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Neuroblastoma is a common pediatric tumor arising from the post-ganglionic sympathetic nervous system and is associated with hypertension in 25% of cases. We describe an unusual case of labile, multi-drug resistant hypertension associated with chemotherapy administration for neuroblastoma and provide potential management strategies in this scenario. We report the case of a 4-year-old female with a history of headaches who presented with hypertensive emergency and evidence of end-organ damage, including posterior reversible encephalopathy syndrome, acute cerebral infarct, concentric left ventricular hypertrophy, and growth failure secondary to a large, abdominal catecholamine-secreting neuroblastoma, which compressed the kidney vasculature and inferior vena cava. She was classified as intermediate risk according to Children's Oncology Group criteria and underwent chemotherapy, complicated by labile hypertension, followed by surgical resection. Vigilance in monitoring and treatment of hypertension is recommended during chemotherapy for neuroblastoma due to the potential catecholamine release in the setting of tumor lysis. [ABSTRACT FROM AUTHOR]

The myocardium is a highly oxidative tissue in which mitochondria are essential to supply the energy required to maintain pump function. When pathological hypertrophy develops, energy consumption augments and jeopardizes mitochondrial capacity. We explored the cardiac consequences of chronic swimming training, focusing on the mitochondrial network, in spontaneously hypertensive rats (SHR). Male adult SHR were randomized to sedentary or trained (T: 8-week swimming protocol). Blood pressure and echocardiograms were recorded, and hearts were removed at the end of the training period to perform molecular, imaging, or isolated mitochondria studies. Swimming improved cardiac midventricular shortening and decreased the pathological hypertrophic marker atrial natriuretic peptide. Oxidative stress was reduced, and even more interesting, mitochondrial spatial distribution, dynamics, function, and ATP were significantly improved in the myocardium of T rats. In the signaling pathway triggered by training, we detected an increase in the phosphorylation level of both AKT and glycogen synthase kinase-3 β, key downstream targets of insulin-like growth factor 1 signaling that are crucially involved in mitochondria biogenesis and integrity. Aerobic exercise training emerges as an effective approach to improve pathological cardiac hypertrophy and bioenergetics in hypertension-induced cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) and cardiac dysfunction are established comorbidities of congenital diaphragmatic hernia (CDH). However, there is very little data focusing on arterial hypertension in CDH. This study aims to investigate the incidence of arterial hypertension in neonates with CDH at hospital discharge. Archived clinical data of 167 CDH infants who received surgical repair of the diaphragmatic defect and survived for > 60 days were retrospectively analyzed. Blood pressure (BP) values were averaged for the last 7 days before discharge and compared to standard BP values for sex, age, and height provided by the AHA in 2004. BP values reaching or extending the 95th percentile were defined as arterial hypertension. The use of antihypertensive medication was analyzed at discharge and during hospitalization. Arterial hypertension at discharge was observed in 19 of 167 infants (11.3%) of which 12 (63%) were not receiving antihypertensive medication. Eighty patients (47.9%) received antihypertensive medication at any point during hospitalization and 28.9% of 152 survivors (n = 44) received antihypertensive medication at discharge, although in 45.5% (n = 20) of patients receiving antihypertensive medication, the indication for antihypertensive medication was myocardial hypertrophy or frequency control. BP was significantly higher in ECMO compared to non-ECMO patients, despite a similar incidence of arterial hypertension in both groups (13.8% vs. 10.1%, p = 0.473). Non-isolated CDH, formula feeding, and minimal creatinine in the first week of life were significantly associated with arterial hypertension on univariate analysis. Following multivariate analysis, only minimal creatinine remained independently associated with arterial hypertension. Conclusion: This study demonstrates a moderately high incidence of arterial hypertension in CDH infants at discharge and an independent association of creatinine values with arterial hypertension. Physicians should be aware of this risk and include regular BP measurements and test of renal function in CDH care and follow-up. What is Known: • Due to decreasing mortality, morbidity is increasing in surviving CDH patients. • Pulmonary hypertension and cardiac dysfunction are well-known cardiovascular comorbidities of CDH. What is New: • There is a moderately high incidence of arterial hypertension in CDH infants at discharge even in a population with frequent treatment with antihypertensive medication. • A more complicated hospital course (ECMO, higher degree of PH, larger defect size) was associated with a higher risk for arterial hypertension. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac organ damage like left ventricular (LV) hypertrophy and left atrial (LA) enlargement is more prevalent in women than men with hypertension, but the mechanisms underlying this gender difference remain unclear. Methods: We tested the association of drug nonadherence with the presence of LV hypertrophy and LA enlargement by echocardiography in 186 women and 337 men with uncontrolled hypertension defined as daytime systolic blood pressure (BP) ≥ 135mmHg despite the prescription of at least two antihypertensive drugs. Drug adherence was assessed by measurements of serum drug concentrations interpreted by an experienced pharmacologist. Aldosterone-renin-ratio (ARR) was measured on actual medication. Results: Women had a higher prevalence of LV hypertrophy (46% vs. 33%) and LA enlargement (79% vs 65%, both p < 0.05) than men, while drug nonadherence (8% vs. 9%, p > 0.514) did not differ. Women were older and had lower serum renin concentration and higher ARR than men, while 24-h systolic BP (141 ± 9 mmHg vs. 142 ± 9 mmHg), and the prevalences of obesity (43% vs. 50%) did not differ (all p > 0.10). In multivariable analyses, female gender was independently associated with a two-fold increased risk of LV hypertrophy (OR 2.01[95% CI 1.30–3.10], p = 0.002) and LA enlargement (OR 1.90 [95% CI 1.17–3.10], p = 0.010), while no association with drug nonadherence was found. Higher ARR was independently associated with LV hypertrophy in men only (OR 2.12 [95% CI 1.12–4.00] p = 0.02). Conclusions: Among patients with uncontrolled hypertension, the higher prevalence of LV hypertrophy and LA enlargement in women was not explained by differences in drug nonadherence. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03209154. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained arrhythmia and it is a major public health problem worldwide. Hypertension is one of the major risk factors for the development of AF. This study is carried out to determine the prevalence and independent risk factors for atrial fibrillation (AF) in hypertensive patients and to evaluate the relationship of AF with left atrial size. This is a retrospective observational cross – sectional study that used a retrospective electronic chart review of all admitted patients to cardiology department at King Abdullah university hospital (KAUH) in Irbid, Jordan, with a diagnosis of hypertension along with various acute cardiac admissions, including AF during 1-year period (January 1st to December 31 of 2021). Risk factors for AF (age, sex, DM, coronary artery disease, valvular heart disease, Cor-pulmonale, obstructive sleep apnea, and congestive cardiac failure) were retrieved from electronic charts of the patients. A total of 958 patients were admitted to the coronary care unit (CCU) and intermediate care unit (IMCU) during a 1-year period. Among them, 276 had 2 or 3 admissions. The main reason of admission was acute coronary syndrome (n = 491), heart failure (n = 180), and AF (n = 144), indicating AF prevalence of 15%. However, there were 40 patients with combined causes. All patients in the study (n = 958) were diagnosed with hypertension, including patients with atrial fibrillation (n = 144). The mean age of patients was 61.4 (± 11.46) years, and approximately two thirds of them were males (65.4%). The binary logistic regression model demonstrated a significant statistical relationship of age, left atrial size, coronary artery disease, left ventricular ejection fraction, left ventricular dimensions in systole and diastole, and heart failure with the occurrence of AF after controlling for gender, smoking, and diabetes. Findings indicate that left atrial size plays a significant role in the development of AF in patients with hypertension. However, the prevalence of AF significantly increased with advancing age in both sexes because of increased left ventricular hypertrophy, which leads to increased left atrial size. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is the most common cause of mortality in chronic kidney disease (CKD). Children with early-onset CKD arguably experience the greatest lifetime CVD burden. We utilized data from the Chronic Kidney Disease in Children Cohort Study (CKiD) to evaluate two pediatric CKD cohorts: congenital anomalies of the kidney and urinary tract (CAKUT) and cystic kidney disease for CVD risks and outcomes. Methods: CVD risk factors and outcomes including blood pressures, left ventricular hypertrophy (LVH), left ventricular mass index (LVMI), and ambulatory arterial stiffness index (AASI) scores were evaluated. Results: Forty-one patients in the cystic kidney disease group were compared to 294 patients in the CAKUT group. Cystic kidney disease patients had higher cystatin-C levels, despite similar iGFR. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) indexes were higher in the CAKUT group, but a significantly higher proportion of cystic kidney disease patients was on anti-hypertensive medications. Cystic kidney disease patients had increased AASI scores and a higher incidence of LVH. Conclusions: This study provides a nuanced analysis of CVD risk factors and outcomes including AASI and LVH in two pediatric CKD cohorts. Cystic kidney disease patients had increased AASI scores, higher incidence of LVH, and higher rates of anti-hypertensive medication use which could imply a greater burden of CVD despite similar GFR. Our work suggests that additional mechanisms may contribute to vascular dysfunction in cystic kidney disease, and that these patients may need additional interventions to prevent the development of CVD. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-2. Long-term consequences of MIS-C remain unknown. The objective was to describe the prevalence and clinical predictors of hypertension (HTN) and elevated blood pressure (BP) following MIS-C. Methods: A retrospective study of children ≤ 18 years admitted to a tertiary center with MIS-C was performed. HTN and elevated BP were classified as per the 2017 American Academy of Pediatrics Clinical Practice Guidelines and indexed to the 95th percentile. Data included demographics, inpatient clinical measures, and echocardiograms over 1-year follow-up. Data were analyzed using Kruskal–Wallis, chi-square, and logistic regression. Results: Among 63 children hospitalized with MIS-C (mean age 9.7 ± 4.2 years, 58.7% male, body mass index (BMI) z-score 0.59 ± 1.9), 14% had HTN, and 4% had elevated BP > 30 days post-hospitalization. Multivariate linear regression analysis showed that BMI z-score was significantly associated with higher mean systolic (β = 2.664, CI = 1.307–3.980, p < 0.001) and diastolic (β = 2.547, CI = 0.605–4.489, p = 0.012) BP index > 30 days post-hospitalization. Acute kidney injury (AKI) (23.8%) (OR = 2.977, CI = 1.778–4.987, p < 0.001), peak inpatient serum creatinine (OR = 2.524, CI = 1.344–4.740, p = 0.004), and maximum CRP (OR = 1.009, CI = 1.002–1.016, p = 0.014) were all associated with increased odds of post-hospitalization HTN. Left ventricular hypertrophy was present in 46% while hospitalized, compared to 10% at last follow-up. All had return of normal systolic function. Conclusions: Post-hospitalization HTN and elevated BP may be associated with MIS-C. Children with greater BMI or AKI may be at greater risk for developing HTN after MIS-C. MIS-C follow-up requires careful BP monitoring and antihypertensive medication consideration. [ABSTRACT FROM AUTHOR]

Background: It is not known whether, in children and adolescents with alterations in weight and/or blood pressure (BP), lifestyle modifications are associated with an improvement of early cardiac damage. Methods: In a pediatric population referred for excess weight, high BP, or both (n = 278, 10.6 (2.3) years), echocardiography was performed at enrollment and after 15 months of follow-up, during which participants received nonpharmacological treatment, based on correcting unhealthy lifestyles and improving dietary habits. Left ventricular mass was indexed for height (g/m2.7, LVMI), and an LVMI value higher than or equal to age- and gender-specific 95th percentile was the criterion for defining left ventricular hypertrophy (LVH). Multiple linear and logistic regression analyses were carried out to determine associations between changes in BMI and BP z-scores and changes of LVMI values and LVH prevalence, from baseline to follow-up. Results: At baseline, 33.1% of study participants were hypertensive, 52.9% obese, and 36.3% had LVH. At follow-up, the prevalence of hypertension, obesity, and LVH was 18.7%, 30.2%, and 22.3%, respectively (p < 0.001 for all). A decrease in LVMI from 37.1 to 35.2 g/m2.7 (p < 0.001) was observed. Only delta BMI z-score positively related to an improvement of LVMI. Reductions of BMI (OR = 0.22, 95% CI 0.07–0.64) and diastolic BP (OR = 0.64, 95% CI 0.42–0.93) z-scores from baseline to follow-up and family history of hypertension (OR = 0.36, 95% CI 0.16–0.78) were associated with a lower prevalence of LVH. Conclusions: In a pediatric population at cardiovascular risk, changing incorrect lifestyle and dietary habits is associated with both reduction of BMI and BP values and regression of early cardiac damage. [ABSTRACT FROM AUTHOR]

The current study was designed to assess the association of serum transforming growth factor β1 (TGF-β1) with left ventricular hypertrophy (LVH) in children with primary hypertension. The present single-center prospective trial examined 182 patients diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics, between January 2021 and September 2022. Clinical data were analyzed, and ambulatory blood pressure was assessed for 24 h. LVH, the commonest subclinical cardiac feature of hypertension, was assessed by echocardiography. According to left ventricular geometry, cases were assigned to the LVH (n = 44) and normal geometry (n = 138) groups. Serum TGF-β1 amounts were quantitated by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves were established to analyze various variables for their predictive values in LVH. Among 182 children with primary hypertension, the concentrations of serum TGF-β1 were higher in stage 2 hypertension than in stage 1 (47.3 (38.8, 52.5) vs. 46.0 (38.6, 48.2) ng/L, Z = − 2.376; P = 0.018). Additionally, serum TGF-β1 content showed a positive correlation with BP levels (P < 0.05). TGF-β1 amounts were significantly elevated in the LVH group compared with the normal geometry group (51.7 (46.1, 54.9) vs. 46.1 (38.7, 48.1) ng/L, Z = − 4.324; P = 0.0000). Serum TGF-β1 content was positively associated with LVH (r = 0.321, P = 0.0000). Multivariable logistic regression analysis showed BMI (OR = 1.188, 95% CI 1.082–1.305; P = 0.0000) and elevated serum TGF-β1 content (OR = 1.063, 95% CI 1.016–1.113; P = 0.009) independently predicted LVH. A multivariable logistic regression model considering BMI and TGF-β1 content in LVH prediction was 0.771, with sensitivity and specificity of 72.7% and 70.3%, respectively. Conclusion: These data revealed an association of serum TGF-β1 with BP in children with primary hypertension. Serum TGF-β1 concentration was positively correlated with hypertensive cardiac damage. Serum TGF-β1 might constitute a valuable molecular marker for the prediction of LVH in children with primary hypertension. The combination of BMI and TGF-β1 has a certain diagnostic and predictive value for LVH in children with primary hypertension, which may provide a new reference index for early clinical identification of hypertensive cardiac damage. What is Known: • Experimental and clinical data indicated TGF-β1 is involved in BP elevation. • TGF-β1 is positively correlated with LVMI and hypertrophy in adults. What is New: • Our current study reveals an association of serum TGF-β1 with BP in children with primary hypertension. • Elevated serum TGF-β1 level is positively associated with LVH in children with primary hypertension. • The combination of BMI and TGF-β1 has a certain diagnostic and predictive value for LVH in children with primary hypertension. [ABSTRACT FROM AUTHOR]

Anemia is a risk factor for adverse cardiovascular disease outcomes in hypertensive patients. Chronic anemia increases preload, reduces afterload, and leads to increased cardiac output in hypertension patients. In the long term, this may result in maladaptive left ventricular hypertrophy, which in turn is a well-recognized risk factor for cardiovascular disease outcomes and all-cause mortality in hypertension. Low hemoglobin and hematocrit levels might be strongly indicate hypertensive end-organ damage, specifically kidney failure. Therefore, this study determined the prevalence of anemia and associated factors among hypertensive patients in Referral Hospitals, Amhara Regional State, Ethiopia, in 2020. An institution-based cross-sectional study was conducted in Amhara Regional Referral Hospitals from February 20 to April 30, 2020. Random and systemic sampling techniques were used to select 428 study participants. Data were entered and coded in to Epi data version 3.0 and then exported into STATA 14 for analysis. In bivariable logistic regression, variables with a p-value of < 0.25 were included in multivariable logistic regression. Using a 95% confidence interval, variables having a p-value ≤ 0.05 in multivariable logistic regression were declared as statistically significant variables. In this study, a total of 428 study participants were involved with 99.5% response rate. The prevalence of anemia among hypertensive patients was 17.6%, with a 95% CI (14.3–21.5%). Estimated glomerular filtration rate (eGFR) < 90 ml/min (AOR = 2.77, 95% CI 1.56- 4.92)], duration of hypertension (HTN) ≥ 5 years (AOR = 2.37, 95% CI 1.36–4.15), uncontrolled blood pressure (AOR = 1.91, 95% CI 1.08–3.35), and higher pulse pressure (AOR = 1.05 (95% CI 1.02–1.08) were significantly associated with anemia. Nearly one out of five hypertensive patients had anemia. Impaired estimated glomerular filtration rate, duration of HTN, blood pressure status, and pulse pressure were the independent predictors of anemia among hypertensive patients. Screening hemoglobin level at a regular interval is recommended for the hypertensive patients to take an appropriate intervention. [ABSTRACT FROM AUTHOR]

Ventricular remodeling is one of the main causes of mortality from heart failure due to hypertension. Exploring its mechanism and finding therapeutic targets have become urgent scientific problems to be solved. A number of studies have shown that Mas, as an Ang-(1-7) specific receptor, was significantly reduced in myocardial tissue of rats undergoing hypertensive ventricular remodeling. It has been reported that Mas receptor levels are significantly downregulated in myocardium undergoing ventricular remodeling, but studies focused on intracellular and post-translational modifications of Mas are lacking. The results of this research are as follows: (1) PDZK1 interacts with the carboxyl terminus of Mas through its PDZ1 domain; (2) the expression of PDZK1 and Mas is decreased in rats undergoing hypertensive ventricular remodeling, and PDZK1 upregulation can ameliorate hypertensive myocardial fibrosis and myocardial hypertrophy; (3) PDZK1 enhances the stability of Mas protein through the proteasome pathway, and the proteasome inhibitor MG132 promotes hypertensive ventricular remodeling. PDZK1 improves ventricular remodeling in hypertensive rats by regulating Mas receptor stability. This study provides a scientific basis for the prevention and treatment of ventricular remodeling. [ABSTRACT FROM AUTHOR]

Population aging combined with higher susceptibility to cardiovascular diseases in older adults is increasing the incidence of conditions such as atherosclerosis, myocardial infarction, heart failure, myocardial hypertrophy, myocardial fibrosis, arrhythmia, and hypertension. sodium–glucose cotransporter 2 inhibitors (SGLT2i) were originally developed as a novel oral drug for patients with type 2 diabetes mellitus. Unexpectedly, recent studies have shown that, beyond their effect on hyperglycemia, SGLT2i also have a variety of beneficial effects on cardiovascular disease. Experimental models of cardiovascular disease have shown that SGLT2i ameliorate the process of aging-related cardiovascular disease by inhibiting inflammation, reducing oxidative stress, and reversing endothelial dysfunction. In this review, we discuss the role of SGLT2i in aging-related cardiovascular disease and propose the use of SGLT2i to prevent and treat these conditions in older adults. [ABSTRACT FROM AUTHOR]

Anemia is a risk factor for adverse cardiovascular disease outcomes in hypertensive patients. Chronic anemia increases preload, reduces afterload, and leads to increased cardiac output in hypertension patients. In the long term, this may result in maladaptive left ventricular hypertrophy, which in turn is a well-recognized risk factor for cardiovascular disease outcomes and all-cause mortality in hypertension. Low hemoglobin and hematocrit levels might be strongly indicate hypertensive end-organ damage, specifically kidney failure. Therefore, this study determined the prevalence of anemia and associated factors among hypertensive patients in Referral Hospitals, Amhara Regional State, Ethiopia, in 2020. An institution-based cross-sectional study was conducted in Amhara Regional Referral Hospitals from February 20 to April 30, 2020. Random and systemic sampling techniques were used to select 428 study participants. Data were entered and coded in to Epi data version 3.0 and then exported into STATA 14 for analysis. In bivariable logistic regression, variables with a p-value of < 0.25 were included in multivariable logistic regression. Using a 95% confidence interval, variables having a p-value ≤ 0.05 in multivariable logistic regression were declared as statistically significant variables. In this study, a total of 428 study participants were involved with 99.5% response rate. The prevalence of anemia among hypertensive patients was 17.6%, with a 95% CI (14.3–21.5%). Estimated glomerular filtration rate (eGFR) < 90 ml/min (AOR = 2.77, 95% CI 1.56- 4.92)], duration of hypertension (HTN) ≥ 5 years (AOR = 2.37, 95% CI 1.36–4.15), uncontrolled blood pressure (AOR = 1.91, 95% CI 1.08–3.35), and higher pulse pressure (AOR = 1.05 (95% CI 1.02–1.08) were significantly associated with anemia. Nearly one out of five hypertensive patients had anemia. Impaired estimated glomerular filtration rate, duration of HTN, blood pressure status, and pulse pressure were the independent predictors of anemia among hypertensive patients. Screening hemoglobin level at a regular interval is recommended for the hypertensive patients to take an appropriate intervention. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of hypertension and hypertension-induced target organ injury by the 2022 American Heart Association (AHA) ambulatory blood pressure threshold as compared with 2014 AHA and 2016 European Society of Hypertension (ESH) thresholds has not been evaluated. Methods: In a cross-sectional study (n = 291, aged 5–18 years, at a tertiary care outpatient clinic), we compared 2022 AHA with 2014 AHA and ESH thresholds (revised with 2018 adult ESH thresholds where applicable) to diagnose ambulatory hypertension (AH), and detect ambulatory arterial stiffness index (AASI) and left ventricular target organ injury (LVTOI). Results: The 2022 AHA threshold diagnosed significantly more AH (53%) than the 2014 AHA (42%, p < 0.01) and ESH (36%, p < 0.001) thresholds. The 2022 AHA threshold demonstrated only a moderate agreement with the 2014 AHA (kappa (k) = 0.77) and ESH (k = 0.66) thresholds to diagnose AH. Adjusted logistic regression analysis found that only the 2022 AHA threshold predicted elevated AASI significantly (odds ratio 2.40, 95% CI 1.09, 5.25, p = 0.02; AUC 0.61, p < 0.01). In those with elevated AASI, more participants had AH by the 2022 AHA threshold (72%) than the 2014 AHA (46%, p = 0.02) and ESH (48%, p = 0.03) thresholds. AH defined by the 2022 AHA threshold continued to maintain higher odds, larger AUC, and higher sensitivity to identify LVTOI than the 2014 AHA and ESH thresholds; however, the difference did not reach a statistically significant level. Conclusions: AH defined by the 2022 AHA threshold diagnoses more children with hypertension and identifies more children with hypertension-induced target organ injury than the 2014 AHA and ESH thresholds. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is a major public health concern. Its outcome is poor and, as of today, barely any treatments have been able to decrease its morbidity or mortality. Cardiosphere-derived cells (CDCs) are heart cell products with anti-fibrotic, anti-inflammatory and angiogenic properties. Here, we tested the efficacy of CDCs in improving left ventricular (LV) structure and function in pigs with HFpEF. Fourteen chronically instrumented pigs received continuous angiotensin II infusion for 5 weeks. LV function was investigated through hemodynamic measurements and echocardiography at baseline, after 3 weeks of angiotensin II infusion before three-vessel intra-coronary CDC (n = 6) or placebo (n = 8) administration and 2 weeks after treatment (i.e., at completion of the protocol). As expected, arterial pressure was significantly and similarly increased in both groups. This was accompanied by LV hypertrophy that was not affected by CDCs. LV systolic function remained similarly preserved during the whole protocol in both groups. In contrast, LV diastolic function was impaired (increases in Tau, LV end-diastolic pressure as well as E/A, E/E'septal and E/E'lateral ratios) but CDC treatment significantly improved all of these parameters. The beneficial effect of CDCs on LV diastolic function was not explained by reduced LV hypertrophy or increased arteriolar density; however, interstitial fibrosis was markedly reduced. Three-vessel intra-coronary administration of CDCs improves LV diastolic function and reduces LV fibrosis in this hypertensive model of HFpEF. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the leading cause of death in pediatric patients with kidney failure. Left ventricular hypertrophy (LVH) is recognized as the most common cardiovascular abnormality in these patients. There remains a paucity of longitudinal studies evaluating LVH during maintenance dialysis in children. NAPRTCS has collected echocardiographic data of pediatric maintenance dialysis patients since 2013 and is one of the largest registries to assess longitudinal changes in LVH. Methods: Patients aged 1–18 years with echocardiographic data and without underlying structural cardiovascular diseases were included. LVH was defined as left ventricular mass index (LVMI, height-indexed) > 95th percentile for age and sex. Univariate and multivariable logistic regression was performed to assess risk factors for LVH at baseline. Generalized estimating equation was used to assess risk factors of changes in LVH during maintenance dialysis. Results: A total of 518 patients had echocardiographic data available for analysis during time on maintenance dialysis. Of 179 patients with baseline echocardiography (within 30 days of dialysis initiation), 67% had LVH. In multivariable logistic regression adjusted for age, race, and sex, uncontrolled hypertension (OR 9.4, 95% CI 2.8–31) and anemia (OR 2.3, 95% CI 1.0–5.3) were associated with LVH at baseline. Prevalence of LVH remained high at 40–50% during follow-up. Controlled and uncontrolled hypertension as well as phosphorus level were independently associated with increased likelihood of LVH during maintenance dialysis. Conclusions: LVH is prevalent in pediatric patients at dialysis initiation and remains prevalent during follow-up. Hypertension is the strongest risk factor for LVH in children on maintenance dialysis. [ABSTRACT FROM AUTHOR]

Background: Children with kidney failure have increased risk for cardiovascular morbidities before and after transplantation. Ejection fraction is often preserved, masking cardiac dysfunction until severe. Data on longitudinal changes in diastolic function and cardiac geometry are limited. Methods: A prospective study was conducted to investigate longitudinal changes in diastolic function and structure pre- and post-kidney transplant compared with healthy peers. Transplant recipients (n = 41) had echocardiograms pre-transplant, 1, 18, 30, and 42 months post-transplant. The controls (n = 26) underwent one echocardiogram. Diastolic function and cardiac geometry were assessed by E/e' lateral, E/A, interventricular septal end diastole diameter, left ventricular internal end diastole diameter, left ventricular posterior wall end diastole diameter, and left atrial dimension. Results: E/e' of patients remained worse than controls until 30 months post-transplant, and E/A was impaired at all time points compared to the controls. Left ventricular geometry was abnormal in 46% pre-transplant and remained altered in 44.7%, 32.3%, 30.7%, and 27.2% at 1, 18, 30, and 42 months post-transplant. Determinants of diastolic dysfunction included hemodialysis, uncontrolled hypertension, steroid exposure, and metabolic syndrome; abnormal geometry was associated with glomerular diagnosis, dialysis duration, obesity, steroids, and metabolic syndrome. Abnormal diastolic function and structure were associated with left ventricular hypertrophy. Conclusion: Diastolic dysfunction and geometry partially improve after transplant but remain abnormal in a subset of patients compared to healthy peers. Traditional indicators of systolic function are preserved. Modifiable risk factors include dialysis modality and duration, uncontrolled hypertension, corticosteroids, obesity, and metabolic syndrome. Attention to diastolic changes provides opportunity for early intervention. [ABSTRACT FROM AUTHOR]

Background: Assessment of fluid status in neonatal dialysis has largely focused on traditional tools including clinical assessment, serial weights, and blood pressure (BP) measurements. However, in infants on kidney replacement therapy, the assessment of fluid overload is problematic due to errors in weight assessment, subtlety of physical exam findings, and inaccuracy of non-invasive BP measurements. Case summary: In this presentation of a neonate with bilateral renal agenesis requiring kidney replacement therapy, the treating team assessed a number of variables in determining the ultrafiltration prescription for dialysis across 2 modalities (hemodialysis and continuous kidney replacement therapy). Complications: Fluid overload, cardiomegaly, and worsened respiratory status occurred when attempting to assess the neonate's fluid status by traditional markers (weights, blood pressures, physical exam findings). B-type natriuretic peptide (BNP) was obtained and was noted to correlate with the degree of fluid overload. Key management points: Compared to traditional tools for assessment of fluid status in pediatric dialysis, BNP assisted the medical team in optimizing the volume status of the subject and determining optimal daily ultrafiltration goals. Due to the rapid release in response to myocardial stretch and the lack of kidney clearance of the peptide, BNP may represent an objective, timely, and reliable index of volume status in the pediatric dialysis patient. [ABSTRACT FROM AUTHOR]

The etiology of peripartum cardiomyopathy (PPCM) is unknown. Therefore, we evaluated the etiology of patients clinically diagnosed with PPCM using endomyocardial biopsy. We studied five patients diagnosed with PPCM following endomyocardial biopsy (age, 28–42 years; mean age, 35 years). Biopsied samples were evaluated using microscopy, including immunostaining and electron microscopy. The pathological findings were as follows: myocardial hypertrophy, myocardial fibrosis, and cell infiltration. Two patients were diagnosed with lymphocytic myocarditis, one with eosinophilic myocarditis, one with hypertensive heart disease, and one with a combination of hypertension and myocarditis. Endomyocardial biopsy suggested that the causes of PPCM were varied and related to myocarditis and myocardial overload due to hypertension. [ABSTRACT FROM AUTHOR]

Objectives: Porto-sinusoidal vascular disorder (PSVD) is a recently defined vascular liver disease. Since diagnosis remains challenging, we aimed to evaluate radiological features that are distinct between PSVD and cirrhosis. Methods: Clinical, laboratory, and radiological parameters (CT/MRI) of patients with histologically-confirmed PSVD vs. cirrhosis vs. non-cirrhotic parenchymal liver disease were retrospectively evaluated. Results: Sixty-three PSVD, 155 cirrhosis, and 41 non-cirrhotic patients were included. As compared to cirrhosis, PSVD patients were younger and had lower HVPG, liver stiffness, and MELD. Routine clinical and imaging findings indicative of portal hypertension were similarly common. Intrahepatic portal tract abnormalities (49% vs. 15%; p < 0.001), FNH-like lesions (30% vs. 1%; p < 0.001), and abnormal liver morphology defined as peripheral parenchymal atrophy and compensatory hypertrophy of central segments (32% vs. 7%; p < 0.001) were significantly more common in PSVD patients. Hypertrophy of segment I (70% vs. 84%; p = 0.019), atrophy of segment IV (24% vs. 47%; p = 0.001), and nodular liver surface (22% vs. 89%; p < 0.001) were more common in patients with cirrhosis. In patients with gadoxetic acid–enhanced MRI, we identified the distinct imaging feature of "periportal hyperintensity" in the hepatobiliary phase (HBP) in 42% of patients with PSVD (14/33) vs. 1% in cirrhosis (1/95) vs. 0% in non-cirrhotic controls (0/41); p < 0.001). Conclusions: Diagnosis of PSVD must be considered in younger patients presenting with clinical features of portal hypertension, portal tract abnormalities, and FNH-like lesions on CT/MRI. 'Periportal hyperintensity' in the HBP of gadoxetic acid–enhanced MRI was identified as a specific radiological feature of PSVD. Key Points: • Cross-sectional imaging can provide essential information to identify patients with porto-sinusoidal vascular disorder (PSVD). • Intrahepatic portal tract abnormalities, FNH-like lesions, and abnormal liver morphology are common in PSVD patients. • Periportal hyperintensity on the hepatobiliary phase of gadoxetic acid–enhanced MRI seems to be specific for patients with PSVD. [ABSTRACT FROM AUTHOR]

Hypertension-related left ventricular hypertrophy is recognized as a good predictor of adverse cardiovascular events. However, the underlying mechanism of left ventricular hypertrophy is still not fully understood. This study employed liquid chromatography coupled with tandem mass spectrometry to investigate global changes in protein profile in myocardium of spontaneously hypertensive rat, a classical animal model of essential hypertension. There were 369 differentially expressed proteins in myocardium between spontaneously hypertensive rats and normotensive rats. Xenobiotic catabolic process, cholesterol binding and mitochondrial proton-transporting ATP synthase were found to be the most significantly enriched biological process, molecular function and cellular component terms of Gene Ontology, respectively. Drug metabolism-cytochrome P450 was revealed to be the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways. FYN proto-oncogene, Src family tyrosine kinase was found to have the most interactions with other proteins. Differentially expressed proteins involved in xenobiotic catabolic process, lipid transport and metabolism, mitochondrial function might be targets for further study of hypertension-related left ventricular hypertrophy. [ABSTRACT FROM AUTHOR]

Introduction: The increase in the pulsatile component of left ventricle afterload is suspected to cause a mismatch between the left ventricle (LV) and the vascular tree. Aim: To demonstrate that ventricular-arterial uncoupling is frequently present in the development of LV hypertrophy (H) and diastolic dysfunction (DD) in hypertension (HBP). Methods: Observational study, HBP patients with ejection fraction > 54%. Conventional 2D echocardiography and tissue Doppler performed following imaging guidelines. LV end systolic elastance (Ees), the effective arterial elastance (Ea), and ventricular-arterial coupling (VAC) measured by Chen single beat method. Results: 288 patients, mean age 56.3 ± 12.5 years and 168 patients (58.3%) males. Mean LV mass index was 87.2 ± 20.4 grs/m2 and frequency of LVH 20.1% (58 patients). The mean VAC was 0.54 ± 9.23. LV Stroke volume, stroke work and systolic stress were 46.2 ± 10.3 cc/m2, 91.4 ± 22.2 g-min/m2, and 57 ± 14.6 dynes/cm2 in quartile 1, and 33.5 ± 6.6 cc/m2, 65.5 ± 15.2 g-min/m2, and 77.8 ± 17.1 dynes/cm2, in quartile 4, respectively (p < 0.001). Peripheral resistance index was 3349 ± 1072 and 4410 ± 1143 dynes*s/cm-5/m2 quartiles 1 vs. 4 (p < 0.005). The frequency of LVH was 31.9% in quartile 1 and 11.3% in quartile 4 (p < 0.005) and LVH or DD was 37.5% and 12.7%, respectively (p < 0.001). Conclusions: Stroke volume and stroke work were significantly increased while systolic stress and peripheral resistance index were significantly reduced in patients with worst VAC. Ventricular-arterial uncoupling is mostly caused by an increase in Ees rather than by an elevation of Ea. LVH or DD are more frequent in the worst cases of ventricular-arterial uncoupling. [ABSTRACT FROM AUTHOR]

Background: Hypertension is an important cardiovascular risk factor that affects cardiac remodeling. Left ventricular hypertrophy (LVH) is a type of cardiac remodeling and a significant risk factor for adverse outcomes. Elite athletes can develop LVH, also called athlete's heart. While LVH is a reversible change, it is sometimes persistent. It is unclear whether athletes with LVH will suffer from future health disadvantages such as hypertension. Lifestyle-related factors may be involved in long-term health problems; nonetheless, the relationship between LVH and lifestyle is unclear. Aims: We investigated the association between LVH and future hypertension in elite athletes, including the effects of lifestyle-related factors. Methods: We evaluated the electrocardiographic data of 61 Japanese athletes who participated in the 1964 Tokyo Olympics to determine whether they had LVH, which was evaluated using the Peguero-Lo Presti criteria. Electrocardiographic and follow-up lifestyle data were obtained from the Japan Sport Association study subjects' biographical information. Results: During the mean follow-up period (47.7 ± 5.1 years), 25 athletes developed hypertension. The LVH group had a significantly higher rate of incident hypertension (60.0% vs. 30.6%, p = 0.02). Multivariate Cox regression analysis revealed that LVH was associated with incident hypertension after adjusting for systolic blood pressure. The relationship was attenuated after including smoking history (LVH: hazard ratio, 2.14; 95% confidence interval, 0.97–4.73; p = 0.06). Conclusions: LVH in athletes was associated with incident hypertension, and smoking attenuated this association. This suggests that LVH is not an independent factor for incident hypertension among elite athletes and that smoking history is an important confounding factor. [ABSTRACT FROM AUTHOR]

Purpose: Hypertension is a major risk factor for cardiovascular disease. Isometric exercise training (IET) reduces resting and ambulatory blood pressure; however, few studies have investigated the myocardial adaptations following IET. Methods: We randomly assigned 24 unmedicated hypertensive patients in a cross-over study design to 4-weeks of IET and control period, separated by a 3-week washout period. Speckle tracking echocardiography was used to measure left ventricular (LV) mechanics, and global myocardial work indices were derived from non-invasive LV pressure-strain loops constructed from global longitudinal strain (GLS) indexed to brachial systolic blood pressure. Results: IET significantly improved GLS (− 2.3 ± 2%, p < 0.001) and global work efficiency (2.8 ± 2%, p < 0.001), and significantly reduced global wasted work (− 42.5 ± 30 mmHg%, p < 0.001) with no significant change during the control period. Conclusions: This is the first evidence to demonstrate that IET significantly improved cardiac health in a relevant patient population. Our findings have important clinical implications for patients with high blood pressure and support the role of IET as a safe and viable therapeutic and preventative intervention in the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Arterial hypertension causes left ventricular hypertrophy leading to dilated cardiomyopathy. Following compensatory cardiomyocyte hypertrophy, cardiac dysfunction develops due to loss of cardiomyocytes preceded or paralleled by cardiac fibrosis. Zyxin acts as a mechanotransducer in vascular cells that may promote cardiomyocyte survival. Here, we analyzed cardiac function during experimental hypertension in zyxin knockout (KO) mice. In zyxin KO mice, made hypertensive by way of deoxycorticosterone acetate (DOCA)-salt treatment telemetry recording showed an attenuated rise in systolic blood pressure. Echocardiography indicated a systolic dysfunction, and isolated working heart measurements showed a decrease in systolic elastance. Hearts from hypertensive zyxin KO mice revealed increased apoptosis, fibrosis and an upregulation of active focal adhesion kinase as well as of integrins α5 and β1. Both interstitial and perivascular fibrosis were even more pronounced in zyxin KO mice exposed to angiotensin II instead of DOCA-salt. Stretched microvascular endothelial cells may release collagen 1α2 and TGF-β, which is characteristic for the transition to an intermediate mesenchymal phenotype, and thus spur the transformation of cardiac fibroblasts to myofibroblasts resulting in excessive scar tissue formation in the heart of hypertensive zyxin KO mice. While zyxin KO mice per se do not reveal a cardiac phenotype, this is unmasked upon induction of hypertension and owing to enhanced cardiomyocyte apoptosis and excessive fibrosis causes cardiac dysfunction. Zyxin may thus be important for the maintenance of cardiac function in spite of hypertension. [ABSTRACT FROM AUTHOR]

Background: Adolescents with chronic kidney disease (CKD) are a unique population with a high prevalence of hypertension. Management of hypertension during the transition from adolescence to adulthood can be challenging given differences in normative blood pressure values in adolescents compared with adults. Methods: In this retrospective analysis of the Chronic Kidney Disease in Children Cohort Study, we compared pediatric versus adult definitions of ambulatory- and clinic-diagnosed hypertension in their ability to discriminate risk for left ventricular hypertrophy (LVH) and kidney failure using logistic and Cox models, respectively. Results: Overall, among 363 adolescents included for study, the prevalence of systolic hypertension was 27%, 44%, 12%, and 9% based on pediatric ambulatory, adult ambulatory, pediatric clinic, and adult clinic definitions, respectively. All definitions of hypertension were statistically significantly associated with LVH except for the adult ambulatory definition. Presence of ambulatory hypertension was associated with 2.6 times higher odds of LVH using pediatric definitions (95% CI 1.4–5.1) compared to 1.4 times higher odds using adult definitions (95% CI 0.8–3.0). The c-statistics for discrimination of LVH was statistically significantly higher for the pediatric definition of ambulatory hypertension (c=0.61) compared to the adult ambulatory definition (c=0.54), and the Akaike Information Criterion was lower for the pediatric definition. All definitions were associated with progression to kidney failure. Conclusion: Overall, there was not a substantial difference in pediatric versus adult definitions of hypertension in predicting kidney outcomes, but there was slightly better risk discrimination of the risk of LVH with the pediatric definition of ambulatory hypertension. [ABSTRACT FROM AUTHOR]

Shear wave (SW) imaging is a novel ultrasound-based technique for assessing tissue characteristics. SW elasticity may be useful to assess the severity of hypertensive left ventricular (LV) hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy using hypertensive rats. Rats were divided into hypertension group and control group. SW elasticity was measured on the excised heart. Myocardial hypertrophy was assessed histologically. LV weight was greater in hypertension group. An increase in interventricular septum and LV free wall thicknesses was observed in hypertension group. SW elasticity was significantly higher in hypertension group than in control group (14.6 ± 4.3 kPa vs. 6.5 ± 1.1 kPa, P < 0.01). The cross-sectional area of cardiomyocytes was larger in hypertension group than in control group (397 ± 50 μm2 vs. 243 ± 14 μm2, P < 0.01), and SW elasticity was positively correlated with the cross-sectional area of cardiomyocytes (R = 0.96, P < 0.01). This study showed that SW elasticity was higher in hypertensive rats and was closely correlated with the degree of myocardial hypertrophy, suggesting the efficacy of SW elasticity for estimating the severity of hypertensive LV hypertrophy. [ABSTRACT FROM AUTHOR]

As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV. [ABSTRACT FROM AUTHOR]

Background: The peculiarity of the cardiovascular risk profile with increased arterial vulnerability is well known in adults with chronic kidney disease (CKD). It is explained by an increased incidence of traditional cardiovascular risk factors together with other comorbidities related to the uremic condition and cardiorenal syndrome (CRS). The present study aimed to determine the cardiovascular impact of the uremic condition in a pediatric population with advanced CKD. Methods: From 2016 to 2018, 39 consecutive patients with advanced CKD who underwent echocardiographic evaluation were included. All echocardiographic examinations were performed by the same operator (FE). Demographic, clinical, biological, and echocardiographic data were collected. Results: The mean age at echocardiographic exam was 9.7 ± 4.6 years. Twenty-four (61.5%) patients were on hemodialysis; 17 (43.6%) patients were in a peritoneal dialysis program of whom 11 switched at a later stage to hemodialysis. Eight (20.5%) patients had an arteriovenous fistula (AVF). Hypertension was present in 30 (76.9%) patients while left ventricular hypertrophy (LVH) was described in 13 (33.3%) patients. Dilatation of the ascending aorta (Z-score > 2) was found in 15 (38.4%) patients and was statistically (in univariate analysis) related to gender, hypertension, the presence of an AVF, and the use of hemodialysis after peritoneal dialysis (p = 0.024, p = 0.016, p = 0.006, p = 0.009, respectively). Conclusion: In addition to classical and predictable abnormalities related to CKD, we found a high prevalence of dilatation of the ascending aorta in children with advanced CKD. Hypertension, AVF, and hemodialysis were associated factors. [ABSTRACT FROM AUTHOR]

Introduction: Hypertensive mediated heart disease is the consequence of anatomical and functional changes in cardiovascular system. The benefits on left ventricular (LV) diastolic impairment and remodeling of hypertension treatment are well established. Aim: To evaluate LV structure, systolic and diastolic function of treated hypertensive patients on a medium to long term follow-up. Methods: Prospectively observational cohort study. Hypertensive patients over 18 years, ultrasound evaluation of LV structure and diastolic and systolic function, follow-up at least once a year. Diastolic function assessed following recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Results: 285 patients, mean follow up of 1731 ± 952 days. Sample mean age 56.3 ± 12.5 years, 166 patients (58.3%) were males. Baseline blood pressure 147.8 ± 19/86.8 ± 11 mm Hg, 5 years blood pressure 134.4 ± 15.7/79 ± 9 mm Hg (p < 0.005 SBP and p < 0.01 DBP). Baseline fixed dose combinations 115 patients (40.4%), follow-up 53.1% (p < 0.05). LV remodeling was detected in 88 patients (30.9%) vs. 30.1% at 5 years (p = NS). The frequency of an E/e′ ratio > 14 was reduced from 38 patients (13.3%) to 3.6% (p < 0.001), e′ septal velocity < 7 cm/sec or e′ lateral velocity < 10 cm/sec was reduced from 38.6% (110 patients) to 19.3% (p < 0.001). Baseline normal diastolic function was detected in 85.6% (244 patients) and 94% at the end of the follow-up (p < 0.02). Conclusions: In this observational cohort followed by a mean of 5 years, the main benefit of hypertension treatment was the prevention or regression of diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Isolated nocturnal hypertension (INH) is associated with increased prevalence of left ventricular hypertrophy (LVH) and cardiovascular morbidity and mortality in adult patients. Unlike in adults, data illustrating the possible association between INH and cardiac target organ damage is lacking in children. This study aimed to investigate whether INH is associated with increased left ventricular mass index (LVMI) and LVH in children. Methods: Retrospective data from all untreated children with confirmed ambulatory hypertension (HT) in our center was reviewed. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed concurrently. Ambulatory normotensive children served as controls. LVH was defined as LVMI ≥ 95th percentile. Results: There were 102 ABPM studies; of these, 79 children had renal HT, and 23 had primary HT. Median age of children was 13.2 years (3.8–18.9). Nineteen children had INH, 9 children had isolated daytime HT, 54 had daytime and nighttime HT, and 20 were normotensive. The LVMI adjusted for age (patient's LVMI/95th percentile of the LVMI) was significantly higher in children with INH than in normotensive children (0.83 ± 0.03 vs. 0.74 ± 0.03, p = 0.03). Left ventricular hypertrophy was present in 11% of children with INH; this was not significantly higher than in normotensive children (0%, p = 0.23). Conclusions: This study investigated the association between INH and cardiac structure in children with primary and renal HT and showed children with INH had higher LVMI adjusted for age than normotensive children and children with INH had similar LVMI adjusted for age to children with isolated daytime HT. [ABSTRACT FROM AUTHOR]

Recently, a new ECG criterion, the Peguero-Lo Presti (PLP), improved overall accuracy in the diagnosis of left ventricular hypertrophy (LVH)—compared to traditional ECG criteria, but with few patients with advanced age. We analyzed patients with older age and examined which ECG criteria would have better overall performance. A total of 592 patients were included (83.1% with hypertension, mean age of 77.5 years) and the PLP criterion was compared against Cornell voltage (CV), Sokolow-Lyon voltage (SL) and Romhilt-Estes criteria (cutoffs of 4 and 5 points, RE4 and RE5, respectively) using LVH defined by the echocardiogram as the gold standard. The PLP had higher AUC than the CV, RE and SL (respectively, 0.70 vs 0.66 vs 0.64 vs 0.67), increased sensitivity compared with the SL, CV and RE5 (respectively, 51.9% [95% CI 45.4–58.3%] vs 28.2% [95% CI 22.6–34.4%], p < 0.0001; vs 35.3% [95% CI 29.2–41.7%], p < 0.0001; vs 44.4% [95% CI 38.0–50.9%], p = 0.042), highest F1 score (58.3%) and net benefit for most of the 20–60% threshold range in the decision curve analysis. Overall, despite the best diagnostic performance in older patients, the PLP criterion cannot rule out LVH consistently but can potentially be used to guide clinical decision for echocardiogram ordering in low-resource settings. [ABSTRACT FROM AUTHOR]

This study aimed to describe the variety of etiologies currently identified in infants with cardiac hypertrophy (CH) and investigate whether there is a relation with hyperinsulinism, echocardiographic characteristics and prognosis. This retrospective cohort study included infants born between 2005 and 2018 with CH measured by echocardiography [interventricular septum (IVS) and/or left ventricular posterior wall (LVPW) thickness with Z-score ≥ 2.0]. Children with congenital heart disease or hypertension were excluded. Underlying diagnosis, echocardiographic and follow-up data were extracted from patient files. Seventy-one infants with CH were included. An underlying cause of CH was identified in two-thirds (n = 47). Most common etiologies of CH were malformation syndromes (n = 23, including Noonan n = 12) and maternal diabetes mellitus (n = 13). Less common causes were congenital hyperinsulinism (n = 3), metabolic- (n = 5), sarcomeric- (n = 2) and neuromuscular disease (n = 1). In half of the identified causes (n = 22) an association with hyperinsulinism was described, including maternal diabetes mellitus (n = 13), malformation syndromes with insulin resistance (n = 6) and congenital hyperinsulinism (n = 3). CH associated with hyperinsulinism was echocardiographically characterized by lower LVPW thickness, higher IVS:LVPW ratio and more frequent sole involvement of the IVS (all, p ≤ 0.02). CH associated with hyperinsulinism normalized more often (41 vs. 0%) with lower mortality rates (14 vs. 44%) compared to CH not associated with hyperinsulinism (all, p ≤ 0.03). Nowadays, an etiology of CH can be identified in the majority of infants. The development of CH is often associated with hyperinsulinism which is mainly characterized by focal hypertrophy of the IVS on echocardiography. Prognosis depends on the underlying cause and is more favorable in CH associated with hyperinsulinism. [ABSTRACT FROM AUTHOR]

The prevalence of non-communicable disease (NCDs) is rising globally, with a large burden recorded in sub-Saharan countries and populations of black race/ethnicity. Accelerated vascular deterioration, otherwise known as early vascular aging (EVA), is the underlying factor for highly prevalent NCDs such as hypertension. The etiology of EVA is multifactorial with a central component being arterial stiffness with subsequent development of hypertension and cardiovascular complications. Although arterial stiffness develops with increasing age, many children and adolescents are subjected to the premature development of arterial stiffness, due to genetic or epigenetic predispositions, lifestyle and behavioral risk factors, and early life programming. Race/ethnic differences in pediatric populations have also been reported with higher aortic stiffness in black (African American) compared with age-matched white (European American) counterparts independent of blood pressure, body mass index, or socioeconomic status. With known evidence of race/ethnic differences in EVA, the pathophysiological mechanisms underlying graded differences in the programming of EVA are still sparse and rarely explored. This educational review aims to address the early life determinants of EVA in children and adolescents with a particular focus on racial or ethnic differences. [ABSTRACT FROM AUTHOR]

Background: Hypertension (HTN) is common in children and often associated with pathologic progression to end organ damage, specifically left ventricular hypertrophy (LVH). Methods: The primary goal of this retrospective chart review is to determine if patients with higher blood pressure were more likely to complete echocardiogram (ECHO) and more likely to have LVH, among a pediatric population referred for hypertension evaluation before the 2017 American Academy of Pediatrics (AAP) guidelines. To meet this goal, the number of patients evaluated by ECHO and prevalence of LVH was examined for independent associations with blood pressure and BMI categories by logistic regression. Results: It was found that higher blood pressure was associated with having an ECHO evaluation (p = 0.012). Among patients evaluated by ECHO, one-third had LVH but the presence of LVH was not associated with blood pressure severity or use of anti-hypertensive medication. Instead, BMI was the only factor associated with LVH cardiac remodeling in our population (p = 0.025). Conclusions: Newly updated AAP practice guidelines recommend evaluation of HTN via ABPM, with ECHO performed only at the initiation of pharmaceutical therapy. It is notable that BMI, the only risk factor of LVH found in this study, is not addressed in the current AAP guidelines for ECHO evaluation among hypertensive children. This study suggests that ECHO evaluation may be warranted in a larger subset of children as is recommended by current European Society of Hypertension pediatric guidelines. [ABSTRACT FROM AUTHOR]

Objectives: To assess the value of cardiac MRI in comparison to echocardiography in consecutive patients with previously diagnosed and new suspected hypertrophic cardiomyopathy (HCM). Methods: All MRI studies of patients with HCM or suspected disease performed at our centre within a 10-year time period were evaluated. Initial diagnoses (echocardiography-based) and final (MRI-based) diagnoses were compared in subgroups, and the discrepancies were recorded. Results: A total of 1006 subjects with HCM or suspected HCM were identified (61% males, 39% females; median age, 49.1 years; interquartile range, 34.9–60.4). In 12 (2.2%) out of 550 patients with known HCM, MRI indicated a diagnosis other than HCM, including but not limited to the subaortic membrane (n = 1, 8.3%) or mild left ventricular hypertrophy (n = 5, 41.7%). Among all patients with suspected HCM (n = 456), MRI diagnosis was different from HCM in 5.3% (n = 24) of patients. In an additional 20.4% of patients (n = 93), no significant hypertrophy was present. In total, among patients with suspected HCM, MRI led to clear HCM diagnosis in 204 (44.7%) patients. Among patients with a history of uncontrolled hypertension suspected of having HCM, MRI aided in identifying cardiomyopathy in 47.9% of patients. This subgroup contained the largest proportion of patients with an ambiguous diagnosis, namely, 29.6% compared with 13.8% in the remaining groups of patients with suspected HCM (p = 0.0001). Conclusions: In a small but important group of patients with ultrasound-based HCM, cardiac MRI can diagnose previously unknown conditions and/or refute suspected cardiomyopathy. The diagnostic yield of MRI when compared to echocardiography in patients suspected of having HCM is 44.7%. Key Points: • Out of 550 patients previously diagnosed with echocardiography but without magnetic resonance imaging (MRI) as having hypertrophic cardiomyopathy (HCM), we diagnosed a different disease in 12 (2.2%) patients using MRI. • Among patients with suspected HCM based on echocardiography, MRI led to clear HCM diagnosis in 44.7% of patients. • In patients with a history of uncontrolled hypertension suspected, based on an echocardiogram, of having HCM, MRI aided in identifying cardiomyopathy in 47.9% of patients. This subgroup contained the largest proportion of patients with an ambiguous diagnosis. [ABSTRACT FROM AUTHOR]

Background: The clinical significance of isolated systolic hypertension with normal central blood pressure known as spurious hypertension (sHT) in adolescents and its evolution over time is not known. Methods: The aim of this study was to analyze changes in office, ambulatory blood pressure (ABPM), central systolic blood pressure (cSBP), hemodynamic parameters, and target organ damage (TOD) over a 1-year follow-up in a group of non-obese children with sHT. Results: Of 294 patients referred for primary hypertension, 138 patients (31 girls; 22%) had hypertension confirmed by ABPM. 48/138 (35%) patients (7 girls; 15%) were diagnosed with sHT (elevated office and ambulatory systolic BP, but normal cSBP); 43 of them (6 girls; 14%) were followed for 12 ± 3 months during non-pharmacological therapy. At baseline 7 (16%) patients had borderline values of cIMT or LVMi indicating mild TOD. After 12 months, 10/43 (3 girls; 23%) patients developed sustained HT (elevated office, ambulatory BP and cSBP), 11/43 (1 girl; 26%) maintained sHT, and 22/43 (2 girls; 51%) evolved to white coat hypertension or normotension. The cSBP values increased in 27 patients (4 girls; 63%), but the group average remained in the normal range. Prevalence of TOD did not change during observation. The multivariate regression analysis showed that the only predictor of cSBP change over time was a change in serum uric acid level. Conclusions: In conclusion, after 1 year of non-pharmacological treatment, 23% of adolescents with sHT developed sustained hypertension, with the main predictor of cSBP change being the change in serum uric acid. [ABSTRACT FROM AUTHOR]

A clinical quiz about the diagnosis of polydipsia, polyuria, and malignant hypertension in pediatric patients is presented.

Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Insulin resistance is defined as a less than expected biologic response to a given concentration of the hormone and plays a pivotal role in the pathogenesis of diabetes. However, over the last decades, it became evident that insulin resistance is not merely a metabolic abnormality, but is a complex and multifaceted syndrome that can also affect blood pressure homeostasis. The dysregulation of neuro-humoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. These mechanisms induce a chronic low grade of inflammation that interferes with insulin signalling transduction. Molecular abnormalities associated with insulin resistance include the defects of insulin receptor structure, number, binding affinity, and/or signalling capacity. For instance, hyperglycaemia impairs insulin signalling through the generation of reactive oxygen species, which abrogate insulin-induced tyrosine autophosphorylation of the insulin receptor. Additional mechanisms have been described as responsible for the inhibition of insulin signalling, including proteasome-mediated degradation of insulin receptor substrate 1/2, phosphatase-mediated dephosphorylation and kinase-mediated serine/threonine phosphorylation of both insulin receptor and insulin receptor substrates. Insulin resistance plays a key role also in the pathogenesis and progression of hypertension-induced target organ damage, like left ventricular hypertrophy, atherosclerosis and chronic kidney disease. Altogether these abnormalities significantly contribute to the increase the risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Physical exercise and antihypertensive drugs contribute to reduce or prevent hypertensive heart disease (HHD). The effect on blood pressure (BP) of both combined therapy is well documented, but not for the left ventricular (LV) function. Aim: A systematic review and meta-analysis was conducted for LV biomarkers analysis regarding to HHD on subjects treated with antihypertensive drugs combined with physical exercise practice. Methods: The search was conducted on the Pubmed, Bireme, Lilacs, Central (Cochrane) and Science direct databases, comprising undetermined period of time, including randomized studies comparing trained and sedentary subjects, both treated with antihypertensive drugs. We analyzed the influence of combined therapy on echocardiogram parameters and BP. A significance level of 5% and 95% CI was considered for all outcomes. Results: Five studies (N = 1738) were included in meta-analysis. Combined therapy decreased significantly LV mass (CI − 21.63 to − 1.81, N = 783) and heart rate (HR; CI − 4.23 to − 1.59, N = 1738), compared to antihypertensive drugs alone. There was a trend to decrease LV mass index (LVMI; CI − 5.57 to 0.71, N = 1674), systolic BP (CI − 2.47 to 1.23, N = 1674) and diastolic BP (CI − 2.16 to 0.28, N = 1674), a trend to increase of ejection fraction (EF; 95% CI − 0.50 to 2.12, N = 783) and LV end-diastolic diameter (CI − 0.85 to 0.92, N = 847) was similar. Conclusion: The antihypertensive therapy combined with physical exercise practice can reduce LV mass and HR. Therefore, combined therapy prescription should be considered for prevention and treatment of LV hypertrophy of hypertensive subjects. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate hemodynamic phenotypes and prevalence of left ventricular hypertrophy in children after coarctation repair with right arm and leg blood pressure difference < 20 mmHg. Secondary objectives were analysis of effects of age at intervention, residual gradient across the descending aorta, and type of correction. Methods: Blood pressure status and left ventricular hypertrophy were diagnosed according to European Society of Hypertension 2016 guidelines. Results: Of 90 patients with a median age 12.5 (8.9–15.8) years, 8.5 (6.0–11.8) years after coarctation repair who were included, 42 (46.7%) were hypertensive. Isolated systolic hypertension dominated among 29 hypertensive patients with uncontrolled or masked hypertension (25 of 29; 86.2%). Of the 48 patients with office normotension, 14.6% (7) had masked hypertension, 8.3% (4) had ambulatory prehypertension, and 54.2% (26) were truly normotensive. Left ventricular hypertrophy was diagnosed in 29 patients (32.2%), including 14 of 42 (33.3%) hypertensive and 15 of 48 (31.3%) normotensive patients. The peak systolic gradient across the descending aorta was greater in hypertensive subjects (33.3 ± 12.7 mmHg) compared with normotensive subjects (25 ± 8.2 mmHg, p = 0.0008). Surgical correction was performed earlier than percutaneous intervention (p < 0.0001) and dominated in 40 of 48 (83.3%) normotensive versus 24 of 42 (57.1%) hypertensive patients (p = 0.006). Conclusions: Arterial hypertension with isolated systolic hypertension as the dominant phenotype and left ventricular hypertrophy are prevalent even after successful coarctation repair. Coarctation correction from the age of 9 years and older was associated with a higher prevalence of hypertension. [ABSTRACT FROM AUTHOR]

Hypertension is a leading cause of cardiovascular mortality and morbidity. The development of left ventricular hypertrophy (LVH) in hypertension is an independent predictor of adverse cardiovascular outcomes. Conversely, regression of LVH is associated with better prognosis. Lowering of blood pressure in patients with hypertension is the unequivocal determinant of regression of LVH. Unless otherwise contraindicated, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are drugs of first choice in patients with essential hypertension with LVH. In this article, we summarise the preclinical and clinical evidence of the last 3 decades that established the preferential use of ACEIs/ARBs in hypertensive heart disease. [ABSTRACT FROM AUTHOR]

Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure. This study was designed to evaluate the influences of long-term xanthine oxidase inhibitor (febuxostat) prescription on left ventricular hypertrophy (LVH), left ventricular (LV) diastolic function, and new-onset heart failure with preserved ejection fraction (HFpEF) in these patients. Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared febuxosatat prescription (n = 96) and non-urate-lowering therapy (n = 192) in patients with hypertensive left ventricular hypertrophy (LVH) and asymptomatic hyperuricemia. With a follow-up of 36 months, febuxostat significantly decreased the level of serum uric acid as well as generated more prominent improvement in LVH and LV diastolic function. Besides, the new-onset symptomatic HFpEF occurred in 2 of 96 patients in febuxostat group and 13 of 192 patients in non-urate-lowering group (P = 0.091). No increased risk for major adverse cardiovascular events in patients prescribed with febuxostat was noted. In conclusion, long-term febuxostat exposure was associated with protective effects in terms of LVH or LV diastolic dysfunction in patients with hypertensive LVH and asymptomatic hyperuricemia. Febuxostat also displayed a trend for reduced risk of new-onset HFpEF in this population. [ABSTRACT FROM AUTHOR]

Background: It is recommended that children with hypertension and loud snoring should be referred for polysomnography. We aimed to compare the frequency of moderate-to-severe obstructive sleep apnea syndrome (OSAS) among snorers with and without hypertension. Thus, it was hypothesized that systolic or diastolic hypertension among children with snoring is a risk factor for moderate-to-severe OSAS. Methods: Data of children with snoring and adenotonsillar hypertrophy and/or obesity referred for polysomnography were retrospectively analyzed. Blood pressure (BP) was measured three times in the morning after polysomnography and percentiles were calculated for the average of the second and third measurement. Association of systolic or diastolic hypertension with moderate-to severe OSAS (apnea-hypopnea index-AHI > 5 episodes/h) adjusted for age and obesity was assessed by logistic regression. Results: Data of 646 children with snoring (median age, 6.5 years; 3–14.9 years; 25.7% obese) were analyzed. Prevalence of systolic or diastolic hypertension was 14.1% and 16.1%, respectively and frequency of AHI > 5 episodes/h was 18.3%. Systolic hypertension was a significant predictor of moderate-to-severe OSAS (OR 1.87; 95% CI 1.10 to 3.17; P = 0.02) after adjustment for age and obesity, but diastolic hypertension was not (OR, 0.96; 0.55 to 1.67; P > 0.05). Odds of AHI > 5 episodes/h prior to considering systolic hypertension was 0.25 and after considering its presence, increased to 0.46 (Bayes' theorem), or for every three children with systolic hypertension and snoring tested, one had AHI > 5 episodes/h. Conclusions: In the context of systolic hypertension and snoring, referral for polysomnography to rule out moderate-to-severe OSAS is a clinically productive practice. [ABSTRACT FROM AUTHOR]

Polygenic risk scores (PRSs) for essential hypertension, calculated from > 900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n ~ 200 for all drugs), we identified a weak, but (after Bonferroni correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic. In addition, we noticed a correlation between high genome-wide PRS and electrocardiographic left ventricular hypertrophy. Finally, using data of the Finnish arm of the LIFE study (n = 346), we found that PRSs for systolic blood pressure were slightly higher in patients with drug-resistant hypertension than in those with drug-controlled hypertension (p = 0.03, not significant after Bonferroni correction). In conclusion, our results indicate that patients with elevated hypertension PRSs may be predisposed to difficult-to-control hypertension and complications thereof. No general association between a high PRS and less efficient drug responsiveness was noticed. [ABSTRACT FROM AUTHOR]

Physical activity is an important component of ideal cardiovascular health. Current guidelines recommend that youth with hypertension participate in competitive sports once hypertensive target organ effects and risks have been assessed and that children with hypertension receive treatment to lower BP below stage 2 thresholds (e.g., < 140/90 mmHg or < 95th percentile + 12 mmHg) before participating in competitive sports. Despite these recommendations, pediatricians and pediatric subspecialists continue to struggle with how best to counsel their patients regarding appropriate forms of physical activity, the impact of exercise on blood pressure, and how best to screen for cardiovascular conditions that place youth at risk for sudden cardiac death. This review provides a summary of our current knowledge regarding the safety and utility of exercise in the management of high blood pressure in youth. We review determinants of blood pressure during exercise, the impact of blood pressure on cardiovascular health and structure, mechanisms for assessing cardiometabolic fitness (e.g., exercise stress test), contraindications to athletic participation, and how best to plan for athletic participation among hypertensive youth. Greater knowledge in these areas may offer clarity to providers faced with the challenge of prescribing exercise recommendations for hypertensive youth. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether early left atrial (LA) dysfunction in hypertension (HTN), with or without left ventricular hypertrophy (LVH), can be detected by cardiovascular magnetic resonance feature tracking (CMR-FT).Methods: Seventy-three HTN patients and 29 healthy controls were retrospectively recruited. HTN patients were divided into the LVH (n = 29) and non-LVH group (n = 44). LA performance was analysed using CMR-FT in 2- and 4-chamber cine images, including LA reservoir function (total ejection fraction [EF], total strain [εs], peak positive strain rate [SRs]), conduit function (passive EF, passive strain [εe], peak early negative strain rate [SRe]) and booster pump function (booster EF, active strain [εa], late peak negative strain rate [SRa]). One-way analysis of variance with post hoc LSD tests, Spearman analysis, receiver operating characteristic curve and intra-class correlation coefficient analysis were applied for statistical analyses.Results: Compared with healthy controls, LA reservoir (LA total EF, εs, SRs) and conduit function (LA passive EF, εe, SRe) were significantly impaired in HTN patients with or without LVH, and these parameters significantly correlated with mitral E/A < 1 (all p < 0.05). However, LA booster pump function was relatively preserved in non-LVH patients, representing an intermediate stage between the LVH group and controls. Among LA deformation parameters, εe showed the highest diagnostic value for differentiation of HTN patients with healthy controls (AUC, 0.82; sensitivity, 80.82%; specificity, 72.41%). Observer reproducibility was good-excellent (ICC, 0.83-0.97) for all CMR-FT derived parameters.Conclusions: CMR-FT is a promising tool for quantification of LA function. LA reservoir and conduit dysfunction might be detected early by CMR-FT in HTN patients before the presence of LVH.Key Points: • CMR-FT is a promising tool in quantifying LA function, including deformation and volumetric parameters. • LA reservoir and conduit dysfunction might be detected early by CMR-FT in HTN patients with or without LVH. • The LA booster pump function was relatively preserved in non-LVH patients. [ABSTRACT FROM AUTHOR]

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study "Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives". This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to examine longitudinal changes in left ventricular (LV) structure and function and evaluate factors associated with LV remodelling in children on chronic haemodialysis. Methods: Retrospective longitudinal study including all children from the start of chronic haemodialysis with two or more m-mode 2D echocardiograms and tissue Doppler studies. Left ventricular mass (LVM) in g/m2.7, geometry and LV function were compared at baseline (dialysis start) with follow-up studies at least 6 months following commencement. Left ventricular hypertrophy (LVH) was defined if greater than 95th percentile as per age-specific centiles. We also defined LVH as indexed LV mass index (LVMI) > 51 g/m2.7 and using LV mass-for-height z-scores greater than the 95th percentile. Biochemical data, interdialytic weight change and blood pressure level were assessed for their association with change in indexed LVM. Results: Twenty-three of the 32 children < 18 years were included (n = 5, < 5 years) with last follow-up study performed following dialysis after a median (IQR) of 21 (10–34) months. The prevalence of LVH reduced significantly (69.6%, (n = 16/23) vs. 39.1% (n = 9/23), P = 0.002); LV geometry improved (13% concentric and 56.5% eccentric vs. 8.7% and 17.4% respectively) with mean ± SD reduction in indexed LVM (50.8 ± 23.1 g/m2.7 vs. 38.6 ± 14.7 g/m2.7, P = 0.002) and LV mass-for-height z-scores (0.67 ± 1.66 vs. − 0.46 ± 1.88, P = 0.002) from baseline to last follow-up respectively. There was no change in systolic function (LV fractional shortening, 37% vs. 38%, P = 0.39) and diastolic function (mean E/E′ 10.8 vs. 9.0, P = 0.09). Multiple regression analysis identified improved systolic BP control (β = 0.41, P = 0.04) as an independent predictor for change in indexed LVM. Conclusions: LV structure and function can improve in children despite long-term chronic intermittent haemodialysis. Cardiovascular health in this population does not always deteriorate but can be stabilised and indeed improved with optimal blood pressure management. [ABSTRACT FROM AUTHOR]

High blood pressure (BP) is becoming a growing health issue even in children and adolescents. Moreover, BP elevation in youth frequently translates into children and adult hypertension contributing to the development of cardiovascular disease. The detection of early markers of vascular damage, potentially leading to overt cardiovascular disease, is important for clinical decisions about if and how to treat hypertension and can be useful in monitoring the effectiveness of the treatment. The purpose of this review is to summarize the actual knowledge about subclinical organ damage (SOD) in hypertensive children and adolescents and its association with cardiovascular disease in children and young adults. Our focus is especially put on left ventricular mass, pulse wave velocity, carotid intima-media thickness and microalbuminuria. We also want to address the scientific evidence about possible regression of SOD and cardiovascular risk with the use of behavioural and specific anti-hypertensive therapy. Indications from current guidelines are critically discussed. [ABSTRACT FROM AUTHOR]