J. Redon

Altered blood pressure during sleep in normotensive subjects with type I diabetes.

This study was designed to examine the circadian pattern of blood pressure in children and young adults with type I diabetes who were completely normotensive by standard criteria. Forty-five patients and the same number of age- and sex-matched control subjects were studied. In diabetic children of 10-14 years of age, the nocturnal fall in systolic and diastolic blood pressures was intact. In diabetics of 15-20 years of age, the fall in systolic blood pressure was blunted; in diabetics of 21-37 years of age, the fall in both systolic and diastolic blood pressures during sleep was blunted. When data from all diabetic subjects were pooled and analyzed in a multiple linear regression model, mean blood pressure during sleep correlated best with urinary albumin excretion (r = 0.60). On the basis of this finding, we subdivided our patients into two groups: a microalbuminuric group (urinary albumin excretion > 30 mg per 24 hours; mean, 160.3 +/- 29.7; n = 11) and a normoalbuminuric group (urinary albumin excretion < 30 mg per 24 hours; mean, 6.6 +/- 6.5; n = 34). Both systolic and diastolic blood pressures during sleep were higher in microalbuminuric (121.1 +/- 3.3 and 69.3 +/- 2.5 mm Hg, respectively) than in normoalbuminuric diabetics (114.2 +/- 1.8 and 60.1 +/- 1.2 mm Hg, p < 0.05) or control subjects (113.3 +/- 1.2 and 60.1 +/- 1.2 mm Hg, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of intracellular pH in the spontaneously hypertensive rat. Role of bicarbonate-dependent transporters.

Previous studies that have evaluated the Na(+)-H+ antiporter in cells from hypertensive subjects were generally performed under conditions in which HCO3-CO2, the physiological buffer system, was absent from the assay media. The objective of this study was to evaluate the activity of the Na(+)-H+ antiporter and that of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchangers in cells assayed in the presence of HCO3-CO2 in the media. Lymphocytes from 6- to 8-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were obtained from the thymus gland and assayed immediately after isolation. The activity of the Na(+)-H+ antiporter after stimulation by cell acidification (pHi approximately 6.4) was similar in SHR and WKY rats (18.67 +/- 1.03 and 16.12 +/- 0.92 mmol H+/L per minute, respectively). Recovery from cell alkalinization was effected by an Na(+)-independent Cl(-)-HCO3- exchanger, with maximal activity at an alkaline pHi (approximately 7.7). The stimulated activity of this Na(+)-independent Cl(-)-HCO3- exchanger was also not different between SHR and WKY cells (2.65 +/- 0.25 and 2.55 +/- 0.32 mmol H+/L per minute, respectively). Acute chloride removal produced a rise in pHi that was Na(+)-dependent and sensitive to 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS) but resistant to ethylisopropylamiloride (EIPA), reflecting the activity of an Na(+)-dependent Cl(-)-HCO3- exchanger. Unlike the Na(+)-H+ exchanger and the Na(+)-independent Cl(-)-HCO3- exchanger, which had their highest activities at extremes of pHi (low pHi, Na(+)-H+ exchanger, and high pHi, Na(+)-independent Cl(-)-HCO3- exchanger), the Na(+)-dependent Cl(-)-HCO3- exchanger had its maximal activity near steady-state pHi (approximately 7.1). No significant differences were found in the stimulated activity of this exchanger between cells from SHR and WKY rats (2.23 +/- 0.26 and 2.50 +/- 0.43 mmol H+/L per minute, respectively). The kinetic properties of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchanger, examined as a function of external Cl-, were also virtually identical in cells from SHR and WKY rats. We conclude that in lymphocytes from SHR and WKY rats, the activity of the two Cl(-)-HCO3- exchangers, like that of the Na(+)-H+ exchanger, is dependent on the prevailing pHi. The Na(+)-dependent Cl(-)-HCO3- exchanger has its highest activity near steady-state pHi, suggesting an important role in the cell defense against intracellular acidosis under physiological conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Secondary Hypertension in Children and Adolescents

Although not all books on hypertension have a section on children and adolescents, there should be one for a number of reasons. To begin with, the diagnosis of hypertension is different from that for adults. Hypertension in children, as defined by casual blood pressure (BP) values, is not well correlated to any particular form of hypertensive target organ damage. No single cutoff point defines hypertension in a pediatrie patient, making identification of childhood hypertension difficult. Physicians have traditionally used population-based percentiles to define pediatrie hypertension. Next, pediatrie hypertension is associated with a broad spectrum of diseases that changes from childhood through adolescence. Definable causes of hypertension are the rule in the early years of life, whereas essential hypertension is more common in adolescence. Consequently, techniques for the evaluation and diagnosis of hypertension differ, at least in part, from those that are used with adult patients.

Ambulatory Blood Pressure Methodology and Norms in Children

Casual blood pressure (BP) measurement is the basis of present knowledge about the risks associated with hypertension (1) and has guided patient management for many years (2). Nevertheless, casual BP is characterized by high variability, and the small number of measurements obtained in medical settings may not necessarily reflect the usual BP of an individual (3). The possibility of carrying out repeated measurements with ambulatory BP monitoring (ABPM) using invasive (4) or noninvasive devices (5) provides more representative values of BP, and permits the observation of the behavior of BP during activity and sleep.

URIC ACID IS ASSOCIATED WITH CARDIOMETABOLIC RISK FACTORS IN OVERWEIGHT AND OBESE CHILDREN AND ADOLESCENTS

Objective: This study examined the association of serum uric acid (UA) with levels of cardiometabolic risk factors in overweight and moderate obese children and adolescents. Design and method: Three hundred and thirty three Caucasians of both sexes (149 females), of European origin, from 5 to 18 years of age (mean age 11.4 2.6) were included. Overweight and obesity were defined based on the extended international body mass index cut-offs. The subjects were divided into 3 groups according to serum UA: <5u200amg/dl nu200a=u200a118 subjects (35%); UA 5-6u200amg/dl nu200a=u200a130 subjects (39%) or UA>6u200amg/dl nu200a=u200a85 subjects (26%). Fasting blood was obtained and uric acid, glucose, insulin, and lipid profile, were measured. Likewise office BP and 24-hour ABPM were assessed. Hyperinsulinemia was defined from norms for pubertal stage. Abnormal fasting lipids were defined from normative data (Daniels et al, 2008). Subjects were qualified as normotensive, high-normal or hypertensive according to the ESH criteria (Lurbe et al, 2016). Results: There were significant differences among groups regarding, BMI, waist, fasting insulin, office SBP and night-time SBP increasing progressively across the serum UA groups. Controlling by age and sex, uric acid was significantly correlated with BMI (ru200a=u200a0.27, pu200a=u200a0.000), waist (ru200a=u200a0.33; pu200a=u200a0.000), birth weight (ru200a=u200a−0.11; pu200a=u200a0.05), office SBP (ru200a=u200a0.21; pu200a=u200a0.000), daytime SBP, (ru200a=u200a0.16; pu200a=u200a0.03), nighttime SBP (ru200a=u200a0.24; pu200a=u200a0.000), insulin (ru200a=u200a0.25; pu200a=u200a0.000), and Log Tryglicerides (ru200a=u200a−0.137; pu200a=u200a0.019). In a multiple regression analysis sex, waist, birth weight, SBP (office, daytime and nighttime), were independent determinants of uric acid when age, BMI, HDL-C and insulin were included (R2u200a=u200a0.29). The prevalence of hyperinsulinemia, low HDL-C, high-normal BP, and hypertension in each UA group are shown in the Figure. Figure. No caption available. Conclusions: In overweight and moderate obese children and adolescents there is a trend toward greater prevalence of cardiometabolic risk factors as the uric acid values rose. The role of hyperuricemia and its association with cardiometabolic risk factors should receive more attention, beginning in early childhood.

DIFFERENCES IN THE PREVALENCE OF BLOOD PRESSURE CONDITIONS USING ESH VS AAP GUIDELINES IN CHILDREN AND ADOLESCENTS

Objective: The objective is to assess differences in the prevalence of blood pressure (BP) conditions according to the European Society of Hypertension (ESH) guidelines (Lurbe, J Hypertens 2016) and the American Academy of Pediatrics (AAP) (Flynn, Pediatrics 2017) in children and adolescents. Design and method: Four thousand two hundred and ninety-six Caucasians of both sexes (1941 females), of European origin, from 5 to 18 years of age (mean age 11.5 3.3) in the absence of antihypertensive treatment were included. Overweight and obesity (nu200a=u200a2243) were defined based on the extended international body mass index cut-offs. Office BP was measured in the non-dominant arm with cuff and bladder size adjusted to upper-arm girth. The three measurements of each office visit were averaged for analysis. Twenty-four-hour ambulatory BP monitoring was performed by using Spacelabs monitor 90207. Subjects were qualified as true normotensive (N), white-coat (WC), masked (M) or sustained hypertensive (HTN) according to the ESH and AAP criteria for office BP, and reference values for 24-hour ambulatory BP (Wühl, J Hypertens 2002). Results: The prevalence of N, WC, M and HTN were significantly different when the ESH or AAP were applied. Overall, the largest differences were observed in the prevalence of WC, which was double when the AAP criteria were used. The differences were larger for boys, older than 13 years of age. The presence of obesity did not reduce the higher prevalence of WC by the AAP criteria. In contrast, M was slightly higher when the ESH criteria were applied. The impact on the prevalence of WC and M is shown in the figure. Figure. No caption available. Conclusions: When applying the AAP criteria, compared with that of the ESH, the main difference is the higher prevalence of WC, especially in boys aged 13 years or older. The consequence is an increment of the HTN work-up in children and adolescents.

[PP.11.28] UNRAVELING THE URIC ACID IN THE CLUSTER OF CARDIOMETABOLIC RISK FACTORS EARLY IN LIFE: A PROSPECTIVE STUDY

Objective: The present prospective research, starting at birth, was undertaken to analyze factors related to the uric acid in children at 5 years old. Design and method: One hundred and fifty four Caucasians of both sexes (77 females), of European origin, born at term were included. After the initial evaluation on the second day of life, infants were followed up and growth pattern prospectively recorded. At five years, office BP measurements were performed and fasting blood sample was obtained to measure glucose, insulin, lipid profile, and uric acid. All subjects were normotensives, no diabetes neither dyslipidemia were present. Results: In this prospective study, uric acid at five years depends positively on the increment of weight from birth (pu200a<u200a0.001) and inversely of the birth weight (pu200a<u200a0.05). Furthermore, uric acid was significantly correlated with current weight (ru200a=u200a0.25; pu200a=u200a0.003), current height (ru200a=u200a0.17; pu200a=u200a0.04), office SBP (ru200a=u200a0.23; pu200a=u200a0005), insulin (ru200a=u200a0.36; pu200a=u200a0.001), and HDL (ru200a=u200a−0.30; pu200a=u200a0.001). In a multiple regression analysis insulin, and HDL cholesterol were independent determinants of uric acid when, sex, current weight, birth weight, SBP, and Log triglycerides were also included (r2u200a=u200a0.23). The weighted impact of uric acid on metabolic parameters and office SBP, adjusted by sex and body weight, are shown in the Table. https://services.aimgroup.it/ASPClient/files/3465/Abstract/669_20170102111446.jpg Figure. No caption available. Conclusions: Uric acid is associated with metabolic parameters independent of office BP. Metabolic status at 5-year-old in children born at term may be influenced by perinatal events and postnatal rapid weight gain with clinical implications that require active intervention to prevent or reverse upward crossing of weight percentiles.

[OP.6A.06] VASCULAR PHENOTYPES BY ASSESSING PERIPHERAL AND CENTRAL BLOOD PRESSURE IN OBESE YOUTH.

Objective: To identify vascular phenotypes across BP conditions in overweight and obese youths, by assessing office (oBP) and central BP (cBP), and pulse pressure amplification. Whether or not 24-hour ambulatory BP monitoring and pulse wave velocity (PWV) add insight to the issue has also been examined. Design and method: White youths of both sexes with overweight or obesity and of European origin, ranging from 8 to 18 years of age, were included. Office BP, cBP, PWV, and 24-hour ABPM were measured. Office BP conditions and “white-coat” HTN were defined as recommend by ESH Guidelines in Children and Adolescents. Subjects were divided into subgroups of “normal” or “high” according to cBP and PP ratio. Results: A total of 593 subjects (mean age, 12.2u200a±u200a2.3 years; 275 females) were included in the study. The largest differences between oSBP and cSBP correspond to the isolated systolic HTN (ISH) group, in which only 25% of subjects have high cBP, in contrast to 50% of the systo-diastolic HTN (SDH) group. In the hypertensive youth two patterns emerged based on cBP and PP ratio. The highest cBP was among the SDH and the highest PP ratio in the ISH group (see Figure). While, 90% of the SDH were confirmed with 24-hour ABPM, 75% of the ISH were white-coat. PWV showed a progressive increment across the groups from NT to SDH. Significant differences were observed only when compared to the NT, but not among all other groups. Figure. No caption available. Conclusions: In overweight and obese hypertensives, ISH is prevalent posing a challenge for the clinician of whether these may therefore be diagnosed and managed as hypertensives. Until prospective studies can give more information, 24-hour ABPM can offer information for making clinical decisions.

CLINICAL PROFILE OF HYPERTENSIVE SUBJECTS NOT CONTROLLED WITH A COMBINATION OF 2 ANTIHYPERTENSIVE DRUGS: PP.33.317

Purpose: Combination therapy is able to produce a more intense BP reduction, thus leading to a better treatment adherence and BP control. However, still a significant proportion of hypertensives remain with values above the goal. The current study aimed to evaluate the clinical profile of hypertensive subjects treated with a combination of 2 antihypertensive drugs whose blood pressure remained above 140/90 mmHg. Patients and Methods: This is an observational, cross-sectional study in a cohort of 816 hypertensive patients attended in primary care centres or referral units. Inclusion criteria were: diagnosis of essential hypertension and treatment with a 2 antihypertensive drug combination (either in a fixed-dose schedule or as a free combination) whose blood pressure remained above or equal 140 and/or 90 mmHg at the time of the visit. Results: Mean age (SD) was 64 (13) years and 39% were women. BMI was 30.1 (5.2) Kg/m2 and waist circumference 102 (12) cm for men and 96 (16) cm for women. Mean systolic and diastolic BP was 147 (17) and 84 (12) mmHg. Additional cardiovascular risk factors were distributed as follows: type 2 diabetes 45%, dislypidemia 75%, smoking habit 25%, and family history of premature cardiovascular disease 18%. Renal disease was present in 36%, coronary heart disease in 27%, previous stroke in 18% and peripheral artery disease in 18%. Diuretic-based combinations (54%) were the most frequently used, either with ARB (34%) or with ACE inhibitors (12%), followed by calcium channel blocker-based combinations (31%), either with ARB (20%) or with ACE inhibitors (6%). 38% of patients received treatment in single pill fixed-dose combination, whereas in the remaining 62% treatment was administered in a 2 pills free combination. Conclusion: Hypertensive patients not controlled with 2 antihypertensive drugs are a group of high cardiovascular risk, with a significant proportion of diabetics or established cardiovascular or renal disease. Most patients still receive this treatment with 2 drugs in a 2 pill free combination, being the diuretic-based combination the most frequently used.

MORBIDITY AND MORTALITY ON COMBINATION VERSUS MONOTHERAPY IN THE SYSTOLIC HYPERTENSION IN EUROPE TRIAL: 2B.02

Objective: The current literature supports the immediate use of combinations of antihypertensive drugs in terms of ease of use and adherence, but the key issue whether combination therapy is more effective than monotherapy in the prevention of cardiovascular complications remains unproven. Design and Method: We analysed the double-blind (median follow-up: 2.0 years) and open follow-up (6.0 years) phases of the Systolic Hypertension in Europe trial. Patients were >60 years with an entry systolic/diastolic blood pressure (BP) of 160–219/<95 mmHg. Antihypertensive treatment started immediately after randomisation in the active-treatment group, but only after completion of the double-blind trial in control patients. Treatment consisted of nitrendipine (10–40 mg/day) with the possible addition of enalapril (5–20 mg/day). We adjusted our analyses for sex, age, history of cardiovascular complications, baseline systolic blood pressure and previous antihypertensive treatment. Results: During the double-blind trial, adding enalapril to nitrendipine (n = 515), compared to the equivalent placebos (n = 559), decreased systolic BP by a further 9.5 mmHg and reduced all cardiovascular events by 51% (P = 0.0035) and heart failure by 66% (P = 0.032) with similar trends for stroke (–51%; P = 0.066) and cardiac events (–44%; P = 0.075). Over the whole duration of follow-up, combination therapy (n = 871), compared to nitrendipine monotherapy (n = 1552) decreased systolic BP by 3.1 mmHg and reduced total mortality (–32%; P = 0.023, Figure), with similar trends for all cardiovascular events (–23%; P = 0.081) and stroke (–42%; P = 0.054). Conclusions: Congruent with the stronger blood pressure reduction, our results suggest that combination therapy with nitrendipine plus enalapril might improve outcome over and beyond the benefits seen with nitrendipine monotherapy. Figure 1. No caption available.