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(Hypertension. 1995;26:1195-1199.)
© 1995 American Heart Association, Inc.
Articles |
Relationship Between Systemic Hemodynamics and Ambulatory Blood Pressure Level Are Sex Dependent
From Unidad de Hipertension Arterial, Servicio de Clinica Medica, Hospital Italiano, Buenos Aires, Argentina.
Correspondence to José Alfie, MD, Unidad de Hipertension Arterial, Servicio de Clinica Medica, Hospital Italiano, Gascon 450 (1181), Buenos Aires, Argentina.
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Abstract |
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Abstract Sex-related differences in systemic hemodynamics were analyzed by means of cardiac index and systemic vascular resistance according to the level of daytime ambulatory blood pressure. In addition, we assessed the relations between ambulatory blood pressure measurements and systemic hemodynamics in male and female patients. We prospectively included 52 women and 53 men referred to our unit for evaluation of arterial hypertension. Women and men were grouped according to the level of daytime mean arterial pressure: <110 or
110 mm Hg. Patients underwent noninvasive
evaluation of resting hemodynamics (impedance
cardiography) and 24-hour ambulatory blood pressure monitoring.
Compared with women men with lower daytime blood pressure had a 12%
higher systemic vascular resistance index (P=NS) and a 14%
lower cardiac index (P<.02), whereas men with higher
daytime blood pressure had a 25% higher vascular resistance
(P<.003) and a 21% lower cardiac index
(P<.0004). Furthermore, in men systemic vascular resistance
correlated positively with both daytime and nighttime systolic
and diastolic blood pressures, whereas cardiac index
correlated negatively only with daytime diastolic blood
pressure. In contrast, women did not exhibit any significant
correlation between hemodynamic parameters
and ambulatory blood pressure measurements. In conclusion,
sex-related differences in systemic hemodynamics
were more pronounced in the group with higher daytime hypertension. The
relations between systemic hemodynamics and ambulatory
blood pressure level depended on the sex of the patient. In men a
progressive circulatory impairment underlies the increasing level of
ambulatory blood pressure, but this was not observed in women.
Key Words: blood pressure, ambulatory • blood pressure measurement • cardiac output • sex • resistance, vascular
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Introduction |
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Previous investigators showed that vascular resistance increases and CO decreases as hypertension severity progresses.1 However, the relative contribution of vascular resistance and CO for a given level of blood pressure varies from patient to patient.2 The patient's sex appears in part to account for this interindividual variability in the hemodynamic pattern. Hypertensive men have been reported to have higher vascular resistance and a lower CI than women matched for mean arterial pressure, age, race, and body surface area.3 In addition, men exhibit a greater susceptibility to development of left ventricular hypertrophy under comparable levels of hypertension.4
On the basis of these previous findings the purpose of this investigation was to assess whether sex-related hemodynamic differences are influenced by the severity of hypertension. In addition we analyzed the influence of sex on the relations between ambulatory blood pressure level and hemodynamic variables.
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Methods |
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Patients
We prospectively included 105 white patients (52 women and 53 men) referred to our unit for evaluation of arterial hypertension. Patients either had never been treated or had discontinued treatment for hypertension at least 2 weeks before study. Women taking contraceptive pills or hormone replacement therapy were excluded. Patients with secondary hypertension or other major diseases were excluded on the basis of clinical and routine laboratory tests. Women and men were grouped according to whether the level of daytime MAP was <110 or
110 mm Hg.
Hemodynamic Measurements
Patients avoided smoking or drinking tea or coffee on the
morning of the hemodynamic study. Blood pressure was
determined with the right arm by a mercury sphygmomanometer. CO was
estimated by impedance cardiography (Minnesota model 304 B) using the
technique and formula proposed by Kubicek et al.5 Briefly,
four longitudinal adhesive electrodes supporting a thin aluminum layer
were attached: one to the forehead and the other three around the base
of the neck, to the thorax at the level of the xiphoids, and to the
abdomen, respectively. A constant sinusoidal alternating current (4 mA,
100 kHz) was transmitted through the thorax between the outer
electrodes. The mean total transthoracic electrical
impedance between the inner electrodes is computed by the impedance
cardiograph.
Blood pressure and tracings of the first derivative of thoracic impedance (dZ/dt) were obtained in duplicate after 10 minutes of supine rest by observers unaware of the patient's ambulatory blood pressure. Tracings including five consecutive cardiac cycles (in apnea immediately after a passive expiration avoiding Valsalva's maneuver) were recorded at a paper speed of 50 mm/s and measured manually. The following formula was used to calculate ventricular stroke volume (SV, in milliliters):
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where p indicates electrical resistivity of blood at 100 kHz; L, the mean distance between electrodes 2 and 3 (in centimeters); Z0, the mean thoracic impedance between electrodes 2 and 3 (in ohms); dZ/dtmax, the peak value of the first derivative of thoracic impedance occurring during ventricular ejection (in ohms per second); and T, ventricular ejection time (in seconds).
CI was calculated as stroke volume multiplied by heart rate divided by meters squared. Heart rate was derived from the interbeat interval. The MAP was calculated as DBP plus one third pulse pressure. SVRI was calculated as SVRI=(MAP-CVP/CI) · 80, where CVP is the central venous pressure, which was assumed to be 4 mm Hg in all cases.
In our laboratory6 the correlation coefficient between the simultaneous CO values obtained by impedance cardiography and thermodilution in 14 patients was 0.94, and the mean of the paired differences between the two methods was 78±380 mL/min. In 12 healthy volunteers the average of the paired differences between two consecutive estimations of CO separated by 1 minute was on average 0.58%, and the 95% confidence interval was -1.7% to 2.8%.7 The reliability of impedance cardiography in measuring central hemodynamics has been documented extensively.8 9 10 11 12 13
Ambulatory Blood Pressure Monitoring
Ambulatory blood pressure was recorded during a 24-hour
working day. In 35 women and 45 men we used a Del Mar P IV 1990 monitor
and in 17 women and 8 men a SpaceLabs 90207 monitor. Ambulatory blood
pressure was monitored every 10 minutes between 7 am and 11 pm and
every 20 minutes between 11 pm and 7 am. Nighttime blood pressure was
considered to be the values recorded during the period of nighttime
sleep. Cuffs were placed around the nondominant arm. The agreement
within 5 mm Hg between the mercury column and the automatic blood
pressure recorder readings was checked simultaneously
on the same arm. Readings of SBP >260 or <70 mm Hg, DBP >150 or
<40, and pulse pressure >150 or <20 mm Hg were automatically
discarded. Only studies with 90% of valid blood pressure
measurements were included.
Statistical Methods
All values are expressed as mean±SD. Two-factor ANOVA was
calculated to assess hemodynamic differences between
sex and blood pressure subgroups. Statistical differences were assessed
further by unpaired Student's t test. Relations between
ambulatory blood pressure measurements and systemic
hemodynamics were assessed by univariate
regression analysis in female and male patients.
STAT-GRAPHICS version 5.1 statistical package was used.
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Results |
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Differences Between Sexes in Systemic Hemodynamics According to Ambulatory Blood Pressure Level
Table 1 lists the mean±SD for age, SVRI, CI, and ambulatory blood pressure measurements according to sex and the level of daytime MAP. Sex subgroups were comparable in age as well as in daytime and nighttime blood pressure levels. Two-factor ANOVA indicated that sex-related differences in CI were highly significant (P<.0001) regardless of the blood pressure subgroup, with a nonsignificant interaction between sex and daytime MAP, indicating that sex plays an independent role in measurement of the CI. Although in men the CI tended to decrease from the lower to the higher blood pressure group, the difference was not significant.
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Sex-related differences in SVRI were also significant (P<.0008) without significant interaction between sex and daytime MAP. In men SVRI was significantly higher in the group with higher compared with the group with lower daytime MAP (P<.01), but this difference was mild and not significant in women.
In addition the SVRI was significantly higher in men than women in the subgroup with higher daytime MAP (P<.003), but the difference did not reached statistic significance in the subgroup with lower daytime MAP.
Furthermore, the CI was significantly lower in men than women in both blood pressure subgroups, but this difference was greater from the lower (P<.02) to the higher daytime MAP groups (P<.0004), respectively.
Relations Between Ambulatory Blood Pressure and Systemic
Hemodynamics
Table 2 lists the results of univariate
analyses among the ambulatory blood pressure measurements,
SVRI, and CI. Both daytime SBP and DBP (Fig 1) were
significantly related to the SVRI in men (P<.001 for SBP
and DBP). In addition nighttime SBP and DBP were less strongly but also
significantly related to SVRI in men (P<.01 for SBP and
DBP). Only daytime DBP correlated, weakly but significantly, with CI
(P<.05) (Fig 2). In contrast, women did not
exhibit any significant correlation between hemodynamic
parameters and hypertension severity as measured by means
of ambulatory blood pressure monitoring (Fig 3).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The present study shows that hypertensive women have a higher CI than men with a comparable level of ambulatory blood pressure. A higher CI and lower SVRI in hypertensive women were previously described using indocyanine green for CO determinations.3 In this study hypertension severity was assessed by means of ambulatory blood pressure monitoring. In addition to the previous evidence we observed that the CI was higher in women regardless of the severity of hypertension. SVRI was lower in women, but the difference was significant in patients with more severe hypertension.
Although the relative contribution of CO and systemic vascular resistance is variable for a given level of hypertension,2 transverse studies in humans have shown a progressive increase in systemic vascular resistance and a mild decrease in CO from borderline to severe hypertension.1 In the present study the relations between the level of ambulatory blood pressure and resting systemic hemodynamic variables were related to the sex of the patient. Our results showed that the expected increment in systemic vascular resistance from the lowest to the highest daytime and nighttime blood pressure was present only in men. The CI showed a significant tendency to decrease with the increase in daytime DBP level. Neither the SVRI nor the CI was related to the ambulatory blood pressure level in women.
Previous studies showed significant correlations between ambulatory blood pressure measurements and both minimal vascular resistance and left ventricular mass in hypertension.14 15 A recent study16 demonstrated significant relations between ambulatory blood pressure measurements and central hemodynamics in patients with moderate to severe hypertension (34 men and 6 women). However, differences between the sexes were not addressed in these studies.
Other authors showed that in men but not women daytime hypertension (either associated or not with a blunted nocturnal decrease in blood pressure) is a sufficient determinant of left ventricular mass.17 Furthermore, they observed that for any quartile of daytime MAP, hypertensive men showed a greater left ventricular mass index than women. A trophic effect of testosterone on the myocardium18 could increase the cardiac susceptibility to develop adaptive hypertrophy in response to pressure overload. Thus, structural factors may in part account for the consistently higher CI in women than men with either a mild or moderate increase in daytime MAP. In addition several neurohumoral differences could participate in the hemodynamic differences between women and men and could offset in women the circulatory impairment related to hypertension severity.
A lower left ventricular end-systolic wall stress (a measure of left ventricular afterload) was observed in premenopausal and postmenopausal hypertensive women than in their respective male control subjects.4 Renin activity was reported to be lower in premenopausal hypertensive women compared with normotensive women,19 whereas hypertensive men of the same age had normal renin like their normotensive counterparts.20 On the other hand, young and old normotensive women showed a lower muscle sympathetic nerve activity at rest (a measure of the sympathetic activity to resistance vessels) than their male control subject counterparts.21 Reduced sympathetic nerve activity could explain in part the lower vascular resistance and low renin activity in hypertensive women.
Recent evidence indicates that estrogens stimulate the production of nitric oxide from vascular endothelium in women.22 23 Furthermore, endothelial function may be less impaired in female spontaneously hypertensive rats24 and hypercholesterolemic women compared with their respective male counterparts.25 Other authors3 found an attenuation of differences between the sexes in systemic hemodynamic variables among hypertensive patients >45 years of age; nevertheless, differences were still significant when young and old women were analyzed together.3 In our study sex-related differences in systemic hemodynamics were evident even though some of the women were of postmenopausal age. In addition, after patients were divided into groups of younger and older than 50 years of age, hemodynamic differences persisted between the sexes (data not shown). Furthermore, sex-related differences in Doppler-derived parameters of aortic flow persist for several years after menopause.26
Blood pressure regulation has shown evidence of a sexual dimorphism in
spontaneously hypertensive rats.27 28
Endogenous androgens stimulate myocardial18
and kidney29 growth and help to regulate several
neurohumoral mechanisms involved in circulatory homeostasis through the
expression of several genes.29 30 31 The androgenic effects
seem to determine sexual dimorphism of spontaneously hypertensive rats
at a young age. Castration of male spontaneously hypertensive rats at 4
weeks of age reduced the subsequent sex-related difference in blood
pressure and renal 
2-adrenergic receptor density by
60%,32 whereas similar treatment at 25 weeks of age had
no effect.33
Androgen treatment increases and estradiol decreases endothelin levels in humans.34 Furthermore, plasma levels of endothelin are higher in men than women.34 In contrast to the stimulation of several neurohumoral systems, testosterone elicits a direct vasodilatory effect in rabbit coronary arteries and aorta.35
In conclusion, we found that for men and women of comparable ages sex-related differences in systemic hemodynamics were more significant in patients with more severe daytime hypertension. The expected relation between hypertension severity and systemic vascular resistance was dependent on the sex of the patient. The progressive increment in either daytime or nighttime blood pressure was associated with a significant increase in systemic vascular resistance only in men.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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We thank Myriam Nuñez for her assistance in the statistical analysis of the data and Maria Gabriela Ameijenda for her technical assistance in the preparation of the manuscript.
Received June 19, 1995; first decision September 16, 1995; accepted October 3, 1995.
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