaires, which introduced the possibility of recall bias or inaccuracies in the data.
Conclusions
We found TyG index was L-shaped associated with the risk of all-cause mortality in middle-aged and elderly with hypertension. A higher TyG index was independently associated with increased risk of all-cause mortality.
Authors’ contributions
Q X designed the study; P J made the statistical analysis; LY Q and XR C prepared the tables; PL wrote the manuscript. All authors approved the final manuscript.
Ethics approval and consent to participate
The protocol was approved by the NCHS Research Ethics Review Board (Protocol #98–12, Protocol #2005–06, and Protocol #2011–17).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
The original data can be obtained from NHANES (https://www.cdc.gov/nchs/nhanes/index.htm).
Additional information
Funding
References
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