Resting Heart Rate is Associated with Blood Pressure in Male Children and Adolescents R^omulo Araujo Fernandes, PhD, Ismael Forte Freitas Junior, PhD, Jamile Sanches Codogno, PhD, Diego Giulliano Destro Christofaro, PhD, Henrique Luiz Monteiro, PhD, and Dalmo Machado Roberto Lopes, PhD Objectives To analyze the association between resting heart rate and blood pressure in male children and adolescents and to identify if this association is mediated by important confounders. Study design Cross-sectional study carried out with 356 male children and adolescents from 8 to 18 years old. Resting heart rate was measured by a portable heart rate monitor according to recommendations and stratified into quartiles. Blood pressure was measured with an electronic device previously validated for pediatric populations. Body fatness was estimated by a dual-energy x-ray absorptiometry. Results Obese subjects had values of resting heart rate 7.8% higher than nonobese (P = .001). Hypertensive children and adolescents also had elevated values of resting heart rate (P = .001). When the sample was stratified in nonobese and obese, the higher quartile of resting heart rate was associated with hypertension in both groups of children and adolescents. Conclusions This study confirms the existence of a relationship between elevated resting heart rate and increased blood pressure in a pediatric population, independent of adiposity, ethnicity and age. (J Pediatr 2011;158:634-7). R esting heart rate (HR) is a simple measurement with important prognostic implications in cardiovascular events.1 In patients with cardiovascular diseases (CVD), resting HR has been a predictor for mortality, independent of other risk factors.2,3 Despite evidence of an association between HR and cardiovascular events, some authors have not considered the elevated HR as a risk factor for CVD.4,5 Recent epidemiologic studies have indicated that, in adults, the relationship between elevated HR and cardiovascular events is independent of high systolic blood pressure, level of physical activity, and increased waist circumference,2 suggesting that HR could be considered as an independent cardiovascular risk factor. Cardiovascular events are the consequence, mainly, of an unhealthy lifestyle that begin at an early age and culminate in the development of diseases such as arterial hypertension, obesity, and insulin resistance.6,7 Thus, the analysis of the prognostic characteristics of resting HR during infancy may be important. The purpose of the present study were (1) to analyze the association between elevated resting HR and elevated blood pressure (EBP) in male children and adolescents and (2) to identify covariates of this association. Methods This was a cross-sectional study carried out in the city of Presidente Prudente (Human Development Index = 0.846), in Southeastern Brazil, from July to November 2008. The initial sample was 358 male children and adolescents from 8 to 18 years (n = 92 from 8 to 10 years and n = 266 from 11 to 18 years). Two subjects did not follow the protocol and were excluded from the sample (n = 356). The sample was selected from three schools and three sports clubs in the city. In each school and sports club, all students/associates from 8 to 18 years were invited to participate as volunteers in the study. Inclusion criteria for participants consisted of a self-declaration of health and that they were neither taking any medication nor undergoing any regular medical treatment. Research participants and parents/guardians gave written informed consent after receiving a thorough explanation of the research project. The study was approved by the ethics committee on human experimentation of the institution involved. Resting HR in beats per minute (beats/min) was measured by a portable HR monitor (S810; Polar Electro, Kempele, Finland). The measurements of HR were made during two 30-second periods (with 3 minutes in between). The HR was registered after 5 minutes with the subCVD DBP DXA-%BF EBP HR OR SBP Cardiovascular disease Diastolic blood pressure Dual-energy X-ray absorptiometry-percentage of body fat Elevated blood pressure Heart rate Odds ratio Systolic blood pressure From the Institute of Bioscience (R.A.F., J.S.C., H.L.M.), UNESP Univ Estadual Paulista, Rio Claro, Brazil; the Department of Physical Education (I.F.F.J.), UNESP Univ Estadual Paulista, Presidente Prudente, Brazil; the Department of Public Health (D.G.D.C.), Universidade Estadual de Londrina, Londrina, Brazil; and the Department of Physical Education (D.M.R.L.), ~o Paulo, Ribeira ~o Preto, Brazil Universidade de Sa The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.10.007 634 Vol. 158, No. 4 April 2011 jects in a sitting position.4 All HR measures were made at a university laboratory in a quiet room with constantly controlled temperature. Body weight (with the subjects wearing light clothing) and height were measured with an electronic scale (precision, 0.1 kg) and a wall-mounted stadiometer (precision, 0.1 cm), respectively. Body mass index was calculated with the values of weight divided by height squared (kg/m2). All anthropometric measurements were performed by the same researcher, according to standardized techniques.8 Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured with an electronic device (MX3 Plus; Omron Corporation, Kyoto, Kansai, Japan), previously validated for pediatric populations.9 After 5 minutes of resting in a sitting position, two measures were taken on the right arm, with a 2-minute interval between them. The mean value was used. For the blood pressure measurement, two types of cuffs were used according to the arm circumference (6 mm 12 mm for children and 9 mm 18 mm for adolescents age 14 to 18 years and for those children with a large arm size). Blood pressure was measured according to the recommendations of the American Heart Association.10 To determine which cuff would be used, the circumference of the arm of each child was measured, and the cuff that had approximately 40% of the width of arm circumference and 80% of length was used. The 95th percentile of the National High Blood Pressure Education Program11 cutoffs adjusted by age and height percentile were applied to indicate EBP. Body composition was estimated by a dual-energy x-ray absorptiometry (DXA) scanner (Lunar DPX-NT; General Electric Healthcare, Little Chalfont, Buckinghamshire, United Kingdom). The software provided measurements of dual-energy X-ray absorptiometry-percentage of body fat (DXA-%BF) and the presence of obesity has been identified as DXA-%BF $25%.12 All DXA measurements were made at the laboratory of the university, in a room with controlled temperature. Each morning before beginning the measurements, the DXA equipment was calibrated by the same researcher and according to the reference values provided by the manufacturer. Statistical Analysis The Kolmogorov-Smirnov test was used to confirm the normality of the numerical data in each quartile HR group. Mean and standard deviations were used as indicators of central tendency and dispersion measurements, respectively. The resting HR values were stratified into quartiles: 1st quartile (<percentile 25 [<70 beats/min]), 2nd quartile ($percentile 25 and <percentile 50 [70 to 77.4 beats/ min]), 3rd quartile ($percentile 50 and <percentile 75 [77.5 to 85.9 beats/min]), and 4th quartile ($percentile 75 [$86 beats/min]). Analyses of variance (one-way), with the post hoc Tukey test, was used to compare the mean values of resting HR according to each quartile. Pearson product-moment correlation coefficients indicated the linear relationship between numerical variables. Linear regression was performed to explain HR as a function of the variables evaluated. For categorical variables, Pearson c2 test was used to compare rates according to the quartiles for resting HR. In contingency tables 2 2, the Yates correction was applied. Logistic regression (odds ratio [OR] and 95% confidence interval [OR95%CI]) was used to construct a multivariate model, in which EBP was the dependent variable and age, ethnicity, and DXA-%BF were included as independent variables. Significance (P) was set at 5%. All analyses were performed using SPSS version 13.00 (SPSS Inc, Chicago, Illinois). Results The sample included white (64.3%), black (19.1%), and other (16.6%) subjects. There were no associations between skin color and either obesity (P = .628) or EBP (P = .229). There also were no differences for mean values of resting HR (P = .449), SBP (P = .117), DBP (P = .478), and DXA%BF (P = .080) by skin color. The group with the lowest HR had higher age, lower DBP, and lower DXA-%BF (Table I). The prevalence of obesity and EBP were positively associated with higher quartiles for resting HR. Obese subjects presented values of resting HR Table I. General characteristics of children and adolescents grouped into quartiles for resting heart rate (n = 356) Quartiles for resting heart rate <70 beats/min 70 to 77.4 beats/min 77.5 to 85.9 beats/min ‡86 beats/min Variables Mean (SD) Mean (SD) Mean (SD) Mean (SD) P n Skin color (white) Age (years) BMI (kg/m2) DXA-%BF SBP (mm Hg) DBP (mm Hg) EBP Obesity 83 61.4% 14.9 (2.9) 19.8 (3.2) 15.1 (9.8) 118.7 (12.4) 65.8 (9.5) 14.5% 15.7% 91 69.2% 13.2 (3.1)* 19.1 (3.8) 17.1 (8.4) 119.1 (14.9) 66.3 (9.8) 23.1% 18.7% 88 62.5% 12.3 (2.7)* 19.3 (4.7) 18.2 (10.2) 118.4 (12.6) 64.1 (8.6) 23.9% 20.5% 94 63.8% 11.7 (2.6)* 19.8 (6.4) 20.9 (10.4)*† 121.2 (14.8) 69.8 (9)*† 41.5% 39.4% .988 .001 .677 .001 .501 .001 .001 .001 SD, standard deviation; BMI, body mass index; DXA, dual-energy x-ray absorptiometry; DXA-%BF, percentage of body fat measured by DXA; SBP, systolic blood pressure; DBP, diastolic blood pressure; EBP, elevated blood pressure. *Significantly different compared with 1st quartile (<70 beats/min). †Significantly different compared with 2nd quartile (70 to 77.4 beats/min). 635 THE JOURNAL OF PEDIATRICS www.jpeds.com 7.8% higher than nonobese (76.9 11 and 82.9 12, respectively [P = .001]). Hypertensive children and adolescents also presented increased values of resting HR (normal blood pressure: 76.4 10 and EBP: 83.6 13; P = .001). DXA-%BF was significantly associated with SBP (r = 0.27; P = .001) and DBP (r = 0.27; P = .001). In the overall sample, resting HR was positively related to DXA-%BF (r = 0.23; P = .001), SBP (r = 0.10; P = .045), and DBP (r = 0.15; P = .003). A linear multivariate model also indentified a positive relationship between HR and both SBP (b = 0.254; P = .001) and DBP (b = 0.168; P = .001) independent of age, ethnicity, and DXA-%BF. In nonobese subjects, EBP was marginally associated with resting HR (1st quartile: 11.4%; 2nd quartile: 18.9%; 3rd quartile: 17.1%; 4th quartile: 24.6% [P = .084]), and, in obese subjects, the EBP was significantly associated with resting HR (1st quartile: 30.8%; 2nd quartile: 41.2%; 3rd quartile: 50%; 4th quartile: 67.6% [P = .011]). Finally, logistic regression and analysis in the overall sample indicated that there was a significant association between resting HR and EBP (OR = 4.71 [OR95%CI = 2.0 to 11.1], which was independent of obesity. When the sample was stratified into nonobese (OR = 4.16 [OR95%CI = 1.4 to 12.2]) and obese (OR = 8.30 [OR95%CI = 1.6 to 41]), the higher quartile of resting HR was associated with EBP in both nonobese and obese children and adolescents (Table II). Discussion The group of children and adolescents in the higher quartile for resting HR were younger. Previously, Al-Qurashi et al13 developed reference resting HR values for Saudi pediatric populations. In their reference table, HR also decreased through higher age groups. Similarly, in Italian adolescents, Rabbia et al,14 using multivariate linear regression, identified that age was a negative and significant determinant of HR (b = 1.143; P = .0003). These results indicate that chronological age was an important effect on HR. Therefore, the absence of age adjustment in the quartile calculation could limit the results. However, in both linear and logistic multivariate models, when all variables were inserted simultaneously, the significance of the relationship between HR and EBP remained. These findings support the concept that the absence Vol. 158, No. 4 of adjustment in resting HR quartile groups has not weakened the findings. Obese subjects presented higher values of HR than nonobese subjects. In adults with elevated resting HR, the mean of body mass index values also are higher.2 The association between obesity and hypertension is well documented, although the exact nature of this relation remains unclear. Some hypotheses indicate that in obese humans, sympathetic nervous system activity is increased.15,16 In addition, adipose tissue secretes angiotensinogen, which may result in the process of angiotensin II formation and further activation of sympathetic nervous system activity.15,16 In the present study, using multivariate analyses, after adjustments, increased resting HR and EBP were positively associated in both obese and nonobese groups. Thus, the main contribution of the present study is to demonstrate that in pediatric populations the relationship between elevated HR and blood pressure is independent of factors that also affect strongly the autonomic nervous system, such as age, obesity, and ethnicity. This is scientifically important because arterial hypertension tracks from childhood to adulthood,6 and it is one of the main risk factors for mortality caused by CVD in adults. The lack of standard methods for measurement of resting HR has been pointed out as an important limitation in previous studies.4 In the present study, the recommendation for the assessment of resting HR was followed, which contributes to the internal validity of the findings. Additionally, the use of a precise method to estimate the body composition is a strength because in previous studies only anthropometric indexes were used.2,14 Our results show that even when using a precise method to estimate body fatness, the relationship between resting HR and blood pressure was independent of adiposity. Limitations of the present research also must be highlighted. The cross-sectional design makes it impossible to determine a casual relationship between dependent and independent variables. This study confirms the existence of a relationship between elevated resting HR and increased blood pressure values in a pediatric population. The results suggest that elevated resting HR is a significant risk factor for EBP in children and adolescents independent of adiposity, ethnicity, and age. A resting HR $86 beats/min was associated with increased likelihood for EBP in both nonobese and obese youngsters. Table II. Association between increased resting heart rate and elevated blood pressure in male children and adolescents (n = 356) Elevated blood pressure Dependent variable Resting HR (beats/min) <70 70–77.4 77.5–85.9 $86 Overall (n = 356) Obese (n = 85) Nonobese (n = 271) ORadj1 (OR95%CI) P ORadj2 (OR95%CI) P ORadj2 (OR95%CI) P 1.00 2.12 (0.91 – 4.95) 2.22 (0.91 – 5.36) 4.71 (2.01 – 11.11) .080 .076 .001 1.00 2.42 (0.46 – 12.71) 3.51 (0.64 – 19.05) 8.30 (1.68 – 41.01) .295 .145 .009 1.00 2.08 (0.77 – 5.63) 2.08 (0.72 – 6.03) 4.16 (1.41 – 12.21) .146 .174 .009 HR, heart rate; ORadj1, odds ratio values adjusted by skin color, age, and obesity; ORadj2, odds ratio values adjusted by skin color and age; OR95%CI, odds ratio 95%confidence interval. 636 Fernandes et al ORIGINAL ARTICLES April 2011 Elevated HR should be considered as a clinical and epidemiological variable in prevention of cardiovascular events. n Submitted for publication Jun 22, 2010; last revision received Sep 8, 2010; accepted Oct 5, 2010. ^ mulo Arau jo Fernandes, PhD, Department of Physical Reprint requests: Dr Ro Education, Rua Roberto Simonsen, 305 Presidente Prudente – SP, Brazil 19060-900. 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