There is a growing body of evidence in detecting mutations and different combinations of genetic variations which may cause HTN and pre-HTN. Potentially variations were identified, which were associated with quantitative differences in the expression of multiple genes such as the differences in expression of the genes coding for the angiotensin-converting enzyme and for the natriuretic peptide receptor.^{22, 42}–⁴⁸ However the etiology is more complex and the gene-gene and gene-environment interactions should be considered in this context.⁴⁹

Exposures to various environmental factors before and after birth have harmful effects on cardiovascular system.⁵⁰ Various environmental risk factors are identified for pre-HTN, the most important ones being air pollution, noise pollution and second-hand smoking.

A growing body of evidence exists about the effect of air pollutants, notably particulate matter (PM) on pre-HTN. This association was found to be independent of aerologic factors like weather, temperature or humidity and of major cardiovascular risk factors such as age, diabetes, dyslipidemia and obesity.⁵¹–⁵⁴

Accumulating evidences suggest that exposure to ambient levels of PM may increase BP within hours to days and can result in a prohypertensive response. The underlying biologic pathways include autonomic nervous system imbalance and arterial vascular dysfunction or vasoconstriction because of systemic oxidative stress and inflammation.^{22, 55, 56} Given the harmful effects of air pollutants, notably PM, on various organs and on underlying mechanisms of atherosclerosis and endothelial dysfunction from childhood,⁵⁷–⁶⁴ preventive measures should be considered from early life. The Multi-Ethnic Study of Atherosclerosis showed that traffic-related exposure may increase systolic BP, and in turn left ventricular mass index. The increase in this index has been consistent with 5.6 mmHg elevation in BP.⁶⁵–⁶⁷ Exposures to air pollutants other than PM, arsenic, lead, cadmium, solvents, and pesticides have also been linked to pre-HTN.⁶⁸

The harmful effects of secondhand smoke on cardiovascular system are comparable to that of smoking.⁶⁹ Some studies have documented the association of exposure to tobacco smoke with elevated BP in children and adolescents. Tobacco smoke exposure of pregnant mothers has a considerable effect on increasing systolic BP of their offspring in early infancy.⁷⁰

A recent large population-based study showed that parental smoking independently affects systolic BP among healthy preschool children even after correction for other risk factors, such as body mass index, parental hypertension, or birth weight.⁷¹ Likewise, a family-centered prospective study revealed this association among children and adolescents.⁷² This widespread and modifiable risk factor should be considered in primordial and primary prevention of pre-HTN.

The cardiovascular effects of environmental noise, notably on high BP, are well documented and rank second in terms of disability-adjusted life year (DALYs) after annoyance.⁷³–⁷⁵ It is also documented that environmental noise exposure may be associated with elevated BP in young adults, especially in female individuals.⁷⁶

Night time noise has an effect on our blood pressure more than day time noise. The HYENA (Hypertension and Exposure to Noise near Airports) study was a large study conducted among individuals who had lived at least 5 years near any of six major European airports. It found significant exposure-response relationships between night-time aircraft and average daily road traffic noise exposure and elevated BP. Monitoring BP showed that systolic BP increased by 6.2 mmHg and diastolic BP by 7.4 mmHg. The association of noise pollution with increased BP remained significant even after adjustment for major confounders as health, socioeconomic and lifestyle factors including diet and physical activity.⁷⁷–⁷⁸

Noise exposure is associated with increased catecholamine secretion. In children, in addition to impairing reading comprehension and long-term memory, chronic noise exposure may be associated with increased BP and a pre-HTN state.⁷⁹–⁸¹ Such association is reported even in pre-school age children.⁸²

Some changes in BP levels cannot be explained by well-known determinants as anthropometric measures and lifestyle factors. For instance, comparison of data from 4 waves of the Korean National Health and Nutrition Examination Survey between 1998 and 2008 among children and adolescents with 10 to 19 years of age revealed significant decrease in mean BP as well as in the prevalence of pre-HTN and HTN. These changes were not explained by secular trend of childhood obesity, cigarette smoking, physical activity, dietary habits, sociodemographic factors and psychological factors as perceived stress and sleep duration.⁸³ Such findings may be confirmatory evidence of the underlying role of environmental factors on BP levels and pre-HTN state in children and adolescents.

The interaction of gene and environment on the development of many chronic diseases and their risk factors is well-established. The discrepancies of human genome and modern lifestyle can, at least in part, explain the ongoing epidemics of chronic non-communicable diseases.⁸⁴–⁹⁰

Likewise, such interaction may have a pivotal role in the development of pre-HTN. A growing body of evidence exists about the link between fetal programming and pre-HTN later in life.⁹¹ The fetal origins of adult disease is related to insults to epigenetic modifications of genes.⁹² Such epigenetic process of establishing future diseases may affect some genes responsible for fetal and placental growth.⁹³

It is suggested that environmental changes during the prenatal and perinatal periods may be associated with altered gene expression by epigenetic mechanisms resulting in pre-HTN, HTN, and other chronic diseases.⁹⁴

The association of environmental fetal programming is documented in young children; it is shown that in 6-year-old children born at full term, intrauterine growth retardation was linked to pre-HTN.⁹⁵ Different mechanisms are considered in this regard, one of them is about the role of oxidative stress. A recent experimental study showed that the intrauterine environment modifies oxidative pathways of gene expression in fetal kidneys, and this may be a mechanism of pre-HTN.⁹⁶ It is also suggested that fetal programming of pre-HTN may be mediated by the fundamental role of hyperinsulinism and hyperleptinemia.⁹⁷

Various factors as maternal obesity,⁹⁸ dietary habits in pregnancy,⁹⁹ and gestational diabetes¹⁰⁰ are considered to be the underlying mechanism of restricted fetal growth, and in turn of pre-HTN. Of special concern in this context is the association of environmental pollutants and other chemical toxins, which may result in intrauterine growth retardation and its sequels. Environmental pollutants may influence vital cellular functions during critical periods of fetal development, and may change the structure or function of vital organs. Developmental epigenetics may lead to “adaptive” phenotypes to respond the needs of the later-life environment. Exposure to environmental pollutants and toxic chemicals may interfere with these programmed adaptive changes, and eventually may result in considerable increase in various disorders as pre-HTN.¹⁰¹–¹⁰⁴

Excess weight is associated with dysfunction of the adipose tissue, consisting of enlarged hypertrophied adipocytes, increased infiltration by macrophages and variations in secretion of adipokines and free fatty acids. These changes would results in chronic vascular inflammation, oxidative stress, activation of the renin-angiotensin-aldosterone system and sympathetic response, and ultimately to pre-HTN.¹⁰⁵ The association of overweight with pre-HTN and HTN in the pediatric age group is well-documented.¹⁰⁶–¹¹⁴

A birth cohort demonstrated that maternal pre-pregnancy weight and BMI, and weight at the end of pregnancy are found to be positively associated with both systolic and diastolic BP in adolescent subjects of both sexes; maternal height was positively associated with systolic BP only among males.¹¹⁵

The strong association of elevated BP with excess weight along with the childhood obesity epidemic has led to increase in the prevalence of the cases of pediatric HTN. Comparison of national data in the US revealed an increase in mean systolic and diastolic BP levels,¹¹⁶ and an overall increase in the prevalence of pre-HTN and HTN in children and adolescents.^{26, 117}

Considering the rapidly escalating trend of childhood obesity, it can be estimated that the population prevalence of pre-HTN and HTN will be increasing from childhood to adulthood. This is of crucial importance for low- and middle-income countries facing increasing levels of childhood obesity¹¹⁸–¹²² as well as an emerging epidemic of non-communicable diseases.¹²³–¹²⁷

The pre-HTN state during childhood and adolescence is associated with various lifestyle factors. Although smoking may be associated with elevated BP, but such evidence is limited in the pediatric age group. Diet and physical activity are known a pivotal role in the development, prevention and control of pediatric pre-HTN. Their impact may begin from early life.^{6, 128}

Various factors have been considered in this regard:

Diet is known to be associated with mean BP level, and pre-HTN; this association is documented from early life. Infant-feeding may have lifelong health impact. The protective role of breast feeding against chronic diseases and cardiometabolic risk factors, including elevated BP, is well-established.¹²⁹–¹³² Accumulating evidence exists on the protective effect of breast feeding during infancy on BP and pre-HTN in later life.^{19, 133}

Results of systematic reviews and meta-analyses confirmed the protective role of breast feeding against elevated BP in later life.¹³³–¹³⁵ Although, the correlations were not strong, but even such small reduction in BP associated with breastfeeding could confer important benefits at population level.

A birth cohort showed that after 7.3 years of follow up, children who were bottle-fed during infancy had significantly higher systolic BP than those who were breast-fed.¹³⁶ However, some studies have shown small effects of breast feeding on children's BP, and have suggested that such effect may become more evident during adolescence.¹³⁷–¹³⁹

In addition to the beneficial effects of breast feeding for future BP of infants, it may have protective effects against elevated BP for mothers. A recent study in Finland found that16-20 years after pregnancy, women who had breast-fed for less than 6 months had higher total body fat and cardiometabolic risk factors than mothers who had breast-fed for longer than 6 months or for longer than 10 months. The protective long-term effects of duration of postpartum lactation on risk factors including systolic and diastolic BP were independent of pre-pregnancy weight and BMI, menopausal status, smoking status, level of education, participation in past and present leisure-time physical activity and current dietary energy intake.¹⁴⁰

The type and the beginning time of complementary foods may have lifelong health impacts.

One of its aspects is the intake of sodium (salt), and related harmful effect on the developing kidneys and blood pressure. One of the recent evidences in this regard came from a large cohort of 8-month-old infants in the UK. It showed that 70% of infants consumed more than 400 mg sodium per day, which is the maximum UK recommendation for sodium intake in infants.¹⁴¹

Given the suggested effect of salt intake from infancy to adulthood on BP, body weight and energy balance,¹⁴² high sodium intake by complimentary foods may increase the cases of pre-HTN in the future.

The important role of taste preference should be taken into account. A recent study showed that healthy and low-sodium foods can be simply introduced in the diet of most infants.¹⁴³ Usually the taste preferences in new food acceptance in early life may persist lifelong, and may have long-term health effects. Pediatricians have a pivotal role in introducing healthy complimentary foods to families;¹⁴⁴ and less-educated mothers need to be learned about infant feeding practices.¹⁴⁵

Different guidelines have suggested low sodium intake in childhood and adolescence for prevention of pre-HTN and HTN.¹⁴⁶–¹⁴⁸ However, the current salt intake is far in excess of nutritional requirements in children and adolescents of many populations.^{126, 149}–¹⁵³ This high intake is reported even in very young children with 3 years of age.¹⁵⁴

Of special concern is that the high sodium content is not limited to unhealthy foods as snacks and processed foods, those foods as bread, cheese and cereals considered as healthy with recommendation of daily consumption, are of main hidden sources of salt intake among children and adolescents.¹⁵⁵

Various types of studies have confirmed the effect of salt intake and pre-HTN in the pediatric age group. A large population-based study in the UK showed that the increase in salt intake by 1g in children is associated with 0.4 mmHg rise in systolic BP and 0.6 mmHg rise in pulse pressure.¹⁵⁶

It is also documented that in addition to the direct association of salt intake on BP, excess dietary sodium intake would affect thirst and may increase consumption of sugary beverages by children and adolescents; and in turn, it would increase the likelihood of obesity and pre-HTN.¹⁵⁷

A meta-analysis of controlled trials assessed the effect of reducing salt intake on BP in children and adolescents demonstrated that a modest reduction in salt intake resulted in immediate decline in BP level.¹⁵⁸

However, the effects of low-sodium intake on pre-HTN are controversial, and may be not generalizable. A Cochrane review suggested that the effect of low versus high sodium intake on blood pressure was greater in Black and Asian patients than in Caucasians. Magnitude of the effect in Caucasians with normal blood pressure does not warrant a general recommendation to reduce sodium intake.¹⁵⁹

On the other hand, some harmful effects of lowering salt intake are reported. In a recent study among healthy participants, low-salt diet was independently associated with an increase in insulin resistance.¹⁶⁰

The dietary recommendations for prevention and control of pediatric pre-HTN are not limited to reducing the salt intake. Findings of the 8-year follow up of children initially 3 to 6 years of age in the prospective Framingham Children's Study showed children who consumed more fruits and vegetables or more dairy products during the preschool age had smaller yearly increase in systolic BP in subsequent years. At early adolescence, children with higher intakes of fruits and vegetables and dairy products had a lower mean systolic BP than those with either high intake of one of these food groups or those with low intake of them. This longitudinal study confirmed that a diet rich in fruits, vegetables, and dairy products may have beneficial effects on BP during childhood.¹⁶¹ This type of diet is consistent with the classic Dietary Approaches to Stop Hypertension (DASH) including a diet high in fresh fruits, vegetables, whole grains, and low-fat dairy products, recommended for adults.¹⁶²

The beneficial effects of a DASH-type diet on cardiometabolic risk factors of children and adolescents were documented too. A large national study in the US showed that after 10 years of follow up, adolescent girls with diet more close to the DASH eating pattern had smaller gains in BMI.¹⁶³ Trials with dietary interventions using the DASH-type diet showed favorable results in controlling pre-HTN state in diabetic^{164, 165} and non-diabetic adolescents.¹⁶⁶ These findings highlight the need to underscore the intake of fruits, vegetables, fiber and dairy in the diets of children and adolescents.

Physical activity is known to positively moderate BP. There is a large body of evidence about the association of physical activity and lower cardiovascular risk factors, including pre-HTN and HTN.^{9, 32, 113, 167, 168} A study among young children showed that physical activity was independently associated with lower BP even in prepubertal children.¹⁶⁹

A recent systematic review confirmed the association of physical activity with lower BP in children, and emphasized on the role of physical fitness on prevention and control of cardiovascular risk factors in children.¹⁷⁰

Although it is well documented that sedentary behaviors are associated with pre-HTN, but a recent study among adolescents demonstrated various correlations between different types of sedentary activities and BP levels. It showed that after adjusting for confounders, while each hour per day spent in screen time, watching TV and playing video games was associated with a significant increase in diastolic BP, each hour per day spent reading was associated with a decrease in systolic and diastolic BP.¹⁷¹

Another national study in the US revealed that high TV use, but not high computer use, and lack of moderate-to-vigorous intensity physical activity was associated with cardiometabolic risk factors among children and adolescents.¹⁷² Office- and population-based interventions have demonstrated that pre-HTN may be reversible by increase in physical activity.¹⁷³–¹⁷⁶

Among different types of physical activities, aerobic exercises are found to be useful for controlling pre-HTN.^{177, 178} Likewise , this kind of exercise has been successful in reducing systolic and diastolic BP among children and adolescents with pre-HTN and HTN.¹⁷⁹

In general, a combination of lifestyle change including healthy dietary pattern and exercise training may improve pre-HTN state and vascular function in children and adolescents.^{6, 180, 181}