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Vasculopathy in the Young Turner Syndrome Population Sarah A. Lawson, Elaine M. Urbina, Iris Gutmark-Little, Philip R. Khoury, Zhiqian Gao, and Philippe F. Backeljauw Division of Endocrinology (S.A.L., I.G-L., P.F.B.) and Division of Cardiology (E.M.U., P.R.K., Z.G.), Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229

Context: Turner syndrome (TS) carries an increased risk for vascular disease, or vasculopathy. Objective: Vasculopathy can be detected in young TS patients. Design and Patients: Vasculopathy was prospectively assessed by measuring vascular function and structure in TS patients (n ⫽ 49) and lean (L) (n ⫽ 76) and obese (O) controls (n ⫽ 52) through noninvasive techniques. Controls were drawn from previously known adolescents who were agematched and disease-free. Data collected: Pulse wave velocity femoral (PWVf), augmentation index (AIx), carotid intima media thickness (cIMT), and Young’s Elastic Modulus (YEM). Results: Mean age and body mass index (BMI) for TS, L, and O subjects were 11.89 years and 21.2 kg/m2, 17.93 years and 20.9 kg/m2, and 18.35 years 36.5 kg/m2, respectively. Blood pressure means (mmHg) in TS, L, and O subjects were 112/65, 103/59, and 113/67, respectively. A greater AIx and YEM were seen in TS patients after adjusting for age plus BMI: AIx ⫽ 12.3% ⫾ 2 (TS), ⫺2% ⫾ 1.7 (L), 5.8% ⫾ 2.2 (O); YEM ⫽ 544.4 mmHg/mm ⫾ 26.75 (TS), 258.1 mmHg/mm ⫾ 22.7 (L), 343.5 mmHg/mm ⫾ 30.6 (O). After adjustment for age and BMI, a greater PWVf was seen in TS vs L controls (P ⬍ .0001). The cIMT was lowest in the TS group: 0.35 mm ⫾ 0.06 vs 0.43 mm ⫾ 0.06 (L) and 0.45 mm ⫾ 0.06 (O) (P ⬍ .001). Conclusions: Vasculopathy, a marker of cardiovascular morbidity in adult TS, is detected in childhood. The findings remained after adjusting for age, demonstrating stiffer arterial vessels in young TS patients. (J Clin Endocrinol Metab 99: E2039 –E2045, 2014)

T

urner syndrome (TS) is associated with a range of comorbidities involving the cardiovascular system. These affect both pediatric and adult TS patients (1). Pathology includes, but is not limited to, hypertension, valvular disease (bicuspid aortic valve (BAV) is the most common), aortic dilatation, and aortic dissection (2, 3). Vasculopathy, which may be manifested by increased intima media vessel wall thickness (4), has also been reported in TS patients (5). Its presence has been considered as a cause for the increased cardiovascular morbidity and mortality described (3, 6). Whether or not vasculopathy exists in the young TS population, and to what degree, is

unknown. Documenting the existence of vasculopathy in TS youth may identify those at risk for increased morbidity and mortality sooner in the disease process. Our study’s primary goal was, therefore, to identify vasculopathy including increased arterial thickness and stiffness in young TS patients. Prior research in TS children and adults demonstrated the presence of cardiac anomalies in 20 – 40%, hypertension in up to 25%, and aortic dilatation in 15–30% of patients (2, 7). Studies evaluating the presence of vasculopathy in the adult TS population have identified vascular changes as early as the third decade of life (1, 5, 8), and

ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2014 by the Endocrine Society Received January 15, 2014. Accepted June 18, 2014. First Published Online June 24, 2014

Abbreviations: Aix, augmentation index; BAV, bicuspid aortic valve; BP, blood pressure; CCHMC, Cincinnati Children’s Hospital Medical Center; cIMT, carotid intima-media thickness; ECHO, echocardiography; PWVf, pulse wave velocity femoral; YEM, Young’s Elastic Modulus.

doi: 10.1210/jc.2014-1140

J Clin Endocrinol Metab, October 2014, 99(10):E2039 –E2045

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ultimately may significantly reduce life expectancy. However, the exact age of onset of vasculopathy in TS is not well described. In addition, correlation between hypertension, aortic dilatation, and the timing of estrogen replacement has also not been well documented in younger TS patients (5, 9, 10). Current guidelines for evaluating the presence of cardiac disease in TS patients include echocardiography (ECHO) and electrocardiogram (ECG) at diagnosis and blood pressure (BP) assessments at each clinic visit (2). Also accepted is vasculopathy screening via cardiac magnetic resonance imaging starting as early as the first decade of life (11). However, this guideline is not widely followed because of the limitations involved in using cardiac magnetic resonance imaging as a screening tool (equipment availability, need for sedation, high cost). In the future, easily accessible and affordable techniques assessing vasculopathy and cardiovascular risk, in adjunct with current modalities, may improve cardiovascular screening in young TS patients.

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that the control cohorts were not completely age-matched because there were too few controls younger than 12 years of age. Controls were defined as lean (BMI ⱕ 85th percentile) or obese (BMI ⬎ 95th percentile) and had ECHO and vascular data entered in the Preventative Cardiology Division’s database. The study abided by the Helsinki declaration. Institutional review board approval was obtained prior to the study’s start date. Adult consent was obtained on all subjects equal to or greater than 18 years of age. Parental consent and child assent were obtained on all subjects between 10 and 17 years of age. Parental consent alone was obtained on all subjects younger than 10 years of age. Funding was provided by Novo Nordisk Inc, Biopharm Research Grant IIS.

Materials and Methods Auxology BP was measured after 5 min of rest with mercury sphygmomanometer according to pediatric guidelines (12). The right arm was supported and feet were flat on the floor. The bladder of the cuff was centered about 1 in. above the elbow. The radial or brachial artery was palpated while the cuff was inflated. Then the cuff was deflated. The patient was then allowed to rest for 1 min. The pulse site was relocated and a BP was obtained via auscultation.

Patients and Methods Pulse wave velocity femoral (PWVf) Patients and study design Our first objective, and main outcome parameter, was to establish the presence of vasculopathy (arterial stiffness) in young TS girls. Second, we attempted to evaluate for potential associations between vasculopathy and coexisting heart disease, GH treatment, and/or estrogen exposure. To accomplish these objectives we prospectively enrolled 49 TS patients from the Cincinnati Children’s Hospital Medical Center (CCHMC) TS Center between the ages of 9 and 20 years who had TS confirmed by cytogenetic testing (minimum of 30 cells). The only exclusion criterion for the TS group was a chronological age above 20 years old. Thirty TS patients had a karyotype of 45, X (60%) and 19 were mosaic (40%). Mosaicism included 45, X/46, XX (35%), 45, X/46, X, Xr (30%), 45, X/47, XXX (10%), 45, X/46, XY (10%), and some rare other types (15%). Historical patient information was collected from the chart review or extracted from the TS Center database. None of the TS participants included in the study had Diabetes Mellitus or a history of smoking. Data on lipid status was only known for a small portion of TS patients. Heart disease was classified in the TS group as follows: 1. no heart disease, 2. history of BAV, 3. history of coarctation (⫾ repair), or 4. history of multiple cardiac defects. All TS patients were seen at a single outpatient evaluation for completion of the vascular assessment. Auxology measurements were obtained on all TS patients only if the last documented clinic measurement was greater than 6 months from the study date. The lean and obese control female cohorts were drawn from a large group of adolescents and young adults, evaluated in the Division of Preventive Cardiology at CCHMC. They were previously part of a study comparing cardiovascular parameters among adolescents who were lean, obese, or obese with type 2 diabetes mellitus. The lean and obese controls in our study were age-matched and free of disease. It should be noted, however,

Pulse wave velocity was measured using the SphygmoCor CPV System (AtCor Medical) (13). For this study a tape measure was used and the average of two separate measures of the carotid to sternal notch and sternal notch to femoral artery distance was calculated. Arterial waveforms gated to the R-wave on the ECG tracing were recorded from the carotid to femoral artery. PWVf is the difference between the carotid-to-distal path length divided by the difference in R-wave-to-waveform foot times. Bland-Altman analyses for reproducibility of PWVf yielded a repeatability coefficient of 2.34 m/s (for mean value of 8.15 ⫾ 3.01 m/s) with between-observer values of 2.50 m/s (14).

Augmentation index (AIx) A SphygmoCor CPV System (AtCor Medical) was used to measure central aortic pressure and AIx. The AIx was correlated to a heart rate of 75 bpm. Radial artery waveforms were recorded with a high-fidelity micromanometer and calibrated with noninvasive MAP and DBP (15–17). Our own validation experiments with a pressure tip catheter in the ascending aorta demonstrated that the transfer function was valid in children (18). AIx is the pressure difference between the primary (main outgoing wave) and the reflected wave of the central arterial waveform, expressed as a percentage of the central pulse pressure (19, 20). The whole procedure was repeated three times per subject and the average value was used for the analysis. Reproducibility data demonstrates an interobserver difference for AIx of 0.23 ⫾ 0.66% and intra-observer difference of 0.49 ⫾ 0.93% (16) as compared to an average AIx in healthy children of greater than 3% (19).

Carotid intima medial thickness (cIMT) and stiffness The carotid arteries were evaluated with high-resolution B-mode ultrasonography using a GE Vivid 7 ultrasound imaging

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doi: 10.1210/jc.2014-1140

Table 1.

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Baseline Mean ⫾ SD Demographic and Hemodynamic Variables

Age (y) Height (m) Weight (kg) BMI (kg/m2) BMIz (kg/m2) SBP (mmHg) DBP (mmHg) SBPz (mmHg) DBPz (mmHg)

Lean Controls n ⴝ 76

Obese Controls n ⴝ 52

Turner Syndrome n ⴝ 49

TS vs L

TS vs O

L vs O

17.93 ⫾ 3.51 1.63 ⫾ 0.08 56.34 ⫾ 10 20.94 ⫾ 2.46 ⫺0.03 ⫾ 0.63 103 ⫾ 7.34 59 ⫾ 11 ⫺0.7 ⫾ 0.67 ⫺0.63 ⫾ 0.95

18.35 ⫾ 3.43 1.63 ⫾ 0.08 97.61 ⫾ 17.13 36.48 ⫾ 5.86 2.05 ⫾ 0.27 113 ⫾ 11.6 67 ⫾ 11.7 0.2 ⫾ 1.06 0.1 ⫾ 1.06

11.89 ⫾ 3.61 1.34 ⫾ 0.16 39.7 ⫾ 17.2 21.16 ⫾ 5.16 0.69 ⫾ 0.97 112 ⫾ 17.8 65 ⫾ 10.6 1.04 ⫾ 1.59 0.36 ⫾ 0.92

P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⫽ .7931 P ⬍ .0001 P ⫽ .0002 P ⫽ .0032 P ⬍ .0001 P ⬍ .0001

P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⫽ .659 P ⫽ .386 P ⬍ .0001 P ⬍ .0001

P ⫽ .51 P ⫽ .99 P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⫽ .009 P ⫽ .007

Abbreviations: L, Lean; O, obese. Overall significance level among the group means was P ⱕ .0002 for all variables.

system with a high resolution linear array, 5.0 –11.0 MHz vascular ultrasound transducer. Subjects were examined in a supine position, and each carotid wall and segments was examined independently from continuous angles to identify the thickest intima-media site. The far wall was measured with a continuous trace technique. Each scan of the common carotid artery begins just above the clavicle, with the transducer being moved cephalad through the bifurcation and along the internal carotid artery. Three segments were identified on the right and left carotid arteries, the distal common carotid proximal to the bifurcation, the bifurcation itself, and the proximal internal carotid artery. At each of these three segments for the far wall of the left and right carotid arteries, the sonographer identified the interface corresponding to the far wall IMT. M-mode measurements of the common carotid were also performed (21). The maximum IMT of the common carotid artery and of the internal carotid artery were defined as the mean of multiple measures of the maximum IMT of the far wall on both the left and right sides (22, 23). The maximal and minimal lumen diameters were also determined for calculations of carotid stiffness (21).

Young’s Elastic Modulus (YEM) Young’s Elastic Modulus was calculated for each patient to obtain an additional measure of vessel stiffness. The following formula was used in this calculation: ([Systolic BP-Diastolic BP]/ [Lumen Diameter in Systole-Lumen Diameter in Diastole] ⫻ (lumen diameter mean/wall thickness) (24). This equation observes the effects seen when the tensile stress is divided by the tensile strain in the initial, or linear, segment of the stress and strain curve. All values obtained were normalized for vessel.

Statistical analysis Power calculations were performed both for cIMT and/or PWV as the primary outcome. Based on the minimum expected sample size of 40 patients and 40 controls, and cIMT as the outcome, the study would have a 99% power to detect a reported clinically meaningful difference of 0.1 mm between cases and controls. Assuming alpha is 0.05, 80% power, 40 cases and 40 controls, and SD of cIMT equal to 0.07, this study would be powered to detect a difference between groups of 0.026 mm. The power was also calculated based on the PWV: assuming an alpha equal to 0.05, equal numbers of cases and controls, and a SD of PWV equal to 0.07, plus a minimum detectable clinically significantly difference of 0.40 m/s, this study would have 80% power to detect difference with 49 cases and 49 controls.

Analyses were done using SAS Version 9.1.3. (SAS Institute). Data were double entered. All variables used in the analyses were examined for extreme values. Any outliers seen were adjudicated for correctness/feasibility before inclusion in the data set. This meant we only excluded tracings with a visible artifact (outlier measurements), and no individual patients were excluded. Variance stabilizing transformations were performed as necessary. Differences between group means for TS patients and controls were assessed using analysis of variance, or analysis of covariance, when it was necessary to adjust for differences in age, height, weight, and BMI. Associations between risk factors within the TS group were evaluated using Spearman rank correlations. Tests for differences in proportions within the TS subgroup were performed using ␹2, or Fisher’s exact tests and were based on clinical presence of each variable.

Results Demographics Table 1 shows the mean ⫾ SD scores for demographic and hemodynamic variables. Lean and obese controls were significantly older than TS patients (TS: 11.89 y, lean: 17.93 y, obese:18.35 y). The mean height was greatest in both lean and obese controls (TS: 134 cm ⫾ 0.16 vs 163 cm ⫾ 0.08 for lean and obese controls). The mean BMI was greatest in obese controls (TS: 21.2 kg/m2, 80th percentile; lean: 20.9 kg/m2, 40th percentile; obese 36.5 kg/m2, ⬎95th percentile). Baseline BP was below the 95th percentile for all groups, but the BP SD scores were higher in the TS group. Pulse wave velocity femoral Table 2 and Figure 1, which report the raw data, show the TS group having the lowest unadjusted PWVf. This was maintained after adjusting for the BP SD score. However, when PWVf was adjusted for age and BMI SD score, the TS group demonstrated a greater PWVf value when compared to lean controls (Figure 2). Adjustments for height as an independent variable were not done for PWVf

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Table 2.

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Mean SD Raw Values of Vasculopathy

cIMT (mm) PWVf (m/s) Aix (%) YEM (mmHg/mm)

Lean Controls n ⴝ 76

Obese Controls n ⴝ 52

Turner Syndrome n ⴝ 49

TS vs L

TS vs O

L vs O

0.43 ⫾ 0.05 5.08 ⫾ 0.57 ⫺1.27 ⫾ 10.93 254.74 ⫾ 108.9

0.45 ⫾ 0.06 6.17 ⫾ 1.02 3.06 ⫾ 9.88 370.34 ⫾ 147.6

0.35 ⫾ 0.06 4.93 ⫾ 0.54 14.28 ⫾ 12.1 517.76 ⫾ 198.5

P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⬍ .0001

P ⬍ .0001 P ⬍ .0001 P ⬍ .0001 P ⬍ .0001

P ⫽ .34 P ⬍ .0001 P ⫽ .02 P ⫽ .06

Abbreviations: L, Lean; O, obese. Overall significance level among the group means was P ⬍ .0001 for all variables.

because the distance used for the calculation was collinear with the patient’s height. Augmentation index and Young’s Elastic Modulus The AIx and YEM showed significantly higher values in the TS group when compared to both lean and obese controls (Table 2 and Figure 1). This difference remained when adjusted for age and BMI SD score (Figure 2) and systolic BP SD score (AIx: TS: 0.33%; lean: 0.15%; obese: 0.18%; YEM: TS: 0.6 mmHg/mm; lean: ⫺0.03 mmHg/

mm; obese: 0.26 mmHg/mm). Additionally, when the AIx was adjusted for height as an independent variable, the TS group maintained the highest value (TS: 58.48%, lean: 51.24%; obese: 55.52%). Carotid intima-media thickness (cIMT) The mean cIMT was significantly different between the TS and the lean and obese control groups (Table 2). This finding remained after adjusting for age and BMI SD score (TS: 0.39 mm, lean: 0.45 mm; obese: 0.47 mm) (P ⬍ .001).

Figure 1. Data represented as mean ⫹ standard deviation. Comparison of unadjusted femoral pulse wave velocity (A), augmentation index (B), and Young’s Elastic Modulus (C) in Turner Syndrome (TS) patients, lean (L) controls, and obese (O) controls.

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trogen-naïve (71%) and 14 patients had ⱖ6 months of estrogen exposure (29%). The finding of a higher AIx in those with prior estrogen exposure (15.8%), vs those without estrogen exposure (10.8%) was not significant (P ⫽ .3).

Discussion Turner syndrome patients are at an increased risk for cardiovascular morbidity, and even mortality due to aortic dissection (2). However, early detection of those at risk for developing aortic dissection is not always Figure 2. Data represented as mean ⫹ standard error. Comparison of femoral pulse wave possible (25). Current noninvasive velocity (A), augmentation index (B), and Young’s Elastic Modulus (C) in TS patients (TS), lean measures of vasculopathy employed controls (L), and obese controls (O) adjusted for age ⫹ BMIz score. Overall significance level among three groups P value ⬍ .001. in the pediatric clinical setting are limited to anthropometric/hemodyAssociations between vasculopathy and Turner namic assessments. This study addressed the potential Syndrome phenotype value of using additional noninvasive imaging as a meaAssociations between physical examination features sure of vasculopathy in combination with the current stancommon to the TS population (neck webbing, lymphedema, dard of care used to assess vascular health in TS patients and cystic hygroma) and vasculopathy were evaluated but (ECHO at diagnosis, BP measurements, and cardiac lacked significance (P ⫽ .2). MRI). Specifically, the noninvasive measurements used to All TS patients had echocardiography studies done describe functional vessel health included: 1. PWV to demprior to being entered in the study, as part of their routine onstrate vessel stiffness by measuring the speed of blood clinical evaluation. The following distribution of heart passing along a specified distance in the vascular bed, 2. anomalies was found in the TS group: BAV in 30%, coAIx to document stiffness through the summation of the arctation in 14%, atrial septal defect (ASD) in 6%, proforward moving pressure wave and the reflected wave (dilonged QT segment in 2% (⬎450 ms being prolonged), rectly assessing the mean arterial pressure), and 3. YEM to other (rare) cardiac defects in 6%, and no heart disease in demonstrate circumferential vessel stiffness (4, 26). 42%. Of note, 87% of those with a history of coarctation Our findings are consistent with data from adult studies had received repair and all but three had an acceptable showing a higher prevalence of vasculopathy in TS papostcoarctation repair peak gradient of ⬍12 mm Hg. tients compared to healthy controls (1, 5, 27). Such studies These three individuals were excluded from the analysis as they could have demonstrated false positive findings sug- confirmed the presence of structural vascular changes (ie, gestive of vasculopathy. An association between the pres- increased cIMT) occurring earlier in TS women when ence of a heart anomaly and the presence of vasculopathy compared to women without TS. In our study, we were only able to find minimal structural differences (cIMT), was also not found. The effect of GH therapy on vasculopathy was also as- but we found significant functional differences (PWVf, sessed at the time of the study and took into account the AIx, YEM). This was observed via a higher PWVf in young duration of GH treatment. Thirty-nine TS subjects were ac- TS patients when compared to lean controls and via a tively receiving GH, 11 had been on GH for ⬍2 years, and 28 higher AIx and YEM in young TS patients when compared had been on GH for ⬎2 years. A significant difference was to both lean and obese controls, even after adjusting for not seen when the duration of GH treatment was assessed as age and adiposity. This is to be interpreted as PWVf, AIx, an independent determinant of vasculopathy in the TS pa- and YEM being representative of functional changes, tients (YEM 506 ⫽ mmHg/mm in those on GH for ⬍2 years which may precede the structural changes of arterial thickness (cIMT). Because our patients were 10 –30 years and 472 mmHg/mm in those on GH ⬎2 years, P ⬎ .2). The association of estrogen and vasculopathy was eval- younger than adult TS patients previously studied (1, 8, uated in all TS patients. Thirty-five TS patients were es- 27, 28), and because they had not been subjected to pro-

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longed environmental exposures commonly associated with atherosclerosis, our data may very well indicate that these functional changes (ie, increased vascular stiffness) could represent an important early marker of vasculopathy entirely inherent to the TS phenotype. These functional changes may be occurring before any structural damage is seen with increasing chronological age. Our assessments of functional vascular integrity specifically identified an increase in vessel stiffness in TS patients as young as 9 years of age when compared to healthy lean and obese controls. To date, no study has been done to validate the use of these noninvasive methods for identifying vasculopathy in the TS pediatric population. In contrast, these modalities are widely used in adult populations and have also been studied in other pediatric populations with known cardiac risk factors (such as type 1 Diabetes Mellitus) (4). The demographic data in our study revealed the highest BMI in the obese cohort, followed by the TS group. Research has shown a higher prevalence of obesity and short stature in TS patients when compared to the general population. This results in a higher BMI, which can ultimately progress to the metabolic syndrome, including the development of coronary heart disease) (29). Adjusting for age plus BMI in our study did not change the observations of increased vessel stiffness in the TS group. This suggests that, although obesity related comorbidities play a role in the progression of vascular damage, inherent early vessel disease likely places the TS population at an additional disadvantage before environmental factors play their part. One could speculate that specific TS phenotype-related vascular disease, manifested through childhood-onset increased vessel stiffness, and followed by premature structural vessel disease, could be related to the increased risk of aortic/vascular dilatation (and potentially dissection) observed in TS patients. This may also explain why TS women are at an increased risk for aortopathy/vasculopathy even if there are no additional risk factors (eg, history of BAV, coarctation, or hypertension) present. There are a number of limitations to this study. First, we acknowledge the fact that there are not enough normative data yet to use vessel stiffness screening as a clinical tool. Our aim was, in part, to explore the use of this screening tool in young TS patients, as the groundwork for future studies. Second, upon initiation of our study, we decided to use a tape measure instead of the gauge method for measuring the distance between the sternal notch and femoral artery. We acknowledge that gauge measurements are more precise, although there is still some controversy on the best measurement method. In addition, because the control cohort measurements were done prior to the newer recommendations of using a gauge, and because

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this was a case-control study, we elected to have all subjects measured by the same technique so that no bias was introduced. Third, we had insufficient power to make additional comparisons within the TS group itself. We had proposed to possibly correlate the presence of vasculopathy with certain phenotypic characteristics commonly seen in the TS population. This assumption was based on previous studies, which have documented clinical correlations in the TS population between aortic disease and the presence of certain cardiac defects, such as BAV and coarctation (25). We also looked for an association between vasculopathy with karyotype (data were not shown), with other clinical characteristics (neck webbing and lymphedema), with the occurrence of prior heart disease, as well as prior estrogen and GH exposure. Our TS sample size was too small to detect such associations, as the study was not powered for this. Additionally, we were not able to directly match pubertal staging for the TS group and controls; however, adjusting for age took this into account given the timing of pubertal initiation in TS usually closely correlates with the average time of endogenous puberty. Finally, there were three TS patients who had undergone coarctation repair and had a postsurgical gradient of ⬎12 mmHg. There is evidence that mild residual aortic narrowing may be associated with vasculopathy, specifically increased cIMT (30). This could have skewed our results if it appeared that inherent vasculopathy was present when it was merely a component of postsurgical changes. Therefore, these patients had to be excluded from the analysis. Our study had as a primary objective to investigate the presence of vasculopathy in young TS patients. With the knowledge that multiple studies have shown a correlation between arterial stiffness and hypertension, and that adult TS women with hypertension have an increased risk for aortic dilation and dissection at a younger age than in the general population, this observation of early-onset vascular disease may turn out to be an additional risk factor that further increases TS patients’ cardiovascular morbidity/ mortality. Additionally, we have shown the potential for assessing early vasculopathy in young TS patients by noninvasively measuring vascular stiffness. Further studies are warranted to look at the natural progression of these vasculopathy findings, and to identify additional potential associations with specific TS genotypes and phenotypes.

Conclusion Results from our study demonstrate two important findings. First, vasculopathy in the TS population is present as early as 9 years of age. Second, TS is an independent

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marker for vasculopathy. Although clinical characteristics common to the TS population could not be correlated with the presence of vasculopathy, we found that the BMI and age did not significantly alter our findings. Assessing vasculopathy by measuring vascular stiffness could be used as an adjunct to current standards of care and, with additional studies still necessary, may ultimately improve identification of those at increased risk for early-onset cardiovascular morbidity or mortality.

Acknowledgments Address all correspondence and requests for reprints to: Sarah Lawson, MD, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3026. E-mail: [email protected]. This work was supported by Novo Nordisk Inc., Biopharm Research Grant IIS. Disclosure Summary: The authors have nothing to disclose.

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Vasculopathy in the young Turner syndrome population.

Turner syndrome (TS) carries an increased risk for vascular disease, or vasculopathy...
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