An overview of essential hypertension in Americans as a multifactorial phenomenon: interaction of biologic and environmental factors

This paper reviews the current literature on essential/primary hypertension in terms of its expression as a multifactorial phenomenon. The genetic and environmental risk factors involved in expression of hypertension and their interactions are discussed. A specific mutation in epithelial sodium channels, T549M, is presented as a genetic risk factor for primary hypertension as expression of this mutation has been reported to result in hyperabsorption of sodium in homozygous individuals. T549M is used in this report to illustrate the multifactorial nature of primary hypertension. Possible interactions of T549M with environmental factors known to promote hypertension and the outcome of these interactions are discussed. Data indicates that both genetic and environmental risk factors must be considered to understand and intervene effectively with patients who have primary or essential hypertension.     

Pathophysiology of hypertension in obese children: a systematic review

Hypertension is increasingly common in overweight and obese children. The mechanisms behind the development of hypertension in obesity are complex, and evidence is limited. In order to effectively treat obese children for hypertension, it is important to have a deeper understanding of the pathophysiology of hypertension in obese children. The present review summarizes the main factors associated with hypertension in obese children and discusses their potential role in its pathophysiology. Systematic searches were conducted in PubMed and EMBASE for articles published up to October 2014. In total, 60 relevant studies were included. The methodological quality of the included studies ranged from weak to strong. Several factors important in the development of hypertension in obese children have been suggested, including endocrine determinants, such as corticosteroids and adipokines, sympathetic nervous system activity, disturbed sodium homeostasis, as well as oxidative stress, inflammation and endothelial dysfunction. Understanding the pathophysiology of hypertension in overweight and obese children is important and could have implications for its screening and treatment. Based on solely cross‐sectional observational studies, it is impossible to infer causality. Longitudinal studies of high methodological quality are needed to gain more insight into the complex mechanisms behind the development of hypertension in obese children.     

Significance of heritability in primary and secondary pediatric hypertension

BACKGROUND: Patient weight and family history are significant risk factors for the development of hypertension in children. Multiple genetic factors have been identified in primary (essential) hypertension in adults; however, the delineation of genetic factors in the separate populations of children with primary or secondary hypertension are not well understood. Heritability is the proportion of observed variation in a particular trait that can be attributed to an inherited genetic factor in contrast to environmental factors. In the consideration of hypertension, heritability can be assessed in terms of an underlying continuous gradient of the liability for developing hypertension. With this assumption it is possible to compute heritability using hypertension incidence among relatives and described by Falconer. Heritability values range from 0 (no genetic contribution) to 1 (complete genetic contribution). The aim of this study was to determine the genetic contribution to primary and secondary hypertension in a pediatric population through heritability analysis. METHODS: This was a retrospective case-control analysis of medical records of children (n=276) followed in the Pediatric Nephrology Clinic over a 4-year period from 1999 to 2002. There were 192 children and adolescents with primary hypertension (124 male, 68 female, age 0 to 21 years) and 84 children and adolescents with secondary hypertension (46 male, 38 female, age 0 to 21 years). Each hypertensive group served as the control for the other. Estimates of heritability were made using Falconer's method 2. The model assumes independence between the environment and genetic factors and that the joint distribution of liabilities between parent and child are normally distributed. Problems can arise from computing heritability due to dominance within loci, correlations between nongenetic familial effects, or the presence of a major gene. RESULTS: Of the children and adolescents with primary hypertension, 49% had parents with primary hypertension; and of the children and adolescents with secondary hypertension, 24% had parents with primary hypertension. Of the children and adolescents with primary hypertension, 10% had parents with secondary hypertension; and of the children and adolescents with secondary hypertension, 46% had parents with secondary hypertension. The estimated heritability for primary hypertension was 0.84 (SE=0.21). The estimated heritability for secondary hypertension was 1.14 (SE=0.21). As the value was >1, this indicates that the fit of the liability model is poor and that a few genes, or even one major gene, were significantly involved in the causes of secondary hypertension in the children and adolescents studied. CONCLUSIONS: The results suggest that primary and secondary hypertension do not share the same type of genetic profile. Primary hypertension in children and adolescents is likely due to a large number of additive contributions of genes, although a highly correlated environmental component can not be excluded. The continuous liability model is inappropriate for secondary hypertension because the estimate was substantially greater than one. This study supports the model that secondary hypertension in children and adolescents may be related to just a few genes.     

Environmental and anthropometric factors associated with childhood arterial hypertension

Childhood obesity is considered pandemic with significant social and economical costs because of its high morbidity and mortality. To evaluate the association between biological and environmental factors and infantile arterial hypertension (AH), a cross-sectional study was performed with 701 children, ranging from 5 to 9 years old, from Feira de Santana, BA. The arterial pressure was measured following the criteria of the Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. Overweight and obesity were defined as body-mass index equal or above the 85th and the 95th percentiles for age and gender, respectively. Interviews with the children's responsible were used to determine the role of gender, ethnic group, age, familiar history of AH, and type of school. Overweight (OR= 4.49; rho= 0.04), obesity (OR= 13.05; rho= 0.000) and studying at private school (OR= 1.93; r= 0.13) were observed as predictive and independent factors associated with hypertension. Therefore, biological and environmental factors seem to be involved on the genesis of AH in children.     

Essential hypertension: a disorder of growth with origins in childhood?

PURPOSE: To review evidence that essential hypertension is a growth-related disorder with origins in childhood and manifestations in adult life. PRINCIPAL EVIDENCE: Blood pressure rises with age in children and adults. In children, the rise closely relates to growth and to skeletal and sexual maturation. Adolescents with highest pressure are heavier and had as children grown fastest; as adults, they show the greatest increase of pressure with age and are more likely to develop hypertension and coronary heart disease. In adults, the rate of increase of pressure relates to earlier pressure. One interpretation of this is that a self-perpetuating mechanism is at work. Genetic and environmental factors influence these events. HYPOTHETICAL MECHANISMS: Most forms of secondary hypertension have two pressor mechanisms; a primary cause, e.g. renal clip, and a second process, which is slow to develop, capable of maintaining hypertension after removal of the primary cause, and probably self-perpetuating in nature. We suggest that essential hypertension also has two mechanisms, both based upon cardiovascular hypertrophy: (1) a growth-promoting process in children (equivalent to the primary cause in secondary hypertension); and (2) a self-perpetuating mechanism in adults.     

The Emerging Epidemic of Hypertension in Asian Children and Adolescents

Hypertension has become a serious global public health burden because of its high incidence and concomitant risk of cardiovascular disease. Many studies have verified that risk factors, such as hypertension and obesity which are responsible for cardiovascular disease, start in early childhood. In Asian countries, the prevalence of hypertension in the pediatric age group has become more prevalent than ever before with the increasing obesity epidemic. To tackle the epidemic of cardiovascular disease, a leading cause of death and disability of non-communicable diseases in Asian countries, population-based measures aiming at reducing harmful environmental factors to blood pressure and body weight must be applied to individuals in their early childhood, as early as the fetal stage. This review focused on the prevalence of pediatric hypertension in Asian countries and outlined several considerations for accurate blood pressure (BP) measurement and evaluation, along with an overview of pathophysiology of fetal programming and obesity related with childhood hypertension.     

Social supports and serotonin transporter gene moderate depression in maltreated children

In this study, measures of the quality and availability of social supports were found to moderate risk for depression associated with a history of maltreatment and the presence of the short (s) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR). The present investigation (i) replicates research in adults showing that 5-HTTLPR variation moderates the development of depression after stress, (ii) extends the finding to children, and (iii) demonstrates the ability of social supports to further moderate risk for depression. Maltreated children with the s/s genotype and no positive supports had the highest depression ratings, scores that were twice as high as the non-maltreated comparison children with the same genotype. However, the presence of positive supports reduced risk associated with maltreatment and the s/s genotype, such that maltreated children with this profile had only minimal increases in their depression scores. These findings are consistent with emerging preclinical and clinical data suggesting that the negative sequelae associated with early stress are not inevitable. Risk for negative outcomes may be modified by both genetic and environmental factors, with the quality and availability of social supports among the most important environmental factors in promoting resiliency in maltreated children, even in the presence of a genotype expected to confer vulnerability for psychiatric disorder.     

High blood pressure in children: problems and guidelines for evaluation and treatment.

Evidence is presented from studies of the authors and of other investigators that primary hypertension is more common in children than was previously thought. Ninety-five percent of 131 asymptomatic children with incidental hypertension were considered to have primary hypertension after investigation for possible causes. The definition of hypertension was based on normal ranges of blood pressure for each age and sex. However, the definition of juvenile hypertension is still unsettled as is the question of treatment. Investigation of the effect of prolonged antihypertensive therapy on growth and development is needed. Primary hypertension in the young makes possible the study of the disease at its inception.     

Obesity hypertension in children: a problem of epidemic proportions

Obesity has become an increasingly important medical problem in children and adolescents. In national surveys from the 1960s to the 1990s, the prevalence of overweight in children grew from 5% to 11%. Outcomes related to childhood obesity include hypertension, type 2 diabetes mellitus, dyslipidemia, left ventricular hypertrophy, nonalcoholic steatohepatitis, obstructive sleep apnea, orthopedic problems, and psychosocial problems. Once considered rare, primary hypertension in children has become increasingly common in association with obesity and other risk factors, including a family history of hypertension and an ethnic predisposition to hypertensive disease. Obese children are at approximately a 3-fold higher risk for hypertension than nonobese children. In addition, the risk of hypertension in children increases across the entire range of body mass index (BMI) values and is not defined by a simple threshold effect. As in adults, a combination of factors including overactivity of the sympathetic nervous system (SNS), insulin resistance, and abnormalities in vascular structure and function may contribute to obesity-related hypertension in children. The benefits of weight loss for blood pressure reduction in children have been demonstrated in both observational and interventional studies. Obesity in childhood should be considered a chronic medical condition that is likely to require long-term management. Ultimately, prevention of obesity and its complications, including hypertension, is the goal.     

"Environmental hypertensionology" the effects of environmental factors on blood pressure in clinical practice and research

Blood pressure (BP) is affected by many environmental factors including ambient temperature, altitude, latitude, noise, and air pollutants. Given their pervasiveness, it is plausible that such factors may also have an impact on hypertension prevalence and control rates. Health care providers should be aware that the environment can play a significant role in altering BP. Although not among the established modifiable risk factors (eg, obesity) for hypertension, reducing exposures when pertinent should be considered to prevent or control hypertension. The authors provide a concise review of the evidence linking diverse environmental factors with BP and suggest an approach for incorporating this knowledge into clinical practice. The authors propose using the term environmental hypertensionology to refer to the study of the effects of environmental factors on BP in clinical and research settings.     

Deveremos avaliar a pressão arterial no recém‐nascido?

Dilated cardiomyopathy is the most common form of cardiomyopathy and the main cause of cardiac transplantation in children and in adults. Infants and children have a wider spectrum of etiologies, hampering their identification. The most frequent initial manifestation of dilated cardiomyopathy is symptomatic heart failure during exercise or at rest (although many patients are asymptomatic). Some causes are potentially reversible, therefore the investigation should be carefully planned and immediately performed after diagnosis. In most children no cause is identified, which limits the targeted therapeutic approach and therefore the effectiveness of the treatment.The authors present a case of dilated cardiomyopathy secondary to renovascular hypertension diagnosed in an infant with 3.5 month‐old, highlighting the etiological investigation, treatment and evolution.The authors present this case emphasising the fact that the arterial hypertension diagnose in infants is not always easy, questioning the current recommendations relating to an initial evaluation on blood pressure. We postulate that the assessment of blood pressure in newborns can detect early renovascular hypertension (and even other cardiovascular diseases) and help prevent the development of deleterious effects, including fatal episodes.     

Gene-environment interactions in hypertension

Environmental factors such as stress, diet, and physical activity have long been recognized as playing an important role in the pathogenesis of essential hypertension. Individuals may vary in their response to these factors depending on differences in genes determining physiologic systems that mediate the response. In this article we discuss geneenvironment interactions that contribute to the development of essential hypertension (environmental susceptibility to hypertension) and those that are involved in control of the disease (pharmacogenetics).     

The Disproportionate Impact of Hypertensive Cardiovascular Disease in African Americans: Getting to the Heart of the Issue

The prevalence of hypertension in African Americans is among the highest in the world. Persons in this group develop hypertension at a younger age than non-African Americans and develop more severe complications, including stroke, cardiovascular disease, and renal failure. The factors that impart this high risk to this population remain poorly understood and, undoubtedly, environmental factors overshadow genetic predisposition. While identifying the pathophysiologic and environmental factors that contribute to ethnic disparity in disease is important, finding a long-term solution is crucial. Steps that can have an important impact on health outcomes of African Americans are presently available. Awareness of ethnicity as a risk factor for hypertension can allow health care providers to identify persons who are likely to benefit most from early, aggressive intervention. Modifiable factors such as smoking, diet, and sedentary lifestyle, as well as undertreatment of hypertension by physicians, can be targeted immediately.     

Arterial hypertension in infancy and childhood Etiologic factors and management

In this survey of arterial hypertension as it occurs in infants and children four points should be emphasized:

1. 1. The determination of blood pressure in infants and children is an important, though sometimes neglected, part of the physical examination.

2. 2. An elevated arterial pressure should be considered an indication for a thorough etiologic investigation.

3. 3. While in most patients a primary renal basis will be found, there are important nonrenal causes of hypertension, the successful management of which depends upon their early recognition and treatment.

4. 4. In general, a specific etiologic basis for childhood hypertension can be found.

     

The risk factors for elevated blood pressure and how to address cardiovascular risk factors: a review in paediatric populations

This paper examines the epidemiology of hypertension and management strategies of cardiovascular diseases (CVDs) in paediatric populations in sub-Saharan Africa and other parts of the world in the 21st century. A computerized literature search was carried out using Medline, Evidence-Based Child Health (A Cochrane Review Journal), the Cochrane Library and Cochrane Child Health Field. A manual search in the African Journal for physical, health education, recreation and dance, the South African Journal for Research in Sports, Physical Education and Recreation and a few individuals in the area were requested to send some of their recent unpublished and published reports in the field. High prevalence rates and high odds ratios for high blood pressure (BP) were recorded in children aged 5-17 years. There is a need for health ministries to improve the public health sector so as to close the gap between the rich and the poor. Although personal and parental responsibility remain crucial, it also falls on the government to help control powerful environmental factors that are leading our children to premature ill-health and mortality. Equally, health professionals are increasingly recognized that they have a significant role to play in delivering medical treatment of hypertension in children.     

Hypertension in young children and neonates

Hypertension is most often considered a disease of old age, but the precursors are often present in young children long before the clinically accepted definitions of hypertension in the adult are manifested. Essential hypertension is by far the most common form of the disease, comprising a complex interaction of genetic and environmental factors. Many individual genes that play a role in the maintenance of blood pressure have been identified; however, none has been shown specifically to be a component of essential hypertension. Hypertension is among the leading risk factors for coronary heart disease, stroke, and end-stage renal disease, making it critically important to identify individuals at risk early in life prior to manifestation of clinical signs and symptoms.     

The role of β2-adrenergic receptor variation in human hypertension

Hypertension results from a complex and diverse array of metabolic and physiologic processes that interact with environmental factors to ultimately determine blood pressure levels and disease. Consequently, the identification of genes related to hypertension is complicated by the heterogeneity of its etiology and the likelihood that several genes with moderate effects, possibly acting in a contextdependent manner, influence blood pressure and the occurrence of hypertension. A number of studies have recently implicated variation within the b2-adrenergic receptor in blood pressure regulation and the development of hypertension. The role of these findings is reviewed here, and their possible clinical implications in human hypertension.     

肠道菌群与高血压研究进展

高血压是以体循环动脉压升高为主要临床表现的心血管综合征,是一种常见的慢性心血管疾病。高血压的发生是遗传因素和环境因素共同作用的结果。目前对于高血压发生的遗传因素、外周血管因素等方面已有相当多的研究,然而对高血压环境因素的研究仍然有所欠缺。作为人体内部的生态系统之一,肠道菌群不仅参与维持消化道的稳态与平衡,还参与到高血压（Hypertention）、糖尿病（Diabetes）、帕金森病（Parkinson’s disease, PD）等许多其他系统疾病的发生发展中。本文对肠道菌群与高血压之间的研究进展进行了综述。     

Experiences of Children with Fetal Alcohol Spectrum Disorder and Their Families: A Critical Review

Evidence suggests that children with fetal alcohol spectrum disorder (FASD) experience challenges across many areas of their daily lives and often require interprofessional supports. Recent studies have emphasized the need for an integrated system of care for children with FASD, incorporating medical, allied health, and education services, to facilitate open communication and support for the complex needs that many children experience. To develop such a system of care, it is important to first understand the impact of FASD on children’s functioning during daily activities in different environmental contexts. A critical review of existing research was conducted using a critical interpretive synthesis approach. Results revealed that while many studies discussed impacts at the body functions and structures level of children with FASD, they often did not consider the activity, participation, and environmental factors also contributing to the daily functioning of this population. Several studies discussed caregiver experiences and challenges raising a child with FASD; however, no studies investigated the lived experiences relating to impacts across activities and environments from children’s perspectives. In addition, the focus on deficits overshadowed investigation into the strengths of children with FASD, leaving a gap in the picture of their daily lives. Further research is required to determine the strengths that children with FASD demonstrate and the challenges impacting their daily functioning within different environmental contexts. Insights gleaned from such research would support intervention practices to become more holistic and interprofessional.     

Childhood predictors of high blood pressure.

Longitudinal studies in children have tracked blood pressure through childhood and from childhood into adult life. However, many children do not maintain their rank during these periods of observation. Several of the factors contributing to maintenance of rank order are reviewed, such as initial level of blood pressure, body size, sexual maturation, and family history of high blood pressure. Children with initially high level of blood pressure are more likely to become adults with high blood pressure, particularly if they are obese as children or become obese as young adults, and if they have a positive family history for hypertension.