Influence of Sex on Arterial Hemodynamics and Blood Pressure
Role of Body Height
Abstract Systolic pressure is lower in premenopausal women than in age-matched men, but underlying alterations are not well characterized. Aging and body size alter arterial function, influencing pressure wave propagation and amplification in peripheral and central arteries. To assess the possibility that systolic pressure differences in women are related to smaller body size, we studied arterial function in 119 men and 104 women. Premenopausal and postmenopausal women were compared with age-matched men. The following parameters were measured: ankle-arm pressure index (Doppler), aortic and arterial distensibility (pulse wave velocity), systolic pressure and the effect and time delay of arterial wave reflections in the common carotid artery (applanation tonometry), and diameters of the abdominal aorta and aortic bifurcation and their ratio (aortic tapering, echography). Premenopausal women had lower brachial (P<.05) and ankle (P<.01) systolic pressures than age-matched men, whereas the ankle-arm pressure index was higher in men (P<.01). In the overall population the ankle-arm index was positively correlated with body height (P<.001). Carotid systolic pressure was similar in women and men, with an increased effect and earlier return of wave reflections in women (P<.01). The effect of wave reflections was inversely correlated with body height (P<.001) and positively associated with aortic tapering (P<.001), which was increased in women (P<.01). In premenopausal women the distensibility of brachial and femoral arteries was higher than in age-matched men (P<.01), whereas aortic distensibility was not different. Postmenopausal women had arterial distensibility similar to that of age-matched men but still had an increased effect of wave reflections. This study shows that body height is positively correlated with systolic pressure amplification from central to peripheral arteries and inversely correlated with the effect of wave reflections in central arteries. Shorter body height in women results in less peripheral systolic pressure amplification, with lower peripheral but not central systolic pressure. Greater arterial distensibility in premenopausal women partially offsets the effects of shorter body height. After menopause, arterial distensibility is similar to that of age-matched men and does not compensate for smaller body size, resulting in a persisting increased effect of wave reflections in central arteries.
In most industrialized populations SBP increases with age,1 although to a different degree in each sex. In younger, premenopausal women SBP is lower than in men of similar age, whereas after menopause it tends to be higher than in age-matched men. It has been shown that the incidence of cardiovascular complications increases with SBP1 2 3 4 and that an increase in the pulsatile components of blood pressure is associated with higher cardiovascular risk in postmenopausal women.5 The mechanisms associated with the sex differences in SBP and pressure pulsatility are poorly understood. The lower SBP and the lower incidence of atherosclerotic diseases and ischemic cardiovascular events in premenopausal women suggest a role for the steroid sex hormones in vascular protection and arterial function. Several studies have shown that vascular smooth muscle cells contain functional estrogen receptors6 7 and that estrogens have short-term vascular effects, potentiating endothelium-dependent vasodilation in conductive and resistive arteries of postmenopausal women8 9 10 and decreasing arterial pulsatility and increasing arterial compliance.11 12 However, SBP and PP are influenced by the pattern of left ventricular ejection and aortic input impedance, principally via the distensibility of large arteries and the intensity and timing of AWRs.13 14 15 Although alterations in arterial distensibility influence SBP in the entire arterial tree, AWRs influence principally SBP and PP in the aorta and central arteries. Studies in humans have shown that body height and arterial PWV are important determinants of the effect of AWRs on SBP and PP amplitude in central arteries16 17 18 19 and on ventricular/vascular coupling.13 15 Therefore, some of the sex-related differences in blood pressure regulation and hemodynamics could be related to the generally smaller body size of women. The purpose of the present study was to analyze the respective influences of sex, body size, and menopause on arterial properties, blood pressure regulation, and ventricular/vascular coupling.
The study included 223 subjects (119 men, 104 women) with no history of cardiovascular disease. Fifty-five subjects were classified as hypertensive, blood pressure >160 (SBP) and/or 90 (DBP) mm Hg on three different occasions. These hypertensive subjects had not been treated and did not receive antihypertensive medications during the study. Subjects were divided into six groups: premenopausal normotensive women (n=44) and age-matched normotensive men (n=40), postmenopausal normotensive women (n=40) and age-matched normotensive men (n=44), and premenopausal hypertensive women (n=20) and age-matched hypertensive men (n=35). Postmenopausal women did not receive hormone replacement therapy. Each subject provided written consent for the study, which had been approved by our institutional review board.
Blood pressure was measured with a mercury sphygmomanometer and cuff adapted to arm circumference after at least 15 minutes of recumbency. The appearance of Korotkoff sounds was taken to be the SBP and their point of disappearance (phase V) the DBP. Because of intersubject variability in the morphology of peripheral arterial pressure waves, MBP was determined by planimetry of the radial artery pressure wave contour recorded by applanation tonometry, as previously described.17 The pressure wave was calibrated to the sphygmomanometric values of SBP and DBP, and MBP was computed from the area of the pressure waveform in the corresponding HP with the use of a Sketch Pro Tablet Digitizer (Hewlett-Packard Co) and a Z-425/SX computer (Zenith Data Systems).
Ankle-Arm Pressure Index
Ankle and arm SBPs were measured simultaneously at the posterior tibial and brachial arteries at both left and right sites with an M842 8-MHz Doppler unit (Sociéte d’Electronique Générale et Appliquée [SEGA]) and a sphygmomanometer with an adapted cuff size. SBP was measured three times on each side with subjects in the supine position. The ratio of SBP at the ankle to that at the arm (ankle-arm pressure index) was calculated for each side; the lower value was used in the study. Subjects with an index less than 0.9 were not included for suspicion of lower limb arterial occlusion, and those with an index greater than 1.3 were excluded because of possible arterial “incompressibility” caused by medial calcifications.20
PWV was determined with the use of the foot-to-foot method.21 Transcutaneous Doppler flow velocity recordings were carried out simultaneously at the base of the neck over the common carotid artery and the femoral artery in the groin (aortic PWV), at the femoral and dorsalis pedis arteries (femoral PWV), and at the carotid and radial arteries (brachial PWV), with a SEGA M842 8-MHz Doppler unit and an 8188 recorder (Gould Electronique). The time delay (t) was measured between the feet of the flow waves recorded at these different points. The distance traveled by the pulse wave was measured over the body surface with a tape measure as the distance between the two recording sites minus that from the suprasternal notch to the carotid (D). PWV was calculated as D/t.21
Carotid Pressure Waveform
The aortic or central artery PP waveform in humans is generally known to manifest an inflection point (Pi) that divides the pressure waveform into early and mid-to-late (Ppk) systolic peaks22 23 (Fig 1⇓). This pressure waveform consists of both a forward or incident wave and a backward or reflected wave.22 23 24 25 Ppk is taken to be the result of the reflected wave returning from peripheral sites and causing an increase in SBP and PP. This increase is the height of Ppk above Pi (ΔP) and the ratio of ΔP to PP (Aix; ΔP/PP, as a percent) represent the effect of wave reflections on the central arterial pressure wave.22 23 24 25 The Δtp value represents the travel time of the pulse wave to peripheral reflecting sites and back23 24 25 (Fig 1⇓).
The common carotid artery pressure waveform and amplitude were recorded noninvasively with a pencil-type probe17 24 25 incorporating a high-fidelity strain-gauge transducer in the tip of the probe (model SPT-301, Millar Instruments). The strain-gauge transducer possesses a small pressure-sensitive ceramic sensor (0.5×1.0 mm) incorporating piezoresistive elements forming two arms of a Wheatstone bridge. The frequency response of the sensor is greater than 2 kHz coplanar with a larger area (7-mm diameter) of flat surface, in contact with the skin overlying the arterial pulse. The tonometer is internally calibrated (1 mV=1 mm Hg) with the use of a conventional preamplifier (TCB-500, Millar Instruments). Waveforms were recorded on a Gould 8188 recorder at 100 or 200 mm/s. The contour of the carotid pressure wave was described according to Murgo et al.22 The following parameters were measured: pulse pressure (PP), early systolic peak (Pi), late systolic peak (ΔP=Ppk−Pi), Aix (as ΔP/PP, as a percent), and Δtp (in milliseconds). HP (in milliseconds) was measured between the foots of the successive pressure waves, and LVET (in milliseconds) was measured from the foot of the pressure wave to the diastolic incisura. Analysis was done by visual inspection by two independent observers with, for Aix, an interobserver SD of difference of 2.1% (ie, percentage of the mean value).26 SBP and PP may increase significantly from central to peripheral arteries. This contrasts with DBP and MBP whose pressure drops from the ascending aorta to the radial artery do not exceed 2 to 3 mm Hg.13 14 15 Therefore, carotid SBP and PP were estimated from the carotid pressure waveform, assuming that brachial and carotid DBP and MBP were equal, with the use of the HP Sketch Pro Tablet Digitizer and Zenith Z-425/SX computer. Carotid MBP on carotid pulse pressure tracing was computed from the area of the carotid pressure waveform in the corresponding HP and set equal to brachial MBP.27 Tonometric recordings showed a pressure wave with harmonic content close to that recorded intra-arterially, and previous studies in humans have also shown close relations between PP amplitude recorded by tonometry and pressures recorded by sphygmomanometry in the brachial artery or by Millar catheters in the central aorta.17 25 28
Determination of Aortic Diameters
AoDren and AoDbif were measured with a Sonel 300 ultrasound device (Compagnie Générale de Radiologie) using 3-MHz transducers. Good-quality measurements were obtained in 102 subjects. Measurements were performed by two observers, with an interobserver SD of ±1 mm (ie, percentage of mean value).26 Aortic tapering was determined as the ratio of AoDren to AoDbif (AoDren/AoDbif).
Data are expressed as mean±SD. ANOVA and Student’s t test with the Bonferroni adjustment when necessary were used to compare the different groups. Univariate and multivariate correlations were done using the least-squares method, and as a categorical variable sex was coded as 1 for men and 2 for women.
The differences observed between the groups of normotensive men and women are shown in Table 1⇓. Younger (premenopausal) women had lower brachial and ankle SBPs (P<.05 and P<.01, respectively) and a lower ankle-arm pressure index (P<.05) than age-matched men. In contrast, carotid artery SBP was not statistically different between younger men and women. As shown in Fig 2⇓ the increase in SBP from carotid to peripheral arteries was greater in younger men than in younger women. SBP increased with age (Table 1⇓); in postmenopausal women ankle SBP remained lower than in age-matched men (P<.05), whereas carotid and brachial pressures were not statistically different. In the overall population the ankle-arm pressure index was positively correlated with body height (P<.001, Fig 3⇓). Multiple regression analysis showed that this correlation was independent (P<.001) of brachial SBP and age and that for any given brachial SBP, the ankle SBP was correlated positively with height (P<.01). After adjustment for body height and age, the ankle-arm pressure index was still lower in women (P<.05).
Brachial and femoral PWV values were significantly lower in premenopausal women (P<.05 and P<.01, respectively), but aortic PWV was not. Multivariate analysis of the younger normotensive population showed that brachial and femoral PWVs were correlated positively with age (P<.05) and SBP (P<.001) and negatively with sex (P<.05), suggesting that smaller female arteries are more distensible for any given age or pressure within the normotensive range. PWVs increased with age (P<.01), the increase being more pronounced in women who after menopause had PWVs similar to those of age-matched men.
Carotid pulse wave analysis showed that Aix was higher (P<.01) in women than in age-matched men. Aix increased with age (P<.01) and was inversely correlated with body height (P<.001). The Δtp was shorter in women (P<.01) and, independently of sex, was correlated positively with body height (P<.001) and negatively with aortic PWV (P<.001). Heart period was longer in men (P<.01), and LVET was similar in men and women, with a shorter diastolic interval in women (P<.01). The slope of the correlation between HP and LVET was different in men and women (P<.02) (LVET=0.104×HP+203 in men, P<.001; LVET=0.145×HP+178 in women, P<.001). Diastolic interval (and HP) was positively correlated with body height (P<.001) independently of sex. LVET was positively correlated with Aix and was longer in subjects with a more pronounced effect of wave reflections (P<.01). The LVET/Δtp and fmin/f ratio (fmin=1/[2×Δtp]; f=1/HP) were increased in women (P<.01). Aortic diameters were positively correlated to body surface area (P<.001) and were decreased in women (P<.01). Aortic diameters increased with age in both sexes (P<.001). AoDren/AoDbif was negatively correlated with body surface area (P<.001, Fig 4⇓) and was greater in women, indicating a greater degree of aortic tapering in women. With aging, AoDren/AoDbif decreased but remained greater in women than in men (P<.01). In the overall population AoDren/AoDbif was correlated positively with Aix (P<.001, Fig 5⇓).
Compared with age-matched normotensive control subjects, hypertensive premenopausal women and age-matched men had decreased arterial distensibility, an increased effect of AWR on carotid pressure, and decreased ankle-arm pressure index (Table 2⇓). Sex differences in arterial hemodynamics were not influenced by blood pressure level and were still observed in the hypertensive subjects.
The results of the present study indicate that compared with age-matched men, premenopausal women have lower SBP in peripheral arteries but not central (carotid) arteries. This augmented central-to-peripheral SBP amplification in men is related to taller body height, longer distance of pulse wave propagation, and increased arterial elastic nonuniformity with decreased distensibility of peripheral arteries. The similar carotid artery SBP in women is related to an early return and increased effect of AWRs because of shorter body height, shorter distance to reflecting sites, and increased aortic tapering.
Epidemiological studies based on brachial artery pressure measurements indicate that SBP is lower in premenopausal women than in age-matched men.1 The present results indicate that sex differences vary according to the site of pressure measurement. At the ankle, the SBP difference between men and women is even greater, so that women have a lower ankle-arm pressure index.29 Pulse amplitude and SBP generally increase as a pulse travels from the aorta toward the periphery, the increase being all the more pronounced as the distance of pulse propagation increases.13 14 15 The posterior tibial artery is more distant from the ascending aorta than the brachial artery; ankle pressure amplification is therefore greater and increases with body height (Fig 3⇑). Because women are generally shorter than men, their peripheral pressure amplification is less marked with lower peripheral SBP and ankle-arm pressure index values. Amplification between central (carotid) and distal peripheral pressures is also influenced by nonuniform arterial elasticity and arterial geometry between the two sites of measurement.13 14 15 The reports in the literature indicate that between 20 and 50 years of age arterial distensibility is greater in women.30 31 Our results concerning the distensibility of peripheral arteries were in agreement with this. Nevertheless, in agreement with Vaitkevicius et al32 we did not observe a significant influence of sex on aortic PWV. Therefore, in men the decrease in arterial distensibility from the aorta toward peripheral arteries was more pronounced, increasing the elastic nonuniformity of the arterial tree.
Contrasting with peripheral SBP, carotid SBP was not different in men and women. This was due to the early return and increased effect of AWR in women, characterized by an increased Aix, shorter Δtp, and increased LVET/Δtp. Arterial distensibility (a determinant of PWV), body height, and shape (determinants of the distance and dispersion of reflecting sites) are important factors influencing the intensity and timing of AWRs.13 14 15 16 17 18 19 22 23 As arterial PWV values in men were higher or similar to those in women, the shorter Δtp in women was related to shorter body height and a shorter effective length of the arterial system. At two successive arterial segments, the reflection coefficient for the pressure wave depends on the area (diameter) and PWV ratios of their junction.13 15 33 Catheterization studies of the aorta in healthy men have shown the existence of a significant discrete reflection point located in the aortic region at the level of the renal arteries.23 The present study shows that more pronounced abdominal aortic tapering (AoDren/AoDbif ratio) was associated with a higher Aix (Fig 5⇑). Regression analysis indicated that aortic tapering was related to body size (Fig 4⇑) but remained higher in women after adjustment for body size. Thus, the greater effect of wave reflections in women was associated with shorter body height (shorter distance to reflecting sites) and altered aortic geometry (increased tapering of the abdominal aorta, with the possible existence of a discrete reflection site at this level).23
Early return of AWRs (shorter Δtp) is characteristic of a frequency shift of the first minimum of impedance modulus (fmin=1/[2×Δtp]) to higher frequencies.13 14 15 To maintain optimal ventricular/vascular coupling (fmin/f ratio), a shorter Δtp (increased fmin) should be paralleled by a shorter HP (ie, increased heart frequency, f), as occurs in small mammals.14 This was in fact observed in women, and despite these changes the fmin/f ratio remained higher than in men. As a determinant of end-systolic pressure the effect of AWRs is related to LVET, which tends to increase when AWRs increase. This was observed in premenopausal women, in whom for any given HP the LVET was longer compared with men, resulting in an increased LVET/Δtp and different HP/LVET relationship.34 35
With aging, the effect of AWRs increases and Aix increases.24 This is due to arterial stiffening and increased PWV values. These changes are partially limited by progressive increases in arterial and aortic diameters and a tendency toward less pronounced aortic tapering. In men, the vascular aging process is progressive and regular, but in women, menopause unduly accelerates this process. In premenopausal women arterial PWVs were lower and peripheral arterial distensibility greater than in age-matched men. This could be related to the specific effects of estrogens, which increase arterial distensibility.11 12 Increased arterial distensibility in these women may partially offset the effects of shorter body height. In postmenopausal women, arterial distensibility and PWV were similar to values in age-matched men, and the effect of wave reflections in central arteries was augmented. Although with aging aortic diameters increased in both sexes and aortic shape tended to be more cylindrical, increased tapering (compared with age-matched men) was still observed in postmenopausal women, increasing the effect of AWRs in this group.
Hypertension induces several alterations in arterial hemodynamics, including an increase in arterial stiffness and an early return of wave reflections. These alterations were also observed in the present study, but hypertension did not alter the sex differences in younger subjects (Table 2⇑).
In conclusion, the present study indicates that some sex differences in blood pressure are related to differences in body height. SBP amplification from central to peripheral arteries increases with body height and elastic nonuniformity and is therefore more pronounced in men. On the other hand, because of usually shorter body height in women, the effect of AWRs in central arteries is more pronounced in premenopausal women, and carotid SBP is not different between the two sexes. The greater arterial distensibility in premenopausal women partially compensates for the differences in body size. This compensatory effect is lost after menopause when sex differences in arterial distensibility disappear.
Selected Abbreviations and Acronyms
|AoDbif||=||internal aortic diameter above the bifurcation|
|AoDren||=||internal aortic diameter above the renal arteries|
|AWR||=||arterial wave reflection|
|DBP||=||diastolic blood pressure|
|LVET||=||left ventricular ejection time|
|MBP||=||mean blood pressure|
|PWV||=||pulse wave velocity|
|SBP||=||systolic blood pressure|
|Δtp||=||travel time of reflected wave|
This work was supported by Groupe d’Etude de la Physiopathologie de l’Insuffisance Rénale (GEPIR) and a grant (BIOMED) from the European Community.
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