Association of HDL-Cholesterol, hypertension and left ventricular hypertrophy in youths with overweight or obesity.

BACKGROUND AND AIM: To evaluate the relationship between HDL-Cholesterol (HDL-C), hypertension, and left ventricular hypertrophy (LVH) in a large sample of Caucasian youths with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional multicenter study was performed in 1469 youths (age 6-16 years) with OW/OB observed in the period 2016-2020. An additional independent sample of 244 youths with an echocardiographic evaluation, observed in a single center was analyzed. The sample was divided in six quantiles (Q) of HDL-C: Q1: >56, Q2: ≤56 > 51, Q3: ≤51 > 45, Q4: ≤45 > 41, Q5: ≤41 > 39, Q6: <39 mg/dL. The nadir of the relationship was identified in youths in the first quantile. Among HDL-Cholesterol quantiles the distribution of hypertension was non-linear with a percentage of 25.0%, 40.1%, 33.6%, 31.3%, 35.2% and 39.7% in the six quantiles, respectively. The percentage of LVH was 21.8%, 43.6%, 48.8%, 35.5%, 38.5% and 52.0% in the six quantiles, respectively. The highest odds [95%Cl] of hypertension were 2.05 (1.33-3.16) (P < 0.01) in Q2, 1.67 (1.10-2.55) (P < 0.05) in Q3 and 1.59 (1.05-2.41) (P < 0.05) in Q6 vs Q1. The odds of LVH were 3.86 (1.15-10.24) (P < 0.05) in Q2, 4.16 (1.58-10.91) (P < 0.05) in Q3 and 3.60 (1.44-9.02) (P < 0.05) in Q6 vs Q1, independently by centers, age, sex, prepubertal stage, and body mass index. CONCLUSION: Contrary to the common belief, the present study shows that high levels of HDL-C may be not considered a negative predictor of hypertension and LVH, two risk factors for future CV disease.

Static cutoffs or tables for the diagnosis of hypertension? Effect on identification of organ damage in youths with obesity.

BACKGROUND AND AIM: Recently, the European Society of Cardiology task force released a Consensus document (ESC-CD) on pediatric hypertension (HTN) supporting the use of normative tables (age range 6-16 years) for the diagnosis of HTN, while the Hypertension Canada Guidelines (HTN-CGs) proposed static cutoffs. We aimed to assess the prevalence of HTN by ESC-CD or HTN-CGs and their association with glomerular function and left ventricular (LV) geometry in youths with overweight/obesity (OW/OB). METHODS AND RESULTS: Data of 3446 youths were analyzed. HTN by was defined using normative tables (ESC-CD) or static cutoffs of BP ≥ 120/80 in children (age <12 years) and ≥130/85 mmHg in adolescents (age ≥12 years) (HTN-CGs). Mildly reduced glomerular filtration rate was defined by GFR <90 ≥ 60 mL/min/1.73 m2. Concentric LV hypertrophy (cLVH) was assessed in 500 youths and defined by LVH and high relative wall thickness as proposed by ESC-CD. Prevalence of HTN was 27.9% by ESC-CD and 22.7% by HTN-CGs. The association with mildly reduced glomerular filtration rate was significant only in hypertensive adolescents classified by HTN-CGs [Odds Ratio (OR), 95%Cl] 2.16 (1.44-3.24), whereas the association with cLVH was significant using both criteria: children OR 2.18 (1.29-3.67) by ESC-CD and 2.27 (1.32-3.89) by HTN-CGs; adolescents OR 2.62 (1.17-5.84) by ESC-CD and 2.83 (1.14-7.02) by HTN-CGs. CONCLUSION: Although static cutoffs may represent a simplification for HTN identification, tables by ESC-CD detect a higher number of hypertensive youths before a clear appearance of glomerular impairment, which offers advantages in terms of primary cardiovascular prevention.

Elevated blood pressure, cardiometabolic risk and target organ damage in youth with overweight and obesity.

BACKGROUND AND AIM: To compare cardiometabolic risk profile and preclinical signs of target organ damage in youth with normal and elevated blood pressure (BP), according to the American Academy of Pediatrics (AAP) guidelines. METHODS AND RESULTS: This cross-sectional multicenter study included 2739 youth (5-17 year-old; 170 normal-weight, 610 overweight and 1959 with obesity) defined non hypertensive by the AAP guidelines. Anthropometric, biochemical and liver ultrasound data were available in the whole population; carotid artery ultrasound and echocardiographic assessments were available respectively in 427 and 264 youth. Elevated BP was defined as BP ≥ 90th to <95th percentile for age, gender and height in children or BP ≥ 120/80 to <130/80 in adolescents. The overall prevalence of elevated BP was 18.3%, and significantly increased from normal-weight to obese youth. Young people with elevated BP showed higher levels of body mass index (BMI), insulin resistance and a higher prevalence of liver steatosis (45% vs 36%, p < 0.0001) than normotensive youth, whilst they did not differ for the other cardiometabolic risk factors, neither for carotid intima media thickness or left ventricular mass. Compared with normotensive youth, individuals with elevated BP had an odds ratio (95%Cl) of 3.60 (2.00-6.46) for overweight/obesity, 1.46 (1.19-1.78) for insulin-resistance and 1.45 (1.19-1.77) for liver steatosis, controlling for centers, age and prepubertal stage. The odds for insulin resistance and liver steatosis persisted elevated after correction for BMI-SDS. CONCLUSION: Compared to normotensive youth, elevated BP is associated with increased BMI, insulin resistance and liver steatosis, without significant target organ damage.

Cardiometabolic phenotype in children with obesity.

OBJECTIVES: To investigate the anthropometric and metabolic correlates of different patterns of left ventricular (LV) geometry in a cohort of outpatient children with high prevalence of obesity. STUDY DESIGN: Anthropometric measures, lipid profile, blood pressure (BP), fasting plasma glucose (FPG), and echocardiographic variables were evaluated in 281 white children (6-16 years), of whom 105 were obese and 105 were morbidly obese. Patterns of LV geometry were defined as follows: normal geometry, eccentric LV hypertrophy (LVH), concentric LV remodeling, and concentric LVH. RESULTS: One hundred forty-eight children exhibited normal LV geometry, 53 eccentric LVH, 36 concentric LV remodeling, and 44 concentric LVH. The 4 groups differed in body mass index, waist circumference, waist-to-height ratio, triglycerides/high-density lipoprotein cholesterol ratio (Tg/HDL-C), and BP (P < .05-.0001). A statistically significant impairment of diastolic function (expressed as greater E/E', P < .002) was observed across patterns of LV geometry. Among anthropometric measures, waist-to-height ratio showed better performance in relation to LVH, with an optimal cut-point of 0.58, compared with body mass index and waist circumference. Children with concentric LVH exhibited the worst metabolic risk profile, with greater prevalence of visceral obesity, high Tg/HDL-C, high BP, and high-normal FPG, than children with normal LV geometry. CONCLUSIONS: In children with high levels of obesity, an unfavorable "cardiometabolic phenotype" can be identified, which includes concentric LVH, visceral obesity, high BP, high Tg/HDL-C, and high-normal FPG.

Cardiovascular Comorbidities and Pharmacological Treatments of COVID-19 Patients Not Requiring Hospitalization.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings. MATERIALS AND METHODS: We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient settings in Naples, Italy between 9 March and 1 May 2020. Data were sourced from the prospectively maintained Health Search (HS)/Thales database, shared by 128 primary care physicians (PCPs) in Naples, Italy. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described. RESULTS: A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ± 17 years; 193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74; 95% CI 1.05 to 13.34; p = 0.04) and hypertension (RR: 1.69; 95% CI 1.05 to 2.7; p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43; 95% CI 1.01 to 5.8; p = 0.03) was significantly associated with heparin administration. CONCLUSIONS: Our data show a high prevalence of hypertension, more likely treated with renin-angiotensin-aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization. Experimental COVID-19 therapies have been prescribed to COVID-19 patients considered at risk for increased venous thromboembolism based on concomitant comorbidities, in particular diabetes and hypertension.

The American Academy of Pediatrics hypertension guidelines identify obese youth at high cardiovascular risk among individuals non-hypertensive by the European Society of Hypertension guidelines.

BACKGROUND: Two different systems for the screening and diagnosis of hypertension (HTN) in children currently coexist, namely, the guidelines of the 2017 American Academy of Pediatrics (AAP) and the 2016 European Society for Hypertension (ESH). The two systems differ in the lowered cut-offs proposed by the AAP versus ESH. OBJECTIVES: We evaluated whether the reclassification of hypertension by the AAP guidelines in young people who were defined non-hypertensive by the ESH criteria would classify differently overweight/obese youth in relation to their cardiovascular risk profile. METHODS: A sample of 2929 overweight/obese young people (6-16 years) defined non-hypertensive by ESH (ESH-) was analysed. Echocardiographic data were available in 438 youth. RESULTS: Using the AAP criteria, 327/2929 (11%) young people were categorized as hypertensive (ESH-/AAP+). These youth were older, exhibited higher body mass index, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), triglycerides, total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, blood pressure, left ventricular mass index and lower HDL-C (p <0.025-0.0001) compared with ESH-/AAP-. The ESH-/AAP+ group showed a higher proportion of insulin resistance (i.e. HOMA-IR ≥3.9 in boys and 4.2 in girls) 35% vs. 25% (p <0.0001), high TC/HDL-C ratio (≥3.8 mg/dl) 35% vs. 26% (p = 0.001) and left ventricular hypertrophy (left ventricular mass index ≥45 g/h2.16) 67% vs. 45% (p = 0.008) as compared with ESH-/AAP-. CONCLUSIONS: The reclassification of hypertension by the AAP guidelines in young people overweight/obese defined non-hypertensive by the ESH criteria identified a significant number of individuals with high blood pressure and abnormal cardiovascular risk. Our data support the need of a revision of the ESH criteria.

Glomerular filtration rate and cardiometabolic risk in an outpatient pediatric population with high prevalence of obesity.

OBJECTIVE: To evaluate the relationship between estimated glomerular filtration rate (eGFR) and cardiometabolic risk factors (CMRF) in an outpatient pediatric population with high prevalence of obesity. DESIGN AND METHODS: eGFR was evaluated in 901 children unselected for chronic kidney disease of whom 694 were overweight/obese (6-16 years) and 207 were age- and sex-matched normal weight (NW). We generated three categories of eGFR: mild-low eGFR (< 20th percentile), high eGFR (>80th percentile) and intermediate eGFR (20-80th percentile), considered as the reference category RESULTS: Children with either mild-low or high eGFR category showed a 2-4 fold higher Odds ratio of high blood pressure, left ventricular hypertrophy, and microalbuminuria compared with children of the intermediate eGFR category. In addition, children with mild-low eGFR levels showed a 1.5-2 fold higher Odds ratio of impaired fasting glucose and high white blood cell count compared with children with intermediate eGFR levels. CONCLUSIONS: In outpatient children with high prevalence of obesity, children with either mildly reduced or high eGFR have an increased burden of CMRF. Children with eGFR < 97 mL/min/1.73 m² show a worse CMR profile. This finding supports the usefulness to assess eGFR to identify children with unfavorable CMR profile.

Usefulness of the high triglyceride-to-HDL cholesterol ratio to identify cardiometabolic risk factors and preclinical signs of organ damage in outpatient children.

OBJECTIVE: To evaluate whether the high triglyceride-to-HDL cholesterol (TG-to-HDL-C) ratio is associated with cardiometabolic risk (CMR) factors and preclinical signs of organ damage in an outpatient population of white children and adolescents. RESEARCH DESIGN AND METHODS: The study population included 884 subjects (aged 6-16 years), of whom 206 (23%) were normal weight, 135 (15%) were overweight, and 543 (61%) were obese. Biochemical variables were analyzed in the whole sample, whereas homocysteine and left ventricular (LV) geometry and function were evaluated in 536 and 258 children, respectively. RESULTS: The percentage of pubertal children (P < 0.001), as well as measurements of BMI, waist circumference, homeostasis model assessment of insulin resistance, white blood cell count, alanine aminotransferase (ALT), systolic blood pressure (P < 0.0001, for all), creatinine (P < 0.001), and diastolic blood pressure (P < 0.02), increased from the lowest to the highest tertile of the TG-to-HDL-C ratio. Age, sex, homocysteine, and glomerular filtration rate did not change. Moreover, interventricular septum thickness, relative wall thickness, and LV mass index (P = 0.01 to P < 0.0001) increased across tertiles of the TG-to-HDL-C ratio. Children with a TG-to-HDL-C ratio ≥2.0 showed a two- to threefold higher risk of elevated ALT levels and concentric LV hypertrophy than those with a TG-to-HDL-C ratio <2.0, independent of confounding factors. CONCLUSIONS: The high TG-to-HDL-C ratio is associated with several CMR factors and preclinical signs of liver and cardiac abnormalities in the outpatient, white pediatric population. Thus, a TG-to-HDL-C ratio ≥2.0 may be useful in clinical practice to detect children with a worsened CMR profile who need monitoring to prevent cardiovascular disease in adulthood.

Preclinical manifestations of organ damage associated with the metabolic syndrome and its factors in outpatient children.

BACKGROUND: To evaluate whether the pediatric metabolic syndrome (MetS) or its factors are useful to detect subclinical abnormalities of cardiac, liver, and glomerular damage in an outpatient population. METHODS: The population study included 799 children (age 10 ± 3 years, mean ± SD), 24% of whom were normalweight, 25% overweight, and 51% obese. Alanine-aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR) and HOMA-IR were analyzed in all children. Microalbuminuria (MA) and left ventricular (LV) geometry and function were evaluated in 501 and 247 children, respectively. MetS was defined using Cook's criteria. RESULTS: MetS was diagnosed in 131 children (16%). Children with MetS+ and MetS- were similar for age, gender and Tanner stage distribution. Children with MetS+ showed higher ALT levels (31 ± 19 vs 21 ± 11 IU/L, p<0.0001), LV mass (39 ± 10 vs 34 ± 10 g/h(2.7), p<0.001) and relative wall thickness (0.37 ± 0.06 vs 0.35 ± 0.05, p<0.01) than MetS-. The two groups were similar for MA and eGFR. At multiple logistic regression analysis, children MetS+ showed a higher risk (OR, 95% Cl) adjusted for confounding factors, of high ALT levels (1.71, 1.12-2.59, p=0.012) and concentric LV hypertrophy (2.17, 1.01-4.66, p=0.047) than children MetS-. The risk of preclinical liver and cardiac damage associated with the MetS phenotype was not higher than predicted by its single components. CONCLUSIONS: Children with MetS show a 2-fold greater risk of having high ALT levels and concentric LV hypertrophy. However, the risk of subclinical manifestations of liver and cardiac damage can be predicted equally well by the single components of the syndrome.

Prehypertension in outpatient obese children.

BACKGROUND: The aim of the study was to analyze the prevalence of prehypertension (PH) in obese (OB) children and its relation with estimated glomerular filtration rate (eGFR) and left ventricular (LV) function. METHODS: The study included 447 OB and 131 normal-weight children. PH was defined according to the criteria proposed by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Insulin sensitivity was evaluated by HOMA(IR), and eGFR was calculated by Schwartz's formula. LV function was analyzed by echocardiography in 165 OB children. RESULTS: PH was observed in 79 OB children (17.7%) and in 2 (1.5%) controls. Among OB children, those with PH had greater percentage of males (P < 0.05), higher level of body mass index (BMI) (P < 0.001), waist circumference (WC) (P < 0.005), and HOMA(IR) (P < 0.001), compared to PH- children. The two groups did not differ for eGFR and LV function. At logistic regression analysis, PH was independently associated with male gender (P < 0.025) and HOMA(IR) (P < 0.002). Gender analysis showed that boys with PH presented higher levels of BMI (P < 0.005), WC (P < 0.01), HOMA(IR) (P < 0.001), and triglycerides (P < 0.005) compared to PH- boys. Females with PH were older and in more advanced postpubertal stage, had higher BMI, WC (P < 0.05, for all), and HOMA(IR) (P < 0.025), compared to PH- girls. CONCLUSIONS: In a population of outpatient OB children, the prevalence of PH was 17.7% and boys were more likely than girls to have PH. This condition is characterized by insulin resistance in both sexes but no impairment in glomerular and LV function.