Comparison of the Relationship Between Calf Circumference and Vitamin D with Orthostatic Intolerance and Vasovagal Syncope in Children

Comparison of the Relationship Between Calf Circumference and Vitamin D with Orthostatic Intolerance and Vasovagal Syncope in Children | 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 Comparison of the Relationship Between Calf Circumference and Vitamin D with Orthostatic Intolerance and Vasovagal Syncope in Children Ahmet irdem, Selma Oktay Ergin, Alper Kaçar, Ayşen Yüksel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4561578/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The aim of this study is to elucidate the relationship between calf circumference, calf circumference to leg length ratio, and vitamin D in patients presenting with orthostatic intolerance (OI) and vasovagal syncope (VVS) Methods This retrospective study included 313 pediatric patients, and 128 healthy pediatric individuals served as the control group. All anthropometric measurements, including body weight, height, body mass index, leg length, calf circumference, and calf circumference to leg length ratio, were performed by the same individual using standardized criteria to ensure reliability. Blood values, including vitamin D, electrocardiography, and echocardiography, were evaluated by the same physician Results There were no significant differences between the two groups in any of the variables in terms of age, body weight, height, body mass index (BMI), serum calcium, phosphorus, magnesium, sodium, TSH, T4, B12 vitamin, and ferritin values. Additionally, no significant differences were observed between the two groups in terms of LVIDd, LVIDs, IVSd, IVSs, LVPWd, LVPWs, and fractional shortening. However, serum vitamin D, calf circumference, calf circumference to leg length ratio, systolic blood pressure, and diastolic blood pressure results were found to be 12.2 ± 4.4, 24.8 ± 7.9, 31.1 ± 3.7, 34.0 ± 3.7, 0.3 ± 0.4, 0.3 ± 0.4, 103.1 ± 10.2, 108.9 ± 10.9, 61.8 ± 8.7, and 68.9 ± 8.8 respectively in the patient and control groups. Serum vitamin D, calf circumference, calf circumference to leg length ratio, systolic blood pressure, and diastolic blood pressure results were found to be significantly lower in the patient group (p < 0.005) Conclusions In this study, we found that calf circumference, calf circumference to leg length ratio, and vitamin D levels were lower in patients presenting with VVS and/or orthostatic intolerance (OI). We believe that measuring vitamin D levels and calf circumference may be considered as a tool for assessing muscle mass in patients with OI and VVS syncope. calf circumference children vasovagal syncope vitamin D Introduction Vasovagal syncope (VVS) is the most common cause of syncope in children. VVS arises from acute orthostatic intolerance (OI) and recurrent syncope attacks, which can significantly impact an individual's quality of life.OI, one of the underlying causes of syncope, may occur secondary to concurrent venous pooling and increased capillary filtration. The pathophysiological mechanisms underlying VVS remain uncertain [ 1 ]. While a range of potential mechanisms play a role in its pathophysiology, the primary cause of symptoms varies among patients. The multifaceted nature of VVS poses a real challenge in understanding this condition and developing preventive strategies [ 2 ]. Vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/L or < 20 ng/mL) is a prevalent health issue worldwide [ 3 ]. Vitamin D deficiency reduces the absorption of calcium and phosphorus from the intestines, resulting in hypocalcemia and hypophosphatemia, which can lead to rickets in children and osteomalacia in adults. The primary cause of vitamin D deficiency is decreased synthesis of vitamin D in the skin, which may be due to factors such as insufficient exposure to UV radiation, excessive use of sunscreen, and limited outdoor activities. Additionally, deficiency is also associated with reduced dietary intake of vitamin D, aging, and liver or kidney disorders [ 4 , 5 ]. Vitamin D has both direct and indirect effects on skeletal muscle. It is believed that it can preserve and enhance muscle strength and physical performance by stimulating the proliferation and differentiation of skeletal muscle fibers [ 6 – 8 ]. Vitamin D may induce muscle protein breakdown by increasing the expression of muscle proteins. As a result, it can reduce grip strength and cause muscle atrophy. Loss of muscle mass and strength due to vitamin D deficiency is a common issue associated with decreased balance and physical performance [ 9 ]. One of the anthropometric approaches that has attracted attention as an indicator of skeletal muscle mass in limited settings is calf circumference (CC) measurement. CC measurements are extensively used as a muscle indicator in geriatric studies and are the most commonly used tool for evaluating muscle mass in clinical practice for diagnosing sarcopenia in the elderly. CC diameter not only varies between men and women but also shows significant differences according to age, ethnicity, and race. In the elderly, cancer patients, and patients admitted to intensive care units (ICUs), CC can provide information about nutritional status and muscle atrophy [ 10 , 11 ]. It can reflect a decrease in muscle mass due to limited physical activity. A result greater than 31 cm is considered normal in adults. When diagnosing sarcopenia, it should be noted that interpretation errors may occur in measurements of arm and calf circumference due to the presence of edema and possible connective and adipose tissue instead of muscle tissue [ 12 , 13 ]. The cutoff value of calf circumference to define low muscle mass varies between 30 and 35 cm depending on the population under study [ 14 ]. Recurrent syncope management is challenging. Patient counseling and lifestyle advice are primary management recommendations, which include patient education, advising the patient to avoid known triggers, increasing fluid intake (often with salt supplementation), and performing physical counter-pressure maneuvers (such as squatting, leg crossing, and tensing limb and/or abdominal muscles). While these recommendations are beneficial when prodromal symptoms are present, they are often insufficient to completely prevent symptoms, especially in severely affected patients, particularly those experiencing frequent attacks. Additionally, counter-pressure maneuvers are only beneficial in patients with prodromes of sufficient duration to perform them and may be difficult to execute in patients with gait disturbances or neuromuscular disorders. Additional strategies used in the treatment of recurrent syncope include pharmacological therapy aimed at increasing vascular resistance (Midodrine) or plasma volume (Fludrocortisone), as well as cardiac pacing for syncope with deep cardioinhibition; however, the effectiveness and benefit of these approaches have been questioned [ 15 ]. Static external compression stockings are often recommended for the treatment of syncope. Prescribed for individuals with orthostatic intolerance, these stockings apply external pressure to the lower extremities or abdominal area, reducing venous pooling and capillary filtration while increasing venous return [ 16 , 17 ]. In this study, we aimed to gather information about calf muscle mass through calf circumference (CC) measurement in patients presenting with orthostatic intolerance (OI) and vasovagal syncope (VVS), particularly those with low vitamin D levels. Additionally, we aimed to evaluate the risk of VVS in patients with low CC-to-height ratio. Methods The healthy control group consisted of 128 healthy children who underwent pre-exercise assessment between June 01, 2022, and June 01, 2023, for cardiac clearance prior to potential medication use with cardiac side effects or referrals due to innocent murmurs. These children had no history of systemic illness, medication use, cardiac or neurological diseases. Their electrocardiography, echocardiography, and cardiac examinations were normal. Furthermore, after obtaining written consent and assent from both parents and children, they were included in the study. The patient group consisted of 313 pediatric patients diagnosed with VVS and/or OI who presented with complaints of dizziness, presyncope, or syncope between January 01, 2022, and June 01, 2023. Patients diagnosed with dizziness, presyncope, or syncope due to systemic, cardiac, neurological, or medication-related causes were not included in the study. Additionally, the electrocardiography, echocardiography, and cardiac examinations of the patients were found to be normal. Since the data of the patient group were obtained retrospectively from hospital records, ethical approval was obtained from the Ethics Committee without the need for parental and child consent and written consent. Anthropometric measurements All anthropometric measurements (body weight, height, leg length, and calf circumference) were performed by the same individual, and standardized criteria were used to ensure reliability. Body mass index (BMI) was determined by dividing body weight (kg) by height (m) squared. The normal BMI range was considered to be 18.5–24.9 kg/m2. Height was measured using a smart device fixed to the wall. Weight was measured using a calibrated scale. Calf circumference was measured sitting or lying down, from the widest part of the calf on the left or right leg. During measurements, care was taken not to apply pressure to the subcutaneous tissue considering subcutaneous edema and adipose tissue [ 18 , 19 ]. Lower extremity length: The distance between the anterior superior iliac spine and the medial malleolus was measured and recorded. Arterial blood pressure and pulse measurement were performed after at least 10 minutes of rest, and then after standing still for 3 minutes, using an appropriate cuff on the right arm. Vitamin D and B12 measurements were obtained from the hospital records of the patients (all patients presenting with complaints of OI and VVS routinely undergo these tests. Patients without B12 and vitamin D results were not included in the study). In the control group, with parental consent, biochemical values including B12 and vitamin D were assessed, and those with low blood values were not included in the study). Echocardiography and electrocardiography studies are routinely performed for all patients presenting to the Pediatric Cardiology outpatient clinic. The studies involving human participants were reviewed and approved by This study was approved by the Research Ethics Committee of the Prof. Dr. Cemil Taşcıoğlu City Hospital (29.08.2023/E-48670771-514.99-223217935). The control patients/participants provided their written informed consent to participate in this study. Results The basic characteristics and biochemical variables of the patient and control groups are shown in Table 1 . A total of 313 pediatric patients presenting with OI and/or VVS and 128 pediatric individuals serving as the control group were included in this study. The male ratio in the patient and control groups was 65.18% and 50%, respectively. The mean age was 13.80 ± 2.32 years (range: 7–18 years) in the patient group and 14.11 ± 1.96 years (range: 7.7–18.80 years) in the control group (p > 0.005). The BMI values were 19.82 ± 3.43 kg/m2 (range: 11–34) in the patient group and 20.35 ± 3.21 kg/m2 (range: 12.9–28.5) in the control group (p > 0.005). There were no significant differences in age, body weight, height, BMI, serum calcium (Ca), phosphorus, magnesium, sodium, TSH, T4, B12 vitamin, and ferritin values between the two groups. Additionally, there were no significant differences between the two groups in terms of LVIDd, LVIDs, IVSd, IVSs, LVPWd, LVPWs, and fractional shortening. However, the results for serum vitamin D were 12.23 ± 4.37 in the patient group and 24.80 ± 7.94 in the control group; serum vitamin D levels were found to be statistically lower in the patient group (p < 0.005). Furthermore, systolic and diastolic blood pressure values were significantly lower in the patient group (p < 0.005) (Table 1 ) Table 1 Comparison of the Basic Characteristics and Laboratory Variables of the Patient and Control Groups Patient (n;313) Control (n;128) P * Gender Male 204 (% 65.18) 64 (%50) Female 109 (%34.82) 64 (%50) Age (years) 13.80 ± 2.32 (7–18 ) 14.11 ± 1.96 (7.7–18.80 ) 0.180 BMI (kg/m 2 ) 19.82 ± 3.43 (11–34) 20.32 ± 3.21 (12.9–28.5) 0.132 Body weight(kg) 51.27 ± 13.21 (20–100) 52.55 ± 10.90 (27–82) 0.303 Height (cm) 159.76 ± 13.55 (115–186) 160.31 ± 9.47(130–179) 0.678 Ca (mg/dl) 9.76 ± 0.4 9.83 ± 0.5 0.120 P (mg/dl) 4.43 ± 0.5 4.45 ± 0.6 0.760 Mg 2.07 ± 0.2 2.08 ± 0.2 0.876 Na 138.90 ± 1.89 138.88 ± 1.71 0.058 Ferritin 24.10 ± 9.6 24.83 ± 5.8 0.422 TSH 2.07 ± 0.9 2.12 ± 1.0 0.562 Pulse rate (beats/min) 83.06 ± 11.22 82.65 ± 11.88 0.735 Systolic blood pressure (mmHg) 103.13 ± 10.16 108.87 ± 10.99 0.000 Diastolic blood pressure (mmHg) 61.77 ± 8.68 68.86 ± 8.77 0.000 LVEDd (mm) 4.00 ± 0.68 3.99 ± 0.71 0.851 LVESd(mm) 2.47 ± 0.55 2.45 ± 0.57 0.852 FS (%) 38.88 ± 5.23 38.98 ± 5.64 0.860 IVSTd(mm) 6.83 ± 1.40 6.81 ± 1.31 0.858 IVSTs(mm) 12.08 ± 1.61 12.16 ± 1.58 0.626 LVPWTd(mm) 6.26 ± 1.36 6.50 ± 1.16 0.084 LVPWTs(mm) 10.91 ± 1.79 11.12 ± 1.55 0.238 Vitamin D 12.23 ± 4.37 24.80 ± 7.94 0.000 Vitamin B12 277.41 ± 104.84 292.70 ± 60.50 0.124 Leg length (cm) 95.34 ± 8.74 96.03 ± 6.38 0.424 *Independent samples test. LVEDd, left ventricular end-diastolic dimension; LVESd, left ventricular end-systolic dimension; IVSTd, interventricular septum thickness in diastole; IVSTs, interventricular septum thickness in systole; FS, fractional shortening; LVPWTd, left ventricular posterior wall thickness in diastole; LVPWTs,, left ventricular posterior wall thickness in systole; BMI, body mass index; Table 2 Comparison of Calf Circumference and Calf Circumference to Leg Length Ratio between the Two Groups Patient (n;313) Control (n;128) P CC mean ± SP 31.08 ± 3.75 34.00 ± 3.75 0.000 * CC/LL^ 0.32 ± 0.4 0.35 ± 0.4 0.000* CC, calf circumference; CC/LL, calf circumference/leg length , * Independent samples T-test Statistical evaluation The data obtained from the study were transferred to a computer and analyzed using the SPSS software package (Version 22 for Windows, SPSS Inc, Chicago, IL, USA) after coding. When evaluating the data, continuous variables were expressed as mean ± standard deviation if they were parametric and as median (minimum and maximum values) if they were non-parametric. Frequency data were expressed as number and percentage (%). For comparisons between groups of continuous variables showing normal distribution, the "Independent Samples T-test" was used. A statistical significance level of p < 0.05 was considered for all tests. Discussion In this study, we observed that calf circumference, the ratio of calf circumference to leg length, and vitamin D levels were lower in patients presenting with VVS and/or OI. We believe that measuring vitamin D levels and calf circumference could serve as a tool for evaluating muscle mass in patients with OI and VVS syncope. Vitamin D deficiency is highly prevalent in the society. Studies have reported vitamin D deficiency in children tor ise up to 80%. Research has also shown a higher incidence of OI and VVS in individuals with low vitamin D levels [ 20 , 21 ]. However, the pathophysiology between vitamin D deficiency and OI/VVS remains debated. It has been suggested that during orthostasis, activation of autonomic nervous system receptors such as aortic, carotid, and cardiopulmonary receptors, as well as cardiac C fibers, may lead to hypotension and bradycardia, resulting in VVS. Additionally, another theory proposes that a decrease in preload may lead to ventricular contraction due to catecholamines, contributing to VVS [ 22 – 25 ].In adult studies, low levels of vitamin D have been associated with reduced muscle strength and poor physical function in elderly individuals. Additionally, vitamin D has been suggested to play an important role in achieving optimal skeletal muscle function [ 26 – 28 ]. Vitamin D has both direct and indirect effects on skeletal muscle. It is proposed that vitamin D deficiency leads to increased expression of muscle proteins, resulting in muscle protein breakdown. Consequently, this may lead to both decreased grip strength and muscle atrophy. Loss of muscle mass and strength due to vitamin D deficiency is a common issue associated with decreased balance and physical performance [ 9 ]. The direct and indirect effects of vitamin D on skeletal muscle support our study findings. Calf circumference (CC); utilizing the lower extremity may be more meaningful in indicating total body muscle mass. When corrected for fat mass, calf circumference measurement provides a good indicator of lower extremity muscle mass, function, quality of life, and risk of falls [ 29 ]. Studies have demonstrated that CC diameter provides information about muscle mass and can be used to assess muscle mass [ 10 , 30 – 32 ]. The decrease in CC diameter is associated with decreased muscle strength and physical performance due to muscle atrophy in the leg region. This supports the increased risk of VVS in these patients. In the pathogenesis of VVS, there is an immediate gravitational redistribution of blood volume due to increased compliance and capacitance in the leg vessels and splanchnic circulation during standing. This redistribution of fluid, termed "venous pooling," reduces effective circulating volume, venous return, blood pressure, and ultimately cerebral blood flow. Static compression garments are often prescribed to patients with recurrent syncope in an attempt to minimize orthostatic fluid shifts and consequent decreases in blood pressure. However, their effectiveness in reducing orthostatic fluid shifts and improving orthostatic tolerance or syncope susceptibility has long been questioned. Below-knee calf compression stockings, by applying external pressure to the calf, are believed to reduce orthostatic fluid shifts and improve hemodynamic control during short periods of orthostatic stress [ 33 , 34 ]. Vitamin D plays a significant role in the pathogenesis of many diseases. Studies have shown low levels of vitamin D in VVS patients. Therefore, attention should be paid to this aspect when approaching VVS [ 21 , 35 , 36 ]. Atrophy and weakening of the calf muscles may increase the risk of VVS. Weakness and atrophy in the calf muscles can result from vitamin D deficiency. Consequently, it can be said that there is a higher risk of OI and VVS due to vitamin D deficiency. The emergence of OI and VVS associated with vitamin D deficiency explains this situation. In conclusion, this study supports the notion that calf circumference (CC) and vitamin D levels are lower in patients with OI and VVS compared to healthy control subjects, indicating the influence of vitamin D on weak muscle mass and strength. This study provides a new approach to the management of VVS and OI, but further research is warranted. Limitations of the study Limitations of the study include its retrospective nature, lack of comparison between pre- and post-treatment outcomes in patients with vitamin D deficiency, and the absence of a prospective randomized controlled trial. Declarations Conflict of interest Authors declare no conflict of interests for this article. Written informed consent was obtained from all patients before participating in the study. Funding İnformation: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector. Author Contribution Ayşen Yüksel; made substantial contributions acquisition, analysis, or interpretation of dataAhmet İrdem: drafted the work or revised it critically for important intellectual content.Alper Kaçar; approved the version to be published.Selma Oktay Ergin; made substantial contributions to the conception or design of the work References Shen WK, Sheldon RS, Benditt DG, Cohen MI, Forman DE, Goldberger ZD et al (2017) ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 1:136:e60–e122. 10.1161/CIR.0000000000000499 Del Rosso A, Alboni P, Brignole M, Menozzi C, Raviele A (2005) Relation of clinical presentation of syncope to the age of patients. Am J Cardiol 15:96:1431–1435. 10.1016/j.amjcard.2005.07.047 Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, Köstenberger M, Tmava Berisha A, Martucci G, Pilz S, Malle O (2020) Vitamin D deficiency 2.0: an update on the current status worldwide. Eur J Clin Nutr 74:1498–1513. 10.1038/s41430-020-0558-y Uchitomi R, Oyabu M, Kamei Y, Vitamin D, Sarcopenia (2020) Potential of Vitamin D Supplementation in Sarcopenia Prevention and Treatment. Nutrients 19:12:3189. 10.3390/nu12103189 Deluca HF (2014) History of the discovery of vitamin D and its active metabolites. Bonekey Rep 8:3:479. 10.1038/bonekey.2013.213 Agergaard J, Trøstrup J, Uth J, Iversen JV, Boesen A, Andersen JL, Schjerling P, Langberg H (2015) Does vitamin-D intake during resistance training improve the skeletal muscle hypertrophic and strength response in young and elderly men? - a randomized controlled trial. Nutr Metab (Lond). 30;12:32. 10.1186/s12986-015-0029-y Granic A, Hill TR, Davies K, Jagger C, Adamson A, Siervo M et al (2017) Vitamin D Status, Muscle Strength and Physical Performance Decline in Very Old Adults: A Prospective Study. Nutrients 13:9:379. 10.3390/nu9040379 Bollen SE, Bass JJ, Fujita S, Wilkinson D, Hewison M, Atherton PJ (2022) The Vitamin D/Vitamin D receptor (VDR) axis in muscle atrophy and sarcopenia. Cell Signal 96:110355. 10.1016/j.cellsig.2022.110355 Yang A, Lv Q, Chen F, Wang Y, Liu Y, Shi W et al (2020) The effect of vitamin D on sarcopenia depends on the level of physical activity in older adults. J Cachexia Sarcopenia Muscle 11:678–689. 10.1002/jcsm.12545 González-Correa CH, Pineda-Zuluaga MC, Marulanda-Mejía F (2020) Skeletal Muscle Mass by Bioelectrical Impedance Analysis and Calf Circumference for Sarcopenia Diagnosis. J Electr Bioimpedance 2411:57–61. 10.2478/joeb-2020-0009 Gonzalez MC, Mehrnezhad A, Razaviarab N, Barbosa-Silva TG, Heymsfield SB (2021) Calf circumference: cutoff values from the NHANES 1999–2006. Am J Clin Nutr 1(6):1679–1687. 10.1093/ajcn/nqab029 Kim GM, Song S, Park JH, Tak YJ, Wang IJ, Huh U, Cho JS (2022) Diagnostic significance of calf circumference in sarcopenia of healthy korean adult males. Front Physiol 16:13:973265. 10.3389/fphys.2022.973265 Hockin BCD, Claydon VE (2020) Intermittent Calf Compression Delays the Onset of Presyncope in Young Healthy Individuals. Front Physiol 23:10:1598. 10.3389/fphys.2019.01598 Champaiboon J, Petchlorlian A, Manasvanich BA, Ubonsutvanich N, Jitpugdee W, Kittiskulnam P et al (2023) Calf circumference as a screening tool for low skeletal muscle mass: Cut-off values in independent Thai older adults. BMC Geriatr 8;23(1):826. 10.1186/s12877-023-04543-4 Furtado JM, Almeida SM, Mascarenhas P, Ferraz ME, Ferreira JC, Vilanova M et al (2018) Anthropometric features as predictors of atherogenic dyslipidemia and cardiovascular risk in a large population of school-aged children. PLoS ONE 113:e0197922. 10.1371/journal.pone.0197922 Privett SE, George KP, Whyte GP, Cable NT (2010) The effectiveness of compression garments and lower limb exercise on post-exercise blood pressure regulation in orthostatically intolerant athletes. Clin J Sport Med 20:362–367. 10.1097/JSM.0b013e3181f20292 Avril S, Bouten L, Dubuis L, Drapier S, Pouget JF (2010) Mixed experimental and numerical approach for characterizing the biomechanical response of the human leg under elastic compression. J Biomech Eng. ;132(3):031006. 10.1115/1.4000967 . PMID: 20459194 Madden AM, Smith S (2016) Body composition and morphological assessment of nutritional status in adults: a review of anthropometric variables. J Hum Nutr Diet 29:7–25. 10.1111/jhn.12278 Rolland Y, Lauwers-Cances V, Cournot M, Nourhashémi F, Reynish W, Rivière D, Vellas B, Grandjean H (2003) Sarcopenia, calf circumference, and physical function of elderly women: a cross-sectional study. J Am Geriatr Soc 51:1120–1124. 10.1046/j.1532-5415.2003.51362.x Xiao P, Dong H, Li H, Yan Y, Cheng H, Liu J et al (2020) Adequate 25-hydroxyvitamin D levels are inversely associated with various cardiometabolic risk factors in Chinese children, especially obese children. BMJ Open Diabetes Res Care 8:e000846. 10.1136/bmjdrc-2019-000846 Khalaji A, Behnoush AH, Tajdini M (2023) Association between vitamin D deficiency and vasovagal syncope: A systematic review and meta-analysis. Clin Cardiol 46:721–728. 10.1002/clc.24035 Brignole M, Moya A, de Lange FJ et al (2018) 2018 ESC guidelines for the diagnosis and management of syncope. Eur Heart J 39:1883–1948. 10.1093/eurheartj/ehy037 van Dijk JG, van Rossum IA, Thijs RD (2021) The pathophysiology of vasovagal syncope: novel insights. Auton Neurosci 236:102899. 10.1016/j.autneu.2021.102899 Wieling W, Jardine DL, de Lange FJ, Brignole M, Nielsen HB, Stewart J et al (2016) Cardiac output and vasodilation in the vasovagal response: an analysis of the classic papers. Heart Rhythm 13:798–805. 10.1016/j.hrthm.2015.11.023 Kitada M, Ogura Y, Koya D (2016) The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging 8:2290–2307. 10.18632/aging.101068 Latham NK, Anderson CS, Reid IR (2003) Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc 51:1219–1226. 10.1046/j.1532-5415.2003.51405.x Ceglia L (2008) Vitamin D and skeletal muscle tissue and function. Mol Aspects Med 29:407–414. 10.1016/j.mam.2008.07.002 Ceglia L (2009) Vitamin D and its role in skeletal muscle. Curr Opin Clin Nutr Metab Care 12:628–633. 10.1097/MCO.0b013e328331c707 Bruyère O, Beaudart C, Reginster JY, Buckinx F, Schoene D, Hirani V et al (2016) Assessment of muscle mass, muscle strength and physical performance in clinical practice: an international survey. Eur Geriatr Med 7:243–246. https://doi.org/10.1016/j.eurger.2015.12.009 Kim GM, Song S, Park JH, Tak YJ, Wang IJ, Huh U, Cho JS (2022) Diagnostic significance of calf circumference in sarcopenia of healthy korean adult males. Front Physiol 13:973265. 10.3389/fphys.2022.973265 Tang T, Zhuo Y, Xie L, Wang H, Yang M (2020) Sarcopenia index based on serum creatinine and cystatin C is associated with 3-year mortality in hospitalized older patients. Sci Rep 10:1260. 10.1038/s41598-020-58304-z Lim WS, Cheong CY, Lim JP, Tan MMY, Chia JQ, Malik NA, Tay L (2022) Singapore Clinical Practice Guidelines For Sarcopenia: Screening, Diagnosis, Management and Prevention. J Frailty Aging 11:348–369. 10.14283/jfa.2022.59 Wade R, Paton F, Woolacott N (2017) Systematic review of patient preference and adherence to the correct use of graduated compression stockings to prevent deep vein thrombosis in surgical patients. J Adv Nurs 73:336–348. 10.1111/jan.13148 Hockin BCD, Claydon VE (2020) Intermittent Calf Compression Delays the Onset of Presyncope in Young Healthy Individuals. Front Physiol 23:10:1598. 10.3389/fphys.2019.01598 Kovalchuk T, Boyarchuk O (2023) Serum Vitamin D Levels in Children and Adolescents with Vasovagal Syncope, Syncope Due to Orthostatic Hypotension, and Cardiac Syncope. Turk Arch Pediatr 58:42–48. 10.5152/TurkArchPediatr.2022.22141 Kong YJ, Bian P, Yang YN, Dong T, Niu SM, Yuan SJ, Dong XY (2022) Association of vitamin D deficiency with severity of symptoms in children with vasovagal syncope. Zhonghua Er Ke Za Zhi 60:557–561. Chinese. 10.3760/cma.j.cn112140-20211009-00854 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-4561578","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":317860080,"identity":"e29827d9-6006-4500-8af8-528fc4e31cc6","order_by":0,"name":"Ahmet irdem","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYDACCRBhwMDYwMB8+MEHIJuNnRgtB8Ba2NIMZ4C0MBOlhQGkhUdBmgckQkgL/+zuxMcfCu7J9oudYTC2+bVNno+ZgfHDxxw8ltw5u9nggEGx8czZuQce5/bdNmxjZmCWnLkNjzU3crdJHDBISNxwOy/BOLfnNiNQCxszLx4t8jdyt/8Aadl/O8dA2rLntj1BLQZAWxjAtkgDtTD8uJ1IUIvhjdzNEmcMEoxn3E5LM+xtuJ3cxszYjNcvcjdyN36o+JMg2z87+fCDH39u285vbz744SM+76MAxjYw2UCsehD4Q4riUTAKRsEoGCkAAE9uWB4cX5V/AAAAAElFTkSuQmCC","orcid":"","institution":"Çanakkale Onsekiz Mart University, Faculty of Medicine, Department of Pediatric Cardiology","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"","lastName":"irdem","suffix":""},{"id":317860081,"identity":"e6e273dc-dcf7-4fbb-8d1f-5a53c8116c93","order_by":1,"name":"Selma Oktay Ergin","email":"","orcid":"","institution":"Okmeydanı Eğitim ve Araştırma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Selma","middleName":"Oktay","lastName":"Ergin","suffix":""},{"id":317860083,"identity":"e0e0b9b2-f30d-4258-9f30-b7195962af4a","order_by":2,"name":"Alper Kaçar","email":"","orcid":"","institution":"Okmeydanı Eğitim ve Araştırma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alper","middleName":"","lastName":"Kaçar","suffix":""},{"id":317860084,"identity":"13f437ca-abf0-4965-87b0-ba852ddbc29d","order_by":3,"name":"Ayşen Yüksel","email":"","orcid":"","institution":"Okmeydanı Eğitim ve Araştırma Hastanesi","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ayşen","middleName":"","lastName":"Yüksel","suffix":""}],"badges":[],"createdAt":"2024-06-11 06:10:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4561578/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4561578/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60592903,"identity":"9459ba78-1b7f-4b98-92e7-b6a9ae81310f","added_by":"auto","created_at":"2024-07-18 15:01:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":410821,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4561578/v1/1a201235-f31f-4939-9397-f245bada0800.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of the Relationship Between Calf Circumference and Vitamin D with Orthostatic Intolerance and Vasovagal Syncope in Children","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVasovagal syncope (VVS) is the most common cause of syncope in children. VVS arises from acute orthostatic intolerance (OI) and recurrent syncope attacks, which can significantly impact an individual's quality of life.OI, one of the underlying causes of syncope, may occur secondary to concurrent venous pooling and increased capillary filtration. The pathophysiological mechanisms underlying VVS remain uncertain [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While a range of potential mechanisms play a role in its pathophysiology, the primary cause of symptoms varies among patients. The multifaceted nature of VVS poses a real challenge in understanding this condition and developing preventive strategies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVitamin D deficiency (serum 25-hydroxyvitamin D\u0026thinsp;\u0026lt;\u0026thinsp;50 nmol/L or \u0026lt;\u0026thinsp;20 ng/mL) is a prevalent health issue worldwide [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Vitamin D deficiency reduces the absorption of calcium and phosphorus from the intestines, resulting in hypocalcemia and hypophosphatemia, which can lead to rickets in children and osteomalacia in adults. The primary cause of vitamin D deficiency is decreased synthesis of vitamin D in the skin, which may be due to factors such as insufficient exposure to UV radiation, excessive use of sunscreen, and limited outdoor activities. Additionally, deficiency is also associated with reduced dietary intake of vitamin D, aging, and liver or kidney disorders [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVitamin D has both direct and indirect effects on skeletal muscle. It is believed that it can preserve and enhance muscle strength and physical performance by stimulating the proliferation and differentiation of skeletal muscle fibers [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Vitamin D may induce muscle protein breakdown by increasing the expression of muscle proteins. As a result, it can reduce grip strength and cause muscle atrophy. Loss of muscle mass and strength due to vitamin D deficiency is a common issue associated with decreased balance and physical performance [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOne of the anthropometric approaches that has attracted attention as an indicator of skeletal muscle mass in limited settings is calf circumference (CC) measurement. CC measurements are extensively used as a muscle indicator in geriatric studies and are the most commonly used tool for evaluating muscle mass in clinical practice for diagnosing sarcopenia in the elderly. CC diameter not only varies between men and women but also shows significant differences according to age, ethnicity, and race. In the elderly, cancer patients, and patients admitted to intensive care units (ICUs), CC can provide information about nutritional status and muscle atrophy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It can reflect a decrease in muscle mass due to limited physical activity. A result greater than 31 cm is considered normal in adults. When diagnosing sarcopenia, it should be noted that interpretation errors may occur in measurements of arm and calf circumference due to the presence of edema and possible connective and adipose tissue instead of muscle tissue [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe cutoff value of calf circumference to define low muscle mass varies between 30 and 35 cm depending on the population under study [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecurrent syncope management is challenging. Patient counseling and lifestyle advice are primary management recommendations, which include patient education, advising the patient to avoid known triggers, increasing fluid intake (often with salt supplementation), and performing physical counter-pressure maneuvers (such as squatting, leg crossing, and tensing limb and/or abdominal muscles). While these recommendations are beneficial when prodromal symptoms are present, they are often insufficient to completely prevent symptoms, especially in severely affected patients, particularly those experiencing frequent attacks. Additionally, counter-pressure maneuvers are only beneficial in patients with prodromes of sufficient duration to perform them and may be difficult to execute in patients with gait disturbances or neuromuscular disorders. Additional strategies used in the treatment of recurrent syncope include pharmacological therapy aimed at increasing vascular resistance (Midodrine) or plasma volume (Fludrocortisone), as well as cardiac pacing for syncope with deep cardioinhibition; however, the effectiveness and benefit of these approaches have been questioned [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStatic external compression stockings are often recommended for the treatment of syncope. Prescribed for individuals with orthostatic intolerance, these stockings apply external pressure to the lower extremities or abdominal area, reducing venous pooling and capillary filtration while increasing venous return [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we aimed to gather information about calf muscle mass through calf circumference (CC) measurement in patients presenting with orthostatic intolerance (OI) and vasovagal syncope (VVS), particularly those with low vitamin D levels. Additionally, we aimed to evaluate the risk of VVS in patients with low CC-to-height ratio.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eThe healthy control group\u003c/b\u003e consisted of 128 healthy children who underwent pre-exercise assessment between June 01, 2022, and June 01, 2023, for cardiac clearance prior to potential medication use with cardiac side effects or referrals due to innocent murmurs. These children had no history of systemic illness, medication use, cardiac or neurological diseases. Their electrocardiography, echocardiography, and cardiac examinations were normal. Furthermore, after obtaining written consent and assent from both parents and children, they were included in the study.\u003c/p\u003e \u003cp\u003e \u003cb\u003eThe patient group\u003c/b\u003e consisted of 313 pediatric patients diagnosed with VVS and/or OI who presented with complaints of dizziness, presyncope, or syncope between January 01, 2022, and June 01, 2023. Patients diagnosed with dizziness, presyncope, or syncope due to systemic, cardiac, neurological, or medication-related causes were not included in the study. Additionally, the electrocardiography, echocardiography, and cardiac examinations of the patients were found to be normal. Since the data of the patient group were obtained retrospectively from hospital records, ethical approval was obtained from the Ethics Committee without the need for parental and child consent and written consent.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAnthropometric measurements\u003c/h2\u003e \u003cp\u003eAll anthropometric measurements (body weight, height, leg length, and calf circumference) were performed by the same individual, and standardized criteria were used to ensure reliability. Body mass index (BMI) was determined by dividing body weight (kg) by height (m) squared. The normal BMI range was considered to be 18.5\u0026ndash;24.9 kg/m2. Height was measured using a smart device fixed to the wall. Weight was measured using a calibrated scale. Calf circumference was measured sitting or lying down, from the widest part of the calf on the left or right leg. During measurements, care was taken not to apply pressure to the subcutaneous tissue considering subcutaneous edema and adipose tissue [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLower extremity length: The distance between the anterior superior iliac spine and the medial malleolus was measured and recorded.\u003c/p\u003e \u003cp\u003eArterial blood pressure and pulse measurement were performed after at least 10 minutes of rest, and then after standing still for 3 minutes, using an appropriate cuff on the right arm.\u003c/p\u003e \u003cp\u003eVitamin D and B12 measurements were obtained from the hospital records of the patients (all patients presenting with complaints of OI and VVS routinely undergo these tests. Patients without B12 and vitamin D results were not included in the study). In the control group, with parental consent, biochemical values including B12 and vitamin D were assessed, and those with low blood values were not included in the study). Echocardiography and electrocardiography studies are routinely performed for all patients presenting to the Pediatric Cardiology outpatient clinic.\u003c/p\u003e \u003cp\u003e The studies involving human participants were reviewed and approved by This study was approved by the Research Ethics Committee of the Prof. Dr. Cemil Taşcıoğlu City Hospital (29.08.2023/E-48670771-514.99-223217935). The control patients/participants provided their written informed consent to participate in this study.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe basic characteristics and biochemical variables of the patient and control groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 313 pediatric patients presenting with OI and/or VVS and 128 pediatric individuals serving as the control group were included in this study. The male ratio in the patient and control groups was 65.18% and 50%, respectively. The mean age was 13.80\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32 years (range: 7\u0026ndash;18 years) in the patient group and 14.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96 years (range: 7.7\u0026ndash;18.80 years) in the control group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.005). The BMI values were 19.82\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43 kg/m2 (range: 11\u0026ndash;34) in the patient group and 20.35\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21 kg/m2 (range: 12.9\u0026ndash;28.5) in the control group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.005). There were no significant differences in age, body weight, height, BMI, serum calcium (Ca), phosphorus, magnesium, sodium, TSH, T4, B12 vitamin, and ferritin values between the two groups. Additionally, there were no significant differences between the two groups in terms of LVIDd, LVIDs, IVSd, IVSs, LVPWd, LVPWs, and fractional shortening. However, the results for serum vitamin D were 12.23\u0026thinsp;\u0026plusmn;\u0026thinsp;4.37 in the patient group and 24.80\u0026thinsp;\u0026plusmn;\u0026thinsp;7.94 in the control group; serum vitamin D levels were found to be statistically lower in the patient group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). Furthermore, systolic and diastolic blood pressure values were significantly lower in the patient group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the Basic Characteristics and Laboratory Variables of the Patient and Control Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient (n;313)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl (n;128)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP *\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e204 (% 65.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64 (%50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109 (%34.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64 (%50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.80\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.32 (7\u0026ndash;18 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.11\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.96 (7.7\u0026ndash;18.80 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.82\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.43 (11\u0026ndash;34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.32\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.21 (12.9\u0026ndash;28.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBody weight(kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.27\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;13.21 (20\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52.55\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;10.90 (27\u0026ndash;82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e159.76\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;13.55 (115\u0026ndash;186)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e160.31\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;9.47(130\u0026ndash;179)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.678\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCa (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.76\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.83\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eP (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.43\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.45\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.760\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.07\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.08\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.876\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e138.90\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e138.88\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFerritin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.10\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.83\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.422\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.07\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.12\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePulse rate (beats/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.06\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;11.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82.65\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;11.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.735\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSystolic blood pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103.13\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;10.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108.87\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;10.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDiastolic blood pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.77\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;8.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.86\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;8.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLVEDd (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.99\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLVESd(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.47\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.45\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.852\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.88\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.98\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIVSTd(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.83\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.81\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.858\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIVSTs(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.08\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.16\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.626\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLVPWTd(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.26\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.50\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLVPWTs(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.91\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.12\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVitamin D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.23\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.80\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;7.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVitamin B12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e277.41\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;104.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e292.70\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;60.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLeg length (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.34\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;8.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96.03\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;6.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.424\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003e*Independent samples test. LVEDd, left ventricular end-diastolic dimension; LVESd, left ventricular end-systolic dimension; IVSTd, interventricular septum thickness in diastole; IVSTs, interventricular septum thickness in systole; FS, fractional shortening; LVPWTd, left ventricular posterior wall thickness in diastole; LVPWTs,, left ventricular posterior wall thickness in systole; BMI, body mass index;\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Calf Circumference and Calf Circumference to Leg Length Ratio between the Two Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient (n;313)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (n;128)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCC mean\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;SP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.08\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCC/LL^\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.32\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.35\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eCC, calf circumference; CC/LL, calf circumference/leg length\u003c/em\u003e, \u003csup\u003e\u003cem\u003e*\u003c/em\u003e\u003c/sup\u003e\u003cem\u003eIndependent samples T-test\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eStatistical evaluation\u003c/h3\u003e\n\u003cp\u003e The data obtained from the study were transferred to a computer and analyzed using the SPSS software package (Version 22 for Windows, SPSS Inc, Chicago, IL, USA) after coding. When evaluating the data, continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation if they were parametric and as median (minimum and maximum values) if they were non-parametric. Frequency data were expressed as number and percentage (%). For comparisons between groups of continuous variables showing normal distribution, the \"Independent Samples T-test\" was used. A statistical significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered for all tests.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we observed that calf circumference, the ratio of calf circumference to leg length, and vitamin D levels were lower in patients presenting with VVS and/or OI. We believe that measuring vitamin D levels and calf circumference could serve as a tool for evaluating muscle mass in patients with OI and VVS syncope.\u003c/p\u003e \u003cp\u003eVitamin D deficiency is highly prevalent in the society. Studies have reported vitamin D deficiency in children tor ise up to 80%. Research has also shown a higher incidence of OI and VVS in individuals with low vitamin D levels [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, the pathophysiology between vitamin D deficiency and OI/VVS remains debated. It has been suggested that during orthostasis, activation of autonomic nervous system receptors such as aortic, carotid, and cardiopulmonary receptors, as well as cardiac C fibers, may lead to hypotension and bradycardia, resulting in VVS. Additionally, another theory proposes that a decrease in preload may lead to ventricular contraction due to catecholamines, contributing to VVS [\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].In adult studies, low levels of vitamin D have been associated with reduced muscle strength and poor physical function in elderly individuals. Additionally, vitamin D has been suggested to play an important role in achieving optimal skeletal muscle function [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Vitamin D has both direct and indirect effects on skeletal muscle. It is proposed that vitamin D deficiency leads to increased expression of muscle proteins, resulting in muscle protein breakdown. Consequently, this may lead to both decreased grip strength and muscle atrophy. Loss of muscle mass and strength due to vitamin D deficiency is a common issue associated with decreased balance and physical performance [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The direct and indirect effects of vitamin D on skeletal muscle support our study findings.\u003c/p\u003e \u003cp\u003eCalf circumference (CC); utilizing the lower extremity may be more meaningful in indicating total body muscle mass. When corrected for fat mass, calf circumference measurement provides a good indicator of lower extremity muscle mass, function, quality of life, and risk of falls [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Studies have demonstrated that CC diameter provides information about muscle mass and can be used to assess muscle mass [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The decrease in CC diameter is associated with decreased muscle strength and physical performance due to muscle atrophy in the leg region. This supports the increased risk of VVS in these patients.\u003c/p\u003e \u003cp\u003eIn the pathogenesis of VVS, there is an immediate gravitational redistribution of blood volume due to increased compliance and capacitance in the leg vessels and splanchnic circulation during standing. This redistribution of fluid, termed \"venous pooling,\" reduces effective circulating volume, venous return, blood pressure, and ultimately cerebral blood flow. Static compression garments are often prescribed to patients with recurrent syncope in an attempt to minimize orthostatic fluid shifts and consequent decreases in blood pressure. However, their effectiveness in reducing orthostatic fluid shifts and improving orthostatic tolerance or syncope susceptibility has long been questioned. Below-knee calf compression stockings, by applying external pressure to the calf, are believed to reduce orthostatic fluid shifts and improve hemodynamic control during short periods of orthostatic stress [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Vitamin D plays a significant role in the pathogenesis of many diseases. Studies have shown low levels of vitamin D in VVS patients. Therefore, attention should be paid to this aspect when approaching VVS [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Atrophy and weakening of the calf muscles may increase the risk of VVS. Weakness and atrophy in the calf muscles can result from vitamin D deficiency. Consequently, it can be said that there is a higher risk of OI and VVS due to vitamin D deficiency. The emergence of OI and VVS associated with vitamin D deficiency explains this situation.\u003c/p\u003e \u003cp\u003eIn conclusion, this study supports the notion that calf circumference (CC) and vitamin D levels are lower in patients with OI and VVS compared to healthy control subjects, indicating the influence of vitamin D on weak muscle mass and strength. This study provides a new approach to the management of VVS and OI, but further research is warranted.\u003c/p\u003e \u003cp\u003eLimitations of the study\u003c/p\u003e \u003cp\u003eLimitations of the study include its retrospective nature, lack of comparison between pre- and post-treatment outcomes in patients with vitamin D deficiency, and the absence of a prospective randomized controlled trial.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eAuthors declare no conflict of interests for this article. Written informed consent was obtained from all patients before participating in the study.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding İnformation:\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAyşen Y\u0026uuml;ksel; made substantial contributions acquisition, analysis, or interpretation of dataAhmet İrdem: drafted the work or revised it critically for important intellectual content.Alper Ka\u0026ccedil;ar; approved the version to be published.Selma Oktay Ergin; made substantial contributions to the conception or design of the work\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShen WK, Sheldon RS, Benditt DG, Cohen MI, Forman DE, Goldberger ZD et al (2017) ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 1:136:e60\u0026ndash;e122. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIR.0000000000000499\u003c/span\u003e\u003cspan address=\"10.1161/CIR.0000000000000499\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDel Rosso A, Alboni P, Brignole M, Menozzi C, Raviele A (2005) Relation of clinical presentation of syncope to the age of patients. Am J Cardiol 15:96:1431\u0026ndash;1435. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.amjcard.2005.07.047\u003c/span\u003e\u003cspan address=\"10.1016/j.amjcard.2005.07.047\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, K\u0026ouml;stenberger M, Tmava Berisha A, Martucci G, Pilz S, Malle O (2020) Vitamin D deficiency 2.0: an update on the current status worldwide. Eur J Clin Nutr 74:1498\u0026ndash;1513. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41430-020-0558-y\u003c/span\u003e\u003cspan address=\"10.1038/s41430-020-0558-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUchitomi R, Oyabu M, Kamei Y, Vitamin D, Sarcopenia (2020) Potential of Vitamin D Supplementation in Sarcopenia Prevention and Treatment. Nutrients 19:12:3189. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/nu12103189\u003c/span\u003e\u003cspan address=\"10.3390/nu12103189\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeluca HF (2014) History of the discovery of vitamin D and its active metabolites. Bonekey Rep 8:3:479. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/bonekey.2013.213\u003c/span\u003e\u003cspan address=\"10.1038/bonekey.2013.213\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgergaard J, Tr\u0026oslash;strup J, Uth J, Iversen JV, Boesen A, Andersen JL, Schjerling P, Langberg H (2015) Does vitamin-D intake during resistance training improve the skeletal muscle hypertrophic and strength response in young and elderly men? - a randomized controlled trial. Nutr Metab (Lond). 30;12:32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12986-015-0029-y\u003c/span\u003e\u003cspan address=\"10.1186/s12986-015-0029-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGranic A, Hill TR, Davies K, Jagger C, Adamson A, Siervo M et al (2017) Vitamin D Status, Muscle Strength and Physical Performance Decline in Very Old Adults: A Prospective Study. Nutrients 13:9:379. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/nu9040379\u003c/span\u003e\u003cspan address=\"10.3390/nu9040379\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBollen SE, Bass JJ, Fujita S, Wilkinson D, Hewison M, Atherton PJ (2022) The Vitamin D/Vitamin D receptor (VDR) axis in muscle atrophy and sarcopenia. Cell Signal 96:110355. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cellsig.2022.110355\u003c/span\u003e\u003cspan address=\"10.1016/j.cellsig.2022.110355\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang A, Lv Q, Chen F, Wang Y, Liu Y, Shi W et al (2020) The effect of vitamin D on sarcopenia depends on the level of physical activity in older adults. J Cachexia Sarcopenia Muscle 11:678\u0026ndash;689. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/jcsm.12545\u003c/span\u003e\u003cspan address=\"10.1002/jcsm.12545\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonz\u0026aacute;lez-Correa CH, Pineda-Zuluaga MC, Marulanda-Mej\u0026iacute;a F (2020) Skeletal Muscle Mass by Bioelectrical Impedance Analysis and Calf Circumference for Sarcopenia Diagnosis. J Electr Bioimpedance 2411:57\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2478/joeb-2020-0009\u003c/span\u003e\u003cspan address=\"10.2478/joeb-2020-0009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonzalez MC, Mehrnezhad A, Razaviarab N, Barbosa-Silva TG, Heymsfield SB (2021) Calf circumference: cutoff values from the NHANES 1999\u0026ndash;2006. Am J Clin Nutr 1(6):1679\u0026ndash;1687. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ajcn/nqab029\u003c/span\u003e\u003cspan address=\"10.1093/ajcn/nqab029\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim GM, Song S, Park JH, Tak YJ, Wang IJ, Huh U, Cho JS (2022) Diagnostic significance of calf circumference in sarcopenia of healthy korean adult males. Front Physiol 16:13:973265. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphys.2022.973265\u003c/span\u003e\u003cspan address=\"10.3389/fphys.2022.973265\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHockin BCD, Claydon VE (2020) Intermittent Calf Compression Delays the Onset of Presyncope in Young Healthy Individuals. Front Physiol 23:10:1598. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphys.2019.01598\u003c/span\u003e\u003cspan address=\"10.3389/fphys.2019.01598\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChampaiboon J, Petchlorlian A, Manasvanich BA, Ubonsutvanich N, Jitpugdee W, Kittiskulnam P et al (2023) Calf circumference as a screening tool for low skeletal muscle mass: Cut-off values in independent Thai older adults. BMC Geriatr 8;23(1):826. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12877-023-04543-4\u003c/span\u003e\u003cspan address=\"10.1186/s12877-023-04543-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFurtado JM, Almeida SM, Mascarenhas P, Ferraz ME, Ferreira JC, Vilanova M et al (2018) Anthropometric features as predictors of atherogenic dyslipidemia and cardiovascular risk in a large population of school-aged children. PLoS ONE 113:e0197922. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0197922\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0197922\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrivett SE, George KP, Whyte GP, Cable NT (2010) The effectiveness of compression garments and lower limb exercise on post-exercise blood pressure regulation in orthostatically intolerant athletes. Clin J Sport Med 20:362\u0026ndash;367. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/JSM.0b013e3181f20292\u003c/span\u003e\u003cspan address=\"10.1097/JSM.0b013e3181f20292\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAvril S, Bouten L, Dubuis L, Drapier S, Pouget JF (2010) Mixed experimental and numerical approach for characterizing the biomechanical response of the human leg under elastic compression. J Biomech Eng. ;132(3):031006. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1115/1.4000967\u003c/span\u003e\u003cspan address=\"10.1115/1.4000967\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 20459194\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadden AM, Smith S (2016) Body composition and morphological assessment of nutritional status in adults: a review of anthropometric variables. J Hum Nutr Diet 29:7\u0026ndash;25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/jhn.12278\u003c/span\u003e\u003cspan address=\"10.1111/jhn.12278\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRolland Y, Lauwers-Cances V, Cournot M, Nourhash\u0026eacute;mi F, Reynish W, Rivi\u0026egrave;re D, Vellas B, Grandjean H (2003) Sarcopenia, calf circumference, and physical function of elderly women: a cross-sectional study. J Am Geriatr Soc 51:1120\u0026ndash;1124. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1532-5415.2003.51362.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1532-5415.2003.51362.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiao P, Dong H, Li H, Yan Y, Cheng H, Liu J et al (2020) Adequate 25-hydroxyvitamin D levels are inversely associated with various cardiometabolic risk factors in Chinese children, especially obese children. BMJ Open Diabetes Res Care 8:e000846. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmjdrc-2019-000846\u003c/span\u003e\u003cspan address=\"10.1136/bmjdrc-2019-000846\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhalaji A, Behnoush AH, Tajdini M (2023) Association between vitamin D deficiency and vasovagal syncope: A systematic review and meta-analysis. Clin Cardiol 46:721\u0026ndash;728. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/clc.24035\u003c/span\u003e\u003cspan address=\"10.1002/clc.24035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrignole M, Moya A, de Lange FJ et al (2018) 2018 ESC guidelines for the diagnosis and management of syncope. Eur Heart J 39:1883\u0026ndash;1948. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehy037\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehy037\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Dijk JG, van Rossum IA, Thijs RD (2021) The pathophysiology of vasovagal syncope: novel insights. Auton Neurosci 236:102899. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.autneu.2021.102899\u003c/span\u003e\u003cspan address=\"10.1016/j.autneu.2021.102899\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWieling W, Jardine DL, de Lange FJ, Brignole M, Nielsen HB, Stewart J et al (2016) Cardiac output and vasodilation in the vasovagal response: an analysis of the classic papers. Heart Rhythm 13:798\u0026ndash;805. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.hrthm.2015.11.023\u003c/span\u003e\u003cspan address=\"10.1016/j.hrthm.2015.11.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitada M, Ogura Y, Koya D (2016) The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging 8:2290\u0026ndash;2307. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.18632/aging.101068\u003c/span\u003e\u003cspan address=\"10.18632/aging.101068\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLatham NK, Anderson CS, Reid IR (2003) Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc 51:1219\u0026ndash;1226. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1532-5415.2003.51405.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1532-5415.2003.51405.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCeglia L (2008) Vitamin D and skeletal muscle tissue and function. Mol Aspects Med 29:407\u0026ndash;414. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.mam.2008.07.002\u003c/span\u003e\u003cspan address=\"10.1016/j.mam.2008.07.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCeglia L (2009) Vitamin D and its role in skeletal muscle. Curr Opin Clin Nutr Metab Care 12:628\u0026ndash;633. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MCO.0b013e328331c707\u003c/span\u003e\u003cspan address=\"10.1097/MCO.0b013e328331c707\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBruy\u0026egrave;re O, Beaudart C, Reginster JY, Buckinx F, Schoene D, Hirani V et al (2016) Assessment of muscle mass, muscle strength and physical performance in clinical practice: an international survey. Eur Geriatr Med 7:243\u0026ndash;246. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.eurger.2015.12.009\u003c/span\u003e\u003cspan address=\"10.1016/j.eurger.2015.12.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim GM, Song S, Park JH, Tak YJ, Wang IJ, Huh U, Cho JS (2022) Diagnostic significance of calf circumference in sarcopenia of healthy korean adult males. Front Physiol 13:973265. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphys.2022.973265\u003c/span\u003e\u003cspan address=\"10.3389/fphys.2022.973265\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang T, Zhuo Y, Xie L, Wang H, Yang M (2020) Sarcopenia index based on serum creatinine and cystatin C is associated with 3-year mortality in hospitalized older patients. Sci Rep 10:1260. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-020-58304-z\u003c/span\u003e\u003cspan address=\"10.1038/s41598-020-58304-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim WS, Cheong CY, Lim JP, Tan MMY, Chia JQ, Malik NA, Tay L (2022) Singapore Clinical Practice Guidelines For Sarcopenia: Screening, Diagnosis, Management and Prevention. J Frailty Aging 11:348\u0026ndash;369. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.14283/jfa.2022.59\u003c/span\u003e\u003cspan address=\"10.14283/jfa.2022.59\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWade R, Paton F, Woolacott N (2017) Systematic review of patient preference and adherence to the correct use of graduated compression stockings to prevent deep vein thrombosis in surgical patients. J Adv Nurs 73:336\u0026ndash;348. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/jan.13148\u003c/span\u003e\u003cspan address=\"10.1111/jan.13148\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHockin BCD, Claydon VE (2020) Intermittent Calf Compression Delays the Onset of Presyncope in Young Healthy Individuals. Front Physiol 23:10:1598. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphys.2019.01598\u003c/span\u003e\u003cspan address=\"10.3389/fphys.2019.01598\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKovalchuk T, Boyarchuk O (2023) Serum Vitamin D Levels in Children and Adolescents with Vasovagal Syncope, Syncope Due to Orthostatic Hypotension, and Cardiac Syncope. Turk Arch Pediatr 58:42\u0026ndash;48. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5152/TurkArchPediatr.2022.22141\u003c/span\u003e\u003cspan address=\"10.5152/TurkArchPediatr.2022.22141\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKong YJ, Bian P, Yang YN, Dong T, Niu SM, Yuan SJ, Dong XY (2022) Association of vitamin D deficiency with severity of symptoms in children with vasovagal syncope. Zhonghua Er Ke Za Zhi 60:557\u0026ndash;561. Chinese. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3760/cma.j.cn112140-20211009-00854\u003c/span\u003e\u003cspan address=\"10.3760/cma.j.cn112140-20211009-00854\" 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":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"calf circumference, children, vasovagal syncope, vitamin D","lastPublishedDoi":"10.21203/rs.3.rs-4561578/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4561578/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe aim of this study is to elucidate the relationship between calf circumference, calf circumference to leg length ratio, and vitamin D in patients presenting with orthostatic intolerance (OI) and vasovagal syncope (VVS)\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 313 pediatric patients, and 128 healthy pediatric individuals served as the control group. All anthropometric measurements, including body weight, height, body mass index, leg length, calf circumference, and calf circumference to leg length ratio, were performed by the same individual using standardized criteria to ensure reliability. Blood values, including vitamin D, electrocardiography, and echocardiography, were evaluated by the same physician\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were no significant differences between the two groups in any of the variables in terms of age, body weight, height, body mass index (BMI), serum calcium, phosphorus, magnesium, sodium, TSH, T4, B12 vitamin, and ferritin values. Additionally, no significant differences were observed between the two groups in terms of LVIDd, LVIDs, IVSd, IVSs, LVPWd, LVPWs, and fractional shortening. However, serum vitamin D, calf circumference, calf circumference to leg length ratio, systolic blood pressure, and diastolic blood pressure results were found to be 12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4, 24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9, 31.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7, 34.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7, 0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4, 0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4, 103.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2, 108.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9, 61.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7, and 68.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8 respectively in the patient and control groups. Serum vitamin D, calf circumference, calf circumference to leg length ratio, systolic blood pressure, and diastolic blood pressure results were found to be significantly lower in the patient group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005)\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this study, we found that calf circumference, calf circumference to leg length ratio, and vitamin D levels were lower in patients presenting with VVS and/or orthostatic intolerance (OI). We believe that measuring vitamin D levels and calf circumference may be considered as a tool for assessing muscle mass in patients with OI and VVS syncope.\u003c/p\u003e","manuscriptTitle":"Comparison of the Relationship Between Calf Circumference and Vitamin D with Orthostatic Intolerance and Vasovagal Syncope in Children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-27 20:44:15","doi":"10.21203/rs.3.rs-4561578/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"aa9bf76b-8ded-46cc-b60e-c5f78fe33965","owner":[],"postedDate":"June 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-18T14:53:52+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-27 20:44:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4561578","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4561578","identity":"rs-4561578","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}