bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-25-4: HIGHER URINARY ANGIOTENSIN CONVERTING ENZYME ACTIVITY IS OBSERVED IN BRAZILIAN CHILDREN AND ADOLESCENTS WITH DYSLIPIDEMIA
Authors: Cruz Nayara Azinheira Nobrega , Oliveira Lilian Caroline Goncalves de , Mill Jose Geraldo , Casarini Dulce Elena 
Published: January 2023

Angiotensin converting enzyme (ACE) is upregulated in patients with hyperlipidemia and atherosclerosis and contributes to oxidation and accumulation of low-density lipoproteins in blood vessels. Blockage of dyslipidemia and ACE have a synergic effect preventing or ameliorating cardiovascular disease.

Objective:
Investigate whether ACE activity is modulated in childhood dyslipidemia and can be associated with high cardiovascular risk profile.

Design and methods:
a cross-sectional study with 360 individuals (190 boys and 170 girls) aged from 6 to 19 year (mean 11.6) was performed. Anthropometric measurements, blood pressure assessment and fasting lipid concentrations were evaluated. Participants were divided according to the levels of each lipoprotein (Total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, and non-HDL) into three groups: normolipidemic, borderline and dyslipidemic. Reference values were according to American Academy of Pediatrics and Brazilian Pediatric Society. ACE activity in urine was measured with the fluorogenic substrates Z-Phe-His-Leu-OH (Z-FHL) and hippuryl-His-Leu-OH (h-HL). ACE activity ratio to infer N-domain activity was calculated (Z-FHL/h-HL).

Results:
Dyslipidemic levels of HDL-C, TG and LDL-C were observed in 23%, 9% and 3% of the participants, respectively. These clinical alterations were more frequent in obese children (Chi-square, p < 0.001). ACE activity measured with Z-FHL was higher in the groups with borderline and dyslipidemic values of HDL-C than in normolipidemic group (0.077 vs 0.070 vs 0.037 nmol/min/mg of creatinine, p = 0.01). The ratio of ACE activity was augmented in HDL-C borderline group when compared to HDL-C normolipidemic group (5.06 vs 2.39, p < 0.01) and in LDL-C dyslipidemic group than in LDL-C borderline and LDL-C normolipidemic groups (8.66 vs 1.84 vs 2.88, p = 0.02). Additionally, volunteers with normal levels of TG presented lower diastolic blood pressure (DBP) mmHg (p = 0.02), percentile of DBP (p < 0.01), and percentile of systolic blood pressure (SBP) (p < 0.01) than volunteers with borderline and dyslipidemic levels of TG. Also, increased DBP mmHg was observed in borderline and dyslipidemic HDL-C groups when compared to normolipidic HDL-C group.

Conclusion:
ACE presented a cross-link with dyslipidemia in childhood and adolescence, as hypertriglyceridemia, HDL-C deficiency and high LDL-C were related to higher ACE activity (mainly N-domain able to inactivate angiotensin 1–7, a vasodilator peptide). ACE upregulation, dyslipidemia and obesity are known to activate molecular mechanism contributing to high cardiovascular risk profile, in agreement, impairment in lipoprotein levels was associated with higher blood pressure. This is relevant evidence that ACE modulation can contribute to higher risk of hypertension and other cardiometabolic alterations still in childhood and adolescence.
S-27-5: DELETION OF AT1A RECEPTORS IN THE PROXIMAL TUBULES AUGMENTS NATRIURETIC RESPONSE TO ATRIAL NATRIURETIC PEPTIDE VIA NPR/CGMP/NO SIGNALING
Authors: Li Xiao C , Wang Chih Hong , Hassan Rumana , Leite Ana Paula Oliveira , Sato Akemi , Dugas Courtney , Sato Ryosuke , Zhuo Jia L 
Published: January 2023

Objective:
The proximal tubules of the kidney play a critical role in maintaining normal body salt and fluid balance and blood pressure homeostasis in part by interactions between two key vasoactive hormone receptors. In the proximal tubules, angiotensin II (Ang II) binds and activate AT1a receptors to stimulate proximal tubule Na+ reabsorption, whereas atrial natriuretic peptide (ANP) binds and activates NPRA receptors to inhibit Ang II-induced proximal tubule Na+ reabsorption. These two vasoactive systems play important counteracting roles in the proximal tubules to control proximal tubule Na+ reabsorption in the kidney and maintain blood pressure homeostasis. However, it is not known whether the hypotensive and natriuretic responses to ANP may be augmented by deletion of AT1 (AT1a) receptors selectively in the proximal tubules of the kidney.

Design and Methods:
The present study used a novel mouse model with proximal tubule-specific knockout of AT1a receptors in the kidney, PT-Agtr1a
-/-, to test the hypothesis that deletion of AT1a receptors selectively in the proximal tubules indeed augments the hypotensive and natriuretic responses to ANP. Four groups (n = 9–12 per group) of adult male wild-type and PT-Agtr1a
-/- mice were infused without (served as time controls) or with ANP via osmotic minipump (10 ng/min, i.p.) continuously for 2 weeks.

Results:
Basal blood pressure was about 16 ± 3 mmHg lower (P < 0.01), fractional proximal tubule Na+ reabsorption was significantly lower (P < 0.05), whereas 24 h urinary Na+ excretion was significantly higher in PT-Agtr1a
-/- mice (P < 0.01), compared with age-matched wild-type mice. ANP infusion significantly decreased blood pressure and increased the natriuretic response in PT-Agtr1a
-/- mice further by inhibiting proximal tubule Na+ reabsorption, compared with wild-type controls (P < 0.01). The augmented hypotensive and natriuretic responses to ANP infusion in PT-Agtr1a
-/- mice was associated with increased plasma and kidney cGMP levels (P < 0.01), kidney cortical NPRA and NPRC mRNA expression (P < 0.05), total endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS proteins (P < 0.01), and urinary nitric oxide (NO) excretion (P < 0.01), respectively.

Conclusions:
Taken together, the results of the present study provide further new insights into the important physiological roles for intratubular Ang II/AT1a and ANP/NPRA in the proximal tubules to regulate proximal tubule Na+ reabsorption and help maintain blood pressure homeostasis. Supported by 2R01DK067299-10A1, 2R01DK102429-03A1, and 1 R01DK123144-01.
S-28-1: CARDIOVASCULAR OUTCOMES IN ADULTS WITH HYPERTENSION WITH EVENING VERSUS MORNING DOSING OF USUAL ANTIHYPERTENSIVES IN THE UK. THE TIME STUDY
Authors: MacDonald Thomas MacLennal , Mackenzie Isla Shelah , Rogers Amy , Poulter Neil R , Williams Bryan , Brown Morris J , Webb David J , Ford Ian , Rorie David , Grieve Kerr , Pigazzani Fillippo , Rothwell Peter M , Young Robin , McConnachie Alex , Lang Chim C 
Published: January 2023

Background:
Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods:
The TIME study is a prospective, pragmatic, decentralised, parallel group study in the UK, that recruited adults with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned 1 to 1, without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning, 0600 to 1000 h, or in the evening, 2000 to 0000 h.. Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non fatal myocardial infarction or non fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention to treat population i.e. all participants randomly assigned to a treatment group.

Findings:
Between Dec 17, 2011, and June 5, 2018, 24610 individuals were screened and 21104 were randomly assigned 10503 to evening and 10601 to morning dosing groups. Mean age at study entry was 65·1 years, SD 9·3, 12136 or 57·5 percent participants were men; 8968, 90·5 percent were White, and 2725 or 13·0 percent had a previous cardiovascular disease. By the end of study follow up on March 31, 2021, median follow up was 5·2 years, IQR 4·9, 5·7, 529 of 10503 participants assigned to evening treatment and 318 of 10601 assigned to morning treatment had withdrawn from all follow up. A primary endpoint event occurred in 362 participants assigned to evening treatment that is 0·69 events per 100 patient years and 390 assigned to morning treatment that is 0·72 events per 100 patient years, unadjusted hazard ratio 0·95, 95percent CI 0·83 to 1·10, p 0·53. No safety concerns were identified. An analysis of outcome by adherence to dosing time will be presented at the meeting.
Interpretation Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects.
Funding British Heart Foundation and the British and Irish Hypertension Society.
S-33-3: EVALUATING THE PREVALENCE, AWARENESS, AND CONTROL OF HYPERTENSION: A COMMUNITY, BASED CROSS SECTIONAL STUDY
Authors: Elamin Maha Ismail , Hassan Dina Ahmed , Elamin Marwa Ismail , Beheri Hind Mamoun , Alall Asma Abd , Fahal Naema Ahmed , Medani Safa Ahmed , Musa Azza Basheir , Ali Ibtisam Ahmed 
Published: January 2023

Objective:
The main objectives of our screening survey is to detect the prevalence, control, awareness and risk factors of hypertension

Design and method:
This cross-sectional screening survey was conducted among 23168 adults, during the May Measurement Month 2018 campaign in six states. Volunteers ≧ 18 years were recruited through opportunistic sampling. Each participant had three blood pressure measurements and completed a questionnaire on demographic and medical history. Hypertensive patients were defined as those having systolic BP ≧ 130mmHg or diastolic BP ≧ 80 mmHg, or taking antihypertensive medication, control of hypertension was defined a systolic BP ≦140 mmHg and a diastolic BP ≦ 90 mmHg.

Results:
The overall prevalence of hypertension was 25.9% among the study participants (14.8% for males and 11.1% for females). The majority of identified hypertensive participants (74.1%) had no previous history of known hypertension. Overall 63.0% were on treatment and 35.6 % had controlled blood pressure. In the multivariable regression model, factors associated with increased awareness of having hypertension included female sex (OR 1.37 95% CI 1.12: 1.69), older age > 60 years (OR 1.81 95%, CI 1.36: 2.40), frequently measured their BP (OR 21.3 95% CI 15.3: 29.7), and presence of comorbidities (P < 0.001), Compared to individuals with a normal BMI, overweight participants were more likely to have hypertension (OR 1.63, 95% CI 1.48: 1.79) and more likely to have the disease uncontrolled (OR1.47, 95% 1.33: 1.63). Diabetic patients also had less BP control, while a history of myocardial infarction or stroke did not influence the rates of BP control among hypertensive subjects.

Conclusion:
Our study suggests that the prevalence of hypertension is increasing. Our data also demonstrated a striking lack of awareness of the disease and alarming levels of poor disease control particularly among young adults, overweight subjects and diabetics.
S-38-6: DYSFUNCTION OF ATP2B1, ONE OF HYPERTENSION ASSOCIATED GENES, IN CD4+ T CELLS INDUCE COLITIS THROUGH THE CD4+ T-CELL DYSREGULATION
Authors: Javkhlant Amarsanaa , Toyama Kensuke , Mogi Masaki 
Published: January 2023

Introduction:
ATP2B1 is known as one of the key genes associated with hypertension developments, which were derived from SNPs analysis. ATP2B1 gene encodes the calcium pumps, which excreting calcium ions from cells and maintaining intracellular calcium homeostasis. Lack of ATP2B1 in CD4-positive (CD4+) T-cells increase an intracellular calcium levels, and which results in the activation of immune responses such as differentiation, cytokine production and proliferation. Immune system of gastrointestinal tract plays an important role in preventing viral and bacterial infection from the foreign environment. Especially, CD4+T-cells play critical roles in the fine tune of an intestinal inflammatory response. We hypothesized that ATP2B1 dysfunction in CD4+T-cell may contribute to the gastrointestinal inflammation. We aimed to clarify the role of ATP2B1 in the CD4+T-cell to the gastrointestinal tract.

Methods:
CD4+T-cell specific knockout of ATP2B1 mice (CD4+T-ATP2B1-KO) were created using the Cre-loxP system (deletion site; exon-10). Lymphocytes were separated from the peripheral blood, spleen, and thymus, and thereafter CD4+T-cells were isolated by the FACS method. Gel electrophoresis-based DNA-sequencing was performed. To quantify mRNA levels, realtime-PCR was performed.

Results:
ATP2B1 gene in CD4+T-cell of thymus, spleen and blood were amplified by PCR, and DNA-sequencing revealed that the exon-10 of ATP2B1 gene was definitely deleted in the CD4+T-ATP2B1-KO mice. Percentages of CD4+T-cell in the thymus were same between KO and control mice, while those in both spleen and blood of the KO mice decreased significantly compared to control mice. Incidentally, blood pressure in KO mice was lower than that in control. Expression levels of both T-bet and GATA3 in the blood of KO mice were significantly increased more than those of control mice, which possibly indicating that Th1 and Th2 are activating. Interestingly, this KO mice show diarrhea and colon wall thickening while control mice did not. There were mucosal changes such as a reduction of intestinal crypts, thickening of intestinal epithelium, and cell clumps in intestinal epithelium (appearing to be inflammatory cells) in the KO mice colon. Surprisingly, colon length of KO mice was significantly shorter than that of controls even before the diarrhea occurred, and TNF-alpha and gp91 expression was increased more in the colon of KO mice than in controls.

Conclusion:
Lack of ATP2B1 in CD4+T-cells lead to the reduction of CD4+T-cells and shift to Th1 and Th2 activation, which may contribute to colitis via the activation of TNF-alpha and/or oxidative stress.
S-44-5: RELATIONS OF AGE, VISCERAL FAT AREA, HOMA-R, AND LIFESTYLE HABITS WITH HYPERTENSION IN THE COMPREHENSIVE HEALTH CHECKUP PROGRAM
Authors: Hirose Hiroshi , Shimizu Ryoko , Mori Masaaki 
Published: January 2023

Objective:
Relations of visceral fat with hypertension (HT) have been reported in both Caucasians and in Asians. However, few studies have examined each systolic and diastolic blood pressure (BP) in detail. We investigated the relations of BP status with various metabolic parameters, including visceral fat area (VFA), subcutaneous fat area (SFA), insulin resistance index HOMA-R and lifestyle habits in participants in our health checkup program.

Design and method:
Cross-sectional study. A total of 3,480 male and 2,467 female subjects, aged 16–93 years (median: 59 years), who participated in the comprehensive health checkup program at our University Hospital, were enrolled in this study. Informed consent was obtained from each subject, and subjects who met the predetermined exclusion criteria or were on treatment for diabetes mellitus (DM) were excluded from the analyses. We divided participants into 4 groups according to BP status criteria: normotensive (NT), high normal (HN), HT, and HT with medication (HT+Tx). We used low-energy computed tomography to measure VFA, SFA, and waist circumference at the umbilical level.

Results:
Participants aged 50–70 years in the HN, HT, and HT+Tx groups had significantly higher mean VFAs compared with subjects in the NT group (P < 0.0001 for both gender). Exercise habit was not related with HT status in either gender. In univariate and multivariate analyses, systolic BP was correlated with age, VFA, and HOMA-R, and diastolic BP was correlated with VFA, family history (FH) of HT, and alcohol intake (> 20 g/day). Furthermore, multiple logistic regression analyses (including HT+Tx group) with HT as a dependent variable revealed that age, FH of HT, VFA, HOMA-R, and alcohol intake were relevant (Table, P < 0.0001).

Conclusions:
These results from our comprehensive health checkup program suggest that age, FH of HT, VFA, HOMA-R, and alcohol intake are independently related to HT status.
S-46-4: NONDIPPER PULSE RATE PATTERN WAS ASSOCIATED WITH BLOOD PRESSURE VARIABILITY AND INCREASE OF BNP: J-HOP STUDY
Authors: Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi 
Published: January 2023

Background:
The association between nondipper pulse rate (PR) pattern was reported. However, the association between nondipper PR pattern, blood pressure variability and hypertensive target organ damage remains unclear.

Methods:
Ambulatory BP monitoring (ABPM) was conducted in 1,003 hypertensive patients enrolled in the Japan Morning Surge Home Blood Pressure (J HOP) Study. Ambulatory BP monitoring was performed on a weekday with an automatic system that recorded the wearers BP and PR every 30 minutes for 24 hours. Nondipper PR status was defined as (awake PR minus sleep PR)/awake PR < 0.1, and we evaluated standard deviation (SD) of systolic BP in daytime and nighttime as BP variability. We also measured the brain natriuretic peptide level (BNP), and conducted echocardiography to estimate the left ventricular mass index (LVMI).

Results:
The SD of systolic BP in nighttime, BNP and LVMI in patients with nondipper PR (N = 247) were higher than that in patients with dipper PR (N = 756, SD of systolic BP: 13.3 ± 4.6 vs. 12.7 ± 4.1 mmHg, p = 0.041; median BNP: 25.2 vs. 17.6 pg/dL, p < 0.001, LVMI: 101.4 ± 29.1 vs. 97.3 ± 42.2 g/m2, p = 0.021). Systolic BP in nighttime in patient with nondipper PR was similar to that in patient with dipper PR (119.5 ± 15.2 vs. 119.9 ± 15.1 mmHg, p = 0.63). The SD of systolic BP in nighttime was associated with BNP and LVMI (BNP: r = 0.08, p = 0.006; LVMI r = 0.10, p = 0.001). Nondipper PR was independently associated with BNP (β = 0.10, p < 0.001), but not with LVMI (β = 0.03, p = 0.37) after adjustment for systolic BP and SD of systolic BP in nighttime.

Conclusions:
Nondipper PR pattern was associated with blood pressure variability and hypertensive target organ damage in patients with cardiovascular risk factor.
S-50-5: SALT SENSITIVITY AS MARKER FOR HYPERTENSION MANAGEMENT
Authors: Lanzani Chiara Livia , Citterio Lorena , Simonini Marco , Laura Zagato , Paolo Manunta 
Published: January 2023

Arterial hypertension is one of the most critical risk factors for cardiovascular (CV) disease, stroke, and chronic kidney disease (CKD). According to the current guidelines on hypertension management, the identification of one or more CV risk factors requires an earlier and more intensive treatment paradigm. Salt sensitivity (SSy), defined as susceptibility to changes in blood pressure related to dietary salt intake, is a well-known independent risk factor for CV disease in both the general and hypertensive population, even though it is not included in current guidelines.
Is has been reported that SSy affects 30_50% of hypertensive and 25% of normotensive subjects. Salt sensitivity is more common in the elderly, women, African Americans, and patients with CKD and insulin resistance.
The diagnosis of SSy is complex and not entirely standardized. The two main methods for SSy assessment are the dietary protocol versus the acute salt load. The dietary protocols typically evaluate the blood pressure variation between short periods of low and high sodium diet and often differ in both the duration and the amount of salt intake. Acute test (which consists of an i.v. infusion of 2 L of physiological solution over 2 hours) evaluates mean blood pressure (MBP) variation between the end and the start of the infusion. Three different blood pressure responses are possible: no substantial variation [salt resistant (SR) subjects], an increase in blood pressure [salt sensitive (SS) subjects], or a paradoxical decrease in blood pressure [reverse salt sensitive (RSS) subjects]. Although RSS subjects have been recognized as a third distinct group since the early 1990 s, many studies included them in the group of SR subjects. Recently, the concept of reverse salt sensitivity has been re-evaluated in relation to CV risk.
Previous studies have shown an increased risk of developing cardiovascular events, hypertensive heart disease and microalbuminuria among SS patients.
In our recent paper, the SS and RSS condition appear to be equivalent risk factors for CV events in hypertensives.
Finally, a J curve relationship between dietary salt and cardiovascular damage has been proposed.
Different pathophysiological mechanisms can be involved in SSy: renal autoregulation (Pressure natriuresis curve), Renin angiotensin aldosterone system, sympathetic nervous system activity, Insulin resistance, peripheral vascular resistances, sodium storage skin, genetic predisposition.
Classification according to salt sensitivity can help in personalization of salt intake indication, intensity of therapy and timing of follow up.
S-51-3: EMPAGLIFLOZIN AMELIORATES CARDIAC HYPERTROPHY AND RENAL INJURY WITH SYMPATHOINHIBITION IN A RAT MODEL OF HYPERTENSIVE HEART FAILURE
Authors: Matsumoto Sho , Shinohara Keisuke , Ikeda Shota , Kashihara Soichiro , Nakashima Ryosuke , Yoshida Daisuke , Ono Yoshiyasu , Tsutsui Hiroyuki 
Published: January 2023

Objective:
SGLT2 inhibitors have been reported to have cardio- and reno-protective effects; however, its mechanisms are not fully understood. Sympathetic activation is critically involved in cardiac and renal damage during the development of hypertensive heart failure. In this study, we examined whether empagliflozin inhibits cardiac and renal damage with sympathoinhibition in the phase of cardiac hypertrophy using a rat model of hypertensive heart failure.

Design and method:
Male Dahl salt-sensitive rats were fed 0.3% low-salt (LS, n = 6) or 8% high-salt diet from 6 weeks of age and the high-salt-fed rats were assigned to the vehicle (HS-VEH, n = 6) or empagliflozin (HS-EMPA, n = 6) treatment groups at 8 weeks. Systolic blood pressure was measured by tail-cuff method at 6, 8, and 12 weeks. At 12 weeks, organ weight, plasma creatinine, and plasma norepinephrine were measured. Renal fibrosis was evaluated by Sirius red staining. The expression of c-Fos, a marker of neuronal activity, in the hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM), in which the presympathetic neurons are located, was evaluated by immunostaining.

Results:
Systolic blood pressure was elevated in HS-VEH and HS-EMPA compared to LS, whereas there was no significant difference between HS-VEH and HS-EMPA (at 12 weeks, LS 127.1 ± 5.3 mmHg, HS-VEH 224.5 ± 20.1 mmHg, HS-EMPA 223.8 ± 24.4 mmHg; p < 0.05 vs LS). Left ventricular weight was increased in HS-VEH compared to LS (1.13 ± 0.02 vs 0.90 ± 0.02 g, p < 0.05), and the increase was attenuated in HS-EMPA (1.06 ± 0.04 g, p < 0.05 vs HS-VEH). Kidney weight was similarly increased both in HS-VEH and HS-EMPA compared to LS; however, empagliflozin significantly attenuated the high salt-induced increases in renal fibrosis and plasma creatinine (LS 0.20 ± 0.02 mg/dL, HS-VEH 0.34 ± 0.06 mg/dL, HS-EMPA 0.20 ± 0.04 mg/dL; p < 0.05 for HS-VEH vs LS and HS-EMPA vs HS-VEH). Plasma norepinephrine was increased in HS-VEH compared to LS (1304 ± 627 vs 268 ± 54.5 pg/mL, p < 0.05) and was suppressed in HS-EMPA (648 ± 419 pg/mL, p = 0.05 vs VEH), which was consistent with the finding that the increase in c-Fos positive neurons within the PVN and RVLM in HS-VEH was significantly attenuated in HS-EMPA.

Conclusions:
In Dahl salt-sensitive hypertensive heart failure model, empagliflozin inhibits sympathetic activation and ameliorates cardiac hypertrophy and renal injury without lowering blood pressure in the pre-heart failure phase.