HTN refers to a common epidemic disease mainly characterized by increased systemic arterial BP, which can be accompanied by functional or organic damage to the heart, brain, and kidneys (1, 2), and is a major risk factor for cardiovascular disease and all-cause mortality (3, 4). According to the world's largest HTN research report, the number of adults aged 30–79 years with HTN increased from 650 million to 1.28 billion over the period 1990–2019 (5); however, nearly half of them are unaware that they have HTN (6). Furthermore, the proportion of patients with HTN who are optimally treated and controlled is low in the general population, especially in those who are in low-resource settings (6, 7). Normal-high BP value is a transitional stage between normotension and HTN; similar to HTN, it also would increase the risk of various cardiovascular diseases and bring a series of complications (8–10), but some studies have put forward different views (11). Overall, evidence based on prospective studies and meta-analyses indicated that the risk of developing chronic HTN in normal-high BP values patients was 2–3 times higher than that of normal people, and the risk of cardiovascular and cerebrovascular diseases was also significantly increased (12–14). Therefore, early identification of patients with normal-high BP values and reduction of potential risk factors to reduce the risk of developing HTN is necessary, which may be feasible and practical to reduce the burden of HTN-related diseases.

Previous studies have suggested that insulin resistance (IR) may be involved in the pathogenesis of HTN by mediating low-grade systemic inflammation (15–17). So far, researchers have proposed a variety of methods to assess IR, among which the gold standard test is the hyperinsulinemic-euglycemic clamp test (18), while the homeostatic model of IR (HOMA-IR) (19) is the most widely used indirect measurement method in clinical practice. However, considering the hyperinsulinemic-euglycemic clamp test is invasive and relatively time-consuming, expensive, and complicated (20), and HOMA-IR is easily affected by the accuracy of insulin measurement and has poor reproducibility (21). Therefore, the development of non-insulin-based IR surrogate indicators may be a more convenient, practical, and cost-effective approach, especially in primary care settings.

TyG-BMI, a recently developed IR surrogate, is an index composed of three easily measurable biochemical parameters [BMI, triglyceride (TG), and fasting plasma glucose (FPG)]. According to Er et al. TyG-BMI has a greater ability to identify IR compared to other non-insulin-based IR indices (22). Furthermore, in several recent epidemiological investigations, TyG-BMI was found to have excellent diagnostic value not only in identifying IR but also in assessing the risk of metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD), HTN combined with hyperuricemia, pre-diabetes and diabetes (23–27). However, it remains unclear whether there is a similar relationship between TyG-BMI and normal-high BP values/HTN, and the diagnostic value of TyG-BMI for normal-high BP values and HTN in the general populations. To address these issues, this study was based on a large sample of 15,464 non-diabetic people in the NAGALA study to investigate the association between TyG-BMI and normal-high BP values and HTN, and to evaluate the accuracy of TyG-BMI in identifying normal-high BP values and HTN.

Between 1994 and 2016, the NAGALA study recruited 20,944 people. A total of 4,339 subjects were excluded due to missing data (n = 863), known liver disease (n = 416), excessive drinking (n = 739), and oral medications at baseline (n = 2,321). In addition, in the baseline examination, 323 diabetic patients and 808 patients with FPG >6.1 mmol/L, and 10 subjects who withdrew from the study for unknown reasons were further excluded. Ultimately, 15,464 individuals were included in this study. The flow chart of subject selection was shown in Figure 1.

Table 1 shows the baseline characteristics of the study population according to the TyG-BMI quartiles. In the quartile with the highest TyG-BMI, the levels of age, weight, height, BMI, WC, ALT, AST, GGT, SBP, DBP, TC, TG, HbA1c, FPG, and TyG index were highest, but HDL-C had the lowest level. The prevalence of normal-high BP values in the highest TyG-BMI group was 11.67%, which was much higher than that in other TyG-BMI groups (Q1: 3.07%, Q2: 5.49%, Q3: 8.33%); similarly, in the highest TyG-BMI group (Q4), the prevalence of HTN was 3.55%, which was also much higher than that in other TyG-BMI groups (Q1: 0.27%, Q2: 0.82%, Q3: 1.60%).

In the current epidemiological survey based on the non-diabetic population, we found that (1) BMI, TyG index, and TyG-BMI were all significantly and independently positively associated with normal-high BP values and HTN in the non-diabetic population; compared with BMI and TyG index alone, TyG-BMI had higher recognition ability for normal-high BP values and HTN. (2) TyG-BMI was more strongly associated with normal-high BP values or HTN in the youth population.

In the past two decades, slightly elevated BP within the normal range has attracted much attention due to its adverse clinical effects (8, 9). Normal-high BP values have been reported to affect approximately 25%–50% of adults worldwide and significantly increase the risk of developing HTN (10). In addition, the risk of cardiovascular disease increases further with increasing BP, and previous studies have shown that the risk of cardiovascular disease was significantly higher in people with BP in the 120–129/80–84 mmHg range and 130–139/85–89 mmHg range than those with the BP in the 120/80 mmHg range (38–40). Therefore, early detection and intervention of normal-high BP values are important to prevent HTN.

The pathogenesis of HTN is complex, and normal-high BP values and HTN individuals are often accompanied by abnormal glucose and lipid homeostasis; it has been reported that about 40% of HTN patients have dyslipidemia and impaired fasting glucose (41–43), and these abnormal glucose and lipid metabolisms will further increase the risk of cardiovascular disease. IR is a key mechanism of glycolipid metabolism (16) and an important precursor to the early stages of the disease. Generally speaking, the physiological function of insulin to lower blood glucose is somewhat limited when IR occurs, and the body then secretes as much insulin as possible. In addition, excessive secretion of insulin tends to produce hyperinsulinemia, which becomes a potential disease hazard (44, 45); hyperinsulinemia can contribute to increased renal tubular sodium reabsorption, sympathetic excitation, accelerated heart rate, increased vascular resistance, dyslipidemia, and narrowing of atherosclerosis, which in turn can increase intracellular calcium ion concentration and sensitivity to elevating substances, leading to the development of HTN (16, 46).

TyG index, a combined marker containing TG and FPG, has previously been extensively studied and is considered an alternative marker for IR (31, 47, 48). In a recent study, Professor Zeng and his team found that the TyG index can also be used to identify individuals at high risk for normal-high BP values (49), and their findings further suggested that IR was strongly associated with normal-high BP values. BMI is the most important anthropometric measure commonly used in clinical practice to evaluate obesity and is a recognized predictor of HTN (50). Obesity is often accompanied by an elevated prevalence of HTN; conversely, weight control is effective in reducing BP (50, 51). TyG-BMI is a newly developed IR surrogate in recent years, which is the product of BMI and TyG index. In one of the earliest TyG-BMI-related studies, Er et al. found that TyG-BMI could better reflect IR compared with lipid parameters, lipid ratios, glucose parameters, TyG index, and obesity-related parameters (22). Several subsequent studies further found that TyG-BMI was also strongly associated with a variety of metabolic diseases (23–27). In March 2021, Raimi et al. analyzed the relationship between TyG-BMI and MS, and they pointed out that the product combination of BMI and TyG index improved the ability to identify MS (23); in May of the same year, in a cross-sectional study by Li et al., they found that TyG-BMI had moderate discriminatory power in distinguishing HTN from hyperuricemia (26). In addition, some observational studies have further found that TyG-BMI also has the potential to predict the risk of NAFLD and diabetes, especially in young and middle-aged and non-obese people (24, 27). Similarly, in a longitudinal cohort study with a median follow-up time of 3.1 years, Jiang et al. also found similar results, in which higher TyG-BMI levels significantly increased the risk of prediabetes (26). These findings all suggested that TyG-BMI has a certain application value in metabolic diseases. However, there are relatively few studies on the associations between TyG-BMI and normal-high BP values and HTN, and in a recent cross-sectional study of Chinese lean-weight adults by Zeng et al., they found that TyG-BMI showed a strong positive correlation with normal-high BP values (49), which was similar to the results of our subgroup analysis, but in further analysis, we found that the associations between TyG-BMI and normal-high BP values/HTN were not significantly different between obese and non-obese groups, further research is needed. Compared with the research of Zeng et al., we further calculated the OR value and 95% CI of the corresponding normal-high BP values and HTN after Z-conversion of BMI, TyG index and TyG-BMI. Before and after the adjustment of the model, among the three parameters, the TyG-BMI index had the strongest correlation with normal-high BP values and HTN, followed by BMI, and finally TyG index. In addition, it is worth mentioning that the current study also found a similar trend in ROC analysis: among the three parameters, TyG-BMI has the highest accuracy in identifying normal-high BP values and HTN, followed by BMI, and finally TyG index. These results together suggested that, after a further combination of TyG index and BMI, BMI-related components may greatly improve the assessment/recognition ability for HTN and normal-high BP values. Based on the background of the current research (15–17), the reason for this result may be closely related to IR, and the combination of the TyG index and obesity index BMI improved the ability to identify IR (22), thereby enhancing the ability to identify HTN/normal-high BP values. In addition, we also constructed natural smoothing splines and found that TyG-BMI was linearly positively correlated with SBP and DBP. This further supported the linear trend of TyG-BMI with HTN/normal-high BP values. To my knowledge, the current study revealed for the first time a linear association between TyG-BMI and SBP/DBP. These new findings may be able to provide new strategies and approaches for the prevention of normal-high BP values and HTN in different populations.

We also found some interesting results in our subgroup analysis: compared with other age groups, the correlation between TyG-BMI and normal-high BP values and HTN was relatively higher in young people. We speculated that the reason for this result may be related to the increasing poor dietary habits as well as lifestyle habits of young people. It has been shown that obesity during childhood and adolescence greatly increases the risk of developing HTN in adulthood (52). Not only that, some poor lifestyles such as a high-salt diet, sedentary lifestyle, excessive alcohol consumption, lack of exercise, chronic mental stress, and sleep deprivation are problems faced by contemporary young people, which greatly contribute to the prevalence of HTN (53). In addition, longitudinal studies have reported that high BP levels measured in childhood and adolescence often transform into stable hypertension in adulthood, with significant and substantial epidemiological implications and clinical relevance, a phenomenon known as “BP tracking” (54–56).

In the non-diabetic population, TyG-BMI was significantly and positively associated with both normal-high BP values and HTN; TyG-BMI has higher values for both normal-high BP values and HTN identification compared to BMI and TyG index alone. TyG-BMI has the potential to be a cost-effective monitoring indicator as well as a non-invasive assessment method in the individual stratified management of normal-high BP value and may serve as an accessible complementary monitoring method in the future risk stratification management of HTN.