JACC Vol. 18, No.1 July 1991 :57-63

57

The Marfan Syndrome: Abnormal Aortic Elastic Properties KAZUHITO HIRATA, MD, FILIPPOS TRIPOSKIADIS, MD, ELIZABETH SPARKS, RN, JUAN BOWEN, MD, CHARLES F. WOOLEY, MD, FACC, HARISIOS BOUDOULAS, MD, FACC Columbus, Ohio

Aortic distensibility and aortic stiffness index were measured at the ascending aorta (3 cm above the aortic valve) and the mid-portion of the abdominal aorta from the changes in echocar­diographic diameters and puIse pressure in 14 patients with the Marfan syndrome and 15 age- and gender-matched normal con­trol subjects. The following formulas were used: 1) Aortic disten­sibility = 2(Changes in aortic diameter)/(Diastolic aortic diame­ter) (Pulse pressure); and 2) Aortic stiffness index = In(Systolic blood pressure)/(Diastolic blood pressure)(Changes in aortic di­ameter)IDiastolic aortic diameter. Pulse wave velocity was also measured.

Compared with normal subjects, patients with the Marfan syndrome had decreased aortic distensibility in the ascending and the abdominal aorta (2.9 ± 1.3 vs. 5.6 ± 1.4 cm2 dynes-I, p < 0.001 and 4.5 ± 2.1, vs. 7.7 ± 2.5, cm2 dynes-I, p < 0.001,

The Marfan syndrome is a heritable connective tissue disor­der with major manifestations in the ocular, skeletal and cardiovascular systems (1-3). Cardiovascular involvement includes aneurysmal dilation of the ascending aorta, aortic valve regurgitation, aortic dissection, mitral valve prolapse and mitral valve regurgitation. Aortic root dilation and related complications are the major causes of death in patients with this syndrome (4).

Histopathologic examination of the aorta in the Marfan syndrome reveals cystic medial necrosis, disruption of col­lagen fibers and degeneration and fibrosis of the media (5-7). Biochemical abnormalities of collagen and elastin, the major structural proteins in the aortic wall, have been demon­strated (8-12) in some patients with this syndrome. Re­cently, decreased content of microfibrillar fibers in the skin or cultured fibroblasts, or both, have been reported (13) in patients with this syndrome. Decreased tensile strength has been reported (11) in the aorta obtained after death from

From the Division of Cardiology, The Ohio State University. Columbus. Ohio. This study was supported by the James Overstreet Cardiovascular Teaching and Research Laboratory. Division of Cardiology. The Ohio State University, Columbus. Ohio.

Manuscript received September 17, 1990; revised manuscript received December 26, 1990, accepted January 17, 1991.

Address for reprints: Harisios Boudoulas. MD. Division of Cardiology, The Ohio State University, 6th Floor Means Hall, 1654 Upham Drive. Columbus, Ohio 43210.

©1991 by the American College of Cardiology

respectively) and had an increased aortic stiffness index in the ascending and the abdominal aorta (10.9 ± 5.6 vs. 5.9 ± 2.2, p < 0.005 and 7.1 ± 3.1 vs. 3.9 ± 1.2, p < 0.005, respectively). Aortic diameters in the ascending aorta were larger in these patients than in normal subjects, but those in the abdominal aorta were similar in the two groups. Linear correlations for both aortic distensibility and stiffness index were found between the ascending and the abdominal aorta (r = 0.85 and 0.71, respectively). Pulse wave velocity was more rapid in the patients than in the normal subjects (11.6 ± 2.5 vs. 9.5 ± 1.4 mis, respectively, p < 0.01).

Thus, aortic elastic properties are abnormal in patients with the Marfan syndrome irrespective of the aortic diameter, which suggests an intrinsic abnormality of the aortic arterial wall.

(J Am Coli CardioI1991;18:57-63)

patients with this syndrome who died from cardiovascular complications.

It was hypothesized that underlying structural abnormal­ities of the aorta in patients with the Marfan syndrome might be manifested by abnormal elastic properties. The present study was undertaken to test this hypothesis.

Methods Study patients. Seventeen patients (12 male and 5 female)

ranging in age from 16 to 41 years (mean 26.1 ± 7.2) who filled the strict diagnostic criteria for the Marfan syndrome (14) were studied. Two patients had mild aortic regurgitation and four had mild mitral regurgitation as defined by Doppler echocardiography. Patients with a history of aortic dissec­tion or aortic surgery were excluded before entry into the study. All medications were discontinued at least 5 half-lives before the study.

Fifteen age- and gender-matched subjects without a his­tory of heart disease and with a normal physical examina­tion, electrocardiogram (ECG), echocardiogram and Dopp­ler echocardiogram constituted the normal control group (Table I).

Standard noninvasive technology that is not associated with any risk or discomfort was used.

Echocardiography. Echocardiographic examination was performed with commercially available equipment (Hewlett­Packard n022-A). After routine conventional echocardio-

0735-1097/91/$3.50

58 HIRATA ET AL. AORTIC ELASTIC PROPERTIES IN MARFAN SYNDROME

Table 1. Demographic Data, Aortic Diameter, Blood Pressure, Aortic Distensibility, Stiffness Index and Pulse Wave Velocity in the Two Groups

Subjects

Age (yr) Malelfemale BSA (m2) Aortic diameter

Asc Ao diastolic Aod (cm) Asc Ao diastolic Aod/(cmlm2) Asc Ao systolic Aod (cm) Asc Ao change in Aod (cm) Ab Ao diastolic Aod (cm) Ab Ao diastolic Aod/(cmlm2) Ab Ao systolic Aod (cm) Ab Ao change in Aod (cm)

Arterial blood pressure (mm Hg) Systolic Diastolic Pulse pressure

Aortic distensibility/aortic stiffness index Asc Ao dist (cm2 dynes-I) Ab Ao dist (cm2 dynes-I) Asc Ao stiffness index Ab Ao stiffness index

Pulse wave velocity (m1s)

Normal (n = 15)

28.9 ± 5.5 1114

1.86 ± 0.2

2.72 ± 0.28 1.46 ± 0.1 2.97 ± 0.27 0.25 ± 0.06 1.45 ± 0.13 0.78 ± 0.08 1.64 ± 0.15 0.20 ± 0.05

122 ± 13.3 74.8 ± 8.9 47.7 :t 8.9

5.6:t 1.4 7.7 :t 2.5 5.9 :t 2.2 3.9 :t 1.2 9.5 :t 1.4

Patients With the Marfan

Syndrome (n = 14) p Value

26.1±7.2 NS 1215 NS

2.0 ± 8.6 <0.05

3.70 ± 1.16 <0.0\ 1.93 ± 0.55 <0.01 3.87 ± 1.18 <0.05 0.17 ± 0.06 <0.005 1.56 ± 0.32 NS 0.80 ± 0.15 NS 1.69 ± 0.33 NS 0.11 ± 0.04 <0.001

126 ± 14.1 NS 81.2 ± 9.6 NS 44.4 :t 7.5 NS

2.9 ± 1.3 <0.001 4.5 ± 2.1 <0.001

10.9 ± 5.6 <0.005 7.1 :t 3.1 <0.005

11.6 :t 2.5 <0.01

Ab Ao = abdominal aorta; Aod = aortic distensibility; Asc Ao = ascending aorta; BSA = body surface area; dist = distensibility.

graphic examination, patients were placed in a mild left recumbent position and the ascending aorta was recorded in the two-dimensional guided M-mode tracings. The mid­portion of the abdominal aorta was also recorded with the patient supine with use of the same technique.

Systolic and diastolic diameters were measured at the ascending aorta 3 cm above the aortic valve and at the mid-portion of the abdominal aorta. For the ascending aorta, diastolic diameter was measured at the peak of the QRS complex on the simultaneously recorded ECG and systolic

~ "........",,~ J~ ---...;/ ""+ -:

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ECG ...... ..... .... , ............. ..

JACC Vol. 18, No. I July 1991 :57-63

............... ... .... ..

ECG---li .. .. . .... ......... .. I , ....... I ........ .

Figure 2. Carotid (left) and femoral (right) artery pulse simulta­neously recorded with the electrocardiogram (ECG). The time from the beginning of the QRS complex to the carotid artery pulse upstroke is shown between the perpendicular lines.

diameter was measured at the maximal anterior motion of the aorta (Fig. 1). For the abdominal aorta, systolic diameter was measured at the maximal anterior motion of the aorta and diastolic diameter was measured lOO ms before the beginning of the anterior motion of the aorta. The average value of 5 to 10 consecutive beats was used for the final analysis. Diastolic aortic diameter was corrected for body surface area for comparisons between patients with the Marfan syndrome and the normal control subjects.

Blood pressure was measured at the brachial artery by sphygmomanometry with the patient supine. Pulse pressure was obtained by subtracting the diastolic blood pressure from the systolic blood pressure.

Left carotid and left femoral artery pulses were recorded with the patient supine. The recordings were obtained simul­taneously with the ECG with use of commercially available mechanocardiographic equipment (Hewlett-Packard 78308-A) (Fig. 2).

Figure 3 summarizes our methods and indicates the levels at which aortic distensibility, stiffness index and pulse wave velocity were measured. High quality echocardiographic and arterial pulse tracing recordings were obtained in 14 patients with the Marfan syndrome and in 13 normal control subjects.

Figure 1. Measurements of the diameters of the ascending aorta (left) and abdominal aorta (right). DD = diastolic diameter; ECG = electrocardiogram; SD = systolic diameter.

JACC Vol. 18, No. I July 1991 :57-63

A

kj; C

B

~ II

t D

AORTIC DISTENSIBILITY (Points C and 0) : Change of the aortic diameter I change of blood pressure

STIFFNESS INDEX (Points C and 0) : Natural logarithm of blood pressure I change of the aortic diameter

PULSE WAVE VELOCITY: Velocity of the pulse wave from point A to B

Figure 3. Aortic distensibility and stiffness index were measured 3 cm above the aortic valve (point C) and at the mid-portion of the abdominal aorta (point D). Pulse wave velocity was measured from the left carotid artery to the left femoral artery (from point A to B).

Only these subjects with high quality recordings were in­cluded in further analyses.

Calculation of aortic distensibility. Aortic distensibility was measured from the changes in echocardiographic aortic diameters and brachial artery pressure with the formula: Aortic distensibility = 2(Changes in aortic diameter)/ (Diastolic aortic diameter)(Pulse pressure) (15,16).

Calculation of stiffness index. Stiffness index was calcu­lated with the formula: Stiffness index = In(Systolic blood pressure)/(Diastolic blood pressure)(Changes in aortic diam­eter)/(Diastolic aortic diameter) (17).

Calculation of pulse wave velocity. The time from the beginning of the QRS complex on the simultaneously re­corded ECG to the upstroke of the left carotid and femoral artery pulses was measured (Fig. 2). The distance from the left carotid artery to the left femoral artery was also mea­sured. The average values from lO consecutive beats were used for the final analysis. Pulse wave velocity was calcu­lated as the ratio of the time required for the pulse wave to travel from the carotid artery to the femoral artery to the distance between these arteries.

Statistical analysis. Values were expressed as mean val­ues ± I SD. An unpaired t test and regression analysis were used where appropriate for statistical evaluation. A p value <0.05 was considered statistically significant.

Results Aortic diameters (Table 1). The diameter of the ascending

aorta corrected for body surface area was larger in patients with the Marfan syndrome than in normal control subjects. The diameter of the abdominal aorta corrected for body surface area was not statistically different between the two groups. Changes in aortic diameter from diastole to systole were significantly less for both the ascending and the abdom-

HIRATA ET AL. AORTIC ELASTIC PROPERTIES IN MARFAN SYNDROME

10.,

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N'

E .!!. ~ 4J 1i Ui c .. 2 I ]i c I

o ~ 0

14 -,

12 J 'i.. .. c '" ... 10

N

E 8 .!!. ?: 6 ~ Ui 4 c .. "' Q 2

0 0

Ascending Aorta

• • .~

j.u • , .J .J

.ll .J

.J :J .J .J

i i i

2 3 4

Diameter (cm)

Abdominal Aorta

• .,. I~.J-:J :I : :I" tJ :J

#-:J-:J

2

Dlamlller (cm)

3

.J Marfan • Normal r = -0.66

.J :J

5

.J Martan • Normal r = -0 39

i

6

4

59

Figure 4. Relation between the aortic diameter and aortic distensi­bility for the ascending aorta (upper panel) and abdominal aorta (lower panel).

inal aorta in patients with the Marfan syndrome than in normal subjects.

Systolic and diastolic blood pressure were slightly greater in patients with the Marfan syndrome than in normal sub­jects, but these differences were not statistically significant. The pulse pressure also was not statistically different be­tween the two groups. Arterial diastolic blood pressure in the two patients with mild aortic regurgitation was 80 and 84 mm Hg, respectively.

Aortic distensibility (Table 1). Aortic distensibility in both the ascending and the abdominal aorta was significantly less in patients with the Marfan syndrome than in normal sub­jects. An inverse correlation was found between aortic diameter and aortic distensibility for the ascending aorta (r = -0.66) (Fig. 4), but there was no correlation between these variables for the abdominal aorta (Fig. 4). However, the range of diameters in the abdominal aorta was not wide enough to permit correlation. A correlation was also found between the distensibility of the ascending aorta and that of the abdominal aorta (r = 0.85, Fig. 5).

No correlations were found between age and distensibil­ity (r = 0.24 for ascending aorta, r = 0.20 for abdominal aorta). However, age distribution was too narrow in both the patient and the normal group to permit good correlations.

Aortic stiffness index (Table 1). The aortic stiffness index in both the ascending and the abdominal aorta was greater in

60

~ .. ~'i" 'tit: • 0

N os E-&~ ~g -'tI :2.0 "'os c-<II 1ii i5

HIRATA ET AL. AORTIC ELASTIC PROPERTIES IN MARFAN SYNDROME

12

10

8

6

4

2

0 0

• • w •• • • 'J •

.J • ~ .. .J.

.J...l .J .J .J

.J

2

i..I Marfan .J • Normal r= 0 85

4 6 8 10

Distensibility (em 2. dynes-1) (ascending aona)

Figure S. Relation between the distensibility of the ascending aorta and abdominal aorta.

patients with the Marfan syndrome than in normal subjects. There was an inverse correlation between the aortic disten­sibility and stiffness index for the ascending aorta (r = -0.93) and the abdominal aorta (r = -0.94) (Fig. 6). A correlation was also found between the stiffness index of the ascending aorta and that of the abdominal aorta (r = 0.71) (Fig. 7).

Pulse wave velocity (Table 1). The pulse wave velocity was significantly greater in patients with the Marfan syn-

Figure 6. Relation between stiffness index and distensibility for the ascending aorta (upper panel) and abdominal aorta (lower panel),

Ascending Aorta 30

a Marfan • Normal

a r --0.93

I 20 a

I cu

! 10 ClaarwCl ..

• Cl~ •• • • 0

0 2 4 6 8 10

DIStensllIIIty (cm2 • dynes")

Abdominal Aorta IJ

a Marfan a • Normal

j <dJ r--O.94 10

a

I a I;

';.~~ Di , •

0 0 2 4 6 8 10 12 14

'*'-lIlly (cm2• dynes")

14

12

2

u

u

••. w 0 U UI.J .6..l. 0 •

• -.Jt •

••

D

u

JACC Vol. 18, No.1 July 1991:57-63

D

o Marfan • Normal r= 0.71

01------.-----.------r-----. o 10

Stiffness Index (ascending aona)

20

Figure 7. Relation between the stiffness index of the ascending aorta and abdominal aorta.

drome than in normal SUbjects. An inverse correlation was found between the pulse wave velocity and aortic distensi­bility for the ascending (r = -0.68) and the abdominal (r = -0.81) aorta (Fig. 8). A direct correlation was also found between the pulse wave velocity and stiffness index for the ascending (r = 0.62) and the abdominal (r = 0.82) aorta (Fig. 9).

Figure 8. Relation between pulse wave velocity and aortic disten­sibility for the ascending aorta (upper panel) and abdominal aorta (lower panel).

Ascending Aorta 16 U DMarfan

I u U • Normal

14 U r--O.68

(j • • 12 OJ ~ 10 U ••• u

• U • ~ .J J.J, • ~ 8 • ~ 6 ~ :I 4 "3 2 II.

0 0 2 4 6 8 10

Distensibility (em2 • dynes")

Abdominal Aorta 16

I :J a Marfan

14 JD.J • Normal r= -0 81

12 a ~iJ • >-= 10 a ... l: I ~ 8 aD· • • a • • • I 6

I 4

i 2

0

0 2 4 6 8 10 12 14 16

DlstenslbllHy (em2• dyn ... ')

JACC Vol. 18, No. I July 1991 :57-63

16

I 14

12

~ 10 j ~ 8

• i 6

J 4

i 2

0 0

16

I 14

12 ,.. :: 10 j ~ 8

• i 6

J 4

i 2

0

0

Ascending Aorta

00 0 0

• • ~O 0

•• • 0 .~. • 0

o Marian • Normal r - 0.62

5 10 15 31

Stiffness Index

Abdominal Aorta

0 0 0 0

• 151~ 0

~ • 0 .. 0. ••

o Marian • Normal r- 0.82

2 4 6 8 10 12 14 16

Stiffness Index

Figure 9. Relation between pulse wave velocity and stiffness index for the ascending aorta (upper panel) and abdominal aorta (lower panel).

Discussion The present study demonstrated abnormal elastic

properties of the aorta, as defined by decreased distensibil­ity, increased stiffness index and increased pulse wave velocity, in patients with the Marfan syndrome. Patients with the Marfan syndrome tended to have less distensibility, greater stiffness index and faster pulse wave velocity than did normal subjects. All three of these indexes have been used previously (15-25) to estimate arterial elastic proper­ties.

Aortic distensibility. An inverse correlation was found between the ascending aortic diameter and aortic distensi­bility, which suggests that the aorta loses its elasticity as it becomes larger. There was no correlation between abdomi­nal aortic diameter and distensibility, but the range of abdominal aortic diameters was too narrow to permit corre­lation. A correlation was found between the distensibility of the ascending and the abdominal aorta; this finding indicates that for each individual patient, the intrinsic elastic proper­ties of the aorta rather than its diameter were the major determinants of distensibility.

Abnormal aortic distensibility has been reported (5-16,20,26-29) in patients with coronary artery disease, post-

HIRATA ET AL. 61 AORTIC ELASTIC PROPERTIES IN MARFAN SYNDROME

stenotic aortic dilation associated with valvular aortic steno­sis, arterial hypertension and advanced age.

Aortic stiffness index. This index was obtained from the logarithmic value of the ratio of systolic and diastolic blood pressure and changes in arterial diameter. It has been proposed as a pressure-independent index for the evaluation of the elastic properties of the aorta. Increased aortic stiff­ness index has been reported (17) in both the carotid artery and the abdominal aorta in patients with coronary artery disease.

Pulse wave velocity. Pulse wave velocity is proportional to the square root of the elastic modulus and inversely proportional to distensibility (21,22,24,25). The stiffer and less distensible the artery, the faster the pulse wave travels along the artery. Increased pulse wave velocity has been reported in patients with arterial hypertension, in elderly individuals (18,22,23) and in experimental animals with atherosclerosis (24,25).

Underlying mechanisms for abnormal elastic properties. A pathologic basis for altered elastic properties of the aorta has been reported (24,25) in experimental animals with athero­sclerosis. Increased stiffness of the artery might be attrib­uted to increased thickness of the intima, severity of ather­osclerosis and decreased vasa vasorum flow (24,25,30). Microscopic pathologic changes of the aorta in the Marfan syndrome include cystic medial necrosis, elastin fragmenta­tion, fibrosis and medionecrosis (5-7). However, those find­ings are not specific for the Marfan syndrome and may be present in elderly individuals and patients with arterial hypertension (5-7). These changes may represent alterations secondary to trauma and the repair process consequent to hemodynamic forces in the presence of the underlying connective tissue abnormalities in patients with the Marfan syndrome.

Biochemical abnormalities in the major components of connective tissue, such as collagen or elastin, have been reported (8,12) in patients with the Marfan syndrome. An abnormal alpha chain in type 1 collagen and a deficiency in chemically stable collagen cross-linking have been reported (9,10) in these patients. A reduction in aortic elastin fibers from patients with the syndrome who died of cardiovascular complications without collagen abnormalities has also been described (11).

Recently, decreased content of microfibrillar fibers in the skin or cultured fibroblasts, or both, has been reported (13) in patients with the Marfan syndrome. Microfibrillar fibers are prominently distributed within the tissues affected in the Marfan syndrome, including ciliary zones and aortic tunica media (13). Functionally incompetent microfibrillar fibers may contribute to the abnormal elastic properties of the aorta.

Decreased distensibility of the ascending aorta in pa­tients with the Marfan syndrome may be secondary to aortic dilation. However, the correlation between the distensibility of the ascending and the abdominal aorta in this study suggests that dilation of the aorta and decreased distensibil-

62 HIRATA ET AL. AORTIC ELASTIC PROPERTIES IN MAR FAN SYNDROME

ity might be attributed to the same underlying abnormalities of aortic connective tissue. Patients with more severe in­volvement of the connective tissue in the media of the aorta tend to develop proximal aortic dilation more rapidly. Fur­thermore, decreased distensibility and increased stiffness index were seen in the abdominal aorta, which was of similar size in patients with the Marfan syndrome and normal subjects.

Other factors that may alter elastic properties of the aorta. Indexes may be influenced by blood pressure, drug therapy and aortic diameter (15,17,22,23). The elastic modulus of both the abdominal aorta and the carotid artery is dependent on systolic blood pressure in both normal subjects and patients with myocardial infarction (17). Elastic modulus is gradually decreased with a reduction in systolic blood pres­sure. In this study, stiffness index, which was obtained from the logarithmic value of the ratio of the systolic and diastolic blood pressure and changes in the diameter of the vessel, was independent of blood pressure. Systolic and diastolic blood pressure and pulse pressure were similar in the two groups in the present study; the slightly different systolic and diastolic blood pressure between the two groups and a 3.3 mg Hg difference in pulse pressure between the groups had either no or minimal effect on the calculated indexes. Furthermore, because the pulse pressure is used as the nominator in the equation for stiffness index and as the denominator for aortic distensibility, a slightly lower pulse pressure tends to underestimate the differences. Thus, blood pressure differences did not account for the abnormal dis­tensibility and stiffness index found in patients with the Marfan syndrome.

Brachial artery blood pressure was used in this study to estimate aortic pulse pressure for the calculation of aortic distensibility and stiffness index. Although pulse pressure obtained from the brachial artery may be slightly different from that obtained from the aorta, previous studies (31) have shown a correlation between aortic distensibility calculated from brachial artery pressure and that calculated from direct aortic pressure. Although two patients had aortic valve regurgitation, the degree of regurgitation was very mild and both patients had normal diastolic blood pressure.

All medications were discontinued at least 5 half-lives before the study. Thus, the effect of pharmacologic agents themselves cannot explain the differences found in aortic distensibility, stiffness index and pulse wave velocity be­tween the two groups.

Distensibility is known to decrease with age (19,23,26,27). Age distribution was similar between normal subjects and patients with the Marfan syndrome and thus was not a factor accounting for the differences found in the elastic properties of the aorta.

Conclusions. Patients with the Marfan syndrome have abnormal elastic properties of the ascending and the abdom­inal aorta. Decreased distensibility, increased stiffness index and increased pulse wave velocity were demonstrated with noninvasive techniques. The abnormal elastic properties of

JACC Vol. 18, No. I July 1991:57-63

the aorta in patients with the Marfan syndrome appear to be secondary to diffuse connective tissue abnormalities of the aortic wall.

References I. Pyeritz RE, Mckusick VA. The Marfan syndrome: diagnosis and manage­

ment. N Engl J Med 1979;300:772-7. 2. Pyeritz RE. Diagnosis and management of cardiovascular disorders in the

Marfan syndrome. J Cardiovasc Med 1980;5:759-69. 3. Bowen J, Boudoulas H, Wooley CF. Cardiovascular disease of connec­

tive tissue origin. Am J Med 1987;82:481-8. 4. Murdoch JL, Walker BA, Halpern BL, Kuzma JW, Mckusick VA. Life

expectancy and causes of death in the Marfan syndrome. N Engl J Med 1972;286:804-8.

5. Roberts WC, Honig HS. The spectrum of cardiovascular disease in the Marfan syndrome: a C\inico-morphologic study of 18 necropsy patients and comparison to 151 previously reported necropsy patients. Am Heart J 1982;104: 115-35.

6. Roberts WC. Aortic dissection: anatomy, consequences and causes. Am Heart J 1981;101:195-214.

7. Schlatmann TJM, Becker AE. Pathogenesis of dissecting aneurysm of aorta: comparative histologic study of significance of medial changes. Am J Cardiol 1977;39:21-6.

8. Prockop OJ, Kivirikko K. Heritable diseases of collagen. N Engl J Med 1984;311:376-86.

9. Byers PH, Siegel RC, Peterson KE, et al. Marfan syndrome: abnormal A chain in type I collagen. Proc Natl Acad Sci USA 1981;78:7745-9.

10. Boucek RJ, Noble NL, Gunja-Smith Z, Butler WT. The Marfan syn­drome: a deficiency in chemically stable collagen cross-links. N Engl J Med 1981 ;305:988-91.

II. Perejda AJ, Abraham PA, Carnes WH, Coulson WF, Uitto J. Marfan's syndrome: structural, biochemical and mechanical studies of the aortic media. J Lab Clin Med 1985;106:376-83.

12. Halme T, Savunen T, Aho H, Vihersaari T, Penttinen R. Elastin and collagen in the aortic wall: changes in the Marfan syndrome and annu­loaortic ectasia. Exp Moll Path 1985;43:1-12.

13. Hollister DW, Godfrey M, Sakai LY, Pyeritz RE. Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N Engl J Med 1990:323:152-9.

14. Beighton p, de Paepe A, Finidori DG, et al. International nosology of heritable disorders of connective tissue, Berlin, 1986. Am J Med Genet 1988;29:581-94.

15. Stefanadis C, Wooley CF, Bush CA, Kolibash AJ, Boudoulas H. Aortic distensibility abnormalities in coronary artery disease. Am J Cardiol 1987;59:1300-4.

16. Stefanadis C, Wooley CF, Bush CA, Kolibash AJ, Boudoulas H. Aortic distensibility in post-stenotic aortic dilatation: the effect of co-existing coronary artery disease. J Cardiol 1988;18:189-95.

17. Hirai T, Sasayama S, Kawasaki T, Yagi S. Stiffness of systemic arteries in patients with myocardial infarction. Circulation 1989;80:78-82.

18. Merillon JP, Motte G, Fruchaud J, Masquet C, Gougon R. Evaluation of the elasticity and characteristic impedance of the ascending aorta in man. Cardiovasc Res 1978;12:401-6.

19. lsnard RN. Pannier BM, Laurent S, London GM, Diebold B, Safar ME. Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: a noninvasive study. J Am Coli CardioI1989;13:399-405.

20. Imura T, Yamamoto K, Kanamori K, Mikami T, Yasuda H. Non-invasive ultrasonic measurement of the elastic properties of the human abdominal aorta. Cardiovasc Res 1986;20:208-14.

21. Patel OJ, Freitas FMD, Greenfield JC Jr, Fry D. Relationship ofradius to pressure along the aorta in living dog. J Appl PhysioI1963;18:1I11-7.

22. Laogun AA, Gosling RO. In vivo arterial compliance in man. Clin Phys Physiol Meas 1982;3:201-12.

23. Kelly R, Avolio A, O'Rourke M. Arterial dilatation and reduced wave reflection. Benefit of dilevalol in hypertension. Hypertension 1989;14: 14-21.

24. Farrar OJ, Green HD, Wagner WD, Bond MG. Reduction in pulse wave velocity and improvement of aortic distensibility accompanying re-

JACC Vol. 18, No. I July 1991:57-63

gression of atherosclerosis in the rhesus monkey. Circ Res 1980;47:425-32.

25. Farrar OJ, Bond MG, Sawyer JK, Green HD. Pulse wave velocity and morphological changes associated with early atherosclerosis progression in the aortas of cynomolgus monkeys. Cardiovasc Res 1984;18: 107-18.

26. Mohiaddin RH, Underwood SR, Bogren HG, et al. Regional aortic compliance studied by magnetic resonance imaging: the effects of age, training, and coronary artery disease. Br Heart J 1989;62:90-6.

27. Mohiaddin RH, Longmore DB. MRI studies of atherosclerotic vascular disease: structural evaluation and physiological measurements. Br Med Bull 1989;45:968-90.

HIRATA ET AL. 63 AORTIC ELASTIC PROPERTIES IN MARFAN SYNDROME

28. Mohiaddin RH, Firman DN, Underwood SR, et aI. Chemical shift magnetic resonance imaging of human atheroma. Br Heart J 1989;62:81-9.

29. Bogren HG, Mohiaddin RH, Klipstein RK, et al. The function ofthe aorta in ischemic heart disease: a magnetic resonance and angiographic study of aortic compliance and blood flow patterns. Am Heart J 1989;118:234-47.

30. Stefanadis C, Karayannakos P, Toutouzas P, Skalkeas G, Boudoulas H. Aortic distensibility: effect of vasa vasorum flow (abstr). Circulation 1988;78(suppl II):II-404.

31. Stefanadis C, Stratos C, Boudoulas H, Kourouklis C, Toutouzas P. Aortic distensibility: comparison of noninvasive and invasive techniques. Eur Heart J 1990;11:990-6.