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Anatomical and functional evaluation of the cardiovascular system in Marfan syndrome

Nollen, G.J.

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Citation for published version (APA):Nollen, G. J. (2004). Anatomical and functional evaluation of the cardiovascular system in Marfan syndrome.

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Download date: 12 Jul 2019

CHAPTER R

Aorticc pressure-area relation in Marfan patientss with and without p-blocking agents:: a new noninvasive approach

GijsJ.. Nollen \ Berend E. Westerhof2, Maarten Groenink \ Anne-Mirjamm Osnabrugge \ Ernst E. van der Wall 3,

Barbaraa J.M. Mulder1

Fromm the Departments of Cardiology1, TNO Biomedical Instrumentation2 of the Academiee Medical Center, Amsterdam, the Department of Cardiology3 Leiden

Universityy Medical Center, The Netherlands

Heartt 2004;90:314-318

Abstract t Objective: : Too investigate the heterogeneous response to & blockade in patients with Marfan syndrome

byy non-invasive assessment of the aortic pressure-area curve.

Designn and patients: 255 patients with the Marfan syndrome who used 6 blocking agents (29 10 years; 20 men,

fivee women), seven without & blockade (34 14 years; five men, two women), and 10

controlss (29 5 years; seven men, three women) underwent magnetic resonance imaging

andd non-invasive continuous blood pressure measurement. Pressure-area curves were

constructedd at the level of the descending thoracic aorta. A transition point was defined as

thee pressure at which the pressure-area relation deviated from its elastic (linear) to the

collagenn (exponential) course.

Setting: : Tertiaryy referral centre for adult congenital heart disease.

688 Results: inn six patients (five with and one without 6 blockade), a transition point in the pressure-

areaa curve was observed, indicating that the load bearing component was not only elastin

butt also collagen. In thetemaining 26 Marfan patients and in the control subjects a linear

pressure-areaa relation was observed.

Conclusions: : Thiss new non-invasive method to derive aortic pressure-area curves showed that most

patientss with Marfan syndrome have a similar pressure-area curve to controls with similar

bloodd pressures. Five patients on 6 blockade showed a transition point in the pressure-

areaa curve which could play a crucial role in the heterogeneous response to & blocker

treatmentt in Marfan patients. Patients with a transition at low blood pressures may not

benefitt from S blocking agents.

Introduction n Marfann syndrome is a heritable disorder of connective tissue resulting in a highly variable

degreee of premature aortic medial degeneration with a high risk of subsequent dissection

orr rupture of the aorta1-3. Mortality from aortic dissection and rupture has been related to

aorticc aneurysm size and expansion rate45. There is evidence that ft blocking agents

reducee the rate of dilatation and the occurrence of dissection in patients with Marfan

syndrome;; however, some patients respond better than others6^.

AA recent study showed that ft blockade increased aortic distensibility and reduced flow

wavee velocity only in Marfan patients and not in control subjects9. A heterogeneous

responsee in aortic elasticity after treatment with ft blockade in Marfan patients has been

reportedd in two other studies1011. The exact mechanism of this heterogeneity remains

undefined.. Investigation of the pressure-area relation of the aorta could provide insight

intoo the mechanism behind this heterogeneous response. When, in addition to elastic

fibres,, collagen fibres are recruited, the pressure-area curve shows a transition from elastic

(linear)) to a stiff (exponential) course12-13. This transition point is a denominator of aortic

elasticc behaviour in the normal blood pressure range, and is of additional importance in

relationn to the forces the aorta can withstand before rupturing1213.

Magneticc resonance imaging (MRI) combined with continuous non-invasive blood pressure

measurement,, such as by the Finapres method14, allows a non-invasive assessment of

aorticc pressure-area curves. In this study we compared the aortic pressure-area curves of

normall subjects with those of patients with Marfan syndrome, with and without ft blocker

treatment.. Ouraims were first, to investigate whether this non-invasive method is suitable

forr assessing the aortic pressure-area relation, and second, to gain insight in the

heterogeneouss response toft blockade in patients with Marfan syndrome.

Methods s Studyy population

Wee studied 34 consecutive patients with Marfan syndrome, inthe age range 19 to 54 years.

Thee diagnosis of Marfan syndrome had been established according to the Ghent criteria15.

Alll subjects underwent MRI immediately followed by finger arterial blood pressure recordings

inn the supine position with the Finometer. Two patients were excluded because of poor

MRII quality. Of the 32 remaining patients, 22 (aged 33 11 years; 16 men, six women) had

previouslyy undergone aortic root replacement. A group of 10 age and sex matched healthy

subjectss (aged 29 5 years; seven men, three women) served as a reference population.

Thee characteristics of the study group are shown in Table 1.

Tablee 1 Clinical characteristics of all 42 subjects.

Agee (yr) Genderr (M/F) Beta-blockerr use Bodyy surface area (m2) Meann blood pressure (mmHg)

333 1 25/7 7

255 (78%) 7 7

866 7

299 5 7/3 3 0 0

1.966 8 877 8

NS S NS S --

0.037 7 NS S

Valuess are mean SD or n (%)

Thee study was approved by the local ethics committee, and individual oral and written

informedd consent was obtained in each patient.

Pressuree recording Fingerr arterial blood pressure was recorded with a Finometer, the most recent device in

thee series of finger arterial blood pressure monitors such as Finapres and Portapres

developedd by TNO Biomedical Instrumentation (Finapres Medical Systems, Arnhem,

Netherlands).. The Finometer displays the beat to beat reconstruction of brachial pressure

andd uses an upper arm cuff for the calibrationof this signal16,17. Signals are digitised using

aa sampling rate of 200 Hz and internally stored. The reconstructed brachial pressure

700 recordings were filtered off-line to derive near-aortic pressures using a generalised filter18-

20.. Pressure drop because of frictional losses is usually negligible in the pressure transfer

overr the brachial artery and therefore mean aortic pressure is equal to mean brachial

pressure.. Pulse shapes, however, are substantially different and this is largely accounted

forr by filtering. From the reconstructed aortic pressure a beat was selected taking care to

matchh the beat to the heart rate and blood pressure values measured during MRI with a

Dinamapp oscillometry blood pressure monitor.

MRII measurements Imagingg was done on a Siemens Magnetom Vision 1.5 Tesla magnetic resonance system

(Siemenss Medical Systems, Erlangen, Germany). Image acquisition was triggered on the

ECG.. The entire aorta was imaged in the transverse and oblique sagittal planes using a

standardd spin echo pulse sequence. Next, a high resolution gradient echo pulse sequence

withh a velocity encoding gradient (cross sectional fast low angle shot (FLASH): time of

repetitionn (TR) 24 ms, time of echo (TE) 5 ms, flip angle , matrix size 256x256) was

appliedd perpendicular to the aorta. This resulted in multiphase image pairs of modulus

andd velocity encoded images with a temporal resolution of 24 ms through the cardiac

cyclee and a spatial resolution of approximately 1 pixel/mm.

Duringg the flow measurement, the blood pressure and the heart rate were measured

usingg a Dinamap oscillometry blood pressure monitor. A workstation (Sparc Ultra; Sun

Microsystems;; Mountain View, California, USA) and the FLOW image analysis software

(Medis,, Leiden, Netherlands) were used for image analysis. Aortic contours were drawn

manuallyy on the modulus images of all cardiac phases, and aortic contours were calculated

Pressure-areaa curve construction

Forr each subject, reconstructed aortic blood pressure and area waveforms

weree assessed at the descending thoracic aorta atthe level of the pulmonary

bifurcationn (Figure 1). This level of the pulmonary bifurcation was chosen for

thee following reasons. First, the filter applied on Finometer recordings produces

descendingthoracicc aortic pressures; second, by choosing this level Marfan

patientss with an aortic root replacement could also be included.

Figuree 1 Aorticc site at which the pressure-area curve was constructed. The arterial pressure waveformm is usually almost identical to the aortic area waveforms.2' The area waveformss assessed by magnetic resonance imaging were then matched in time withh the reconstructed aortic pressure waveform.

Calculations s

Transitionn point (TP, mm Hg) was defined as the pressure at which the pressure-area

relationn deviated from its initial linear behaviour (Figure 2A). In this report, E is used for

elastancee and not for the Young's modulus of the wall material.

Elastancee of elastin (Ee, mm Hg/mm2) was calculated as the slope of the first (linear) part

off the pressure-area curve.

Elastancee of collagen (Ec, mm Hg/mm2) was calculated as the slope of the exponential

partt of the pressure-area curve after the transition point.

Distensibilityy (D, mm Hg1) was calculated by means of the equation:

AA A

DD = Amin x AP

inn which A = area change (mm2), Amin = minimum area (mm2), and P = pressure change

(mmm Hg).

120 0

100 0

80 0

60 0

collagen n

3000 350 400 450 500 550

Areaa (mm2)

Figuree 2 Pressure-areaa curves (solid lines) of (A)) six Marfan patients wi th a transitionn point and (B) 26 wi thout a transitionn point. Dotted l ine: elastancee of elastin. Striped line: elastancee of collagen. E, elastance; TP,, transition point.

600 0

72 2

i i E E

140 0

120 0

100 0

80 0

60 0

-- /

"" / /

-- r/ --

i i

300 0

B B

900 0

Statistics s Dataa are given as mean SD. Differences between the groups were assessed by the

unpairedd Student t test. Logistic regression analysis was done to assess independent

predictorss of the occurrence a transition point. Statistical analysis was undertaken using

thee SPSS statistical package (SPSS Inc, Chicago, Illinois, USA). The level of significance

wass set at p < 0.05.

Tablee 2 Aort ic diameters and aortic elasticity in Marfan patients w i th and wi thout p-blocking agents.

p-value e Marfann patients (n=7)) p blockade + (n=25)

Transitionn point Diameterr descending thoracic aorta (mm) Distensibilityy (10'3 mrnHg"1) Meann blood pressure (mmHg)

11 (14%) 244 2

3.88 9 900 6

55 (20%) 244 3

3.22 5 866 8

NS S NS S NS S NS S

Valuess are mean SD or n (%)

Results s Pressuree recording Reconstructedd brachial systolic pressures were close to the Dinamap oscillometry systolic

pressures,, 0 mm Hg, respectively (NS). Reconstructed brachial

diastolicc pressures differed significantly from the Dinamap oscillometricdiastolic pressures

(733 8 and 61 9 mm Hg; p < 0.01). Reconstructed aortic heart rate was similar to the

heartt rate during MRI, at 63 11 v64 11 beats/min (NS).

Pressure-areaa curves and transition point Pressure-areaa curves were successfully recorded in all 42 subjects. In the group of 10

controll subjects no transition point in the pressure-area curves was observed. However,

inn six of the 32 patients with the Marfan syndrome (19%), atransition point in the pressure-

areaa curve was demonstrated (Figure 2). We found no significant difference in the

occurrencee of a transition point in the pressure-area curve between Marfan patients with

ftft blocker treatment and those without (Table 2). There was no difference in the slope of

thee linear part of the pressure-area curve (Ee) between control subjects, patients without a

transitionn point, and patients with a transition point (Table 3). There was a trend towards

decreasedd distensibility in patients with a transition point in the pressure-area curve

comparedd with those without (Table 3).

Tablee 3 Aortic diameters and aortic elasticity in control subjects and Marfan patients with and without aa transition point. E = elastance, TP = transition point.

EE elastin (mmHg/mm2) 0.46 4 0.49 1 0.36 0 NS Diameterr descending thoracic aorta (mm) 20 3 24 2 24 2 NS Distensibilityy dO^mmHg-1) 4.6 9 3.6 5 2.6 7 NS Meann blood pressure (mmHg) 86 7 87 8 86 5 NS

Valuess are mean SD or n (%)

Aorticc dimensions and distensibility Distensibilityy was decreased in all Marfan patients compared with the control subjects, at

3.33 1.4 v4.6 0.9 10~3 mm Hg"1, respectively (p < 0.02). Descending aortic diameters

weree increased in the Marfan patients, at 24 2 mm v20 3 mm in the controls (p < 0.01).

Thee difference in aortic dimensions or distensibility between Marfan patients with and

withoutt B blocker treatment was not significant (Table 2).

Discussion n Inn this study we describe a new non-invasive method to evaluate aortic pressure-area

relationss in individuals with Marfan syndrome, with and without S blocker treatment,

andd in normal subjects. In six Marfan patients (five with and one without G blockade) a

transitionn point in the pressure-area curve was observed, indicating that the load bearing

componentt contained collagen as well as elastin. In the resting blood pressure range, we

foundd no significant differences between Marfan patients with and without ft blocker

treatmentt in aortic distensibility, the slope of the linear part of the pressure-area curve,

bloodd pressure, or aortic dimensions.

Pressuree recording

Aorticc blood pressures can only be recorded invasively, and reconstruction techniques

aree helpful tools to estimate more central pressures from non-invasive recordings. As it is

nott yet possible to use the Finometer front end in the MRI scanner, pressure recording

wass done immediately after imaging. Both measurements were assessed under similar

circumstances,, confirmed by the similarity of heart rate and systolic blood pressure in the

twoo measurements. There was a significant difference between Finometer brachial diastolic

pressuress and Dinamaposcillometricdiastolic pressures. It is well known from published

reportss that Dinamap oscillometric readings are usually below intra-arterial brachial

pressure,, especially diastolic pressure2223.

Pressure-areaa curves and transition point

Severall studies have reported aortic pressure-area curves with invasive local intravascular

measurements24-26,, while others used brachial pressure measured by a sphygmomanometer

ass a surrogate for aortic pressure2728. MRI combined with non-invasive continuous

measuredd blood pressure, such as by the Finapres method, allows non-invasive assessment

off aortic pressure-area curves14. Because the relation between pressure and area is not

linear,, the pressure-area curve gives additional information on the load bearing component.

Overr a century ago Roy recognised that the more an artery is stretched the harder it

becomess to stretch it further29. This phenomenon occurs because at lower pressures elastin

iss the major load bearing component. Collagen fibres, which are far stronger but more

difficultt to stretch, are recruited progressively as the load increases. In the pressure-area

curvee this process can be seen as a transition from the elastic (linear) course to a stiff

(exponential)) course. The blood pressure at which this transition occurs is defined as the

transitionn point. Bader studied the pressure-area relation in elderly people and showed

thatt with increasing age, the great arteries became more dilated and the elastin determined

(linear)) part of the pressure-area relation shifted to lower pressures13. As changes in the

aorticc tunica media in the Marfan syndrome do not differ essentially from degenerative

alterations,, it seems reasonable to assume a similar causative mechanism30-31. In subjects

withoutt a transition point in the resting blood pressure range (normal subjects and the

majorityy of Marfan patients), the load bearing component is elastin. In the six Marfan

patientss with a transition point, the far stiffer collagen fibres are recruited. A correlation

hass been shown between a transition point in the pressure-area curve and both

susceptibilityy to permanent dilatation and breaking stress of the thoracic aorta12.

Heterogeneouss response to ft blocking agents Itt is generally accepted that ft blockade protects the Marfan aorta from both dilatation

andd dissection. Shores et al. found a heterogeneous response, with some patients deriving

greaterr benefit from ft blockade (that is, retardation of aortic dilatation), whereas in others

thee course of the disease seemed to be unaffected6. A retrospective historically controlled

triall of propranolol or atenolol treatment in 113 patients found similar effects7. The effect

off ft blockade on aortic elasticity in Marfan patients has been described in several

studies7'910.. Aortic distensibility is decreased in Marfan disease and the values in our

studyy are comparable with those previously reported9-32-34. The effect of ft blockade on

thee aortic elastic properties has been assessed non-invasively by Groenink et al., comparing

normall controls with patients with Marfan syndrome after two weeks of ft blocker

treatment9.. They observed a significant decrease in aortic elasticity only in the Marfan

patients9.. Haouzi et al. found a heterogeneous response on aortic root elasticity after a

singlee dose of metoprolol in patients with Marfan syndrome10. Rios et al. also found a

non-uniformm response to long term oral atenolol, although as a group there was a significant

increasee in distensibility and a trend toward lowering the stiffness index in the Marfan

patients11.. An important observation described by Yin et al. was that in some patients

withh moderate to severe dilatation of the aortic root, worsening of aortic properties occurred

whenn they were taking ft blocking agents, raising questions about the beneficial

prophylacticc effect35.

Thee presence of a transition point in the pressure-area curve may play a crucial role in the

heterogeneouss response to ft blockade in Marfan patients. In view of the pressure-area

relationn of the great arteries36, a decrease in mean blood pressure following ft blockade

couldd result in increased distensibility when systolic aortic area shifts from the collagen

determinedd (exponential) part of the pressure-area curve to the elastin (linear) determined

Figuree 3 Curvee of the aortic pressure-area

ii relation in a patient with Marfan // syndrome and the influence of ii lowering the blood pressure on // distensibility. The solid lines indicate

// the aortic area change at a blood // pressure of 120/90 mm Hg.

^s*^s* Lowering the blood pressure to 100/ ^ X ^^ 70 mm Hg (dotted lines) will result

.,—— in an increase in area change, ^ ^^ because the working area is shifted

^s^^s^ to the linear part of the curve.

jj i i I i I I i i

5255 535 545 555 565 575 585 595

Areaa (mm2)

partt (Figure 3). When B blockade causes a decrease in blood pressure in the linear part of

thee curve, distensibility is not expected to increase because the area change remains

similar.. We found that in the majority of patients with Marfan syndrome and in all our

controls,, the pressure-area curve did not show a transition point. Because the slope of the

linearr part of the pressure-area curve was similar to the slope of normal subjects, it is

reasonablee to assume that the transition point in these subjects was at a higher aortic

pressuree than their resting blood pressure. Only in six patients with Marfan syndrome was

aa transition point in the pressure-area curve observed, indicating that the load bearing

componentt in the resting blood pressure range involved collagen as well as elastin. In

thesee patients the transition point was shifted to much lower pressures, which could

indicatee more pronounced degeneration of the medial layer of the aortic wall than in

patientss without a transition point. This suggests that the presence of a transition point in

thee pressure-area curve could play a role in the heterogeneous response to ft blocker

treatmentt in relation to the elastic properties and dilatation rate. The transition point in

thee pressure-area curve in Marfan patients may vary as a result of different degrees of

aorticc media degeneration. Patients with a transition point at lower blood pressures are

nott expected to benefit from R. blocker treatment.

Limitationss of the study Thee use of ft blocking agents was not equally distributed between the two groups: there

weree considerably more patients in the group with ft blocking agents than in the group

withoutt (27 vs. 7 patients). The lack of a difference observed between patients with and

withoutt S blocker treatment may reflect the small sample size.

140 0

EE 120 E E

100 0

X! ! O O

55 80

c n n

Furthermore,, blood pressure and area should ideally be measured simultaneously and at

thee same level in the aorta for reliable assessment of pressure-area curves. MRI and

Finometerr blood pressure recordings were done separately, because it is not yet possible

too use the Finometer front end in the strong magnetic field of the magnetic resonance

scanner.. However, as Marfan patients regularly undergo MRI for monitoring aortic

dimensions,, physical and emotional stress during the procedure is limited. This was

confirmedd by similar blood pressure and heart rates during both MRI and Finometer

recording,, indicating comparable conditions. Although the Finometer blood pressure

recordingss were not at the site of the area measurement, the filter developed on the basis

off unpublished data corresponds well with other pulse wave filters from brachial artery to

aortaa described in published reports18-20.

Futuree developments

Adaptationn of the Finometer device to ensure reliable function in the strong magnetic

fieldd of the magnetic resonance scanner, combined with new developments in MRI as

"reall time" or techniques with a smaller temporal resolution, will further improve the

non-invasivee assessment of pressure-area curves in the near future. Until the Finometer is

adaptedd for use in the magnetic resonance scanner, the method can be validated by

meanss of transoesophageal echocardiography combined with non-invasive or invasive

aorticc pressure measurement. Further prospective randomised research on the effect of ft

blockerr treatment on the aortic pressure-area relation in Marfan patients is required.

Conclusions s Ourr new non-invasive method to derive aortic pressure-area curves showed that the

greatt majority of patients with Marfan syndrome on ft blocking agents had pressure-area

curvess similar to control subjects with comparable blood pressures. The variable position

off the transition point in the aortic pressure-area curve in individual patients could play a

cruciall role in the heterogeneous response to ft blockade in Marfan patients. We

hypothesisee that patients with a transition at low blood pressures will not benefit from ft

blockingg agents.

References s 1.. Dietz HC, Cutting GR, Pyeritz RE, etal.

Marfann syndrome caused by a recurrent de novoo missense mutation in the fibrillin gene.. Nature 1991;352:337-339.

2.. Murdoch JL, Walker BA, Halpern BL, etal. Lifee expectancy and causes of death in the Marfann syndrome. N Engl J Med 1972;286:804-808. .

3.. Silverman Dl, Burton KJ, GrayJJ, etal. Life expectancyy in the Marfan syndrome. Am J CardiolCardiol 1995;75:157-160.

4.. Sütch G, Jenni R, von Segesser L, etal. Predictabilityy of aortic dissection as a functionn of aortic diameter. Eur Heart J 1991;12:1247-1256. .

5.. Groenink M, Lohuis TAJ, Tijssen JGP, etal. Survivall and complication-free survival in Marfan'ss syndrome: implications of current guidelines.. Heart 1999;82:499-504.

6.. Shores J, Berger KR, Murphy EA, etal. Progressionn of aortic dilatation and the benefitt of long-term beta-adrenergic blockadee in Marian's syndrome. N Engl J MedMed 1994;330:1335-41.

7.. Salim MA, Alpert BS, Ward JC, ef al. Effect off beta-adrenergic blockade on aortic root ratee of dilation in the Marfan syndrome. AmAm J Cardiol 1994;74:629-33.

8.. Marsalese DL, Moodie DS, Vacante M, ef al.al. Marian's syndrome: natural history and long-termm follow-up of cardiovascular involvement.. J Am Coll Cardiol 1989;14:422-428. .

9.. Groenink M, de Roos A, Mulder BJM, etal. Changess in aortic distensibility and pulse wavee velocity assessed with magnetic resonancee imaging following beta-blocker therapyy in the Marfan syndrome. Am J CardiolCardiol 1998;82:203-8.

10.. Haouzi A, Berglund H, Pelikan PC, etal. Heterogeneouss aortic response to acute beta-adrenergicc blockade in Marfan syndrome.. Am Heart J 1997;133:60-63.

11.. Rios AS, Silber EN, Bavishi N, ef al. Effect off long-term beta-blockade on aortic root compliancee in patients with Marfan syndrome.. Am Heart J 1999;137:1057-1061. .

12.. Groenink M, Langerak SE, Vanbavel E ef al.al. The influence of aging and aortic stiffnesss on the resistance to permanent dilationn and breaking stress of the thoracic descendingg aorta. Cardiovasc Res 1999;43:471-480. .

13.. Bader H. Dependence of wall stress in the humann thoracic aorta on age and pressure. CirculationCirculation Res 1967;20:354-361.

14.. Imholz BP, Wieling W, van Montfrans GA, etal.etal. Fifteen years experience with finger arteriall pressure monitoring: assessment of thee technology. Cardiovasc Res 1998;38:605-616. .

15.. DePaepe A, Devereux RB, Dietz HC, etal. Revisedd diagnostic criteria for the Marfan syndrome.. Am J Med Genet 1996;62:417-426. .

16.. Bos WJ, van Goudoever J, van Montfrans GA,, ef al. Reconstruction of brachial artery pressuree from noninvasive finger pressure measurements.. Circulation 1996;94:1870-1877. .

17.. Guelen I, Westerhof BE, Van Der Sar GL, etal.etal. Finometer, finger pressure measurementss with the possibility to reconstructt brachial pressure. Blood Press MonitMonit 2003;8:27-30.

18.. Lasance HAJ, Wesseling KH, Ascoop CA. Peripherall pulse contour analysis in determiningg stroke volume. In Progress Reportt 5, Institute of Medical Physics. Utrecht:: Institute of Medical Physics; 1976;59-62. .

19.. Karamanoglu M, O'Rourke MF, Avolio AP, etal.etal. An analysis of the relationship betweenn central aortic and peripheral upperr limb pressure waves in man. Eur Heart]Heart] 1993,14:160-167.

20.. Chen CH, Nevo E, Fetics B, ef al. Estimationn of central aortic pressure waveformm by mathematical transformation off radial tonometry pressure. Circulation 1997;95:1827-1836. .

21.. Sugawara M, Niki K, Furuhata H, etal. Relationshipp between the pressure and diameterr of the carotid artery in humans. HeartHeart Vessels 2000; 15:49-51.

22.. van Popele NM, Bos WJW, de Beer NAM, etal.etal. Arterial stiffness as underlying mechanismm of disagreement between an oscillometricc blood pressure monitor and a sphygmomanometer.. Hypertension 2000;36:484-488. .

23.. Hasan MA, Thomas TA, Prys-Roberts C. Comparisonn of Automated oscillometric arteriall pressure measurement with conventionall auscultatory measurement in thee labour ward. BrJAnaesth 1993;70:141-144. .

24.. Bogren HG, Mohiaddin RH, Klipstein RK, etet al. The function of the aorta in ischemic heartt disease: a magnetic resonance and angiographicc study of aortic compliance andd blood flow patterns. Am Heart J 1989;118:234-247. .

25.. Heintz B, Gillessen T, Walkenhorst F, et al. Evaluationn of segmental elastic properties of thee aorta in normotensive and medically treatedd hypertensive patients by intravascularr ultrasound. J Hypertens 1993;11:1253-1258. .

26.. Stefanadis C, Stratos C, Vlachopoulos C, et al.al. Pressure-diameter relation of the human aorta.. A new method of determination by thee application of a special ultrasonic dimensionn catheter. Circulation 1995;92:2210-2219. .

27.. Honda T, Yano K, Matsuoka H, etal. Evaluationn of aortic distensibiltty in patients withh essential hypertension by using cine magneticc resonance imaging. Angiology 1994;45:207-212. .

28.. Mohiaddin RH, Firmin DN, Longmore DB. Age-relatedd changes of human aortic flow wavee velocity measured noninvasively by magneticc resonance imaging. J Appl PhysiolPhysiol 1993; 74:492-497.

29.. Roy CS. Elastic properties of the arterial wall.. Journal Physiology 1880;3:125-159.

30.. Carlson RS, Lillehei CW, Edwards JE. Cysticc media necrosis of ascending aorta in relationn to age and hypertension. Am J CardiolCardiol 1970;25:411.

31 .. Schlatmann TJM, Becker AE. Histologic changess in the normal aging aorta: implicationss for dissecting aortic aneurysm. AmAm J Cardiol 1977;39:13-20.

32.. Adams JN, Brooks M, Redpath TW, et al. Aorticc distensibility measured by magnetic resonancee imaging in patients with Marfan's syndrome.. Br Heart) 1995;73:265-269.

33.. Hirata K, Triposkiadis F, Sparks E, etal. The Marfann syndrome: abnormal elastic properties.. J Am Coll Cardiol 1991 ;18:57-63. .

34.. Groenink M, de Roos A, Mulder BJM, et al. Biophysicall properties of the normal-sized aortaa in patients with marfan syndrome: evaluationn with mr flow mapping. RadiologyRadiology 2001 ;219:535-540.

35.. Yin F, Brin K, Ting C, etal. Arterial hemodynamicc indexes in Marfan's syndrome.. Circulation 1989;79:854-862.

36.. Greenfield JC, Patel DJ. Relation between pressuree and diameter in the ascending aortaa of man. Ore Res 1962;10:778-781.