BACKGROUND

Short-term therapy can decrease blood pressure (BP) to less than the 95th percentile in only about 50% of children. The aim of our study was to investigate the long-term control of hypertension (HT) in children using ambulatory BP monitoring (ABPM).

METHODS

We analyzed data from all children who started ramipril monotherapy in our center. Controlled HT was defined according to the most current guidelines as systolic and diastolic BP at daytime and nighttime <90th percentile in primary HT and <75th percentile in renoparenchymal HT.

RESULTS

Thirty-eight children who were on therapy ≥1 year were included. Thirty-two children had renoparenchymal, and 6 had primary HT. The median age at the beginning of therapy was 13.6 years (range = 4.1–18.0 years), and the median time of antihypertensive therapy was 2.6 years (range = 1.0–11.8 years). Thirty-four percent of children received combination therapy; the median number of antihypertensive drugs was 1.5 drugs/patient (range = 1–4). Sixty-eight percent of children had BP <95th percentile, but only 34% of the children had controlled HT. Children with uncontrolled HT had a tendency to have a higher daytime diastolic BP index before the start of therapy than children with controlled HT (0.99±0.11 vs. 0.94±0.11; P = 0.09). There was a significant decrease in prevalence of nondipping (from 47% to 16%; P = 0.006) with therapy.

CONCLUSIONS

This first pediatric study focusing on long-term control of HT using ABPM showed that long-term control of HT is better than short-term control, but still only one-third of children achieve the new BP goals. The low control of HT might be improved by more intensive therapy.

Treatment of hypertension (HT) is of great important for prevention of cardiovascular and renal diseases; patients with uncontrolled HT have higher prevalence of hypertensive target organ damage such as left ventricular hypertrophy, cardiovascular morbidity and mortality, and chronic kidney diseases (CKDs) than patients with controlled HT.13 In adults, the control of HT achieved by antihypertensive drugs is often inadequate.4 There are only a few studies on control of HT in children treated for HT.5,6 They have shown by using clinic blood pressure (BP) measurement that it is inadequate in 25%–65% of patients.5,6 We have shown in our previous short-term studies using ambulatory BP monitoring (ABPM) that adequate control of HT is achieved only in about 50% of patients.7,8 The study period in our previous short-term studies was only 6 months, and it was not known whether longer duration of treatment can improve the unsatisfactorily low control of ambulatory HT. Long-term control of HT in prospectively treated children using ABPM had not yet been investigated. Therefore, we evaluated the long-term control of HT in children who started ramipril therapy in our previous prospective short-term studies.7,8 The aim of our study was to investigate the long-term control of HT in children using ABPM and to examine the risk factors for uncontrolled HT.

METHODS

We analyzed data from all children who started ramipril monotherapy during our previous 6-month prospective interventional study,7 continued to be followed-up in our Department of Pediatrics center between January 1999 and December 2011, and had done ABPM at least 1 year after starting ramipril therapy (prospective open-label extension study). Inclusion criteria for the study were (i) HT confirmed by ABPM treated initially with ramipril monotherapy, (ii) follow-up ABPM study at least 1 year after starting ramipril therapy, and (iii) sufficient number of BP measurements during ABPM study (only recordings with a minimum of 40 readings and without breaks longer than 2 hours). In children with >1 ABPM study on antihypertensive drugs, only the most recent ABPM study was used for the analysis. Exclusion criteria for the study were (i) children treated by dialysis or after renal transplantation or (ii) noncompliance with the study medication.

ABPM studies were carried out using oscillometric monitors SpaceLabs 90207 or 90217 (SpaceLabs Medical, Redmont, WA). An appropriate cuff was placed on the nondominant arm by a physician who also informed the child and parents in detail how to operate the monitoring system. Monitors were programmed to measure BP automatically every 20 minutes during the day and every 30 minutes at night. The criteria for omitting BP outliers from ambulatory BP recordings were systolic BP > 200mm Hg or < 70mm Hg, diastolic BP > 150mm Hg or < 40mm Hg, and mean arterial pressure (MAP) > 200mm Hg or < 40mm Hg. According to the reference values by Soergel et al.,9 data were analyzed by using standardized daytime (8 am to 8 pm) and nighttime (12 am to 6 am) periods. Mean systolic and diastolic BP at daytime and at nighttime were calculated. BP index was calculated as mean BP divided by the 95th percentile, which was determined according to the body height and sex of the patient.9 Controlled HT was defined according the most current guidelines10 as systolic and diastolic BP at daytime and nighttime <90th percentile in children with primary HT and <75th percentile in children with renoparenchymal HT on antihypertensive therapy. The prevalence of children with all ambulatory BP values <95th percentile (definition of controlled HT according the old guidelines11) was also assessed. Clinic BP was measured at the day of ABPM using a conventional mercury manometer, and clinic HT was defined as systolic or diastolic BP ≥95th percentile according to appropriate guidelines.3

Chronic renal failure was defined as CKD stage 2–4 according to the Kidney Disease Outcomes Quality Initiative (K-DOQI) Guidelines.12 Overweight was defined as body mass index between 1 and 2 SD of the national standards for children of the Czech Republic,13 and obesity was defined as body mass index ≥ 2 SDs. The children had either primary or secondary (renoparenchymal) HT. The diagnosis of primary HT was established after comprehensive diagnostic evaluation that included appropriate clinical, laboratory, and radiographic studies according to appropriate guidelines.3,11

Statistical analysis

Data were expressed as mean ± SD, median (range), or as percentages. The comparisons between groups were made using nonparametric Mann–Whitney U test or parametric t test and paired t test or Wilcoxon signed rank test for comparisons between baseline and follow-up parameters in the same subjects. Fisher exact test was used to examine differences in proportions between groups. The data were tested also in univariable and multivariable regression analysis. Graph Pad Prism 5.02 (Graph Pad, La Jolla, California) was used to perform the statistical analysis. P < 0.05 was regarded as statistically significant.

RESULTS

Demographics and antihypertensive therapy

Altogether 44 children started ramipril therapy in our pediatric department between January 1999 and December 2010. Six children were excluded from this long-term study because of a short observational period of <1 year (n = 3), non-compliance with the study medication (n = 2), or refusal to perform ABPM with the study medication (n = 1). A total of 38 children fulfilled the inclusion criteria. All patients were white. The patient’s characteristics are shown in Table 1. CKDs in children with renoparenchymal HT consisted of congenital anomalies of the kidney and urinary tract (n = 10), autosomal dominant and recessive polycystic kidney disease (n = 8 and n = 3, respectively), cystic kidney diseases of unknown etiology (n = 3), chronic glomerulonephritis (n = 3), neurofibromatosis (n = 2), residual renal anomaly after hemolytic uremic syndrome (n = 2), and diabetic nephropathy (n = 1).

Table 1.

Baseline demographic and clinical data of children with treated hypertension

Parameter All children Primary hypertension Renal hypertension P value 
No. of patients (%) 38 (100%) 6 (16%) 32 (84%) NA 
Boys/girls 20/18 3/3 17/15 NA 
Median age, y 13.6 (4.1–18.0) 16.6 (7.4–17.8) 12.2 (4.1–18.0) 0.09 
Median body height, percentile 37 (1–100) 39 (1–88) 30 (1–100) 0.35 
Mean BMI, percentile 61±32 77±35 58±31 0.10 
Obesity 16% 50% 9% 0.09 
Baseline mean ambulatory daytime systolic BP index 1.02 (0.85–1.18) 1.05 (1.02–1.09) 1.02 (0.85–1.18) 0.32 
Baseline mean ambulatory daytime diastolic BP index 0.95 (0.79–1.30) 1.01 (0.91–1.08) 0.95 (0.79–1.30) 0.20 
Baseline mean ambulatory nighttime systolic BP index 1.05 (0.88–1.32) 1.03 (0.96–1.18) 1.06 (0.88–1.32) 0.39 
Baseline mean ambulatory nighttime diastolic BP index 1.02 (0.82–1.44) 1.03 (0.88–1.23) 1.02 (0.82–1.44) 0.41 
Baseline office systolic BP index 1.10 (0.77–1.29)  1.11 (1.00–1.29) 1.10 (0.77–1.25) 0.30 
Baseline office diastolic BP index 1.06 (0.69–1.44) 1.13 (0.91–1.44) 1.04 (0.69–1.40) 0.31 
Parameter All children Primary hypertension Renal hypertension P value 
No. of patients (%) 38 (100%) 6 (16%) 32 (84%) NA 
Boys/girls 20/18 3/3 17/15 NA 
Median age, y 13.6 (4.1–18.0) 16.6 (7.4–17.8) 12.2 (4.1–18.0) 0.09 
Median body height, percentile 37 (1–100) 39 (1–88) 30 (1–100) 0.35 
Mean BMI, percentile 61±32 77±35 58±31 0.10 
Obesity 16% 50% 9% 0.09 
Baseline mean ambulatory daytime systolic BP index 1.02 (0.85–1.18) 1.05 (1.02–1.09) 1.02 (0.85–1.18) 0.32 
Baseline mean ambulatory daytime diastolic BP index 0.95 (0.79–1.30) 1.01 (0.91–1.08) 0.95 (0.79–1.30) 0.20 
Baseline mean ambulatory nighttime systolic BP index 1.05 (0.88–1.32) 1.03 (0.96–1.18) 1.06 (0.88–1.32) 0.39 
Baseline mean ambulatory nighttime diastolic BP index 1.02 (0.82–1.44) 1.03 (0.88–1.23) 1.02 (0.82–1.44) 0.41 
Baseline office systolic BP index 1.10 (0.77–1.29)  1.11 (1.00–1.29) 1.10 (0.77–1.25) 0.30 
Baseline office diastolic BP index 1.06 (0.69–1.44) 1.13 (0.91–1.44) 1.04 (0.69–1.40) 0.31 

Data are means ± SD or medians (range).

Abbreviations: BMI, body mass index; NA, not applicable.

The reason for obtaining the follow-up ABPM study was routine yearly BP check in stable treated hypertensive children regardless of clinic BP values. The mean time studied by ABPM was 23.8±1.7 hours; the mean number of BP readings during this time was 56.6±7.8; and ABPM was generally well tolerated by the children (90% of attempted readings were successful).

The median time of duration of HT at the start of antihypertensive drug therapy was 0.3 years (range = 0.0–6.8). The median time of antihypertensive drug therapy at the follow-up study (time of follow-up) was 2.6 years (range = 1.0–11.8). The mean number of prescribed antihypertensive drugs was 1.5±0.8 (range = 1–4). The drugs at the follow-up ABPM study were angiotensin-converting enzyme inhibitors (ramipril: mean dose = 3.6±1.8mg/m2/day; n = 37, morning dose n = 25, and evening dose n = 12), diuretics (hydrochlorothiazide: n = 9; furosemide: n = 1), beta-blockers (atenolol: n = 4), calcium channel blockers (amlodipin: n = 2; felodipin: n = 1), and angiotensin receptor blockers (losartan: n = 1). Twenty-five children (66%) were on monotherapy (ramipril in all); 13 children (34 %) were on combination therapy of 2–4 antihypertensive drugs.

Control of HT

Thirteen out of 38 children (34%) had controlled HT. The control of HT in children with primary HT was not significantly different from children with secondary HT (17% vs. 38%; P = 0.64). Twenty-six children (68%) had all ambulatory BP values <95th percentile (old criteria). The results of the prevalence of controlled HT according to the new and old criteria are summarized in Table 2.

Table 2.

Prevalence of short-term and long-term controlled hypertension (HT) based on old and new criteria

Parameter Definition of controlled HT BP measurement Prevalence of controlled HT Reference 
Short-term controlled HT (1–12 months) Systolic and diastolic BP <95th percentile in all types of HT (old) ABPM 55% Seeman et al. 20047 
ABPM 53% Seeman et al. 200714 
ABPM 74% Litwin et al. 201015 
Long-term controlled HT (>1 year) Systolic and diastolic BP <95th percentile in all types of HT (old) Clinic BP 75% Sieber et al. 20035 
Clinic BP 35% Silverstein et al. 20066 
ABPM 68% This study 
 Systolic and diastolic BP <90th percentile in all types of HT (old) Clinic BP 100% Flynn 200516 
Clinic BP 79% DiPietro et al. 200917 
 Systolic and diastolic BP <90th percentile in primary HT and <75th percentile in renal HT (new) ABPM 34% This study 
Parameter Definition of controlled HT BP measurement Prevalence of controlled HT Reference 
Short-term controlled HT (1–12 months) Systolic and diastolic BP <95th percentile in all types of HT (old) ABPM 55% Seeman et al. 20047 
ABPM 53% Seeman et al. 200714 
ABPM 74% Litwin et al. 201015 
Long-term controlled HT (>1 year) Systolic and diastolic BP <95th percentile in all types of HT (old) Clinic BP 75% Sieber et al. 20035 
Clinic BP 35% Silverstein et al. 20066 
ABPM 68% This study 
 Systolic and diastolic BP <90th percentile in all types of HT (old) Clinic BP 100% Flynn 200516 
Clinic BP 79% DiPietro et al. 200917 
 Systolic and diastolic BP <90th percentile in primary HT and <75th percentile in renal HT (new) ABPM 34% This study 

Abbreviations: ABPM, ambulatory 24-hour blood pressure monitoring; BP, blood pressure.

In children with uncontrolled HT at the follow-up ABPM study on therapy (n = 25 of 38; 66%), 7 (28% of uncontrolled HT) had isolated systolic HT, 3 (12%) had isolated diastolic HT, 15 (60%) had systolic and diastolic HT, 6 (25%) had isolated daytime HT, 6 (24%) had isolated nighttime HT, and 13 (52%) had daytime and nighttime HT.

There was no significant difference in age, mean body mass index SDs, obesity, sex, number of antihypertensives, percentage of combined antihypertensive therapy, duration of HT before start of therapy, duration of therapy, daytime systolic BP, and nighttime systolic and diastolic BP before start of therapy between children with controlled and uncontrolled HT (Table 3). There was a trend for higher daytime diastolic BP index before the start of therapy in the group of children with uncontrolled HT. The multivariable regression analysis did not reveal any significant independent predictors for control of HT. The demographic data and data on antihypertensive therapy in children with controlled and uncontrolled HT are given in Table 3.

Table 3.

Demographic data and antihypertensive therapy in children with controlled and uncontrolled hypertension

Parameter Controlled hypertension Uncontrolled hypertension P value 
No. of patients (%) 13 (34) 25 (64)  
Median age at follow-up, y 17.5 (6.0–18.7) 17.8 (13.0–19.0) 0.45 
Duration of hypertension before start of therapy, y 0.1 (0.0–8.3) 0.7 (0.0–6.8) 0.46 
Duration of therapy, y 2.4 (1.1–11.8) 2.8 (1.3–10.8) 0.34 
Daytime systolic BP index before start of therapy  1.02±0.07 1.04±0.06 0.26 
Daytime diastolic BP index before start of therapy 0.94±0.11 0.99±0.11 0.09 
Nighttime systolic BP index before start of therapy 1.05±0.11 1.07±0.08 0.45 
Nighttime diastolic BP index before start of therapy 1.02±0.17 1.06±0.12 0.14 
BMI (SDs) at follow-up 1.04±0.75 0.22±1.69 0.17 
Obesity, % 23 16 0.67 
Female sex, % 38 52 0.50 
No. of antihypertensive drugs per patient 1.3±0.6 1.6±0.8 0.32 
Combined antihypertensive therapy, % of patients 23 40 0.47 
Ramipril dose, mg/m2/day 3.5±1.8 3.7±1.8 0.70 
Parameter Controlled hypertension Uncontrolled hypertension P value 
No. of patients (%) 13 (34) 25 (64)  
Median age at follow-up, y 17.5 (6.0–18.7) 17.8 (13.0–19.0) 0.45 
Duration of hypertension before start of therapy, y 0.1 (0.0–8.3) 0.7 (0.0–6.8) 0.46 
Duration of therapy, y 2.4 (1.1–11.8) 2.8 (1.3–10.8) 0.34 
Daytime systolic BP index before start of therapy  1.02±0.07 1.04±0.06 0.26 
Daytime diastolic BP index before start of therapy 0.94±0.11 0.99±0.11 0.09 
Nighttime systolic BP index before start of therapy 1.05±0.11 1.07±0.08 0.45 
Nighttime diastolic BP index before start of therapy 1.02±0.17 1.06±0.12 0.14 
BMI (SDs) at follow-up 1.04±0.75 0.22±1.69 0.17 
Obesity, % 23 16 0.67 
Female sex, % 38 52 0.50 
No. of antihypertensive drugs per patient 1.3±0.6 1.6±0.8 0.32 
Combined antihypertensive therapy, % of patients 23 40 0.47 
Ramipril dose, mg/m2/day 3.5±1.8 3.7±1.8 0.70 

Data are means ± SD or medians (range) unless otherwise noted. Controlled hypertension is defined as mean daytime and nighttime systolic and diastolic blood pressure (BP) <90th percentile in primary hypertension or <75th percentile in renal hypertension. Uncontrolled hypertension is defined as mean daytime and nighttime systolic and diastolic BP ≥90th percentile in primary hypertension or ≥75th percentile in renal hypertension. BP index was calculated as mean BP divided by the 95th percentile that was determined according to the body height and sex of the patient.9

Abbreviation: BMI, body mass index.

Children who reached follow-up with all mean ambulatory BP values of at least <95th percentile had a significantly longer duration of therapy (median duration = 3.5 years; range = 1.1–11.8) than children who did not have all ambulatory BP values <95th percentile (median duration = 1.5 years; range = 1.0–6.8; P = 0.04).

Changes in BP

The data on treatment-induced changes in ambulatory and clinic BP during the follow-up of the patients are given in Table 4. There was a statistically significant decrease of all ambulatory BP values, a nondipping phenomenon, and an increase in nocturnal BP dip. Masked HT (clinic BP <95th percentile but daytime BP ≥ 95th percentile) was found in 3 children (8%), isolated nocturnal HT (clinic BP and daytime BP < 95th percentile but nighttime BP ≥ 95th percentile) was found in 4 children (11%), and the white coat effect (clinic BP ≥ 95th percentile but daytime or nighttime BP < 95th percentile) was found in 16 treated children (42%).

Table 4.

Changes in ambulatory and office blood pressure (BP) in treated children

Variable Baseline Follow-up (median = 2.6 years) P value 
Mean ambulatory daytime systolic BP, mm Hg 135 (111–154) 125 (106–149) 0.0012 
Mean ambulatory daytime diastolic BP, mm Hg 81 (67–109) 72 (62–93) <0.0001 
Mean ambulatory nighttime systolic BP, mm Hg 120 (104–138) 108 (95–132) <0.0001 
Mean ambulatory nighttime diastolic BP, mm Hg 68 (55–91) 58 (49–74) <0.0001 
Mean ambulatory daytime systolic BP index 1.02 (0.85–1.18) 0.93 (0.86–1.10) <0.0001 
Mean ambulatory daytime diastolic BP index 0.95 (0.79–1.30) 0.85 (0.73–1.09) <0.0001 
Mean ambulatory nighttime systolic BP index 1.05 (0.88–1.32) 0.94 (0.85–1.09) <0.0001 
Mean ambulatory nighttime diastolic BP index 1.02 (0.82–1.44) 0.87 (0.73–1.12) <0.0001 
Nocturnal dip of systolic BP, % 10 (–4 to 22) 13 (0–23) 0.016 
Nocturnal dip of diastolic BP, % 17 (–6 to 27) 21 (0–34) 0.015 
Prevalence of nondipping phenomenon 47% 16% 0.006 
Office systolic BP, mm Hg 140 (85–163) 132 (95–174) 0.36 
Office diastolic BP, mm Hg 88 (50–118) 81 (57–100) 0.021 
Office systolic BP index 1.10 (0.77–1.29) 1.02 (0.81–1.36) 0.0029 
Office diastolic BP index 1.06 (0.69–1.44) 0.95 (0.71–1.19) 0.0003 
Variable Baseline Follow-up (median = 2.6 years) P value 
Mean ambulatory daytime systolic BP, mm Hg 135 (111–154) 125 (106–149) 0.0012 
Mean ambulatory daytime diastolic BP, mm Hg 81 (67–109) 72 (62–93) <0.0001 
Mean ambulatory nighttime systolic BP, mm Hg 120 (104–138) 108 (95–132) <0.0001 
Mean ambulatory nighttime diastolic BP, mm Hg 68 (55–91) 58 (49–74) <0.0001 
Mean ambulatory daytime systolic BP index 1.02 (0.85–1.18) 0.93 (0.86–1.10) <0.0001 
Mean ambulatory daytime diastolic BP index 0.95 (0.79–1.30) 0.85 (0.73–1.09) <0.0001 
Mean ambulatory nighttime systolic BP index 1.05 (0.88–1.32) 0.94 (0.85–1.09) <0.0001 
Mean ambulatory nighttime diastolic BP index 1.02 (0.82–1.44) 0.87 (0.73–1.12) <0.0001 
Nocturnal dip of systolic BP, % 10 (–4 to 22) 13 (0–23) 0.016 
Nocturnal dip of diastolic BP, % 17 (–6 to 27) 21 (0–34) 0.015 
Prevalence of nondipping phenomenon 47% 16% 0.006 
Office systolic BP, mm Hg 140 (85–163) 132 (95–174) 0.36 
Office diastolic BP, mm Hg 88 (50–118) 81 (57–100) 0.021 
Office systolic BP index 1.10 (0.77–1.29) 1.02 (0.81–1.36) 0.0029 
Office diastolic BP index 1.06 (0.69–1.44) 0.95 (0.71–1.19) 0.0003 

Values are median (range).

Association of CKD stages with BP control

Seventeen children (45%) had CKD stage 2–4 at follow-up. There was no significant difference in the prevalence of controlled HT between patients with CKD stages 2–4 and children without CKD stages 2–4 (35% vs. 33%).

DISCUSSION

This is the first study focusing on the long-term control of HT in treated children using ABPM. It has shown that long-term control of HT is better than short-term control according to the old criteria, but still only one-third of children reach the recently recommended more strict BP goal (new criteria). Table 2 shows comparison between short-term and long-term control of HT in different pediatric studies according to the old and new criteria.57,1417 Until now there have been absolutely no data on the long-term control of ambulatory HT in children using the most recent guidelines with the BP goal of <75th percentile for CKD patients (renal HT).10 Our study using ABPM, which is a better tool for management of HT in children,18,19 showed that only a minority of hypertensive children with CKD achieved the most recent treatment BP goal (new criteria).

The factors associated with poor control of HT have only rarely been elucidated. They are disease associated (true therapy resistant HT), physician associated (i.e., no treatment, low doses of drugs, reluctance for combination therapy, not recommended nonpharmacological therapy), or patient associated (poor adherence to pharmacological or nonpharmacological therapy). In previous studies, obesity, primary HT, noncompliance, and antihypertensive monotherapy have been shown to be associated with poor BP control in treated patients.5,6,20 In our study using multivariable regression analysis, including obesity, body mass index, etiology of HT, severity of HT before treatment, and number of antihypertensive drugs or combination therapy, we could not find any independent predictor for uncontrolled HT. We can therefore only speculate that one of the reasons for a low control of HT could be that the new BP targets were published in 2009 and physicians still hesitate to decrease BP to levels lower than the 95th percentile and even more so to lower than the 75th percentile in CKD patients. Furthermore, we can speculate that the mean number of antihypertensive drugs (n = 1.5 per patient) and the use of combination therapy (only 34% of children) are too low for controlling HT in the majority of children. Moreover, the mean dose of ramipril (3.6mg/m2/day) is only about half of the fixed dose used in the ESCAPE trial.21 Children with treatment-induced ambulatory BP values at least <95th percentile (old target BP)11 had significantly longer duration of therapy than children with ambulatory BP values ≥95th percentile. Therefore, it seems that the decrease of BP at least to the old BP target needs time to be achieved. Similar results have been demonstrated in dialyzed and transplanted children.22

We could not find any association between CKD stages and control of HT, which is in contrast with result from an observational Chronic Kidney Disease in children (CKiD) study23 but in agreement with our previous retrospective study8 and with the results of the largest interventional BP study in children (ESCAPE trial).21 These encouraging results demonstrate that it is nowadays possible to control HT in children with CKD stages 2–4 as well as in children without CKD stages 2–4, thereby retarding the progression of CKD and inducing regression of left ventricular hypertrophy8,14,21 However, it has to be said that the control of HT in CKD children was quite low—only 35% of them reached the new goal of BP < 75th percentile. Treatment intensification (more combination therapy, higher doses) can improve BP control in adults24 and is necessary also in children to achieve new BP goals. The strategies to improve the low long-term control of HT are targeted mainly to the physician-associated and patient-associated reasons for inadequate BP control. These strategies include better prescription of antihypertensive drugs (increase to maximal doses, earlier and more common use of combination therapy), more consultation regarding nonpharmacological therapy, better knowledge of HT by physicians (better interpretation of measured BP values, better detection of HT by using ABPM more often), and better compliance of the patients and their parents with the recommended pharmacological and also nonpharmacological therapy. Children with ambulatory BP still ≥95th percentile at the last follow-up had a history of untreated HT lasting at least twice as long as children who reached all BP values <95th percentile (data not shown). Therefore, it seems that the delay of the start of pharmacological therapy can negatively influence the long-term therapeutic control of HT. This suggests that an earlier start of drug therapy in children might improve the long-term control of HT.

Reduced nocturnal decrease of BP (nondipping) is associated with increased cardiovascular morbidity and mortality and progression of CKDs in adults and children.2529 Therefore, restoration of normal nocturnal dip of BP is becoming a new treatment target in hypertensive patients. Therapeutic improvement of dipping by bedtime dosing of antihypertensives is associated with decreased cardiovascular events in adults.30 In our study, we were able to increase nocturnal dip and to decrease the prevalence of nondipping. Therefore, we can hypothetically further decrease the cardiovascular and renal risk profile in our patients. We were able to improve the BP dip not only by treating some of the patients with bedtime dosing (n = 14 of 38 children) but apparently also by other mechanisms. One of these possible mechanisms could be a decrease of total body sodium content due to the recommended low-sodium diet or the use of diuretics (n = 10 children).28,31 Changes of nocturnal BP dipping during antihypertensive therapy are only rarely reported in pediatric studies. In our previous short-term study with ramipril, the nocturnal dip did not change significantly (decrease in systolic/diastolic BP dip of 2%/1%), which is maybe due to evening dose in only 1 of 19 children.14 Further studies are needed to investigate whether decreased prevalence of nondipping is associated with decreased cardiovascular and renal adverse events.

The advantage of our study over other previous studies is the presence of data on pretreatment BP levels and data on the duration of untreated HT. We could therefore demonstrate for the first time that the severity and duration of untreated HT as well as the duration of antihypertensive therapy have a tendency to influence the control of HT. A further advantage is the long duration of therapy and a very small selection bias (only 6 of 44 children).

There are some limitations of our study, mainly a relatively small number of patients and single-center design. Larger prospective interventional studies are needed for definitive conclusions if even longer duration of therapy and treatment intensification would result in improved control of HT. Despite these limitations, our study is the longest study on the control of HT in children using ABPM and the first using the new BP goals for hypertensive children.

In conclusion, this study is the first pediatric study focusing on long-term control of HT in children using ABPM. It indicates that the long-term control of HT is better than the short-term control using the old criteria, but still only one-third of children reach the recently recommended new BP goal.

DISCLOSURE

The authors declared no conflict of interest.

ACKNOWLEDGMENTS

This study was supported by the project CZ.1.05/2.1.00/ 03.0076 from the European Regional Development Fund and by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic). We thank Ondrej Hradsky for performing regression analysis and Adam Whitley for reviewing the manuscript.

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