Knowledge gaps and future directions in cognitive functions in children and adolescents with primary arterial hypertension: A systematic review.

Arterial hypertension (AH) among adults is known to be associated with worse cognitive outcomes. Similarly, children and adolescents with AH could be expected to underperform during neuropsychological evaluations when compared with healthy peers. Our aims were to review the existing literature on cognitive functioning among children and adolescents with primary AH and to identify what additional evidence may be needed to substantiate the impact of hypertension on poor cognitive outcomes in this population. We conducted a systematic review of articles in PubMed and Web of Science published before 17 January 2022, reporting on cognitive testing among children and adolescents with primary AH. From 1,316 records, 13 were included in the review-7 used battery-testing while other employed indirect measures of cognitive functions. Most of the studies reported worse results among individuals with AH. Results of two prospective trials suggested that cognitive functioning may improve after starting antihypertensive treatment. Ambulatory blood pressure monitoring was shown to be more strongly related to cognitive testing results than office measures of blood pressure. Significant confounders, namely obesity and sleep apnea, were identified throughout the studies. Our review indicates that evidence relating AH with poor cognitive functioning among youth is usually based on indirect measures of executive functions (e.g., questionnaires) rather than objective neuropsychological tests. Future prospective trials set to test different cognitive domains in children and adolescents undergoing treatment for AH are endorsed and should consider using standardized neuropsychological batteries as well as adjust the assessing results for obesity and sleep disorders.

Prevalence of left ventricular hypertrophy in children and young people with primary hypertension: Meta-analysis and meta-regression.

Background: Left ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH). Methods: A meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity. Results: The search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m2.7 in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2-33.9), while heterogeneity was high (I 2 = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity (I 2 = 84%). Two studies involving patients identified through community screening (n = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08-0.39, p = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%). Conclusion: Left ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.

Associations of the eNOS G894T gene polymorphism with target organ damage in children with newly diagnosed primary hypertension.

BACKGROUND: The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism is associated with the risk of primary hypertension (PH) and vascular complications in adults with PH. METHODS: We explored the associations of the G894T polymorphism with 24-h ambulatory blood pressure, left ventricular mass (LVM), carotid intima media thickness (cIMT), urinary albumin excretion, oxidative stress and inflammatory parameters in 126 children with newly diagnosed PH and in 83 healthy children. RESULTS: Among the 126 children with PH 92 (73%) had ambulatory hypertension and 34 (27%) had severe ambulatory hypertension. Left ventricular hypertrophy (LVH) was detected in 39 (31%) patients, cIMT of >2 standard deviation scores in 21 (16.6%) patients, albuminuria of >30 mg/24 h in 18 (14.3%) patients and metabolic syndrome (MS) in 22 (17.5%) patients. The frequency of the T allele was 52.4% in the PH group and 54.2% in the control group (not significant), and in both groups the frequency of the T allele was consistent with the Hardy-Weinberg equilibrium. Compared with G allele carriers, hypertensive T allele carriers had increased cIMT (p < 0.05) and more severe albuminuria (not significant, p = 0.1); there was no difference between the groups in hypertension severity and LVM. T and G allele distribution did not differ between patients with and without metabolic syndrome. No significant correlations between the assessed parameters and the eNOS G894T gene polymorphism were found in the controls, although T allele carriers tended to have an increased cIMT (p = 0.09). CONCLUSION: The eNOS T allele is not more prevalent among hypertensive children than among healthy ones, but it is associated with early vascular damage in children with PH, independent of metabolic abnormalities. No associations between the eNOS G894T polymorphism and metabolic abnormalities were found.

Oxidative stress in hypertensive children before and after 1 year of antihypertensive therapy.

BACKGROUND: The relation between primary hypertension (PH), target organ damage (TOD) and oxidative stress (SOX) is not known. METHODS: We assessed SOX in 86 children with PH before and after 12 months of standard non-pharmacological and pharmacological therapy based on renin-angiotensin system blockade. RESULTS: Patients with left ventricular hypertrophy (LVH) and with carotid intima-media thickness (cIMT) >2SDS had higher thiobarbituric acid reactive substances (TBARS) concentrations in comparison to patients without LVH or with normal cIMT. Patients with metabolic syndrome (MS) had lower activity of gluthatione peroxidase, higher asymmetric dimethyloarginine (ADMA) and oxidized LDL cholesterol (oxyLDL) in comparison to patients without MS. TBARS correlated with left ventricular concentric hypertrophy, cIMT, albuminuria and SBP/24 h. ADMA and oxyLDL correlated with CRP and TG/HDL ratio. After 1 year of antihypertensive treatment blood pressure, TOD and prevalence of MS decreased. TBARS decreased and glutathione concentrations increased. The decrease of TBARS concentration correlated with the decrease of body mass index (BMI). Decrease of oxyLDL and ADMA correlated with increased insulin sensitivity, however markers of SOX did not correlate with BP decrease. CONCLUSION: SOX in children with PH correlates with TOD, metabolic abnormalities, changes in fat amount and improvement of insulin sensitivity, but not with BP decrease.

Change in left ventricular geometry during antihypertensive treatment in children with primary hypertension.

The pattern of the left ventricle (LV) has important significance in adults with hypertension. The aim of the present study was to analyze changes and determinants of LV geometry after 1 year of antihypertensive treatment in children with primary hypertension (PH) in relation to metabolic abnormalities and anthropometrical parameters. In 86 children (14.1 ± 2.4 years) with newly diagnosed PH, LV geometry and biochemical parameters before and after 12 months of standard antihypertensive therapy were assessed. At baseline, normal LV geometry (NG) was found in 42 (48.9%), concentric remodeling (CR) in 4 (4.6%), concentric hypertrophy (CH) in 8 (9.3%), and eccentric hypertrophy (EH) in 32 (37.2%) patients. The prevalence of NG in patients with severe hypertension was significantly lower than in patients with ambulatory hypertension. There were no differences in dipping status in relation to LV geometry. Patients with CH and EH were more viscerally obese than patients with NG. Patients with CH had higher diastolic blood pressure in comparison with EH patients (p < 0.05). The main predictor of relative wall thickness (RWT) was the triglycerides to high density lipoprotein cholesterol (TG/HDL) ratio (R(2 ) = 0.319, ß = 0.246, p = 0.004). Patients received 12 months of antihypertensive treatment, either lifestyle modification only (n = 37) or lifestyle modification plus antihypertensive medications (n = 49) if severe ambulatory hypertension or target organ damage were present. After 12 months of treatment the prevalence of EH (37.2% vs 18.6%, p = 0.003) decreased but prevalence of CH did not change. Patients in whom RWT decreased also decreased waist circumference and TG/HDL; the main predictor of RWT decrease was a decrease of the TG/HDL ratio (ß = 0.496, R (2) = 0.329, p = 0.002). In adolescents with PH, LV geometry is related to central obesity and insulin resistance. Decrease of abdominal obesity and insulin resistance are the most important predictors of normalization of LV geometry, however CH has lower potential to normalize LV geometry.

Regression of target organ damage in children and adolescents with primary hypertension.

We assessed the effects of 12 months of non-pharmacological and pharmacological therapy on 24-h ambulatory blood pressure, regression of target organ damage (TOD) and metabolic abnormalities in 86 children (14.1 ± 2.4 years) with primary hypertension. Twenty-four hour systolic and diastolic blood pressure (BP) decreased (130 ± 8 vs 126 ± 8, 73 ± 7 vs 70 ± 7, p = 0.0001 and 0.004 respectively). Body mass index (BMI) did not change, but waist-to-hip (0.85 ± 0.07 vs 0.83 ± 0.05, p = 0.01) and waist-to-height ratio (WHtR; 0.49 ± 0.07 vs 0.48 ± 0.05, p = 0.008) decreased. Left ventricular mass index (LVMi; 38.5 ± 10.7 vs 35.2 ± 7.5 g/m(2.7), p = 0.0001), prevalence of left ventricular hypertrophy (46.5% vs 31.4%; p = 0.0001), carotid intima-media thickness (cIMT; 0.44 ± 0.05 vs 0.42 ± 0.04 mm, p = 0.0001), wall cross sectional area (WCSA; 7.5 ± 1.3 vs 6.9 ± 1.2 mm(2), p = 0.002), hsCRP (1.1 ± 1.0 vs 0.7 ± 0.7 mg/l, p = 0.002), and LDL-cholesterol (115 ± 33 vs 107 ± 26 mg/dl, p = 0.001) decreased. Patients who had lowered BP had a lower cIMT at the second examination (0.41 ± 0.04 vs 0.43 ± 0.04 mm, p = 0.04) and lower initial hsCRP values (0.9 ± 0.7 vs 1.5 ± 1.3 mg/l, p = 0.04) in comparison to non-responders. Regression analysis revealed that the main predictor of LVMi decrease was a decrease in abdominal fat expressed as a decrease in waist circumference (WC) (R (2) = 0.280, ß = 0.558, p = 0.005), for WCSA-SDS a decrease in WC (R (2) = 0.332, ß = 0.611, p = 0.009) and for a cIMT-SDS decrease the main predictor was a decrease in hsCRP concentrations (R (2) = 0.137, ß = 0.412, p = 0.03). Standard antihypertensive treatment lowered BP and led to regression of TOD in hypertensive children. Lean body mass increase and decrease in abdominal obesity correlated with TOD regression.