As hypertensive target-organ damage has been associated with diminished diurnal blood pressure (BP) variation in adults, we compared diurnal BP patterns of hypertensive adolescents with left ventricular hypertrophy with normotensive and hypertensive adolescents with normal left ventricular mass. In addition, the frequency of microalbuminuria (Malb), hyperfiltration, and reduced renal functional reserve (RFR) was evaluated in adolescents with normal BP and untreated borderline and mild essential hypertension. Thirty-three normotensive (NT) adolescents, 14.5+/-2.1 years (mean +/- SD), and 29 untreated borderline and mildly hypertensive (HT) adolescents, 14.6+/-2.4 years, wore the SpaceLabs 90207 ambulatory BP monitor for 24 h. Left ventricular mass was measured by M-mode echocardiography and then indexed (LVMI) to the cube of height. Creatinine clearance (Clcr) and urine Malb was measured on 24 h collection and RFR by change in creatinine clearance after an oral protein load. Diurnal BP change was expressed as the absolute and percent day-night BP fall and cusum derived plot height (CPH) and circadian alteration magnitude (CDCAM). Groups were compared using analysis of covariance with adjustments for race, gender, and body mass index. All NT and 19 HT subjects (HT-1) had normal LVMI at 22.2+/-5.3 and 25.8+/-3.8 g/m3, respectively. Ten HT (HT-2) had increased LVMI of 36.9+/-5.2 g/m3. No significant difference was found for absolute or percent day-night BP fall or CDCAM between groups. Nocturnal systolic BP was correlated most closely with LVMI (r = 0.41, p = .001). Clcr, Malb, and RFR did not differ between the groups. In conclusion, adolescents with borderline and mild essential hypertension and left ventricular hypertrophy have similar levels of diurnal BP fall, urine Malb excretion, and RFR compared to normotensive and hypertensive adolescents with normal left ventricular mass.
Despite widespread use to treat childhood hypertension, enalapril has never been studied systematically to determine effectiveness, dose response, and safety in a pediatric population. This study was conducted prospectively in 110 hypertensive children ages 6 to 16 years in two sequential phases. The primary outcome variable for both phases of the study was trough (24-h postdose) sitting diastolic blood pressure. The primary objective of the first phase of the study was to determine whether enalapril lowered blood pressure in children in a dose-dependent manner. During a 2-week, double-blind, randomized, dose-response period, patients were stratified by weight (< 50 kg or > or = 50 kg), then assigned to one of three dosing groups: low(0.625 or 1.25 mg), middle (2.5 or 5 mg), or high dose (20 or 40 mg). Reduction in blood pressure was examined as a function of dose ratio (1:4:32) and on a weight-adjusted basis. On completion of the dose-response phase of the study, patients entered a 2-week, double-blind, randomized withdrawal to either enalapril or placebo. Antihypertensive effectiveness, defined as the difference in sitting diastolic blood pressure between the placebo and enalapril groups, was determined. Adverse events were carefully recorded throughout the study. The dose-response relationship for enalapril had a negative slope and was linear over the chosen dosing range, suggesting that larger doses of enalapril were associated with a greater reduction in blood pressure. Randomized withdrawal to active drug orplacebo confirmed the antihypertensive effectiveness of enalapril in the middle- and high-dose groups. The antihypertensive effect of enalapril was maintained across age, gender, race, and Tanner stage. Enalapril appears to be an effective and generally well-tolerated antihypertensive agent in children ages 6 to 16 years. An initial dose of 2.5 mg in children weighing < 50 kg and 5 mg in children weighing > 50 kg (mean = 0.08 mg/kg) administered once daily effectively lowered blood pressure within 2 weeks in most patients. Blood pressure was reduced in a dose-dependent fashion, with larger doses resulting in a greater reduction.
The effectiveness and safety of valsartan have not been assessed in hypertensive children. Therefore, hypertensive patients aged 6 to 16 years (n=261) were randomized to receive weight‐stratified low‐ (10/20 mg), medium‐ (40/80 mg), or high‐dose (80/160 mg) valsartan for 2 weeks. After 2 weeks, patients were randomized to a 2‐week placebo‐controlled withdrawal phase. Dose‐dependent reductions in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) were observed after 2 weeks (low dose, −7.9/−4.6 mm Hg; medium dose, −9.6/−5.8 mm Hg; high dose, −11.5/−7.4 mm Hg [P<.0001 for all groups]). During the withdrawal phase, SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group (SSBP, −2.7 mm Hg [P=.0368]; SDBP, −3.0 mm Hg [P=.0047]). Similar efficacy was observed in all subgroups. Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double‐blind and 52‐week open‐label phases. J Clin Hypertens (Greenwich). 2011;13:357–365. ©2011 Wiley Periodicals, Inc.
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