The Change in Blood Pressure during Pubertal Growth
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《临床内分泌与代谢杂志》
Abstract
Blood pressure (BP) in children may increase more during puberty. Using a cohort of children where BP and body size had been closely monitored, we compared the rates of change in BP during the 3-yr period before puberty, during puberty (4.5-yr period), and the 3-yr period after puberty. Because there was no specific staging information with respect to puberty, we used pubertal growth (PG) as a surrogate of puberty. The latter was determined from serial measurements of height. All subjects (n = 151) were followed from before the period of PG to the period after PG; none were related. An age-dependent increase in systolic BP in the pre-PG period was similar regardless of sex or race. During PG, systolic BP in males increased three to six times faster than in the pre-PG period. In females, systolic BP increased less than in males during PG but still increased two to four times faster than in the pre-PG period. The increase in males was significantly greater than in females (P < 0.001). Post-PG changes in BP were similar to changes in pre-PG BP. In summary, PG was associated with profound increases in systolic BP. There were noticeably greater increments in males than in females consistent with the emergence of the well known sexual dimorphism in BP.
Introduction
ALTHOUGH BLOOD PRESSURE (BP) increases as children become older, during puberty the rate of change in BP may accelerate (1, 2, 3). Indeed, the influence of puberty on BP may be greater than any other normal physiological event, possibly setting the stage for future levels of BP. We have closely followed a cohort of children into adolescence with frequent measurements of their BP and body size (4). This afforded us a unique opportunity to study how BP changes in the same individual over the important years of increased growth and development. We were particularly interested in the BP changes that occur during puberty and how the BP responses in males and females might differ because of the disparate actions of the sex hormones testosterone and estradiol, whose secretion during this period greatly increases. Because changes in stature are closely linked to the Tanner staging for pubertal development (5, 6), we assessed the change in BP in relation to pubertal growth (PG), which was estimated from serial measurements of height.
Subjects and Methods
Subjects
Subjects were from a larger cohort (n = 715) that has been followed longitudinally for the purpose of studying BP regulation (4). For the current analyses, subjects were selected based on their having had a minimum of two measurements of BP (at intervals of at least 6 months) in both the pre- and postpubertal periods as assessed from PG. None had hypertension, renal or cardiac disease, or diabetes mellitus, and none were taking medication that might affect BP. None of the subjects were related to other subjects. The subjects whose data were used in the current analysis differed somewhat from the cohort as a whole to the extent that they were more likely to be white (64 vs. 51%) and more likely to be male (52 vs. 46%). The Institutional Review Board of Indiana University-Purdue University of Indianapolis approved the study. In the case of minors, informed consent was obtained from a parent or a legal guardian as well as the subject.
Measurements
Subjects were visited mostly at their schools for purposes of measuring BP, height, and weight; less than 5% of the measurements were made in an outpatient facility of the General Clinical Research Center. BP was measured in the right arm using a random zero sphygmomanometer (Hawksley and Sons, Lansing, UK) with the subject seated. The first and fifth Korotkoff sounds were used to designate systolic and diastolic BP, respectively. Three BP readings were obtained, and the average of the last two was used as the final BP. The measurements were made approximately every 6 months in most of the subjects, with nearly 90% of the visits 4.5–8 months apart and most of the remaining visits approximately 1 yr apart because of missed visits.
Body mass index (BMI) was calculated as weight (kg)/height (m)2, and BMI percentiles were computed using codes available from the Centers for Disease Control (CDC) website (www.cdc.gov).
Estimations of the PG from the maximum height velocity
The change in height between two consecutive measurement visits was computed, and the two visits between which the maximum rate of change in height occurred was identified. The ages at the two visits were averaged to define the age of maximum height velocity. Only subjects where the age at maximum height velocity was identified between the ages of 10 and 17 yr in males and 8 and 15 yr in the females (the normal age ranges for onset of puberty) were included in the analyses. Height velocity charts published by the CDC (Atlanta, GA) were used to exclude subjects if the maximum height velocity for the identified age was below the third percentile lines on the chart (to remove those who might have reached maximum height velocity before entering the study). The distributions of the age at peak height velocity and the age when height velocity dropped less than 2 cm/yr compared favorably to the data in published CDC charts.
The age 2 yr before the age at maximum height velocity was considered the age when onset of PG occurred. The end of PG was defined as the age (after the onset of the pubertal growth spurt) when height velocity first decreased to less than or equal to 2 cm/yr, which is the point where near final adult height is achieved (www.cdc.gov/growthcharts). Using these conservative definitions to estimate both the onset and end of PG, we reduced the risk of contaminating the pre-PG and post-PG periods with data occurring during PG. Ages were redefined relative to the onset and end of the PG period. For example, 1 yr before onset of PG was –1 and 2 yr after the end of PG was +2.
Statistical methods
All analyses were performed using mixed-model ANOVA. A term allowing discontinuity in the regression line pre-PG vs. post-PG, along with interactions between this term and sex and race, was included in the models. A term allowing different slopes for age relative to pre-PG vs. post-PG, along with interactions between this term and sex and race, was also included in the models. Random intercept and slope terms correlated the longitudinal measurements within each subject. Model-based means were calculated at four prespecified time points: 3 yr before the onset of PG, at the onset of PG, at the end of PG, and 3 yr after the end of PG. The models were used to summarize the BMI percentile and height data at the specified time points as well as to compare sex and race differences in BP. The data are presented as mean (SEM) unless otherwise specified. The BP was adjusted for both BMI percentile and height, both of which are strong predictors of BP (7). Although height is used to calculate BMI, height remained a significant independent predictor of BP and thus was included as a covariate.
Results
Subjects
One hundred fifty-one subjects had measurements made in both the pre- and post-PG periods and thus were eligible for inclusion in the study. There were 16 black females, 49 white females, 22 black males, and 64 white males. Table 1 summarizes the number of observations per subject in the pre-PG and post-PG periods. All the subjects had a minimum of four observations with at least two in the pre-PG period and two in the post-PG period.
Ages at onset and end of PG
Table 2 shows the ages at peak height velocity and the estimated ages for the onset and the end of the PG periods. The distributions of the age of peak height velocity and the age when height velocity dropped to less than or equal to 2 cm/yr were consistent with the height velocity charts published by the CDC. Onset of PG occurred earlier in the females than the males. Black females had an earlier onset and end of PG compared with the white females; there was no similar race difference in the males. The duration of the PG period ranged between 4.5 and 5 yr depending on the group.
Characteristics of subjects and changes in BP in relation to PG
In Table 3 are depicted the height, weight, BMI percentile, and the adjusted BP for subjects at 3 yr before the PG period, at the onset of the PG period, at the end of the PG period, and then at 3 yr from when the PG period ended. The BP results (adjusted for BMI percentile and height) are presented in Fig. 1 as the means of systolic and diastolic BP for pre- and post-PG periods. Over the 3 yr before PG, the rate of increase in systolic BP was significant (P = 0.029) with increases of 1.3–3.0 mm Hg during the 3-yr period depending on the group. There was no significant sex difference in BP or in the rate of increase.
Systolic BP increased significantly in both the males and the females between the onset and the end of the PG period but increased significantly more in the males (P < 0.001). Increments in systolic BP during the PG period were 15 mm Hg in the white males and 13.8 mm Hg in the black males compared with increases of 8.2 mm Hg in the white females and 8.9 mm Hg in the black females. Diastolic BP increased less than systolic in the males, but for all groups diastolic BP also increased significantly during the PG period (P < 0.001 for all groups), but the increment was less than for systolic and was greater in the females than the males (P = 0.034).
At the end of PG, systolic BP continued to increase at rates similar to those seen before PG (Fig. 1), with increases of 2.1–4.0 mm Hg over the 3-yr post-PG period depending on the group. Although there was no significant sex difference in the rate of change for either systolic or diastolic BP after the PG period, there was a trend toward a greater rate of BP change (systolic and diastolic) in the males (Fig. 1).
We observed no race difference in any of the relationships to BP.
Discussion
We provide a description of the change in BP that accompanies the rapid physical growth associated with puberty by following the same individuals from the period before PG to the period after PG. To our knowledge, this is the first prospective study where there was frequent monitoring of BP and body size (approximately every 6 months) over the period of rapid development. The changes in BP observed were apart from those that are secondary to changes in body size, because adjustments were made for growth parameters; the BP values observed were thus primarily a product of the sole influence of pubertal events. We found that the increases in systolic BP were much greater during the PG period than either before or after. The rates of increase in systolic BP in males during PG were three to six times greater than those in the pre-PG period. In females, the increases in systolic BP during PG, although lower than in males, were still two to four times greater compared with the pre-PG period. Although the PG period lasted approximately 4.5 yr, it is likely that the accelerated phase of BP change that accompanied puberty was actually confined to a much shorter time period and that the peak effect was even more marked. In the post-PG period, the increases in systolic BP returned to levels similar to those observed in the pre-PG period. The changes in diastolic BP during PG were much less with more variation depending on the sex and race group.
The technique used to estimate the occurrence of PG, and to a large extent puberty, was novel. We took advantage of the fact that PG is temporally linked to puberty (5, 6), more than would be the case for chronological age where there is considerable variability with respect to onset of puberty. PG was based on an easily and precisely obtainable measurement, that of height.
In the present study, we relied on systolic BP more than diastolic BP. Studies of young people have often used systolic rather than diastolic BP (8, 9). Diastolic readings can be less accurate in children because of the potential difficulty in distinguishing fourth and fifth Korotkoff sounds. In addition, systolic BP, determined by the force of ventricular contraction, may be more reflective of the influences of growth and the overall changing physiology than diastolic BP, which is more a parameter of ventricular filling.
The increase in BP during PG is likely related to increases in gonadal hormones, although other hormones might also participate, such as GH. An intriguing consideration is the extent to which the high levels of these hormones function in establishing a more permanent level of BP. They could have important transcriptional effects on maturing organ systems such as kidney and vasculature with lasting consequences for BP. In countries where sodium intake is much lower than in Western societies and where the BP does not increase with advancing age, the lifetime maximal level of BP is achieved with puberty (10, 11). Interestingly, male-replacement doses of testosterone given to adult females (in female-to-male transsexuals) had no effect on BP (12), consistent with testosterone affecting BP primarily in preadulthood.
Increased hormone secretion during puberty might interact with known pressor systems to influence future risk for hypertension. For example, estrogens have been shown to increase peripheral levels of angiotensinogen (13) and increase expression of epithelial sodium channel subunits (14). In an exploratory subanalysis, we tested the hypothesis that the increase in BP during PG was related to family history of hypertension. In the currently studied cohort, family histories were obtained as part of the overall assessment of factors influencing BP. There were 71 in whom both parents were normotensive and 28 in whom at least one parent was hypertensive. Although family history of hypertension was significantly related to the subjects’ systolic BP, we did not find a relation between family history and the change in systolic BP during PG. We did on the other hand observe a significant interaction with race (P = 0.038) where blacks with a parent with hypertension (n = 9) had a greater increment in systolic BP during PG than blacks with two normotensive parents (n = 10). The findings, although extremely preliminary, suggest that the changes in BP with puberty or PG could have value as a phenotype.
Males typically have higher BP than females (15), and men are more likely to develop hypertension than premenopausal women of equivalent age (16, 17). In experimental animal models of hypertension, the males again have a higher BP than the females (18, 19). In the current study where subjects were followed prospectively, a higher systolic BP in the males emerged during PG. There was no significant sex difference in the rate of change in BP before PG, and only a nonsignificant trend toward a higher rate of increase of BP in the males compared with the females during post-PG.
The difference in the actions of the gonadal hormones secreted during puberty would seem to best explain the sexual dimorphism in BP. Testosterone has been shown to be an important determinant of BP in animal studies. Ely et al. (20) showed that insertion of the Y chromosome from a spontaneously hypertensive rat (SHR) into the genome of the Wistar-Kyoto male rat (a normotensive strain) resulted in an elevation in BP, a hypertensive model known as SHR/y. They subsequently showed that the SHR/y had an earlier pubertal increase in testosterone production and that an androgen receptor blocker decreased the BP (21). In other studies, castration of the male SHR was shown by Reckelhoff et al. (22) to reduce the BP. The factor responsible for the sexual dimorphism could result from an additional influence of the Y chromosome that is separate from gonadal hormone effects. Y-chromosomal polymorphisms have been shown to associate with BP in adult men (23, 24). However, the pre-PG males of the present study did not have a higher BP compared with the pre-PG females, which one might expect if it was a Y-chromosomal effect that was independent of gonadal function.
In the current study, we did not observe race differences in the rate of rise in BP, which differed from what we reported earlier for the same cohort when the mean age of the subjects was younger (4). The absence of any observable race difference in the current study may be related to the relatively small numbers of blacks studied. In addition and probably more importantly, the subjects in the current study were examined in relation to the onset of PG (not in relation to chronological age), and thus the previously reported higher BP in blacks (4, 9) might have been a partial consequence of not having adjusted for the earlier onset of puberty and, in turn, PG in blacks (25).
In summary, using a novel method to estimate PG, we observed a greatly heightened increase in BP during this period. It was during this interval that the sexual dimorphism in BP emerged. We deduce from the findings that during sexual maturation, gonadal hormones are affecting BP importantly with possibly a preponderant effect of testosterone.
Footnotes
This work was supported by National Institutes of Health Grants R01-HL-35795, RO1-HL67360, and M01-RR00750, a grant from the Nicholas H. Noyes, Jr., Memorial Foundation, Inc., and the United States Department of Veterans Affairs.
First Published Online October 27, 2004
Abbreviations: BMI, Body mass index; BP, blood pressure; PG, pubertal growth; SHR, spontaneously hypertensive rat.
Received May 15, 2004.
Accepted October 1, 2004.
References
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Blood pressure (BP) in children may increase more during puberty. Using a cohort of children where BP and body size had been closely monitored, we compared the rates of change in BP during the 3-yr period before puberty, during puberty (4.5-yr period), and the 3-yr period after puberty. Because there was no specific staging information with respect to puberty, we used pubertal growth (PG) as a surrogate of puberty. The latter was determined from serial measurements of height. All subjects (n = 151) were followed from before the period of PG to the period after PG; none were related. An age-dependent increase in systolic BP in the pre-PG period was similar regardless of sex or race. During PG, systolic BP in males increased three to six times faster than in the pre-PG period. In females, systolic BP increased less than in males during PG but still increased two to four times faster than in the pre-PG period. The increase in males was significantly greater than in females (P < 0.001). Post-PG changes in BP were similar to changes in pre-PG BP. In summary, PG was associated with profound increases in systolic BP. There were noticeably greater increments in males than in females consistent with the emergence of the well known sexual dimorphism in BP.
Introduction
ALTHOUGH BLOOD PRESSURE (BP) increases as children become older, during puberty the rate of change in BP may accelerate (1, 2, 3). Indeed, the influence of puberty on BP may be greater than any other normal physiological event, possibly setting the stage for future levels of BP. We have closely followed a cohort of children into adolescence with frequent measurements of their BP and body size (4). This afforded us a unique opportunity to study how BP changes in the same individual over the important years of increased growth and development. We were particularly interested in the BP changes that occur during puberty and how the BP responses in males and females might differ because of the disparate actions of the sex hormones testosterone and estradiol, whose secretion during this period greatly increases. Because changes in stature are closely linked to the Tanner staging for pubertal development (5, 6), we assessed the change in BP in relation to pubertal growth (PG), which was estimated from serial measurements of height.
Subjects and Methods
Subjects
Subjects were from a larger cohort (n = 715) that has been followed longitudinally for the purpose of studying BP regulation (4). For the current analyses, subjects were selected based on their having had a minimum of two measurements of BP (at intervals of at least 6 months) in both the pre- and postpubertal periods as assessed from PG. None had hypertension, renal or cardiac disease, or diabetes mellitus, and none were taking medication that might affect BP. None of the subjects were related to other subjects. The subjects whose data were used in the current analysis differed somewhat from the cohort as a whole to the extent that they were more likely to be white (64 vs. 51%) and more likely to be male (52 vs. 46%). The Institutional Review Board of Indiana University-Purdue University of Indianapolis approved the study. In the case of minors, informed consent was obtained from a parent or a legal guardian as well as the subject.
Measurements
Subjects were visited mostly at their schools for purposes of measuring BP, height, and weight; less than 5% of the measurements were made in an outpatient facility of the General Clinical Research Center. BP was measured in the right arm using a random zero sphygmomanometer (Hawksley and Sons, Lansing, UK) with the subject seated. The first and fifth Korotkoff sounds were used to designate systolic and diastolic BP, respectively. Three BP readings were obtained, and the average of the last two was used as the final BP. The measurements were made approximately every 6 months in most of the subjects, with nearly 90% of the visits 4.5–8 months apart and most of the remaining visits approximately 1 yr apart because of missed visits.
Body mass index (BMI) was calculated as weight (kg)/height (m)2, and BMI percentiles were computed using codes available from the Centers for Disease Control (CDC) website (www.cdc.gov).
Estimations of the PG from the maximum height velocity
The change in height between two consecutive measurement visits was computed, and the two visits between which the maximum rate of change in height occurred was identified. The ages at the two visits were averaged to define the age of maximum height velocity. Only subjects where the age at maximum height velocity was identified between the ages of 10 and 17 yr in males and 8 and 15 yr in the females (the normal age ranges for onset of puberty) were included in the analyses. Height velocity charts published by the CDC (Atlanta, GA) were used to exclude subjects if the maximum height velocity for the identified age was below the third percentile lines on the chart (to remove those who might have reached maximum height velocity before entering the study). The distributions of the age at peak height velocity and the age when height velocity dropped less than 2 cm/yr compared favorably to the data in published CDC charts.
The age 2 yr before the age at maximum height velocity was considered the age when onset of PG occurred. The end of PG was defined as the age (after the onset of the pubertal growth spurt) when height velocity first decreased to less than or equal to 2 cm/yr, which is the point where near final adult height is achieved (www.cdc.gov/growthcharts). Using these conservative definitions to estimate both the onset and end of PG, we reduced the risk of contaminating the pre-PG and post-PG periods with data occurring during PG. Ages were redefined relative to the onset and end of the PG period. For example, 1 yr before onset of PG was –1 and 2 yr after the end of PG was +2.
Statistical methods
All analyses were performed using mixed-model ANOVA. A term allowing discontinuity in the regression line pre-PG vs. post-PG, along with interactions between this term and sex and race, was included in the models. A term allowing different slopes for age relative to pre-PG vs. post-PG, along with interactions between this term and sex and race, was also included in the models. Random intercept and slope terms correlated the longitudinal measurements within each subject. Model-based means were calculated at four prespecified time points: 3 yr before the onset of PG, at the onset of PG, at the end of PG, and 3 yr after the end of PG. The models were used to summarize the BMI percentile and height data at the specified time points as well as to compare sex and race differences in BP. The data are presented as mean (SEM) unless otherwise specified. The BP was adjusted for both BMI percentile and height, both of which are strong predictors of BP (7). Although height is used to calculate BMI, height remained a significant independent predictor of BP and thus was included as a covariate.
Results
Subjects
One hundred fifty-one subjects had measurements made in both the pre- and post-PG periods and thus were eligible for inclusion in the study. There were 16 black females, 49 white females, 22 black males, and 64 white males. Table 1 summarizes the number of observations per subject in the pre-PG and post-PG periods. All the subjects had a minimum of four observations with at least two in the pre-PG period and two in the post-PG period.
Ages at onset and end of PG
Table 2 shows the ages at peak height velocity and the estimated ages for the onset and the end of the PG periods. The distributions of the age of peak height velocity and the age when height velocity dropped to less than or equal to 2 cm/yr were consistent with the height velocity charts published by the CDC. Onset of PG occurred earlier in the females than the males. Black females had an earlier onset and end of PG compared with the white females; there was no similar race difference in the males. The duration of the PG period ranged between 4.5 and 5 yr depending on the group.
Characteristics of subjects and changes in BP in relation to PG
In Table 3 are depicted the height, weight, BMI percentile, and the adjusted BP for subjects at 3 yr before the PG period, at the onset of the PG period, at the end of the PG period, and then at 3 yr from when the PG period ended. The BP results (adjusted for BMI percentile and height) are presented in Fig. 1 as the means of systolic and diastolic BP for pre- and post-PG periods. Over the 3 yr before PG, the rate of increase in systolic BP was significant (P = 0.029) with increases of 1.3–3.0 mm Hg during the 3-yr period depending on the group. There was no significant sex difference in BP or in the rate of increase.
Systolic BP increased significantly in both the males and the females between the onset and the end of the PG period but increased significantly more in the males (P < 0.001). Increments in systolic BP during the PG period were 15 mm Hg in the white males and 13.8 mm Hg in the black males compared with increases of 8.2 mm Hg in the white females and 8.9 mm Hg in the black females. Diastolic BP increased less than systolic in the males, but for all groups diastolic BP also increased significantly during the PG period (P < 0.001 for all groups), but the increment was less than for systolic and was greater in the females than the males (P = 0.034).
At the end of PG, systolic BP continued to increase at rates similar to those seen before PG (Fig. 1), with increases of 2.1–4.0 mm Hg over the 3-yr post-PG period depending on the group. Although there was no significant sex difference in the rate of change for either systolic or diastolic BP after the PG period, there was a trend toward a greater rate of BP change (systolic and diastolic) in the males (Fig. 1).
We observed no race difference in any of the relationships to BP.
Discussion
We provide a description of the change in BP that accompanies the rapid physical growth associated with puberty by following the same individuals from the period before PG to the period after PG. To our knowledge, this is the first prospective study where there was frequent monitoring of BP and body size (approximately every 6 months) over the period of rapid development. The changes in BP observed were apart from those that are secondary to changes in body size, because adjustments were made for growth parameters; the BP values observed were thus primarily a product of the sole influence of pubertal events. We found that the increases in systolic BP were much greater during the PG period than either before or after. The rates of increase in systolic BP in males during PG were three to six times greater than those in the pre-PG period. In females, the increases in systolic BP during PG, although lower than in males, were still two to four times greater compared with the pre-PG period. Although the PG period lasted approximately 4.5 yr, it is likely that the accelerated phase of BP change that accompanied puberty was actually confined to a much shorter time period and that the peak effect was even more marked. In the post-PG period, the increases in systolic BP returned to levels similar to those observed in the pre-PG period. The changes in diastolic BP during PG were much less with more variation depending on the sex and race group.
The technique used to estimate the occurrence of PG, and to a large extent puberty, was novel. We took advantage of the fact that PG is temporally linked to puberty (5, 6), more than would be the case for chronological age where there is considerable variability with respect to onset of puberty. PG was based on an easily and precisely obtainable measurement, that of height.
In the present study, we relied on systolic BP more than diastolic BP. Studies of young people have often used systolic rather than diastolic BP (8, 9). Diastolic readings can be less accurate in children because of the potential difficulty in distinguishing fourth and fifth Korotkoff sounds. In addition, systolic BP, determined by the force of ventricular contraction, may be more reflective of the influences of growth and the overall changing physiology than diastolic BP, which is more a parameter of ventricular filling.
The increase in BP during PG is likely related to increases in gonadal hormones, although other hormones might also participate, such as GH. An intriguing consideration is the extent to which the high levels of these hormones function in establishing a more permanent level of BP. They could have important transcriptional effects on maturing organ systems such as kidney and vasculature with lasting consequences for BP. In countries where sodium intake is much lower than in Western societies and where the BP does not increase with advancing age, the lifetime maximal level of BP is achieved with puberty (10, 11). Interestingly, male-replacement doses of testosterone given to adult females (in female-to-male transsexuals) had no effect on BP (12), consistent with testosterone affecting BP primarily in preadulthood.
Increased hormone secretion during puberty might interact with known pressor systems to influence future risk for hypertension. For example, estrogens have been shown to increase peripheral levels of angiotensinogen (13) and increase expression of epithelial sodium channel subunits (14). In an exploratory subanalysis, we tested the hypothesis that the increase in BP during PG was related to family history of hypertension. In the currently studied cohort, family histories were obtained as part of the overall assessment of factors influencing BP. There were 71 in whom both parents were normotensive and 28 in whom at least one parent was hypertensive. Although family history of hypertension was significantly related to the subjects’ systolic BP, we did not find a relation between family history and the change in systolic BP during PG. We did on the other hand observe a significant interaction with race (P = 0.038) where blacks with a parent with hypertension (n = 9) had a greater increment in systolic BP during PG than blacks with two normotensive parents (n = 10). The findings, although extremely preliminary, suggest that the changes in BP with puberty or PG could have value as a phenotype.
Males typically have higher BP than females (15), and men are more likely to develop hypertension than premenopausal women of equivalent age (16, 17). In experimental animal models of hypertension, the males again have a higher BP than the females (18, 19). In the current study where subjects were followed prospectively, a higher systolic BP in the males emerged during PG. There was no significant sex difference in the rate of change in BP before PG, and only a nonsignificant trend toward a higher rate of increase of BP in the males compared with the females during post-PG.
The difference in the actions of the gonadal hormones secreted during puberty would seem to best explain the sexual dimorphism in BP. Testosterone has been shown to be an important determinant of BP in animal studies. Ely et al. (20) showed that insertion of the Y chromosome from a spontaneously hypertensive rat (SHR) into the genome of the Wistar-Kyoto male rat (a normotensive strain) resulted in an elevation in BP, a hypertensive model known as SHR/y. They subsequently showed that the SHR/y had an earlier pubertal increase in testosterone production and that an androgen receptor blocker decreased the BP (21). In other studies, castration of the male SHR was shown by Reckelhoff et al. (22) to reduce the BP. The factor responsible for the sexual dimorphism could result from an additional influence of the Y chromosome that is separate from gonadal hormone effects. Y-chromosomal polymorphisms have been shown to associate with BP in adult men (23, 24). However, the pre-PG males of the present study did not have a higher BP compared with the pre-PG females, which one might expect if it was a Y-chromosomal effect that was independent of gonadal function.
In the current study, we did not observe race differences in the rate of rise in BP, which differed from what we reported earlier for the same cohort when the mean age of the subjects was younger (4). The absence of any observable race difference in the current study may be related to the relatively small numbers of blacks studied. In addition and probably more importantly, the subjects in the current study were examined in relation to the onset of PG (not in relation to chronological age), and thus the previously reported higher BP in blacks (4, 9) might have been a partial consequence of not having adjusted for the earlier onset of puberty and, in turn, PG in blacks (25).
In summary, using a novel method to estimate PG, we observed a greatly heightened increase in BP during this period. It was during this interval that the sexual dimorphism in BP emerged. We deduce from the findings that during sexual maturation, gonadal hormones are affecting BP importantly with possibly a preponderant effect of testosterone.
Footnotes
This work was supported by National Institutes of Health Grants R01-HL-35795, RO1-HL67360, and M01-RR00750, a grant from the Nicholas H. Noyes, Jr., Memorial Foundation, Inc., and the United States Department of Veterans Affairs.
First Published Online October 27, 2004
Abbreviations: BMI, Body mass index; BP, blood pressure; PG, pubertal growth; SHR, spontaneously hypertensive rat.
Received May 15, 2004.
Accepted October 1, 2004.
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