Abstract
Background
High blood pressure (BP) in children and adolescents is a major public health concern globally, including in India. It is typically defined by BP > 95th percentile of normative BP distribution, with the American Academy of Pediatrics Clinical Practice Guidelines (AAP-CPG 2017) being most widely used. However, Indian-specific reference derived from healthy children set higher BP cut-offs than AAP-CPG 2017, leading to debate about their suitability. This study compares high BP prevalence using both references and examines how each classification by the 2 reference standards relates to cardiometabolic risk factors.
Methods
A secondary analysis of cross-sectional data from the Comprehensive National Nutrition Survey (2016–2018) was conducted to compare the prevalence of high BP in Indian adolescents aged 10–16 years using Indian and AAP-CPG 2017 references. The association between cardio-metabolic risk markers and high BP classified by these references was examined by survey weighted multiple log-binomial regression to examine the validity of each reference standard.
Results
In young adolescents aged 10–12 years, the prevalence of high BP was 16% (95% confidence interval [CI], 13.6–19%) and 33.6% (95% CI, 30.4–37%) by Indian and AAP-CPG reference respectively. Similarly, in older adolescents aged 13–16 years, the prevalence of high BP was lower with Indian reference. The adjusted risk ratios (ARRs) for high triglycerides, total cholesterol, and low-density lipoprotein were significantly elevated in young adolescents with high BP by AAP-CPG 2017 reference but not with Indian reference.
Conclusions
The prevalence of high BP among Indian adolescents differed significantly based on the BP reference standard used. Clustering of cardiometabolic risk markers with high BP was observed when using the AAP-CPG reference but not with Indian reference. However, these findings should be interpreted cautiously given the cross-sectional study design with single visit BP measurement and limited generalizability of the Indian BP reference standard. Larger, nationally representative studies using standardized BP measurement methods are essential to establish validated BP norms for Indian adolescents.
Keywords: Blood pressure nomogram or reference range, Hypertension, Adolescents, CNNS
BACKGROUND
High blood pressure (BP) or hypertension in adolescents is a growing public health problem worldwide and is associated with obesity, metabolic syndrome, and cardiovascular disease [1]. The diagnosis of hypertension in adolescents is a statistical definition based on the normative BP distribution measured by an auscultatory method in healthy adolescents according to sex, age, and height and is defined as systolic BP (SBP) and/or diastolic BP (DBP) ≥ 95th percentile. The most widely used reference for BP is provided in the updated Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents by the American Academy of Pediatrics in 2017 (AAP-CPG 2017). In a recent study using the reference recommended by AAP-CPG 2017, the prevalence of high BP was found to be high in Indian adolescents (35% in adolescents between 10–12 years and 25% in adolescents ≥ 13 years) [2]. The reference for BP values used in the AAP-CPG 2017 guidelines were derived from data of several studies conducted in the United States (US) (49,967 children and adolescents from the 1996 National High Blood Pressure Education Program Working Group) [3]. There are concerns that BP might differ according to ethnicity or race since it is well-known that both genetic and environmental determinants impact the distribution of BP in a population [4]. Therefore, the appropriateness of identifying high BP using normative data of BP established for one population in other settings is questionable.
Several countries have established population-specific BP references or nomograms according to the age, sex, and height of their population for specific age groups [5,6]. In India, a single-center study deriving population specific reference for BP values was published in 2009 [7].
This study aimed to compare the BP reference values (i.e., 95th centile of SBP and DBP) and the prevalence of high BP in Indian adolescents aged 10–16 years from the Comprehensive National Nutrition Survey (CNNS) by applying Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents 2017 [3] hereinafter called the AAP-CPG reference and BP reference for Indian children obtained from a single center [7], hereinafter referred to as the Indian reference. The clustering of cardio-metabolic risk markers such as high blood sugar, high glycosylated hemoglobin (HbA1c), high triglyceride, high cholesterol, high low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and creatinine in those with high BP by each of these references were also examined.
METHODS
The study is based on a secondary analysis of data of adolescents from CNNS, a nationally representative cross-sectional survey undertaken between 2016 and 2018 under the aegis of the Ministry of Health and Family Welfare, Government of India. Details of survey design and sampling methods are published elsewhere [8]. The ethical approval was obtained from the ethics committee of the Post Graduate Institute of Medical Education and Research in Chandigarh, India.
Although BP data for adolescents aged 10–19 years is available in the CNNS, we restricted the comparative analysis of the 2 references up to 16 years of age since the Indian reference was applicable to adolescents only up to 16 years of age.
Measurement of BP
The details of the measurement of BP are provided in the CNNS report [8]. Briefly, 3 BP readings were measured with a gap of 2 minutes using automated devices to reduce the observer’s bias and digit preferences. The mean of the last 2 readings of SBP and DBP was used for the analysis. All BP readings more than 200 mmHg were deemed inaccurate (less than 0.05% of all BP readings) and were not considered for this analysis.
Since there are no follow-up BP measurements for the confirmation of true hypertension status, the term “high BP” was used instead of hypertension. To compare the performance of the 2 different references, high BP was defined as values above the 95th percentile value based on age, sex, and height-specific normative distribution of BP by each of the references. The criteria for selecting healthy children and adolescents in the development of these references are detailed in Supplementary Table 1.
Cardio-metabolic risk markers
Biochemical indicators for cardio-metabolic risk markers including blood glucose, HbA1c, lipid profile (serum cholesterol, LDL, HDL, and triglyceride), as well as serum creatinine, were measured in adolescents using established international methods [3,8]. Dysglycemia in adolescents was identified when the fasting glucose level exceeded 100 mg/dL or the HbA1c value was ≥ 5.7%. The threshold for total cholesterol was set at 200 mg/dL, while thresholds for elevated LDL, low HDL, and increased triglyceride levels were ≥ 110 mg/dL, ≤ 45 mg/dL, ≥ 90 mg/dL, respectively [9,10,11,12].
Measurement of serum creatinine
Kidney function among children and adolescents was assessed by estimating serum creatinine by spectrophotometry, Alkaline picrate - kinetic International Federation of Clinical Chemistry and Laboratory Medicine Isotope Dilution Mass Spectrometry standardized Jaffe rate method (National Health and Nutrition Examination Survey, 2007–2008) in the CNNS survey [8].
The estimated glomerular filtration rate (eGFR) was estimated by modified Schwartz equation [13].
Measurement of anthropometry
Body mass index (BMI)-for-age z score (BAZ) was calculated using the World Health Organization Growth Reference Standard [14] and adolescents were classified into 4 categories of BAZ—underweight (≤ −2 standard deviation [SD]), normal (−1 SD to 1 SD), overweight (1 SD to 2 SD), and obese (≥ 2 SD). All BAZ scores < −5 and > 5 were excluded from the analysis.
The wealth index, a proxy for socio-economic status, and area of residence (rural/urban), based on the participant’s geographical location, were obtained directly from the CNNS dataset and were used for further analysis.
Statistics
The distribution of high BP prevalence and its 95% confidence interval (CI) based on the 2 references (Indian and AAP-CPG) are reported separately for different age groups (less than 13 years and 13–16 years), sex (male and female), and BMI categories (underweight, normal, overweight, and obese). Mc Nemar’s χ2 test was used to examine differences in the prevalence of high BP between the Indian and AAP-CPG reference values.
The impact of the different cut-offs recommended by the references on cardio-metabolic risk markers was done by classifying the adolescents into 3 categories: the first category included adolescents as having high BP by both Indian and AAP-CPG reference. The second category consisted of adolescents classified as high BP by AAP-CPG reference alone but not by Indian reference. This is the category of interest as we intend to examine if higher risk of cardio-metabolic risk markers exists for adolescents classified in this category who are classified as normal BP by Indian reference. The third category included those classified as having normal BP by both Indian and AAP-CPG reference and served as the comparator group for analysis. Since only 6 adolescents were classified as high BP by Indian reference alone and not by American Academy of Pediatrics (AAP) reference, it was not considered as separate group for comparative analysis. Multiple log-binomial regression was used to evaluate if the group of adolescents identified as high BP by the AAP-CPG reference alone but not by Indian reference are also at risk of higher proportion of cardio-metabolic risk markers. It was expected that these adolescents will have higher adjusted risk ratios (ARRs, 95% CI) for each cardio-metabolic risk marker compared to adolescents classified as normal (normal BP by both references). The initial minimally adjusted model included adjustment for sex alone, given the known differences in high BP prevalence between males and females, and to specifically examine the effect of the reference used and later models included sex, age, BMI categories, wealth index, and area of residence as covariates. The association of serum creatinine with high BP was examined only in a subset (77.5% of the included sample) in whom this data was available. All statistical analyses were survey-weighted and carried out using R software (version: 4.2.1; R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
The final sample sizes for comparing BP cut-offs by the 2 different references for < 13 years and 13–16 years were 3,862 and 4,995, respectively (Fig. 1). The characteristics of the participants are presented in Table 1.
Fig. 1. Flowchart of sample size for BP among adolescents.
CNNS, Comprehensive National Nutrition Survey; BP, blood pressure.
Table 1. Distribution of high BP by demographic characteristics of study participants.
| Characteristics | High BP percent (95% confidence interval) | |||
|---|---|---|---|---|
| Indian reference | AAP reference | |||
| All adolescents (n = 8,857) | 12.06 (10.58–13.71) | 27.20 (25.03–29.50) | ||
| Age categories (yr) | ||||
| Age < 13 (n = 3,862) | 15.98 (13.62–18.67) | 33.62 (30.43–36.96) | ||
| Age 13–16 (n = 4,995) | 8.90 (7.31–10.80) | 22.06 (19.72–24.58) | ||
| Sex categories | ||||
| Male (n = 4,599) | 14.30 (12.31–16.56) | 26.39 (23.69–29.28) | ||
| Female (n = 4,258) | 9.68 (8.08–11.55) | 28.06 (25.36–30.93) | ||
| BMI categories | ||||
| Underweight (BMI z score < −2, n = 1,728) | 11.77 (9.38–14.67) | 24.73 (21.47–28.30) | ||
| Normal weight (BMI z score −2 to 1, n = 6,231) | 11.57 (9.89–13.49) | 27.22 (24.65–29.94) | ||
| Overweight (BMI z score 1 to 2, n = 600) | 11.16 (7.35–16.57) | 30.98 (24.52–38.28) | ||
| Obese (BMI z score > 2, n = 194) | 23.25 (12.61–38.88) | 38.76 (26.25–52.95) | ||
| Cardio metabolic risk factors | ||||
| Blood glucose | ||||
| Normal (n = 5,749) | 11.47 (9.71–13.51) | 25.57 (23.15–28.15) | ||
| High glucose (n = 1,152) | 15.41 (11.28–20.69) | 30.91 (25.47–36.94) | ||
| Triglyceride | ||||
| Normal (n = 4,108) | 12.53 (10.57–14.79) | 26.70 (24.9–29.70) | ||
| High triglyceride (n = 3,453) | 11.92 (9.56–14.77) | 27.78 (24.73–30.03) | ||
| HbA1c | ||||
| Normal (n = 7,096) | 11.72 (10.11–13.55) | 27.18 (24.78–29.72) | ||
| High HbA1c (n = 496) | 11.77 (8.03–16.94) | 25.64 (19.56–32.84) | ||
| Total cholesterol | ||||
| Normal (n = 7,208) | 12.35 (10.71–14.21) | 27.61 (24.81–29.64) | ||
| High cholesterol (n = 347) | 10.52 (4.83–21.38) | 27.21 (16.74–40.99) | ||
| High LDL | ||||
| Normal (n = 6,488) | 12.22 (10.49–14.17) | 26.68 (24.24–29.27) | ||
| High LDL (n = 1,042) | 11.92 (8.30–16.83) | 30.04 (24.43–36.31) | ||
| Low LDL | ||||
| Normal (n = 7,309) | 12.22 (10.54–14.14) | 27.28 (24.97–29.72) | ||
| Low LDL (n = 221) | 10.63 (5.53–19.45) | 20.85 (13.85–30.14) | ||
BMI z score computed according to World Health Organization standards [14].
BP, blood pressure; AAP, American Academy of Pediatrics; BMI, body mass index; HbA1c, glycosylated hemoglobin; LDL, low-density lipoprotein.
Comparison of 95th centile BP values
The cut-off values for SBP and DBP in the 2 references corresponding to the 50th percentile of height for each age and sex is presented in Table 2. When we compare at the 50th percentile of height, the SBP and DBP cut-offs derived from Indian reference standards were consistently higher than those from AAP across most ages in both boys and girls. For boys, from ages 10–13 years, Indian SBP cut-offs were 1–3 mmHg higher than AAP, while DBP values were 4–5 mmHg higher. From age 14 years onwards, the pattern reversed for SBP, with Indian cut-offs being 1–3 mmHg lower than AAP though DBP cut-offs remained 3–4 mmHg higher (Table 2). In contrast, for girls Indian cut-offs were consistently 5–7 mmHg higher for SBP and 6–8 mmHg higher for DBP across all ages from 10–16 years.
Table 2. Systolic and diastolic BP threshold for classification of high BP (95th percentile) by Indian and AAP reference.
| Age (yr) | Indian [7] | AAP [3] | Difference between Indian and AAP; International cut-offs (systolic/diastolic BP) | |||
|---|---|---|---|---|---|---|
| BP cut-off (systolic/diastolic, mmHg) | 50th centile of height (cm)a | BP cut-off (systolic/diastolic, mmHg) | 50th centile of height (cm)a | |||
| Boys | ||||||
| 10 | 119/81 | 137 | 116/77 | 139 | (+3/+4) | |
| 11 | 120/82 | 142 | 118/78 | 144 | (+2/+4) | |
| 12 | 122/83 | 146 | 121/78 | 149 | (+1/+5) | |
| 13 | 125/84 | 153 | 125/78 | 156 | (+0/+6) | |
| 14 | 127/85 | 161 | 130/81 | 164 | (−3/+4) | |
| 15 | 130/86 | 164 | 132/83 | 170 | (−2/+3) | |
| 16 | 133/88 | 166 | 134/84 | 174 | (−1/+4) | |
| Girls | ||||||
| 10 | 122/82 | 132 | 116/76 | 138 | (+6/+6) | |
| 11 | 125/84 | 143 | 118/77 | 144 | (+7/+7) | |
| 12 | 127/86 | 149 | 122/78 | 151 | (+5/+8) | |
| 13 | 130/87 | 152 | 124/79 | 157 | (+6/+8) | |
| 14 | 132/88 | 154 | 125/80 | 160 | (+7/+8) | |
| 15 | 133/89 | 156 | 126/81 | 162 | (+7/+8) | |
| 16 | 133/89 | 155 | 127/81 | 163 | (+6/+7) | |
BP, blood pressure; AAP, American Academy of Pediatrics.
aThe 50th percentile of height distribution considered in the reference data for the development of BP references [3,7]. The difference is calculated as (Indian − AAP). The first value in the parentheses represents the difference between Indian and AAP systolic and diastolic BP, respectively.
Prevalence of high BP according to reference
Overall (10–16 years; n = 8,857), the prevalence of high BP by each of the 2 references were different with the proportion by Indian and AAP-CPG references being 12.1% and 27.2%, respectively (Table 1). In young adolescents aged 10–12 years, the prevalence of high BP by Indian reference was almost half (16%; 95% CI, 13.6–19) compared to that by AAP-CPG reference (33.6%; 95% CI, 30.4–37.0). Similarly, in older adolescents aged 13–16 years, the prevalence of high BP was lower with Indian reference (8.9%; 95% CI, 7.3–11) compared to AAP-CPG references (22.1%; 95% CI, 19.7–25). Among adolescents classified as high BP by any of the 2 references, only 16% of young adolescents and 9% of older adolescents (13–16 years) were classified as high BP by 2 references (Supplementary Fig. 1).
Association of high BP with cardio-metabolic risk factors
The prevalence of high BP as classified by AAP-CPG references monotonically increased by BMI categories from underweight to obese whereas by Indian reference, the prevalence of high BP was higher only in the obese group but not in the other groups.
The prevalence of high BP by 2 references was comparable within the abnormal levels of cardio-metabolic risk markers such as blood glucose, HbA1c, total cholesterol, and HDL except with triglyceride and LDL. The prevalence of high BP by AAP-CPG references was higher than reported by Indian reference among individuals with abnormal triglyceride and LDL levels (Supplementary Figs. 2 and 3).
The sex ARR of abnormal metabolic biomarkers among adolescents classified as high BP by Indian and AAP references is shown in Supplementary Table 2. Further the ARR adjusted for sex, age, BMI categories, wealth index, and area of residence is shown in Fig. 2 respectively. Among young adolescents 10–12 years, the ARR of high blood glucose was significantly higher in adolescents with high BP classified by both, Indian and AAP-CPG references (ARR = 1.73; 95% CI, 1.38–2.16) and also by AAP-CPG alone (ARR = 1.31; 95% CI, 1–1.63) compared to those classified as normal by both references. The ARR of high triglyceride (ARR = 1.12; 95% CI, 1–1.25), high total cholesterol (1.52; 95% CI, 1.07–2.15) and high LDL (1.57; 95% CI, 1.28–1.93) were also higher with high BP by AAP-CPG reference alone (Fig. 2A) compared to those classified as normal by both references. However, among older adolescents (13–16 years), there was no association between cardio-metabolic risk markers and high BP by either of the reference (Fig. 2B). Also, the ARR for low eGFR (< 60 mL/min/1.73 m2) among young adolescents with high BP by only AAP-CPG reference was 1.96 (95% CI, 1.31–2.93) compared to the normal BP category by both Indian and AAP reference (Supplementary Table 3).
Fig. 2. ARR of cardio-metabolic risk markers in adolescents classified as high BP by Indian and AAP references. ARR of elevated cardio-metabolic markers in adolescents classified with high BP according to Indian and AAP references, adjusted for sex, area, body mass index, and wealth index. (A) Young adolescents aged 10–12 years. (B) Older adolescents aged 13–16 years. The dashed vertical line at RR = 1 indicates no risk. The text labels display the percentage of adolescents with elevated cardio-metabolic markers across different BP categories. Each color represents a specific high BP classification: Blue: reference (normal by Indian & AAP [n10–12 yr: 2,382; n13–16 yr: 3,733]), Red: both Indian & AAP (n10–12 yr: 633; n13–16 yr: 464) and Green: AAP alone (n10–12 yr: 846; n13–16 yr: 793).
ARR, adjusted risk ratio; BP, blood pressure; AAP, American Academy of Pediatrics; RR, relative risk; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HbA1c, glycosylated hemoglobin.
DISCUSSION
In the study which included 8,857 adolescents, we aimed to assess the impact of using the AAP-CPG and Indian BP reference values in adolescents and the clustering of cardio-metabolic risk markers among those with high BP. We observed that reference values differed systematically between Indian and APP reference standards, with Indian cut-offs generally higher than AAP values, particularly for DBP and among girls. According to the BP reference used, the diagnosis of high BP varied with prevalence being notably lower when applying the Indian reference compared to the AAP reference in both younger and older adolescents. This difference in prevalence of high BP is attributed to differences in variability of 95th centile cut-off between the 2 references.
Since the definition of hypertension is based on the normative distribution of BP, the reference values or the 95th centile BP are crucial. The differences in the reference values may occur due to many factors. Heterogeneity in the methodology employed to perform the measurements (auscultatory versus oscillometric), and the criteria of inclusion/exclusion of adolescents for deriving the normative BP distribution. The 2 references, however, used mercury sphygmomanometer for measuring BP. Even though only non-overweight children and adolescents were selected by the 2 references for deriving BP centiles, it is important to note that children and adolescents with genetic diseases, acute, or serious chronic diseases were not excluded or description related to this were not provided (Supplementary Table 1).
Since height is an important factor affecting BP, the 95th percentile SBP and DBP values at the 50th percentile height in different age groups and sex were also compared between the 2 references (Table 2). It is to be noted that the median height was lower in the Indian reference across all age and sex groups compared to AAP-CPG reference, but the SBP and DBP values corresponding to the 95th percentile of the BP distribution in Indian reference were 1 to 7 mmHg and 3 to 8 mmHg higher, respectively. This explains the reduced prevalence of high BP noted with the Indian reference, compared to AAP-CPG. However, this remains a paradox, as BP is expected to increase with age and the taller population is the one that is expected to have higher BP cut-off. The impact of weight variability across age and sex on BP could not be assessed due to the unavailability of their weights in the reference dataset.
Whether the higher SBP and DBP observed in the Indian reference could be generalized to the Indian population is unclear since the Indian reference is derived from a single region and does not represent the ethnic and socio-economic diversity of Indian population. Therefore, we examined the distribution of SBP and DBP with the National Family Health Survey (NFHS)-4th round [15] conducted in 2015–16, which is a larger and more representative sample of the Indian population. In this data of 15,936 boys and 1,04,132 girls aged 15–19 years in the NFHS-4 survey [16], the 95th centile SBP and DBP for 50th centile height were 129.8 mmHg and 84.1 mmHg in boys 15–16 years and 125.65 mmHg and 88.1 mmHg in girls 15–16 years of age. The SBP and DBP values were higher compared to AAP-CPG reference and were also higher than corresponding Indian reference values by 1.7 mmHg and 2.9 mmHg in boys and 7.35 mmHg and 0.9 mmHg in girls, respectively. This suggests that BP may be higher in apparently healthy Indian adolescents compared to American adolescents. A possible pathophysiological explanation for higher SBP and DBP in healthy Indian adolescents is lacking but could be due to the high prevalence of low birth weight in both urban and rural Indian children [17]. However, the data on birth weight is not available in the current study. Controversies remain regarding the specific influence of regions and ethnicity on BP values in children and adolescents. A possible geographic influence is obvious from examining region-specific childhood BP distributions among different countries. Sánchez et al. [18] found that SBP and DBP values were higher in 34,946 Spanish children and adolescents than in their US counterparts. Furthermore, Tobagonian adolescents had SBP and DBP that were 10 mmHg lower and higher, respectively, than their United Kingdom counterparts [19]. Similarly, in National Blood Pressure Reference for Chinese Han [6], the 95th percentile SBP were higher for boys aged 7 to 15 years and lower for boys aged 16 to 17 years relative to the US reference values for the median height. In girls, relative to the US reference values, the 95th percentile of SBP were similar for ages 7 to 11 years and lower at ages 12 and older. However, 95th percentiles of DBP in both sexes were similar in both references [6]. The comparisons between different country-specific references in Fig. 3 shows that the BP reference centile for India is quite high compared to other country-specific BP reference norms (Korea [20], China [6], Turkey [21]) with APP-CPG.
Fig. 3. Comparison of SBP and DBP among boys and girls across different country-specific cut-offs. The 95th BP percentile for boys and girls for different country-specific references. (A) Comparison of SBP among boys. (B) Comparison of SBP among girls. (C) Comparison of DBP among boys. (D) Comparison of DBP among girls.
SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure; AAP, American Academy of Pediatrics.
Cardio-metabolic risk markers are important markers for the potential development of non-communicable diseases. High BP is often linked with many cardio-metabolic risk markers such as elevated fasting blood glucose levels, obesity, kidney function, and abnormal lipid profiles even in adolescents [22,23,24]. Many studies have consistently demonstrated a positive association between BMI and both SBP and DBP among adolescents, indicating that higher BMI levels are associated with elevated BP [25,26,27]. However, in the current study an association of BMI with high BP was observed with AAP-CPG reference and not with Indian reference. High BP and abnormal lipids have been identified as the most important risk factors of cardio vascular diseases [28]. The stronger association of high BP with total cholesterol, LDL and triglyceride by AAP-CPG than by the Indian reference indicate that adolescents who had higher risk of these conditions could have been missed by the Indian reference. Although cardiovascular assessment such as echocardiogram may have been a more confirmatory measure, it was not done in this survey. The stronger association of high BP with metabolic markers when using AAP-CPG may be partly explained by threshold bias arising from systematically lower BP cut-offs in the AAP reference rather than true physiological differences. This emphasizes the need for larger representative reference data linking BP thresholds with cardiovascular outcomes in Indian adolescents to determine optimal cut-off values.
The strengths of our study include robust design of the survey and a large nationally representative sample size, which allowed us to perform subgroup analyses. However, the study also has several limitations. The diagnosis of pediatric hypertension must be based on BP measurement at least on 3 separate occasions. However, BP measurements were performed on only one occasion in the CNSS survey using an undocumented oscillometric device for BP measurement. Due to this reason, we have used the word high BP instead of hypertension for classification of BP. The BP in CNNS was measured using oscillometric devices and compared to reference standards developed based on auscultatory method. This can introduce a bias in the classification of high BP. Besides, the present study excluded late adolescents (17–19 years) as Indian reference data included only until age 16, thereby limiting the generalizability of our findings to the whole adolescent population (10–19 years). Being a cross-sectional study, follow-up data was not available to examine the later consequences of high BP measured in these children and a conclusion on the choice of reference needs further longitudinal data. Also, cardiovascular outcomes were not recorded in the participant children, which is a limitation for validation. Future studies incorporating echocardiographic or vascular structural markers (e.g., left ventricular hypertrophy, carotid intima-media thickness, arterial stiffness) would provide stronger clinical validation of which BP reference more accurately predicts cardiovascular risk. In addition, the CNNS dataset lacked information on several key determinants of BP, including salt intake, physical activity, family history, stress, sleep patterns, and environmental factors such as temperature, which could have influenced BP distribution.
CONCLUSIONS
The results highlight the significant difference in the prevalence of high BP among adolescents between the Indian reference and AAP-CPG 2017 reference with AAP-CPG reference identifying more adolescents with cardiometabolic risk factors. Given the cross-sectional design and single-visit BP measurement as well as limitations of single center Indian reference data, these findings should be viewed as preliminary and hypothesis-generating. The study underscores the pressing need to establish and validate a nationally representative BP reference for Indian children and adolescents using standardized measurement methods.
Abbreviations
- AAP
American Academy of Pediatrics
- AAP-CPG
American Academy of Pediatrics Clinical Practice Guidelines
- ARR
adjusted risk ratio
- BAZ
body mass index-for-age z score
- BMI
body mass index
- BP
blood pressure
- CDC
Centers for Disease Control and Prevention
- CI
confidence interval
- CNNS
Comprehensive National Nutrition Survey
- DBP
diastolic blood pressure
- eGFR
estimated glomerular filtration rate
- HbA1c
glycosylated hemoglobin
- HDL
high-density lipoprotein
- LDL
low-density lipoprotein
- NFHS
National Family Health Survey
- NHANES
National Health and Nutrition Examination Survey
- RR
relative risk
- SBP
systolic blood pressure
- SD
standard deviation
- US
United States
Footnotes
Funding: None.
Competing interest: The authors declare that they have no competing interests.
Availability of data and materials: The data underlying this article were accessed from Ministry of Health and Family Welfare, Government of India; UNICEF; and Population Council. Comprehensive National Nutrition Survey National Report. New Delhi: Ministry of Health and Family Welfare; 2019.
Ethics approval and consent to participate: The study is based on a secondary analysis of data from Comprehensive National Nutrition Survey. The ethical approval was obtained from the ethics committee of the Post Graduate Institute of Medical Education and Research in Chandigarh, India.
Consent for publication: Not applicable.
- Conceptualization: Saji A, Thomas T, Sachdev HS, Kurpad AV, Vasudevan A.
- Data curation: Saji A.
- Formal analysis: Saji A.
- Investigation: Thomas T.
- Methodology: Saji A, Thomas T, Sachdev HS, Vasudevan A.
- Software: Saji A.
- Supervision: Thomas T, Sachdev HS, Kurpad AV, Vasudevan A.
- Validation: Thomas T, Sachdev HS, Kurpad AV, Vasudevan A.
- Visualization: Saji A.
- Writing - original draft: Saji A, Thomas T, Vasudevan A.
- Writing - review & editing: Saji A, Thomas T, Sachdev HS, Kurpad AV, Vasudevan A.
SUPPLEMENTARY MATERIALS
Inclusion criteria for deriving reference for blood pressure
RR of high cardio-metabolic makers for adolescents classified as high BP by Indian and AAP references
RR of low eGFR for adolescents classified as high BP by Indian and AAP references
Venn diagram showing concordance between AAP and Indian BP references in adolescents. (A) Distribution of high and normal BP in adolescents 10–12 years by different BP references. (B) Distribution of high and normal BP in adolescents 13–16 years by different BP references.
Prevalence of high BP by different references in adolescents 10–12 years classified with high and normal cardio-metabolic markers. Prevalence of high BP by Indian and AAP references among children 10–12 years old classified with high and normal cardio-metabolic markers. (A) High blood glucose vs. normal blood glucose; (B) High triglyceride vs. normal triglyceride; (C) High HbA1c vs. normal HbA1c; (D) High cholesterol vs. normal cholesterol; (E) High LDL vs. normal LDL; (F) Low HDL vs. normal HDL. The solid line represents high BP prevalence with 95% confidence interval among children (10–12 years) with high cardio-metabolic markers and the dashed line represents high BP prevalence with confidence interval among children (10–12 years) with normal cardio-metabolic markers.
Prevalence of high BP among different references in adolescents 13–16 years. Prevalence of high BP by Indian and AAP references among adolescents 13–16 years old classified with high and normal cardio-metabolic markers. (A) High blood glucose vs. normal blood glucose; (B) High triglyceride vs. normal triglyceride; (C) High HbA1c vs. normal HbA1c; (D) High cholesterol vs. normal cholesterol; (E) High LDL vs. normal LDL; (F) Low HDL vs. normal HDL. The solid line represents high BP prevalence with 95% confidence interval among adolescents (13–16 years) with high cardio-metabolic markers and the dashed line represents high BP prevalence with confidence interval among adolescents (13–16 years) with normal cardio-metabolic markers.
References
- 1.Rutigliano I, De Filippo G, Pastore L, Messina G, Agostoni C, Campanozzi A. Obesity-related hypertension in pediatrics, the impact of American Academy of Pediatrics guidelines. Nutrients. 2021;13:2586. doi: 10.3390/nu13082586. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Sharma AK, Metzger DL, Rodd CJ. Prevalence and severity of high blood pressure among children based on the 2017 American Academy of Pediatrics guidelines. JAMA Pediatr. 2018;172:557–565. doi: 10.1001/jamapediatrics.2018.0223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140:e20171904. doi: 10.1542/peds.2017-1904. [DOI] [PubMed] [Google Scholar]
- 4.Wang B, Wu T, Neale MC, Verweij R, Liu G, Su S, et al. Genetic and environmental influences on blood pressure and body mass index in the National Academy of Sciences-National Research Council World War II veteran twin registry. Hypertension. 2020;76:1428–1434. doi: 10.1161/HYPERTENSIONAHA.120.15232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.El-Shafie AM, El-Gendy FM, Allhony DM, Abo El Fotoh WMM, Omar ZA, Samir MA, et al. Establishment of blood pressure nomograms representative for Egyptian children and adolescents: a cross-sectional study. BMJ Open. 2018;8:e020609. doi: 10.1136/bmjopen-2017-020609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Dong Y, Ma J, Song Y, Dong B, Wang Z, Yang Z, et al. National blood pressure reference for Chinese Han children and adolescents aged 7 to 17 years. Hypertension. 2017;70:897–906. doi: 10.1161/HYPERTENSIONAHA.117.09983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Raj M, Sundaram R, Paul M, Kumar K. Blood pressure distribution in Indian children. Indian Pediatr. 2010;47:477–485. doi: 10.1007/s13312-010-0089-z. [DOI] [PubMed] [Google Scholar]
- 8.Ministry of Health and Family Welfare, Government of India; UNICEF; Population Council. Comprehensive National Nutrition Survey national report. New Delhi: Ministry of Health and Family Welfare; 2019. [Google Scholar]
- 9.Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128 (Suppl 5):S213–S256. doi: 10.1542/peds.2009-2107C. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33:S62–S69. doi: 10.2337/dc10-S062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Ogata E, Asahi K, Yamaguchi S, Iseki K, Sato H, Moriyama T, et al. Low fasting plasma glucose level as a predictor of new-onset diabetes mellitus on a large cohort from a Japanese general population. Sci Rep. 2018;8:13927. doi: 10.1038/s41598-018-31744-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Leite HP, Rodrigues da Silva AV, de Oliveira Iglesias SB, Koch Nogueira PC. Serum albumin is an independent predictor of clinical outcomes in critically ill children. Pediatr Crit Care Med. 2016;17:e50–e57. doi: 10.1097/PCC.0000000000000596. [DOI] [PubMed] [Google Scholar]
- 13.Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20:629–637. doi: 10.1681/ASN.2008030287. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.World Health Organization (WHO) WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. Geneva: WHO; 2006. [Google Scholar]
- 15.International Institute for Population Sciences (IIPS); ICF International. National Family Health Survey (NFHS-4), 2015-16: India. 2017. [Accessed 15 Sep 2024]. https://dhsprogram.com/pubs/pdf/fr339/fr339.pdf .
- 16.Jaiswal A, Dwarakanathan V, Selva Das PA, Singh G, Sathiyamoorthy R, Deori TJ, et al. Establishing nomogram of blood pressure for late adolescents in India: secondary analysis of NFHS-4 data. J Family Med Prim Care. 2022;11:5834–5848. doi: 10.4103/jfmpc.jfmpc_161_22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Ediriweera DS, Dilina N, Perera U, Flores F, Samita S. Risk of low birth weight on adulthood hypertension - evidence from a tertiary care hospital in a South Asian country, Sri Lanka: a retrospective cohort study. BMC Public Health. 2017;17:358. doi: 10.1186/s12889-017-4268-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Sánchez RG, Labarthe DR, Forthofer RN, Fernández-Cruz A. National standards of blood pressure for children and adolescents in Spain: international comparisons. The Spanish Group for the Study of Cardiovascular Risk Factors in Childhood and Youth. Int J Epidemiol. 1992;21:478–487. doi: 10.1093/ije/21.3.478. [DOI] [PubMed] [Google Scholar]
- 19.Nichols S, Cadogan F. Blood pressure and its correlates in Tobagonian adolescents. West Indian Med J. 2006;55:305–312. doi: 10.1590/s0043-31442006000500003. [DOI] [PubMed] [Google Scholar]
- 20.Kim SH, Park Y, Song YH, An HS, Shin JI, Oh JH, et al. Blood pressure reference values for normal weight Korean children and adolescents: data from the Korea National Health and Nutrition Examination Survey 1998-2016: the Korean Working Group of Pediatric Hypertension. Korean Circ J. 2019;49:1167–1180. doi: 10.4070/kcj.2019.0075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Keskinoğlu A, Keskinoglu P, Özgür S, Köse T. Blood pressure percentiles in Turkish children and adolescents. J Pediatr Res. 2020;7:279–285. [Google Scholar]
- 22.Vasudevan A, Thomas T, Kurpad A, Sachdev HS. Prevalence of and factors associated with high blood pressure among adolescents in India. JAMA Netw Open. 2022;5:e2239282. doi: 10.1001/jamanetworkopen.2022.39282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Šebeková K, Gurecká R, Csongová M, Koborová I, Šebek J. Elevated blood pressure-associated cardiometabolic risk factors and biomarkers in 16-23 years old students with or without metabolic abnormalities. J Hum Hypertens. 2021;35:37–48. doi: 10.1038/s41371-020-0309-5. [DOI] [PubMed] [Google Scholar]
- 24.Fuchs FD, Whelton PK. High blood pressure and cardiovascular disease. Hypertension. 2020;75:285–292. doi: 10.1161/HYPERTENSIONAHA.119.14240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Chorin E, Hassidim A, Hartal M, Havakuk O, Flint N, Ziv-Baran T, et al. Trends in adolescents obesity and the association between BMI and blood pressure: a cross-sectional study in 714,922 healthy teenagers. Am J Hypertens. 2015;28:1157–1163. doi: 10.1093/ajh/hpv007. [DOI] [PubMed] [Google Scholar]
- 26.James BC, Venkateswaran A, A A, Premkumar B, B S. The prevalence of elevated blood pressure and its association with obesity in children aged 6-13 years in rural India: a cross-sectional study. Cureus. 2023;15:e37916. doi: 10.7759/cureus.37916. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Goel M, Pal P, Agrawal A, Ashok C. Relationship of body mass index and other life style factors with hypertension in adolescents. Ann Pediatr Cardiol. 2016;9:29–34. doi: 10.4103/0974-2069.171393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis. 1996;124(Suppl):S1–S9. doi: 10.1016/0021-9150(96)05851-0. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Inclusion criteria for deriving reference for blood pressure
RR of high cardio-metabolic makers for adolescents classified as high BP by Indian and AAP references
RR of low eGFR for adolescents classified as high BP by Indian and AAP references
Venn diagram showing concordance between AAP and Indian BP references in adolescents. (A) Distribution of high and normal BP in adolescents 10–12 years by different BP references. (B) Distribution of high and normal BP in adolescents 13–16 years by different BP references.
Prevalence of high BP by different references in adolescents 10–12 years classified with high and normal cardio-metabolic markers. Prevalence of high BP by Indian and AAP references among children 10–12 years old classified with high and normal cardio-metabolic markers. (A) High blood glucose vs. normal blood glucose; (B) High triglyceride vs. normal triglyceride; (C) High HbA1c vs. normal HbA1c; (D) High cholesterol vs. normal cholesterol; (E) High LDL vs. normal LDL; (F) Low HDL vs. normal HDL. The solid line represents high BP prevalence with 95% confidence interval among children (10–12 years) with high cardio-metabolic markers and the dashed line represents high BP prevalence with confidence interval among children (10–12 years) with normal cardio-metabolic markers.
Prevalence of high BP among different references in adolescents 13–16 years. Prevalence of high BP by Indian and AAP references among adolescents 13–16 years old classified with high and normal cardio-metabolic markers. (A) High blood glucose vs. normal blood glucose; (B) High triglyceride vs. normal triglyceride; (C) High HbA1c vs. normal HbA1c; (D) High cholesterol vs. normal cholesterol; (E) High LDL vs. normal LDL; (F) Low HDL vs. normal HDL. The solid line represents high BP prevalence with 95% confidence interval among adolescents (13–16 years) with high cardio-metabolic markers and the dashed line represents high BP prevalence with confidence interval among adolescents (13–16 years) with normal cardio-metabolic markers.