(Hypertension. 2000;35:637.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Effect of Age on Brachial Artery Wall Properties Differs From the Aorta and Is Gender Dependent
A Population Study
From the Department of Pharmacology (J.J.H.-S., H.A.S.B., L.M.V.B.) and Biophysics (A.P.H.), Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands, and the Hypertension and Cardiovascular Rehabilitation Unit (J.A.S., R.H.F.), Department of Molecular and Cardiovascular Research, University of Leuven, Leuven, Belgium.
Correspondence to Janneke J. van der Heijden-Spek, MD, Department of Pharmacology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
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Abstract |
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Abstract—Compliance and distensibility are wall properties of large arteries, which may play a role in cardiovascular disease. The purpose of this study was to investigate whether the influence of age on these vessel wall properties differs between vascular territories and is gender-dependent. In a population sample of 498 men and women 20 to 79 years of age, diameter, distensibility, and compliance coefficient of the muscular brachial artery were measured with an echo-tracking device. Distensibility of the aorta was measured with the use of pulse-wave velocity. The effects of age and gender were assessed and adjusted for confounding factors such as mean blood pressure, pulse rate, body mass index, smoking, alcohol intake, and antihypertensive treatment. Covariance analysis showed no relation between gender and distensibility of the elastic aorta. Distensibility of the muscular brachial artery was lower in men, whereas men had a larger diameter and larger compliance of the brachial artery. With age, distensibility of the aorta decreased in both sexes to the same extent, whereas distensibility of the brachial artery did not change significantly. With age, brachial artery diameter increased; this increase was more pronounced in women. In men brachial artery compliance did not change with age, whereas in women compliance of the brachial artery increased with age. This study (1) confirms that distensibility of the aorta, an elastic artery, decreases with age. (2) In contrast to the aorta, after adjustment for confounding factors, in both men and women, no relation exists between age and distensibility of the muscular brachial artery. (3) Brachial artery diameter increase with age is more pronounced in women than in men. (4) In contrast to the well-known decrease in arterial compliance of elastic arteries with age, brachial artery compliance is not decreased with age and is increased in women. In conclusion, the effect of age on large-artery wall properties is not uniform but depends on gender and vascular territory.
Key Words: aorta • arteries • compliance • aging • gender
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Introduction |
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Compliance and distensibility are vessel wall properties of large arteries. Arterial compliance, defined as the absolute change in volume per unit of pressure (
V/P), reflects
the buffering capacity of an artery; a decrease in compliance increases
cardiac afterload and the risk of cardiac
hypertrophy.1 2 3 Arterial
distensibility, defined as the relative change in volume per unit of
pressure ([V/V]/P), reflects mainly the elasticity of the wall
and is considered a determinant of strain on the vessel
wall.4 A local decrease in distensibility might be
associated with an increased risk of arterial wall damage,
an important feature in atherosclerotic disease.5
Preservation of distensibility might be important in protecting the
arterial wall against damage at a particular
site.6
From 1880 on, several groups have investigated the effect of age
on elastic properties of the arterial system.7
The first studies were postmortem studies,8 9 10 later
followed by in vivo measurements of regional
distensibility.11 12 At the age of 20 years, the vascular
system is considered to be mature, but it is unclear from which age
distensibility starts to decrease. Several studies reported the
influence of age on wall properties of elastic large arteries. It has
been suggested that aortic distensibility reaches its peak at 
10
years of age11 and starts to decrease in the third age
decade.9 13 With advancing age, elastic arteries, like the
aorta and common carotid artery, dilate, become stiffer, and show an
increase in wall thickness.8 11 12 13 14 15 16 17 18 The
arterial tree, however, is composed not only of elastic
arteries but also medium-sized muscular arteries such as the brachial
artery. Whether the effect of age on arterial wall
properties of these arteries is similar to the effect on elastic
arteries is not known. In addition, no study investigated whether the
effect of age is gender dependent. The aim of the present study was
to investigate the effects of age and gender on wall properties of the
medium-sized muscular brachial artery compared with the elastic aorta
in a general population.
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Methods |
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A random population sample was identified in a rural area of Belgium.19 The population sample was stratified by sex and age (20 to 39, 40 to 59, and
60 years) in an attempt to recruit the
same number of subjects in each stratum. From population registers, a
random sample of the households was drawn. All household members 20
years were eligible except if they were foreign nationals or if the
quota of their age-sex stratum had been fulfilled. Of 974 subjects
invited, 614 agreed to take part. Of these participants, 116 subjects
were withdrawn because of technical and logistic problems. The number
of subjects finally considered in the analysis totalled 250 men
and 248 women.
All participants refrained from smoking and caffeine-containing
beverages for 3 hours before being examined. First, the participants
were seated and were asked to relax for 5 minutes. The same nurses who
had previously visited the participants at home then measured
consecutively (5 times) their sitting blood pressure conventionally,
with a sphygmomanometer on the left side. Data of systolic
blood pressure (SBP) and diastolic blood pressure (DBP) are
the mean of 5 measurements. Mean blood pressure was calculated as
(2xDBP+SBP)/3. The nurses also interviewed the participants
about their current health status, smoking (yes/no) and drinking habits
(yes/no), and intake of drugs. After 15 minutes of supine rest in a
quiet room, aortic and brachial artery wall properties were measured.
Vessel wall properties of the aorta were measured with the use of
pulse-wave velocity as described below. Vessel wall properties of the
right brachial artery were measured with a vessel wall movement
detector system.20 This device measures accurately
diastolic diameter (D) and change in diameter during the
heart cycle (D). All measurements were made by the same observer.
The mean of 3 consecutive measurements (15 heart beats) were taken
as the patient’s reading.
Brachial artery compliance was expressed as compliance coefficient (CC)
and was defined as the compliance per unit of length (L), which is the
change in cross-sectional area (A) per unit of pressure (P).
Likewise, brachial artery distensibility was expressed as
distensibility coefficient (DC), defined as the relative change in
cross-sectional area (A/A) of the vessel per unit of pressure.
Simultaneously with the vascular measurements, blood
pressure was measured at the left arm with a semiautomated device
(Dinamap). Pulse pressure was calculated as SBP-DBP. P during the
heart cycle equals pulse pressure.
From D, D, and P, brachial artery wall properties were calculated
by use of the following equations:
 | (1) |
 | (2) |
The vessel wall movement detector system also calculates the
delay time from the ECG trigger (R-top) to the 10% level of the
ascending limb of the distension waveform of the artery measured. The
difference between the delay times to the femoral and carotid arteries
was used as an estimate of the carotid-femoral transit time (T). The
mean of 3 recordings was taken as the subject’s reading. The
distances from the sternal notch to the site of measurement of the
common carotid artery and femoral artery were measured with a tape
measure. The difference between these 2 distances was used as an
estimate of the length of the carotid-femoral segment
(Lao).21 The average pulse-wave
velocity (PWV) in this segment was calculated as
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=blood density (Moens
Korteweg23,24).
Database management and statistical analyses were performed
with SAS software (SAS Institute Inc). The methods of analysis
included Mann-Whitney U tests for continuous variables
and 
2 tests for the dichotomous
parameters. To test the influence of gender, an ANCOVA was
used with factors for mean arterial pressure (measured by
sphygmomanometer), pulse rate, body mass index, smoking, use of
alcohol, and antihypertensive treatment. Factors with a value of
P>0.10 were dropped from the model. To get the relation
between vessel wall properties and age, age was also added as a
covariate. To investigate the difference of the age effect among the
sexes, the interaction of age and sex was also tested. A value of
P<0.05 was considered statistically significant.
The study was approved by the ethics committee of Leuven University, and all subjects gave their written informed consent.
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Results |
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The subjects, 250 men and 248 women, were 50±13 years old, with a range from 26 to 82 years (Table 1). The distribution of age was similar among men and women: 6.0% were 20 through 29 years old, 16.1% 30 through 39, 31.5% 40 through 49, 23.1% 50 through 59, 16.3% 60 through 69, and 7.0% were
70 years. The conventionally measured SBP
and DBP were slightly higher in men than in women. Current smoking was
reported by 160 participants (median 15 cigarettes per day; range 1 to
70), and 113 subjects reported regular alcohol consumption (median
20 g per day; range 1 to 196). A total of 77 subjects were taking
antihypertensive treatment either in monotherapy or in combination. Of
these, 36.4% (8 men and 20 women) were taking diuretics,
57.1% (22 men and 22 women) were taking ß-blockers, 7.8% (4 men and
2 women) were taking angiotensin-converting enzyme
inhibitors, and 26.0% (13 men and 7 women) were taking
calcium antagonists.
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Differences in vessel wall properties between men and women are shown in Table 2. Because vessel wall properties can be influenced by confounders, which might differ between men and women, values were calculated and adjusted for confounders such as mean arterial pressure, pulse rate, body mass index, smoking, use of alcohol, and antihypertensive treatment. After adjustment, PWV of the aorta, a measure of aortic distensibility, was not different between men and women. Distensibility of the brachial artery was larger in women (P<0.001), but diameter and compliance of the brachial artery were smaller (P<0.001) in women compared with men.
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Descriptive analysis of the effect of age on vessel wall properties in men and women is shown in Figures 1 and 2. Figures 1a and 2a show mean±SEM values of the vessel wall properties for each 10-year age class before adjustment for confounders mentioned above. In a further step of the analysis, a linear as well as a curvilinear (ie, including both age and the quadratic term of age) model were fitted to the relations between age and large-artery wall properties for men and women separately. These analyses showed that a linear model (Table 3, unadjusted values) was sufficient to fit all age relations. The relation was also analyzed after adjusting for the confounders (Table 3, adjusted values). All individual data were recalculated according to the adjusted linear regression model and are shown in Figures 1b and 2b.
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PWV of the aorta increased with age to the same extent in both sexes. Although visual inspection of adjusted data suggests a more pronounced decrease in brachial artery distensibility in women than in men, the linear regression model could neither in men nor in women show a statistically significant change in brachial artery distensibility with age (men: P=0.76; women: P=0.61) after adjustment for confounders (Table 3). Visual inspection of the relation between age and brachial artery diameter or compliance is in accordance with the linear regression model: After adjustment for confounders (Table 3) with advancing age, brachial artery diameter increased more in women (P=0.013) than in men. Brachial artery compliance increased in women (P=0.002), whereas it remained unchanged in men.
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Discussion |
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The present study investigated whether the well-known decrease in aortic distensibility with age was also present in the muscular brachial artery and whether it was similar in men and women. Changes in vessel wall properties with age are not only the effect of aging but also can be the effect of other interrelating factors that change with age. From previous studies blood pressure, body mass index, and antihypertensive treatment have been identified25 26 27 as confounding factors. The effects of other factors, such as smoking and pulse rate, are not always clear.28 29 30 In the present study, to get the relation between vessel wall properties and age, values were adjusted for mean auscultatory blood pressure, pulse rate, antihypertensive treatment, body mass index, smoking, and use of alcohol for each gender.
Gender Differences in a Random Population
In this population sample, distensibility of the aorta did
not differ between men and women. Kupari et al,31 who
investigated men and women 36 and 37 years old, also reported a gender
independence of the aortic stiffness. Laogun and Gosling,
11 however, showed a higher aortic distensibility in women
15 to 45 years old compared with age-matched men. This contradictory
result could be due to the use of a smaller study population in the
latter study. In addition, in this study no corrections were made for
confounders such as mean arterial pressure and body mass
index, which are important determinants of large-artery properties and
often differ between men and women. Also in the present study, the
unadjusted data showed a higher aortic distensibility in women compared
with men. However, after adjustment there was no difference. In
contrast to the aorta, distensibility of the muscular brachial artery
was larger in women compared with men. The reason for this gender
difference is not clear. One reason could be a difference in smooth
muscle tone and vessel wall structure (elastin/collagen) between men
and women, possibly related to hormonal influences, for instance,
effects of estrogen. Constitutional differences between men and women
also might play a role. Diameter of the brachial artery was larger in
men compared with women. Other authors also showed larger diameters of
different arteries in men.10 14 15 Because the caliber of
vessels is related to body size (height and weight)16 32
and the size of women is smaller than of men, this could explain the
smaller vessel diameter in women.32 Because of the larger
diameter in men, compliance of the brachial artery was higher in men
than in women, despite the lower distensibility of the brachial
artery.
Effect of Age and Gender
Distensibility of the aorta decreased with age in both sexes to
the same extent. These results confirm earlier
studies.11 18 Several studies showed that distensibility
of another elastic artery, the carotid artery, also decreases with
age.13 18 In contrast, the present study showed that
distensibility of the muscular brachial artery was not related to age,
as already observed by Kawasaki and coworkers.18 In
addition, the present study showed that this was the case for both
men and women.
The mechanism by which aging causes a decrease in distensibility of the aorta and common carotid artery is not fully clear. Several hypotheses have been proposed. First, the fatiguing effect of cyclic stress on the elastic fibers could play a role.33 34 Aging may lead to degeneration of the elastic fibers, with stretching and remodeling of the arterial wall33 34 resulting in a loss of elasticity and a parallel increase in collagen and mucopolysaccharides. This hypothesis is supported by the observation that the decrease in distensibility with age is proportional to the increase in collagen with age.34 Degeneration of elastin fibers also may explain arterial dilation with age. This dilation is greater in elastic than in muscular arteries, as would be predicted from theory. Second, with age, vascular smooth muscle cells accumulate in the arterial wall. Third, atherosclerosis could play a role.34 35 The exact relation between atherosclerosis and arterial wall stiffness is still unclear. Besides, it has been shown that in a population without atherosclerosis, compliance decreased with age.12 Fourth, early and advanced wave reflections, seen with increasing age, could boost pulse pressure and decrease distensibility.36
In the present population sample, the diameter of the brachial artery increased with age. The results concerning changes in diameter of the brachial artery with age are not consistent in the literature. Some authors have found an increase in diameter,18 whereas others have found no relation between age and arterial diameter.14 There also appears to be a gender difference; in the present study the increase in diameter of the muscular brachial artery was more pronounced in women than in men.
Compliance of the brachial artery was not related to age in men. Surprisingly, compliance of the brachial artery increased with age. This increase was statistically significant in women but not in men. The increase in compliance of the brachial artery is caused by a larger diameter, without a statistical change in distensibility. The increase in arterial diameter with age is also found in other arteries.16 17 18 It has been suggested that the larger diameter with age is due to loss of elastic fibers in the arterial wall. Because brachial artery elasticity (reflected by distensibility) appears to be not significantly changed with age, an alternative explanation could be an adaptive remodeling of the brachial artery. If this latter hypothesis is true, then this adaptive remodeling of the brachial artery with age may be more pronounced in women than in men.
In conclusion, this study confirms that distensibility of the aorta, an elastic artery, decreases with age. This study shows that (1) in contrast to the aorta, after adjustment for confounding factors, in both men and women no relation exists between age and distensibility of the muscular brachial artery. (2) Brachial artery diameter increase with age is more pronounced in women than in men. (3) In contrast to the well-known decrease in arterial compliance of elastic arteries with age, brachial artery compliance is not decreased with age but even increased in women. (4) The effect of age on large-artery wall properties is not uniform but depends on gender and vascular territory.
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Acknowledgments |
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The PheeCad study was supported by the municipality Hechtel-Eksel (Belgium), the National Fund for Medical Research Vlaanderen, the International Lead Zinc Research Organization (Research Triangle Park, NC), and the 1995 Schwarz Pharma (Mannheim, Germany) Research Grant awarded to Jan Staessen. The PheeCad study would not have been possible without the collaboration of the General Practitioners. The field work was coordinated by Sylvia Van Hulle and conducted with the assistance of Odette Bomans, Lieve Gijsbers, Alida Hermans, Marie-Jeanne Jehoul, Yvette Toremans, and Renilde Wolfs. The statistical analysis was conducted by Bart van Baelen.
Received March 9, 1999; first decision April 12, 1999; accepted October 7, 1999.
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 P.H. Whincup, J.A. Gilg, A.E. Donald, M. Katterhorn, C. Oliver, D.G. Cook, and J.E. Deanfield Arterial Distensibility in Adolescents: The Influence of Adiposity, the Metabolic Syndrome, and Classic Risk Factors Circulation, September 20, 2005; 112(12): 1789 - 1797. [Abstract] [Full Text] [PDF]
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G. Schillaci, M. Pirro, G. Vaudo, M. R. Mannarino, G. Savarese, G. Pucci, S. S. Franklin, and E. Mannarino Metabolic Syndrome Is Associated With Aortic Stiffness in Untreated Essential Hypertension Hypertension, June 1, 2005; 45(6): 1078 - 1082. [Abstract] [Full Text] [PDF]
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R. S. Reneman, J. M. Meinders, and A. P.G. Hoeks Non-invasive ultrasound in arterial wall dynamics in humans: what have we learned and what remains to be solved Eur. Heart J., May 2, 2005; 26(10): 960 - 966. [Abstract] [Full Text] [PDF]
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G. de Simone, S. R. Daniels, T. R. Kimball, M. J. Roman, C. Romano, M. Chinali, M. Galderisi, and R. B. Devereux Evaluation of Concentric Left Ventricular Geometry in Humans: Evidence for Age-Related Systematic Underestimation Hypertension, January 1, 2005; 45(1): 64 - 68. [Abstract] [Full Text] [PDF]
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 F. Wiesmann, S. E. Petersen, P. M. Leeson, J. M. Francis, M. D. Robson, Q. Wang, R. Choudhury, K. M. Channon, and S. Neubauer Global impairment of brachial, carotid, and aortic vascular function in young smokers: Direct quantification by high-resolution magnetic resonance imaging J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2056 - 2064. [Abstract] [Full Text] [PDF]
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Z. Lenard, P. Studinger, B. Mersich, L. Kocsis, and M. Kollai Maturation of Cardiovagal Autonomic Function From Childhood to Young Adult Age Circulation, October 19, 2004; 110(16): 2307 - 2312. [Abstract] [Full Text] [PDF]
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 M. E. J. Lott, M. D. Herr, and L. I. Sinoway Effects of age on brachial artery myogenic responses in humans Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2004; 287(3): R586 - R591. [Abstract] [Full Text] [PDF]
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G. F. Mitchell, H. Parise, J. A. Vita, M. G. Larson, E. Warner, J. F. Keaney Jr, M. J. Keyes, D. Levy, R. S. Vasan, and E. J. Benjamin Local Shear Stress and Brachial Artery Flow-Mediated Dilation: The Framingham Heart Study Hypertension, August 1, 2004; 44(2): 134 - 139. [Abstract] [Full Text] [PDF]
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G. F. Mitchell, H. Parise, E. J. Benjamin, M. G. Larson, M. J. Keyes, J. A. Vita, R. S. Vasan, and D. Levy Changes in Arterial Stiffness and Wave Reflection With Advancing Age in Healthy Men and Women: The Framingham Heart Study Hypertension, June 1, 2004; 43(6): 1239 - 1245. [Abstract] [Full Text] [PDF]
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A. U. Ferrari, A. Radaelli, and M. Centola Invited Review: Aging and the cardiovascular system J Appl Physiol, December 1, 2003; 95(6): 2591 - 2597. [Abstract] [Full Text] [PDF]
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A. D. Stewart, S. C. Millasseau, M. T. Kearney, J. M. Ritter, and P. J. Chowienczyk Effects of Inhibition of Basal Nitric Oxide Synthesis on Carotid-Femoral Pulse Wave Velocity and Augmentation Index in Humans Hypertension, November 1, 2003; 42(5): 915 - 918. [Abstract] [Full Text] [PDF]
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G. F. Mitchell, Y. Lacourciere, J.-P. Ouellet, J. L. Izzo Jr, J. Neutel, L. J. Kerwin, A. J. Block, and M. A. Pfeffer Determinants of Elevated Pulse Pressure in Middle-Aged and Older Subjects With Uncomplicated Systolic Hypertension: The Role of Proximal Aortic Diameter and the Aortic Pressure-Flow Relationship Circulation, September 30, 2003; 108(13): 1592 - 1598. [Abstract] [Full Text] [PDF]
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 J. D. Cameron, C. J. Bulpitt, E. S. Pinto, and C. Rajkumar The Aging of Elastic and Muscular Arteries: A comparison of diabetic and nondiabetic subjects Diabetes Care, July 1, 2003; 26(7): 2133 - 2138. [Abstract] [Full Text] [PDF]
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 H. J. Willens, W. Davis, D. M. Herrington, K. Wade, K. Kesler, S. Mallon, W. V. Brown, J. H. C. Reiber, and J. K. Raines Relationship of Peripheral Arterial Compliance and Standard Cardiovascular Risk Factors Vascular and Endovascular Surgery, May 1, 2003; 37(3): 197 - 206. [Abstract] [PDF]
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R. Dammers, F. Stifft, J. H. M. Tordoir, J. M. M. Hameleers, A. P. G. Hoeks, and P. J. E. H. M. Kitslaar Shear stress depends on vascular territory: comparison between common carotid and brachial artery J Appl Physiol, February 1, 2003; 94(2): 485 - 489. [Abstract] [Full Text] [PDF]
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M. Frick, S. P. Schwarzacher, H. F. Alber, A. Rinner, H. Ulmer, O. Pachinger, and F. Weidinger Morphologic rather than functional or mechanical sonographic parameters of the brachial artery are related to angiographically evident coronary atherosclerosis J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1825 - 1830. [Abstract] [Full Text] [PDF]
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 S. A. Hope, D. B. Tay, I. T. Meredith, and J. D. Cameron Comparison of generalized and gender-specific transfer functions for the derivation of aortic waveforms Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1150 - H1156. [Abstract] [Full Text] [PDF]
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C. Giannattasio, F. Achilli, M. Failla, A. Capra, A. Vincenzi, F. Valagussa, and G. Mancia Radial, carotid and aortic distensibility in congestive heart failure: effects of high-dose angiotensin-converting enzyme inhibitor or low-dose association with angiotensin type 1 receptor blockade J. Am. Coll. Cardiol., April 17, 2002; 39(8): 1275 - 1282. [Abstract] [Full Text] [PDF]
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I. B. Wilkinson, D. J. Webb, J. R. Cockcroft, S. Kinlay, P. Ganz, and M. A. Creager Nitric Oxide and the Regulation of Arterial Elasticity: Right Idea, Wrong Vascular Bed? Hypertension, April 1, 2002; 39 (4): e26 - e27. [Full Text] [PDF]
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D. R. Kaiser, K. Mullen, and A. J. Bank Brachial Artery Elastic Mechanics in Patients With Heart Failure Hypertension, December 1, 2001; 38(6): 1440 - 1445. [Abstract] [Full Text] [PDF]
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C. Vlachopoulos, K. Hirata, and M. F. O'Rourke Pressure-Altering Agents Affect Central Aortic Pressures More Than Is Apparent From Upper Limb Measurements in Hypertensive Patients: The Role of Arterial Wave Reflections Hypertension, December 1, 2001; 38(6): 1456 - 1460. [Abstract] [Full Text] [PDF]
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 K. A Dettwyler, W. Holmes, T. Greiner, J. Sikorski, C. Dezateux, A. Holt, I. B Wilkinson, J. R Cockcroft, P. M. Dark, M.-J. Rolli, et al. Duration of breast feeding and adult arterial distensibility BMJ, September 22, 2001; 323(7314): 689 - 689. [Full Text]
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K. Sevre, J. D. Lefrandt, G. Nordby, I. Os, M. Mulder, R. O. B. Gans, M. Rostrup, and A. J. Smit Autonomic Function in Hypertensive and Normotensive Subjects : The Importance of Gender Hypertension, June 1, 2001; 37(6): 1351 - 1356. [Abstract] [Full Text] [PDF]
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H. Smulyan, R. G. Asmar, A. Rudnicki, G. M. London, and M. E. Safar Comparative effects of aging in men and women on the properties of the arterial tree J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1374 - 1380. [Abstract] [Full Text] [PDF]
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A. Benetos, K. Okuda, M. Lajemi, M. Kimura, F. Thomas, J. Skurnick, C. Labat, K. Bean, and A. Aviv Telomere Length as an Indicator of Biological Aging : The Gender Effect and Relation With Pulse Pressure and Pulse Wave Velocity Hypertension, February 1, 2001; 37(2): 381 - 385. [Abstract] [Full Text] [PDF]
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