Original Article

Pubertal Hypertension is a Strong Predictor for the Risk of Adult Hypertension*

LIANG YaJun^1,2 and MI Jie^1,#

1. Department of Epidemiology, Capital Institute of Pediatrics, Beijing 100020, China; 2. School of Public Health, Jining Medical University, Jining 272067, Shandong, China

 

INTRODUCTION

ypertension is a worldwide public health problem. The prevalence of adult hypertension has increased over the last 2 decades^[1]. Along with the epidemic of childhood obesity, primary hypertension has already become common in children and adolescents^[2-3], while this was once considered to be rare in pediatrics^[4].

The origin of hypertension in adulthood has been observed to extend back to childhood^[5]. Many studies have shown that blood pressure (BP) tracks from childhood to adulthood^[6], and hypertensive children are more likely to develop hypertension in adulthood^[7]. An increase in childhood hypertension likely increases the prevalence of hypertension in adults in later decades, and further increases cardiovascular morbidity and mortality^[8].

However, BP tracking from childhood to adulthood changes with the growth and development of children and adolescents^[6]. Therefore, the predictive effect of adult hypertension might vary with the hypertension in different stages during childhood and adolescence. It is unknown which stage of hypertension predicts the strongest risk of adult hypertension?

In the present study, we aimed to assess and compare the predictive effects of hypertension before puberty and during puberty on adult hypertension. Our study was based on a longitudinal study-called the “Beijing children and adolescents BP study (BBS)”, in which 412 subjects were followed-up after18 years.

SUBJECTS AND METHODS

Study Population

All study participants came from the “BBS” cohort, which was initially conducted to evaluate high BP and related risk factors among children and adolescents of Beijing in 1987^[9]. The BBS was supported by the national project of The 7^th Five Year Plan, which tackled key problems in science and technology in China, and was conducted by the Capital Institute of Pediatrics who cooperated with Beijing Pediatric Hospital and Beijing Anzhen Hospital. During a baseline survey, 3 185 children and adolescents aged 6 to 18 years old (males, 53.1%) were randomly recruited from Chaoyang, Xicheng, and Haidian districts in Beijing. At baseline, children who suffered from secondary hypertension derived from chronic diseases of the heart, kidney, liver, endocrine system or vascular tissue were excluded from this study. A total of 412 adults (males, 53.2%) from the BBS cohort were followed up and invited to participate in a clinical examination in 2005. Their systolic and diastolic BP, height, and weight in childhood were measured at a baseline survey in 1987. Information on adult BP, anthropometric indices and life style were collected through questionnaire and physical examination. Loss to follow-up was mainly because of failure to trace the subjects (36.4%), being busy with work (44.5%), migration (3.3%), and other reasons of refusal.

In this study, follow-up participants were divided into pre-puberty and puberty sub-cohorts according to their pubertal stages at baseline. During the baseline survey, girls after menarche were classified as the pubertal sub-cohort, while other girls were considered as pre-pubertal. However, data on boys’ puberty stages were not collected during the baseline survey. Fortunately, we found data of boys’ first emission ages from the “Report on the Physical Fitness and Health Surveillance of Chinese School Students (1991)”^[10]. In this report, the mean age of boys’ first emission ages was 13.84 years in Beijing in 1991, which was almost the same period as the BBS baseline study. Therefore, we classified boys according to this report. Boys aged ≥13.84 years were classified as the pubertal sub-cohort, while the other boys were classified as the pre-pubertal sub-cohort.

This study was approved by the Institutional Review Boards and Ethics Committees of the Capital Institute of Pediatrics. Participants’ informed consents were obtained from children and their parents.

Measurements

Height and weight were measured to calculate body mass index (BMI, weight in kilograms divided by the square of height in meters).

BP at baseline and follow-up was measured by auscultation with a mercury sphygmomanometer according to a standard protocol^[11]. After each subject rested at least 15 minutes in the sitting position, BP was measured on the right arm, which was supported at heart level. The cuff size was determined according to the size of the subject’s arm to cover at least two-thirds of the upper arm. Subjects received three measurements of BP on one visit during each survey. The three measurements were separated by at least a 1-2 minutes’ interval, during which the right arm was raised up for 5-6 seconds. Differences in two consecutive readings of BP at the same sitting should not have been no more than 4 mmHg. The last two readings of BP one visit were averaged and reported as the BP values in this study^[9]. At the baseline survey, the first and the fourth Korotkoff sounds were defined as systolic BP (SBP) and diastolic BP (DBP) of children and adolescents, respectively.

Definitions

Being overweight and obesity in children and adolescents (7-18 years old) were defined according to the age- and sex-specific BMI reference values proposed by the Working Group on Obesity in China^[12]. This local reference did not include BMI cut-off points for children aged 6 years old. For children aged 6 years old, we used the age- and sex-specific 85^th and 95^th BMI percentiles from the US Center for Disease Control and Prevention 2 000 Growth Charts to define being overweight and obesity, respectively^[13]. In adults, being overweight was defined as a BMI ≥24 kg/m² and a BMI <28 kg/m², and obesity was defined as BMI ≥28 kg/m².

Among children and adolescents, we used the age- and sex-specific BP reference standard of Chinese children and adolescents to define pre-hypertension and hypertension (see Appendix)^[14]. Both SBP and DBP <90^th percentile was defined as normal BP; SBP and/or DBP ≥90^th percentile and <95^th percentile was defined as pre-hypertension; and SBP and/or DBP ≥95^th percentile was defined as hypertension. In adulthood, pre-hypertension and hypertension were diagnosed according to the China Guideline for Hypertension Prevention and Control issued in 2009^[15]. Adult hypertension was diagnosed as SBP ≥140 mmHg and/or DBP ≥90 mmHg or currently taking anti-hypertensive drugs, while pre-hypertension was defined as SBP ≥120 mmHg and <140 mmHg or DBP ≥80 mmHg and <90 mmHg.

APPENDIX. Recommended Blood Pressure Reference Cut-offs for Chinese Children and Adolescents Aged 6-17 Years (mmHg)

Note. SBP: Systolic blood pressure; DBP: Diastolic blood pressure, defined as the fourth Korotkoff sound; P₉₀: the 90^th percentile; P₉₅: the 95^th percentile.

Statistical Analysis

Statistical analysis was performed using SPSS 13.0 (SPSS Inc., Chicago, Illinois, USA). We used t-test to compare mean age, and the chi-square test to compare differences in the proportion of males, prevalence of being overweight, obesity, pre-hypertension, and hypertension between the pre-pubertal and pubertal sub-cohorts. Covariance analysis was used to compare the differences in height, weight, BMI, SBP, and DBP between the two sub-cohorts, with age and sex as concomitant variables. Regression coefficients were calculated through linear regression analysis to assess the correlations of BP from childhood to adulthood, after adjustment for age, sex, and BMI in childhood and adulthood. Multivariate logistic regression analysis was conducted to assess the predictive effects of adult hypertension based on pre-pubertal hypertension and pubertal hypertension. Odds ratios (ORs) and 95% confidence intervals (CIs) of hypertension in adulthood were evaluated after adjustment for age, sex, family history of hypertension, and obesity in childhood and adulthood. Statistical significance was set at P<0.05.

RESULTS

Characteristics of Subjects

Table 1 shows the characteristics and measurements at baseline in follow-up subjects and the entire BBS cohort. In follow-up subjects, the mean age was older (11.9±3.8 years vs. 11.3±3.7 years, P=0.001), the prevalence of pre-hypertension was lower (7.5% vs. 10.9%, P=0.034), and the proportion of family history of hypertension was higher (19.6% vs. 15.1%, P=0.021) compared with those in the entire BBS cohort. The proportion of males, height, weight, BMI, SBP, DBP, prevalence of being overweight, obesity, and hypertension were similar between follow-up subjects and the entire BBS cohort (all P>0.05). There were no significant differences in age, sex and all the other indices between follow-up and the entire BBS cohort with hypertension in childhood (all P>0.05).

Comparison between two Sub-cohorts

Table 2 shows the comparison of measurements between pre-pubertal and pubertal participants at the baseline and follow-up surveys. Pubertal participants were older than their pre-pubertal counterparts (P<0.001), with similar male proportions in the two sub-cohorts (P=0.764).

Table 1. Characteristics and Measurements at Baseline in Follow-up Subjects and the Entire BBS Cohort [？ ±s / n(%)]

Note. BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure. ^aMean and standard error were listed through covariance analysis, with age and sex as concomitant variables.

Table 2. Comparison of Characteristics between Pre-pubertal and Pubertal Participants [？ ±s /n(%)]

Note. BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure. ^aMean and standard error were listed through covariance analysis, with age and sex as concomitant variables.

At baseline, pubertal subjects had higher weight, SBP, DBP, and prevalence of pre-hypertension, and a lower prevalence of obesity (all P<0.05), and similar height, BMI, prevalence of being overweight and hypertension compared with those in the pre-pubertal sub-cohort (all P>0.05). In the follow-up period, mean SBP and the prevalence of pre-hypertension were lower in the pubertal sub-cohort than those in the pre-pubertal sub-cohort (both P<0.05), while height, weight, BMI, DBP, prevalence of being overweight, obesity, and hypertension were similar in the two sub-cohorts (all P>0.05).

Changes in BP between 1987 and 2005

Table 3 shows the changes and regression coefficients of BP from childhood to adulthood. BP increased more in pre-pubertal subjects than in pubertal participants from 1987 to 2005, with similar results in boys and girls. Greater increases in BP were observed in boys than in girls in either sub-cohort.

Table 3. Changes and Regression Coefficients of Blood Pressure between 1987 and 2005 (？ ±s)

Note. ^aStandardized regression coefficient through linear regression analysis after adjustment for age, sex, body mass index in childhood and adulthood.

From childhood to adulthood, the regression coefficients of SBP were similar in the two sub-cohorts (both　β=0.34, P<0.001). Pubertal boys had a higher coefficient of SBP than their pre-pubertal counterparts, while the result was the opposite in girls. For both sexes, the regression coefficient of DBP was larger in the pubertal sub-cohort (β=0.31, P<0.001) than that in the pre-pubertal sub-cohort (β=0.12, P=0.017), while results were similar in boys and girls.

Predictive Effect of Adult Hypertension

Table 4 shows the ORs and 95% CIs for adult hypertension based on pre-pubertal and pubertal hypertension. More children with pre-hypertension or hypertension in puberty developed hypertension during adulthood compared with pre-pubertal subjects (20.0% vs. 9.1% for pre-hypertension; 50.0% vs. 34.3% for hypertension).

Table 4. Odds Ratios and 95% Confidence Intervals for Adult Hypertension

Note. OR: Odds ratio; CI: Confidence interval; BP: Blood pressure. ^aAdjustment for age, sex, family history of hypertension, obesity in childhood and adulthood;  ^bpower=0.036; ^cpower=0.576; ^dpower=0.115.

After adjustment for age, sex, family history of hypertension, obesity in childhood and adulthood, children with pre-pubertal pre-hypertension or hypertension had a similar risk of developing adult hypertension, with an OR (95% CI) of 0.76 (0.08-7.77) and 2.71 (0.83-8.85), respectively, compared with children with normal BP in pre-puberty. In the pubertal sub-cohort, pubertal pre-hypertension predicted a similar risk for adult hypertension as normotension, with an OR (95% CI) of 1.50 (0.34-6.58). However, individuals with pubertal hypertension were at a 10-fold risk of developing adult hypertension compared with their normotensive counterparts, with an OR (95% CI) of 10.00 (3.03-33.07).

DISCUSSION

In this study, 253 pre-pubertal children and 159 pubertal adolescents were followed-up after 18 years. We found that the association of BP between childhood and adulthood was stronger in the pubertal sub-cohort, and individuals with pubertal hypertension had a higher risk of developing hypertension in adulthood compared with the pre-pubertal sub-cohort.

Adolescents experience complex physiological and hormonal changes during puberty. During adolescence, BP is related to pubertal status^[16], with great increases with age^[17]. Sexual maturation during adolescence is positively associated with the level of BP^[18-19], and it is also a predictor of BP when the effect of weight and skeletal age are omitted^[20]. This could partly explain our results of higher BP levels at baseline in pubertal subjects than those in pre-pubertal participants, after adjustment for sex and age.

In the current study, BP levels increased from childhood to adulthood. The association between childhood and adulthood was stronger for SBP than for DBP, after adjustment for age, sex and BMI. This finding is probably because SBP increases with increasing height and adiposity^[21-23], but DBP does not appear to rise consistently with height^[23]. We found that SBP and DBP were greatly increased in the pre-pubertal sub-cohort compared with those in the pubertal sub-cohort. After adjustment for age, sex and BMI, the associations of SBP and DBP levels between childhood and adulthood were stronger in the pubertal sub-cohort than those in the pre-pubertal sub-cohort. This can be explained by previous findings that BP tracking increases with baseline age, ie, older children have a strong BP tracking into adulthood^[6].

The pattern of BP is different between adolescent boys and girls^[20]. It has been shown that BP markedly increases during pre-pubescence and stabilizes after puberty in girls, while BP gradually increases from pubescence through the age of 18 years in boys^[20]. In our study, a greater change in BP from 1987 to 2005 was observed in boys than in girls. This is in agreement with other findings that males have higher mean SBP and a greater rise over time in SBP than in females^[21]. Some studies have also shown no significant sex difference in SBP tracking, and women have weaker DBP tracking than men^[6]. The sex differences of BP tracking still need further investigation.

Puberty may be a vulnerable period in the development of high SBP and cardiovascular disease in adult life^[24]. Hypertension in youth has been observed to increase, and higher BP in childhood and adolescence is also predictive of sustained hypertension in adulthood^[25]. Age differences have been reported in the associations between childhood risk factors (including high BP) and subclinical atherosclerosis in adulthood, and these associations are stronger with increasing age^[26]. In our study, individuals with pubertal hypertension had a 10-fold risk of developing hypertension in adulthood compared with children with normal BP. However, we didn’t find any risks of adult hypertension based on pre-pubertal hypertension, which is different from a previous finding that young children with elevated SBP were at greater risks of developing adult hypertension than older children and adolescents^[7]. The probable reason for this discrepancy between studies is that the statistical power in the pre-pubertal group might have been too small to observe the risks of adult hypertension.

It still remains unclear whether the timing of puberty has a long-term effect on BP in adult life^[27]. A previous study showed that age at puberty may be an important marker in the later development of hypertension^[28]. Any association of age at puberty with adult BP may simply reflect the effect of differences in maturation on adult body size. Unfortunately, pubertal stages of the participants were not measured at the baseline survey in our study. Because of the small sample, we didn’t divide the sample into detailed subgroups to analyze the association of age at puberty with hypertension in childhood and adulthood.

The major strength of our study is that we used a longitudinal cohort to observe the predictive effect of adult hypertension. An accurate correlation of BP levels and hypertension between childhood and adulthood could be determined. Therefore, this study may provide valuable information on the tracking of BP and predictive effect of hypertension from childhood to adulthood.

However, there are several limitations in this study. First, only 13.1% of children and adolescents at baseline were visited in 2005. Many subjects were too busy at work to participate in this follow-up study, which was the main reason of loss to follow-up. Therefore, there was possible bias due to differential loss to follow-up in this study. Although many subjects were not followed up, many characteristics tended not to be substantially different between follow-up subjects and the entire BBS cohort. Second, the statistical power was reduced because of the small sample, especially in multiple logistic regression analysis. Further follow-up studies with a large sample should be conducted to retest this result. Furthermore, because of the small number of hypertensive children, we didn’t observe any changes in the categories of hypertension (including systolic and diastolic hypertension) from childhood to adulthood. Third, pubertal information for boys was not collected at baseline. Many boys might have been misclassified in this study according to our grouping method of pre-puberty and puberty. Pubertal stages were also not measured at the baseline survey in this study. Fourth, the time interval between baseline and follow-up was too long, and some changes during this period might not have been observed. Hypertension is a disease, which can be affected by many factors including genetic and environmental risk factors. Furthermore, excessive salt intake may partly contribute to the onset of hypertension. Unfortunately, we didn’t investigate these related risk factors of hypertension in the present study, except for obesity and a family history of hypertension. Further studies on salt consumption and other factors of hypertension are necessary to explain the associations of BP and hypertension from childhood to adulthood.

In conclusion, adolescents with hypertension during puberty are more likely to develop adult hypertension. Further longitudinal studies with a large amount of subjects should be conducted to retest this association.

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