Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe

Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Registry of whom 464 were on hemodialysis, 851 on peritoneal dialysis, and 2023 had received a renal allograft. Hypertension was defined as either systolic or diastolic blood pressures in the 95th percentile or greater for age, height, and gender or use of antihypertensive medication. Analyses were adjusted for age, gender, duration, and modality of renal replacement therapy. In 10 countries in which information on the use of antihypertensive medication was available, hypertension was present in over two-thirds of hemodialysis, peritoneal dialysis, or transplant patients. Blood pressure values above the 95th percentile were significantly more prevalent in very young patients (under 3 years) compared to 13- to 17-year olds (odds ratio 2.47), during the first year compared to over 5 years of renal replacement therapy (odds ratio 1.80), and in patients on hemodialysis compared to transplant recipients or those on peritoneal dialysis (odds ratios of 2.48 and 1.59, respectively). Over time, mean blood pressures decreased in both hemodialysis and transplant patients, but not in peritoneal dialysis patients. Hence, our findings highlight the extent of the problem of hypertension in children with end-stage renal disease in Europe.

Arterial hypertension in children

PURPOSE OF REVIEW Although arterial hypertension is less common in children than in adults, there is growing concern about elevated blood pressure (BP) in children and adolescents not only because of the association of elevated values with the overweight epidemic, but also as cardiovascular functions are determined in childhood and track into adulthood. The purpose of the review is to discuss new aspects of childhood hypertension. RECENT FINDINGS Guidelines advocate determining BP in children as part of routine health maintenance. This recommendation was recently subject to review by the US Preventive Services Task Force. It was concluded that evidence is insufficient to assess the benefits of this screening. In our opinion, however, assessing BP is part of any thorough physical examination.Sophisticated approaches demonstrate the role of sympathetic nervous system overdrive in the field of sympathetic cardiovascular modulation of childhood arterial hypertension. SUMMARY Elevated BP in children is increasing in frequency and is now recognized as having relevant short-term and long-term consequences. Although efforts to address the childhood overweight epidemic may eventually reduce the number of young patients with hypertension, improved therapies for childhood hypertension also offer the potential for preventing or ameliorating early cardiovascular disease.

Altered cardiovascular rhythmicity in children with white coat and ambulatory hypertension

Adults with ambulatory hypertension or white coat hypertension (WCH) display abnormal cardiovascular rhythms. We studied cardiovascular rhythms by Fourier analysis of 24-h ambulatory blood pressure (BP) measurement profiles in 129 hypertensive children, 54 children with WCH, and 146 age-, height-, and gender-matched healthy subjects. The day/night mean arterial pressure ratio was lower in hypertensive and patients with WCH compared with controls (1.13 versus 1.16 versus 1.21, respectively; p < 0.0001). Eighty-five percent of controls were dippers compared with 74% of WCH (n.s.) and 64% of patients with ambulatory hypertension (p < 0.0001). The prevalence of 24-h rhythms was similar among the groups, but prevalence of 12-h BP rhythms was increased in hypertensive (67%) and WCH (72%) compared with controls (51%, p < 0.0001). The amplitudes of the 24-, 8-, and 6-h BP rhythms were reduced in hypertensive and WCH compared with controls (p < 0.05). Hypertensive and patients with WCH displayed delayed 24-, 12-, 8-, 6-h acrophases in comparison with controls (p < 0.05). In conclusion, hypertensive children exhibit abnormal cardiovascular rhythmicity compared with controls, especially a higher prevalence of nondipping compared with normotensive children. Abnormalities in patients with WCH are intermediate between healthy children and patients with ambulatory hypertension.

Candesartan cilexetil in children with hypertension or proteinuria: preliminary data

The angiotensin II receptor blockers irbesartan and losartan effectively reduce blood pressure and proteinuria in childhood. We were impressed by the neutral taste and the small size of the candesartan cilexetil tablets. This angiotensin II receptor blocker was used during 4 months in 17 pediatric patients (aged 0.5-16, median 4.5 years) with chronic arterial hypertension (n=6), overt proteinuria (n=2), or both (n=9). The initial candesartan dose of 0.23 (0.16-0.28) mg/kg body weight once daily (median and interquartile ranged) was doubled in ten patients [final dose 0.35 (0.22-0.47) mg/kg body weight]. No adverse clinical experiences were noted on candesartan. Candesartan increased plasma potassium by 0.3 (0.0-0.8) mmol/l (P<0.01). In children with arterial hypertension, blood pressure decreased by 9 (3-13)/9 (3-18) mmHg (P<0.01); in those with overt proteinuria the urinary albumin/creatinine ratio decreased by 279 (33-652) mg/mmol (P<0.05). In conclusion, in children candesartan reduces blood pressure and proteinuria with an excellent short-term tolerability profile.

Pulmonary artery pressure and cardiac function in children and adolescents after rapid ascent to 3,450 m

High-altitude destinations are visited by increasing numbers of children and adolescents. High-altitude hypoxia triggers pulmonary hypertension that in turn may have adverse effects on cardiac function and may induce life-threatening high-altitude pulmonary edema (HAPE), but there are limited data in this young population. We, therefore, assessed in 118 nonacclimatized healthy children and adolescents (mean ± SD; age: 11 ± 2 yr) the effects of rapid ascent to high altitude on pulmonary artery pressure and right and left ventricular function by echocardiography. Pulmonary artery pressure was estimated by measuring the systolic right ventricular to right atrial pressure gradient. The echocardiography was performed at low altitude and 40 h after rapid ascent to 3,450 m. Pulmonary artery pressure was more than twofold higher at high than at low altitude (35 ± 11 vs. 16 ± 3 mmHg; P < 0.0001), and there existed a wide variability of pulmonary artery pressure at high altitude with an estimated upper 95% limit of 52 mmHg. Moreover, pulmonary artery pressure and its altitude-induced increase were inversely related to age, resulting in an almost twofold larger increase in the 6- to 9- than in the 14- to 16-yr-old participants (24 ± 12 vs. 13 ± 8 mmHg; P = 0.004). Even in children with the most severe altitude-induced pulmonary hypertension, right ventricular systolic function did not decrease, but increased, and none of the children developed HAPE. HAPE appears to be a rare event in this young population after rapid ascent to this altitude at which major tourist destinations are located.

Absolute height-specific thresholds to identify elevated blood pressure in children

Identification of children with elevated blood pressure (BP) is difficult because of the multiple sex, age, and height-specific thresholds to define elevated BP. We propose a simple set of absolute height-specific BP thresholds and evaluate their performance to identify children with elevated BP in two different populations.

Respiratory nitric oxide and pulmonary artery pressure in children of aymara and European ancestry at high altitude

Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.

Salt intake in children and its consequences on blood pressure.

Sodium is the most abundant extracellular cation and therefore pivotal in determining fluid balance. At the beginning of life, a positive sodium balance is needed to grow. Newborns and preterm infants tend to lose sodium via their kidneys and therefore need adequate sodium intake. Among older children and adults, however, excessive salt intake leads to volume expansion and arterial hypertension. Children who are overweight, born preterm, or small for gestational age and African American children are at increased risk of developing high blood pressure due to a high salt intake because they are more likely to be salt sensitive. In the developed world, salt intake is generally above the recommended intake also among children. Although a positive sodium balance is needed for growth during the first year of life, in older children, a sodium-poor diet seems to have the same cardiovascular protective effects as among adults. This is relevant, since: (1) a blood pressure tracking phenomenon was recognized; (2) the development of taste preferences is important during childhood; and (3) salt intake is often associated with the consumption of sugar-sweetened beverages (predisposing children to weight gain).

Antioxidants improve vascular function in children conceived by assisted reproductive technologies: A randomized double-blind placebo-controlled trial.

AIMS Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability. METHODS AND RESULTS In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children. CONCLUSIONS Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.

Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies.

Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.