Systematic review and Meta-analysis of prevalence of Prehypertension in Adolescent Population.

Keywords

Adolescents • Hypertension • Meta-analysis • Prehypertension • Systematic review

Introduction

Worldwide, raised blood pressure is main public health problem because of its association with more risks of cardiovascular diseases. It is one of the leading causes of morbidity and mortality worldwide. It is leading causes of morbidity and mortality worldwide. In 2000, one billion of adult world population had hypertension and by 2025, this is often expected to extend to 2 billion.In India, hypertension is the primaryNon-Communicable Disease with 10% of alldeaths. [1] Now a days, childhood hypertension has reached epidemic problem worldwide which is associated with childhood obesity [2]. Because of under diagnosis and lack of awareness in children and adolescents, Hypertension once was ignoredbut now has become a major public health challenge as it is associated with increase risk of coronary artery calcification,increased carotid intima media thickness and ventricular hypertrophy.Raised blood pressure is the strongest indicator of adult blood pressure [2]. In short, Hypertension is the primary cause of worldwide disease burden [3].

Hypertension, at present becoming a source of main concern in children in developing countries. Therefore, measurement of blood pressure and early detection of prehypertension and hypertension is necessary to reduce complications later in life [4]. Hypertension is the common chronic disease of childhood which predisposes to adult hypertension [5].

Adolescence (10-19 years) is a crucial period of growth and maturation of children. Most of the mental and physical changes occurs during this period which continues till adulthood. It is a most vital developmental phase (transition period) within the lifetime of adolescents from childhood to adulthood. Here children start to form their individual choices and develop personallifestyles. Unfortunately, most of the lifestyle patterns adopted by adolescentchildren are really a dangerous to their physical and psychological state also to wellbeing. Nearly two- third of premature death and one- third of disease burden are related with conditions or behaviors that began in adolescence including diet pattern, exercise, tobacco and alcohol use.With the help of proper lifestyle and behavioralmodification, these risk factors are preventable. Early phase of adolescence childhood is the proper time for these interventions [1]. The prognosis and outcome of hypertension in an adult life are laid in childhood and adolescence. There is a tendency for blood pressure to gradually rises with age [6].

Risk for cardiac disease starts at low levels of blood pressure so the identification of the precursors of cardiac diseases in childhood is the very important. The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (Working Group-2004) with latest recommendations for the evaluation of raised blood pressure in adults formed a new designation of “Prehypertension” to identify children and adolescents for risk of developing hypertension. Hypertension and prehypertension are well-defined, prevalent, asymptomatic, chronic conditions in children and adolescents [7,8].

According to the Fourth Report ‘‘Prehypertension'' is an indicator for lifestyle modification and blood pressure monitoring for every 6 months [9].

American medical classification states Prehypertension (high normal blood pressure or borderline hypertension) is raised blood pressure above normal but not up to the level of to be considered as hypertension. Prehypertension has prognostic value for intervention to be made to prevent cardiac and renal diseases.

Prehypertension is crucial and is a single significant risk factor for future development of hypertension in adolescents. Overweight and obesity are important risk factors for adolescent prehypertension. Hypertension relatedwith obesity in childhood is preventable [11].

Increasing prevalence of prehypertension and hypertension in urban as well as rural population alerts for a combined effort targeted at identifying asymptomatic cases of hypertension and prehypertension in children and adolescents. Earlier is the age of onset of untreated hypertension responsible for reduction in life expectancy [10].

Materials

Search strategy and selection criteria

• For this systematic review and meta-analysis,comprehensive search of Pub Med, Embase, MEDLINE, Global Health, and Global Health Library were searched from inception until June 2020, using search terms related to prehypertension in adolescent children. (Prehypertension, hypertension or high blood pressure or elevated blood pressure), children (children OR adolescents), and prevalence (prevalence OR epidemiology).

We focused on the past 20 years to provide recent estimates and to reduce the heterogeneity between studies

. • Terms used for prehypertension and hypertension included the following: “prehypertension, hypertension”, “blood pressure”, “systolic hypertension”, and “diastolic hypertension”. For children and adolescents, we used “child”, “children”, “childhood”, “adolescent”, “teens”, “teenage”, “youth”, “infant”, and “pediatric”.

• The main search strategy done in PubMed is available in the review protocol.This search strategy was adapted to fit with other databases. To supplement these bibliographic database searches, references of all relevant research articles and reviews were also scrutinized to identify additional potential data sources.

• To be included in this systematic review, primary studies had to be observational studies of adolescents aged 12–19 years irrespective of ethnic, socioeconomic, and educational backgrounds, reporting the prevalence of elevated blood pressure or with enough data to compute these estimates.

• We excluded studies on non-systemic hypertension (intracranial or pulmonary hypertension) and studies including both adult and paediatric populations in which it was not possible to disaggregate data for children or adolescents.

• We also excluded case series with a small sample size (<50 participants), letters, reviews, commentaries, editorials, and studies without primary data or explicit description of methods. For studies published in more than one report (duplicates), we considered the most comprehensive report with the largest sample size.

• Two investigators independently screened the titles and abstracts of articles retrieved from the literature search, and full texts of articles found potentially eligible were obtained and further assessed for final inclusion.

• All duplicates were removed during the study selection process.

• Disagreements were resolved through discussions between investigators until a consensus was reached.

Data extraction

• Two investigators independently extracted relevant data from individual studies using a preconceived and standardized data extraction form.

• Information extracted included first author’s name, year of publication, recruitment period, area (rural vsurban), country, study design, setting, sample size, mean or median age, age range, proportion of male participants, proportion of participants with obesity, ascertainment of elevated blood pressure and diagnostic criteria, and the number of participants with slightly elevated blood pressure (systolic or diastolic blood pressure ≥90th percentile and <95th percentile) and elevated blood pressure (systolic or diastolic blood pressure ≥95th percentile).

• Disagreements between authors were reconciled through discussion and consensus.

• Where relevant data were not available, we directly contacted the corresponding author to request the information.

Data analysis

• We used a meta-analysis to summarize prevalence data.

• We determined SEs for study-specific estimates from the point estimate and the appropriate denominators.

• We pooled the study-specific estimates using a random-effects meta-analysis model to obtain an overall summary estimate of the prevalence across studies after stabilizing the variance of individual studies.

• We assessed heterogeneity using the χ² test on Cochran’s Q statistic26 and quantified heterogeneity by calculating the I² (with values of 25%, 50%, and 75% representing low, medium, and high heterogeneity, respectively).

• To be included in the meta-analysis, studies had to define elevated blood pressure (or hypertension) as systolic or diastolic blood pressure greater than or equal to the 95th percentile (for all ages) or slightly elevated blood pressure (or pre-hypertension) as systolic or diastolic blood pressure in the 95th percentile but greater than or equal to the 90th percentile, with a random selection of participants with no specific disease or profile, low risk of bias in their methodological quality, and prospective data collection.

• If substantial heterogeneity was detected, we did subgroup analysis when possible to investigate the possible sources of heterogeneity using the following grouping variables: age group, sex, study setting, number of blood pressure measurements, representativeness of sample, sample size, period of participants’ recruitment, and bodymass index (BMI).

• Subgroup comparisons used the Q test based on ANOVA.

• We considered a subgroup difference p value less than 0·05 to be indicative of significant difference between subgroups.

• We analysed data using Stata version 13.0 for Windows.

• The meta-analysis was preceded by a qualitative synthesis of data.

Statistical software used was Medcalc , cited as MedCalc Statistical Software version 16.4.3 (MedCalc Software bv, Ostend, Belgium; https:// www.medcalc.org; 2016i

This review was registered in the PROSPERO International Prospective Register of systematic reviews, registration number CRD- 42020156424 and its protocol has been published.

Discussion

• This systematic review and meta-analysis of data from 18 studies involving 2123 individuals found an overall prevalence of prehypertension of 15.38% in adolescents

• Prehypertension estimates around 17.57% of boys and 13.09% of Girls

• Prevention of development of cardiovascular disease and hypertension in those who are prehypertensive in childhood and adolescent is the primary aim of study. Since high blood pressure is associated with increased cardiovascular effects in children and adolescents there is no direct evidence exist to estimate the absolute risk of cardiovascular disease associated to a particular level of blood pressure in childhood.

• The importance of hypertension tracking should be further assessed given the trouble of obtaining absolute blood pressure measurements, especially in children and adolescents.

• Primary prevention of raised blood pressure in children and adolescents should be rely on population interventions directing blood pressure determinants which are modifiable like—weight control, unhealthy diet and regular physical activity.

• In most of countries’ primary focus of blood pressure control and cardiovascular disease is on modifiable risk factor, but are mostly designated for adults. Their implementation should be extended to children and adolescent age group. Existing programmes, like child and maternal health programmes, as well as school programmes could be useful.

• Second, weight control should be the main determinant for prevention of raised blood pressure at individual level. (as weight excess is by far the main determinant of raised blood pressure in children).

• Secondary hypertension (eg, due to renal or endocrine disorders) detection could be possible because of blood pressure screening in the very few cases of children with elevated blood pressure who are not obese, considering existing local resources.

• If blood pressure is persistently elevated despite lifestyle modification, drug therapy might be considered. However, unsolved queries regarding drug therapy for raised blood pressure in children and adolescents concern its absolute cardiovascular disease risk reduction following blood pressure reduction and its effect on prevention of hypertension in adulthood (and thus duration of treatment), as well as risk–benefit ratio.

Limitations

- Hypertension definition is a major problem in both adult and Paediatrics studies given the high correlation between blood pressure and weight,growth stature, and sexual maturity in children and adolescent age group.

- Hence, the situation might not be well reflected in studies with unacceptable definitions of elevated blood pressure and studies involving only participants with high BMI.

- Even the definition of high blood pressure in children and adolescents considered acceptable in this review might not be suitable for other children and adolescents.

- The results from ongoing endeavors to establish international blood pressure references among children and adolescents will help in comparisons of the prevalence of elevated blood pressure in children and adolescents between countries and regions.

Conclusion

- This study suggests a high prevalence of raised blood pressure among children and adolescents in andobesity and overweight being important risk factors. - More detailed studies using uniform and reliable diagnostic methods are needed to better estimate the prevalence of elevated blood pressure and its determinants in children and adolescents within and across countries.

Role of the funding source

There was no funding source for this study. The corresponding author had full access to all study data and had final responsibility for the decision to submit the paper for publication.

Declaration of interests

We declare no competing interests.

References

1. Amma, Geethadevi Madhavikutty, Bindhu Vasudevan, and Sobha Akshayakumar. “Prevalence and determinants of prehypertension and hypertension among adolescents: a school-based study in a rural area of Kerala, India.” Int J Res Med Sci3 (2015): 58-64.
2. Dong, Yanhui, Yi Song, Zhiyong Zou, and Jun Ma, et al. “Updates to pediatric hypertension guidelines: influence on classification of high blood pressure in children and adolescents.” J Hypertens 37 (2019): 297-306.
3. Koebnick, Corinna, Mary H Black, Jun Wu, and Mayra P Martinez, et al. “The prevalence of primary pediatric prehypertension and hypertension in a real‐ world managed care system. ”J Clin Hypertens (Greenwich) 15 (2013): 784-792.
4. Okpokowuruk, Frances Sam, Mkpouto Udeme Akpan, and Enobong Emmanuel Ikpeme. “Prevalence of hypertension and prehypertension among children and adolescents in a semi-urban area of Uyo Metropolis, Nigeria.” Pan Afr Med J 28 (2017): 303.
5. https://medicalxpress.com/news/2016-11-hypertension-prehypertensionunderdiagnosed- undertreated-children.html.
6. Tony, Lawrence, Binu Areekal, AT Surendran Nair, and R Ramachandran, et al. “Prevalence of hypertension and pre-hypertension among adolescent school children in Thiruvananthapuram, Kerala, India.” Int J Community Med Public Health 312 (2016): 79-81.
7. Hansen, Matthew L, Paul W Gunn, and David C Kaelber. “Underdiagnosis of hypertension in children and adolescents.” JAMA 298 (2007): 874-879.
8. Redwine, Karen M, and Stephen R Daniels. “Prehypertension in adolescents: risk and progression.” J Clin Hypertens 14 (2012): 360-364.
9. Falkner, Bonita. “Prehypertension in adolescents: how high is the risk for hypertension?” The Journal of pediatrics 160 (2012): 7-9.
10. Ujunwa, Fortune A, Anthony N Ikefuna, Ada RC Nwokocha, and Josephat M Chinawa. “Hypertension and prehypertension among adolescents in secondary schools in Enugu, South East Nigeria. ”Italian Journal of Pediatrics 39 (2013): 70.
11. https://en.wikipedia.org/wiki/Prehypertension.