Search

It is hypothesized that primary hypertension (PH) is a disorder with origins in childhood linked to, at least in part, aberrations of growth and maturation processes. To evaluate the possible relation between the rate of biological maturity and development of PH, bone age (BA) assessments on the basis of dual x-ray absorptiometry-derived hand scans were performed in 54 newly diagnosed children and adolescents with PH and 54 healthy controls matched for body mass index (BMI), age and sex. Chronological age (CA), body height (in centimeters), body weight (in kilograms), BMI (in kilograms per meter squared), and blood pressure were assessed. Healthy controls had a mean BA of 14.7+/-2.3 years that was not significantly different from their mean CA of 14.2+/-2.1 years. In the PH group, the BA of 16.0+/-2.0 years was higher by 1.9+/-0.9 years compared with their CA of 14.1+/-2.0 years (P<0.0001). The magnitude of acceleration of skeletal maturation (BA-CA) and its prevalence (88.9%) were significantly higher in PH compared with BMI-matched controls (37.0%; chi(2)=31.4; P<0.0001). BA-CA values of PH patients were higher by 1.24 years in normal weight (P<0.0001), 1.80 years in overweight (P<0.01), and 1.40 years in obese (P<0.0001) subgroups of BMI z score-matched controls. Stepwise regression revealed that predictors of blood pressure status from normotension through prehypertension stages 1 and 2 of hypertension were BA-CA (beta=0.530; P<0.0.001), height (beta=-0.379; P<0.01), and CA (beta=0.298; P<0.05; R(2)=0.43). In conclusion, irrespective of BMI, advanced biological maturation should be considered as an independent marker for the development of hypertension.

Obesity is the main intermediate phenotype of primary hypertension (PH), and increased fat mass is directly related to target organ damage (TOD) and metabolic syndrome (MS). The aim of the study was to assess the sensitivity and specificity of body mass index (BMI), percentile-based, definitions of obesity [BMI > 95th percentile (pc)], and overweight (BMI > 85th pc), and BMI thresholds for cardiovascular (cv) complications (BMIcv) described by Katzmarzyk et al. (Pediatrics 114:198-205, 2004) in predicting risk of TOD and MS in 122 adolescents with PH. Our results indicated that the prevalence of left ventricular hypertrophy (LVH) and carotid intima-media thickness (cIMT) above 2 standard deviations (SDS) was the same, irrespective of the criteria used. BMIcv was more sensitive as a marker of LVH than were the cut-off values of the 85th pc and 95th pc of BMI (87.5%, 75%, 62.5%, respectively; P < 0.0001). BMIcv thresholds and cut-off values of the 85th pc of BMI were of the same sensitivity in predicting the presence of MS (95.8% and 95.8%, respectively) and were more sensitive than the cut-off values of the BMI 95th pc (87.5%; P = 0.02). Metabolic abnormalities, including insulin resistance, were more marked in patients with greater BMI, irrespective of cut-off value. However, only when a stratification system using the 85th pc of BMI was used, were the differences significant for a homoeostasis model assessment for insulin resistance (HOMA-IR) and for serum concentrations of high-density lipoprotein (HDL)-cholesterol, triglycerides and adiponectin. We concluded that BMIcv is more sensitive for diagnosing the presence of LVH and that the cut-off value of the 85th pc of BMI is more sensitive for predicting presence of MS in children with PH.

Because primary hypertension (PH) is associated with calcium metabolism, it is hypothesized that PH may be related to osteoporosis risk. The study aimed to evaluate the relationship between body composition and bone strength in hypertensive adolescents. Total body scans using x-ray absorptiometry (DPX-L, GE Healthcare) were performed in 94 PH children aged 6 to 18 years (21 girls and 73 boys). References of healthy control subjects were used for the calculation of Z scores (age and gender matched), SD scores (height and gender matched), and SDs scores (weight and gender matched). Total body bone mineral density, total body bone mineral content (TBBMC), lean body mass (LBM), and fat mass (FM) were investigated. Relative bone strength index was calculated as the TBBMC:LBM ratio. As evidenced by Z scores, PH case subjects had slightly higher total body bone mineral density, TBBMC, and LBM compared with healthy subjects. Reduced LBM/body weight (BW) Z scores of -1.9+/-1.5 and -1.2+/-1.4, increased FM Z scores of +2.5+/-2.5 and +1.7+/-2.0, and increased FM/BW Z scores of +1.6+/-1.3 and +1.1+/-1.4 were noted in girls and boys compared with healthy subjects, respectively (P<0.001). When increased BW was controlled for, PH girls differed in SDs scores for LBM (-1.4+/-1.7; P<0.01), FM (+1.6+/-2.2; P<0.05), FM/BW (+0.9+/-1.0; P<0.05), and FM/LBM (+1.3+/-1.4; P<0.01) but not for total body bone mineral density (+0.2+/-1.0; P value not significant), TBBMC (-1.2+/-1.6; P=0.07), LBM/BW (-0.7+/-1.0; P=0.07), and TBBMC/LBM (-1.0+/-2.1; P value not significant), when compared with respective SDs scores of -0.3+/-1.1, +0.3+/-1.1, +0.3+/-1.0, +0.3+/-1.0, -0.2+/-1.0, -0.6+/-1.9, -0.3+/-1.0, and -0.2+/-1.0 in PH boys. In conclusion, PH adolescents had increased FM and an imbalanced relationship among BW, FM, and LBM. In PH girls, bone strength, although proper for chronological age and body height, was lower than expected for BW.

Unlabelled: The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-beta1 and VEGF(165) was evaluated in 303 children with CKD stage II-IV (GFR 48 +/- 22 ml/min/1.73 m(2)) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20)., Results: The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 +/- 2042 vs 216 +/- 335 fmol/g creatinine for ET-1; 252 +/- 338 vs 155 +/- 158 ng/g for VEGF; 31.6 +/- 37.0 vs 10.9 +/- 9.8 ng/g for TGF-beta1 (each P < 0.0001). The excretion of ET-1 and TGF-beta1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-beta1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P < 0.005) and renal function (r = -0.21, -0.13 and -0.15; P < 0.001; < 0.05; < 0.01; respectively) VEGF and TGF-beta1 excretion rates were positively correlated both in patients and controls., Conclusions: Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-beta1 and VEGF(165) in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-beta1 and VEGF(165) excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.

The standard renoprotection is based on the inhibition of the renin-angiotensin system (RAS) by angiotensin convertase inhibitors (ACEi) or angiotensin II receptor 1 blockers (AT1B). The aim of our study was to analyze the effects of the addition of AT1B to ACEi-based renoprotection in children with chronic kidney disease. We examined 11 children with a mean age of 10.5 years (range, 0.5-18 years) with a mean glomerular filtration rate (GFR) of 61+/-61 ml/min/1.73 m(2). In four patients, the primary renal disease was hemolytic uremic syndrome, in three congenital nephrotic syndrome (CNS), in two reflux nephropathy, prune-belly syndrome in one and acute cortical necrosis in one. All patients were treated with complex hypotensive ACEi-based therapy. AT1B losartan was added in a mean dose of 0.9 mg/kg/day. The change in GFR, proteinuria and blood pressure at two 12-month intervals before and after adding AT1B was compared. The results showed that during the 12 months preceding AT1B therapy, there was no change in blood pressure and proteinuria, but the GFR declined in 7 of 11 patients. After the 12th month of add-on therapy with AT1B, there was a significant decrease in both absolute and indexed blood pressure values. Proteinuria decreased in eight patients, did not change in one and increased in two, including one with CNS. The GFR stabilized or increased in eight patients and decreased in three patients with CNS. In 7 of 11 patients, there was a significant, but not threatening increase in serum potassium. In conclusion, add-on renoprotection with AT1B added to ACEi is safe and significantly improves the renoprotective effects of ACEi treatment in children with progressive nephropathies, including patients with advanced CKD.

Objective: Our aim was to determine the prevalence of left ventricular hypertrophy (LVH) and increased intima-media thickness (IMT) in Caucasian children with newly diagnosed, untreated essential hypertension (EH)., Participants: Our study cohort consisted of 72 children with EH (mean age: 14.5 years; range: 5-18 years). The control groups consisted of 103 age-matched, healthy children., Methods: We evaluated the left ventricular mass (LVM), intima-media thickness in the carotid (cIMT) and superficial femoral (fIMT) arteries, 24-h ambulatory blood pressure, and biochemical cardiovascular risk factors., Results: Of the hypertensive children examined, 41.6% had LVM above the 95th percentile, and 13.2% had LVM above 51 g/m2.7. Of the hypertensive subjects, the cIMT was above 2 SDS of normal values in 38.8%, and the flMT was above 2 SDS of normal values in 17.5%. Patients with LVM above 51 g/m2.7 had a higher birth weight than other patients. LVM, cIMT, and fIMT correlated with 24-h SBP and pulse pressure; LVM also correlated with homocysteine and serum uric acid concentrations. fIMT correlated with low Aprotein A1 (ApoA1), higher ApoB and C reactive protein, and daily sodium excretion. Step-wise regression analysis revealed that serum uric acid and higher birth weight were predictors for LVM, pulse pressure was a predictor for cIMT, and ApoB was a predictor for fIMT., Conclusions: A significant number of adolescents with EH already had cardiovascular damage at diagnosis. LVM and markers of arterial injury correlate with SBP, biochemical, and perinatal cardiovascular risk factors. Serum uric acid and higher birth weight are predictors of LVM.

Unlabelled: The aim of the study was to assess the rate of development of voiding dysfunction (VD) in patients with reflux nephropathy. We investigated 150 pts with vesicoureteral reflux (VUR): 33 boys and 117 girls in mean age 9 +/- 3.3 years with normal renal function. In all pts we performed renal scintigraphy (DMSA) and ABPM. Renal scarring by DMSA scan was categorized into grades 1-4. In all pts we assessed high and laterality of VUR, renal function (clearance creatinine--Ccr) and occurency of hypertension (HT)., Results: Of 150 pts, 80 (53.3%) developed VD (54.5% boys and 52% girls). DMSA grade: 1--27 pts, 2--85 pts; 3--31 pts; 4--7 pts. No statistically significant difference was found depends of: sex, age, laterality of renal damage in DMSA, unilateral and bilateral reflux for the development of VD. The incidence 3-4 grade in DMSA scan was significantly higher in pts with IV-V grade of VUR in comparison to pts with lower grade of VUR in group with and without voiding dysfunction. IV-V grades of VUR were observed more frequently in pts with bladder/sphincter dysfunction. The occurency of HT in group with VD and without VD was 12 pts (15%) and 8 (11.4%) respectively (ns). Pts with VD have lower Ccr in comparison with pts without VD (129.1 vs 136.3 ml/min/1.73 m2; p<0.05)., Conclusions: Approximately 50% of patients with VUR demonstrated VD. VD occurred independent of age. IV-V degrees VUR and more severe changes in DMSA scan were seen in pts with bladder/sphincter dysfunction.

Unlabelled: Low birth weight (bw) has been related to low nephron number and hypertension. Age is an important predictor of developing hypertension in patients with reflux nephropathy (RN). The aim of the study was to assess the relationships between birth weight and blood pressure in children with RN. We investigated 150 patients in mean age 9 +/- 3.3 years with vesicoureteral reflux. In all patients we collected birth weight, we also performed renal scintigraphy (DMSA) and 24-hour ambulatory blood pressure monitoring (ABPM). Standard deviation score body mass index (BMI SDS) was calculated. In ABPM mean value of systolic and diastolic blood pressure (sBP, dBP), blood pressure load during 24 hour and during day and nighttime (LsBP, LdBP) were analyzed. As objective parameters of BP in children in different age and hight, systolic and diastolic BP indices (sBPI, dBPI) were calculated., Results: In analyzed group of children mean bw was 3340 +/- 587 g (from 1300 to 5000 g); in 10 children bw was <2500 g. In 20 children (13%), in 3 with bw <2500 g (30%) and in 17 (12.5%) with normal bw hypertension was diagnosed. The mean age and BMI SDS were lower in children with bw < 2500 g and HT than in children with normal bw and HT (8.2 vs 9.9 years and median -0.53 vs -0.22 respectively). In children with HT mean bw was 3247 +/- 666 g and in children without HT 3293 +/- 461 g (NS). No statistically significant difference was found depends of grades of renal damage in DMSA scan for bw. The negative correlation was found between bw and sBPI, LsBP during 24h and sBPI i LsBP during nighttime (p<0.05 r=-20, p<0.05 r=-19; p<0.05 r=-16, p<0.01 r=-26 respectively). No correlation was found between bw and dBP values., Conclusion: In children with RN low bw may be a potential risk factor for developing hypertension independent of severity of renal scarring.

Unlabelled: Target organ damage in the course of essential hypertension (EH) may develop already in childhood. The aim of the study was to determine the prevalence of left ventricular hypertrophy (LVH) and arterial damage and its main determinants in children with newly diagnosed, untreated EH. PATIENTS (pts): 87 children (22 girls and 65 boys) with EH, age 14.4 +/- 3 (5-18) yrs., Control Group: 104 healthy children (51 girls and 53 boys) aged 13.3 +/- 3.3 (5-20) yrs., Study Design: cross-sectional, controlled study., Methods: evaluation of anthropometrical data, birth weight, family history towards cardiovascular diseases, serum biochemical cardiovascular risk factors (lipids, sCRP, homocysteine, uric acid), carotid (cIMT) and superficial femoral artery intima-media thickness (fIMT). In EH children ambulatory blood pressure monitoring (ABPM), echocardiography, ophthalmoscopy, microalbuminuria were evaluated., Results: EH pts were significantly higher, heavier and had greater body mass index (BMI) (p<0.05). 59% of pts were overweight compared to 19% in control group (p<0.05). Carotid (cIMT) and superficial femoral artery intima-media thickness (fIMT) was greater in children with EH (0.47 +/- 0,05 v 0.43 +/- 0.04 and 0.36 +/- 0.04 v 0.33 +/- 0.04) (p<0.05) respectively. 41% and 19% of pts had cIMT and fIMT above 2 SDS of normal values respectively. The prevalence of LVH was 45%, and in 12% of pts severe (left ventricular mass index--LVMi > 51 g/m2.7) LVH was diagnosed. Pts with LVH had higher birth weight than other pts 3525 < or = 598 v 3136 +/- 635 g (p=0.04) and LVMi correlated with higher birth weight (p=0.0001; r=0.358), 24-hour heart rate (p=0.01; r= -0.361), serum uric acid (p=0.01; r=0.286), homocysteine (p=0.01; r=0.309) and apolipoprotein B (p=0.0001; r=0.258). LVMi correlated with fIMT (p=0.02; r=0.292), but not with cIMT. cIMT correlated with 24-hour systolic blood pressure (SBP)(p=0.01; r=0.305), SBP load (p=0.01; r=0.377), puls pressure (PP) (p=0.01; r=0.292), and heart rate (HR) (p=0.01; r=-0.285). 46% of pts had primary retinopathy, and 1 boy had secondary retinopathy. All pts had normal renal function, and mean microalbuminuria was 29.3+/-11.4 mg/d. Positive family history towards EH was confirmed in 80% of pts vs 29% in controls (p<0.05)., Conclusions: 1. Target organ damage is present already at the time of diagnosis in significant number of children with EH. 2. Overweight was 59% of pts and only 19% of healthy children. 3. LVMi and markers of arterial injury correlate with SBP, PP and HR, fIMT, uric acid, homocysteine, apolipoprotein B and birth weight.

Unlabelled: Metabolic alterations related to obesity are regarded as significant risk factor for target organ damage in hypertensive patients. Fat tissue distribution seems to play significant role in metabolic alterations related to cardiovascular damage. The aim of the study was to test hypothesis that fat tissue distribution and excess of visceral fat is related to cardiovascular damage and metabolic cardiovascular risk factors in obese boys with yet untreated, primary hypertension., Patients: 40 boys (14.8 +/- 3.0 yrs) with untreated essential hypertensions., Methods: amount of visceral (VAT), intraperitoneal visceral (ipVAT), extraperitoneal visceral (epVAT) and subcutaneous fat (SAT) was measured by nuclear magnetic imaging (NMR). Carotic intima media thickness (cIMT), fenoral intima media thickness (fIMT) and left ventricular mass index (LVMi) were evaluated by sonography. Oral glucose loading test was done, lipids, homocysteine, CRP, uric acid, microalbuminuria, adipocytokines, IGF-1 and IGF binding proteins (IGFBP) were determined., Results: The ratio of VAT to epVAT (V/Ve) correlated with carotid IMT (p=0.0001; r=0.561), standard deviation from median of the norm of cIMT (cIMT-SDS) (p=0.0001; r=0.681), femoral IMT (p=0.015; r=0.480) and fIMT-SDS (p=0.002; r=0.579). SAT correlated negatively with cIMT (p=0.0016; r=-0.355) and cIMT-SDS (p=0.01; r=-0.391). Waist to hip ratio (WHR) correlated with cIMT-SDS (p=0.03; r=0.401). VAT correlated positively and SAT negatively with HDL, apoA1, uric acid concentration and HOMA-IR value. VAT/epVAT correlated with HOMA-IR (p=0.02; r=0.402), free IGF-1 (p=0.001; r=0.478). epVAT also correlated with free IGF-1 (p=0.006; r=-0.494) and IGFBP3 (p=0.02; r=-0.471). Step-wise regression analysis revealed that relative excess of intraperitoneal visceral fat (VAT/epVAT) and WHR were independent predictors of cIMT-SDS(p=0.022, R2=0.755)., Conclusions: Fat tissue distribution correlates with early vascular injury and metabolic alterations in boys with primary hypertension. Relative excess of visceral fat assessed by NMR and truncal obesity expressed as WHR are independent risk factors for early vascular damage in overweight boys with primary hypertension.

Unlabelled: Hypertensive arteriopathy and intima-media (IMT) thickening is observed already in adolescents with primary hypertension (PH) at diagnosis. The injury of arterial wall may cause also generation of free radicals and free radicals may by itself perpetuate arterial wall injury. The aim of the study was to verify the hypothesis that children with PH are exposed to oxidative injury (Sox) due to impaired antioxidant barrier, and that markers of Sox correlate with IMT and metabolic risk factors of arteriosclerosis., Study Design: controlled, cross-sectional., Patients: 76 children with untreated PH, aged 14.7 yrs (5-20): 23 girls, 53 boys., Controls: 83 healthy children aged 13.4 yrs (4-23): 44 girls, 39 boys., Methods: Sono-graphic assessment of IMT in common carotid (cIMT) and superficial femoral arteries (cIMT). Sox was assessed as thiobarbituric acid reactive substances plasma concentration (TBARS), glutathione plasma concentration (GSH) as well as, glutathione peroxidase activity (GPX) were tested to demonstrate free radical scavenger activity., Results: PH pts had greater cIMT (p<0.0001), carotid wall cross sectional area (WCSA) (p<0.0001), fIMT (p<0.0001), lower HDL-cholesterol, apoA1/apoB than control group (p<0.05). GSH and GPX did not differ between groups but TBARS was significantly greater in PH pts (p <0.05). In control group fIMT significantly correlated with hCRP (r=0.30, p<0.01), homocysteine (r=0.3, p< 0.05), apoA1 (r=-0.2417, p<0.05), TBARS (r=0.329, p<0.01), GPX (r=-0.241, p<0.05) and with GSH (r=-0.22, p=0.05). In pts group, there were similar correlations between fIMT and hCRP (r=0.29, p<0.05), apoA1/apoB (r=-0.28, p<0.05)., Conclusions: PH pts are exposed to significantly higher Sox than controls. The significant correlations between markers of Sox and biochemical parameters suggest that hypertensive arteriopathy is an effect of complex interplay between Sox, metabolic and hemodynamic insults.