Systolic Blood Pressure, Cardiovascular Health, and Neurocognitive in Adolescents.

BACKGROUND: We studied whether increased systolic blood pressure (SBP), as determined by auscultatory SBP, ambulatory SBP, and the number of cardiovascular health risk indicators, are associated with neurocognition in adolescents. METHODS: This cross-sectional study included 365 adolescents (mean age, 15.5 years) from 6 academic medical centers in the United States. The sample was 59.5% male, 52.6% White, with 23.9% of the caregivers having less than or equal to a high school degree. Primary exposures included the following: auscultatory SBP, ambulatory SBP, and the number of cardiovascular risk factors. Neurocognitive outcomes comprised nonverbal IQ, attention, and parent ratings of executive functions. RESULTS: After examining the models for the effects of targeted covariates (eg, maternal education), higher auscultatory SBP was associated with lower nonverbal IQ (ß=-1.39; P<0.001) and verbal attention (ß=-2.39; P<0.05); higher ambulatory 24 hours. SBP (ß=-21.39; P<0.05) and wake SBP (ß=-21.62; P<0.05) were related to verbal attention; and all 3 ambulatory blood pressure measures were related to sustained attention accounting for small to medium amounts of variance (adjusted R2=0.08-0.09). Higher ambulatory blood pressure sleep SBP also was significantly associated with parent ratings of behavior regulation (ß=12.61; P<0.05). These associations remained stable after a sensitivity analysis removed cases with hypertension. Number of cardiovascular risk factors performed similarly, with more risk factors being associated with lower nonverbal IQ (ß=-1.35; P<0.01), verbal attention (ß=-1.23; P<0.01), and all parent ratings of executive functions. CONCLUSIONS: Elevated SBP, even below the hypertension range, and general cardiovascular health are associated with neurocognitive outcomes in adolescents. How these findings might guide clinical care is worthy of additional study.

A Multi-Omics Approach to Defining Target Organ Injury in Youth with Primary Hypertension.

BACKGROUND: Primary hypertension in childhood tracks into adulthood and may be associated with increased cardiovascular risk. Studies conducted in children and adolescents provide an opportunity to explore the early cardiovascular target organ injury (CV-TOI) in a population free from many of the comorbid cardiovascular disease risk factors that confound studies in adults. METHODS: Youths (n=132, mean age 15.8 years) were stratified by blood pressure (BP) as low, elevated, and high-BP and by left ventricular mass index (LVMI) as low- and high-LVMI. Systemic circulating RNA, miRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques. RESULTS: VASH1 gene expression was elevated in youths with high-BP with and without high-LVMI. VASH1 expression levels positively correlated with systolic BP (r=0.3143, p=0.0034). The expression of hsa-miR-335-5p, one of the VASH1-predicted miRNAs, was downregulated in high-BP with high-LVMI youths and was inversely correlated with systolic BP (r=-0.1891, p=0.0489). GSE1 hypermethylation, circulating PROZ upregulation (log2FC=0.61, p=0.0049 and log2FC=0.62, p=0.0064), and SOD3 downregulation (log2FC=-0.70, p=0.0042 and log2FC=-0.64, p=0.010) were observed in youths with elevated BP and high-BP with high-LVMI. Comparing the transcriptomic and proteomic profiles revealed elevated HYAL1 levels in youths displaying high-BP and high-LVMI. CONCLUSIONS: The findings are compatible with a novel blood pressure-associated mechanism that may occur through impaired angiogenesis and extracellular matrix degradation through dysregulation of Vasohibin-1 and Hyaluronidase1 was identified as a possible mediator of CV-TOI in youth with high-BP and suggests strategies for ameliorating TOI in adult-onset primary hypertension.

Body mass index in pediatric kidney transplant selection criteria.

BACKGROUND: Obesity is associated with increased complications, rejection, and graft loss after kidney transplantation in adult and pediatric recipients. Elevated body mass index (BMI) is a common contraindication to transplant at adult kidney transplant programs; however, there is no data on such limitations for pediatric patients. METHODS: Between October and December 2022, we conducted a survey of Pediatric Nephrology Research Consortium centers assessing the use of BMI in pediatric kidney transplant evaluation. Centers reporting utilization of BMI cutoffs were invited to submit patient-level data on children declined for active transplant listing due to BMI. RESULTS: Thirty-nine centers responded to the survey (42% response rate); 51% include BMI in their written listing criteria, with a median BMI "cutoff" of 39 kg/m2 (range 30-50 kg/m2). Between January 1, 2016, and December 31, 2021, 30 children at 15 transplant centers were declined for listing status due to BMI. Patient-level data was provided for 19 children (63%) who were denied active listing status; median BMI was 42 kg/m2 (range 35.8-49.4 kg/m2) and 84% were on dialysis. One year after evaluation, seven patients (37%) had proceeded to active wait list status. Eight (42%) remained in inactive status and four (21%) were unlisted; ten of these 12 patients (83%) were on dialysis. CONCLUSIONS: The use of BMI in pediatric kidney transplant evaluation and listing varies among centers, but BMI limits access to transplant for some children. More information is needed on the outcomes of obese pediatric kidney candidates who are and are not transplanted, to guide development of national and international consensus.

Medication fill duration in pediatric hypertension: adherence, blood pressure control, and disparities.

BACKGROUND: Medication nonadherence is a barrier to hypertension control. The Centers for Disease Control and Prevention recommends prescribing 90-day fills for maintenance medications yet antihypertensives are often dispensed as 30-day fills. Our objectives were to examine how often patients receive 30-day supplies of medication despite prescriptions for longer duration and to examine the effect of medication fill duration on adherence and hypertension control. METHODS: We conducted a retrospective cohort study of pediatric patients with hypertension over a 3-year period. For each patient, days prescribed per fill were compared to days dispensed per fill using pharmacy reports and insurance claim data. Proportion of Days Covered (PDC) was calculated to estimate adherence. Hypertension control was determined by provider assessment of control and blood pressure measurement at the final visit. RESULTS: Final cohort included 449 patients. A total of 70% had at least one prescription for ≥ 90 days but only 37% had at least one dispense for ≥ 90 days. There was no difference in the likelihood of being prescribed a 90-day fill by insurance type (public vs. private); however, patients with public insurance were less likely to be dispensed a 90-day fill (OR = 0.068, p < 0.001). Patients who received 90-day fills had better adherence (median PDC 77.5% vs. 58.1%, p < 0.001) and were more likely to have hypertension control based on provider assessment. CONCLUSIONS: Longer fill duration is associated with improved adherence and hypertension control. Patients with public insurance are markedly less likely to be dispensed 90-day fills, a modifiable barrier to improving adherence.

Ambulatory Blood Pressure and Number of Subclinical Target Organ Injury Markers in Youth: The SHIP AHOY Study.

Background: Hypertension in adolescence is associated with subclinical target organ injury (TOI). We aimed to determine whether different blood pressure (BP) thresholds were associated with increasing number of TOI markers in healthy adolescents. Methods: 244 participants (mean age 15.5±1.8 years, 60.1% male) were studied. Participants were divided based on both systolic clinic and ambulatory BP (ABP), into low- (<75 th percentile), mid- (75 th -90 th percentile) and high-risk (>90 th percentile) groups. TOI assessments included left ventricular mass, systolic and diastolic function, and vascular stiffness. The number of TOI markers for each participant was calculated. A multivariable general linear model was constructed to evaluate the association of different participant characteristics with higher numbers of TOI markers. Results: 47.5% of participants had at least one TOI marker: 31.2% had one, 11.9% two, 3.7% three, and 0.8% four. The number of TOI markers increased according to the BP risk groups: the percentage of participants with more than one TOI in the low-, mid-, and high groups based on clinic BP was 6.7%, 19.1%, and 21.8% (p=0.02), and based on ABP was 9.6%, 15.8%, and 32.2% (p<0.001). In a multivariable regression analysis, both clinic BP percentile and ambulatory SBP index were independently associated with the number of TOI markers. When both clinic and ABP were included in the model, only the ambulatory SBP index was significantly associated with the number of markers. Conclusion: High SBP, especially when assessed by ABPM, was associated with an increasing number of subclinical cardiovascular injury markers in adolescents.

Longitudinal changes of health-related quality of life in childhood chronic kidney disease.

BACKGROUND: Few longitudinal studies have evaluated the impact of chronic kidney disease (CKD) duration on health-related quality of life (HRQOL). The study's aim was to determine how HRQOL changes over time in childhood CKD. METHODS: Study participants were children in the chronic kidney disease in children (CKiD) cohort who completed the pediatric quality of life inventory (PedsQL) on three or more occasions over the course of two or more years. Generalized gamma (GG) mixed-effects models were applied to assess the effect of CKD duration on HRQOL while controlling for selected covariates. RESULTS: A total of 692 children (median age = 11.2) with a median of 8.3 years duration of CKD were evaluated. All subjects had a GFR greater than 15 ml/min/1.73 m2. GG models with child self-report PedsQL data indicated that longer CKD duration was associated with improved total HRQOL and the 4 domains of HRQOL. GG models with parent-proxy PedsQL data indicated that longer duration was associated with better emotional but worse school HRQOL. Increasing trajectories of child self-report HRQOL were observed in the majority of subjects, while parents less frequently reported increasing trajectories of HRQOL. There was no significant relationship between total HRQOL and time-varying GFR. CONCLUSIONS: Longer duration of the disease is associated with improved HRQOL on child self-report scales; however, parent-proxy results were less likely to demonstrate any significant change over time. This divergence could be due to greater optimism and accommodation of CKD in children. Clinicians can use these data to better understand the needs of pediatric CKD patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

School-Based Telemedicine for Hypertension Management in Urban Adolescents.

PURPOSE: The aim of this study is to determine if hypertensive adolescents from impoverished neighborhoods in Rochester, New York have improved blood pressure (BP) control with the use of school-based telemedicine. METHODS: Adolescents receiving antihypertensive medication had monthly study telemedicine visits at school. BP was measured by a telehealth clinical assistant (CTA) at the school using standard procedures, followed in real time by a teleconferencing visit with the study physician. RESULTS: Six participants were enrolled, and all completed school-based telemedicine visits prior to school closure due to the SARS-CoV-2 pandemic. Mean systolic and diastolic BP at baseline were 139 ± 5 and 75 ± 8 mmHg. All six participants had significant improvement in their blood pressure (final school mean BPs, 127 ± 4 and 67 ± 5 mmHg; systolic, baseline vs. final, p = .003). DISCUSSION: In this pilot study, adolescents with very high levels of neighborhood disadvantage had consistent adherence with school-based telemedicine and significant improvement in hypertension (HTN) control.

Case report and review of the literature: Successful transition from acute continuous veno-venous hemodiafiltration therapy to chronic peritoneal dialysis in a chronically ventilated child with hypoplastic left heart syndrome following fontan.

Fontan palliation depends on low pulmonary vascular resistance in order to maintain pulmonary blood flow and adequate oxygenation. This physiology results in higher central venous pressures with limited renal perfusion pressure and cardiac output. Positive pressure ventilation with mechanical ventilation increases intrathoracic pressure and raises central venous pressure and can further limit pulmonary and renal perfusion. Fluid removal with intermittent hemodialysis can be challenging in Fontan patients and can cause intolerable hypotension, however the increased abdominal filling pressures during peritoneal dialysis dwells can exacerbate systemic venous hypertension seen in Fontan patients and threaten adequate pulmonary blood flow and cardiac output. Successful transition to peritoneal dialysis in a chronically ventilated patient with hypoplastic left heart syndrome, end-stage renal disease and Fontan physiology has not been described. We present details outlining the successful transition across multiple modalities of renal replacement therapy to assist other teams faced with similar challenges in chronically ventilated Fontan patients with end-stage renal disease.

Blood pressure in children with sickle cell disease is higher than in the general pediatric population.

BACKGROUND: Sickle cell disease (SCD) is associated with an increased risk of cardiovascular disease that may be due to a variety of possible risk factors, including abnormal blood pressure. Blood pressure (BP) of children and adolescents with SCD has been reported to be lower compared to the BP of the general pediatric population. METHODS: To confirm this prior observation, we compared reference BP values for children with SCD with reference BP values of the general pediatric population. We hypothesized that children with SCD do not have lower BPs than children without SCD. RESULTS: Systolic BP differed for both males and females, over the different age groups between pediatric subjects with and without SCD. Systolic BP was higher in children with SCD, in both obese and non-obese populations. Diastolic BP did not differ between the groups. CONCLUSIONS: Our analysis demonstrated that systolic BP values are indeed higher in children with SCD than in the general pediatric population. This finding is consistent with the most recent literature showing abnormal BP patterns in the SCD pediatric population utilizing 24-hour BP monitoring devices. This is an important step for recognizing abnormal BP as a risk factor for cardio- and neurovascular events in SCD.

Association of Blood Pressure-Related Increase in Vascular Stiffness on Other Measures of Target Organ Damage in Youth.

BACKGROUND: Hypertension-related increased arterial stiffness predicts development of target organ damage (TOD) and cardiovascular disease. We hypothesized that blood pressure (BP)-related increased arterial stiffness is present in youth with elevated BP and is associated with TOD. METHODS: Participants were stratified by systolic BP into low- (systolic BP <75th percentile, n=155), mid- (systolic BP ≥80th and <90th percentile, n=88), and high-risk BP categories (≥90th percentile, n=139), based on age-, sex- and height-specific pediatric BP cut points. Clinic BP, 24-hour ambulatory BP monitoring, anthropometrics, and laboratory data were obtained. Arterial stiffness measures included carotid-femoral pulse wave velocity and aortic stiffness. Left ventricular mass index, left ventricular systolic and diastolic function, and urine albumin/creatinine were collected. ANOVA with Bonferroni correction was used to evaluate differences in cardiovascular risk factors, pulse wave velocity, and cardiac function across groups. General linear models were used to examine factors associated with arterial stiffness and to determine whether arterial stiffness is associated with TOD after accounting for BP. RESULTS: Pulse wave velocity increased across groups. Aortic distensibility, distensibility coefficient, and compliance were greater in low than in the mid or high group. Significant determinants of arterial stiffness were sex, age, adiposity, BP, and LDL (low-density lipoprotein) cholesterol. Pulse wave velocity and aortic compliance were significantly associated with TOD (systolic and diastolic cardiac function and urine albumin/creatinine ratio) after controlling for BP. CONCLUSIONS: Higher arterial stiffness is associated with elevated BP and TOD in youth emphasizing the need for primary prevention of cardiovascular disease.

Cardiovascular Risk Factors and Target Organ Damage in Adolescents: The SHIP AHOY Study.

BACKGROUND: Development of cardiovascular disease in adults has been directly linked to an adverse metabolic phenotype. While there is evidence that development of these risk factors in childhood persists into adulthood and the development of cardiovascular disease, less is known about whether these risk factors are associated with target organ damage during adolescence. METHODS: We collected data from 379 adolescents (mean age 15.5, 60% male) with blood pressure between the 75th and 95th percentile to determine if there is a metabolic phenotype that predicts cardiovascular changes (left ventricular mass, systolic and diastolic function, pulse wave velocity, and renal function). We determined the number of risk factors for cardiovascular disease (hypertension, dyslipidemia, obesity, and insulin resistance) present in each participant. Generalized linear models were constructed to determine if the number of cardiovascular risk factors (CVRFs) were associated with measures of target organ damage. RESULTS: The number of CVRFs present were associated with statistically significant differences in increased left ventricular mass index, increased pulse wave velocity, decreased peak longitudinal strain, urine albumin to creatine ratio and echocardiographic parameters of diastolic dysfunction. Generalized linear models showed that dyslipidemia and insulin resistance were independently associated with markers of diastolic dysfunction (P ≤ .05) while increased blood pressure was associated with all makers of target organ damage (P ≤ .03). CONCLUSIONS: These data suggest the of the number of CVRFs present is independently associated with early changes in markers of target organ damage during adolescence.

White Coat Hypertension Persistence in Children and Adolescents: The Pediatric Nephrology Research Consortium Study.

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM. STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We used multivariable generalized linear mixed effect models to estimate the association of baseline characteristics with abnormal ABPM phenotype progression. RESULTS: Eighty-nine patients met the inclusion criteria (median age, 13.9 years; 78% male). Median interval time between ABPM measurements was 14 months. On follow-up ABPM, 61% progressed to an abnormal ABPM phenotype (23% ambulatory hypertension, 38% ambulatory prehypertension). Individuals age 12-17 years and those with stable white coat hypertension had greater proportions progressing to either prehypertension or ambulatory hypertension. In the multivariable models, baseline wake systolic BP index ≥0.9 was significantly associated with higher odds of progressing to ambulatory hypertension (OR 3.07, 95% CI 1.02-9.23). CONCLUSIONS: The majority of the patients with white coat hypertension progressed to an abnormal ABPM phenotype. This study supports the 2017 American Academy of Pediatrics Clinical Practice Guideline's recommendation for follow-up of ABPM in patients with white coat hypertension.

Overview of the findings and advances in the neurocognitive and psychosocial functioning of mild to moderate pediatric CKD: perspectives from the Chronic Kidney Disease in Children (CKiD) cohort study.

The Chronic Kidney Disease in Children (CKiD) prospective cohort study was designed to address the neurocognitive, growth, cardiovascular, and disease progression of children and adolescents with mild to moderate CKD. The study has had continuous funding from NIDDK for 17 years and has contributed significant advances in pediatric CKD. The goals of this educational review are threefold: (1) to provide an overview of the neurocognitive and psychosocial studies from CKiD to date; (2) to provide best practice recommendations for those working with the neurocognitive and psychosocial aspects of pediatric CKD based on CKiD findings; and (3) to help chart future goals and directives for both research and clinical practice. This collection of 22 empirical studies has produced a number of key findings for children and adolescents with mild to moderate CKD. While various studies suggest a relatively positive presentation for this population as a whole, without evidence of significant impairment or deterioration, findings do indicate the presence of neurocognitive dysfunction, emotional-behavioral difficulties, and lower quality of life for many children with CKD. These findings support the promotion of best practices that are accompanied by additional future clinical and research initiatives with this patient population.

The Effect of a Short Course of Tocolytic Indomethacin on Urinary Biomarkers in Premature Infants.

OBJECTIVE: The aim of this study was to determine the effects of a 2-day prenatal course of indomethacin on the premature kidney as reflected by serum creatinine and urinary biomarkers. STUDY DESIGN: Urine of infants ≤32 weeks was collected for the first 14 days and analyzed for cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, ß2 microglobulin, epidermal growth factor, uromodulin, and microalbumin. Bivariate analysis compared serum creatinine and biomarkers of exposed (INDO) and unexposed (CONT) subjects. RESULTS: Fifty-seven infants (35 CONT and 22 INDO) were studied. The cohorts were similar in gestational age, birthweight, race, gender, nephrotoxic medication exposure, and Apgar's scores. CONT had more dopamine exposure and included more pre-eclamptic mothers (p = 0.005). No difference in creatinine-based acute kidney injury or the log transformed mean, maximum, and minimum values of urinary biomarkers was detected. CONCLUSION: Our findings suggest that a short course of tocolytic indomethacin does not result in neonatal acute kidney injury. KEY POINTS: · A short prenatal course of indomethacin does not result in neonatal acute kidney injury (AKI).. · Urinary EGF might have a promising role as a more sensitive biomarker for early detection of AKI in premature infants..

Pediatric and Adult Ambulatory Blood Pressure Thresholds and Blood Pressure Load as Predictors of Left Ventricular Hypertrophy in Adolescents.

[Figure: see text].

Magnetic Resonance Imaging in Childhood Primary Hypertension: Potential in the Study of Cognitive Outcomes.

Primary hypertension in youth and young adulthood is associated with decreased neurocognitive test performance both in midlife and during youth itself, leading to concern of subsequent cognitive decline and dementia in later life. The early vascular effects of hypertension in youth are likely involved in the pathogenesis of hypertensive target organ damage to the brain, but the potential impact of antihypertensive treatment from youth on subsequent cognitive health is not known. This review will highlight the need to answer the question of whether treatment of hypertension from early in life would slow cognitive decline in adulthood, and will then outline, for the nonneurologist, magnetic resonance imaging techniques potentially useful in the study of the pathogenesis of decreased cognition in hypertensive youth and for use as potential biomarkers for early antihypertensive treatment interventions.

The Similarities and Differences Between Glomerular vs. Non-glomerular Diagnoses on Intelligence and Executive Functions in Pediatric Chronic Kidney Disease: A Brief Report.

Pediatric chronic kidney disease (CKD) appears to be a heterogeneous group of conditions, but this heterogeneity has not been explored with respect to its impact on neurocognitive functioning. This study investigated the neurocognitive functioning of those with glomerular (G) vs. non-glomerular (NG) diagnoses. Data from the North American CKiD Study were employed and the current study included 1,003 children and adolescents with mild to moderate CKD. The G Group included 260 participants (median age = 14.7 years) and the NG Group included 743 individuals (median age = 9.0 years). Neurocognitive measures assessed IQ, inhibitory control, attention regulation, problem solving, working memory, and overall executive functioning. Data from all visits were included in the linear mixed model analyses. After adjusting for sociodemographic and CKD-related covariates, results indicated no differences between the diagnostic groups on measures of IQ, problem solving, working memory, and attention regulation. There was a trend for the G group to receive better parent ratings on their overall executive functions (p < 0.07), with a small effect size being present. Additionally, there was a significant G group X hypertension interaction (p < 0.003) for inhibitory control, indicating that those with both a G diagnosis and hypertension performed more poorly than the NG group with hypertension. These findings suggest that the separation of G vs. NG CKD produced minimal, but specific group differences were observed. Ongoing examination of the heterogeneity of pediatric CKD on neurocognition, perhaps at a different time point in disease progression or using a different model, appears warranted.

Hypertension and childhood stroke.

Cerebrovascular disease (stroke) is one of the ten leading causes of death in children and adolescents. Multiple etiologies, from arteriopathies to prothrombic states, can cause stroke in youth. In adult stroke, hypertension has been shown to be the single most important modifiable risk factor. Although hypertension has not been strongly identified as a risk factor in childhood stroke to date, there is preliminary evidence that suggests that hypertension may also be associated with stroke in children. In this review, we summarize the literature that may link hypertension to stroke in the young. We have identified a series of barriers and limitations in the fields of pediatric hypertension and pediatric neurology that might explain why hypertension has been overlooked in childhood stroke. We suggest that hypertension may be a relevant risk factor that, alone or in combination with other multiple factors, contributes to the development of stroke in children. Currently, there are no consensus guidelines for the management of post-stroke hypertension in children. Thus, we recommend that blood pressure be assessed carefully in every child presenting with acute stroke in order to better understand the effects of hypertension in the development and the outcome of childhood stroke. We suggest a treatment algorithm to help practitioners manage hypertension after a stroke.

Subclinical Systolic and Diastolic Dysfunction Is Evident in Youth With Elevated Blood Pressure.

Hypertension is associated with cardiovascular events in adults. Subclinical changes to left ventricular strain and diastolic function have been found before development of decreased left ventricular ejection fraction and cardiovascular events. Our objective was to study effects of blood pressure (BP) on ventricular function in youth across the BP spectrum. Vital signs and labs were obtained in 346 participants aged 11 to 19 years who had BP categorized as low-risk (N=144; systolic BP <75th percentile), mid-risk (N=83; systolic BP ≥80th and <90th percentile), and high-risk (N=119; systolic BP ≥90th percentile). Echocardiography was performed to assess left ventricular strain and diastolic function. Differences between groups were analyzed by ANOVA. General linear models were constructed to determine independent predictors of systolic and diastolic function. Mid-risk and high-risk participants had greater adiposity and more adverse metabolic labs (lower HDL [high-density lipoprotein], higher glucose, and higher insulin) than the low-risk group. Mid-risk and high-risk participants had significantly lower left ventricular ejection fraction and peak global longitudinal strain than the low-risk group (both P≤0.05). The E/e' ratio was higher in the high-risk group versus the low-risk and mid-risk groups, and the e'/a' ratio was lower in the high-risk versus the low-risk group (both P≤0.05). BP and adiposity were statistically significant determinants of left ventricular systolic and diastolic function. Subclinical changes in left ventricular systolic and diastolic function can be detected even at BP levels below the hypertensive range as currently defined.