Age-Related Changes in Total Arterial Capacitance From Birth to Maturity in a Normotensive Population
Abstract We evaluated the effect of body growth and aging on the ratio of echocardiographic (Teichholz) stroke volume to pulse pressure (SV/PP ratio) in 373 normal-weight, normotensive children to adolescents (1 day to 17 years old; 166 girls, 87 nonwhite) and 393 normal adults (17 to 85 years old; 164 women, 112 nonwhite). Stroke volume increased with age in children (r=.64, P<.0001) and was stable in adults; pulse pressure decreased slightly with age in children (r=−.10, P=.06) and increased in adults (r=.29, P<.0001). As a consequence, SV/PP ratio increased with age in children (r=.51, P<.0001) and decreased in adults (r=−.18, P=.0004). To control for changes in body size that influence the size of the arterial tree, we used ANCOVA to adjust SV/PP for body size. Body size–adjusted SV/PP ratio was no longer related to age in children, whereas the negative relation with aging in adults remained statistically significant (r=−.19, P<.0002). Heart rate was negatively related to SV/PP ratio in both children and adolescents and adults, but this relation did not influence the relation with age. In multivariate analysis, high SV/PP ratio was predicted by greater height (P<.002) and weight (P<.04) and nonwhite race (P<.001) in children and adolescents and by younger age (P<.0001), greater weight (P<.0001), and low heart rate (P<.001) in adults. Sex did not enter the regression models. Thus, (1) SV/PP ratio is a measure of increasing capacity of the arterial tree during growth, whereas it depends on arterial compliance during adulthood through old age; (2) arterial compliance decreases progressively with aging; (3) the apparent difference between males and females might be due to their different body sizes.
The capacity of the arterial tree to receive blood pumped with each heart beat is related both to its ability to distend for a given pressure and to its size. Thus, the increase in pulse pressure for a given stroke volume is directly related to vascular stiffness.1 The ratio between stroke volume and pulse pressure (SV/PP ratio) has been proposed as a crude measure of total arterial compliance.2 3
Arterial compliance is an important component of the resistance to ejection, of myocardial afterload, and of the consequent geometric modifications of the left ventricle.4 5 6 It has been demonstrated that arterial compliance decreases with aging in adults,7 8 but there is little information about the physiological evolution of arterial compliance during the different phases of human life from birth to old age in females and males. Accordingly, we designed this study to investigate the relation of the SV/PP ratio and its physiological meaning in an age span encompassing the entire human life.
Seven hundred sixty-six normal-weight, normotensive individuals, aged 1 day to 85 years, were studied at three centers: 212 men and 138 women from a cohort of employed adults evaluated at the New York Hospital–Cornell Medical Center; 139 boys and 127 girls as part of a population-based epidemiological study at the Children’s Hospital, University of Cincinnati; and 69 boys, 42 girls, 16 men, and 23 women as part of population-based studies at Federico II University of Naples, Italy. Among the 766 subjects, 393 were older than 17 years, and 330 were female (166 children to adolescents and 164 adults). Among the 373 children and adolescents, 286 were white (126 females), 86 were black (40 females), and 1 boy was Hispanic. Among the 393 adults, 281 were white (103 women), 78 were black (41 women), 19 were Hispanic (10 women), 10 were Asian (8 women). and 5 were Native Americans (2 women).
All participants had blood pressures (BPs) that were consistently normal, according to traditional clinical criteria for adults (<140/90 mm Hg) and according to the definition of hypertension in children based on age, sex, and height presented by Rosner et al9 for American children and by the Italian Blood Pressure Tables of the Italian Society of Pediatrics for Italian children who have been reported to have higher average BP than children of the same age from other European countries.10 Children younger than 1 year old were assumed to have normal BP when systolic and diastolic pressures were lower than 101/55 mm Hg (the 95th percentile of BP values in 1-year-old boys at the 25th percentile of height).9 All participants were also normal-weight according to the 1985 National Institutes of Health Consensus Conference11 or the Himes and Dietz simplified criteria for children.12
Informed consent was obtained from all adult volunteers and from parents or guardians of children under protocols approved by the Institutional Review Boards for Research in Human Subjects in the United States and the Ethics Committee of Federico II University Hospital in Naples. Because the echocardiographic study in Italy was performed in a school site, formal approval by the School Authority was also required.
Two-dimensionally targeted M-mode echocardiograms were performed as previously described,13 with the subjects in a partial left decubitus position and in held expiration when possible, using commercially available echocardiographs. Tracings were recorded on strip-chart paper at 50 mm/s, coded, and interpreted blindly in each center. Measurements of interventricular septal thickness, posterior wall thickness, and left ventricular (LV) dimensions were taken at or just below the mitral valve tips, by the leading edge–to–leading edge method, according to recommendations of the American Society of Echocardiography.14 Segmental wall motion abnormalities were excluded by two-dimensional echocardiographic recording in multiple standard projections. LV end-diastolic and end-systolic volumes were calculated with the Teichholz correction of the cube formula.15 LV chamber volumes and stroke volume determined with this approach have been shown to correlate well with invasive and two-dimensional and Doppler echocardiographic volume measurements in a variety of populations with symmetric LV wall motion.16 BP was recorded at the end of the echocardiographic examination with an arm-cuff sphygmomanometer and appropriately sized cuffs for children and infants. BP values were used to calculate pulse pressure as the difference between systolic and diastolic values. Stroke volume was therefore divided by pulse pressure (SV/PP ratio) to provide a measure of total systemic arterial compliance.
Because Italian children had BP values slightly higher than same-age American children, analyses have been adjusted for “center effect” using the following procedure: Primary echocardiographic measurements (end-diastolic and end-systolic LV internal dimension and wall thickness), BP, and heart rate were related as dependent variables to a dichotomous variable representing the center in age-matched groups of subjects. Thus, Italian children were combined with Cincinnati children in the same age range (6 to 11 years) and Italian adults were combined with New York adults in the same age range (20 to 69 years), and dependent variables were related to the dummy variable indicating the center (1 or 2). The variables considered in this preliminary analysis were therefore adjusted using the linear coefficient of regression (b). Thus the adjusted variable (adjV) was adjV=V−b(x−μ), where V is the observed value of the dependent variable, x is the dummy variable representing the center, and μ is the average value of the variable representing the centers. When needed, this approach was also used to adjust SV/PP ratio to body size or heart rate.
Data are expressed as mean±SD. For categorical variables, χ2 statistics was used. One-factor ANOVA was used to detect between-group differences. Least-squares linear regression was used to assess univariate relations. ANCOVA was used to control for confounders. The SV/PP ratio was adjusted for relevant correlates using regression coefficients as indicated above. To compare the rates of change in SV/PP ratio, pulse pressure, and stroke volume with age, the slopes of the age-specific regression lines were examined after standardization of variables to a mean of 1 and an SD corresponding to the coefficient of variability of the original variables.17 With this approach, the slopes of the lines relating SV/PP ratio, pulse pressure, and stroke volume to age could be compared with F statistics based on between-slopes sum of squares.
Stepwise multiple regression analysis was used to study the independent correlate of the SV/PP ratio, by considering variables initially identified as having statistically significant relations to the SV/PP ratio in univariate analyses. F to enter and F to remove were set to P<.05 and P<.10, respectively. Sex was treated as a dummy variable by assigning 1 to males and 2 to females. Race was also treated as a dichotomous variable (white=1 and nonwhite=2). A two-tailed value of P≤.05 was considered statistically significant, but higher P values also are reported.
Table 1⇓ shows the demographic characteristics of this study population. All individuals were, by inclusion criteria, of normal weight and normotensive.
Effect of Body Growth on SV/PP Ratio
In children and adolescents, stroke volume increased with age (Fig 1⇓, top, P<.0001), whereas pulse pressure tended to decrease slightly (Fig 1⇓, bottom, P=.06). As a consequence, SV/PP ratio markedly increased with age from birth to adolescence (Fig 2⇓, top, P<.0001). This increase was completely due to body growth, as the relations became flat when the SV/PP ratio was adjusted for mean values of body weight and height (Fig 2⇓, bottom).
The relation between SV/PP ratio and age was close in the 188 children up to 10 years old (r=.56, SEE=0.31 mL/beat/mm Hg, P<.0001), with an increase of 0.11 mL/beat/mm Hg per year. This was more than twofold greater than the increase in SV/PP ratio detected in the 183 children and adolescents 11 to 17 years old (0.05 mL/beat/mm Hg per year; r=.20, SEE=0.5 mL/beat/mm Hg, P<.0002; slope difference: P<.001). The increase in SV/PP ratio with age was significantly closer in white (r=.53, P<.0001, y=0.42+0.07x) than nonwhite (r=.24, P<.02, y=0.97+0.04x; between-slope difference: P=.051) children and adolescents.
The rate of change of SV/PP ratio with age was significantly higher (standardized slope=1.48) than the change in the inverse of pulse pressure (standardized slope=0.22; between-slope difference: P<.0001), whereas it was not statistically different from the rate of change in stroke volume (standardized slope=1.26).
Effect of Aging on SV/PP Ratio in Adults
In adults, stroke volume was not related to age (r=.01, P=.9, Fig 3⇓, top), whereas pulse pressure increased significantly (r=.29, SEE=8 mm Hg, P<.0001, Fig 3⇓, bottom). The SV/PP ratio was therefore negatively related to age from 18 to 85 years (Fig 4⇓, top, P<.0001), with parallel regression lines in women and men. In contrast with findings in children and adolescents, this decrease was independent of the variance of body size in the population, as demonstrated by the persistence of relation between the body size–adjusted SV/PP ratio and age (Fig 4⇓, bottom). White and nonwhite adults exhibited similar regression lines (r=−.16, P<.008, y=1.89−0.005x in whites; r=−.26, P<.006, y=1.99−0.009x in nonwhites). The negative relation detected in the entire group was due to a faster reduction of SV/PP ratio with age in the 123 adults older than 50 years (0.02 mL/beat/mm Hg per year, r=−.32, SEE=0.39 mL/beat/mm Hg, P<.0003), whereas the regression line was actually flat in the 270 adults between 18 and 50 years of age (r=.08, P=.2).
The rate of change of SV/PP ratio with age was similar (standardized slope=−0.12) to the change in the inverse of pulse pressure (standardized slope=−0.11; between-slope difference: P=.89), whereas it was statistically higher than the rate of change in stroke volume (standardized slope=−0.005; between-slope difference: P=.01).
Influence of Heart Rate on SV/PP Ratio
Heart rate was inversely related to SV/PP ratio. This relation was steeper in children and adolescents (reduction of 0.10 mL/beat/mm Hg for each increase in heart rate of 10 beats per minute; r=−.33, P<.0001) than in adults (reduction of 0.05 mL/beat/mm Hg for each increase in heart rate of 10 beats per minute; r=−.18, P<.007; slope difference: P<.02). The SV/PP ratio was adjusted to the age group–specific average heart rate using the age-specific coefficient of regression. After heart rate adjustment, the SV/PP ratio remained positively related to age in children and adolescents (r=.34, P<.0001) and negatively related to age in adults (r=−.18, P<.0003).
Sex Differences in SV/PP Ratio
Although the SV/PP ratio changed similarly with age in males and females, in either age group (Figs 2⇑ and 4⇑), the average values were higher in adult men than women (Table 2⇓ and Fig 5⇓). This difference persisted when the SV/PP ratio was adjusted for heart rate (P<.0001) but was eliminated after the SV/PP ratio was adjusted for weight and height or after the use of stroke volume normalized for body surface area (Table 2⇓). No sex differences were detected in children and adolescents up to 17 years of age.
To better investigate the interrelations between sex, race, age, and body size, we examined the correlates of the SV/PP ratio by multiple linear regression models in each age stratum. In children and adolescents, the SV/PP ratio was independently associated with greater height (Ht, β=0.32, P<.002) and body weight (BW, β=0.22, P<.03) and with nonwhite race (β=0.15, P<.001); the regression equation was SV/PP Ratio=0.70·Ht+0.007·BW+0.18·Race−0.26±0.39 mL/beat/mm Hg (multiple R2=.36, P<.0001). Age, sex, and heart rate did not enter the model.
In adults, the SV/PP ratio was independently related to higher body weight (β=0.41, P<.0001), younger age (β=−0.21, P<.0001), and lower heart rate (HR, β=−0.15, P<.01); the regression equation was SV/PP Ratio=0.015·BW−0.007·Age−0.006·HR+1.27±0.36 mL/beat/mm Hg (multiple R2=.22, P<.0001). Body height, sex, and race did not enter the model.
The SV/PP ratio has been proposed as an approximate measure of arterial compliance2 3 based on the principle that the arterial tree can be modeled as an elastic chamber with a constant compliance (two-element Windkessel model). In this model, the blood flow from the heart in systole (stroke volume) produces an increase in arterial pressure. The simplicity of such an assumption is questionable, but recently, measurements of arterial compliance based on the two-element Windkessel model have been shown to be more accurate than measurements based on the three-element Windkessel model (a model taking into account also the characteristic ascending aortic impedance, placed proximally to the two-element Windkessel model).18 The present study demonstrates that the SV/PP ratio identifies the expected age-related changes in total arterial compliance in adults, when physiological body growth is complete, and reveals an increase in the absolute capacitance of the arterial tree in children and adolescents during body growth.
SV/PP Ratio in Children and Adolescents
During body growth, stroke volume increases markedly with age in boys and girls. In a system with a constant size and compliance, pulse pressure should increase concomitant with the increase in stroke volume. In children, pulse pressure does not change with increasing age; in fact, we observed a weak trend toward a decrease of pulse pressure during childhood and adolescence. The marked increase in SV/PP ratio can therefore be attributed to an age-related increase in “arterial capacitance” caused by the increasing body size and parallel growth in the arterial tree, which increases its internal volume (capacitance). As a consequence, adjustment for body height and weight completely eliminated the positive relation between age and SV/PP ratio in children and adolescents (Fig 2⇑, bottom).
SV/PP Ratio in Adults
When body growth is complete, total arterial compliance is the result of the ability of the arterial tree to distend in relation to a given input of blood flow. Whereas a reduction of this ability has been documented during adulthood,5 7 8 19 20 this reduction became evident after age 50 in the present normal-weight, normotensive study population (Fig 5⇑). In early adulthood, between 18 and 50 years, age did not affect the SV/PP ratio. Men and women exhibited the same behavior compared with aging, although average values were lower in women than men.5 19 21 22 We found that this sex difference was eliminated when body size was considered as a covariate, suggesting that the reduced SV/PP ratio in women compared with men might be at least partly due to the smaller body size in women; stepwise regression also suggested that body proportions might be more important than sex in explaining the magnitude of the SV/PP ratio in adults. A potential explanation for the apparent effect of body size on SV/PP ratio is the known parallelism between body size and the size of the aorta23 24 and of medium-sized capacitance vessels (eg, common carotid artery).25 However, the SV/PP ratio is a pure hemodynamic parameter, reflecting the compliance of the arterial tree for that given stroke volume. Although in our subjects, indexation of stroke volume for body surface area eliminated the difference between normal men and women (the SVi/PP ratio), this observation does not establish whether it is physiologically appropriate or potentially misleading to index stroke volume for body surface area for incorporation into the ratio. Unless the size of the arterial tree closely parallels the chosen measure of body size, normalizing stroke volume in adults might actually yield a less accurate estimate of arterial compliance. Further research on this question is needed.
The SV/PP ratio is an easy-to-calculate, approximate index of total arterial capacitance that may be useful in epidemiological studies. The ratio increases during body growth because of the increased size of the arterial tree; remains stable during early adulthood, after the end of body growth; and decreases during late adulthood to old age because of a decrease in arterial compliance. After adjustment for body size, no difference could be detected between adult men and women. Race does not influence the SV/PP ratio in adults, whereas in children and adolescents, the increase of the ratio with body growth is faster in white than nonwhite individuals.
This work was supported in part by grants HL-18323, HL-30605, HL-47540, and HL-34698 from the National Heart, Lung, and Blood Institute, Bethesda, Md, and by grant MURST-158-1993 and 1994 of the Ministry of University and Research, Italy.
- Received September 3, 1996.
- Revision received October 8, 1996.
- Accepted November 29, 1996.
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