Progression of aortic dilation in children with a functionally normal bicuspid aortic valve

Adults with bicuspid aortic valves (BAVs) are at risk for progressive aortic dilation independent of valve function. The evolution of aortic dilation in children with functionally normal BAVs has not been studied. In this study, ascending aortic diameters were assessed in a group of children with functionally normal BAVs (peak gradient < or =16 mm Hg) to determine whether progressive dilation occurs during childhood. A cohort of 101 patients and 97 controls were studied with echocardiography. There were no differences in mean age (9.0 +/- 4.8 vs 8.7 +/- 6.1 years, p = 0.7) or body surface area (1.1 +/- 0.4 vs 1.1 +/- 0.5 m2, p = 0.9). Patients had significantly greater aortic dimensions than controls in all measured regions of the aorta, with the most striking discrepancy in the ascending aorta (2.3 +/- 0.6 vs 1.8 +/- 0.5 cm, p <0.0001). The size discrepancy was present from birth and persisted throughout childhood. Repeated measurements were performed in a subgroup of 28 patients and 25 controls. Patients had significantly greater increases in ascending aortic dimension than controls per year of follow-up (1.2 +/- 0.08 vs 0.6 +/- 0.08 mm/year, p <0.0001). In conclusion, BAV is complicated by progressive aortic dilation beginning in childhood.     

Reduced aortic elasticity and dilatation are associated with aortic regurgitation and left ventricular hypertrophy in nonstenotic bicuspid aortic valve patients.

OBJECTIVES: This study sought to assess elasticity and dimensions of the aorta and their impact on aortic valve competence and left ventricular (LV) function in patients with a nonstenotic bicuspid aortic valve (BAV). BACKGROUND: Intrinsic pathology of the aortic wall is a possible explanation for reduced aortic elasticity and aortic dilatation in patients with BAVs, even in the absence of a stenotic aortic valve. The relationship between aortic wall elasticity, aortic dimensions, aortic valve competence, and LV function in patients with BAVs has not previously been studied with magnetic resonance imaging. METHODS: Magnetic resonance imaging was performed in 20 patients with nonstenotic BAVs (mean +/- SD, age 27 +/- 11 years) and 20 matched control patients. RESULTS: The BAV patients showed reduced aortic elasticity as indicated by increased pulse wave velocity in the aortic arch and descending aorta (5.6 +/- 1.3 m/s vs. 4.5 +/- 1.1 m/s, p = 0.01; and 5.2 +/- 1.8 m/s vs. 4.3 +/- 0.9 m/s, p = 0.03, respectively), and reduced aortic root distensibility (3.1 +/- 1.2 x 10(-3) mm Hg(-1) vs. 5.6 +/- 3.2 x 10(-3) mm Hg(-1), p < 0.01). In addition, BAV patients showed aortic root dilatation as compared with control patients (mean difference 3.6 to 4.2 mm, p < or = 0.04 at all 4 predefined levels). Minor degrees of aortic regurgitation (AR) were present in 11 patients (AR fraction 6 +/- 8% vs. 1 +/- 1%, p < 0.01). The LV ejection fraction was normal (55 +/- 8% vs. 56 +/- 6%, p = 0.61), whereas LV mass was significantly increased in patients (54 +/- 12 g/m2 vs. 46 +/- 12 g/m2, p = 0.04). Dilatation at the level of the aortic annulus (r = 0.45, p = 0.044) and reduced aortic root distensibility (r = 0.37, p = 0.041) correlated with AR fraction. Increased pulse wave velocity in the aortic arch correlated with increased LV mass (r = 0.42, p = 0.041). CONCLUSIONS: Reduced aortic elasticity and aortic root dilatation were frequently present in patients with nonstenotic BAVs. In addition, reduced aortic wall elasticity was associated with severity of AR and LV hypertrophy.     

Ascending aorta elasticity in children with isolated bicuspid aortic valve

Background

Aortic dilation is common in children with bicuspid aortic valve (BAV) but aortic complications are infrequent. The aim of this study was to investigate elastic properties of the ascending aorta (AAo) and its relation to AAo size in children with isolated BAV without significant valve dysfunction.

Methods

24 children with isolated BAV and 24 healthy controls with tricuspid aortic valve (TAV) matched by gender, age and body surface area (BSA) were studied. Aortic strain (AS), aortic distensibility (DIS) and aortic stiffness index (SI) were derived from M-mode echocardiography at the AAo together with cuff blood pressure recordings. BAV children with dilated AAo (z score ≥ 2) and non dilated (z score < 2) were compared.

Results

BAV children had larger aortas than controls at the sinuses of Valsalva, sinotubular junction and AAo (p < 0.05). AS was lower in BAV than in controls (10.15 ± 4.93 vs 16.93 ± 5.17 p = 0.000), DIS was lower in BAV than in controls (8.51 ± 3.90 vs 14.37 ± 4.20 p = 0.000) and SI was higher in BAV than in controls (7.19 ± 4.45 vs 4.05 ± 2.33 p = 0.04). There were no significant differences in AS, DIS and SI between children with dilated and non-dilated AAo. AS, DIS and SI were not related to BSA, age or AAo size.

Conclusions

AAo elasticity assessed by transthoracic echocardiography is impaired in BAV children without significant valve dysfunction compared to TAV children. Impaired elasticity seems to be independent from aortic dilation. Measuring aortic elasticity may help to identify children at greater risk for complications as adults.     

Bicuspid aortic valve: abnormal aortic elastic properties

BACKGROUND AND AIMS OF THE STUDY: Bicuspid aortic valve (BAV) is frequently associated with clinically relevant abnormalities of the aorta, suggesting the existence of a common underlying developmental defect involving the aortic valve and wall of the ascending aorta. The study aim was to evaluate noninvasively the elastic properties of the aortic root in young males with BAV, to discover whether structural abnormalities of the aorta might be manifested by impairment in elasticity. METHODS: Forty-nine young male subjects with isolated BAV were consecutively detected during preenrollment military screening, and studied using transthoracic echocardiography. Data were compared with those obtained in 45 normal subjects, matched for gender and age. RESULTS: Patients and controls were comparable for body size, and systolic and diastolic blood pressures. BAVs were normally functioning in 18 patients (37%), and mildly regurgitant in 31 (63%). Measurements made by two-dimensional echocardiography showed that BAV patients had significantly larger aortic root dimensions at the annulus (2.4+/-0.2 versus 2.2+/-0.2 cm, p <0.001), at the sinus of Valsalva (3.3+/-0.4 versus 2.6+/-0.3 cm, p <0.001), at the sinotubular junction (2.9+/-0.3 versus 2.5+/-0.2 cm, p <0.001), and at the proximal ascending aorta (2.8+/-0.3 versus 2.5+/-0.2 cm, p <0.001). Measurements made using M-mode echocardiography at 3 cm from the annulus, showed the difference between systolic and diastolic diameters of the aortic root to be significantly smaller in patients than in controls (2.1+/-1.2 versus 3.0+/-1.1 mm, respectively, p <0.001). In patients and in controls, both aortic distensibility (2.7+/-1.5 versus 4.8+/-2.2 x 10(-6) cm2 dyne(-1), respectively, p <0.001) and aortic stiffness index (10.2+/-5.3 versus 5.03+/-1.97, respectively, p <0.001) were significantly different. CONCLUSION: Young male subjects with BAV and no or mild aortic regurgitation display large aortic size and abnormal elastic properties of the ascending aorta compared with controls. These findings confirm the notion that, in these patients, aortic root dilatation is a morphological correlate of intrinsic structural aortic abnormality.     

A larger aortic annulus causes aortic regurgitation and a smaller aortic annulus causes aortic stenosis in bicuspid aortic valve

A bicuspid aortic valve (BAV) often causes aortic stenosis (AS) or regurgitation (AR). In 54 patients with a BAV (48 +/- 16 years), transthoracic and transesophageal echo were performed to measure aortic annulus diameter (AAD), to evaluate the severity of aortic valve disease (AVD) and to calculate the area eccentricity index (AEI) of a BAV defined as a ratio of the larger aortic cusp area to a smaller aortic cusp area. By multiple linear regression analysis, the severity of AR correlated significantly with the AAD (r = 0.38) and AEI (r = 0.35) (P < 0.05) and that of AS correlated significantly with the AAD (r =-0.40) and AEI (r = 0.34) (P < 0.05). Thirty-six patients showed anteroposteriorly (A-P) located BAVs and 18 patients showed right-left (R-L) located BAVs. The AAD was larger in A-P type than in R-L type (15 +/- 3 vs 13 +/- 2 mm/BSA, P < 0.05) and there was no difference in the age and AEI between the two groups. AR was more severe in A-P type than in R-L type while AS was more severe in R-L type than in A-P type (P < 0.05). Twenty-nine patients showed raphes. The AEI was larger in raphe (+) type than in raphe (-) type (1.83 +/- 0.53 vs 1.51 +/- 0.47, P < 0.05) and there was no difference in the AAD and severity of AVD between the two groups. In conclusion, a BAV with larger aortic annulus or A-P located will tend to cause AR while a BAV with smaller aortic annulus or R-L located will tend to cause AS.     

Impaired aortic elastic properties in young patients with prehypertension

OBJECTIVES: Although hypertension has been shown to be one of the most important predictors of reduced arterial elasticity, there is not enough data about aortic elastic properties in patients with prehypertension. Accordingly, the current study was designated to evaluate aortic elastic features in young patients with prehypertension. MATERIAL AND METHODS: The study population consisted of 25 newly diagnosed prehypertensive individuals (18 men, mean age=34+/-6 years) and 25 healthy controls (16 men, mean age=33+/-6 years) eligible for the current study. Aortic strain, distensibility index and stiffness index beta were calculated from aortic diameters measured by echocardiography and blood pressures simultaneously measured by sphygmomanometry. RESULTS: Prehypertensive patients were detected to have significantly lower aortic distensibility and strain indexes than the controls: (5.77+/-1.91 vs. 8.63+/-2.67 cm dynx10, respectively, P<0.001; strain index: 13.81+/-4.50 vs. 17.47+/-4.25%, respectively, P=0.005). Aortic stiffness index beta of the prehypertensive group, however, was significantly higher than that of the control group (3.73+/-1.41 vs. 2.97+/-0.82, P=0.02). CONCLUSION: Whatever the mechanism, young patients with prehypertension have impaired aortic elasticity compared with healthy controls. This finding has suggested that the development of overt hypertension may be prevented or delayed by using the agents that have the ability to reduce arterial stiffness by regressing and/or preventing functional and structural changes on the arterial wall.     

Effect of obstructive sleep apnea on aortic elastic parameters: relationship to left ventricular mass and function.

BACKGROUND: Obstructive sleep apnea (OSA) syndrome has a critical association with cardiovascular mortality and morbidity. Aortic elastic parameters are important markers for left ventricular (LV) function and are deteriorated in cardiovascular disease. METHODS AND RESULTS: Aortic elastic parameters and LV functions and mass were investigated in 40 patients with OSA (apnea - hypopnea index (AHI) >or=5) (mean age 51.3 +/-9 years, 32 males) and 24 controls (AHI <5) (mean age 51.9+/-5.2 years, 19 males). All subjects underwent polysomnographic examination and recordings were obtained during sleep. They also underwent a complete echocardiographic examination and systolic and diastolic aortic measurements were noted from M-mode traces of the aortic root. There were no significant differences in the demographic data of the patients with OSA and the controls. Subjects with OSA demonstrated higher values of aortic stiffness (7.1+/-1.88 vs 6.42+/-1.56, p=0.0001), but lower distensibility (9.47+/-1.33 vs 11.8+/-3.36, p=0.0001) than the controls. LV ejection fraction was significantly lower in patients with OSA when compared with the control group (61.3+/-5.2% vs 65.9+/-8.4%, p=0.0001). LV diastolic parameters were also compared and were worse in the subjects with OSA than in the control subjects (mitral E/A: 0.91 +/-0.42 vs 1.35+/-0.66, p=0.001; Em/Am: 0.86+/-0.54 vs 1.23+/-0.59, p=0.021). Respiratory disturbance index had a positive correlation with aortic stiffness (r=0.63, p=0.0001 and negative correlation with distensibility (r=-0.41, p=0.001). CONCLUSION: Aortic elastic parameters are deteriorated in OSA, which has an extremely high association with cardiovascular disease. Increased aortic stiffness might be responsible for the LV systolic and diastolic deterioration in OSA syndrome.     

Increased aortic stiffness in patients with coronary artery ectasia

OBJECTIVE: Alterations in aortic stiffness may reflect the elastic properties of the larger arteries. In many diseases, aortic elastic properties have been investigated to show whether the larger arteries are involved. The elastic properties of aorta in patients with coronary artery ectasia, however, have not been studied yet. We aimed to investigate aortic stiffness parameters in patients with coronary artery ectasia and to compare patients with coronary artery ectasia and coronary artery disease with the control group. METHOD: Thirty-three patients with coronary artery ectasia, 31 patients with coronary artery disease and 30 patients with angiographically normal coronary arteries were included in this study. Aortic diameters were measured on the M-mode tracing obtained at a level 3 cm beyond the aortic valve at parasternal long-axis view. Aortic diameter change, aortic strain, aortic distensibility and stiffness parameters were measured as aortic stiffness parameters. RESULTS: Aortic diameter changes were fewer in the coronary artery ectasia and coronary artery disease group than in the control group (0.4 +/- 0.1 and 0.3 +/- 0.1 vs. 0.8 +/- 0.2; P < 0.001). Aortic distensibility and aortic strain were significantly lower in patients with coronary artery ectasia and coronary artery disease than in the controls (for aortic distensibility P < 0.001 and for aortic strain P < 0.001, < 0.001, respectively). In contrast, a significantly higher aortic stiffness index was observed in patients with coronary artery ectasia and coronary artery disease than in the control group (14.2+/-2.6 and 18.1 +/- 2.9 vs. 5.9 +/- 1.8; P < 0.001, respectively). CONCLUSIONS: The impairment in aortic elastic properties in patients with coronary artery ectasia indicates that this disease is a generalized disease rather than a localized disease of the coronary arteries.     

Progression rate of ascending aortic dilation in patients with normally functioning bicuspid and tricuspid aortic valves

Dilation of the ascending aorta (AA), which is disproportionate to associated valvular lesions, is a relatively well-recognized phenomenon in patients with a bicuspid aortic valve (BAV). The aim of this study was to evaluate the rate of changes in the AA dimensions and the outcome in patients with AA dilation and BAVs compared with patients with AA dilation and tricuspid aortic valves (TAVs). Serial transesophageal echocardiograms (>12 months apart) were performed in 113 consecutive patients (BAV, n=27 and TAV, n=86) with AA diameters of >or=40 and 相似文献   

Effects of angiotensin-converting enzyme polymorphism on aortic elastic parameters in athletes

BACKGROUND: Physiologic adaptations in an athlete's heart include increased left and right ventricular chamber size, left ventricular wall thickness and mass. Angiotensin-converting enzyme (ACE) is a key enzyme in angiotensin II production causing cardiac hypertrophy. The cloning of the ACE gene has made it possible to identify a deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. Therefore, the ACE genes, which have been shown to be polymorphic, could be candidate genes for large-artery stiffness. METHODS: 56 endurance athletes and 46 sedentary subjects were included in this study, and they underwent both complete echocardiographic examination, and analysis of ACE insertion (I) and deletion (D) allele frequencies in peripheral blood. The aortic diameter was recorded by M-mode echocardiography at a level 3 cm above the aortic valve. Aortic systolic diameter was measured at the time of full opening of the aortic valve, and diastolic diameter was measured at the peak of QRS. Aortic strain, stiffness index and distensibility were calculated. RESULTS: Left ventricular mass index and left ventricular ejection fraction were significantly higher in athletes than controls (p < 0.001). The aortic distensibility index and strain were significantly greater in athletes compared with controls (respectively: 5.8 +/- 2.7 vs. 4.7 +/- 1.8 cm(-2) dyn(-1) 10(-6), p = 0.017; 12.3 +/- 2.4 vs. 9.3 +/- 3.1, p < 0.001). The aortic stiffness index was significantly lower in athletes than in controls (4.8 +/- 1.9 vs. 6.1 +/- 2.1, p < 0.001). The aortic distensibility index and strain were statistically different in ACE DD vs. DI groups and DD vs. II groups of athletes. The aortic stiffness index was statistically different in ACE DD vs. II groups of athletes. Aortic parameters were similar according to ACE genotypes in controls. CONCLUSION: The results of this study indicate that aortic distensibility was increased by prolonged training in endurance athletes, particularly in those with the ACE II genotype. This effect represents an extracardiac adaptation to chronic prolonged training in athletes.     

Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. METHODS: 40 patients with OSA showing an apnea-hypopnea index (AHI) > or =5 (mean age 51.3 +/- 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 +/- 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. RESULTS: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 +/- 1.88 vs. 6.42 +/- 1.56, respectively) and IMT (0.85 +/- 0.13 vs. 0.63 +/- 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 +/- 1.33 vs. 11.8 +/- 3.36 cm(2)/dyn/10(6)) and FMD (4.57 +/- 1.3 vs. 6.34 +/- 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. CONCLUSION: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.     

Progressive dilation of the ascending aorta in children with isolated bicuspid aortic valve

Although patients with bicuspid aortic valves (BAVs) are predisposed to ascending aortic (AA) dilation, stenosis, and dissection, the development of aortic disease in children with BAVs is poorly described. The purposes of this study were to determine the rate of change of AA diameter in children with BAVs and to identify risk factors for the development of aortic dilation. The echocardiograms of 276 children aged<19 years (mean 8.5+/-5.3) with isolated BAVs were reviewed. Aortic measurements were normalized to z scores on the basis of body surface area. In a subset of 112 patients with serial examinations, aortic growth rates were calculated and risk factors for more rapid aortic growth determined. At presentation, 33 patients (12%) demonstrated marked AA dilation (z>4), and 70 (25%) were moderately abnormal (z between 2 and 4). The mean+/-SD AA diameter increased more than expected, at a rate of 0.18+/-0.30 z score per year (p<0.0001). In 61 patients with normal AA diameters on initial study, 22 (36%) had abnormal diameters, with z scores>2, at follow-up. Univariate analysis demonstrated right-noncoronary commissural fusion (p<0.02) and aortic valve gradient on initial examination (p<0.02) as significant predictors of AA growth. In multivariate analysis, however, the significance of gradient and valve morphology was diminished (p = 0.06 for both). In conclusion, the progression of AA diameter in patients with normal z scores on initial examination suggests that serial echocardiograms are required to screen for the development of significant aortic dilation.     

The relationship between echocardiographic features of mitral valve and elastic properties of aortic wall and Beighton hypermobility score in patients with mitral valve prolapse

The present study was designed to investigate the incidence of benign joint hypermobility syndrome (BJHMS) in mitral valve prolapse (MVP) and the correlation between the echocardiographic features of the mitral valve and elastic properties of the aortic wall and Beighton hypermobility score (BHS) in patients with MVP and BJHMS. Fourty-six patients with nonrheumatic, uncomplicated, and isolated mitral anterior leaflet prolapse (7 men and 39 women, mean age; 26.1 +/- 5.9) and 25 healthy subjects (3 men and 22 women, mean age, 25.4 +/- 4.3) were studied. Patients were divided into two groups according to their BHS (group I, MVP+BJHMS; group II, MVP-BJHMS). Individuals with accompanying cardiac or systemic disease were excluded. Echocardiographic examination was performed in all subjects. The presence of BJHMS was evaluated according to Beighton's criteria. The incidence of BJHMS in patients with MVP was found to be significantly higher than that of controls (45.6%, (21/46) vs 12% (3/25), P < 0.0001). Group I (MVP + BJHMS) had significantly increased anterior mitral leaflet thickness (AMLT, 3.4 +/- 0.4 vs 3.1 +/- 0.3; P < 0.005), maximal leaflet displacement (MLD, 2.4 +/- 0.4 vs 1.7 +/- 0.4; P < 0.005), and degree of mitral regurgitation (DMR, 17.1 +/- 7.2 vs 11.2 +/- 4.4; P < 0.01) compared to group II. However, the index of aortic stiffness (IAOS) was found to be lower (17.6 +/- 6.9 vs 23.9 +/- 7.6; P < 0.005) and aortic distensibility (AOD) to be higher (0.0035 +/- 0.007 vs 0.0024 +/- 0.005; P < 0.005) in group I. There was a significant correlation between AMLT, MLD and DMR, and BHS (r = 0.57/P = 0.007, r = 0.55/P < 0.009, r = 0.51/P < 0.01, respectively). In addition, AOD correlated positively with BHS (r = 0.53/P < 0.005), but the index of aortic stiffness correlated inversely with BHS (r = -0.49/P < 0.007). The incidence of BJHMS in patients with MVP was more frequent than the normal population and there was a significant correlation between the severity of BJHMS (according to BHS) and echocardiographic features of the mitral leaflets and elastic properties of the aortic wall.     

Augmentation of central arterial pressure in Type 2 diabetes.

AIMS: Aortic systolic blood pressure has been shown to be augmented in Type 1 diabetes, indicative of more rapid pulse wave reflection due to increased arterial stiffness. This abnormality is more pronounced in diabetic males. The aim of this study was to examine the effects of diabetes on augmentation of aortic systolic pressure in subjects with Type 2 diabetes. METHODS: Radial artery pressure waveforms were obtained non-invasively by applanation tonometry. A central aortic waveform can be derived using a transfer function obtained from previous studies during cardiac catheterization. A total of 88 subjects with Type 2 diabetes (51 men and 37 women, aged 55.8 years (interquartile range (IR) 49.7-64.1), duration of diabetes 7.5 years (IR 2.4-12.4), HbA1c 7.6% (IR 6.6-8.7)) and 85 controls subjects (40 men and 45 women, aged 55.3 years (IR 44.2-66.4)) were studied. The central aortic waveform allowed determination of the: (i) aortic augmentation index and (ii) subendocardial viability ratio. RESULTS: Similar to Type 1 diabetic subjects, patients with Type 2 diabetes had a significantly higher aortic augmentation index (136.1 +/- 18.0% vs. 128.3 +/- 19.2%, t = 2.8, P = 0.006) and lower subendocardial viability ratio (137.4 +/- 25.0% vs. 155.1 +/- 25.9%; t = 4.6, P = 0.0001) compared with controls. Multivariate analysis identified diabetes as an important determinant of aortic augmentation index (t = 4.0, P = 0.0001). The higher aortic augmentation index was due mainly to the male cohort (t = 2.6; P = 0.01) and was not apparent for females with diabetes (P = 0.2). CONCLUSIONS: Type 2 diabetes is characterized by higher augmentation of aortic systolic pressure and unfavourable ratio of myocardial perfusion to cardiac workload. These results are consistent with increased arterial stiffness. The age-related progression of arterial stiffness is similar in Type 1 and Type 2 diabetes. Anti-hypertensive agents that reduce wave reflection and augmentation may help to prevent systolic hypertension and cardiac hypertrophy in diabetes.     

Vasculopathy in Turner syndrome: arterial dilatation and intimal thickening without endothelial dysfunction

CONTEXT: Women with Turner syndrome (TS) have an increased cardiovascular mortality rate from both structural and ischemic heart disease, especially aortic dissection. OBJECTIVE: We hypothesized that TS women have a fundamental arterial wall defect that may be due to genetic factors or estrogen deficiency. DESIGN, SETTING, AND PATIENTS: TS women (n = 93) were compared with normal controls (n = 25) and women with 46,XX primary amenorrhea (PA) (n = 11) with a similar history of estrogen deficiency. Clinical parameters, aortic root diameter, extraaortic arterial structure [common carotid (CD), brachial artery diameter, and carotid intima-media thickness (IMT)], arterial stiffness (pulse-wave velocity, augmentation index), and endothelial function (flow-mediated dilatation) were assessed. MAIN OUTCOME MEASURES: These included arterial diameters and vascular physiology parameters. RESULTS: Differences in arterial structure were observed among TS, normal controls, and 46,XX PA women: IMT (0.61 +/- 0.07 vs. 0.55 +/- 0.06 vs. 0.60 +/- 0.05 mm, respectively; P < 0.001), CD (5.71 +/- 0.64 vs. 5.27 +/- 0.34 vs. 5.22 +/- 0.38 mm; P < 0.001), and brachial artery diameter (3.29 +/- 0.44 vs. 3.06 +/- 0.36 vs. 2.97 +/- 0.30 mm; P = 0.006). Aortic root diameter was greater in TS than normal control women. TS status, height, weight, and IMT were independently associated with increased CD after multivariate adjustment (P < 0.05). TS status, age, diastolic blood pressure, and CD remained independently associated with increased IMT after multivariate adjustment (P < 0.05). Pulse-wave velocity and flow-mediated dilatation were similar among the three groups. CONCLUSION: Women with TS have greater IMT and conduit artery diameters than normal controls. Similarly, increased IMT in TS and 46,XX PA women suggests that estrogen deficiency contributes to intimal thickening. Interventional studies are required to determine the extent to which blood pressure and estrogen deficiency may be appropriate therapeutic targets to reduce cardiovascular risk in TS.     

Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study

OBJECTIVES: Hypopituitary adults with growth hormone deficiency (GHD) have an increased cardiovascular mortality, although the mechanisms remain unclear. Endothelial dysfunction, characterized by reduced nitric oxide (NO) bioavailability, is a key early event in atherogenesis and is associated with increased vascular smooth muscle tone and arterial stiffening. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study, we investigated the effects of GH replacement on endothelial function and large-artery stiffness in 32 GHD adults (19 males, 13 females) (age range 19-64 years) over a 6-month period. Thirty-two age- and sex-matched healthy controls were also studied. MEASUREMENTS: Endothelial function was assessed using ultrasonic wall tracking to measure flow-mediated dilatation (FMD) of the brachial artery. Large artery stiffness was assessed by pulse wave analysis of the radial artery pressure waveform, allowing determination of the corresponding central arterial pressure waveform and derivation of the augmentation index. Fasting lipid profiles, glucose and insulin were also measured. RESULTS: At baseline, FMD (mean +/- SD) was impaired in GH-deficient subjects vs. controls (3.4 +/- 2.3 vs. 5.7 +/- 2.0%, P < 0.0001), although endothelium-independent dilatation was similar. The augmentation index was higher in GH-deficient subjects vs. controls (23 +/- 12 vs. 14 +/- 14%, P < 0.01). GH-deficient subjects had higher LDL cholesterol (4.1 +/- 0.8 vs. 3.5 +/- 0.8 mmol/l, P < 0.01) and lower HDL cholesterol (1.1 +/- 0.3 vs. 1.4 +/- 0.4 mmol/l, P < 0.01). In GH-deficient subjects, there were inverse correlations between LDL cholesterol and FMD (r = -0.40, P < 0.05) and between FMD and the augmentation index (r = - 0.58, P < 0.01). Regression analysis identified FMD as an independent predictor of the augmentation index (P < 0.0001). In comparison with baseline, GH replacement resulted in an increase in FMD (5.0 +/- 2.6 vs. 2.8 +/- 1.9%, P < 0.01). There were decreases in central aortic systolic pressure (117 +/- 15 vs. 123 +/- 17 mmHg, P < 0.01), diastolic pressure (82 +/- 10 vs. 86 +/- 8 mmHg, P < 0.01) and the augmentation index (22 +/- 8% vs. 26 +/- 10%, P < 0.05) despite unchanged brachial pressure indices. LDL cholesterol also decreased (3.5 +/- 0.8 vs. 4.2 +/- 0.8 mmol/l, P < 0.01). There were no significant changes in the placebo group. CONCLUSIONS: Adult GHD is associated with endothelial dysfunction and increased large-artery stiffness. An improvement in endothelial function and a reduction in arterial stiffness following GH replacement suggests an important therapeutic role for GH in reducing cardiovascular risk associated with adult GHD.     

Augmentation of central arterial pressure in mild primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular risk, although the mechanisms involved remain unclear. Recent evidence has shown increased pulse pressure to be a powerful predictor of cardiovascular events. As increases in pulse pressure are due largely to arterial stiffening, we measured arterial stiffness in 21 subjects with PHPT (18 women and 3 men; 46-71 yr old) and 21 age- and sex-matched healthy controls using pulse wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and augmentation index, a measure of vessel stiffness. Metabolic parameters were also measured. The serum calcium level among PHPT subjects was (mean +/- SD) 2.74+/-0.14 mmol/L. pulse wave analysis showed that both augmentation and the augmentation index were significantly higher in the PHPT group vs. controls [16+/-5 vs. 10+/-4 mm Hg (P < 0.001) and 36+/-9% vs. 25+/-6% (P < 0.001)] despite comparable brachial systolic pressures between groups (136+/-13 vs. 134+/-18 mm Hg). Patients with PHPT had higher fasting serum insulin levels [median (range), 15.8 (7.4-39.4) vs. 11.6 (5.1-23) mU/L; P < 0.05] and triglyceride (1.6+/-0.6 vs. 1.2+/-0.4 mmol/L; P < 0.05), but lower high density lipoprotein cholesterol (1.4+/-0.4 vs. 1.6+/-0.3 mmol/L; P < 0.05). These data indicate that subjects with mild PHPT (calcium, <3.0 mmol/L) have increased arterial stiffness, as evidenced by higher augmentation of central aortic pressures. Enhanced vessel stiffness may arise from a combination of structural and functional vascular changes due to hypercalcemia and/or metabolic abnormalities. Increased vascular stiffness in subjects with PHPT may account in part for the increased cardiovascular risk in this group.     

Relationship between arterial stiffness and myocardial damage in patients with newly diagnosed essential hypertension

BackgroundArterial stiffness increases in hypertensive individuals. Arterial stiffness is associated with impairment of systolic and diastolic myocardial function in hypertension (HT). However, the relationship between arterial stiffness and serum heart-type fatty acid-binding protein (H-FABP) levels, a sensitive marker of myocardial damage, has not been previously examined in patients with HT. We investigate the relationship between serum H-FABP levels and arterial stiffness in patients with newly diagnosed HT.MethodsWe studied 46 (48.5 +/- 10.6, years) never-treated patients with HT and age-matched control group of 40 (47 +/- 8.6, years) normotensive individuals. H-FABP levels were determined in all subjects. We evaluated arterial stiffness and wave reflections of study population, using applanation tonometry (Sphygmocor). Carotid-femoral pulse wave velocity (PWV) was measured as indices of elastic-type, aortic stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as a marker of wave reflections.ResultsCarotid-femoral PWV (10.5 +/- 2.2 vs. 8.7 +/- 1.6, m/s, P = 0.0001) and AIx@75 (22.7 +/- 9.5 vs. 15 +/- 11, %, P = 0.001) were significantly higher in patients with HT than control group. H-FABP levels were increased in hypertensive patients compared with control group (21.1 +/- 14.8 vs. 12.9 +/- 8.5, ng/ml, P = 0.002). In multiple linear regression analysis, we found that the body mass index (beta = 0.42, P = 0.0001) and carotid-femoral PWV (beta = 0.23, P = 0.03) were significant determinants of H-FABP levels.ConclusionArterial stiffness is associated with serum H-FABP levels, a sensitive marker of myocardial damage, in patients with newly diagnosed HT.American Journal of Hypertension (2008). doi 10.1038/ajh.2008.235American Journal of Hypertension (2008); 21, 9, 989-993. doi 10.1038/ajh.2008.235.     

Increased central arterial stiffness in hypothyroidism

Hypothyroidism is associated with cardiovascular dysfunction. It is increasingly apparent that stiffening of central arteries may lead to increased afterload and cardiac dysfunction. We noninvasively studied the peripheral and central pressure waveforms in 12 untreated hypothyroid patients as well as in 12 age-, sex-, and body mass index-matched controls using the technique of pulse wave analysis from recordings at the radial artery. Indexes of arterial stiffness, augmentation index (AI) and augmentation of central arterial pressure (AG), were derived as well as time of travel of the reflected wave (TR), a direct estimate of aortic pulse wave velocity. At baseline, there were no significant differences between the 2 groups in brachial and aortic blood pressures. Hypothyroid patients had significantly higher AI than controls (mean +/- SEM[SCAP], 32.0 +/- 3.4% vs. 17.0 +/- 2.4%; P < 0.0005) even when corrected for heart rate (AI(C); 28.0 +/- 3.2% vs. 17.0 +/- 2.4%; P < 0.006) and AG (13.0 +/- 2.2 vs. 7.0 +/- 2.1 mm Hg; P < 0.03) together with a lower TR (132.0 +/- 4.1 vs. 142.0 +/- 1.5 msec; P < 0.03). After 6 months of therapy with T(4), all patients were euthyroid. AI(C) had decreased in the patient group (23.0 +/- 3.2% vs. 28.0 +/- 3.2%; P < 0.01) as had AG (9.0 +/- 1.5 vs. 13.0 +/- 2.2 mm Hg; P < 0.008), but TR was significantly higher (142.0 +/- 3.0 vs. 132.0 +/- 4.1 msec; P < 0.008). AI correlated with age in all groups (hypothyroid group: r = 0.937; P < 0.0005; control group: r = 0.804; P < 0.0005), but correlated with TSH level only among controls (r = 0.591; P < 0.05). This study confirms that hypothyroidism is associated with increased cardiovascular risk, as evidenced by increased augmentation of central aortic pressures and central arterial stiffness. Furthermore, these abnormalities are reversed after adequate T(4) replacement.     

Usefulness of bicuspid aortic valve phenotype to predict elastic properties of the ascending aorta

Bicuspid aortic valve (BAV) affects about 0.5% to 2% of the population and predisposes patients to aortic dilation and dissection. We hypothesized that aortic size and elastic properties are related to BAV phenotype. In a retrospective study of 158 consecutive patients with BAV referred for echocardiography, the phenotype was defined as anterior-posterior (A-P) leaflet orientation or right-left (R-L) leaflet orientation. The 29 subjects with R-L BAV were matched 1:1 for age, gender, and grade of aortic valve dysfunction with 29 subjects with A-P BAV. Aortic dimensions were measured at the sinuses of Valsalva, ascending aorta, and aortic arch. Distensibility and stiffness index were calculated using cuff blood pressure. Mean age was 41.5 years (range 21 to 67), and 59% were men. Aortic diameter was larger with A-P BAV than R-L at the sinuses (mean +/- 1 SD 3.48 +/- 0.49 vs 3.06 +/- 0.59, p <0 .01) and smaller at the arch (2.34 +/- 0.40 vs 2.83 +/- 0.45, p <0.001). At the sinuses, A-P BAV had a higher stiffness index (median 12.98, range 2.78 to 42.07 vs 6.41, range 2.75 to 59.72, p <0.01) and lower distensibility. Stiffness index in the ascending aorta and arch (but not at the sinus) increased with age. In conclusion, A-P BAV is associated with a larger stiffer sinus of Valsalva and smaller arch diameter. The potential impact of BAV phenotype and aortic elasticity on clinical outcomes merits further study.