Tp-e Interval, Tp-e/QT, Tp-e/QTc ratios are associated with Resistant Hypertension Running Tittle: Tp-e Interval and Repolarization Markers in Resistant Hypertension

Tp-e Interval, Tp-e/QT, Tp-e/QTc ratios are associated with Resistant Hypertension Running Tittle: Tp-e Interval and Repolarization Markers in Resistant Hypertension | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Tp-e Interval, Tp-e/QT, Tp-e/QTc ratios are associated with Resistant Hypertension Running Tittle: Tp-e Interval and Repolarization Markers in Resistant Hypertension Necmettin Korucuk, Veysel Tosun, Eyyup Tusun, Meryem Keleş, Fatih Yılmaz This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8629687/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Objective Resistant hypertension (RHTN) is associated with increased cardiovascular morbidity and mortality. This study aimed to evaluate T-peak-to-T-end (Tp-e) and Tp-e/QTc ratios in patients with RHTN. Methods This study included 133 patients and 32 healthy controls. Patients with hypertension were divided into two groups: 52 with RHTN and 81 with controlled hypertension (CHTN). RHTN was defined as blood pressure (BP) ≥ 140/90 mmHg while taking ≥ 3 antihypertensive medications, or BP < 140/90 mmHg while taking ≥ 4 medications. The Tp-e, Tp-e/QT, and Tp-e/QTc ratios were measured using a 12-lead electrocardiogram. Results There were no significant differences among the groups in age, sex distribution, body mass index, smoking, heart rate, and diabetes mellitus frequency. The Tp-e, Tp-e/QT, and Tp-e/QTc ratios were significantly higher in patients with RHTN than in those with CHTN and healthy controls. Tp-e and Tp-e/QTc ratios were significantly positively correlation with 24 h ambulatory blood pressure (ABPM), systolic blood pressure, and diastolic blood pressure. In addition, age, C-reactive protein, diabetes, urinary albumin excretion, 24-h ABPM, and pill burden were independent predictors of an increased Tp-e/QTc ratio. Conclusion Increased Tp-e and Tp-e/QTc ratios are associated with RHTN. Resistant hypertension electrocardiography Tp-e interval Tp-e/QT Tp-e/QTc 1. Introduction Essential hypertension (EHTN) is associated with increased cardiovascular morbidity and mortality rates. The effects of EHTN on the cardiovascular system include an increased risk of atherosclerosis, myocardial repolarization changes, ventricular arrhythmias caused by left ventricular hypertrophy, and sudden cardiac death. Resistant hypertension (RHTN) is defined in the 2024 ESC/ESH guidelines as an office blood pressure (OBP) of ≥ 140 and/or 90 mmHg despite the use of optimal or best-tolerated doses of three or more drugs with appropriate lifestyle measures [ 1 ] . The estimated frequency of RHTN is approximately 10% in treated hypertensive patients, and cardiovascular events and all-cause mortality are observed at a higher rate in RHTN [ 2 ] . The diagnosis of RHTN should be confirmed by ambulatory blood pressure measurement (ABPM) or home blood pressure measurements (HBPM) [ 1 ] . There is a relationship between autonomic disorders and disease severity in patients with EHTN [ 3 ] . RHTN is characterized by marked neuro-adrenergic activation compared with that in the normotensive state [ 4 ] . Electrocardiography (ECG) is a simple and widely used diagnostic tool that reveals myocardial electrical changes. ECG measurements of repolarization parameters can be used to determine the risk of cardiac arrhythmia. Abnormal ventricular repolarisation is an established mechanism of arrhythmogenesis. QT interval, QT interval dispersion (QTd), prolongation of the heart rate-corrected QT interval (QTc), and transmural dispersion of repolarization are traditional indicators of abnormal ventricular repolarization and are used to evaluate cardiovascular risk [ 5 ] . These parameters are known as ventricular repolarization markers, and they cause sudden cardiac death by inducing malignant ventricular arrhythmias. It has been shown that QTc is a widely used risk of arrhythmia and increases to risk of morbidity and mortality in cardiac and non-cardiac disease [ 5 , 6 ] . A prolonged T-peak-to-T-end (Tp-e) interval was associated with malignant ventricular arrhythmia and sudden cardiac death. At the same time, the Tp-e/QT and Tp-e/QTc ratios are also used as predictors for the development of ventricular arrhythmias and show an increased cardiovascular mortality rate [ 7 , 8 ] . Studies have shown that EHTN increases the risk of ventricular arrhythmias. The Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios are linked to malignant ventricular arrhythmia and sudden cardiac death in several patient groups: hypertensive, hypertensive primary hyperaldosteronism [ 8 , 9 ] , non-dipper hypertension [ 10 ] , prehypertensive, newly diagnosed hypertensive [ 11 ] , and metabolic syndrome patients [ 12 ] . Few studies have evaluated ventricular repolarization indices in patients with RHTN [ 5 , 13 ] . In this study, we assessed ventricular repolarization in patients with RHTN using the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio on ECG. 2. Methods 2.1. Study population This was a single-center retrospective cross-sectional study. The study took place between April 2018 and May 2022. We included 133 consecutive patients with EHTN who visited the nephrology and cardiology outpatient clinics and underwent 24 h-ABPM for various reasons. We recorded the basic demographics, office systolic and diastolic blood pressure, heart rate (HR), and drugs used. The control group included 32 healthy volunteers (15 male and 17 female; mean age 56.7 ± 10.9 years) with similar demographics and no systemic disease. Height (m) and body weight (kg) were measured to calculate BMI (kg/m2). Secondary hypertension (aortic coarctation, primary hyperaldosteronism, Cushing’s syndrome, pheochromocytoma, unilateral or bilateral renal artery stenosis), atrial fibrillation, bundle branch block, atrioventricular block, pacemaker, coronary artery disease, heart valve disease, heart failure, pregnancy, hypothyroidism, hyperthyroidism, chronic kidney disease, chronic obstructive pulmonary disease, asthma, pulmonary hypertension, cerebrovascular disease, electrolyte disturbances, net analyzable QT, patients who did not have a normal ST segment, ST-T abnormalities, Tp-e, or any drug (macrolide antibiotics, antiarrhythmic, antihistaminic, tricyclic antidepressants, or antipsychotic drugs) that could affect the QT interval were not included in the study. 2.2. Office Blood Pressure Measurement OBP was measured according to the guidelines of the European Society of Hypertension guidelines [ 1 ] . The OBP of the patient was measured in a sitting position with the arm supported at the heart level and a cuff size suitable for the patient. OBP measurements of patients were recorded using the same sphygmomanometer (OMRON M3 Comfort (HEM-7134-E), OMRON HEALTHCARE Co., Ltd., KYOTO, 617-0002 JAPAN). According to the OBP measurement, controlled hypertension (CHTN) was < 140/90 mmHg and hypertension was ≥ 140/90 mmHg. 2.3. Ambulatory blood pressure measurement ABPM was applied in patients with high OBP, inconsistent office and HBPM, fluctuations in HBPM, and suspicious blood pressure measurements. ABPM was performed using a Mobil-O‐Graph Arteriograph (I.E.M. GmbH, Stolberg, Germany) device. Patients continued their usual physical activities during ABPM. Patients were asked to record their sleep and wake times. The ABPM device was set to obtain blood pressure measurements at 15-minute intervals during the daytime (awake) (07:00 AM–11:00 PM) and at 30-minute intervals during the nighttime (sleep) (11:00 PM–07:00 AM). According to ABPM, hypertension was defined as a 24-hour mean blood pressure ≥ 130/80 mmHg, daytime blood pressure ≥ 135/85 mmHg, and night-time blood pressure ≥ 120/70 mmHg [ 1 , 12 ] . RHTN was defined as blood pressure ≥ 140/90 mmHg while taking ≥ 3 antihypertensive medications, or blood pressure < 140/90 mmHg while taking ≥ 4 medications. Patients with an OBP or ABPM-daytime below these values with three or fewer antihypertensive drugs were allocated to the controlled hypertension (CHTN) group. According to ABPM, patients were divided into two groups: RHTN and CHTN. 2.4. Electrocardiography All ECGs were obtained while the patient was at rest and between 08:00–10:00 in the morning. An ECG speed of 25 mm/s and amplitude of 10 mm/mV were used for the analyses (CardioFax S device, Nihon Kohden, Tokyo, Japan). All the patients had sinus rhythm and were asymptomatic in terms of cardiac signs or symptoms. The R-R interval was measured and used to calculate the HR. All patients presenting with a biphasic or negative T wave and U wave on the surface ECG were excluded. The QT interval was measured as the distance from the beginning of the QRS complex to the end of the T-wave. The corrected QT (QTc) interval was calculated using Bazett’s formula: QTc = QT/√ (R-R interval) [ 14 ] . A prolonged QTc interval was defined as a duration of > 440 ms. QT dispersion (QTd) was defined as the QTmax-QTmin interval, and corrected QTd (QTcd) was calculated according to Bazett’s formula adjusted according to heart rate [ 11 ] . QRS voltages were measured, and electrocardiographic left ventricular hypertrophy (ECG-LVH) was defined by a Cornell voltage (RaVL + SV3) > 2.6 mV in men, and/or > 2.0mV in women. The Tp-e interval was measured as the interval between the peak and the end of the T wave in the precordial leads (V2 and V5) [ 14 ] . The Tp-e/QT and Tp-e/QTc ratios were calculated as the Tp-e interval divided by QT and QTc intervals, respectively. 2.5. Laboratory analysis Venous blood samples were obtained from patients after 12 h of fasting. All laboratory results were obtained from the clinical database. Biochemical parameters were measured and recorded using standard methods. A urinary albumin excretion (UAE) rate < 30 mg/day was considered normoalbuminuria, with values in the range of 30 to 299 mg/day as microalbuminuria, and ≥ 300 mg/day as macro-albuminuria. 2.6. Statistical analysis A prior sample size estimation was conducted to determine the minimum number of participants required to compare the prevalence of Tp-e interval between resistant HT and controlled HT groups. Assuming a two-sided alpha of 0.05, a statistical power of 80%, and an expected prevalence of Tp-e interval of 60% in the HT groups versus 30% in the healthy controls, the minimum required sample size was calculated as 84 patients (42 per group). To account for potential data loss, the target enrollment was set at ≥ 50 participants per patient groups, and ultimately, 133 patients were prospectively included in the study. Continuous variables were expressed as mean ± standard deviation for parameters with normal distribution and median (interquartile range) for parameters without normal distribution, and categorical variables were expressed as numbers and percentages. The chi-square test was used to compare categorical variables. Continuous variables were compared using the ANOVA variance. When the p-value from the one-way ANOVA test was statistically significant, post-hoc Tukey tests were used to compare the groups. The relationships between the clinical and laboratory results of the patients and repolarization parameters were examined. Pearson correlation analysis was performed to examine the relationship between the Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios, and other variations. Statistical significance was set at P < .05 were considered to be statistically significant. All statistical analyses were performed using the Statistical Package for Social Sciences version 23.0 (SPSS Inc., Chicago, IL, USA). 3. Results 3.1. Demographic Characteristics A total of 165 participants were included in the study. The mean age of the patients was 56.6 ± 11.8 (range 29–73 years), and 88 patients (53.3%) were female. 32 patients were in the normotensive controls (NT-C) (59.1 ± 11.8 years), while 133 patients (52 RHTN, 81 CHTN) had EHTN (56.2 ± 11.3 years). No statistically significant differences were found between the two groups in terms of their basic characteristics (Table 1 ). In the RHTN patients, 24-h ABPM systolic and diastolic blood pressure were higher than in CHTN patients (138.3 ± 30.4 versus 124.7 ± 28.6 mm Hg, and 89.7 ± 18.5 versus 82.3 ± 17.2 mm Hg; P < 0.001, for all). RHTN patients were taking a mean of 3.7 (3 to 6) antihypertensive drugs, while CHTN subjects were 1.6 (1–3) ( P = .03). The rate of patients who were non-dippers was higher in patients with RHTN (30.7% vs. 14.8%, P = 0.04). The main characteristics of the three patient groups are shown in Table 1 . Table 1 Baseline demographic and clinical parameters of the groups Variables Group I: RHTN (n = 52) Group II: CHTN (n = 81) Group III: NT-C (n = 32) p Age (years) 58.2 ± 11.3 55.4 ± 10.2 59.1 ± 11.8 0.43 Gender (F, %) 28 (53.8) 40 (49.3) 20 (62.5) 0.38 BMI (kg/m 2 ) 29.2 ± 3.8 28.3 ± 3.4 27.6 ± 3.3 0.22 Smoking (n, %) 16 (30.7) 27 (33.3) 13 (40.6) 0.37 Diabetes Mellitus (n, %) 9 (17.3) 11 (13.5) 0.18 Office SBP (mmHg) 142.3 ± 17.8 123.4 ± 12.7 118.5 ± 11.6 < 0.001 **, + Office DBP (mmHg) 91.8 ± 12.2 81.1 ± 10.6 77.6 ± 10.2 < 0.001 **, + 24-h ABPM SBP (mmHg) 138.3 ± 30.4 124.7 ± 28.6 < 0.001 * 24-h ABPM DBP (mmHg) 89.7 ± 18.5 82.3 ± 17.2 < 0.001 * Non-dipper (n, %) 16 (30.7) 12 (14.8) 0.04 * Pill burden (Anti HTN) 3–6 (3.7) 1–3 (1.6) 0.03 * Use of Anti HTN (n,%) 1 2 3 ≥ 4 0(0) 0(0) 27(51.9) 25(48.1) 45 (55.5) 29 (35.8) 7 (8.7) 0(0) Antihypertensive drugs ACEI ARB CCB BB AB Diuretics Others 20 (38.4) 23 (44.2) 43 (82.6) 37 (71.1) 13 (25) 51 (100) 9 (17.3) 26 (32.1) 31 (38.2) 40 (49.3) 16 (19.7) 5 (6.1) 39 (48.1) 0 (0) 0.34 0.27 0.04 * 0.42 0.09 0.03 * Other medications ASA Statin SUA lowering drugs 29 (55.7) 17 (32.7) 14 (26.9) 44 (54.3) 20 (24.7) 11 (13.5) 0.36 0.29 0.53 Data are expressed in frequencies (percentages) or mean ± standard deviation. Abbreviations : RHTN: Resistant hypertension, CHTN: Controlled hypertension, NT-C: normotensive controls, SBP: systolic blood pressure, ABPM: Ambulatory blood pressure monitoring, BMI: Body mass index, ACEI: Angiotensin converting enzyme inhibitor, ARB: Angiotensin receptor blocker, BB: Beta blocker, CCB: Calcium channel blocker, DM: Diabetes mellitus, AB: Alpha blockers, ASA: Acetyl salicylic acid, SUA: Serum uric acid. *Between RHTN and CHTN groups **Between RHTN and NT-C groups +Between CHTN and NT-C groups Biochemical parameters of the study groups are shown in Table 2 . Glucose, creatinine, eGFR, uric acid, and electrolyte levels were similar between the RHTN and CHTN groups ( P > 0.05). Microalbuminuria value was significantly higher in patients with RHTN than in patients with CHTN (103.4 ± 11.2 mg/dL, 25.7 ± 3.2 mg/dL, P = .013). The frequency of LVH was 25% in patients with RHTN and 12.3% in patients with CHTN, and this difference was statistically significant ( P = .025). C-reactive protein (CRP) value was significantly higher in patients with RHTN than patients with CHTN (13.2 ± 1.1 mg/L, 6.7 ± 0.5 mg/L, P = .034, respectively). The albumin level was statistically different between the RHTN, CHTN, and NT-C groups (4.0 ± 0.3, 4.2 ± 0.4, and 4.3 ± 0.3 g/dL, respectively; P = .028). Table 2 Comparison of the biochemical parameters of the groups Variables RHTN CHTN NT-C p Glucose (mg/dL) 93.5 ± 11.6 89.2 ± 10.8 90.4 ± 11.9 0.36 Creatinine (mg/dL) 0.89 ± 0.14 0.93 ± 0.18 0.91 ± 0.13 0.67 Uric acid (mg/dL) 6.9 ± 0.5 6.6 ± 0.5 6.2 ± 0.4 0.15 Sodium (mmol/L) 139.1 ± 18.4 140.8 ± 11.6 138.7 ± 11.2 0.47 Potassium (mmol/L) 4.3 ± 0.7 4.4 ± 0.7 4.2 ± 0.6 0.36 Calcium (mg/dL) 9.1 ± 1.2 8.8 ± 1.1 9.0 ± 0.9 0.31 Albumin (g/dL) 4.0 ± 0.3 4.2 ± 0.4 4.3 ± 0.3 0.028 ** Triglycerides (mg/dL) 139.3 ± 61.9 150.4 ± 80.1 144.5 ± 79.3 0.18 TC (mg/dL) 182.4 ± 28.5 189.7 ± 30.4 184.6 ± 31.7 0.26 LDL-c (mg/dL) 116.1 ± 33.9 114.6 ± 29.2 101.4 ± 34.8 0.13 HDL-c (mg/dL) 43.8 ± 5.4 45.3 ± 6.2 41.9 ± 6.8 0.63 TSH (µIU/mL) 2.33 ± 0.25 2.47 ± 0.31 - 0.83 CRP (mg/L) 13.2 ± 1.1 6.7 ± 0.5 - 0.034 * Leukocytes (*10 9 /L) 6.14 ± 0.32 6.38 ± 0.43 7.05 ± 0.49 0.28 Hemoglobin (g/dL) 13.6 ± 1.2 13.8 ± 1.4 13.9 ± 1.3 0.21 Platelet (*10 9 /L) 276 ± 32 264 ± 26 290 ± 33 0.43 UAE (mg/dL) 103.4 ± 11.2 25.7 ± 3.2 - 0.013 * Abbreviations : TC: Total cholesterol, LDL-c: Low density lipoprotein, HDL-c: High density lipoprotein, TSH: Thyroid stimulating hormone, CRP: C-reactive protein, UAE: Urinary albumin excretion. *Between RHTN and CHTN groups **Between RHTN and NT-C groups 3.2. Electrocardiographic measurements The mean QT and QTc intervals were 391 ± 32 ms and 408 ± 34 ms, respectively, in the RHTN group and 375 ± 36 ms and 392 ± 33 ms, respectively, in the CHTN group. QT and QTc intervals were significantly longer in the RHTN group than in the CHTN group ( P = .023, P = .019, respectively). The mean QTd was higher in RHTN than in CHTN (44.3 ± 4.2 ms vs. 36.9 ± 3.1 ms, P = .021). The mean QTcd was higher in RHTN than in CHTN (47.9 ± 5.4 ms vs. 40.2 ± 3.8 ms, P = .038). The mean Tp-e interval was significantly prolonged in patients with RHTN than in those with CHTN (80 ± 9 and 72 ± 8, respectively; P < 0.001). The mean TP-e/QT and TP-e/QTc ratios in the RHTN group were 0.22 ± 0.05 and 0.19 ± 0.02, respectively, while they were 0.19 ± 0.03 and 0.16 ± 0.02 in the CHTN group. Table 3 shows the Tp-e, Tp-e/QT, and Tp-e/QTc ratios for RHTN, CHTN, and NT-C. Table 3 Comparison of electrocardiographic measurements between the resistant hypertension and controlled hypertension group Variables RHTN CHTN NT-C p HR (beat/min) 81 (63–92) 76 (54–89) 79 (60–96) 0.124 QT (ms) 391 ± 32 375 ± 36 360 ± 31 0.023 *, ** QTc (ms) 408 ± 34 392 ± 33 379 ± 30 0.019 *, ** QTd (ms) 44.3 ± 4.2 36.9 ± 3.1 30.6 ± 3.0 0.021 *, ** cQTd (ms) 47.9 ± 5.4 40.2 ± 3.8 33.8 ± 3.3 0.038 *, ** Tp-e (ms) 80 ± 9 72 ± 8 68 ± 7 < 0.001 *, ** Tp-e/QT 0.22 ± 0.05 0.19 ± 0.03 0.16 ± 0.03 0.017 *, ** Tp-e/QTc 0.19 ± 0.02 0.16 ± 0.02 0.16 ± 0.02 0.026 *, ** LVH, (n, %) 13 (25) 10 (12.3) 0 0.025 * Data are represented as mean values ± SD, and frequency. Abbreviations : HR: Heart rate, RHTN: Resistant hypertension, CHTN: Controlled hypertension, HR: Heart rate, LVH: Left ventricular hypertrophy. *Between RHTN and CHTN groups **Between RHTN and NT-C groups 3.3. Correlation analysis Pearson’s correlation analysis was performed between the clinical variables, Tp-e interval, and Tp-e/QTc ratio. There was no significant correlation between UAE, albumin, and GFR and the Tp-e interval and Tp-e/QTc ratios. A weak positive correlation was observed between age, Tp-e interval, and the Tp-e/QTc ratio. There was also a statistically significant positive correlation between 24 h-ABPM systolic and diastolic blood pressure with the Tp-e interval and Tp-e/QTc ratio (Table 4 ). Table 4 Correlation between Tpe interval and Tpe/QT ratio with clinical parameters Parameter Tp-e r p Tp-e/QTc r p Age (years) 0.260 0.006 0.353 0.025 BMI (kg/m 2 ) 0.302 0.045 0.124 0.233 CRP (mg/dL) 0.317 0.001 0.179 0.067 UAE (mg/dL) 0.087 0.664 0.094 0.719 24-ABPM SBP (mmHg) 0.447 0.023 0.551 0.016 24-ABPM DBP (mmHg) 0.405 0.019 0.654 0.004 Albumin (g/dL) 0.118 0.763 0.371 0.148 GFR (ml/min/1.73m 2 ) 0.089 0.528 0.025 0.651 Abbreviations : CRP: C-reactive protein, BMI: Body mass index, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, UAE: Urinary albumin excretion 3.4. Logistic regression analysis Multivariate logistic regression analysis indicated that diabetes (β 2.031, 95% CI 1.387–4.108, P = .012), pill burden (β 1.293, 95% CI 1.086–1.872, P = .033), 24-h ABPM systolic blood pressure (β 1.419, 95% CI 1.158–2.094, P = .016), UAE (β 1.332, 95% CI 1.064–1.719, P = .041), CRP (β 1.451, 95% CI 1.252–2.357, P = .014), age (β 1.535, 95% CI 1.275–3.314, P = .025) were significant and independently predicted Tp-e/QT ratio. In the multivariate linear regression analysis, RHTN was found to be an independent risk factor for increased Tp-e/QTc ratio (Table 5 ). Table 5 Multivariate logistic regression analysis to assess independent predictors of increased Tp-e/QTc ratio Variables β Odds ratio (95% CI) p Age (years) 1.535 1.275–3.134 0.025 Pill burden 1.293 1.086–1.872 0.033 CRP (mg/dL) 1.451 1.252–2.357 0.014 Diabetes Mellitus 2.031 1.387–4.108 0.012 24-h SBP (mmHg) 1.419 1.158–2.094 0.016 24-h DBP (mmHg) 1.034 0.097–1.127 0.085 UAE (mg/dL) 1.332 1.064–1.719 0.041 Abbreviations : CRP: C-reactive protein, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, UAE: Urinary albumin excretion 4. Discussion The present study showed that Tp-e, Tp-e/QT, and Tp-e/QTc ratios were prolonged in patients with RHTN compared to CHTN and control patients. 24 h-ABPM systolic and diastolic blood pressure were associated with the Tp-e interval and the Tp-e/QTc ratio. Age, CRP, diabetes, pill burden (antihypertensive drug), UAE (mg/dL), and 24-h ABPM systolic blood pressure were independent predictors of Tp-e/QTc in the multivariate logistic regression analysis. Prolongation of the QT and QTc intervals is predictive of cardiovascular mortality and the risk of sudden cardiac death in the general population and in many patient groups. QT and QTc intervals reflect both depolarization and repolarization in the ventricles. The QT interval is influenced by many factors, such as electrolytes, drugs, endocrine factors, autonomic nervous system, and heredity [ 15 ] . In this study, endocrine factors, electrolyte disturbances, and drug use were excluded as much as possible. QTd, which reflects the degree of regional repolarization disorder, is an independent risk factor for increased risk of ventricular arrhythmias in EHTN patients [ 11 ] . Prolonged Tp-e and QT distances and increased Tp-e/QT and Tp-e/QTc ratios in patients with RHTN indicate an increased risk of death due to non-atherosclerotic events. Kohno et al. showed that electrical abnormalities predicted by QTd are more sensitive than anatomical abnormalities assessed by echocardiography in assessing end-organ damage in hypertensive patients [ 15 ] . It is also stated that the Tp-e/QT ratio can be used for risk stratification in coronary artery disease [ 16 ] . The ventricular myocardium consists of three cell layers (endocardial, epicardial, and myocardial M cells) with different electrophysiological characteristics. The Tp-e interval and the Tp-e/QT ratio are considered new indicators of impaired ventricular repolarization. Repolarization ends first in the epicardial layer, coinciding with the peak point (Tp) of the T wave. It ends in the repolarization of the mid-myocardial layer during the period until the end of the T wave (Tp-e). The Tp-e interval can be used as an index of the total (transmural, apical-basal, and global) dispersion of the repolarization. Accurate measurement of Tp-e, which is a very short range on ECG, should be performed carefully. Thus, Tp-e only shows the transmural distribution of repolarization. The Tp-e interval and Tp-e/QT ratio reflect repolarization heterogeneity better than the QT interval and reflect the transmural distribution of repolarization. While the Tp-e and QT intervals are affected by body mass index and heart rate, the Tp-e/QT ratio is not affected by these factors and is more sensitive in predicting ventricular arrhythmia [ 7 ] . Tp-e/QT is considered a more sensitive index of arrhythmogenesis than Tp-e or QT intervals alone. The Tp-e/QT ratio is a relatively new index and remains constant when the heart rate is 60–100 per minute and has a mean value of 0.21 in the precordial leads [ 17 ] . The Tp-e/QT ratio is significantly increased in patients with both arrhythmogenic (short QT, long QT, and Brugada syndrome) and atherosclerotic (acute myocardial infarction) heart diseases [ 17 ] . The Tp-e/QT ratio is high in patients with malignant ventricular arrhythmias and is a strong predictor of sudden cardiac death [ 18 ] . Previous studies have shown that ventricular repolarization is associated with age, blood pressure, and diabetes [ 19 , 20 ] . The association between EHTN and ventricular arrhythmias is well established. It has been shown that QT and Tp-e intervals are prolonged in previous studies in different hypertensive patient groups [ 5 , 8 – 13 ] . In EHTN, the QT interval is often prolonged, regardless of antihypertensive therapy. Increased left ventricular wall tension in patients with hypertension stimulates myofibroblast activity and fibrosis. Increasing fibrosis triggers changes in mechanical and electrical activity (low conduction velocity, re-entry phenomenon, and ectopic impulses) in the atrial and ventricular myocardium [ 11 ] . Several studies have shown that ventricular repolarization time is prolonged with the development of LVH. LVH is associated with an increased QT interval, Tp-e interval, and Tp-e/QT ratio [ 21 ] . An important result of this study is that microalbuminuria, which is a marker of hypertensive end-organ damage, is a predictor of increased Tp-e and Tp-e/QT ratios. Inflammation may be one of the potential mechanisms underlying the association between RHTN and a prolonged QTc interval. It has been shown that levels of inflammatory cytokines (interleukin (IL) 1b, IL-6, and tumor necrosis factor-α (TNF-α)) and prognostic nutritional index increase in patients with RHTN [ 22 , 23 ] . Inflammatory processes trigger fibrosis in the left ventricle, causing arrhythmias. Many basic studies have shown that inflammatory cytokines prolong the QT interval by changing cardiac electrophysiology, especially the expression and function of calcium and potassium channels [ 24 ] . Some mechanisms may explain the long QT interval. These gene mutations affect the functions of cardiac ion channels in cardiac repolarization, cardiac autonomic neuropathy, sympathetic-vagal irregularities, electrolyte disorders, slow or absent conduction systems due to ischemia and fibrosis, different components of insulin resistance syndrome, systolic dysfunction, and LVH [ 13 ] . Another possible mechanism explaining the relationship between RHTN and prolonged QT interval is the heart rate variation caused by the sympathetic nervous system. RHTN is associated with increased sympathetic nervous system activity, which is closely associated with an increased risk of ventricular arrhythmias. 5. Limitations This study had some limitations. First, this was a retrospective and observational study conducted at a single center with a small number of patients. Second, the intervals and ratios used in this study were measured manually. Additionally, although the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio showed a predisposition to arrhythmia, clinical and rhythm holter follow-ups were not performed to detect arrhythmia. Another limitation is the lack of echocardiographic evaluation and ventricular arrhythmia follow-up. The fact that the exclusion criteria used when including patients with RHTN were quite comprehensive can be considered a positive feature. 6. Conclusion In conclusion, this study shows that the Tp-e Interval, Tp-e/QT, and Tp-e/QTc ratios in patients with RHTN are longer than those in patients with CHTN. These parameters are simple and noninvasive methods that are valuable for detecting ventricular repolarization in patients with RHTN. Declarations Ethical statement The Clinical Research Ethics Committee of Akdeniz University Medical Faculty approved this study (20.07.2022/479). This study was conducted in compliance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all the patients. Consent for publication: Not applicable Conflict of interest: The authors declare that there are no conflicts of interest. Funding: No funding was received for this commentary. Author Contribution Conceptualization: NK, FY; Data Curation: NK, FY, MK; Formal analysis: NK, FY, MK; Investigation: NK, FY; Methodology: NK, FY, VT; Project administration: NK, FY; Software: NK, FY, MK; Supervision: VT, ET; Validation: VT, NK, ET; Visualization: NK, VT; Writing original draft: NK, FY, VT; Writing- review: NK, ET, VT Acknowledgement: The authors wish to acknowledge the personnel who performed the ECG recording and the participants of the study for their support during the data collection process. Data Availability The dataset is available from the corresponding author upon reasonable request. References McEvoy JW, McCarthy CP, Bruno RM, ESC Scientific Document Group, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912–4018. 10.1093/eurheartj/ehae178 . Lamirault G, Artifoni M, Daniel M, Barber-Chamoux N, Nantes University Hospital Working Group On Hypertension. Resistant Hypertension: Novel Insights. Curr Hypertens Rev. 2020;16(1):61–72. 10.2174/1573402115666191011111402 . Ay SA, Bulucu F, Karaman M, et al. Cardiac Autonomic Neuropathy and Complications of Primary Hypertension: Is Autonomic Neuropathy a Cause or a Result? Turk Neph Dial Transpl. 2016;25(1):65–72. Dell'Oro R, Quarti-Trevano F, Seravalle G, et al. Sympathetic Nerve Traffic and Arterial Baroreflex Function in Apparent Drug Resistant Hypertension. Hypertension. 2019;74(4):903–9. 10.1161/HYPERTENSION AHA.119.13009 . Salles GF, Cardoso CR, Leocadio SM, Muxfeldt ES. Recent ventricular repolarization markers in resistant hypertension: are they different from the traditional QT interval? Am J Hypertens. 2008;21(1):47–53. 10.1038/ajh.2007.4 . De Bruyne MC, Hoes AW, Kors JA, Hofman A, van Bemmel JH, Grobbee DE. Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam study. Eur Heart J. 1999;20:278–84. Gupta P, Patel C, Patel H, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567–74. 10.1016/j.jelectrocard.2008.07.016 . Mozos I, Serban C. The relation between QT interval and T-wave variables in hypertensive patients. J Pharm Bioallied Sci. 2011;3(3):339–44. 10.4103/0975-7406.84433 . Demirtas D, Sumbul HE, Bulut A, et al. Tp-e interval, Tp-e/QT and Tp-e/QTc ratio in hypertensive patients with primary aldosteronism. Clin Exp Hypertens. 2020;42(1):93–8. 10.1080/10641963.2019.1632341 . Demir M, Uyan U. Evaluation of Tp-e interval and Tp-e/QT ratio in patients with non dipper hypertension. Clin Exp Hypertens. 2014;36(5):285–8. 10.3109/10641963.2013.810233 . Suner A, Akgungor M, Kaya H, et al. Novel ventricular repolarization indexes in prehypertensive and newly diagnosed hypertensive patients: Tp-e interval and Tp-e/QT ratio. Int J Clin Exp Med. 2016;9(8):16710–6. Karaagac K, Tenekecioglu E, Yontar OC, et al. Effect of non-dipper and dipper blood pressure patterns on Tp-Te interval and Tp-Te/QT ratio in patients with metabolic syndrome. Int J Clin Exp Med. 2014;15(5):7. Salles GF, Cardoso CR, Muxfeldt ES. Prognostic value of ventricular repolarization prolongation in resistant hypertension: a prospective cohort study. J Hypertens. 2009;27(5):1094–101. 10.1097/HJH.0b013e32832720b3 . Mansiroglu AK, Coşgun M, Sincer I, Gunes Y. The role of baseline and post-treatment frontal QRS-T angle for detecting arterial blood pressure control. Clin Exp Hypertens. 2021:19;43(4):363–7. 10.1080/10641963.2021.1890763 Kohno I, Takusagawa M, Yin D, et al. QT dispersion in dipper- and nondipper-type hypertension. Am J Hypertens. 1998;11(3 Pt 1):280–5. Şaylık F, Çınar T, Selçuk M, Akbulut T. Association of Tp-e/QT ratio with SYNTAX score II in patients with coronary artery disease. Scand Cardiovasc J. 2022;56(1):325–30. Gupta P, Patel C, Patel H, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008;41(6):567–74. 10.1016/j.jelectrocard.2008.07.016 . Morin DP, Saad MN, Shams OF, et al. Relationships between the T-peak to T-end interval, ventricular tachyarrhythmia, and death in left ventricular systolic dysfunction. Europace. 2012;14:1172–9. Miki T, Tobisawa T, Sato T, et al. Does glycemic control reverse dispersion of ventricular repolarization in type 2 diabetes? Cardiovasc Diabetol. 2014;13:125. Mangoni AA, Kinirons MT, Swift CG, Jackson SH. Impact of age on QT interval and QT dispersion in healthy subjects: A regression analysis. Age Ageing. 2003;32:326–31. Yayla Ç, Bilgin M, Akboğa MK, et al. Evaluation of Tp-E Interval and Tp-E/QT Ratio in Patients with Aortic Stenosis. Ann Noninvasive Electrocardiol. 2016;21(3):287–93. Pioli MR, de Faria AP. Pro-inflammatory Cytokines and Resistant Hypertension: Potential for Novel Treatments? Curr Hypertens Rep. 2019;21(12):95. 10.1007/s11906-019-1003-2 . Yılmaz F, Keleş M, Bora F. Relationship between the prognostic nutritional index and resistant hypertension in patients with essential hypertension. Clin Exp Hypertens. 2022;18:1–8. 10.1080/10641963.2022.2036995 . Lazzerini PE, Capecchi PL, Laghi-Pasini F. Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis. Eur Heart J. 2017;7(22):1717–27. 10.1093/eurheartj/ehw208 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 24 Feb, 2026 Reviewers agreed at journal 18 Feb, 2026 Reviewers invited by journal 11 Feb, 2026 Editor invited by journal 22 Jan, 2026 Editor assigned by journal 21 Jan, 2026 Submission checks completed at journal 21 Jan, 2026 First submitted to journal 18 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8629687","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":591175052,"identity":"06a97775-cd86-49ea-8796-7d71a945c905","order_by":0,"name":"Necmettin Korucuk","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBADHiA2fABi8BGnIcEApMXYAKSFjVgtINJMAkQS1GLO3vx0w8cff2TMxQ5vq/yaYyfDxsD88NENPFose46Z3ZwBdJjl7LSy27LbkoEOYzM2zsGjxeBGDtttHqAWg9s5ZrcltzEDtfCwSePVcv8N2+0/UC3FktvqidByg4ftNgNUC+PHbYeJ0HImzexmT5oxUEtasTTjtuM8bMyE/HL88LMbP2zk7A1uJ2/8+HNbtT0/e/PDx/i0oABmHjBJrHIQYPxBiupRMApGwSgYMQAAsZdE4O35U+UAAAAASUVORK5CYII=","orcid":"","institution":"Antalya City Hospital, Department of Cardiology, Antalya, Türkiye","correspondingAuthor":true,"prefix":"","firstName":"Necmettin","middleName":"","lastName":"Korucuk","suffix":""},{"id":591175056,"identity":"854c2453-c917-4bb9-9bc5-96ede1f1ab05","order_by":1,"name":"Veysel Tosun","email":"","orcid":"","institution":"Mehmet Akif Inan Training and Research Hospital, Department of Cardiology, Sanliurfa, Türkiye","correspondingAuthor":false,"prefix":"","firstName":"Veysel","middleName":"","lastName":"Tosun","suffix":""},{"id":591175057,"identity":"c02cb0f6-690e-4cca-976a-a3e7fd71045d","order_by":2,"name":"Eyyup Tusun","email":"","orcid":"","institution":"Mehmet Akif Inan Training and Research Hospital, Department of Cardiology, Sanliurfa, Türkiye","correspondingAuthor":false,"prefix":"","firstName":"Eyyup","middleName":"","lastName":"Tusun","suffix":""},{"id":591175058,"identity":"8c222315-ef8b-46cd-9481-b1c7eb03cc4e","order_by":3,"name":"Meryem Keleş","email":"","orcid":"","institution":"Bilkent City Hospital, Department of Nephrology, Ankara, Türkiye","correspondingAuthor":false,"prefix":"","firstName":"Meryem","middleName":"","lastName":"Keleş","suffix":""},{"id":591175059,"identity":"5fb6d36a-5206-4d87-ad89-7da5ac3978f0","order_by":4,"name":"Fatih Yılmaz","email":"","orcid":"","institution":"Antalya City Hospital, Department of Nephrology, Antalya, Türkiye","correspondingAuthor":false,"prefix":"","firstName":"Fatih","middleName":"","lastName":"Yılmaz","suffix":""}],"badges":[],"createdAt":"2026-01-18 07:23:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8629687/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8629687/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105562488,"identity":"ea8e0ef7-756e-4d9e-b12e-9385424880c5","added_by":"auto","created_at":"2026-03-27 12:41:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1036424,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8629687/v1/621f7ecf-be28-42f2-8e2f-99802cf2257a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Tp-e Interval, Tp-e/QT, Tp-e/QTc ratios are associated with Resistant Hypertension Running Tittle: Tp-e Interval and Repolarization Markers in Resistant Hypertension","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eEssential hypertension (EHTN) is associated with increased cardiovascular morbidity and mortality rates. The effects of EHTN on the cardiovascular system include an increased risk of atherosclerosis, myocardial repolarization changes, ventricular arrhythmias caused by left ventricular hypertrophy, and sudden cardiac death. Resistant hypertension (RHTN) is defined in the 2024 ESC/ESH guidelines as an office blood pressure (OBP) of \u0026ge;\u0026thinsp;140 and/or 90 mmHg despite the use of optimal or best-tolerated doses of three or more drugs with appropriate lifestyle measures \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The estimated frequency of RHTN is approximately 10% in treated hypertensive patients, and cardiovascular events and all-cause mortality are observed at a higher rate in RHTN \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The diagnosis of RHTN should be confirmed by ambulatory blood pressure measurement (ABPM) or home blood pressure measurements (HBPM) \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. There is a relationship between autonomic disorders and disease severity in patients with EHTN \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. RHTN is characterized by marked neuro-adrenergic activation compared with that in the normotensive state \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eElectrocardiography (ECG) is a simple and widely used diagnostic tool that reveals myocardial electrical changes. ECG measurements of repolarization parameters can be used to determine the risk of cardiac arrhythmia. Abnormal ventricular repolarisation is an established mechanism of arrhythmogenesis. QT interval, QT interval dispersion (QTd), prolongation of the heart rate-corrected QT interval (QTc), and transmural dispersion of repolarization are traditional indicators of abnormal ventricular repolarization and are used to evaluate cardiovascular risk \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. These parameters are known as ventricular repolarization markers, and they cause sudden cardiac death by inducing malignant ventricular arrhythmias. It has been shown that QTc is a widely used risk of arrhythmia and increases to risk of morbidity and mortality in cardiac and non-cardiac disease \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. A prolonged T-peak-to-T-end (Tp-e) interval was associated with malignant ventricular arrhythmia and sudden cardiac death. At the same time, the Tp-e/QT and Tp-e/QTc ratios are also used as predictors for the development of ventricular arrhythmias and show an increased cardiovascular mortality rate \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eStudies have shown that EHTN increases the risk of ventricular arrhythmias. The Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios are linked to malignant ventricular arrhythmia and sudden cardiac death in several patient groups: hypertensive, hypertensive primary hyperaldosteronism \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, non-dipper hypertension \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, prehypertensive, newly diagnosed hypertensive \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, and metabolic syndrome patients \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Few studies have evaluated ventricular repolarization indices in patients with RHTN \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. In this study, we assessed ventricular repolarization in patients with RHTN using the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio on ECG.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study population\u003c/h2\u003e \u003cp\u003eThis was a single-center retrospective cross-sectional study. The study took place between April 2018 and May 2022. We included 133 consecutive patients with EHTN who visited the nephrology and cardiology outpatient clinics and underwent 24 h-ABPM for various reasons. We recorded the basic demographics, office systolic and diastolic blood pressure, heart rate (HR), and drugs used. The control group included 32 healthy volunteers (15 male and 17 female; mean age 56.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9 years) with similar demographics and no systemic disease. Height (m) and body weight (kg) were measured to calculate BMI (kg/m2).\u003c/p\u003e \u003cp\u003eSecondary hypertension (aortic coarctation, primary hyperaldosteronism, Cushing\u0026rsquo;s syndrome, pheochromocytoma, unilateral or bilateral renal artery stenosis), atrial fibrillation, bundle branch block, atrioventricular block, pacemaker, coronary artery disease, heart valve disease, heart failure, pregnancy, hypothyroidism, hyperthyroidism, chronic kidney disease, chronic obstructive pulmonary disease, asthma, pulmonary hypertension, cerebrovascular disease, electrolyte disturbances, net analyzable QT, patients who did not have a normal ST segment, ST-T abnormalities, Tp-e, or any drug (macrolide antibiotics, antiarrhythmic, antihistaminic, tricyclic antidepressants, or antipsychotic drugs) that could affect the QT interval were not included in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Office Blood Pressure Measurement\u003c/h2\u003e \u003cp\u003eOBP was measured according to the guidelines of the European Society of Hypertension guidelines \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The OBP of the patient was measured in a sitting position with the arm supported at the heart level and a cuff size suitable for the patient. OBP measurements of patients were recorded using the same sphygmomanometer (OMRON M3 Comfort (HEM-7134-E), OMRON HEALTHCARE Co., Ltd., KYOTO, 617-0002 JAPAN). According to the OBP measurement, controlled hypertension (CHTN) was \u0026lt;\u0026thinsp;140/90 mmHg and hypertension was \u0026ge;\u0026thinsp;140/90 mmHg.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Ambulatory blood pressure measurement\u003c/h2\u003e \u003cp\u003eABPM was applied in patients with high OBP, inconsistent office and HBPM, fluctuations in HBPM, and suspicious blood pressure measurements. ABPM was performed using a Mobil-O‐Graph Arteriograph (I.E.M. GmbH, Stolberg, Germany) device. Patients continued their usual physical activities during ABPM. Patients were asked to record their sleep and wake times. The ABPM device was set to obtain blood pressure measurements at 15-minute intervals during the daytime (awake) (07:00 AM\u0026ndash;11:00 PM) and at 30-minute intervals during the nighttime (sleep) (11:00 PM\u0026ndash;07:00 AM). According to ABPM, hypertension was defined as a 24-hour mean blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;130/80 mmHg, daytime blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;135/85 mmHg, and night-time blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;120/70 mmHg \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. RHTN was defined as blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;140/90 mmHg while taking\u0026thinsp;\u0026ge;\u0026thinsp;3 antihypertensive medications, or blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;140/90 mmHg while taking\u0026thinsp;\u0026ge;\u0026thinsp;4 medications. Patients with an OBP or ABPM-daytime below these values with three or fewer antihypertensive drugs were allocated to the controlled hypertension (CHTN) group. According to ABPM, patients were divided into two groups: RHTN and CHTN.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Electrocardiography\u003c/h2\u003e \u003cp\u003eAll ECGs were obtained while the patient was at rest and between 08:00\u0026ndash;10:00 in the morning. An ECG speed of 25 mm/s and amplitude of 10 mm/mV were used for the analyses (CardioFax S device, Nihon Kohden, Tokyo, Japan). All the patients had sinus rhythm and were asymptomatic in terms of cardiac signs or symptoms. The R-R interval was measured and used to calculate the HR. All patients presenting with a biphasic or negative T wave and U wave on the surface ECG were excluded. The QT interval was measured as the distance from the beginning of the QRS complex to the end of the T-wave. The corrected QT (QTc) interval was calculated using Bazett\u0026rsquo;s formula: QTc\u0026thinsp;=\u0026thinsp;QT/\u0026radic; (R-R interval) \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. A prolonged QTc interval was defined as a duration of \u0026gt;\u0026thinsp;440 ms. QT dispersion (QTd) was defined as the QTmax-QTmin interval, and corrected QTd (QTcd) was calculated according to Bazett\u0026rsquo;s formula adjusted according to heart rate \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. QRS voltages were measured, and electrocardiographic left ventricular hypertrophy (ECG-LVH) was defined by a Cornell voltage (RaVL\u0026thinsp;+\u0026thinsp;SV3)\u0026thinsp;\u0026gt;\u0026thinsp;2.6 mV in men, and/or \u0026gt;\u0026thinsp;2.0mV in women. The Tp-e interval was measured as the interval between the peak and the end of the T wave in the precordial leads (V2 and V5) \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. The Tp-e/QT and Tp-e/QTc ratios were calculated as the Tp-e interval divided by QT and QTc intervals, respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Laboratory analysis\u003c/h2\u003e \u003cp\u003eVenous blood samples were obtained from patients after 12 h of fasting. All laboratory results were obtained from the clinical database. Biochemical parameters were measured and recorded using standard methods. A urinary albumin excretion (UAE) rate\u0026thinsp;\u0026lt;\u0026thinsp;30 mg/day was considered normoalbuminuria, with values in the range of 30 to 299 mg/day as microalbuminuria, and \u0026ge;\u0026thinsp;300 mg/day as macro-albuminuria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Statistical analysis\u003c/h2\u003e \u003cp\u003eA prior sample size estimation was conducted to determine the minimum number of participants required to compare the prevalence of Tp-e interval between resistant HT and controlled HT groups. Assuming a two-sided alpha of 0.05, a statistical power of 80%, and an expected prevalence of Tp-e interval of 60% in the HT groups versus 30% in the healthy controls, the minimum required sample size was calculated as 84 patients (42 per group). To account for potential data loss, the target enrollment was set at \u0026ge;\u0026thinsp;50 participants per patient groups, and ultimately, 133 patients were prospectively included in the study. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for parameters with normal distribution and median (interquartile range) for parameters without normal distribution, and categorical variables were expressed as numbers and percentages. The chi-square test was used to compare categorical variables. Continuous variables were compared using the ANOVA variance. When the p-value from the one-way ANOVA test was statistically significant, post-hoc Tukey tests were used to compare the groups. The relationships between the clinical and laboratory results of the patients and repolarization parameters were examined. Pearson correlation analysis was performed to examine the relationship between the Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios, and other variations. Statistical significance was set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05 were considered to be statistically significant. All statistical analyses were performed using the Statistical Package for Social Sciences version 23.0 (SPSS Inc., Chicago, IL, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1. Demographic Characteristics\u003c/h2\u003e\n \u003cp\u003eA total of 165 participants were included in the study. The mean age of the patients was 56.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 (range 29\u0026ndash;73 years), and 88 patients (53.3%) were female. 32 patients were in the normotensive controls (NT-C) (59.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 years), while 133 patients (52 RHTN, 81 CHTN) had EHTN (56.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3 years). No statistically significant differences were found between the two groups in terms of their basic characteristics (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In the RHTN patients, 24-h ABPM systolic and diastolic blood pressure were higher than in CHTN patients (138.3\u0026thinsp;\u0026plusmn;\u0026thinsp;30.4 versus 124.7\u0026thinsp;\u0026plusmn;\u0026thinsp;28.6 mm Hg, and 89.7\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5 versus 82.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2 mm Hg; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, for all). RHTN patients were taking a mean of 3.7 (3 to 6) antihypertensive drugs, while CHTN subjects were 1.6 (1\u0026ndash;3) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.03). The rate of patients who were non-dippers was higher in patients with RHTN (30.7% vs. 14.8%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04). The main characteristics of the three patient groups are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline demographic and clinical parameters of the groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup I: RHTN (n\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup II: CHTN (n\u0026thinsp;=\u0026thinsp;81)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup III: NT-C (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender (F, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (40.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes Mellitus (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOffice SBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e123.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e118.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e**, +\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOffice DBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e**, +\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-h ABPM SBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e138.3\u0026thinsp;\u0026plusmn;\u0026thinsp;30.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124.7\u0026thinsp;\u0026plusmn;\u0026thinsp;28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-h ABPM DBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89.7\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-dipper (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePill burden (Anti HTN)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u0026ndash;6 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u0026ndash;3 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUse of Anti HTN (n,%)\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003cp\u003e27(51.9)\u003c/p\u003e\n \u003cp\u003e25(48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45 (55.5)\u003c/p\u003e\n \u003cp\u003e29 (35.8)\u003c/p\u003e\n \u003cp\u003e7 (8.7)\u003c/p\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cspan class=\"BoldUnderline\"\u003eAntihypertensive drugs\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003eACEI\u003c/p\u003e\n \u003cp\u003eARB\u003c/p\u003e\n \u003cp\u003eCCB\u003c/p\u003e\n \u003cp\u003eBB\u003c/p\u003e\n \u003cp\u003eAB\u003c/p\u003e\n \u003cp\u003eDiuretics\u003c/p\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (38.4)\u003c/p\u003e\n \u003cp\u003e23 (44.2)\u003c/p\u003e\n \u003cp\u003e43 (82.6)\u003c/p\u003e\n \u003cp\u003e37 (71.1)\u003c/p\u003e\n \u003cp\u003e13 (25)\u003c/p\u003e\n \u003cp\u003e51 (100)\u003c/p\u003e\n \u003cp\u003e9 (17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (32.1)\u003c/p\u003e\n \u003cp\u003e31 (38.2)\u003c/p\u003e\n \u003cp\u003e40 (49.3)\u003c/p\u003e\n \u003cp\u003e16 (19.7)\u003c/p\u003e\n \u003cp\u003e5 (6.1)\u003c/p\u003e\n \u003cp\u003e39 (48.1)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cspan class=\"BoldUnderline\"\u003eOther medications\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003eASA\u003c/p\u003e\n \u003cp\u003eStatin\u003c/p\u003e\n \u003cp\u003eSUA lowering drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (55.7)\u003c/p\u003e\n \u003cp\u003e17 (32.7)\u003c/p\u003e\n \u003cp\u003e14 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44 (54.3)\u003c/p\u003e\n \u003cp\u003e20 (24.7)\u003c/p\u003e\n \u003cp\u003e11 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eData are expressed in frequencies (percentages) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: RHTN: Resistant hypertension, CHTN: Controlled hypertension, NT-C: normotensive controls, SBP: systolic blood pressure, ABPM: Ambulatory blood pressure monitoring, BMI: Body mass index, ACEI: Angiotensin converting enzyme inhibitor, ARB: Angiotensin receptor blocker, BB: Beta blocker, CCB: Calcium channel blocker, DM: Diabetes mellitus, AB: Alpha blockers, ASA: Acetyl salicylic acid, SUA: Serum uric acid.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e*Between RHTN and CHTN groups\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e**Between RHTN and NT-C groups\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e+Between CHTN and NT-C groups\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eBiochemical parameters of the study groups are shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Glucose, creatinine, eGFR, uric acid, and electrolyte levels were similar between the RHTN and CHTN groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Microalbuminuria value was significantly higher in patients with RHTN than in patients with CHTN (103.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2 mg/dL, 25.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2 mg/dL, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.013). The frequency of LVH was 25% in patients with RHTN and 12.3% in patients with CHTN, and this difference was statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.025). C-reactive protein (CRP) value was significantly higher in patients with RHTN than patients with CHTN (13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 mg/L, 6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 mg/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.034, respectively). The albumin level was statistically different between the RHTN, CHTN, and NT-C groups (4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3, 4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4, and 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 g/dL, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.028).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of the biochemical parameters of the groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRHTN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCHTN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNT-C\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlucose (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e93.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUric acid (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSodium (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e139.1\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e140.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e138.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePotassium (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCalcium (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.028\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e**\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTriglycerides (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e139.3\u0026thinsp;\u0026plusmn;\u0026thinsp;61.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e150.4\u0026thinsp;\u0026plusmn;\u0026thinsp;80.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144.5\u0026thinsp;\u0026plusmn;\u0026thinsp;79.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTC (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e182.4\u0026thinsp;\u0026plusmn;\u0026thinsp;28.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e189.7\u0026thinsp;\u0026plusmn;\u0026thinsp;30.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e184.6\u0026thinsp;\u0026plusmn;\u0026thinsp;31.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLDL-c (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e116.1\u0026thinsp;\u0026plusmn;\u0026thinsp;33.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e114.6\u0026thinsp;\u0026plusmn;\u0026thinsp;29.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101.4\u0026thinsp;\u0026plusmn;\u0026thinsp;34.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHDL-c (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTSH (\u0026micro;IU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLeukocytes (*10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatelet (*10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e276\u0026thinsp;\u0026plusmn;\u0026thinsp;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e264\u0026thinsp;\u0026plusmn;\u0026thinsp;26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e290\u0026thinsp;\u0026plusmn;\u0026thinsp;33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUAE (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e103.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.013\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: TC: Total cholesterol, LDL-c: Low density lipoprotein, HDL-c: High density lipoprotein, TSH: Thyroid stimulating hormone, CRP: C-reactive protein, UAE: Urinary albumin excretion.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e*Between RHTN and CHTN groups\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e**Between RHTN and NT-C groups\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2. Electrocardiographic measurements\u003c/h2\u003e\n \u003cp\u003eThe mean QT and QTc intervals were 391\u0026thinsp;\u0026plusmn;\u0026thinsp;32 ms and 408\u0026thinsp;\u0026plusmn;\u0026thinsp;34 ms, respectively, in the RHTN group and 375\u0026thinsp;\u0026plusmn;\u0026thinsp;36 ms and 392\u0026thinsp;\u0026plusmn;\u0026thinsp;33 ms, respectively, in the CHTN group. QT and QTc intervals were significantly longer in the RHTN group than in the CHTN group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.023, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.019, respectively). The mean QTd was higher in RHTN than in CHTN (44.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 ms vs. 36.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 ms, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.021). The mean QTcd was higher in RHTN than in CHTN (47.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4 ms vs. 40.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8 ms, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.038). The mean Tp-e interval was significantly prolonged in patients with RHTN than in those with CHTN (80\u0026thinsp;\u0026plusmn;\u0026thinsp;9 and 72\u0026thinsp;\u0026plusmn;\u0026thinsp;8, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean TP-e/QT and TP-e/QTc ratios in the RHTN group were 0.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 and 0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02, respectively, while they were 0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03 and 0.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02 in the CHTN group. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the Tp-e, Tp-e/QT, and Tp-e/QTc ratios for RHTN, CHTN, and NT-C.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of electrocardiographic measurements between the resistant hypertension and controlled hypertension group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRHTN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCHTN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNT-C\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHR (beat/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81 (63\u0026ndash;92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76 (54\u0026ndash;89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79 (60\u0026ndash;96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQT (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e391\u0026thinsp;\u0026plusmn;\u0026thinsp;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e375\u0026thinsp;\u0026plusmn;\u0026thinsp;36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e360\u0026thinsp;\u0026plusmn;\u0026thinsp;31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*, **\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQTc (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e408\u0026thinsp;\u0026plusmn;\u0026thinsp;34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e392\u0026thinsp;\u0026plusmn;\u0026thinsp;33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e379\u0026thinsp;\u0026plusmn;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*, **\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQTd (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*, **\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecQTd (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.038\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*, **\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTp-e (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*, **\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTp-e/QT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*, **\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTp-e/QTc\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*, **\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLVH, (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.025\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eData are represented as mean values\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, and frequency.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: HR: Heart rate, RHTN: Resistant hypertension, CHTN: Controlled hypertension, HR: Heart rate, LVH: Left ventricular hypertrophy.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e*Between RHTN and CHTN groups\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e**Between RHTN and NT-C groups\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3. Correlation analysis\u003c/h2\u003e\n \u003cp\u003ePearson\u0026rsquo;s correlation analysis was performed between the clinical variables, Tp-e interval, and Tp-e/QTc ratio. There was no significant correlation between UAE, albumin, and GFR and the Tp-e interval and Tp-e/QTc ratios. A weak positive correlation was observed between age, Tp-e interval, and the Tp-e/QTc ratio. There was also a statistically significant positive correlation between 24 h-ABPM systolic and diastolic blood pressure with the Tp-e interval and Tp-e/QTc ratio (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCorrelation between Tpe interval and Tpe/QT ratio with clinical parameters\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eTp-e\u003c/p\u003e\n \u003cp\u003er p\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eTp-e/QTc\u003c/p\u003e\n \u003cp\u003er p\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.260\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.302\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.045\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.317\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUAE (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-ABPM SBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.447\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.551\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-ABPM DBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.405\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.654\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.763\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.148\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGFR (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.528\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.651\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: CRP: C-reactive protein, BMI: Body mass index, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, UAE: Urinary albumin excretion\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4. Logistic regression analysis\u003c/h2\u003e\n \u003cp\u003eMultivariate logistic regression analysis indicated that diabetes (\u0026beta; 2.031, 95% CI 1.387\u0026ndash;4.108, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.012), pill burden (\u0026beta; 1.293, 95% CI 1.086\u0026ndash;1.872, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.033), 24-h ABPM systolic blood pressure (\u0026beta; 1.419, 95% CI 1.158\u0026ndash;2.094, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.016), UAE (\u0026beta; 1.332, 95% CI 1.064\u0026ndash;1.719, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.041), CRP (\u0026beta; 1.451, 95% CI 1.252\u0026ndash;2.357, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.014), age (\u0026beta; 1.535, 95% CI 1.275\u0026ndash;3.314, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.025) were significant and independently predicted Tp-e/QT ratio. In the multivariate linear regression analysis, RHTN was found to be an independent risk factor for increased Tp-e/QTc ratio (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariate logistic regression analysis to assess independent predictors of increased Tp-e/QTc ratio\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026beta;\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOdds ratio (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.535\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.275\u0026ndash;3.134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.025\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePill burden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.293\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.086\u0026ndash;1.872\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.252\u0026ndash;2.357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes Mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.387\u0026ndash;4.108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-h SBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.419\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.158\u0026ndash;2.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24-h DBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.097\u0026ndash;1.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUAE (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.064\u0026ndash;1.719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.041\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: CRP: C-reactive protein, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, UAE: Urinary albumin excretion\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe present study showed that Tp-e, Tp-e/QT, and Tp-e/QTc ratios were prolonged in patients with RHTN compared to CHTN and control patients. 24 h-ABPM systolic and diastolic blood pressure were associated with the Tp-e interval and the Tp-e/QTc ratio. Age, CRP, diabetes, pill burden (antihypertensive drug), UAE (mg/dL), and 24-h ABPM systolic blood pressure were independent predictors of Tp-e/QTc in the multivariate logistic regression analysis.\u003c/p\u003e \u003cp\u003eProlongation of the QT and QTc intervals is predictive of cardiovascular mortality and the risk of sudden cardiac death in the general population and in many patient groups. QT and QTc intervals reflect both depolarization and repolarization in the ventricles. The QT interval is influenced by many factors, such as electrolytes, drugs, endocrine factors, autonomic nervous system, and heredity \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. In this study, endocrine factors, electrolyte disturbances, and drug use were excluded as much as possible. QTd, which reflects the degree of regional repolarization disorder, is an independent risk factor for increased risk of ventricular arrhythmias in EHTN patients \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Prolonged Tp-e and QT distances and increased Tp-e/QT and Tp-e/QTc ratios in patients with RHTN indicate an increased risk of death due to non-atherosclerotic events. Kohno et al. showed that electrical abnormalities predicted by QTd are more sensitive than anatomical abnormalities assessed by echocardiography in assessing end-organ damage in hypertensive patients \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. It is also stated that the Tp-e/QT ratio can be used for risk stratification in coronary artery disease \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe ventricular myocardium consists of three cell layers (endocardial, epicardial, and myocardial M cells) with different electrophysiological characteristics. The Tp-e interval and the Tp-e/QT ratio are considered new indicators of impaired ventricular repolarization. Repolarization ends first in the epicardial layer, coinciding with the peak point (Tp) of the T wave. It ends in the repolarization of the mid-myocardial layer during the period until the end of the T wave (Tp-e). The Tp-e interval can be used as an index of the total (transmural, apical-basal, and global) dispersion of the repolarization. Accurate measurement of Tp-e, which is a very short range on ECG, should be performed carefully. Thus, Tp-e only shows the transmural distribution of repolarization.\u003c/p\u003e \u003cp\u003eThe Tp-e interval and Tp-e/QT ratio reflect repolarization heterogeneity better than the QT interval and reflect the transmural distribution of repolarization. While the Tp-e and QT intervals are affected by body mass index and heart rate, the Tp-e/QT ratio is not affected by these factors and is more sensitive in predicting ventricular arrhythmia \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Tp-e/QT is considered a more sensitive index of arrhythmogenesis than Tp-e or QT intervals alone. The Tp-e/QT ratio is a relatively new index and remains constant when the heart rate is 60\u0026ndash;100 per minute and has a mean value of 0.21 in the precordial leads \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. The Tp-e/QT ratio is significantly increased in patients with both arrhythmogenic (short QT, long QT, and Brugada syndrome) and atherosclerotic (acute myocardial infarction) heart diseases \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. The Tp-e/QT ratio is high in patients with malignant ventricular arrhythmias and is a strong predictor of sudden cardiac death \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePrevious studies have shown that ventricular repolarization is associated with age, blood pressure, and diabetes \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. The association between EHTN and ventricular arrhythmias is well established. It has been shown that QT and Tp-e intervals are prolonged in previous studies in different hypertensive patient groups \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. In EHTN, the QT interval is often prolonged, regardless of antihypertensive therapy. Increased left ventricular wall tension in patients with hypertension stimulates myofibroblast activity and fibrosis. Increasing fibrosis triggers changes in mechanical and electrical activity (low conduction velocity, re-entry phenomenon, and ectopic impulses) in the atrial and ventricular myocardium \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Several studies have shown that ventricular repolarization time is prolonged with the development of LVH. LVH is associated with an increased QT interval, Tp-e interval, and Tp-e/QT ratio \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. An important result of this study is that microalbuminuria, which is a marker of hypertensive end-organ damage, is a predictor of increased Tp-e and Tp-e/QT ratios.\u003c/p\u003e \u003cp\u003eInflammation may be one of the potential mechanisms underlying the association between RHTN and a prolonged QTc interval. It has been shown that levels of inflammatory cytokines (interleukin (IL) 1b, IL-6, and tumor necrosis factor-α (TNF-α)) and prognostic nutritional index increase in patients with RHTN \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Inflammatory processes trigger fibrosis in the left ventricle, causing arrhythmias. Many basic studies have shown that inflammatory cytokines prolong the QT interval by changing cardiac electrophysiology, especially the expression and function of calcium and potassium channels \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Some mechanisms may explain the long QT interval. These gene mutations affect the functions of cardiac ion channels in cardiac repolarization, cardiac autonomic neuropathy, sympathetic-vagal irregularities, electrolyte disorders, slow or absent conduction systems due to ischemia and fibrosis, different components of insulin resistance syndrome, systolic dysfunction, and LVH \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAnother possible mechanism explaining the relationship between RHTN and prolonged QT interval is the heart rate variation caused by the sympathetic nervous system. RHTN is associated with increased sympathetic nervous system activity, which is closely associated with an increased risk of ventricular arrhythmias.\u003c/p\u003e"},{"header":"5. Limitations","content":"\u003cp\u003eThis study had some limitations. First, this was a retrospective and observational study conducted at a single center with a small number of patients. Second, the intervals and ratios used in this study were measured manually. Additionally, although the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio showed a predisposition to arrhythmia, clinical and rhythm holter follow-ups were not performed to detect arrhythmia. Another limitation is the lack of echocardiographic evaluation and ventricular arrhythmia follow-up. The fact that the exclusion criteria used when including patients with RHTN were quite comprehensive can be considered a positive feature.\u003c/p\u003e"},{"header":"6. Conclusion","content":"\u003cp\u003eIn conclusion, this study shows that the Tp-e Interval, Tp-e/QT, and Tp-e/QTc ratios in patients with RHTN are longer than those in patients with CHTN. These parameters are simple and noninvasive methods that are valuable for detecting ventricular repolarization in patients with RHTN.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthical statement\u003c/strong\u003e \u003cp\u003e The Clinical Research Ethics Committee of Akdeniz University Medical Faculty approved this study (20.07.2022/479). This study was conducted in compliance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all the patients.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflict of interest:\u003c/h2\u003e \u003cp\u003eThe authors declare that there are no conflicts of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNo funding was received for this commentary.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: NK, FY; Data Curation: NK, FY, MK; Formal analysis: NK, FY, MK; Investigation: NK, FY; Methodology: NK, FY, VT; Project administration: NK, FY; Software: NK, FY, MK; Supervision: VT, ET; Validation: VT, NK, ET; Visualization: NK, VT; Writing original draft: NK, FY, VT; Writing- review: NK, ET, VT\u003c/p\u003e\u003ch2\u003eAcknowledgement:\u003c/h2\u003e \u003cp\u003eThe authors wish to acknowledge the personnel who performed the ECG recording and the participants of the study for their support during the data collection process.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe dataset is available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcEvoy JW, McCarthy CP, Bruno RM, ESC Scientific Document Group, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912\u0026ndash;4018. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehae178\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehae178\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamirault G, Artifoni M, Daniel M, Barber-Chamoux N, Nantes University Hospital Working Group On Hypertension. Resistant Hypertension: Novel Insights. Curr Hypertens Rev. 2020;16(1):61\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2174/1573402115666191011111402\u003c/span\u003e\u003cspan address=\"10.2174/1573402115666191011111402\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAy SA, Bulucu F, Karaman M, et al. 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Eur Heart J. 2017;7(22):1717\u0026ndash;27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehw208\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehw208\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Resistant hypertension, electrocardiography, Tp-e interval, Tp-e/QT, Tp-e/QTc","lastPublishedDoi":"10.21203/rs.3.rs-8629687/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8629687/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e \u003cp\u003eResistant hypertension (RHTN) is associated with increased cardiovascular morbidity and mortality. This study aimed to evaluate T-peak-to-T-end (Tp-e) and Tp-e/QTc ratios in patients with RHTN.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study included 133 patients and 32 healthy controls. Patients with hypertension were divided into two groups: 52 with RHTN and 81 with controlled hypertension (CHTN). RHTN was defined as blood pressure (BP)\u0026thinsp;\u0026ge;\u0026thinsp;140/90 mmHg while taking\u0026thinsp;\u0026ge;\u0026thinsp;3 antihypertensive medications, or BP\u0026thinsp;\u0026lt;\u0026thinsp;140/90 mmHg while taking\u0026thinsp;\u0026ge;\u0026thinsp;4 medications. The Tp-e, Tp-e/QT, and Tp-e/QTc ratios were measured using a 12-lead electrocardiogram.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere were no significant differences among the groups in age, sex distribution, body mass index, smoking, heart rate, and diabetes mellitus frequency. The Tp-e, Tp-e/QT, and Tp-e/QTc ratios were significantly higher in patients with RHTN than in those with CHTN and healthy controls. Tp-e and Tp-e/QTc ratios were significantly positively correlation with 24 h ambulatory blood pressure (ABPM), systolic blood pressure, and diastolic blood pressure. In addition, age, C-reactive protein, diabetes, urinary albumin excretion, 24-h ABPM, and pill burden were independent predictors of an increased Tp-e/QTc ratio.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIncreased Tp-e and Tp-e/QTc ratios are associated with RHTN.\u003c/p\u003e","manuscriptTitle":"Tp-e Interval, Tp-e/QT, Tp-e/QTc ratios are associated with Resistant Hypertension Running Tittle: Tp-e Interval and Repolarization Markers in Resistant Hypertension","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-16 11:06:40","doi":"10.21203/rs.3.rs-8629687/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-24T07:16:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"178866815453422377618155446830522422826","date":"2026-02-18T11:54:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-11T07:36:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-22T10:13:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-21T10:38:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-21T10:37:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-01-18T07:03:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"42c60355-afd2-4ea4-8388-68fac1746312","owner":[],"postedDate":"February 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T11:06:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-16 11:06:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8629687","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8629687","identity":"rs-8629687","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}