https://orcid.org/0000-0001-9183-477X
?Mathematical formulae have been encoded as MathML and are displayed in this HTML version using MathJax in order to improve their display. Uncheck the box to turn MathJax off. This feature requires Javascript. Click on a formula to zoom.ABSTRACT
Background: Major adverse cardiovascular events (MACE) are common in patients with hypertension and are associated with higher mortality.
Methods: This study aimed to observe the incidence of MACE in hypertensive patients and the correlation between the electrocardiogram (ECG) T-wave abnormalities and echocardiographic changes. This retrospective cohort study analyzed the incidence of adverse cardiovascular events and changes in echocardiographic features in 430 hypertensive patients admitted to Zhongnan Hospital of Wuhan University from January 2016 to January 2022. Patients were grouped according to a diagnosis of electrocardiographic T-wave abnormalities.
Results: Compared with the normal T-wave group, the incidence of adverse cardiovascular events was significantly higher in hypertensive patients with abnormal T-wave (141 [54.9%] vs 120 [69.4%], x^2 = 9.113, P = .003). However, Kaplan-Meier survival curve showed that no survival advantage was observed in the normal T-wave group at all in the hypertensive patients (P = .83). Echocardiographic values associated with cardiac structural markers, including ascending aorta diameter (AAO), left atrial diameter (LA), and interventricular septal thickness (IVS), were significantly higher in the group with abnormal T-wave than those in the group with normal T-wave at baseline and follow-up (P <.05 for all). In addition, in an exploratory Cox regression analysis model stratified by clinical characteristics of hypertensive patients, the forest plot indicated that the variables, including the age (>65 years), hypertension history (>5 years), premature atrial beats, and severe valvular regurgitation were significantly associated with adverse cardiovascular events (P <.05).
Conclusion: Hypertensive patients with abnormal T-wave show a higher incidence of adverse cardiovascular events. The values of cardiac structural markers were significantly higher in the group with abnormal T-wave.
Introduction
Hypertension is a leading cause of long-term adverse cardiovascular events. Early detection and prompt management of cardiovascular disease (CVD) risk in hypertensive patients is imperative to guide clinicians and decrease CVD burdens worldwide (Citation1,Citation2).
In clinical practice, ECG is often used as a screen tool for CVD because of its inexpensiveness and large-scale applicability to CVD. T-wave abnormalities are easily noticed in ECG and have been reported to be associated with typical myocardial ischemic changes, such as T-wave inversion (TWI), ST-segment depression (STD), ST-segment elevation (STE) and other ST-T abnormalities (STT) (Citation3–5). It is precisely because T-wave abnormalities can be used to diagnose certain cardiovascular diseases and predict clinical prognosis that there is growing interest in the long-term clinical significance(Citation6).
On the other hand, hypertension can lead to changes in both structure and function within the heart over time(Citation7). Changes in cardiovascular cardiac structure and function in hypertensive patients can be examined noninvasively by echocardiography (Citation8,Citation9).
However, whether T-wave abnormalities are also related to cardiac structure and function and CVD risk in hypertensive patients is unknown. Therefore, we conducted a retrospective, observational cohort study to investigate the echocardiographic variables of hypertensive patients with T-wave abnormalities at baseline and during follow-up, and to assess possible associations between CVD and T-wave abnormalities in patients with hypertension.
Methods
Study design and setting
The study population was derived from Zhongnan Hospital of Wuhan University. This retrospective, single-center observational cohort study was conducted from January 2016 to January 2022. General inclusion criteria included patients older than 18 years who were first diagnosed with hypertension according to the 2017 ACC/AHA blood pressure guidelines and were readmitted to the hospital for follow-up(Citation10). Patients with previous cardiovascular and cerebrovascular diseases, a history of malignancy, severe underlying liver and kidney diseases, and insufficient clinical data were not included in the study. Therefore, a total of 430 hypertensive patients were included in this study and divided into abnormal T-wave group and normal T-wave group according to ECG diagnosis (). The diagnostic criteria of T-wave abnormalities in this study included T-wave inversion (TWI), T-wave depression (TWD), and other ST-T abnormalities (STT)(Citation5). The primary endpoint was major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, acute coronary syndrome, malignant arrhythmia, acute decompensated heart failure, and death from cardiovascular causes.
Figure 1. Selection of the study population according to inclusion and exclusion criteria.
Data collection
The data were obtained and refined from previous inpatient and outpatient medical records, and retrospectively analyzed to determine the patient’s demographic and clinical characteristics such as age, gender, blood pressure, heart rate, ECG abnormalities and underlying disease (hyperlipidemia, diabetes mellitus); laboratory tests such as blood glucose, lipid profile and level of serum myocardial enzyme; echocardiography features such as AAO, LA, IVS, left ventricular diameter (LV), pulmonary artery diameter (PA), and left ventricular ejection fraction (LVEF).
Statistical analysis
Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were expressed as numbers and percentages. Significant differences in the clinical characteristics between the two study groups were compared with t-test for continuous variables and chi-square test for categorical variables. Survival curves were estimated with the Kaplan-Meier method and compared using the two-sided log-rank test. Exploratory multivariable analyses were performed using the Cox proportional hazards model and presented in forest plots, including hazard ratios (HRs) and 95% confidence intervals (CIs). A value of P <.05 was considered as statistical significance in two-tailed tests. Statistical analyses were conducted by RStudio (version 2021.09.1.0).
Results
Demographic and baseline characteristics
A total of 173 (40.2%) patients presented with abnormal T-wave and 257 (59.8%) with normal T-wave. Baseline characteristics of the patients with different T-wave are shown in . Among the patients, 199 were males (46.3%) and 231 were females (53.7%), with an average age of 64.8 ± 14.1 years. Patients were followed up for a mean period of 24.06 ± 16.16 months. Previous comorbidities included hyperlipidemia in 56 patients (13.02%) and diabetes mellitus in 81 (18.84%) patients. Statins were used in 41 (9.53%) patients, ACEi/ARB in 187 (43.48%) patients, and aspirin in 17 (3.95%) patients. In addition, of the 168 patients with left ventricular hypertrophy (LVH) on echocardiography, 94 (55.95%) showed abnormal T-waves on ECG. Hypertensive patients with abnormal T-wave had significantly higher systolic blood pressure than patients with normal T-wave (143.69 ± 19.83 vs 137.77 ± 17.42, P = .001).
Table 1. Comparison of baseline characteristics of the two groups of hypertensive patients.
The baseline ECG characteristics and clinical findings of 430 hypertensive patients are summarized in . Sinus bradycardia, atrial premature beat, and ventricular premature beat were most common in patients with normal T-wave (p <.05 for all). No differences were observed between patients with abnormal and normal T-wave in terms of blood glucose, lipid profile, and serum myocardial enzyme levels. Furthermore, LVEF and LV were comparable between groups in echocardiographic findings at baseline. However, hypertensive patients with abnormal T-wave had higher AAO (33.38 ± 4.25 vs 31.24 ± 4.23, P <.001), LA (35.41 ± 6.34 vs 33.09 ± 5.33, P = .001), IVS (11.45 ± 2.01 vs 10.93 ± 1.65, P = .017), and PA (25.08 ± 3.35 vs 24.34 ± 2.69, P = .042) compared to patients with normal T-wave. Similarly, the mean values of serum creatinine (Cr) and blood urea nitrogen (BUN) in the abnormal T-wave group were significantly higher than those in the normal T-wave group (P <.05 for all).
Table 2. Comparison of clinical findings of the two groups of hypertensive patients.
Clinical outcomes
During the 5-year follow up period, MACE occurred in 120 (69.4%) hypertensive patients with abnormal T-wave, and 141 (54.9%) hypertensive patients with normal T-wave. Here it is important to note that our results only indicated that the incidence of adverse cardiovascular events was significantly higher in hypertensive patients with abnormal T-wave than those with normal T-wave (141 [54.9%] vs 120 [69.4%], =9.113, P = .003).
According to whether T waves were abnormal or not, the survival curves and incidence of MACE in hypertensive patients are presented in . The Kaplan-Meier survival curve showed no significant difference in survival benefit between the abnormal and normal T-wave group of hypertensive patients (P = .83). Our further analysis indicated that compared with patients with normal T waves, the HR for adverse cardiovascular events in hypertensive patients with abnormal T waves was 0.93 (95% CI 0.70–1.23, P = .602).
Figure 2. Kaplan-Meier curves of event-free survival for adverse cardiovascular events over 5 years in hypertensive patients.
Echocardiographic changes
A second clinical findings were recorded several months after the baseline examinations in 430 hypertensive patients. Echocardiographic changes associated with T-wave abnormalities are presented in and . We compared the differences between baseline and follow-up in each group and compared the clinical findings and echocardiographic characteristics between the two groups at follow-up. For hypertensive patients, significant increase in LA (36.78 ± 9.43 vs 33.09 ± 5.33, P <.001), LV (44.66 ± 5.10 vs 43.55 ± 4.13, P = .001) and significant decrease in LVEF (63.87 ± 7.92 vs 67.06 ± 6.20, P <.001) levels were observed among all hypertensive patients with and without T-wave abnormalities. It is also worth noting that echocardiographic values associated with markers of cardiac structural, including AAO (33.84 ± 4.76 vs 32.20 ± 4.35, P = .002), LA (38.34 ± 9.41 vs 35.65 ± 9.30, P = .012), LV (45.33 ± 5.69 vs 44.18 ± 4.58, P = .047) and IVS (11.26 ± 2.06 vs 10.73 ± 1.61, P = .009), were significantly higher in the abnormal T-wave group than in the normal T-wave group during follow-up.
Figure 3. Abnormal T-wave vs. normal T-wave during follow-up. (A) Ascending aorta diameter, (B) Left atrial diameter, (C) Left ventricular diameter, (D) Interventricular septal thickness, (E) Pulmonary artery diameter and (F) Left ventricular ejection fraction. Statistically significant differences are indicated as *P <.05, **P <.01, and ***P <.001.
Table 3. Comparison of baseline and follow-up clinical findings of hypertensive patients.
In our analysis, no significant differences were observed in IVS, creatine kinase (CK), lactate dehydrogenase (LDH), and brain natriuretic peptide (BNP) between baseline and follow-up periods in hypertensive patients (P > .05 for all). In contrast, the mean values of blood glucose (6.02 ± 2.01 vs 5.77 ± 1.95, P = .024), Cr (82.70 ± 41.46 vs 76.90 ± 28.40, P <.001), BUN (6.27 ± 2.91 vs 5.60 ± 1.83, P <.001) and uric acid (380.16 ± 127.98 vs 364.07 ± 113.84, P = .002) during follow-up were statistically higher than baseline in all hypertensive patients (P < .05 for all) (). In addition, except Cr (89.16 ± 51.82 vs 78.29 ± 31.92, P = .015) and BUN (6.77 ± 3.40 vs 5.92 ± 2.47, P = .005), there were no significant differences in laboratory test results between the abnormal and normal T-wave groups ().
Exploratory secondary analyses
In order to explore the risk factors for MACE in hypertensive patients, Cox proportional hazards models were performed stratified by clinical characteristics. The risks of MACE associated with hypertensive patients during the complete follow-up were presented in the forest plot (). In exploratory secondary analyses, age (HR 1.57, 95% CI 1.16–2.13, P = .004), hypertension history (HR 1.48, 95% CI 1.14–1.93, P = .003) and severe valve regurgitation (HR 1.42, 95% CI 1.00–2.02, P = .049) were independent predictors of MACE in hypertensive patients ().
Figure 4. Hazard ratios for adverse cardiovascular events stratified by clinical characteristics in hypertensive patients.
Discussion
An increasing number of studies have observed the changes in cardiac structure and function as well as the occurrence of long-term adverse cardiovascular events in hypertensive patients. Therefore, effective diagnostic methods are essential for timely prevention and treatment of MACE in hypertensive patients. ECG has long been used as an important auxiliary clinical examination for various forms of heart disease in many areas of medical practice due to its simple clinical operation and high safety. The most common minor ECG abnormalities were abnormal T-wave inversion and minor isolated ST abnormalities(Citation11). Patients with minor nonspecific ST-segment and T-wave abnormalities on ECG may benefit from annual ECG to refine risk estimates for future CVD and coronary heart disease (CHD) events (Citation12–14).
Previous studies of patients with nonspecific major T-wave abnormalities have observed that isolated minor T-wave abnormalities are associated with an increased risk of cardiovascular disease and coronary heart disease mortality (Citation15–17). In addition, a review of the clinical significance of minor nonspecific ST-segment and T-wave abnormalities in asymptomatic subjects suggested that minor T-wave abnormalities are important risk factors for coronary and cardiovascular mortality(Citation18). In order to investigate the clinical effect of T-wave abnormalities on this specific population of hypertensive patients and so as to further clarify the predictive value of T-wave abnormalities in ECG for CVD in hypertensive patients, we only included patients who were first diagnosed with hypertension in this analysis, and the results showed that the incidence of MACE was significantly higher in hypertensive patients with abnormal T-wave than those with normal T-wave (141 [54.9%] vs 120 [69.4%], P = .003).
However, no survival advantage was observed in the normal T-wave group in the survival curve analysis. The reason may be that our study was a retrospective clinical study, and there was a significant difference in follow-up time between the abnormal T-wave group and the normal T-wave group (16.58 ± 1.26 vs 14.78 ± 0.92, P = .014). Therefore, the incidence of MACE in the two groups identified in our study was not as accurate as survival analysis, which appears to influence the judgment of the effect of T-wave abnormalities in hypertensive patients. Although previous studies suggest that the high prevalence of minor nonspecific ST-segment and T-wave abnormalities may indicate increased and persistent hypertension or atherosclerosis, the underlying physiological mechanisms by which T-wave abnormalities are associated with CVD and CHD events have not been identified, and further studies are necessary to understand the potential relationship between T-wave abnormalities and the risk of CVD and CHD events (Citation19–21).
A systematic review of the relationship between traditional cardiovascular risk factors and the development of ECG abnormalities suggests that asymptomatic ECG abnormalities are prospectively and independently associated with CVD events, and may be caused by cardiac structural changes or arrhythmias(Citation12). Evidence from previous studies suggests that minor nonspecific ST-segment and T-wave abnormalities may associate with early left ventricular hypertrophy (LVH), or increased left ventricular (LV) mass (Citation11,Citation22,Citation23). To identify changes in cardiac structure and function in hypertensive patients with abnormal T-wave on ECG, 430 hypertensive patients were analyzed for echocardiographic changes in this study. The result suggested that echocardiographic changes were common in hypertensive patients regardless of T-wave abnormalities, which were generally consistent with those reported in the literature that increased risk of cardiac structural and functional alterations in patients with hypertension (Citation24–27).
Our study innovatively found that hypertensive patients in the abnormal T-wave group had altered cardiac structure and function at baseline, mainly with significantly higher AAO, LA, IVS, and PA than those in the normal T-wave group. In addition, LA and LV were significantly higher and PA and LVEF were significantly lower in hypertensive patients in the abnormal T-wave group compared to baseline during follow-up. Similarly, hypertensive patients in the normal T-wave group also had higher LA and lower LVEF. In summary, the novel finding of this study was that the most common echocardiographic changes in hypertensive patients, whether T-waves were abnormal or not, were increased LA and decreased LVEF. The key finding of this study was that LV was significantly increased in the abnormal T-wave group compared with the normal T-wave group during the follow-up period (45.33 ± 5.69 vs 44.18 ± 4.58, P = .047). In addition, severe valve regurgitation was also found in hypertensive patients during follow-up (33.3%), with a significantly higher proportion of valve regurgitation in the abnormal T-wave group (35.8%) than in the normal T-wave group (31.5%).
Then, in order to further investigate the relationship between hypertension and the occurrence of MACE, we analyzed possible independent predictors of MACE in hypertensive patients. The result indicated that age, hypertension history and severe valve regurgitation were three independent factors for the development of MACE, and supported the findings of other observational studies that age and mean platelet volume was found to be independent predictors of MACE (Citation28,Citation29). Although this study did not find the relationship between T-wave abnormalities and MACE-free survival in hypertensive patients, our findings still provide important evidence for current knowledge and remain beneficial for clinicians to early detect hypertensive patients at high risk of MACE and intervene in advance.
The main strength of our study is its novelty. We extend these findings to a more heterogeneous population of hypertensive patients, demonstrating the role of T-wave abnormalities in the prognosis of hypertensive patients and in monitoring changes in cardiac structure and function. Our study had potential limitations and should be considered. First, conducting a study at a single center may impact its external validity. Second, this study had small sample sizes, which reduced the statistical power and increased the chance of type 2 errors. In addition, electrolyte imbalances not considered in this study may be associated with T-wave changes. Some potentially important parameters such as antiplatelet drug, the severity scale of coronary artery stenosis may have been excluded from the retrospective analysis. Finally, some trends should be interpreted with caution due to the long-time span of study group enrollment. Despite the limitations, our findings allow some useful clinical speculations. Further prospective studies are needed to corroborate our findings.
Conclusion
Hypertensive patients with abnormal T-wave show a higher incidence of adverse cardiovascular events. The values of cardiac structural markers were significantly higher in the group with abnormal T-wave.
Author contributions
All authors contributed significantly to the work reported, gave consent to the journal in which the article was submitted, and agreed to be accountable for all aspects of the work.
Acknowledgments
We would like to gratefully acknowledge the support of Zhongnan Hospital of Wuhan University for investigators participating in this work.
Disclosure statement
The funding body was not involved in the design of the study as well as in the collection, analysis and interpretation of data and in writing the manuscript.
Data availability statement
Data are available from the corresponding author upon reasonable request for reproducing the results.
Additional information
Funding
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