Introduction

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. CVD mortality rates are influenced by several risk factors, such as smoking, changes in cholesterol and glucose levels, and also treatment availability and quality [1]. Hypertension is one of the most challenging risk factors in public health [2]. Although hypertension is more prevalent in the elderly, there has been an increase in the prevalence of hypertension in adolescents worldwide. During adolescence, hypertension is usually essential, not secondary, and influenced by the excess of weight, metabolic syndrome (MetS), and genetic factors [3].

Adolescence is a stage between the ages of 12 to 18 years, during which a series of psychological, hormonal, and anthropometric changes occur. Obesity is the most common chronic disease in this age group [4] and is related to a future decrease in life expectancy [5]. Among several cardiovascular (CV) risk factors evaluated in children and adolescents, overweight was associated with a higher prevalence of high cholesterol levels, diastolic blood pressure (BP), triglyceride level, and fasting glucose level [6, 7]. Body mass index (BMI) is the most widely method used for assessing overweight. However, it is mainly the excess of body fat that is related to the risk of chronic diseases, not being overweight [8]. BMI does not provide information on abdominal fat, which is metabolically more active and is well defined as an independent risk factor for CVDs in adults [9]. On the other hand, waist circumference (WC) is a better marker of abdominal fat and has a stronger association with CV risk factors [10].

In adolescents, the use of WC is limited due to changes in body composition caused by growth and development [10]. WC increase is not necessarily associated with BMI increase, and can be abnormal even when it is within the normal range [11]. In addition, many CV risk factors are present in children and adolescents with normal weight [12]. Therefore, measures such as neck circumference, WC, hip circumference, and waist-to-hip ratio, can be used to predict arterial hypertension, glucose metabolism, others CVD changes, and thus help identify those who need more attention [13].

The Study of Cardiovascular Risk in Adolescents – ERICA was the first nationally represented Brazilian study, designed to provide estimates of the prevalence of diabetes mellitus, obesity, CV risk factors, insulin resistance, and inflammatory markers in adolescents [14, 15, 16, 17]. The present study aims to evaluate the association between WC and elevated BP in adolescents aged 12 to 17 years with a normal BMI.

Methods

Study design and sample

The data analyzed were obtained from ERICA, a cross-national, school-based study. It is one of the most comprehensive studies on the prevalence of CV risk factors in adolescents ever conducted in Brazil and was approved by the Research Ethics Committees of the study’s central coordinating institution (IESC/UFRJ) and of each Brazilian state.

The sample was divided into 32 strata consisting of the 27 Brazilian capital cities and five sets of countryside cities containing more than 100,000 inhabitants from each of the country’s five macro-regions. Thus, the sample is representative nationally, regionally and for the capitals and the Federal District. Schools were sampled using probability proportional to size (PPS), with the measure of the size equal to the ratio between the number of the students of the school, and the distance, in kilometers, between the municipality where the school was located and the capital of the state, to avoid the spread of the sample. The systematic PPS selection was used, with schools sorted by geographic stratum, location (urban x rural) and administrative dependency (public or private). In the second stage of sampling, three combinations of shift and grade were sampled. All eligible students of the sampled classes were included. The sampling process has been described in prior publications [18, 19].

The observers were trained by ERICA’s central coordination team, according to the study protocol. An operation manual and videos were especially produced for the training of anthropometric and BP measures. The observers were trained in anthropometric measurements using the Habicht’s criterion [20] as a guide to assess inter and intra variability. Checks were conducted regularly to identify outliers, discrepancies or digit preference in measurements [18].

Between March 2013 and December 2014, a pre-trained team evaluated adolescents aged 12 to 17 years attending 1,248 schools in 121 Brazilian municipalities. An anthropometric and BP evaluation was performed; furthermore, 24-hour food abstinence was instructed, and blood laboratory tests were performed. A self-filled questionnaire with items on socio-demographic and lifestyle information was also employed.

Exclusion criteria

The study used data from adolescents of both sexes with a normal BMI [21]. We excluded from the analysis: pregnant adolescents; those with temporary or permanent physical disabilities; those who refused to participate in the study; those who did not sign the informed consent form (ICF) or did not bring the ICF signed by the individual responsible, when required by the municipality.

Ethical issues

This study was conducted according to the principles of the Helsinki declaration. The approval of the Ethical Committee at each of the 26 States and for the Federal District was obtained. Permission to conduct the study was obtained in all State and local Departments of Education and in all schools. Written informed consent was obtained from each student after carefully explanation about the study and its procedures, and also from their parents for those who are invited to take blood collection (those studying in the morning). The student’s privacy and confidentiality were guaranteed throughout the study.

Data collection

Weight was evaluated using the Leader model P200M electronic scale with a capacity of up to 200 kg and variation of 50 g. Stature was measured twice using the Exact Height portable stadiometer with a variation of 0.1 cm, considering the average of the two values obtained. Weight and height were used to classify the nutritional status from the BMI calculation (weight/height); the specific BMI curves proposed by the World Health Organization (2007) for age and sex were employed. The cut-off point used was as follows: Z score of –2 to 1 (adequate weight) [22].

WC was measured using a Sanny inextensible measuring tape with a variation of 0.1 cm at the midpoint between the lower curvature of the last fixed rib and the superior curvature of the iliac crest, with the adolescents standing and with their arms alongside the body, feet together, and abdomen relaxed [17]. The WC was categorized into quartiles for sex and age in adolescents with a normal BMI.

BP was measured and classified according to the Fourth Diagnosis, Evaluation [23], and High Blood Pressure Treatment in Children and Adolescents, which considers sex, height, and age. A digital monitor (Omron 705-IT) validated for use in adolescents was used with a cuff appropriate for the arm perimeter of the right arm. The students were seated with their feet flat on the floor. Three measurements were obtained at 3-minute intervals, using the average of the last two measurements. According to the proposed classification, adolescents are considered normotensive when BP is below 90 percentile; pre-hypertensive (normal-elevated BP) when BP is between the 90th and the 95th percentiles; and hypertensive when BP is equal or above 95th percentile. In the present study, BP values ≥ 90th percentile were defined as ‘elevated BP’.

Statistical analysis

For each sex and age (12 to 17 years), restricted to adolescents with adequate nutritional status, the quartiles of the WC measures were calculated. Thereafter, the adolescents were classified into one of the quartiles according to their age and sex. Age was analyzed in two aged - groups, 12–14 years and 15–17 years, due to the homogeneity in anthropometric and blood pressure parameters in each age group.

The association between WC and BP, considering two BP levels (normal and elevated), was analyzed by adjusting the Poisson Regression model, estimating the prevalence ratio (PR) and the respective 95% confidence intervals. All analyses were performed considering the complex sampling design. Data were analyzed using the Stata/SE v.14.1 survey module (StataCorp LP, US). In addition to the natural weights of the sample design, post-stratification estimators that modified natural weights by calibration factors were used. Those calibration factors were obtained by dividing population totals by totals estimated by natural weights for the post-strata, defined as 12 estimation domains, corresponding to age and sex combinations, considering the population data of adolescents enrolled in all schools). P values of < 0.05 were considered to indicate statistical significance.

Results

Discussion

The correlation between excess of weight, evaluated by BMI, and elevation of blood pressure is well known, but the role of other anthropometric measures to identify individuals at risk when BMI is normal has been poorly explored so far. In this study, we demonstrated in a large population of adolescents between 12 and 17 years old within the normal range of BMI that increased WC is associated with a higher prevalence of elevated BP. This is a novel finding with clinical implication for the screening of elevated blood pressure among adolescents, especially considering the growing prevalence of hypertension worldwide [24].

The prevalence of high blood pressure among adolescents is increasing [3]. In our study, the prevalence of elevated BP was compatible with recent reports which grouped pre-hypertensive and hypertensive status in the analysis [25, 26]; and also with the total population of ERICA study, in which 14.5% pre-hypertensive and 9.6% hypertensive adolescents were identified, aiming total prevalence of elevated BP of 24.1% [14]. Despite that, it is a not common practice to screen for hypertension among children and adolescents routinely [27]. Many countries and organizations have established their own BP reference values [28], without a consensus, making hypertension identification even more difficult. In fact, recommendation of screening for hypertension is insufficient [29], and is currently under review. At the present, only the evaluation of BP in individuals above the age of 18 years is recommended [30]. Our results reinforce the need for screening, indicating that WC is a valuable marker to help in the identification of those at risk for hypertension, even when BMI is normal.

BMI and WC are both indicators of adiposity that correlate with hypertension in the general population [27, 31, 32]. In adults, WC is a reliable marker of abdominal fat as demonstrated by imaging methods and is an independent and well-established risk factor for CVDs [33]. WC is also considered a predictor of visceral adiposity and hypertension in the young population [27, 31]. Data describing noninvasive biomarkers for use in screening of adolescents and young adults are limited [13]. When comparing anthropometric measurements and abdominal fat assessment using imaging methods for children and adolescents, WC shows a better correlation with visceral adiposity then other anthropometric parameters, although only a few studies have proposed this analysis [34]. In obese Mexican adolescents, the waist-to-hip ratio was superior in identifying cardio-metabolic risk factors [35] but in larger samples, BMI and WC performed better [27, 36]. Recently, neck and wrist circumferences have emerged as useful measures in demonstrating the central distribution of fat; however, they could only serve as an alternative, as the predictive potential is still undetermined [37, 38]. There is a criticism regarding WC in that it does not allow the quantification of adipose tissues, nor does it distinguish visceral fat from subcutaneous fat. Also, there is no standardized method for measuring WC or defined reference values for children and adolescents [37, 39].

Although our study has the strength of a very large sample, it has also some limitations. Similar to several studies that analyzed anthropometric measures and associated factors in children and adolescents, this is a cross-sectional study that does not allow clinical diagnosis of hypertension to be established. Also, BP levels were obtained at a single visit, which may overestimate elevated BP prevalence. However, because of the young age of the study population it is unlikely that the association observed is due to reverse causality or survival bias, two important problems related to inference in cross-sectional studies. The categorization of the waist perimeter per quartile minimizes measurement variation problems, since no cutoff values are defined for this population. Besides that, we were able to evaluate the WC independent of BMI.

Conclusion

We have demonstrated that even in adolescents with a normal BMI, increased WC is strongly associated with elevated BP. Our findings reinforce the need of assessment of blood pressure in adolescents, and evaluation of obesity in this population shall not be restricted to BMI assessment, but also WC. Moreover, definition of cut-off points for WC in adolescents would facilitate its use in clinical practice.