Usefulness of Somatostatin Receptor Scintigraphy (Tc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography.

AIMS: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. METHODS: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. RESULTS: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). CONCLUSION: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

Growth, body composition, and cardiovascular and nutritional risk of 5- to 10-y-old children consuming vegetarian, vegan, or omnivore diets.

BACKGROUND: Plant-based diets (PBDs) are increasingly recommended for human and planetary health. However, comprehensive evidence on the health effects of PBDs in children remains incomplete, particularly in vegans. OBJECTIVES: To quantify differences in body composition, cardiovascular risk, and micronutrient status of vegetarian and vegan children relative to omnivores and to estimate prevalence of abnormal micronutrient and cholesterol status in each group. METHODS: In a cross-sectional study, Polish children aged 5-10 y (63 vegetarian, 52 vegan, 72 matched omnivores) were assessed using anthropometry, deuterium dilution, DXA, and carotid ultrasound. Fasting blood samples, dietary intake, and accelerometry data were collected. RESULTS: All results are reported relative to omnivores. Vegetarians had lower gluteofemoral adiposity but similar total fat and lean mass. Vegans had lower fat indices in all regions but similar lean mass. Both groups had lower bone mineral content (BMC). The difference for vegetarians attenuated after accounting for body size but remained in vegans (total body minus the head: -3.7%; 95% CI: -7.0, -0.4; lumbar spine: -5.6%; 95% CI: -10.6, -0.5). Vegetarians had lower total cholesterol, HDL, and serum B-12 and 25-hydroxyvitamin D [25(OH)D] without supplementation but higher glucose, VLDL, and triglycerides. Vegans were shorter and had lower total LDL (-24 mg/dL; 95% CI: -35.2, -12.9) and HDL (-12.2 mg/dL; 95% CI: -17.3, -7.1), high-sensitivity C-reactive protein, iron status, and serum B-12 (-217.6 pmol/L; 95% CI: -305.7, -129.5) and 25(OH)D without supplementation but higher homocysteine and mean corpuscular volume. Vitamin B-12 deficiency, iron-deficiency anemia, low ferritin, and low HDL were more prevalent in vegans, who also had the lowest prevalence of high LDL. Supplementation resolved low B-12 and 25(OH)D concentrations. CONCLUSIONS: Vegan diets were associated with a healthier cardiovascular risk profile but also with increased risk of nutritional deficiencies and lower BMC and height. Vegetarians showed less pronounced nutritional deficiencies but, unexpectedly, a less favorable cardiometabolic risk profile. Further research may help maximize the benefits of PBDs in children.

Metabolic abnormalities, insulin resistance, and metabolic syndrome in children with primary hypertension.

BACKGROUND: We sought to describe the prevalence of metabolic abnormalities and of metabolic syndrome (MS) and its relationship to target-organ damage in children with primary hypertension (PH). METHODS: Patients included 113 children with untreated PH at a mean age of 14.6 years (range, 5 to 18 years). The control group consisted of 134 healthy children at a mean age of 13.5 years (range, 5 to 20 years). We performed a cross-sectional assessment of anthropometric and biochemical cardiovascular risk factors, homeostatic metabolic assessment (HOMA-IR), the insulin sensitivity index (ISI[0,120]), and adiponectin. RESULTS: Metabolic syndrome, as defined by classic criteria, was present in 4 of 134 (3%) of controls versus 23 of 113 (20.4%) patients (P=.0001), but when PH was not taken as a criterion of MS, MS was diagnosed in 6.2% of patients (no significance). Left-ventricular hypertrophy (LVH) was found in 46 of 113 patients (40.7%), and severe LVH was found in 14 of 113 patients (12.5%). Patients with LVH had a greater body mass index, greater waist-to-hip-ratio, and greater number of parameters of metabolic syndrome (overall P<.05). Carotid (cIMT) and femoral superficial artery intima-media thicknesses correlated positively with HOMA-IR and negatively with ISI[0.120] and serum adiponectin (P<.05). The main predictor for cIMT was adiponectin (R2=0.178, beta=-0.466, P=.002). Left-ventricular hypertrophy was predicted (R2=0.332) by body mass index-standard deviation score (beta=0.551, P=.005) and HOMA-IR (beta=0.380, P=.04). CONCLUSIONS: Metabolic syndrome, as defined by classic criteria, was diagnosed in 20% of children with PH, but when PH was not a criterion, MS was present in 6.2% of patients. Irrespective of the definition of MS, the applied markers of MS and insulin resistance were the main predictors of target-organ damage.

[Fat tissue distribution and metabolic alterations in boys with primary hypertension]. / Rozklad tkanki tluszczowej a uszkodzenie narzadowe u chlopców z nadcisnieniem tetniczym pierwotnym (NTP).

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.

[Target organ damage in children with newly diagnosed and untreated essential hypertension]. / Powiklania narzadowe u dzieci z rozpoznanym i nieleczonym nadcisnieniem tetniczym pierwotnym.

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.

[Oxidative stress and hypertensive arteriopathy in children with primary hypertension--preliminary results]. / Stres oksydacyjny a uszkodzenie tetnic u dzieci z nadcisnieniem tetniczym pierwotnym--wyniki wstepne.

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.

Different BMI cardiovascular risk thresholds as markers of organ damage and metabolic syndrome in primary 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.

Bone mass and body composition in children and adolescents with primary hypertension: preliminary data.

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.

Add-on therapy with angiotensin II receptor 1 blocker in children with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors.

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.

Left ventricular hypertrophy and arterial wall thickening in children with essential hypertension.

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.

Intima-media thickness and arterial elasticity in hypertensive children: controlled study.

The objective of this cross-sectional controlled study was to evaluate the intima-media thickness (IMT) of the common carotid artery (cIMT) and superficial femoral artery (fIMT), as well as the elastic properties of the common carotid artery, in children with essential arterial hypertension. The study included 49 children with newly detected essential hypertension [mean age 14.5 (range 6-20) years] and 61 healthy normotensive children [mean age 13.5 (range 6-20) years]. The cIMT and fIMT were evaluated by ultrasonography. The elastic properties of the carotid artery were calculated from actual blood pressure values, arterial dimensions, and carotid wall thickness. Hypertensive children had greater values of both cIMT (0.45+/-0.05 mm) ( P=0.0001) and fIMT (0.37+/-0.05 mm) ( P=0.005) than controls (0.41+/-0.04 and 0.33+/-0.06 mm, respectively). The internal systolic and diastolic diameters of the common carotid artery were also significantly greater in hypertensive patients. The distensibility and elasticity of the common carotid artery were significantly decreased in hypertensive patients, while arterial compliance was significantly greater than in controls. cIMT and fIMT correlated with systolic and pulse pressure values, body mass index (BMI), homocysteine, low high-density lipoprotein, and apolipoprotein AI. After subdividing the control group and patients according to BMI below or above the 95th percentile for age and sex, there were differences only between normal-weight normotensive children and the two groups of hypertensive children. The stepwise regression analysis showed that the predictive factor for cIMT was pulse pressure and for fIMT body mass and homocysteine. Hence, in newly diagnosed children with essential hypertension, functional and anatomical changes in elastic and muscular arteries are observed. Pulse pressure and biochemical risk factors for cardiovascular damage were predictors of vessel wall injury, even if it remained within the normal range. BMI is an important factor influencing IMT values.