Introduction

Low cardiorespiratory fitness seems to be an important health problem (Lee et al. 1999; Carnethon et al. 2003; Mora et al. 2003; Myers et al. 2002). It has been recently shown that low cardiorespiratory fitness is a strong and independent predictor of incident metabolic syndrome (i.e. hypertension, dyslipidemia, impaired glycemic control and obesity) in men and women (LaMonte et al. 2005), which could be one of the mechanism of overall cardiovascular disease. Moreover, cardiorespiratory fitness seems to prevent premature mortality regardless of body-weight status or the presence of metabolic syndrome in adult men (Katzmarzyk et al. 2004, 2005).

High cardiorespiratory fitness during childhood and adolescence has been associated not only with healthier cardiovascular profile during these years but also later in life (Twisk et al. 2002). However, the association between cardiorespiratory fitness and cardiovascular risk factors in children is uncertain, probably because of low research priority. Furthermore, most children are asymptomatic for cardiovascular disease. Cardiorespiratory fitness has been suggested to be included in the European Health Monitoring System for the adult population (Sjöström et al. 2005), but the question as to whether fitness should be assessed in European health monitoring systems from the early stages of life remains to be answered. Understanding the association between a low cardiorespiratory fitness and cardiovascular-disease-related outcomes in children would support the question as to whether cardiorespiratory fitness might or might not be proposed as a health marker at these ages. Therefore, the aim of the present report was to examine the associations of cardiorespiratory fitness to health-related variables in a wide cohort of children aged 9–10 years and to relate the findings with corresponding results from recent cross-sectional and prospective cohort studies.

Research design and methods

The present cross-sectional study involved 873 children aged 9–10 years (444 girls, 429 boys). The subjects comprised Estonian and Swedish children who were part of the European Youth Heart Study (EYHS) (Poortvliet et al. 2003). The pooling of data was assumed to be possible because of the use of common protocols in both countries (Poortvliet et al. 2003; Wennlof et al. 2003). Study design, selection criteria and sample calculations have been reported elsewhere (Riddoch et al. 2005).

In Estonia, the city of Tartu and its surrounding rural area was the geographical sampling area. In Sweden, seven municipalities in the Stockholm area and one in Örebro were chosen for data collection. The local ethical committees approved the study (University of Tartu no. 49/30-1997, University Hospital no. 474/98 Huddinge, and Örebro City Council no. 690/98). The study procedures were explained verbally and in written text to all parents and children. One parent or legal guardian provided written informed consent, and all children gave verbal consent.

Data collection

Physical examination

Height and weight were measured by standardized procedures. Body mass index was calculated as weight/height squared (kg/m2). Skinfold thicknesses were measured with a Harpenden caliper at the biceps, triceps, subscapular, suprailiac and triceps surae areas on the left side of the body. These measures have been shown to highly correlate with dual-energy X-ray absorptiometry-measured body fat percentage in children of similar ages (Gutin et al. 1996). All measurements were taken twice and in rotation, and the mean was calculated. If the difference between the two measurements differed by >2 mm, a third measurement was taken, and the two closest measurements were averaged. The sum of five skinfold thicknesses was used as an indicator of body fat.

Blood pressure

The systolic and diastolic blood pressures were measured with an automatic oscillometric method (Dinamap model XL Critikron, Inc., Tampa, Florida.). The equipment has been validated in children (Park and Menard 1987). An appropriate cuff size was chosen according to the manufacturer’s recommendation after checking the arm circumference. The subject was in a sitting, relaxed position, and recordings were made every second minute for 10 min with the aim of obtaining a set of systolic recordings not varying by more than 5 mmHg. The mean value of the last three recordings was used as the resting systolic and diastolic blood pressure in millimeters of mercury (mmHg).

Blood samples

With the subject in the supine position, blood samples were taken by venipuncture after an overnight fast, using vacuum tubes (Vacuette, Greiner Lab Technologies Inc). The fasting state was verbally confirmed by the subject before blood sampling. Blood was centrifuged for 10 min at 2,000 g, serum was separated within 30–60 min, and the samples were stored at −80°C. Serum concentrations of triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), and glucose were measured on an Olympus AU600 autoanalyser (Olympus Diagnostica GmbH, Hamburg, Germany). The insulin for the Estonian subjects was analyzed with an enzyme immunoassay (DAKO Diagnostics Ltd., Ely, England). All analyses were performed at Bristol Royal Infirmary, UK, with the exception of insulin for the Swedish subjects, which was performed at Huddinge University Hospital, Sweden (Elecsys, Roche Diagnostics GmbH, Mannheim, Germany). A more detailed description of the blood analysis has been reported elsewhere (Wennlof et al. 2005). Insulin resistance was estimated from fasting glucose and insulin according to the homeostasis model assessment (HOMA) (Matthews et al. 1985), and the ratio TC/HDLc was also calculated.

Cardiorespiratory fitness test

Cardiorespiratory fitness was determined by a maximum cycle-ergometer test, as described elsewhere (Hansen et al. 1989). Briefly, the workload was preprogrammed on a computerized cycle ergometer (Monark 829E Ergomedic, Vansbro, Sweden) to increase every third minute until exhaustion. Heart rate was registered continuously by telemetry (Polar Sport Tester, Kempele, Finland). Criteria for exhaustion were a heart rate ≥185 beats per minute, failure to maintain a pedaling frequency of at least 30 revolutions per minute, and a subjective judgment by the observer that the child could no longer keep up, even after vocal encouragement. The power output was calculated as =W1+(W2 · t/180), where W1 is a work rate at fully completed stage, W2 is the work rate increment at final incomplete stage, and t is time in second at final incomplete stage. The “Hansen formula” for calculated maximum oxygen consumption (VO2max) in ml/min was = 12 x calculated power output + 5 x body weight in kg (Hansen et al. 1989). Cardiorespiratory fitness was expressed as VO2max per kilogram of body mass.

Metabolic risk score

The metabolic risk score was computed from the following six variables: insulin, glucose, HDLc, triglycerides, the sum of five skindfolds, and blood pressure (systolic and diastolic blood pressure). Each of these variables was standardized as follow: standardized value = (value − mean)/SD. The HDLc standardized value was multiplied by −1 to indicate higher cardiovascular risk with increasing value. The standardized values of systolic and diastolic blood pressure were averaged. The metabolic risk score was compiled by the sum of the six standardized scores divided by six. The resulting risk score is a continuous variable with a mean of zero by definition, with lower scores denominating a more favorable profile.

Statistical analysis

All variables were checked for normality of distribution before the analysis, and appropriate transformations were applied when necessary. Sum of five skinfolds, triglycerides, low-density lipoprotein cholesterol (LDLc), TC, and TC/HDLc were logarithmically transformed, and HOMA was transformed by taking it by the power of (1/3). Differences between metabolic syndrome individual variables and cardiorespiratory fitness quartiles, and metabolic syndrome risk score and cardiorespiratory fitness quartiles were assessed by analysis of variance (ANOVA). Differences of metabolic syndrome individual variables among cardiorespiratory fitness quartiles were assessed by Tukey’s test. All analyses were performed using the Statistical Package for Social Sciences (SPSS, version 13.0 for WINDOWS; SPSS Inc, Chicago, IL,USA), and the level of significance was set at P<0.05.

Results

The descriptive characteristics of the study sample are shown in Table 1. All subjects in this study were within the normal healthy ranges for all studied variables. The ANOVA showed significant differences among cardiorespiratory fitness quartiles for sum of five skinfolds, insulin resistance, triglycerides and TC/HDLc in girls whereas in boys, only sum of five skinfolds and insulin resistance were significantly different. Significant differences among cardiorespiratory fitness quartiles were also observed for metabolic risk score in girls and boys.

Table 1 Baseline characteristics of 873 children (444 girls, 429 boys)
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The Tukey’s test showed that the sum of five skinfolds was significantly higher in the first cardiorespiratory fitness quartile compared with the second, third and fourth cardiorespiratory fitness quartiles in girls and boys (Fig. 1). Moreover, sum of five skinfolds was significantly higher in the second cardiorespiratory fitness quartile compared with the fourth cardiorespiratory fitness quartile in girls. In boys, the sum of five skinfolds was significantly lower in the fourth cardiorespiratory fitness quartile compared with the first, second and third cardiorespiratory fitness quartiles (Fig. 1).

Fig. 1
figure 1

Associations between sum of five skinfolds and cardiorespiratory fitness quartiles in girls and boys. Data shown as mean and 95% confidence interval (CI). Girls in the first quartile (*) had a higher sum of five skinfolds than in superior quartiles (P<0.001), and girls in the second quartile (†) had a higher sum of five skinfolds than in the fourth quartile (P=0.004). Boys in the first quartile (‡) had a higher sum of five skinfolds than in superior quartiles. (P=0.007)

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Insulin resistance was significantly higher in the first cardiorespiratory fitness quartile compared with the fourth cardiorespiratory fitness quartile in both girls and boys. Moreover, insulin resistance was significantly higher in the second cardiorespiratory fitness quartile compared with the fourth cardiorespiratory fitness quartile in girls (Fig. 2).

Fig. 2
figure 2

Associations between insulin resistance estimated from the homeostasis model assessment (HOMA) equation and cardiorespiratory fitness quartiles in girls and boys. Data shown as mean and 95% confidence interval (CI). Girls in the first quartile (*) had a higher HOMA than in the fourth quartile (P<0.001), and girls in the second quartile (†) had a higher sum of five skinfolds than in the fourth quartile (P<0.001). Boys in the first quartile (‡) had a higher HOMA than in the fourth quartile (P=0.007)

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Triglyceride values were significantly higher in the first cardiorespiratory fitness quartile compared with the fourth cardiorespiratory fitness quartile in girls (Fig. 3). The ratio of TC/HDLc was significantly higher in the first cardiorespiratory fitness quartile compared with the second and fourth cardiorespiratory fitness quartiles in girls (Fig. 4).

Fig. 3
figure 3

Associations between triglycerides (TG) and cardiorespiratory fitness quartiles in girls and boys. Data shown as mean and 95% confidence interval (CI). Girls in the first quartile (*) had a higher TG values than in the fourth quartile (P<0.001)

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Fig. 4
figure 4

Associations between total cholesterol (TC) and high-density lipoprotein cholesterol (HDLc) ratio and cardiorespiratory fitness quartiles in girls and boys. Data shown as mean and 95% confidence interval (CI). Girls in the first quartile (*) had a higher TC/HDLc ratio than in the second and fourth quartiles (P<0.001)

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Metabolic risk score was significantly higher in the first cardiorespiratory fitness quartile than in the second, third and fourth cardiorespiratory fitness quartiles in girls and boys (Fig. 5). Significant differences were also found between metabolic risk score in the second and fourth cardiorespiratory fitness quartiles in girls (Fig. 5).

Fig. 5
figure 5

Associations between metabolic risk score and cardiorespiratory fitness quartiles in girls and boys. Data shown as mean and 95% confidence interval (CI). Girls in the first quartile (*) had a higher risk score than in the second, third and fourth quartiles (P<0.007), and girls in the second quartile (‡) had a higher risk score than in the fourth quartile (P<0.02). Boys in the first quartile (†) had a higher risk score than in the second, third and fourth quartiles (P=0.007)

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Discussion

The association between cardiorespiratory fitness and features of metabolic syndrome was investigated in a population sample of Swedish and Estonian children aged 9–10 years. Cardiorespiratory fitness was negatively associated with a clustering of metabolic risk factors in girls and boys, and the lowest values of sum of five skinfolds, insulin resistance, triglyceride and TC/HDLc were in the highest cardiorespiratory fitness quartile.

Theses results may suggests that cardiorespiratory fitness should be proposed as a health marker in children. In fact, it is biologically plausible that a high cardiorespiratory fitness provides more health protection than low cardiorespiratory fitness, even in healthy children as well as it has been found in adults (Balady 2002; Myers et al. 2002; Carnethon et al. 2003; Gulati et al. 2003; Kurl et al. 2003; Mora et al. 2003; Church et al. 2005; Katzmarzyk et al. 2004, 2005; LaMonte el al. 2005). Risk-factor levels are lower in children than in adults, but similar patterns have been seen in children. Previous cross-sectional studies in children have shown significant associations between cardiorespiratory fitness and plasma lipids and between cardiorespiratory fitness and clustering of metabolic syndrome risk factors (Table 2). In our study, triglyceride and TC/HDLc values differed among cardiorespiratory fitness quartiles (Fig. 3). Moreover, negative associations between increased cardiorespiratory fitness and clustering of metabolic syndrome risk factors in both girls and boys have been shown here (Fig. 5). Cardiorespiratory fitness has recently been associated with arterial compliance in children aged 9–11 years, which may support the concept that fitness may exert a protective effect on the cardiovascular system (Reed et al. 2005).

Table 2 Summary of recent cross-sectional studies examining the associations between cardiorespiratory fitness and health-related variables in children and adolescents
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Associations between cardiorespiratory fitness and cardiovascular risk factors have also been found in adolescents (Table 2). Gutin et al. (2004) found inverse associations between cardiorespiratory fitness and insulin concentrations. Furthermore, inverse associations between cardiorespiratory fitness and the likelihood of having hypertension were shown in 15- to 20-year-old subjects (Nielsen and Andersen 2003). In the present study, insulin resistance was significantly lower in the fourth cardiorespiratory fitness quartile compared with the first cardiorespiratory fitness quartile in both girls and boys (Fig. 2). However, no differences were found in systolic or diastolic blood pressure among cardiorespiratory fitness quartiles (data not shown).

A summary of recent prospective cohort studies examining the associations between cardiorespiratory fitness and health-related variables in children and adolescents is shown in Table 3. A number of longitudinal studies have suggested that a low cardiorespiratory fitness during childhood and adolescence is associated with later cardiovascular risk factors, such as hyperlipidemia, hypertension and obesity (Boreham et al. 2001, 2002; Hasselstrøm et al. 2002; Janz et al. 2002; Twisk et al. 2002; Ferreira et al. 2005). In an 8-year follow-up study, fitness during adolescence was not associated to risk factors of cardiovascular disease in adulthood, but changes in fitness from adolescence to adulthood were related to risk in adulthood. Moreover, subjects who decreased their fitness levels also changed to a worse risk factor profile (Hasselstrøm et al. 2002). Changes in cardiorespiratory fitness from adolescence to adulthood were also inversely and significantly associated with large arterial stiffness (a major risk factor for cardiovascular disease) (Ferreira et al. 2003; Boreham et al. 2004). Taken together, these results seem to support the existence of a strong association between cardiorespiratory fitness and health-related outcomes in the young population, which may suggest the importance of including cardiorespiratory fitness tests in the monitoring system.

Table 3 Summary of recent prospective cohort studies examining the associations between cardiorespiratory fitness and health-related variables in children and adolescents
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The test used to calculate cardiorespiratory fitness in this study was objectively and accurately measured, and it has been previously validated in children of the same age (Riddoch et al. 2005). However, laboratory tests present some disadvantages, as necessity of sophisticated instruments, qualified technicians and cost and time constraints, and it may cause problems for the subjects to go to the laboratory, etc. Therefore, in some circumstances, field tests may be a better option because a large number of subjects can be tested at the same time, as the tests are simple, safe and often the only feasible methods.

The cross-sectional nature of this study limits the ability to determine any causality in the results. We also do not know if an extrapolation of the association may be made for overweight and obese children or those with subclinical manifestations of cardiovascular pathologies. Nevertheless, with regular reports of increasing childhood obesity and related disease prevalence world wide, the results of this study are noteworthy. The ideal study to answer the question as to whether high levels of cardiorespiratory fitness during childhood lower the risk of developing cardiovascular diseases later in life is a randomized controlled trial with a lifetime follow-up, in which a large number of children is assigned to either an active or a sedentary life style.

In conclusion, the present study shows negative associations between cardiorespiratory fitness and features of metabolic syndrome in children aged 9–10 years. The results suggest that cardiorespiratory fitness in children, as has been shown in adults, is potentially an important health marker and should be considered to be included in a pan-European health monitoring system.