RESUMEN
This 4-week randomized, double blind, placebo-controlled study (N=240), 1-year open label trial (N=233), and single-dose pharmacokinetic study (N=22) evaluated candesartan cilexetil (3 doses) in hypertensive children aged 6 to 17 years. Seventy-one percent were 12 years of age or older, 71% were male, and 47% were black. Systolic (SBP)/diastolic (DBP) blood pressure declined 8.6/4.8-11.2/8.0 mm Hg with candesartan and 3.7/1.8 mm Hg with placebo (P<.01 compared to placebo for SBP and for the mid and high doses for DBP; placebo-corrected 4.9/3.0-7.5/6.2 mm Hg). The slopes for dose were not, however, different from zero (P>.05). The response rate (SBP and DBP <95th percentile) after 1 year was 53%. The pharmacokinetic profiles in 6- to 12- and 12- to 17-year-olds were similar and were comparable to adults. Eight candesartan patients discontinued treatment because of an adverse event. Candesartan is an effective, well-tolerated antihypertensive agent for children aged 6 to 17 years and has a pharmacokinetic profile that is similar to that in adults.
Asunto(s)
Antihipertensivos/farmacocinética , Bencimidazoles/farmacocinética , Compuestos de Bifenilo/farmacocinética , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Tetrazoles/farmacocinética , Adolescente , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/efectos adversos , Niño , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Tetrazoles/administración & dosificación , Tetrazoles/efectos adversos , Resultado del TratamientoRESUMEN
The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recently recommended staging hypertension (HTN) in children and adolescents based on blood pressure severity. The use of blood pressure staging and its corresponding therapeutic approach was examined in this pooled analysis assessing the risk for end-organ damage, specifically left ventricular hypertrophy among hypertensive adolescents stratified by working group criteria. Newly diagnosed hypertensive adolescents and normotensive control subjects similar in age, race/ethnicity, gender, and body mass index completed casual and 24-hour ambulatory blood pressure measurements, M-mode echocardiography, and fasting serum laboratories. Hypertensive subjects had higher insulin and cholesterol but similar glucose levels as compared with control subjects. Among subjects with stage 1 HTN by casual blood pressure, 34% had white-coat HTN as opposed to 15% of stage 2 hypertensive subjects. Of the subjects with normal casual measurements, 20% had HTN by ambulatory monitoring. Subjects with stage 2 HTN by casual measurement alone (odds ratio: 4.13; 95% CI: 1.04 to 16.48) and after 24-hour ambulatory confirmation (odds ratio: 7.23; 95% CI: 1.28 to 40.68) had increased odds for left ventricular hypertrophy. In addition, the risk for left ventricular hypertrophy was similar for subjects with masked and confirmed stage 1 HTN, whereas subjects with white-coat HTN had a risk comparable to normotensive subjects. Thus, recommendations that adolescents with stage 2 HTN by casual measurements alone receive medication initially along with therapeutic lifestyle counseling are reasonable, though ambulatory blood pressure monitoring remains a valuable tool for evaluating children with stage 2 HTN, because >10% have white-coat HTN.
Asunto(s)
Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Guías de Práctica Clínica como Asunto , Adolescente , Monitoreo Ambulatorio de la Presión Arterial , Comorbilidad , Intervalos de Confianza , Estudios Transversales , Ecocardiografía Doppler , Femenino , Educación en Salud/organización & administración , Humanos , Incidencia , Modelos Logísticos , Masculino , Oportunidad Relativa , Probabilidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To determine the prevalence of hypertension and pre-hypertension on the basis of the 2004 National High Blood Pressure Education Program Working Group guidelines in an adolescent school-screening population. STUDY DESIGN: Cross-sectional assessment of blood pressure (BP) in 6790 adolescents (11-17 years) in Houston schools was conducted from 2003 to 2005. Initial measurements included height, weight, and 4 oscillometric BP readings. Repeat measurements were obtained on 2 subsequent occasions in students with persistently elevated BP. Final prevalence was adjusted for loss to follow-up and logistic regression used to assess risk factors. RESULTS: BP distribution at initial screen was 81.1% normal, 9.5% pre-hypertension, and 9.4% hypertension (8.4% Stage 1; 1% Stage 2). Prevalence after 3 screenings was 81.1% normal, 15.7% pre-hypertension, and 3.2% hypertension (2.6% Stage 1; 0.6% Stage 2). Hypertension and pre-hypertension increased with increasing body mass index. Sex, race, and classification as either at-risk for overweight or overweight were independently associated with pre-hypertension. Only classification as overweight was associated with hypertension. CONCLUSIONS: Application of new classification guidelines for adolescents with elevated BP reveals approximately 20% are at risk for hypertension. Further research determining the significance of each BP category and refining definitions to account for BP variability is warranted.
Asunto(s)
Hipertensión/epidemiología , Adolescente , Negro o Afroamericano/estadística & datos numéricos , Estudios Transversales , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Hipertensión/etnología , Masculino , Texas/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
OBJECTIVE: To evaluate the efficacy, tolerability, and blood pressure (BP) lowering effect of extended release metoprolol succinate (ER metoprolol) in children 6 to 16 years of age with established hypertension. STUDY DESIGN: Patients were randomized to one of four treatment arms: placebo or ER metoprolol (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg). Data were analyzed on 140 intent-to-treat patients. RESULTS: Mean age (+/-SD) was 12.5 +/- 2.8 years and mean baseline BP was 132/78 +/- 9/9 mmHg. Following 4 weeks of treatment, mean changes in sitting BP were: placebo = -1.9/-2.1 mmHg; ER metoprolol 0.2 mg/kg = -5.2/-3.1 mmHg; 1.0 mg/kg = -7.7/-4.9 mmHg; 2.0 mg/kg = -6.3/-7.5 mmHg. Compared with placebo, ER metoprolol significantly reduced systolic blood pressure (SBP) at the 1.0 and 2.0 mg/kg dose (P = .027 and P = .049, respectively), reduced diastolic blood pressure (DBP) at the 2.0 mg/kg dose (P = .017), and showed a statistically significant dose response relationship for the placebo-corrected change in DBP from baseline. There were no serious adverse events or adverse events requiring study drug discontinuation among patients receiving active therapy. CONCLUSION: These data indicate that ER metoprolol is an effective and well-tolerated treatment for hypertension in children.
Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Hipertensión/tratamiento farmacológico , Metoprolol/análogos & derivados , Administración Oral , Adolescente , Antagonistas Adrenérgicos beta/efectos adversos , Análisis de Varianza , Determinación de la Presión Sanguínea , Niño , Intervalos de Confianza , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/diagnóstico , Masculino , Metoprolol/administración & dosificación , Metoprolol/efectos adversos , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
To define the effect of short-term rosuvastatin treatment on the estimated glomerular filtration rate (eGFR), the database of controlled clinical trials in the Rosuvastatin Clinical Development Program was reviewed. Thirteen studies comprising 3,956 rosuvastatin-treated patients were selected based on a serum creatinine measurement at 6 or 8 weeks after initiation of rosuvastatin treatment, randomization to approved and marketed rosuvastatin doses (5 to 40 mg), and unchanged rosuvastatin dose from treatment initiation (baseline) through 6 to 8 weeks of treatment. eGFR was determined with the Modification of Diet in Renal Disease formula. eGFR significantly increased for each dose of rosuvastatin individually and for all doses combined compared with baseline (range +0.9 to +3.2 ml/min/1.73 m2). Further analysis of 5 blinded, placebo-controlled trials comprising 525 patients showed an increase in eGFR of +0.8 ml/min/1.73 m2 (95% confidence interval +0.1 to +1.5) for all rosuvastatin-treated patients, which was significantly different from baseline (p <0.04) and from a change of -1.5 ml/min/1.73 m2 in the placebo-treated patients (95% confidence interval -2.5 to -0.5, p <0.001). The increase in eGFR for rosuvastatin-treated patients was consistent across all major demographic and clinical subgroups of interest, including patients with baseline proteinuria, baseline eGFR <60 ml/min/1.73 m2, and in patients with hypertension and/or diabetes. In conclusion, these results are consistent with previous rosuvastatin studies that showed an upward trend in eGFR with long-term treatment (> or =96 weeks) and with the hypothesis that statins may have pleiotropic mechanisms of action that include beneficial renal effects.
Asunto(s)
Fluorobencenos/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , LDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rosuvastatina Cálcica , Factores de Tiempo , Resultado del TratamientoRESUMEN
Millions of children with attention deficit hyperactivity disorder (ADHD) are treated with stimulant medications. To evaluate cardiovascular risk, 24-h ambulatory blood pressure monitoring (ABPM) was performed on and off medication. Thirteen subjects underwent APBM both on stimulant therapy and placebo using a placebo-controlled, double-blind, randomized, cross-over design. After a 3-day run-in followed by a 24-h monitoring period, subjects crossed over to the alternate therapy for repeated ABPM. Subjects demonstrated elevations in most hemodynamic parameters derived from ABPM during the active treatment period. Total diastolic blood pressure (69.7 mmHg vs 65.8 mmHg, p =0.02) and waking diastolic blood pressure (75.5 mmHg vs 72.3 mmHg, p =0.03) were significantly higher during active treatment. Total heart rate was also significantly higher during active treatment (85.5 beats/min vs 79.9 beats/min, p =0.004). The rate-pressure product (the product of systolic blood pressure x heart rate), an index of myocardial oxygen demand, was higher during active treatment (9,958 vs 9,076, p =0.008). This study provides evidence for a possible negative cardiovascular effect of stimulant medications in children with ADHD. This potential cardiovascular risk should be balanced against the beneficial behavioral effects of this class of medication.
Asunto(s)
Anfetamina/farmacología , Anfetamina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Presión Sanguínea/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Dextroanfetamina/farmacología , Dextroanfetamina/uso terapéutico , Metilfenidato/farmacología , Metilfenidato/uso terapéutico , Anfetamina/efectos adversos , Monitoreo Ambulatorio de la Presión Arterial , Estimulantes del Sistema Nervioso Central/efectos adversos , Niño , Estudios Cruzados , Dextroanfetamina/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Metilfenidato/efectos adversos , Factores de TiempoRESUMEN
OBJECTIVES: To determine whether there are clinical differences between children referred for hypertension evaluation from a primary care practice and children with hypertension detected through school-based screening. Study design Referral patients (n=58) were compared with 44 screening patients with hypertension from school-based screening of 5102 students. All subjects underwent 24-hour ambulatory blood pressure (BP) monitoring. White coat hypertension was defined as 24-hour mean BP <95th percentile and BP load <25%. RESULTS: Referral subjects were more likely to be male and had higher body mass index than screening subjects but did not differ by age or ethnic distribution. Average clinic BP values tended to be higher among referral patients (140/79 vs 135/76 mm Hg, P=.07); however, the hypertension severity was closely matched when clinic BP was indexed to the subject-specific 95th percentile. Ambulatory mean BP, BP indices, and BP loads showed no differences by subject source for 24-hour, wake, or sleep periods. White coat hypertension prevalence did not differ between referral and screening subjects (28% vs 30%, P=.83). CONCLUSION: These findings suggest that hypertensive children identified by subspecialty referral are representative of the overall population of hypertensive children in the community, thereby supporting the generalizability of clinic-based research in pediatric hypertension.
Asunto(s)
Hipertensión/diagnóstico , Tamizaje Masivo , Atención Primaria de Salud/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Servicios de Salud Escolar/estadística & datos numéricos , Adolescente , Adulto , Instituciones de Atención Ambulatoria , Índice de Masa Corporal , Niño , Femenino , Humanos , Masculino , Factores Sexuales , TexasRESUMEN
OBJECTIVES: To describe the current prevalence of pediatric hypertension and the relationships between gender, ethnicity, overweight, and blood pressure. METHODS: School-based screening was performed in 5102 children (13.5 +/- 1.7 years) from May through November 2002. Age, gender, ethnicity, weight, and height were ascertained, and body mass index (BMI) was calculated as weight (kg)/height (m2). Overweight was defined as BMI > or =95th percentile. Students with blood pressure >95th percentile on the first screening underwent a second screening 1 to 2 weeks later, and then a third screening if blood pressure was >95th percentile at the second screening. RESULTS: Ethnicity distribution was 44% white, 25% Hispanic, 22% African American, and 7% Asian. Overall, overweight prevalence was 20%, which varied significantly by ethnicity (31% Hispanic, 20% African American, 15% white, and 11% Asian). The prevalence of elevated blood pressure after first, second, and third screenings was 19.4%, 9.5%, and 4.5%, respectively. Elevated blood pressure on first screening was highest among Hispanics (25%) and lowest among Asians (14%). Ethnic differences in the prevalence of hypertension (elevated blood pressure on 3 screenings) were not significant after controlling for overweight. The prevalence of hypertension increased progressively as the BMI percentile increased from < or =5th percentile (2%) to > or =95th percentile (11%). After adjustment for gender, ethnicity, overweight, and age, the relative risk of hypertension was significant for gender (relative risk: 1.50; confidence interval: 1.15, 1.95) and overweight (relative risk: 3.26; confidence interval: 2.50, 4.24). CONCLUSIONS: These results confirm an evolving epidemic of cardiovascular risk in youth, as evidenced by an increase in the prevalence of overweight and hypertension, notably among ethnic minority children.
Asunto(s)
Hipertensión/epidemiología , Obesidad/epidemiología , Adolescente , Presión Sanguínea , Índice de Masa Corporal , Niño , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/etnología , Masculino , Obesidad/complicaciones , Obesidad/etnología , Prevalencia , Texas/epidemiologíaRESUMEN
The prevalence of overweight in youth is increasing dramatically in the United States. The intimate relationship of obesity and overweight with cardiovascular risk factors and diabetes in adults raises concern for the likelihood of subsequent disease development in children. Ethnic minorities are so disproportionately affected by overweight that a call to action is necessary. The International Society on Hypertension in Blacks convened this work group as part of a larger effort to focus on cardiovascular risk protection beginning in childhood and adolescence, entitled the "Children are Our Messengers: Changing the Health Message" initiative. This summary article reviews the data on cardiovascular risk factors and overweight in ethnic children and adolescents, and culminates in a practical algorithm for evaluating overweight children for cardiovascular risk.
Asunto(s)
Enfermedades Cardiovasculares/etnología , Obesidad/etnología , Adolescente , Negro o Afroamericano/estadística & datos numéricos , Peso Corporal/etnología , Peso Corporal/fisiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Niño , Humanos , Americanos Mexicanos/estadística & datos numéricos , Obesidad/complicaciones , Obesidad/terapia , Factores de Riesgo , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
To determine whether systematic differences exist between hypertensive children referred for evaluation by primary care providers and children identified through community-based screening, cardiovascular risk factors and surrogate markers of hypertensive injury were compared based on subject source (referral versus screening). Children referred to a hypertension clinic for persistently elevated blood pressure were compared with children identified as hypertensive during school screening of 5102 students in Houston public schools. M-mode echocardiography of the left ventricle was performed and subsequently reviewed by 2 independent sonographers blinded to identifying subject information. Subsets of subjects also underwent carotid artery ultrasound for measurement of intimal-medial thickness, overnight urine collections for microalbuminuria, and fasting serum cholesterol, triglycerides, and glucose. Ninety-seven total subjects (54 screening and 43 referral) met inclusion criteria and had technically adequate echocardiography performed. The prevalence of left ventricular hypertrophy (LVH) was 37%. Referral subjects demonstrated significantly greater left ventricular mass index (38.8 versus 34.2 g/m(2.7); P<0.01) and a higher prevalence of LVH (49% versus 28%; P<0.05). Among subjects who underwent carotid ultrasound (n=75), carotid intimal-medial thickness was significantly higher in referral subjects (0.61 versus 0.57, P<0.05). When controlling for BMI z score, which was significantly higher in referral subjects, systematic differences by subject source did not persist. These findings suggest that hypertensive children who are predominantly overweight, independent of the manner in which patients come to medical attention, will manifest evidence of more severe cardiovascular disease assessed by surrogate markers such as left ventricular mass index or carotid artery intimal medial thickness.
Asunto(s)
Enfermedades Cardiovasculares/diagnóstico , Hipertensión/diagnóstico , Adolescente , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Arterias Carótidas/diagnóstico por imagen , Niño , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/epidemiología , Masculino , Tamizaje Masivo , Obesidad/complicaciones , Derivación y Consulta , Factores de Riesgo , Servicios de Salud Escolar , UltrasonografíaRESUMEN
To determine whether hypertension and overweight status are associated with increased carotid intimal-medial thickness (cIMT) in children, vascular ultrasonography was performed in newly diagnosed hypertensive patients ( n=53) and normotensive controls ( n=33). Hypertensive subjects were identified either by referral or by systematic school-based hypertension screening. Hypertension was defined as blood pressure above the 95th percentile based on current Task Force criteria, and overweight was defined as body mass index (BMI) >25 kg/m(2). cIMT was assessed by high-resolution vascular ultrasonography of the distal common carotid artery. Hypertensive subjects had a higher cIMT than normotensive subjects (0.62 vs. 0.53 mm, P<0.00001). This difference remained significant after controlling for the effects of gender, race, age, height, weight, and BMI. Similarly, overweight subjects had a higher cIMT than normal-weight subjects (0.63 vs. 0.54 mm, P<0.0001). Subjects with both systolic and diastolic hypertension had higher cIMT than those with isolated systolic hypertension (0.67 vs. 0.60, P<0.05). cIMT showed significant positive pairwise correlation with age, height, weight, BMI, and systolic blood pressure. Among all clinical variables analyzed, cIMT was most strongly correlated with BMI ( r=0.53, P<0.001). These results provide further evidence that vasculopathy occurs in association with known cardiovascular risk factors such as hypertension and obesity during childhood.
Asunto(s)
Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/etiología , Hipertensión/complicaciones , Adolescente , Presión Sanguínea , Índice de Masa Corporal , Enfermedades de las Arterias Carótidas/epidemiología , Niño , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Obesidad/complicaciones , Obesidad/epidemiología , Factores de Riesgo , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen , UltrasonografíaRESUMEN
OBJECTIVES: To determine the association between carotid artery intimal-medial thickness (cIMT) and left ventricular mass index (LVMI) in children with elevated blood pressure. METHODS: Study subjects (n = 32; mean age: 13.9 +/- 2.7 years) were untreated new referrals to a pediatric hypertension clinic with confirmed elevated blood pressure. LVM was calculated from 2-dimensionally guided m-mode echocardiographic measurements of the left ventricle. LVMI was calculated as LVM (g)/height (m)2.7, and left ventricular hypertrophy (LVH) was defined as LVMI >95th percentile. Carotid artery duplex ultrasound was performed by protocol by experienced vascular sonographers who were unaware of the echocardiography results. The thickest IMT complex of the far wall of the distal common carotid artery was measured in longitudinal B-mode section using a high-resolution linear array of 8 MHz. RESULTS: The prevalence of LVH and increased cIMT was 41% and 28%, respectively. Subjects with increased cIMT had higher LVMI (46.8 g/m2.7 vs 31.4 g/m2.7) than those with normal cIMT. The LVH prevalence was 89% (8 of 9) among subjects with increased cIMT as compared with 22% (5 of 23) in subjects with normal cIMT. cIMT was positively correlated with body mass index (r = 0.43), interventricular septal thickness (r = 0.58), posterior wall thickness (r = 0.54), and LVMI (r = 0.54). cIMT and LVMI were positively associated after accounting for age, gender, and body mass index. CONCLUSIONS: These findings raise the possibility that carotid duplex ultrasound, by indicating the presence of early arterial wall changes, may be useful for predicting other cardiovascular sequelae in hypertensive children.
Asunto(s)
Arterias Carótidas/diagnóstico por imagen , Hipertensión/epidemiología , Hipertrofia Ventricular Izquierda/epidemiología , Adolescente , Comorbilidad , Ecocardiografía , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Prevalencia , Análisis de RegresiónRESUMEN
OBJECTIVE: To determine the factors that contribute to the pathogenesis of isolated systolic hypertension in children. METHODS: School-based measurement was performed of blood pressure (BP), heart rate, weight, and height in 2460 students (49% Hispanic, 31% black, 13% white) 12 to 16 years of age in 8 urban public schools. An independent group of 71 untreated children underwent 24-hour ambulatory BP monitoring (ABPM) to confirm clinic hypertension and assess circadian BP patterns. RESULTS: Hypertension and obesity were found in 17% and 23% of students, respectively. Among hypertensive students, 88% (363/413) had isolated systolic hypertension. Hypertension was more prevalent in obese than nonobese students (33% vs 11%, P <.0001). Obese hypertensive students had higher resting heart rate than nonobese normotensive patients (85.9 vs 79.6 beats/min, P <.001). Among patients who underwent ABPM, isolated systolic hypertension was found in 51% (36/71) by clinic BP and in 62% (18/29) with confirmed hypertension by ABPM. Blood pressure variability during daytime and sleep periods was higher in obese than nonobese patients for systolic BP (P <.01) and diastolic BP (P <.05). CONCLUSIONS: The findings of increased heart rate and BP variability in obese children with isolated systolic hypertension suggest that sympathetic nervous system hyperactivity may contribute to its pathogenesis.
Asunto(s)
Hipertensión/fisiopatología , Obesidad/fisiopatología , Adolescente , Índice de Masa Corporal , Niño , Diástole , Femenino , Hemodinámica , Humanos , Masculino , Estudios Retrospectivos , Sistema Nervioso Simpático/fisiopatología , SístoleRESUMEN
Antihypertensive medications are used extensively in children despite a paucity of randomized, placebo-controlled trials. This study was among the first randomized, controlled pediatric antihypertensive medication trials, in which the combination drug bisoprolol fumarate/hydrochlorothiazide (B/HT) was compared with placebo. The study comprised a 2-week single-blind placebo screening period, a 6-week double-blind dose titration period, a 4-week double-blind dose maintenance period, and a 2-week double-blind dose-tapering period. One hundred and forty subjects were enrolled to achieve 94 randomized subjects treated either with B/HT ( n=62) or placebo ( n=32). B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure (SiSBP) (9.3 vs. 4.9 mmHg, P<0.05) and sitting diastolic blood pressure (SiDBP) (7.2 vs. 2.7 mmHg, P<0.05). The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension. The percentage of subjects with BP less than the 90th percentile at study completion was 45% for B/HT and 34% for placebo ( P=NS). Although the study demonstrated that B/HT reduced BP safely compared with placebo, the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension, particularly in adolescents with mild-to-moderate BP elevation.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Bisoprolol/uso terapéutico , Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Adolescente , Antagonistas Adrenérgicos beta/administración & dosificación , Bisoprolol/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Niño , Diuréticos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Hipertensión/fisiopatología , Masculino , Placebos , Método Simple Ciego , Inhibidores de los Simportadores del Cloruro de Sodio/administración & dosificación , Insuficiencia del TratamientoRESUMEN
To determine whether ambulatory blood pressure is more predictive of left ventricular hypertrophy than is casual blood pressure in hypertensive children, echocardiography and ambulatory blood pressure data from 37 untreated hypertensive children were analyzed. Left ventricular mass was calculated using the Devereux equation, left ventricular mass index was calculated as left ventricular mass (in grams)/height(2.7) (in meters), and left ventricular hypertrophy was defined as left ventricular mass index >51 g/m(2.7). Average blood pressure, blood pressure load, and blood pressure index (average blood pressure divided by pediatric ambulatory blood pressure 95th percentile) were calculated. Left ventricular mass index was strongly correlated with 24-hour systolic blood pressure index (r=0.43, P=0.008) and was also correlated with 24-hour systolic blood pressure (r=0.34, P=0.037), 24-hour systolic blood pressure load (r=0.38, P=0.020), wake systolic blood pressure load (r=0.37, P=0.025), sleep systolic blood pressure (r=0.33, P=0.048), and sleep systolic blood pressure load (r=0.38, P=0.021). Left ventricular mass index did not correlate with age, weight, clinic blood pressure, or ambulatory diastolic blood pressure. The overall prevalence of left ventricular hypertrophy was 27%. The prevalence of left ventricular hypertrophy was 47% (8 of 17) in patients with both systolic blood pressure load >50% and 24-hour systolic blood pressure index >1.0, compared with 10% (2 of 20) in patients without both criteria (P=0.015). These data suggest ambulatory blood pressure monitoring may be useful for the clinical assessment of hypertensive children by identifying those at high risk for the presence of end organ injury.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial/métodos , Hipertensión/diagnóstico , Hipertrofia Ventricular Izquierda/diagnóstico , Adolescente , Niño , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Factores de Riesgo , UltrasonografíaRESUMEN
Systolic blood pressure (SBP) has become the major criterion for the diagnosis, staging, and treatment of hypertension in adults, based on the epidemiology and pathophysiology of adult hypertension, linkage between SBP levels and disease, and benefits of treatment of isolated SBP hypertension. Although children do not typically suffer overt hypertensive disease, an accumulation of data suggests that SBP elevation is as important a factor in the morbidity of hypertension in children as in adults. Systolic BP hypertension is more common in children, whether examining an unselected sampling of patients by routine screening or a selected sampling of referred hypertensive patients. Mild-to-moderate BP elevation in children is associated with increased left ventricular mass (LVM), with SBP more closely linked to LV morphology than diastolic BP (DBP). Furthermore, SBP is associated with increased LVM even in patients with SBP within the normal range. Among hypertensive children, the reported prevalence of left ventricular hypertrophy (LVH) ranges from 30% to 70%, and LVH is more closely related to SBP than to DBP. These data suggest that treatment of hypertension should be directed at normalization of SBP, even when DBP is within the normal range. In addition, trials of antihypertensive medications in children should incorporate SBP hypertension into study inclusion criteria.