Download Is the SPRINT Blood Pressure Treatment Target of 120/80 mm Hg

SPRINT Commentary
Is the SPRINT Blood Pressure Treatment Target
of 120/80 mm Hg Relevant for Children?
Bonita Falkner, Samuel S. Gidding
T
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he Systolic Blood Pressure Intervention Trial (SPRINT),
conducted on older adults with markedly elevated risk
for cardiovascular events, demonstrated significant outcome
benefit with treatment of blood pressure (BP) to a goal of
≤120/80 mm Hg.1 Results of the SPRINT trial would not
seem generalizable to children and adolescents because the
SPRINT focus was on older adults at high risk for cardiovascular events. Inclusion criteria for sprint were elevated
BP and additional high-risk criteria including Framingham
risk score >15%, prior cardiovascular disease, reduced glomerular filtration rate, or age >75 years. This trial seems far
removed from a pediatric setting. However, the relevance of
SPRINT, when one considers pediatric prevention, is that
hypertension accelerates cardiovascular disease. With the
exception of age, SPRINT inclusion criteria are often consequences of long-standing hypertension. The success of
SPRINT raises the question of whether there is benefit from
lifelong BP <120/80 mm Hg.
Substantial data on hypertension in adults link adverse
cardiovascular outcomes with BP levels >140/90 mm Hg, thus
supporting pharmacological treatment for primary prevention
of cardiovascular events. Based on a body of epidemiological
data demonstrating a rise in cardiovascular risk beginning at
a BP level ≥120/80 mm Hg, the Joint National Commission
7 (JNC7) guidelines on hypertension in adults introduced
the concept of prehypertension for BP levels from 120/80 to
139/89 mm Hg. The intent was to alert patients to modify lifestyle behaviors to prevent further rise in BP.2
There are no data that link a BP threshold in childhood with
cardiovascular events decades later in adulthood. Children
have lower BP than adults. BP levels in children increase
with age, and by early to midadolescence, the likelihood of a
child meeting the JNC VII criteria for prehypertension passes
10%.3 Beginning in the 1970s, hypertension in childhood has
been defined statistically as BP levels that exceed the 95th
percentile of the normative BP distribution. The 95th percentile was a conservative estimate of high BP in childhood that
was originally intended to enable detection of children with
secondary hypertension.4 The 95th percentile is well below
the conventional adult threshold defining hypertension of
140/90 mm Hg especially in younger children. Using the criteria of BP level ≥95th percentile on repeated measurement,
the prevalence childhood hypertension is ≈3.5% and includes
primary as well as secondary hypertension.5,6 Prehypertension
in childhood was defined as systolic or diastolic BP ≥90th percentile and <95th percentile. Beginning at 12 years of age,
systolic BP levels at the 90th percentile are greater than the
adult prehypertension threshold of 120 mm Hg. To be consistent with the adult definition, prehypertension in adolescence
was adjusted to BP ≥120/80 to <95th percentile from age 12
years through adolescence.3 Thus, 120/80 mm Hg became an
easy BP number to remember and also a BP level that defined
some level of risk.
The normal rise in BP in childhood is related to growth
as well as age. Reference tables that provide the BP value for
the 90th, and 95th percentile are determined by sex, age, and
height in childhood. These tables are complex and cumbersome to use, especially in primary pediatric care. Although BP
measurement has become routine in pediatric health encounters, because of the complexity of the BP reference tables,
abnormal BP levels are frequently not identified in asymptomatic children and adolescents.6–8 It would be a great advantage
to have a single number as a BP threshold to separate children with normal BP and from those for whom the BP tables
should be consulted.
Another new recommendation in the 2004 childhood BP
guidelines was the recommendation that evaluation of a child
with confirmed hypertension also include an evaluation for
target organ damage.3 Subsequent clinical studies reported
echocardiographic evidence of left ventricular hypertrophy
in a substantial portion of hypertensive children and adolescents.9,10 Evidence for target organ damage in hypertensive
youth now includes vascular stiffness and increased carotid
intimal thickness.11 Moreover, left ventricular hypertrophy
has also been reported in adolescents with prehypertension.12,13 In addition, there is emerging evidence that obesity
in childhood also contributes to increases in cardiac mass that
are in addition to BP level.12,14 These reports call attention to
the fact that a BP level of 120/80 mm Hg in adolescence may
already be associated with early cardiovascular target organ
damage. Based on recent BP data on children and adolescents from the National Health and Nutrition Examination
Surveys, ≈10% of adolescents enter young adulthood with a
BP ≥120/80 mm Hg.15
The importance of BP of 120 to 139/80 to 89 mm Hg measured at age 18 to 30 years for the development of cardiovascular target organ damage in middle age has been emphasized in
the Coronary Artery Risk Development in Young Adults study.
When coronary artery calcium assessed on computerized
The opinions expressed in this editorial are not necessarily those of the
editors or of the American Heart Association.
From the Departments of Medicine and Pediatrics (B.F.), Thomas
Jefferson University, Philadelphia, PA; and Department of Pediatrics,
Nemours/A.I. DuPont Hospital for Children, Wilmington, DE (S.S.G.).
Correspondence to Bonita Falkner, Thomas Jefferson University, 833
Chestnut St. Ste.700, Philadelphia, PA 19107. E-mail bonita.falkner@
jefferson.edu
(Hypertension. 2016;67:00-00.
DOI: 10.1161/HYPERTENSIONAHA.116.06934.)
© 2016 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.116.06934
1
2 Hypertension May 2016
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tomography scan and left ventricular structure and function
measured by echocardiography were assessed in middle age,
strong predictors of target organ damage were BP and other
risk factors measured at 18 to 30 years. Chronic exposure over
the next 20 to 25 years to elevated BP and other risk factors
contributed to worsening of target organ injury.16–18
The relationship between childhood BP and BP status in
young adulthood was further delineated in an analysis of data
from the Dunedin Multidisciplinary Health and Development
Study, a prospective cohort study that included periodic BP
and other risk factor measurements from age 7 to 38 years.
Four distinct BP trajectory groups were identified according
to BP status at age 38 years; normal, high-normal, prehypertensive, and hypertensive. The hypertensive trajectory had
the highest BP levels in childhood, and the prehypertensive
trajectory had the next highest childhood BP levels, with systolic BP levels above 120 mm Hg in adolescence. For those
with normal and high-normal BP at age 38 years, systolic
BP throughout childhood and adolescence was below 120
mm Hg. An increase in body mass index was found to be significantly associated with an upward shift in all 4 BP trajectory groups.19
The above trajectory data and emerging evidence on
BP-associated target organ damage in youth, as well as
population genetic studies20 support a paradigm shift on the
approach to childhood BP from primary prevention to primordial prevention. If primary prevention is intervention to
lower BP to prevent cardiovascular events, then primordial
prevention would be interventions to prevent development
of prehypertension/hypertension in childhood and lower BP
levels would extend into early-mid adulthood. There are BP
risk factors that are modifiable for primordial prevention.
The longitudinal relationship between overweight/obesity in
youth and future hypertension has been well understood for
many years.21,22 Physical activity in youth and physical fitness in young adulthood blunt the rise in BP with age and are
associated with reduced likelihood of future hypertension.23,24
Because of secular changes in dietary patterns, dietary
sodium intake in childhood is far above recommended levels.
Reports from analysis of recent National Health and Nutrition
Examination Surveys data demonstrate a positive association
of sodium intake with BP in childhood.25 There is also an independent effect of sodium intake, as well as body mass index
and waist circumference, on the increasing trend in childhood
BP levels.26 These findings indicate potential BP benefits of
reducing excessive sodium intake.
If prehypertension in young individuals is the threshold
for target organ damage and likely sets the stage for a higher
BP trajectory, then primordial prevention should focus on conserving normal BP. A normal (optimal) BP for adolescents is
<120/80 mm Hg. Based on child BP percentile tables, <110/70
mm Hg is likely an optimal BP for children <12 years. These
are easy numbers to remember and could make it easier to
identify children and adolescents who could benefit from
efforts to modify factors known to increase BP in the young. If
the SPRINT target of 120/80 mm Hg could be achieved in all
those at 18 years of age and maintained for decades, the only
SPRINT inclusion criteria that would still be relevant might
be age >75 years.
Disclosures
None.
References
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Jacobson M, Mahoney L, Mietus-Snyder M, Rocchini A, Steinberger J,
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HYPERTENSIONAHA.109.192639.
12. Falkner B, DeLoach S, Keith SW, Gidding SS. High risk blood pressure
and obesity increase the risk for left ventricular hypertrophy in AfricanAmerican adolescents. J Pediatr. 2013;162:94–100. doi: 10.1016/j.
jpeds.2012.06.009..
13.Urbina EM, Khoury PR, McCoy C, Daniels SR, Kimball TR,
Dolan LM. Cardiac and vascular consequences of pre-hypertension
in youth. J Clin Hypertens (Greenwich). 2011;13:332–342. doi:
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14. Brady TM. The Role of Obesity in the Development of Left Ventricular
Hypertrophy Among Children and Adolescents. Curr Hypertens Rep.
2016;18:3. doi: 10.1007/s11906-015-0608-3.
15.Kit BK, Kuklina E, Carroll MD, Ostchega Y, Freedman DS, Ogden
CL. Prevalence of and trends in dyslipidemia and blood pressure
among US children and adolescents, 1999–2012. JAMA Pediatrics.
2015;169:272–279.
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JJ, Vittinghoff E, McCulloch CE, Hulley SB. Prehypertension during
young adulthood and coronary calcium later in life. Ann Intern Med.
2008;149:91–99.
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DR Jr, Liu K, Lloyd-Jones D. Blood pressure trajectories in early adulthood and subclinical atherosclerosis in middle age. JAMA. 2014;311:490–
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Falkner and Gidding SPRINT and Youth 3
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19.Theodore RF, Broadbent J, Nagin D, Ambler A, Hogan S, Ramrakha
S, Cutfield W, Williams MJ, Harrington H, Moffitt TE, Caspi A, Milne
B, Poulton R. Childhood to Early-Midlife Systolic Blood Pressure
Trajectories: Early-Life Predictors, Effect Modifiers, and Adult
Cardiovascular Outcomes. Hypertension. 2015;66:1108–1115. doi:
10.1161/HYPERTENSIONAHA.115.05831.
20.Ference BA, Julius S, Mahajan N, Levy PD, Williams KA Sr,
Flack JM. Clinical effect of naturally random allocation to lower
systolic blood pressure beginning before the development of
hypertension. Hypertension. 2014;63:1182–1188. doi: 10.1161/
HYPERTENSIONAHA.113.02734.
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22.Tu W, Eckert GJ, DiMeglio LA, Yu Z, Jung J, Pratt JH. Intensified
effect of adiposity on blood pressure in overweight and obese children.
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NL, Robson AM, Stevens VJ, Van Horn L, Simons-Morton DG. Higher
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24. Carnethon MR, Gidding SS, Nehgme R, Sidney S, Jacobs DR Jr, Liu
K. Cardiorespiratory fitness in young adulthood and the development
of cardiovascular disease risk factors. JAMA. 2003;290:3092–3100. doi:
10.1001/jama.290.23.3092.
25. Yang Q, Zhang Z, Kuklina EV, Fang J, Ayala C, Hong Y, Loustalot F, Dai
S, Gunn JP, Tian N, Cogswell ME, Merritt R. Sodium intake and blood
pressure among US children and adolescents. Pediatrics. 2012;130:611–
619. doi: 10.1542/peds.2011-3870.
26. Rosner B, Cook NR, Daniels S, Falkner B. Childhood blood pressure
trends and risk factors for high blood pressure: the NHANES experience
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Is the SPRINT Blood Pressure Treatment Target of 120/80 mm Hg Relevant for Children?
Bonita Falkner and Samuel S. Gidding
Hypertension. published online March 28, 2016;
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Comentario sobre el estudio SPRINT
¿Es relevante para los niños el objetivo terapéutico del estudio
SPRINT de lograr una presión arterial de 120/80 mmHg?
Bonita Falkner, Samuel S. Gidding
E
l estudio SPRINT (Systolic Blood Pressure Intervention
Trial) realizado en adultos mayores con riesgo muy elevado de eventos cardiovasculares demostró un beneficio significativo de los resultados derivados del tratamiento de la presión
arterial (PA) para alcanzar un objetivo de ≤120/80 mmHg.1 Los
resultados del estudio SPRINT no serían generalizables para
niños y adolescentes porque dicho estudio se centró en adultos mayores con alto riesgo de eventos cardiovasculares. Los
criterios de inclusión del estudio fueron PA elevada y criterios
adicionales de alto riesgo como una puntuación del riesgo de
Framingham >15 %, enfermedad cardiovascular anterior, tasa
de filtración glomerular reducida o edad >75 años. Este estudio aparenta no estar relacionado con un entorno pediátrico.
Sin embargo, la importancia del estudio SPRINT, cuando se
considera la prevención pediátrica, es que la hipertensión acelera la enfermedad cardiovascular. Con excepción de la edad,
los criterios de inclusión del estudio SPRINT a menudo son
consecuencia de la hipertensión de larga data. El éxito del estudio SPRINT plantea el interrogante de si existe un beneficio
derivado de la PA <120/80 mmHg de por vida.
Datos considerables sobre la hipertensión en adultos vinculan los desenlaces cardiovasculares adversos con niveles de
PA >140/90 mmHg, lo que avala el tratamiento farmacológico
para la prevención primaria de eventos cardiovasculares. Conforme a un conjunto de datos epidemiológicos que demuestran
un aumento del riesgo cardiovascular a partir de un valor de PA
≥120/80 mmHg, las guías de la Joint National Commission 7
(JNC7) sobre hipertensión en adultos introdujo el concepto de
prehipertensión para valores de PA de 120/80 a 139/89 mmHg.
El propósito fue advertir a los pacientes que modificaran sus
conductas del estilo de vida para prevenir un aumento mayor
de la PA.2
No existen datos que vinculen un valor umbral de la PA en
la infancia con eventos cardiovasculares décadas después en
la adultez. Los niños tienen PA más baja que los adultos. Los
niveles de PA en los niños aumentan con la edad, y desde el
inicio hasta mediados de la adolescencia, la probabilidad de
Las opiniones expresadas en este editorial no necesariamente son
las de los editores o de la American Heart Association.
De los Departments of Medicine and Pediatrics (B.F.), Thomas Jefferson University, Philadelphia, PA; y Department of Pediatrics, Nemours/A.I. DuPont Hospital for Children, Wilmington, DE (S.S.G.).
Dirigir la correspondencia a: Bonita Falkner, Thomas Jefferson
University, 833 Chestnut St. Ste.700, Philadelphia, PA 19107. Correo
electrónico: bonita.falkner@ jefferson.edu
(Hypertension. 2016;67:826-828.
DOI: 10.1161/HYPERTENSIONAHA.116.06934.)
© 2016 American Heart Association, Inc.
Hypertension se encuentra disponible en http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.116.06934
que un niño cumpla los criterios de la JNC VII para prehipertensión supera el 10 %.3 A partir de la década del 70, la hipertensión en la infancia se ha definido estadísticamente como el
nivel de PA que supera el percentil 95 de la distribución normativa de la PA. El percentil 95 fue una estimación conservadora de la PA alta en la infancia que originalmente tuvo como
propósito permitir la detección de niños con hipertensión secundaria.4 El percentil 95 se encuentra muy por debajo del valor umbral convencional para adultos que define hipertensión
en 140/90 mmHg, particularmente en niños más pequeños.
Usando los criterios de un nivel de PA ≥ al percentil 95 con
mediciones repetidas, la prevalencia de hipertensión infantil
es ≈3,5 % e incluye hipertensión primaria y secundaria.56 La
prehipertensión en la infancia se definió como la PA sistólica
o diastólica ≥ al percentil 90 y < al percentil 95. A partir de los
12 años de edad, el nivel de PA sistólica en el percentil 90 es
mayor que el valor umbral de prehipertensión de 120 mmHg
en adultos. Para que sea coherente con la definición en adultos,
la prehipertensión en la adolescencia se ajustó a PA ≥120/80
< al percentil 95 desde los 12 años de edad y durante toda la
adolescencia.3 Así, 120/80 mmHg se convirtió en un valor de
PA fácil de recordar y además un nivel de PA que definió algún
nivel de riesgo.
El aumento normal de la PA en la infancia se relaciona con
el crecimiento y la edad. Las tablas de referencia que proporcionan el valor de PA para los percentiles 90 y 95 se determinan según el sexo, la edad y la altura en la infancia. Estas
tablas son complejas y engorrosas de usar, particularmente en
la atención pediátrica primaria. Aunque la medición de la PA
se ha convertido en una rutina en los visitas pediátricas, debido a la complejidad de las tablas de referencia de la PA, con
frecuencia no se identifican los niveles anormales de PA en
niños y adolescentes asintomáticos.6-8 Sería una gran ventaja
contar con un único valor como umbral de la PA para separar
a los niños con PA normal de aquellos para quienes deberían
consultarse las tablas de PA.
Otra nueva recomendación en las guías de práctica clínica
de 2004 para la PA infantil fue que la evaluación de un niño
con hipertensión confirmada también incluya una evaluación
del daño en órganos blanco.3 Estudios clínicos posteriores informaron evidencia ecocardiográfica de hipertrofia ventricular
izquierda en una porción considerable de niños y adolescentes hipertensos.9,10 La evidencia del daño en órganos blanco
en jóvenes hipertensos actualmente incluye rigidez vascular
y mayor espesor íntima carotídeo.11 Asimismo, también se ha
informado hipertrofia ventricular izquierda en adolecentes con
prehipertensión.12,13 Además, existe evidencia emergente respecto de que la obesidad en la infancia también contribuye a
aumentar la masa cardíaca, además del nivel de PA.12,14 Estos
informes atraen la atención al hecho de que un nivel de PA de
26
Hypertension
Mayo 2016
120/80 mmHg en la adolescencia ya puede estar relacionado
con el daño temprano en el órgano blanco cardiovascular. Conforme a datos recientes sobre la PA en niños y adolescentes
provenientes de la Encuesta Nacional de Examen de Salud y
Nutrición (National Health and Nutrition Examination Surveys), ≈10 % de adolescentes ingresan a la adultez joven con
una PA ≥120/80 mmHg.15
La importancia de la PA de 120 a 139/80 a 89 mmHg medida entre los 18 y 30 años de edad para el desarrollo del daño
en el órgano blanco cardiovascular en la mediana edad se ha
enfatizado en el estudio Coronary Artery Risk Development
in Young Adults. Cuando se evaluaron, en la mediana edad,
el calcio en las arterias coronarias mediante tomografía computarizada y la estructura y función del ventrículo izquierdo
mediante ecocardiograma, los factores predictivos sólidos del
daño en órgano blanco fueron la PA y otros factores de riesgo
medidos entre los 18 y 30 años. La exposición crónica durante
los siguientes 20 a 25 años a PA elevada y otros factores de
riesgo contribuyeron al empeoramiento de la lesión en el órgano blanco.16-18
La relación entre la PA infantil y la condición de la PA en
la adultez joven se delineó aún más en un análisis de datos del
estudio Dunedin Multidisciplinary Health and Development,
un estudio prospectivo de cohortes que incluyó mediciones periódicas de la PA y de otros factores de riesgo desde los 7 años
de edad hasta los 38. Se identificaron cuatro grupos distintos
de trayectoria de la PA de acuerdo con la condición de la PA a
los 38 años de edad; normal, normal-alta, prehipertensa e hipertensa. La trayectoria hipertensa tuvo los niveles de PA más
altos en la infancia, y la trayectoria prehipertensa presentó los
niveles subsiguientes más altos de PA infantil, con valores de
PA sistólica por encima de 120 mmHg en la adolescencia. Para
aquellos con PA normal y normal-alta a los 38 años de edad, la
PA sistólica durante toda la infancia y la adolescencia estuvo
por debajo de 120 mmHg. Un aumento del índice de masa corporal resultó estar muy relacionado con un cambio ascendente
en los 4 grupos de trayectoria de la PA.19
Los datos anteriores sobre la trayectoria de la PA y la evidencia emergente sobre el daño en órgano blanco relacionado
con la PA en la juventud, como también estudios genéticos en
la población20 avalan un cambio de paradigma en el enfoque
de la PA infantil que va de la prevención primaria a la prevención primordial. Si la prevención primaria es la intervención
para bajar la PA a fin de prevenir eventos cardiovasculares,
entonces la prevención primordial serían intervenciones para
prevenir el desarrollo de prehipertensión/hipertensión en la infancia, y bajar los niveles de la PA se extendería a la adultez
temprana-media. En cuanto a la prevención primordial, existen
factores de riesgo de la PA que son modificables. La relación
longitudinal entre sobrepeso/obesidad en la juventud y la futura hipertensión ha sido bien comprendida durante muchos
años.21,22 La actividad física en la juventud y la aptitud física en
la adultez joven moderan el aumento de la PA con la edad y se
relacionan con una reducida probabilidad de hipertensión futura.23,24 Debido a cambios seculares en los patrones alimentarios,
el consumo dietario de sodio durante la infancia se encuentra
muy por encima de los niveles recomendados. Los informes de
análisis de datos recientes de la Encuesta Nacional de Examen
de Salud y Nutrición demuestran una relación positiva entre
el consumo de sodio y la PA en la infancia.25 Existe además
un efecto independiente derivado del consumo de sodio, como
también del índice de masa corporal y la circunferencia de la
cintura, en la tendencia creciente de los niveles de PA infantil.26 Estos hallazgos indican potenciales beneficios en la PA al
reducir el consumo excesivo de sodio.
Si la prehipertensión en los individuos jóvenes es el umbral
para el daño en órgano blanco y probablemente crea el marco
para la trayectoria más alta de la PA, entonces la prevención
primordial debería centrarse en conservar la PA normal. Una
PA normal (óptima) para adolescentes es <120/80 mmHg.
Conforme a las tablas de percentiles para la PA infantil,
<110/70 mmHg es probablemente una PA óptima para niños
menores de 12 años. Esta son cifras fáciles de recordar y podrían hacer más sencillo identificar a niños y adolescentes que
podrían beneficiarse de los esfuerzos por modificar los factores
conocidos que aumentan la PA en los jóvenes. Si la PA objetivo de 120/80 mmHg del estudio SPRINT se pudiera alcanzar
en todas las personas a los 18 años de edad y mantenerse por
décadas, el único criterio de inclusión del estudio SPRINT que
aún sería relevante sería ser mayor de 75 años.
Declaración de conflictos de interés
Ninguna.
1.
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