INTRODUCTION

As of 2020, the global prevalence of metabolic syndrome (MetS) in adolescents was 4.8%, representing 21.3 to 63.0 million; prevalence was even higher (7.0%) in low-income countries ¹. The weighted prevalence was estimated from studies that used different diagnostic criteria; this lack of consensus is due to several reasons. First, some criteria extrapolate adult cut-off points. In addition, waist circumference is used to determine central obesity, but it varies according to the percentiles calculated with data from specific populations. Each component of MetS is dichotomous in measurement, which does not reflect the continuous quantitative nature of the original measures. Most criteria assume that their components contribute equally, that is, they define MetS by the number of components. Finally, adolescents of different races have different metabolic characteristics, which complicates having a single definition difficult ².

In Peru, the frequency of MetS in adolescents in high Andean areas varies between 3.2% ³ and 4.6% ⁴, both figures were estimated using the Third Adult Treatment Panel (ATP-III) criteria modified by Cook. Another Peruvian study on children and adolescents with obesity attended in a specialized center in Lima found a prevalence of 22.3% ⁵. This study applied the International Diabetes Federation (IDF) criteria. ATP-III and IDF use blood pressure, some indicator of obesity, HDL cholesterol, triglycerides and serum glucose as components, which are the most frequently used components in cross-sectional studies to measure MetS in the population living at high altitudes ⁶.

The IDF, ATP-III and Ferranti criteria have been found to estimate different magnitudes of MetS in children and adolescents ⁷. These differences may be due to the particularities of the individuals in the sample of each study, such as ethnicity, eating habits and physical activity, socioeconomic status, age, among other variables; however, the fundamental element is the diagnostic criterion applied ⁸. Criteria with lax cut-off points generate higher prevalence of the MetS components; the definition of the presence of a component based on specific percentiles for age, sex and race, constructed from data from the reference population, also cause higher prevalence ⁹.

The concordance of different criteria for MetS in adolescents has been evaluated in several countries ^(10-15; however, these studies were conducted at altitudes of less than 2000 meters above sea level (masl). The frequency of MetS has been reported to be lower at high altitudes ^16,17, and the presence of its components may vary; for example, reports show a higher frequency of hypertriglyceridemia in Ecuador ¹⁸, as well as a lower frequency of hypercholesterolemia and hyperglycemia ¹⁶. A study on Tibetans reported higher blood pressure levels ¹⁹ and frequency of hypertension at higher altitudes ¹⁷. The lower frequency of MetS at high altitude could be explained by the inverse correlation between body mass index (BMI) and altitude above sea level, reflected in a lower prevalence of obesity and overweight in these populations ²⁰; and by the lower frequency of dyslipidemia at high altitudes ^16,17.

Therefore, there is no information available on the concordance of the different criteria for MetS in adolescents living in high Andean areas. In Peru, a study on adults over 40 years of age living at 3635masl found that the IDF and ATP-III criteria had a concordance index of 0.775 ²¹. Because of this knowledge gap and the difficulties in measuring MetS in high Andean areas, this study aimed to determine the concordance between five diagnostic criteria for MetS among adolescents living in a high Andean area of Peru.

MATERIALS AND METHODS

RESULTS

Concordance of criteria

The highest percentage of total concordance was found between the AHA and ATP-III criteria (99.2%). The IDF criteria had percentages of concordance of 97.0% and 97.7% with the AHA and WHO, respectively. The proportion of concordance between the criteria differed between men and women (Table 4).

Table 4 Number of concordant cases and percentage of concordance between five diagnostic criteria for metabolic syndrome. 

Group	ATP III				De Ferranti				IDF				AHA
	+	-	Total	%	+	-	Total	%	+	-	Total	%	+	-	Total	%
Total
De Ferranti	17	329	346	87.2
IDF	7	375	382	96.2	11	328	339	85.4
AHA	15	379	394	99.2	16	329	345	86.9	8	377	385	97.0
OMS	8	375	383	96.5	13	329	342	86.1	8	380	388	97.7	8	376	384	96.7
Men
De Ferranti	11	157	168	85.7
IDF	4	184	188	95.9	5	157	162	82.7
AHA	9	185	194	99.0	9	157	166	84.7	4	186	190	96.9
OMS	6	181	187	95.4	10	157	167	85.2	5	186	191	97.4	6	183	189	96.4
Women
De Ferranti	6	172	178	88.6
IDF	3	191	194	96.5	6	171	177	88.1
AHA	6	194	200	99.5	7	172	179	89.1	4	191	195	97.0
OMS	2	194	196	97.5	3	172	175	87.1	3	194	197	98.0	2	193	195	97.0

+: concordance in positive cases, -: concordance in negative cases, %: percentage of total concordance.

ATP-III: Third Adult Treatment Panel, IDF: International Diabetes Federation, AHA: American Heart Association, WHO: World Health Organization.

An “almost perfect” concordance was found between the AHA and ATP-III criteria (k = 0.905); this level of agreement was observed in men (k = 0.895) and in women (k = 0.921). “Substantial” concordance was found between the WHO and IDF criteria (k = 0.628); however, this level of concordance was not observed among women (k = 0.592). A “moderate” level of concordance was found between the IDF criteria and the ATP-III and AHA criteria, as well as between the WHO criteria and the ATP-III and AHA criteria. The Ferranti criterion had an “acceptable” level of concordance with the other criteria (Figure 1).

Figure 1 Estimation of the concordance between five diagnostic criteria of metabolic syndrome among schoolchildren from two public educational institutions in a high Andean district (Cajamarca, Peru). 

The five criteria coincided in classifying 6 adolescents (1.5%) as MetS, four criteria coincided in 3 (0.8%), three criteria in 9 (2.3%) and two criteria in 6 (1.5%). Finally, 45 (11.3%) adolescents were identified as MetS by one of the criteria used.

DISCUSSION

The AHA and ATP-III criteria had “almost perfect” concordance for identifying MetS among adolescents residing in a high Andean area of Peru; on the other hand, the Ferranti criteria had the lowest levels of agreement with respect to the IDF, AHA, WHO and ATP-III criteria. The estimated concordance coefficient between the AHA and ATP-III criteria was higher than what was found in a study of 1004 European adolescents aged 12.5 to 17 years. In that study, the AHA and ATP-III criteria reached a kappa between 0.73 and 0.80; however, as in our study, this coefficient was the highest among those generated by the comparison of five different criteria (ATP-III, AHA, WHO, IDF and those of Jolliffe & Janssen) ¹⁴.

The level of concordance between AHA and ATP-III could be explained by the fact that both criteria only differ in the definition of one component. The ATP-III criterion modified by Cook considers low HDL cholesterol when it is lower than 40 mg/dL, whereas the AHA uses values equal to or below the 10th percentile for race and sex. Due to the absence of reference values for Peruvian adolescents or residents of high Andean areas, we used the percentile values defined by a national health and nutrition survey of the United States of America ²⁸, which Cook used to define the value of 40 mg/dL for HDL cholesterol.

“Substantial” concordance was found between the WHO and IDF criteria; only one study has reported concordance between these criteria. In European adolescents, a kappa coefficient between 0.29 and 0.38 was found ¹⁴, which, according to the cutoffs applied in our study, corresponds to an “acceptable” agreement. The WHO criterion is different from the others: i) it uses BMI instead of waist circumference; ii) it defines hypertension at values equal to or higher than the 95th percentile of blood pressure; and iii) it uses the most restrictive cutoff to define low HDL cholesterol (< 35 mg/dL). Despite these differences, we found a higher concordance with the IDF criteria than previously reported. One possible explanation is that both criteria did not identify cases of arterial hypertension, another explanation may be the fact that both use the highest and closest cutoffs for defining hypertriglyceridemia.

Concordance between the ATP-III and IDF criteria has been the most studied among adolescents from different countries, with very different levels of concordance. In Latin America, the total concordance between these criteria was 97.5%, and the kappa coefficient was 0.95 among 241 adolescents aged 10 to 14 years in the state of Paraná in Brazil ¹². Another study conducted on 1200 adolescents aged 12 to 17 years in the state of Santa Cruz do Sul in Brazil estimated a kappa of 0.53 ¹⁵. A kappa of 0.39 was estimated in 851 adolescents aged 10 to 18 years in the city of Medellín in Colombia ¹⁰; while a kappa of 0.28 was estimated in 916 children and adolescents aged 9 to 18 years in the city of Mérida in Venezuela, ²⁹. Among the studies in Europe, one conducted on 379 Spanish adolescents aged 12 to 16.9 years found a kappa of 0.82 ³⁰. Another study conducted on adolescents aged 10 to 16 years in Italy reported a kappa of 0.71 ³¹, while a kappa of 0.47 was estimated in 1004 adolescents living in 10 European cities ¹⁴.

The different concordance coefficients between the ATP-III and IDF criteria can be explained by the fact that although they use the same components, the IDF criterion requires the presence of central obesity, a component that, in turn, is determined differently from ATP-III. The IDF criterion applies a cut-off determined by the 90th percentile for those under 16 years of age, while using 94 and 80 cm as cut-off points for males and females 16 years and older, respectively. Other differences are the cut-off points for defining hyperglycemia and hypertriglyceridemia, the cut-off for glycemia in IDF is lower compared to ATP-III; while the cut-off for triglyceride concentration is higher in ATP-III. Finally, IDF uses fixed cutoff points (≥130/85 mmHg) to define arterial hypertension, whereas ATP-III uses percentiles. Based on these differences, the ATP-III criterion classifies a higher proportion of adolescents as MetS when compared to IDF; this has been reported in Brazil ¹², Spain ³⁰, Colombia ¹⁰, several European countries ¹⁴, and by our study.

The Ferranti criterion identified MetS in a higher proportion of adolescents (17.1%), on average, it identified three to four times more cases than the other criteria. This finding has been reported by other studies, for example, in Brazil, the Ferranti criterion identified 17.4% of adolescents as having MetS, higher than that identified by the ATP-III criteria modified by Cook (3.3%) and IDF (1.7%) ¹². In Colombia, Ferranti’s criteria found 11.4% of MetS, also higher than the ATP-III criteria modified by Cook (3.8%) and IDF (0.9%) ¹⁰. This finding may be due to the less restrictive cut-off points of the Ferranti criteria for defining central obesity, hypertriglyceridemia and low cholesterol levels.

We found that low HDL cholesterol was the component most frequently identified by all the criteria. The Ferranti criterion defined this component in 90.4% of adolescents, followed by the ATP-III criteria modified by Cook (65%) and the IDF (63.5%). The second most frequent component was hypertriglyceridemia; likewise, the Ferranti criteria identified 48.9% of adolescents with this condition, followed by the ATP-III and AHA criteria. This pattern is similar to that found in adolescents in Colombia ¹⁰, but differs from that found in other adolescent populations. For example, the most frequent component in Spanish adolescents was abdominal obesity ^13,30, as in Mexican-American adolescents in the USA ³²; while in Brazil, the most frequent component was arterial hypertension ^12,15.

Several studies show a particular lipid profile in adolescents and adults in the Andes, characterized by high serum triglyceride levels, low HDL cholesterol levels and hypercholesterolemia ^3,33, such profile has also been found in Tibetan adults (3660 masl) ³⁴, while the prevalence of hypertriglyceridemia or low HDL cholesterol was 9.1% in adults residing above 2000 masl in China ¹⁷. It is reported that dyslipidemias may be a frequent problem in adolescents. The high frequency of dyslipidemias found in adolescents residing at almost 3000 masl could be explained by genetic factors ³⁵, and the influence of metabolic and hormonal adaptations to altitude; however, this hypothesis requires specific research.

Only the IDF and AHA criteria identified one case of elevated glycemia, both criteria have a cut-off point of 100 mg/dL. The low frequency of this component has been previously reported, with a cutoff of 110 mg/dL in adolescents in the city of Cajamarca ³, as well as in other studies on the concordance of MetS criteria in Colombia ¹⁰, Brazil ^11,15 and Spain ¹³. This finding is consistent with the adaptations of the cellular response to chronic hypoxia at high altitudes ^17,36, and with the low frequency of abdominal obesity and the consequent low risk of insulin resistance.

What we described in this concordance analysis shows how complex the diagnosis of MetS in adolescents is. These results have implications for future research in adolescents living at high altitude, as they show how crucial the selection of the diagnostic criterion is and how this decision can affect the frequency estimates of MetS. In general, Ferranti’s criterion classifies a higher proportion of adolescents as MetS; this finding does not imply better diagnostic performance; in fact, it is the criterion with the lowest concordance with the others. Secondarily, our analysis identified the high frequency of hypertriglyceridemia and low HDL cholesterol as a potential public health problem. Therefore, the diagnosis of MetS in adolescents requires criteria that considers the continuous nature of its components and the construction of scores that define cardiometabolic risk based on population-based and representative data at different altitudinal levels. Adequately defining the presence of each component will make it possible to improve the identification of MetS and to establish intervention and prevention strategies in adolescents with or without MetS.

The study has some limitations. Percentile values for systolic and diastolic blood pressure and HDL cholesterol were not available, so we used data available from NHANES III conducted in the United States. Since this was a secondary source study, no a priori calculation of the sample size was made in order to estimate concordance coefficients. The WHO criterion assesses glycemic homeostasis by means of insulin levels, glucose intolerance and fasting glucose; only the latter was used in this analysis. Finally, several criteria use arbitrary cut-off points to define the presence of a component, especially for hyperglycemia and hypertriglyceridemia; such cut-offs may vary and require reevaluation when the lifestyles and risk factors of populations change, as well as laboratory procedures. Besides, our results should be interpreted with caution. We studied a single district located in the Peruvian Andes; therefore, in view of the diverse altitudinal levels, lifestyles, and ethnicities, our results are not representative for adolescents living in the Peruvian Andes. Our results do not evaluate or conclude which criterion has the best diagnostic performance for MetS; future studies should be conducted to evaluate criterion validity compared to a reference diagnosis.The complexity of this lies in the fact that to date there is no consensus on the diagnosis of MetS in adolescents.

In conclusion, the five criteria agree by less than 2% when identifying the same group as having MetS, which produces different prevalence estimates in adolescent schoolchildren living in a high Andean area in the city of Cajamarca, Peru. The AHA and ATP-III criteria modified by Cook had “almost perfect” concordance; this level of concordance was found for both sexes. The Ferranti criterion identified MetS in 17.1% of adolescents; this criterion identified three to four times more MetS cases than the others.