|Year : 2018 | Volume
| Issue : 2 | Page : 102-107
Relationship between some electrocardiographic parameters of ventricular repolarization and Vitamin D status in apparently healthy individuals
Erdogan Sokmen1, Cahit Uçar2, Mustafa Çelik1, Serkan Sivri1, Yalçin Boduroglu1, Sinan Cemgil Özbek1, Alp Yildirim1
1 Department of Cardiology, Ahi Evran University Training and Research Hospital, Kirsehir, Turkey
2 Department of Internal Medicine, Ahi Evran University Training and Research Hospital, Kirsehir, Turkey
|Date of Web Publication||3-Jul-2019|
Dr. Erdogan Sokmen
Department of Cardiology, Ahi Evran University Training and Research Hospital, Kirsehir 40100
Source of Support: None, Conflict of Interest: None
Background: Vitamin D (VitD) is a vitamin affective on the cardiovascular system. VitD deficiency has been related to increased cardiac and all-cause mortality even in healthy controls. Evidence showed that such relatively novel electrocardiographic (ECG) parameters of ventricular repolarization (EPVR) as Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios might be related to increase cardiac arrhythmias and even sudden cardiac death. Little data are available about the effect of VitD deficiency on EPVR. The purpose of this study was to evaluate the EPVR in apparently healthy controls with VitD deficiency.
Methods: A total of 72 consecutive VitD deficient and 51 consecutive VitD nondeficient healthy controls who presented to our hospital's outpatient clinics were included in the study as two different groups. The relevant data were obtained through physical examination, electrocardiography, and echocardiography. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were calculated from surface ECG and compared between the two groups using the Mann–Whitney U-test.
Results: Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were all observed to be greater in VitD deficient group compared with the VitD nondeficient group, with robust statistical significance (68.1 ms [61.7–75.4] vs. 58 ms [54–66.2]; 0.197 [0.179–0.210] vs. 0.164 [0.147–0.187]; and 0.172 (0.156–0.191) versus 0.150 (0.137–0.164); respectively; P ≤ 0.001]).
Conclusion: Our study reveals that Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio increase in VitD deficiency in apparently healthy controls, which may be related to SCD. Further studies are needed to support our results.
Keywords: Parameters of ventricular repolarization, sudden cardiac death, Vitamin D deficiency
|How to cite this article:|
Sokmen E, Uçar C, Çelik M, Sivri S, Boduroglu Y, Özbek SC, Yildirim A. Relationship between some electrocardiographic parameters of ventricular repolarization and Vitamin D status in apparently healthy individuals. Nig J Cardiol 2018;15:102-7
|How to cite this URL:|
Sokmen E, Uçar C, Çelik M, Sivri S, Boduroglu Y, Özbek SC, Yildirim A. Relationship between some electrocardiographic parameters of ventricular repolarization and Vitamin D status in apparently healthy individuals. Nig J Cardiol [serial online] 2018 [cited 2019 Jul 19];15:102-7. Available from: http://www.nigjcardiol.org/text.asp?2018/15/2/102/262008
| Introduction|| |
Vitamin D (VitD) is a fat-soluble vitamin which acts as a steroid hormone and fulfills a vast realm of functions throughout the human body. While the term “VitD” covers some inactive prohormones such as VitD2 and D3, it is calcitriol (1–25-dihydroxyvitamin D) which is biologically active. Calcitriol is generated as a result of 1α-hydroxylation of 25-hydroxyvitamin D, a process occurring primarily in the kidneys. Circulating level of inactive 25-hydroxyvitamin D in the bloodstream represents a more reliable indicator of bodily VitD status as well as its anticipated clinical results, compared with the active 1–25-hydroxyvitamin D. Besides its most prominent role in mineral homeostasis and bone metabolism, VitD also possesses a variety of endocrine, autocrine, and paracrine functions encompassing nervous, cardiovascular (CVS), immune, and renin-angiotensin systems.
Deficiency of VitD has gradually been escalating into a more serious problem worldwide and appeals more and more to the healthcare professionals owing to its independent association with elevated risk of sudden cardiac death (SCD), CVS events and all-cause mortality,, possibly through mechanisms at the cellular and neuroendocrine levels.
Cardiac autonomic nervous system (ANS) comprises sympathetic plexus and parasympathetic vagus nerve, both of which operate harmoniously with each other in normal circumstances. Previous studies reported that activated VitD contributed to the functioning of cardiac ANS , both at neural and cardiac cellular levels. Deterioration of cardiac ANS translates into an increased CVS mortality, even in healthy controls. Increased sympathetic tone at the expense of decreased vagal tone was suggested to be associated with increased ventricular arrhythmias and eventually SCD. Moreover, VitD deficiency was reported to be implicated in the impairment of cardiac autonomic functions in apparently healthy individuals.
QT interval (QT), corrected QT interval (QTc), QT dispersion, and parameters of transmural dispersion of repolarization are among the relatively novel, simple and readily-available electrocardiographic (ECG) parameters that can be used to evaluate ventricular repolarization. Moreover, the time interval from the peak to the end of the T-wave electrocardiographically referred to as Tp-e interval appears as an index for transmural dispersion of ventricular repolarization, and is associated with varying durations of the action potential in endocardium, myocardium, and epicardium. Tp-e/QT and Tp-e/QTc ratios are among the other ECG indices representing the ventricular arrhythmogenic potential of different degrees. These ECG parameters, accordingly, were suggested to be useful indices to anticipate patients at higher risk for cardiac arrhythmia development in diverse clinical conditions.
In the light of the above-mentioned premises, we intended to evaluate the status of ventricular repolarization in apparently healthy individuals with VitD deficiency by using the ECG parameters of Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio.
| Methods|| |
Study design and participants
A total of 123 consecutive and apparently healthy individuals between the age group of 18 and 50 years (73 [59.3%] females and 50 [40.7%] males) who presented to outpatient clinics of our hospital for a routine check-up between September 2017 and January 2018 were included in the study. Blood VitD level was measured in these individuals with the widespread mild pain of musculoskeletal character in an attempt to inquire about probable VitD deficiency. Furthermore, all the individuals recruited were divided further into two subgroups on the basis of VitD levels as VitD deficient (n = 72, 25 (OH) D <20 ng/mL) and nondeficient (n = 51, 25 (OH) D ≥20 ng/mL) groups. Due to controversy regarding the optimal cutoff values for VitD deficiency and sufficiency,,, we preferred to use the cutoff for deficiency (<20 ng/mL) defined by The Endocrine Society Clinical Practice Guideline, which was more extensively cited in previous studies. Among the exclusion criteria were renal, gastrointestinal or hepatic dysfunction, smoking, alcoholism, any known history for cardiac disease, malignancy, diabetes mellitus, and medication use of any kind, endocrine pathology, hypertension, obesity, and supplementation therapy of any kind. Informed consent was obtained from every participant, and the local ethics committee approved our study.
Demographic, ECG, and echocardiographic information were collected on the day of the presentation. A comprehensive physical examination was performed in all the participants, followed by ECG and transthoracic echocardiography scans. Each individual was interrogated thoroughly for any past and/or present medical disease, and smoking and alcohol habits. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Moreover, blood samples were obtained through venipuncture from all the patients centrifuged for 10 min and analyzed immediately. The 25-OH-D level was measured using quantitative electrochemiluminescence binding assay, with detection of 25 OHD, (Roche Diagnostics, Mannheim, Germany). Within-day interassay and intraassay coefficients of variation were 3.4%–13.1% and 2.2%–6.8%, respectively.
Electrocardiography and echocardiography
12-lead ECGs were obtained from all the participants in the supine position using a standard ECG system (Nihon Kohden, Tokyo, Japan) at a paper speed of 50 mm/s. All of the ECG papers were scanned and transferred to the digital media, and the digital records were analyzed under ×300% magnification in personal computers. RR interval, QT interval, and Tp-e interval were measured using the precordial lead V5. QTc intervals were obtained using Bazett's formula: QTc = QT/√(RR). Then, Tp-e/QT and Tp-e/QTc ratios were calculated. There are two commonly used methods of measuring Tp-e interval: Tangent method and tail method., We used in our study the tangent method, which refers to the time interval between the peak of the T wave and the point where the tangent of to the steepest down-slope of the T-wave intersects with the isoelectric line. Three consecutive beats were averaged to obtain the ultimate measurement for each parameter. All the ECG parameters were assessed by two experienced cardiologists blinded to the study design. The interobserver and intraobserver coefficient of variation were 2.5% and 2.1%, respectively. All the transthoracic echocardiographic assessment of the study participants were performed using Vivid S5 (GE Vingmed Ultrasound AS, Horten, Norway) in the left lateral decubitus position. The left ventricular dimensions, wall thicknesses, and left atrial diameters were measured in the parasternal long-axis view. Left ventricular ejection fraction was calculated using the modified Simpson's rule. In apical four-chamber view, early (E) and late (A) diastolic transmitral velocities, as well as deceleration time of E velocity, were measured with a sample volume located between the tips of the mitral leaflets using pulsed wave Doppler. Moreover, pulse-wave tissue Doppler imaging was implemented with sample volume at the septal and lateral side of the mitral annulus, thus obtaining respective septal and lateral early (E') and late (A') diastolic mitral annular velocities. Then, E/E' was calculated for each participant. All the conventional echocardiographic examination were performed according to the standards of the American Society of Echocardiography.
Statistical analysis of the study data was performed using SPSS Version 22.0 (SPSS Inc., Chicago, IL, USA). Numbers, percentage, mean ± standard deviation, median, minimum (min), maximum (max) and 25–75 percentiles were used for the descriptive statistics. Chi-square test was used for the comparison of categorical variables, while continuous variables were compared using the Shapiro–Wilk test. Because the data were found to be nonnormally distributed, the study groups were compared using Mann–Whitney U test. Moreover, receiver operating characteristics (ROC) curve analysis was applied to find, if any, the most appropriate cutoff values, as well as the sensitivity, specificity, and negative and positive predictive value of the ECG parameters. P < 0.05 was accepted to be statistically significant.
| Results|| |
Baseline demographic features of the study groups on the basis of blood VitD measurements are presented in [Table 1]. VitD deficient group was composed of 72 participants (44 female [61.1%]), whereas VitD nondeficient group was composed of 51 participants (29 female [56.9%]). The participants comprising the VitD nondeficient group was a little bit older than those comprising the VitD deficient group (37 ± 10 years vs. 33 ± 10 years, respectively; P = 0.023). Furthermore, total cholesterol levels were a little lower in VitD deficient group compared with VitD nondeficient group (184 ± 31 mg/dL vs. 190 ± 20 mg/dL, respectively; P = 0.035). All the participating individuals were normotensive and nonobese, and the other demographic features such as gender, BMI, systolic and diastolic blood pressure, hemoglobin level, calcium level, aspartate transaminase level, glucose level, C-reactive protein level, and ratio of white blood cell count to mean platelet volume (WMR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio were similar between two groups. As for the echocardiography, both systolic and diastolic parameters measured showed no statistically significant differences between the groups. Respective mean levels of 25-OH VitD were 11.79 ± 3.67 ng/mL and 27.92 ± 6.36 ng/mL in the deficiency and the nondeficiency groups (P ≤ 0.001).
|Table 1: Baseline demographics of the study population according to Vitamin D measurements|
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Comparison of the ECG parameters of ventricular repolarization is presented in [Table 2]. Although mean QTc duration was similar between two groups (397 ms [386–409] and 388 ms [373–403]; P = 0.069]), QT duration was interestingly found to be shorter, although in mild statistical significance, in the deficiency group compared with the nondeficiency group (345 ms [335–365] vs. 360 ms [340–375]; respectively; P = 0.027). Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were all observed to be greater in VitD deficient group compared with the VitD nondeficient group, which showed a robust statistical significance (68.1 ms [61.7–75.4] vs. 58 ms [54–66.2; 0.197 [0.179–0.210] vs. 0.164 [0.147–0.187]; and 0.172 [0.156–0.191] vs. 0.150 [0.137–0.164]; respectively; P ≤ 0.001]).
|Table 2: Comparison of the parameters of ventricular repolarization between the groups|
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A further ROC curve analysis was implemented in an attempt to define a probable cutoff value for each of Tp-e interval, Tp-e/QT and Tp-e/QTc ratios to predict otherwise healthy individuals with serum 25-OH VitD level <20 ng/mL, which revealed the following cutoff values: Tp-e interval, >63 ms with sensitivity of 70.8% and specificity of 70.6 (AUC: 0.746732, P ≤ 0.0001); Tp-e/QT ratio, >0.175 ms with sensitivity of 83.3% and specificity of 64.7 (AUC: 0,804194, P ≤ 0.0001); and Tp-e/QTc ratio, >0,167 ms with sensitivity of 59.7% and specificity of 80.3% (AUC: 0.747549, P ≤ 0.0001) [Figure 1].
|Figure 1: Depiction of receiver operating characteristic curves for Tp-e value, Tp-e/QT ratio and Tp-e/QTc ratio to identify individuals with Vitamin D deficiency (AUC = 0,746732; 0,804194; 0,747549; respectively)|
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| Discussion|| |
The study results indicated mainly that such relatively novel ECG parameters of ventricular repolarization as Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio increased significantly in apparently healthy individuals with VitD deficiency, compared with VitD nondeficient counterparts. To the best of our knowledge, this study is the first to compare the status of cardiac repolarization assessed using such simple ECG parameters in apparently healthy individuals with different VitD levels.
Previous studies have already documented a clear and positive correlation between prolonged QT and QTc intervals and ventricular arrhythmias and mortality.,, Tp-e interval has been a relatively new parameter of cardiac repolarization, and its prolongation was reported to be associated with ventricular arrhythmias and SCD.,, More recently, Tp-e/QT showed up as new index of ventricular repolarization and was proposed to be more accurate predictor of ventricular arrhythmias due to its being more stable despite distinctions in body weight and dynamic heart rate changes within a given subject., Furthermore, it provides more accurate data regarding the status of ventricular repolarization compared with Tp-e interval or QT interval alone. Hence, we can extrapolate from these premises that statistically significant increase in Tp-e/QT and Tp-e/QTc ratios is likely to be more predictive regarding the status of ventricular repolarization in VitD deficient group of our study, despite appearance of shorter mean QT interval in the same group.
VitD acts through binding to its intracellular receptor. Many previous reports seem entangled chiefly with autonomic dysfunction emerging as a result of VitD deficiency that has been held responsible for the likely arrhythmic cardiac implications. As was suggested previously, however, a constellation of other mechanisms such as endocrine, paracrine, and autocrine signaling could also exert some effects in this regard, since endothelial cells, myocardial cells, and vascular smooth muscle cells as well as rennin-angiotensin system have all VitD receptors. A recent meta-analysis by Burgaz et al. comprising four prospective and 14 cross-sectional studies reported an inverse association between 25-OH VitD and hypertension. In another study by Schmidt et al. performed in mouse models, VitD receptor knockout as well as diet low in VitD was reported to be associated with vascular calcification and atherosclerotic changes. In another experimental study, VitD receptor knockout mouse models showed ventricular hypertrophy. Iannuzzo et al. reported a significant correlation between peripheral arterial diseases and VitD insufficiency in their recent and comprehensive meta-analysis.
Cardiac autonomic functions are affected by VitD., In addition, increased cardiac sympathetic tone along with decreased parasympathetic vagal stimuli is associated with increased sudden arrhythmic cardiac death. Canpolat et al. reported in their study conducted on 50 VitD sufficient and 24 VitD deficient apparently healthy individuals that heart rate variability and heart rate recovery index, which are both indices of cardiac autonomic functioning, impaired in VitD deficient individuals. Yagishita et al. induced a cardiac sympathetic stimulation through the right and the left stellate ganglia and observed significant prolongation of Tp-e interval as well as global dispersion of repolarization. Vaseghi et al. also found similar results. Moreover, VitD supplementation was reported to improve cardiac autonomic functioning in healthy subjects. Considering all these findings, one can expect that VitD deficiency may be implicated in the disruption of parameters of ventricular repolarization. Our study findings, accordingly, support this premise.
Our study should be assessed with some limitations. First, our study population was relatively small. Furthermore, we did not evaluate the ECG parameters of ventricular repolarization after VitD supplementation.
| Conclusion|| |
Our study results reveal that such relatively novel ECG parameters of ventricular repolarization as Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio increase in VitD deficiency in apparently healthy individuals, which may be related to cardiac arrhythmic complications and SCD. Considering VitD deficiency gradually becoming a serious health problem worldwide, we hope that our results operate as an additional incentive to overcome this worldwide problem. However, further large-scale studies are needed to support our results.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]