Abstract
Cardiopulmonary fitness benefits cardiovascular health. Various studies have shown a strong negative correlation between exercise capacity and arterial stiffness in adults. However, evidence for this connection in children and adolescents is scarce. About 320 healthy children and adolescents (252 male, 14.0±2.1 years) were evaluated with regard to their demographic, anthropometric and hemodynamic parameters, and their peak oxygen uptake. Peripheral and central systolic blood pressures were measured with patients in a supine position using an oscillometric device. Peak oxygen uptake was assessed by cardiopulmonary exercise testing. In multivariate regression, only peripheral systolic blood pressure (β=0.653, P<.001) and body weight (β=0.284, P<.001) emerged as independent determinants for central systolic blood pressure. Body weight therefore determines central systolic blood pressure in children and adolescents rather than measures of cardiorespiratory fitness. The prevention of overweight in childhood is necessary to reduce stiffening of the arteries and delay the onset of cardiovascular disease.
Central systolic blood pressure (CSBP) is the pressure in the aorta and can be used as a surrogate measure for the stiffness of the arteries. It is composed by a forward‐traveling wave generated by left ventricular ejection and a subsequent wave reflected from the periphery. With increasing stiffness, the arterial transmission velocity of both––forward and reflected waves––increases. This causes the reflected wave to arrive earlier in the central aorta and augment central blood pressure (BP) in late systole.1, 2 Studies have shown that CSBP is a valid and better predictor of cardiovascular events than peripheral BP.3, 4, 5
Regardless of individual factors, age related stiffening occurs when the elastic fibers within the arterial wall begin to fray as a result of mechanical stress. In addition, general risk factors such as BP, smoking, reduced cardiopulmonary fitness, and overweight contribute to cardiovascular stiffening and increase the risk for cardiovascular events.6, 7, 8, 9 Results from the Amsterdam Growth and Health Longitudinal Study10 confirm that especially BP and central body fat are important factors for the pathogenesis of arterial stiffness and cardiovascular disease in adolescents aged 12 to 14 years.
Evidence suggests that the beneficial impact of cardiopulmonary fitness on the arterial system can already be observed in children.11, 12, 13 It is currently unknown whether different levels of physical activity in healthy children have the same implications on the arterial system as that seen in adults.13, 14 Some studies have investigated the impact of physical training in obese children and found positive effects on vascular and anthropometric parameters.11 However, in children of normal weight as well as in adolescents, the correlation between cardiorespiratory fitness (CRF) and health of the cardiovascular system currently remain controversial.14
Therefore, the aim of this study was to shed light on the controversial results between CRF and CSBP in children and adolescents.
Patients and Methods
Study Patients
From April 2011 to August 2014, 320 healthy children and adolescents younger than 20 years (252 male, 14.0±2.1 years) were prospectively investigated for their anthropometric, hemodynamic, and cardiopulmonary parameters. The study cohort consisted of individuals evaluated in a school project15 and healthy patients assessed in our department. All patients underwent the same measurement of their anthropometric, hemodynamic, and cardiopulmonary parameters. All of the included patients were free from acute or chronic diseases. If patients were investigated twice, only the first examination was included. In this study, overweight was defined as a body mass index (BMI) above the 90th percentile and obesity above the 97th percentile according to the German reference population.16
Study characteristics are displayed in Table 1. All patients gave written informed consent.
Table 1.
Epidemiological Data of 320 Study Patients According to Age Group
| Study Group (N=320) | ≤13 y (n=102) | 13–15 y (n=157) | 16–19 y (n=61) | |
|---|---|---|---|---|
| Age, y | 14.0±2.1 | 11.9±1.0 | 14.0±0.7 | 17.4±0.9 |
| Body weight, kg | 53.9±13.0 | 44.2±11.5 | 54.8±10.2 | 68.1±7.0 |
| Body length, cm | 163.9±12.3 | 152.9±9.9 | 165.6±8.6 | 177.7±6.8 |
| Body mass index, kg/m2 | 19.8±3.0 | 18.7±3.4 | 19.9±2.3 | 21.6±1.8 |
| Systolic blood pressure, mm Hg | 115.4±8.7 | 114.2±7.1 | 114.4±8.8 | 120.0±9.5 |
| Diastolic blood pressure, mm Hg | 63.4±6.8 | 63.9±6.8 | 62.7±7.0 | 64.2±6.1 |
| Mean arterial pressure, mm Hg | 80.7±6.3 | 80.7±5.9 | 79.9±6.4 | 82.8±6.1 |
| Central systolic blood pressure, mm Hg | 104.3±9.4 | 101.8±7.1 | 103.6±9.2 | 109.9±10.9 |
| Heart rate at rest, beats per min | 69.3±12.1 | 72.1±12.2 | 71.0±11.6 | 60.0±8.1 |
| Heart rate at peak exercise, beat per min | 186±10.7 | 186±11 | 186±11 | 183±10 |
| Peak workload, W | 216.2±72.8 | 156.7±37.6 | 217.0±58.6 | 313.7±34.5 |
| Peak oxygen uptake, mL/min/kg | 45.4±9.2 | 41.5±8.7 | 45.2±9.0 | 52.2±6.2 |
| Respiratory exchange ratio | 1.12±0.07 | 1.09±0.07 | 1.13±0.07 | 1.13±0.08 |
Values are expressed as mean±standard deviation.
Measurement of CSBP and Arterial Stiffness
Peripheral BP was measured automatically on the left upper arm with the oscillometric cuff‐based Mobil‐O‐Graph (IEM Healthcare, Stolberg, Germany) device with patients in the supine position after 5 to 10 minutes of rest. CSBP was calculated with an ARCSolver Algorithmus (Austrian Institute of Technology, Vienna, Austria) based on the recorded brachial pulse waves. This method takes into account the influence of arterial impedance and the aortic hemodynamics by using a generalized transfer function and a mathematical model. It is confirmed that the results of this noninvasive cuff‐based method of calculating central BP is highly congruent with invasive measurement of central BP.17
Cardiopulmonary Exercise Testing
All patients underwent a symptom‐limited Cardiopulmonary Exercise Testing (CPET) on a bicycle ergometer in an upright position. The protocol starts with a 2‐minute warm‐up without load, followed by a ramp‐wise increase of 10 W/min, 15 W/min, 20 W/min, or 30 W/min, depending on the body composition and the expected physical capacity of the patients. The exercise test featured a breath‐by‐breath gas exchange analysis using a metabolic chart (Ergostick, Geratherm Respiratory GmbH, Bad Kissingen, Germany). Peak oxygen uptake was defined as the highest mean uptake of any 30‐second time interval during exercise.
Patients with an expiratory exchange ratio (RER) <1.0 or a peak heart rate <85% of their predicted maximum were excluded from the study due to lack of compliance as previously described.18
Data Analyses
All analyses were performed using SPSS version 22.0 software (IBM Corp, Armonk, NY). Descriptive data were expressed in mean values and standard deviations (mean±SD).
As a first step, partial correlation, correcting for age and sex, was used to find bivariate associations between CSBP and anthropometric, cardiopulmonary, and hemodynamic variables. As a second step, multivariate linear stepwise regression was performed to find the strongest independent determinant on CSBP by including peak oxygen uptake, peak workload, age, sex, body height, body weight, BMI, heart rate at rest, and peripheral systolic, diastolic, and mean arterial pressure into the model. Two‐sided P values <.05 were considered significant. Cook's distance was evaluated to identify potential influential outliers (D i<4/n).
Results
As seen in Table 2, after correction for age and sex in partial correlation, CSBP increased with peripheral systolic, diastolic, and mean arterial BP (all P<.001). Moreover, CSBP increased with body weight (r=0.364, P<.001 (Figure)), body height (r=0.194, P=.001), and BMI (r=0.310, P<.001). CSBP was also significantly higher in boys than in girls (male 105.2 mm Hg vs female 100.9 mm Hg, P<.001).
Table 2.
Partial Correlation of Central Systolic Blood Pressure Corrected for Age, and Sex With Demographic, Anthropometric, Cardiorespiratory, and Hemodynamic Variables
| Variable | Partial Correlation r | P Value |
|---|---|---|
| Height, cm | 0.190 | .001 |
| Weight, kg | 0.362 | <.001 |
| Body mass index, kg/m2 | 0.318 | <.001 |
| Systolic blood pressure, mm Hg | 0.715 | <.001 |
| Diastolic blood pressure, mm Hg | 0.277 | <.001 |
| Mean arterial pressure, mm Hg | 0.526 | <.001 |
| Heart rate at rest, beats per min | 0.086 | NS |
| Heart rate at peak exercise, beats per min | −0.013 | NS |
| Peak oxygen uptake, mL/min/kg | −0.148 | .011 |
| Peak oxygen uptake (% predicted) | −0.149 | .010 |
| Peak workload, W/kg | −0.140 | .016 |
Abbreviation: NS, not significant.
Figure 1.
Scatterplot illustrating the positive associations between bodyweight and central systolic blood pressure.
There was only a weak association of percentage of predicted peak oxygen uptake (r=−0.149, P=.010) and peak workload (Watt/kg) (r=−0.140 P=.016) with CSBP.
In a multivariate regression model, only peripheral systolic BP (β=0.653, P<.001) and body weight (β=0.284, P<.001) emerged as independent determinants for CSBP and accounted for 60.8% of the total variance (Table 3). There was no independent impact of peak oxygen uptake, peak workload, age, sex, body length, BMI, heart rate at rest, or peripheral diastolic and mean arterial pressure on CSBP in the multivariate model.
Table 3.
Multivariate Regression Analysis on Central SBP Including All Significant Demographic Variables
| Variable | Regression Coefficient | SEE | β | P Value | r 2 Change, % |
|---|---|---|---|---|---|
| SBP, mm Hg | 0.703 | 0.039 | 0.653 | <.0001 | 53.3 |
| Weight, kg | 0.204 | 0.026 | 0.284 | <.0001 | 7.5 |
Abbreviations: SBP, systolic blood pressure; SEE, standard error of the estimation.
Cook's distance showed no significant influence of potential outliers (D i=0.004).
Discussion
This study could not find an association of CRF on CSBP in healthy children and adolescents. However, in childhood and adolescence, body weight in addition to peripheral systolic BP is an independent determinant of CSBP.
This finding seems to be in contrast to current research and in comparison to observations in adults. Prior investigations verified the thesis of a beneficial association between cardiopulmonary fitness and cardiovascular health in youth and in adulthood.11, 19, 20, 21 Silva and colleagues19 identified CRF as an even better predictor of cardiovascular disease than obesity. Our results suggest different connections, however.
In this study, peripheral systolic BP primarily and body weight secondarily emerged as determinants of CSBP independent of cardiopulmonary and anthropometric factors such as sex, age, and height. Because of the noninvasive calculation of CSBP via the peripheral one, peripheral systolic BP is logically a cofounder of CSBP. However, the second determinant––body weight––seems to be of special interest. As seen in in our study cohort, CRF level was high and mean BMI values were lower than 20 (Table 1). Hence, in this population, higher body weight did not occur because of overweight or obesity but because of higher body length. Based on this assumption, body weight and not BMI emerged as a predictor. Nevertheless, as seen in Table 3, the relationship between higher body weight and higher levels of CSBP is proven and might become more obvious in overweight or obese patients. Sakuragi and colleagues20 investigated the CRF of 573 healthy children with a 20‐m shuttle run. They found that obesity as well as CRF had an impact on the arterial system. Indeed, obesity emerged as a stronger determinant in their study.
In contrast to that study,20 we measured CRF with a cardiopulmonary exercise testing––the gold standard for CRF––and could not confirm the negative association between CRF and arterial stiffness. Particularly in children and adolescents, body weight was shown to be the critical predictor of cardiovascular health, in contrast to CRF. Consequently, the widely used slogan “fat but fit”19 was not supported by our results for the arterial system in childhood. From our results “slim but lazy” seems to be the better slogan for promoting cardiovascular health in children.
In accordance with other studies, our results suggest that in childhood the prevention of overweight is one of the most important factors to delay the onset and reduce the risk of cardiovascular stiffening. The first signs of atherosclerosis, called fatty streaks, arise from birth on in obese and normal‐weight children.6, 11 In this context, promoting an active lifestyle and healthy diet is crucial in childhood.
There are several possible explanations for the mechanism whereby higher bodyweight promotes a stiffer arterial system and, hence, higher CSBP. One obvious possibility might be the overweight‐related burden for the cardiovascular system, which becomes apparent in higher heart rate,22 higher peripheral BP,23 and higher CSBP, as well as in deconditioned patients. Some investigations equally found that endothelial dysfunction caused by insulin resistance24 or remodeling of the arterial wall25 plays an important role in the pathogenesis of adiposity. More specific research is needed to understand these mechanisms and interactions.
Finally, the measurement of CSBP is feasible, inexpensive, fast, and noninvasive and therefore a justified method for the evaluation of cardiovascular risk.26
Study Limitations
A better specification of body weight by muscle mass and body fat would be beneficial to verify the results and to compare them with other investigations.11, 19, 20 Pubertal status as a possible confounder was not assessed. In general, findings are based on a predominately male sample with a high level of CRF, which might result in a lack of generalizability of the study to less‐fit or overweight patients. The influence of body weight is quite small and there may be other factors contributing to higher central BP not assessed in the current study.
Conclusions
Body weight emerged as an independent determinant for CSBP in children and adolescents. Prevention of overweight and obesity is therefore key in delaying the early development of cardiovascular stiffening and the onset of cardiovascular disease. The role of CRF on cardiovascular prevention might be more important in adulthood. Further research is needed to clarify whether CRF, body weight, or even BMI are more important factors for arterial stiffening and cardiovascular risk.
Disclosures
The authors have no funding or conflicts of interest to disclose.
Acknowledgments
We thank Lukas Steinheber for proofreading the manuscript.
J Clin Hypertens (Greenwich). 2016;18:762–765. DOI: 10.1111/jch.12754. © 2015 Wiley Periodicals, Inc.
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