Positive association between triglyceride glucose index and arterial stiffness in hypertensive patients: the China H-type Hypertension Registry Study

Data analyzed in this study was the baseline of the ongoing China H-type Hypertension Registry Study (Registration number: ChiCTR1800017274). The method of data collection and the exclusion criteria have been described previously [27]. Briefly, the study is a real-world, multicenter, observational study, conducted from Wuyuan, Jiangxi province of China, which conducted in March 2018. Eligible participants were adults aged 18 years and older who had hypertension, defined as seated, resting systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg at the screening, or who were on antihypertensive medications. The exclusion criteria included neurological abnormalities, unable to be followed-up according to the study protocol, or plans to relocate shortly, and the patients, who are not suitable for inclusion or for long-term follow-up as assessed by study physicians. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Institute of Biomedicine, Anhui Medical University. All participants provided written informed consent.

This study was restricted to a subset of participants with baPWV data available at baseline (n = 5233). Participants with an ankle-brachial index (ABI) < 0.90 (n = 124), taking statins (n = 181), or using glucose-lowering medications (n = 210), were excluded. Finally, 4718 subjects were analyzed. The selection process of study analytic sample was detailed description in Additional file 1: Figure S1.

According to a standard operating procedure, the baseline data of clinical examination and detailed questionnaires were collected by trained researchers. The standard questionnaire included age, sex, education, physical activity, current medication from pill bottles, previous medical diagnoses, smoking history, and drinking history. Anthropometric parameters indicators of the clinical examination included weight, height, waist circumference, SBP, DBP. The body mass index (BMI) was calculated as weight (kg)/height (m²). Blood pressure (BP) was measured using an electronic sphygmomanometers (Omron; Dalian, China) with the subject in the sitting position after resting for 10 min, the average of the three measurements was used.

Fasting venous blood samples were collected at the baseline, and were processed and analyzed at the clinical laboratory of the National Clinical Research Center for Kidney Disease, Guangzhou, China. Fasting plasma glucose, fasting lipids (total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides), serum homocysteine, serum uric acid, and creatinine were determined using automatic clinical analyzers (Beckman Coulter). The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The formula for estimated glomerular filtration rate (eGFR) was used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [28].

The ankle-brachial index (ABI) and baPWV were measured simultaneously with Omron Colin BP-203RPE III device (Omron Health Care, Kyoto, Japan). After having rest for more than 5 min in the supine position, 4 cuffs were wrapped around bilateral brachia and ankles and connected to a plethysmographic sensor and oscillometric pressure sensor. ABI was measured by the ankle SBP divided by the brachial SBP. Pressure waveforms were recorded using semiconductor pressure sensors to assess the transmission time between the initial rises in both the brachial and tibial arteries waves. The distance between sampling points of baPWV was estimated based on height. The baPWV was calculated using the formula (La-Lb)/Tba. La is the distance from the heart to the ankle, Lb is the distance from the heart to the brachium, and Tba is the time interval between the brachial and ankle waveforms. Two trained technicians were performed twice, and the average values of the left and right side assessments was used as a marker of arterial stiffness.

Data are presented as mean ± standard deviation (SD) for continuous variables and as frequency (%) for categorical variables. The baseline characteristics of the different groups by TyG index quartiles were compared using ANOVA tests or Chi square tests. The relationships between the TyG index and cardiometabolic risk factors were examined using Pearson’s correlation. Because the predictive value of baPWV in cardiovascular events was not available. Elevated baPWV was defined as a value greater than 75th percentile of baPWV value in present study, which was greater than 20.02 m/s. The independent association of the TyG index with baPWV and elevated baPWV were evaluated using multivariate linear regression models (beta coefficient [β] and 95% confidence interval [CI]) and multivariate logistic regression models (odds ratio [OR] and 95% CI) with adjustment for major covariables in three models. Model 1: adjusted for age; Model 2: further adjusted for age, sex, education, BMI, waist circumference, physical activity, current smoking, current drinking, SBP, DBP; Model 3: additionally adjusted for age, sex, education, BMI, waist circumference, physical activity, current smoking, current drinking, SBP, DBP, serum uric acid, serum homocysteine, HDL-C, LDL-C, eGFR, self-reported diabetes, antihypertensive drugs, antiplatelet drugs. In the regression analyses model, the following variables were selected because of their clinical importance, statistical significance in the univariable analysis, and the potential confounders effect estimates individually changed by at least 10%. Dose–response association of TyG index with baPWV and elevated baPWV were conducted using generalized additive model (GAM) and a fitted smoothing curve (penalized spline method). In addition, possible modifications on the association between TyG index and baPWV were also evaluated by stratified analyses and interaction testing.

All data analyzed were using the statistical package R (http://​www.​r-project.​org) and Empower (R) (www.​empowerstats.​com; X&Y Solutions, Inc., Boston, MA). A 2-tailed P < 0.05 was considered to be statistically significant.

Data of 4718 participants were included in current analysis. The mean (SD) age of the participants was 64.41 (9.48) years; 2346 were men (49.72%). The mean baseline TyG index was 8.84 (0.63). Mean baPWV was 18.05 (3.85) m/s. The characteristics of the participants by TyG index quartiles are presented in Table 1. TyG index was inversely associated with age, serum homocysteine, HDL-C, and positively associated with BMI, waist circumference, DBP, fasting plasma glucose, total cholesterol, triglycerides, serum uric acid, LDL-C, and eGFR. Moreover, participants with higher TyG index were significantly more likely to have diabetes mellitus, higher education levels, and using antihypertensive drugs. Participants with lower TyG index were significantly more likely to men, current smokers, and current drinkers.

The results of pearson’s correlation analysis for the relationship between the TyG index and cardiometabolic risk factors were described in Table 2. The TyG index was significantly correlated with BMI, waist circumference, SBP, DBP, HDL-C, LDL-C, serum uric acid, and eGFR, but not serum homocysteine, after adjusted for age and sex.

Overall, there were significant positive associations of TyG index with baPWV and the risk of elevated baPWV (Fig. 1a, b). Per 1 unit increment in TyG index, baPWV is changed in 1.02 m/s (95% CI 0.83, 1.20) according to the estimation from regression coefficients indication, and the odds ratios (OR) of the risk of elevated baPWV was 2.12 (95% CI 1.80, 2.50).

As shown in Table 3, after adjustment for different confounders, the positive association between TyG index and baPWV was found in all models (model 1–3). When TyG index was assessed as quartiles, in the fully adjusted model (model 3), the adjusted β of baPWV for participants in quartile 2, quartile 3, and quartile 4 were 0.59 (95% CI 0.33, 0.85), 0.89 (95% CI 0.61, 1.18), and 1.56 (95% CI 1.25, 1.88), respectively, compared with those in quartile 1 (P for trend < 0.001). Consistently, Table 4 presented the relative odds of having an elevated baPWV. Compared to participants in the lowest TyG index quartile, the adjusted OR for participants in the second, third and fourth quartiles were 1.49 (95% CI 1.18, 1.88), 2.07 (95% CI 1.60, 2.67), and 3.35 (95% CI 2.52, 4.45), respectively. Also, P for trend in all models was significant (P for trend < 0.001), suggesting a dose–response relation between TyG index and baPWV and elevated baPWV.

We further performed stratified analyses to assess the effect of TyG index (per 1 unit increment) on baPWV in various subgroups. The association between TyG index and baPWV were consistent in the following subgroups: age (< 65 vs. ≥ 65 y; P-interaction = 0.11), BMI (< 25 vs. ≥ 25 kg/m²; P-interaction = 0.15), physical activity (mild, moderate, vigorous; P-interaction = 0.71), current smoking (no vs. yes; P-interaction = 0.37), current alcohol drinking (no vs. yes; P-interaction = 0.97), SBP (< 140, 140-159, ≥ 160 mmHg; P-interaction = 0.99), DBP (< 90, 90-99, ≥ 100 mmHg; P-interaction = 0.30), self-reported diabetes (no vs. yes; P-interaction = 0.68), LDL-C (median, < 2.85 vs. ≥ 2.85 mmol/L; P-interaction = 0.38), and eGFR (< 60 vs. ≥ 60 mL/min per 1.73 m²; P-interaction = 0.55).

However, there was a significant interaction between TyG index and sex on baPWV. A stronger positive association between TyG index and baPWV was found in men (β, 1.21; 95% CI 0.95, 1.46) compared with women (β, 0.75; 95% CI 0.49, 1.00; P-interaction = 0.02) (Fig. 2, Additional file 1: Figure S2). In addition, We further converted TyG index from a continuous variable to a categorical variable (quartiles) to explored the association of TyG index with baPWV and elevated baPWV in different gender. The Magnitude of the effect of increase of the TyG index on baPWV and elevated baPWV were greater in men than in women (Additional file 1: Table S1).