Left ventricular hypertrophy in children and adolescents with arterial hypertension

    Authors

    Abstract

    The growing prevalence of arterial hypertension in children and adolescents is becoming an ever-greater public health problem. Longitudinal studies show that children and in particular adolescents with arterial hypertension are highly likely to become hypertensive adults, including the risk of cardiovascular disease. Although cardiovascular diseases are very rare in childhood, elevated arterial pressure can cause lesions of target organs already in childhood and adolescence. Left ventricular hypertrophy is a target organ lesion that is most frequently searched for in pediatric hypertension. Several studies have reported positive correlation between arterial pressure and left ventricular mass index, while the prevalence of left ventricular hypertrophy in children with hypertension was 8–41%. An association was found of arterial hypertension in children and adolescents with arterial stiffness, intima-media thickness, and other cardiovascular risks.

    Keywords

    KLJUČNE RIJEČI: arterijska hipertenzija, djeca, adolescenti, hipertrofija lijeve klijetke, arterial hypertension, children, adolescents, left ventricular hypertrophy

    DOI

    https://doi.org/10.15836/ccar2017.302

    Full Text

    ## Introduction The growing prevalence of arterial hypertension (AH) in children and adolescents is becoming an ever-greater public health problem. The prevalence of AH in children aged 8–18 years has been estimated to 2–3.6% and in adolescents aged 18 to 10% ( 1 ). Primary AH currently is one of the most common chronic diseases in adolescents. The epidemic of obesity witnessed in recent years has contributed considerably to the increase in the prevalence of AH, which is as high as 27–47% in overweight and obese children, respectively ( 2 ). Longitudinal studies have indicated that children and in particular adolescents with AH are likely to suffer from hypertension as adults, including the risk of cardiovascular disease (CVD) ( 3 ). ## Target organ lesions in children with arterial hypertension Although CVDs are very rare in children, elevated arterial pressure can cause damage to target organs, such as increased carotid artery intima-media thickness (cIMT), decreased brachial artery elasticity, increased pulse wave velocity (PWV) through the arterial wall and augmentation index (AIx), pointing to increased arterial stiffness, left ventricular hypertrophy, kidney damage and ocular fundus changes already in childhood and adolescence ( 4 - 9 ). Target organ lesions due to AH in adolescence imply a considerable risk of cardiovascular events in adulthood. Wide availability of echocardiography to detect left ventricular hypertrophy (LVH) makes it a target organ damage most frequently searched for in pediatric AH. The prognostic value of LVH in adults with AH as an independent risk factor for CVD has been definitely verified ( 10 ). Recommendations issued in The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents from 2004 include screening for LVH as a factor to initiate or intensify antihypertensive treatment in the routine work-up for children with AH ( 11 ). ## Left ventricular hypertrophy and left ventricular mass assessment In children, left ventricular mass (LVM) correlates primarily with body mass, but the amount of adipose tissue, gender and arterial pressure also are contributing factors ( 12 ). Repeated LVM measurements in the Bogalusa study suggested that somatic growth was the main determinant of heart growth, but that excessive body mass contributed to increased myocardial mass to greater extent than expected ( 13 ). Determination of LVM in children is complicated due to the cardiac mass association with body mass of a growing child. Numerous studies have demonstrated that LVM index (LVMI), which also includes body height of the child, is the best method of expressing LVM in children. LVMI is the ratio of left ventricular mass and child’s height raised to the 2.7 power (LVMI = LVM (g)/height (m) 2.7 ) ( 14 ). A variety of LVMI borderline values for LVH in children are reported in the literature. The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents states a borderline LVMI value for LVH of 51 (g)/height (m) 2.7 , the same as in adults, and this value has been frequently used in pediatric patients as well ( 11 ). However, using percentile curves is recommended in children aged ≤9 years, whereas 95 th percentile of 40 (g)/height (m) 2.7 and 45 (g)/height (m) 2.7 should be employed in female and male children aged ≥9 years, respectively ( 15 ). ## Left ventricular hypertrophy and arterial hypertension Identifying children with AH that are at risk of poor cardiovascular outcome relies primarily on determination of surrogate markers, firstly LVH as a well-known risk factor in adults. Several studies report on positive correlation between arterial pressure level and LVMI ( 16 - 18 ). Daniels et al. found LVMI above 95 th percentile in 8–41% of children with AH, of which 10–15.5% had LVMI >51 g/m 2.7 . In the study by Stabouli et al. ( 9 ), LVH was recorded in 20% of children with AH. Interestingly, LVH was detected in the same percentage of children with pre-hypertension and those with AH. This finding indicates that pre-hypertension also poses a risk of cardiovascular sequels and target organ damage as AH. Higher LVMI values were also recorded in the group of children with AH as confirmed by 24-hour continuous noninvasive arterial pressure monitoring (CNAP). Richey et al. found higher LVMI in children with AH as recorded by 24-hour CNAP ( 19 ). McNiece et al. recorded a higher risk of LVH in children with AH grade I and II ( 7 ). Left ventricular hypertrophy was also detected in children with white-coat hypertension, suggesting that it is by no means a harmless but a clinically relevant condition ( 20 ). ## Left ventricular hypertrophy and vascular phenotype Arterial hypertension can be the cause but also the sequel of impaired vascular function. Increased arterial stiffness is an independent risk factor for development of CVD in adults. In young individuals, AH and obesity lead to reversible functional changes of vascular tree, which may later become fixed and irreversible. In the initial stage, vascular lesions are reversible, therefore early recognition and treatment of AH is of utmost importance ( 21 ). The most commonly used parameters for the assessment of vascular function in adults are cIMT, PWV and AIx; however, they have not yet been widely adopted in pediatric practice due to unavailable equipment, inadequate method standardization, inappropriately defined diagnostic role, and lack of validation in pediatric patients. There are several studies reporting normal PWV and cIMT values in children and adolescents ( 22 - 24 ). Other studies point to the association of AH with arterial stiffness and cardiovascular risk in children and adolescents ( 25 , 26 ). In some studies, increased cIMT, reduced arterial elasticity and arterial stiffness parameters were found to correlate with LVH independently of obesity ( 16 , 27 ). ## Left ventricular hypertrophy and obesity Obesity and AH have been on a progressive increase in the last few decades. There is a growing body of evidence pointing to the role of these risk factors for CVD in target organ damage such as LVH in children. Although obesity and AH frequently coexist, several studies have demonstrated that obesity has an independent role in LVH development, irrespective of hypertension ( 28 ). Hypertension is present in about 30% of obese children ( 29 ). LVH is frequent in obese children and is associated with systolic hypertension and insulin resistance. In children with AH who are at the same time overweight or obese, LVMI is higher than it would be in the presence of hypertension alone. Obesity in childhood is an independent risk factor for higher LVM in adult age ( 30 ). Numerous hemodynamic and non-hemodynamic factors explain the role of obesity in the development of LVH and cardiac remodeling. ## Left ventricular hypertrophy in children with chronic kidney disease The risk of premature cardiovascular lesion is significantly higher in children with chronic kidney disease (CKD) ( 31 ). LVH is already found in the early stage of CKD in pediatric patients, and at the introduction of dialysis therapy it is present in 69–82% of these patients ( 32 ). LVH is frequently found in patients following kidney transplantation. A correlation was recorded between glomerular filtration decrease and LVM increase ( 33 ). In children with CKD, there are multiple factors favoring LVH development, including AH, increased arterial stiffness and diastolic dysfunction of the heart. As LVH is occasionally found in adults with a history of kidney disease in childhood, echocardiographic monitoring at 6- to 12-month intervals is recommended in CKD patients and those on dialysis, along with reducing other CVD risk factors ( 34 ). ## Conclusion Left ventricular hypertrophy is a measure of heart damage as a target organ in children with AH and CKD. Echocardiographic determination of LVM is part of the algorithm recommended for the work-up of children with AH and is used when deciding on the introduction of medicamentous therapy, as well as in therapeutic response evaluation. Therefore, it is recommended that every child with hypertension and CKD undergoes initial and then follow up echocardiography.

    Cardiologia Croatica
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    Left ventricular hypertrophy in children and adolescents with arterial hypertension

    Professional Article
    Issue7-8
    Published
    Pages302-306
    PDF via DOIhttps://doi.org/10.15836/ccar2017.302
    KLJUČNE RIJEČI: arterijska hipertenzija
    djeca
    adolescenti
    hipertrofija lijeve klijetke
    arterial hypertension
    children
    adolescents
    left ventricular hypertrophy

    Authors

    Vesna Herceg-Čavrak*ORCIDUniversity Children’s Hospital Zagreb, Zagreb, Croatia

    Abstract

    The growing prevalence of arterial hypertension in children and adolescents is becoming an ever-greater public health problem. Longitudinal studies show that children and in particular adolescents with arterial hypertension are highly likely to become hypertensive adults, including the risk of cardiovascular disease. Although cardiovascular diseases are very rare in childhood, elevated arterial pressure can cause lesions of target organs already in childhood and adolescence. Left ventricular hypertrophy is a target organ lesion that is most frequently searched for in pediatric hypertension. Several studies have reported positive correlation between arterial pressure and left ventricular mass index, while the prevalence of left ventricular hypertrophy in children with hypertension was 8–41%. An association was found of arterial hypertension in children and adolescents with arterial stiffness, intima-media thickness, and other cardiovascular risks.

    Full Text

    ## Introduction The growing prevalence of arterial hypertension (AH) in children and adolescents is becoming an ever-greater public health problem. The prevalence of AH in children aged 8–18 years has been estimated to 2–3.6% and in adolescents aged 18 to 10% ( 1 ). Primary AH currently is one of the most common chronic diseases in adolescents. The epidemic of obesity witnessed in recent years has contributed considerably to the increase in the prevalence of AH, which is as high as 27–47% in overweight and obese children, respectively ( 2 ). Longitudinal studies have indicated that children and in particular adolescents with AH are likely to suffer from hypertension as adults, including the risk of cardiovascular disease (CVD) ( 3 ). ## Target organ lesions in children with arterial hypertension Although CVDs are very rare in children, elevated arterial pressure can cause damage to target organs, such as increased carotid artery intima-media thickness (cIMT), decreased brachial artery elasticity, increased pulse wave velocity (PWV) through the arterial wall and augmentation index (AIx), pointing to increased arterial stiffness, left ventricular hypertrophy, kidney damage and ocular fundus changes already in childhood and adolescence ( 4 - 9 ). Target organ lesions due to AH in adolescence imply a considerable risk of cardiovascular events in adulthood. Wide availability of echocardiography to detect left ventricular hypertrophy (LVH) makes it a target organ damage most frequently searched for in pediatric AH. The prognostic value of LVH in adults with AH as an independent risk factor for CVD has been definitely verified ( 10 ). Recommendations issued in The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents from 2004 include screening for LVH as a factor to initiate or intensify antihypertensive treatment in the routine work-up for children with AH ( 11 ). ## Left ventricular hypertrophy and left ventricular mass assessment In children, left ventricular mass (LVM) correlates primarily with body mass, but the amount of adipose tissue, gender and arterial pressure also are contributing factors ( 12 ). Repeated LVM measurements in the Bogalusa study suggested that somatic growth was the main determinant of heart growth, but that excessive body mass contributed to increased myocardial mass to greater extent than expected ( 13 ). Determination of LVM in children is complicated due to the cardiac mass association with body mass of a growing child. Numerous studies have demonstrated that LVM index (LVMI), which also includes body height of the child, is the best method of expressing LVM in children. LVMI is the ratio of left ventricular mass and child’s height raised to the 2.7 power (LVMI = LVM (g)/height (m) 2.7 ) ( 14 ). A variety of LVMI borderline values for LVH in children are reported in the literature. The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents states a borderline LVMI value for LVH of 51 (g)/height (m) 2.7 , the same as in adults, and this value has been frequently used in pediatric patients as well ( 11 ). However, using percentile curves is recommended in children aged ≤9 years, whereas 95 th percentile of 40 (g)/height (m) 2.7 and 45 (g)/height (m) 2.7 should be employed in female and male children aged ≥9 years, respectively ( 15 ). ## Left ventricular hypertrophy and arterial hypertension Identifying children with AH that are at risk of poor cardiovascular outcome relies primarily on determination of surrogate markers, firstly LVH as a well-known risk factor in adults. Several studies report on positive correlation between arterial pressure level and LVMI ( 16 - 18 ). Daniels et al. found LVMI above 95 th percentile in 8–41% of children with AH, of which 10–15.5% had LVMI >51 g/m 2.7 . In the study by Stabouli et al. ( 9 ), LVH was recorded in 20% of children with AH. Interestingly, LVH was detected in the same percentage of children with pre-hypertension and those with AH. This finding indicates that pre-hypertension also poses a risk of cardiovascular sequels and target organ damage as AH. Higher LVMI values were also recorded in the group of children with AH as confirmed by 24-hour continuous noninvasive arterial pressure monitoring (CNAP). Richey et al. found higher LVMI in children with AH as recorded by 24-hour CNAP ( 19 ). McNiece et al. recorded a higher risk of LVH in children with AH grade I and II ( 7 ). Left ventricular hypertrophy was also detected in children with white-coat hypertension, suggesting that it is by no means a harmless but a clinically relevant condition ( 20 ). ## Left ventricular hypertrophy and vascular phenotype Arterial hypertension can be the cause but also the sequel of impaired vascular function. Increased arterial stiffness is an independent risk factor for development of CVD in adults. In young individuals, AH and obesity lead to reversible functional changes of vascular tree, which may later become fixed and irreversible. In the initial stage, vascular lesions are reversible, therefore early recognition and treatment of AH is of utmost importance ( 21 ). The most commonly used parameters for the assessment of vascular function in adults are cIMT, PWV and AIx; however, they have not yet been widely adopted in pediatric practice due to unavailable equipment, inadequate method standardization, inappropriately defined diagnostic role, and lack of validation in pediatric patients. There are several studies reporting normal PWV and cIMT values in children and adolescents ( 22 - 24 ). Other studies point to the association of AH with arterial stiffness and cardiovascular risk in children and adolescents ( 25 , 26 ). In some studies, increased cIMT, reduced arterial elasticity and arterial stiffness parameters were found to correlate with LVH independently of obesity ( 16 , 27 ). ## Left ventricular hypertrophy and obesity Obesity and AH have been on a progressive increase in the last few decades. There is a growing body of evidence pointing to the role of these risk factors for CVD in target organ damage such as LVH in children. Although obesity and AH frequently coexist, several studies have demonstrated that obesity has an independent role in LVH development, irrespective of hypertension ( 28 ). Hypertension is present in about 30% of obese children ( 29 ). LVH is frequent in obese children and is associated with systolic hypertension and insulin resistance. In children with AH who are at the same time overweight or obese, LVMI is higher than it would be in the presence of hypertension alone. Obesity in childhood is an independent risk factor for higher LVM in adult age ( 30 ). Numerous hemodynamic and non-hemodynamic factors explain the role of obesity in the development of LVH and cardiac remodeling. ## Left ventricular hypertrophy in children with chronic kidney disease The risk of premature cardiovascular lesion is significantly higher in children with chronic kidney disease (CKD) ( 31 ). LVH is already found in the early stage of CKD in pediatric patients, and at the introduction of dialysis therapy it is present in 69–82% of these patients ( 32 ). LVH is frequently found in patients following kidney transplantation. A correlation was recorded between glomerular filtration decrease and LVM increase ( 33 ). In children with CKD, there are multiple factors favoring LVH development, including AH, increased arterial stiffness and diastolic dysfunction of the heart. As LVH is occasionally found in adults with a history of kidney disease in childhood, echocardiographic monitoring at 6- to 12-month intervals is recommended in CKD patients and those on dialysis, along with reducing other CVD risk factors ( 34 ). ## Conclusion Left ventricular hypertrophy is a measure of heart damage as a target organ in children with AH and CKD. Echocardiographic determination of LVM is part of the algorithm recommended for the work-up of children with AH and is used when deciding on the introduction of medicamentous therapy, as well as in therapeutic response evaluation. Therefore, it is recommended that every child with hypertension and CKD undergoes initial and then follow up echocardiography.