bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P283: Gamma Delta T Cells Drive CD4
+
and CD8
+
T Cell Activation in Hypertension
Authors: Paradis Pierre , Caillon Antoine , Schiffrin Ernesto L
Published: December 2018

Objective:
Both innate (monocyte/macrophages) and adaptive immune cells (T lymphocytes) have been shown to play a role in hypertension and vascular injury. Recently, we demonstrated that a small subset of “innate-like” T lymphocytes, expressing the γδ T cell receptor (TCR) rather than the αβ TCR, plays a key role in hypertension and vascular injury. We demonstrated an increased number and activation (CD69
+
) of γδ T cells during the development of hypertension caused by angiotensin (Ang) II infusion, and that deficiency in γδ T cells prevented Ang II-induced hypertension, resistance artery endothelial dysfunction and spleen T-cell activation in mice. We hypothesized that γδ T cells mediate activation of other T cells in hypertension.

Method:
C57BL/6 male mice were infused with Ang II (490 ng/kg/min, SC) for 7 and 14 days (n=5-7). All mice were 14-15 week-old at the end of the study. Spleen T cell profile was determined by flow cytometry. γδ and αβ T cells were isolated using magnetic beads from peripheral lymph nodes and spleen of 8 to 9-week-old C57BL/6 male mice. αβ T cells were cultured alone or with γδ T cells (5:1) in presence of anti-CD3 antibodies plus or minus Ang II, and αβ T cell activation was evaluated by flow cytometry.

Results:
Close correlations were demonstrated between the number (#) of activated CD69
+
γδ T cells and CD4
+
CD69
+
T cells (r
2
=0.74,
P
<0.01) and CD8
+
CD69
+
T cells (r
2
=0.64,
P
<0.01) after 7-day Ang II. These correlations decreased after 14-day Ang II. Correlations were also shown between the # of CD27
+
CD69
+
γδ T cells and CD4
+
CD69
+
T cells (r
2
=0.76,
P
<0.001) and CD8
+
CD69
+
T cells (r
2
=0.65,
P
<0.01) after 7-day Ang II.
In vitro
, Ang II increased the fraction of CD69
+
αβ T cells when αβ T cells were co-cultured with γδ T cells (% of αβ T cells: 19.9±2.9 vs. 16.4±2.6,
P
<0.001) but not when cultured alone (% of αβ T cells: 13.7±0.7 vs. 12.7±0.6). A correlation between the fraction of CD69
+
γδ T cells and CD69
+
αβ T cells was also observed (r
2
=0.69,
P
<0.001).

Conclusion:
These results suggest that γδ T cells mediate activation of αβ T cells in Ang II-induced hypertension. Targeting γδ T cells may contribute to reduce the low-grade inflammation found in hypertension.
Abstract P298: Combination of Systolic Blood Pressure and Non-HDL Cholesterol Categories Increased the Risk of Incident Latent Heart Failure: The Suita Study
Authors: Kokubo Yoshihiro , Watanabe Makoto , Higashiyama Aya , Miyamoto Yoshihiro
Published: December 2018

Objective:
There are few population based prospective studies on heart failure (HF) in non-Western populations. We hypothesized that the combination of systolic blood pressure (SBP) and non-HDL cholesterol (non-HDLC) categories affect the risk of incident latent HF (LHF) in a general Japanese population.

Methods:
We prospectively followed-up 2,774 Suita Study subjects (average age 66.7±10.4 years, initially free of LHF) for incident LHF. BP were taken as the average of the first and second measurements. Each subject was classified into an SBP category: normal SBP, <120 mmHg; systolic prehypertension (preHT), 120-139 mmHg; or systolic hypertension (HT), ≥140 mmHg or antihypertensive drug use. The subjects' non-HDLC levels were calculated by subtracting the HDLC from the total cholesterol. B-type natriuretic peptide (BNP) was measured by the CLEIA method. LHF was defined as BNP ≥100 pg/mL or HF medication from medical records. Each subject’s health status and BNP were checked in biannual medical examinations, and all subjects completed annual questionnaires. The endpoint of the follow-up period for incident LHF was whichever occurred first: the date of the first diagnosis of LHF, the date of the last examination, or December 31, 2017. We analyzed Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) for incident LHF after adjusting for cardiovascular risk factors.

Results:
In 18,134 person-years of follow-up, 294 incident LHF events occurred. Compared to the normal SBP subjects, the adjusted HR (95% CIs) of incident LHF in the systolic HT subjects was 1.64 (1.16-2.30). The adjusted HR (95% CIs) of incident LHF per 20 mmHg of SBP was 1.18 (1.04-1.34). Compared to the normal non-HDLC (130-179 mg/dL) subjects, the adjusted HR (95% CIs) of incident LHF in the low non-HDLC (<130 mg/dL) subjects was 1.47 (1.15-1.88). Compared to the normal non-HDLC subjects with normal SBP, the adjusted HRs (95% CIs) of incident LHF in the normal non-HDLC subjects with systolic HT and low non-HDLC subjects with systolic preHT and HT were 1.53 (1.01-2.31), 1.76 (1.02-3.04), and 2.44 (1.58-3.76), respectively.

Conclusion:
This is the first demonstration that systolic preHT and low non-HDLC were positively associated with incident LHF in a general Japanese population.
Abstract P306: Preterm Birth is Associated with Increased Blood Pressure and Increased Urinary Angiotensinogen in Young Adults
Authors: South Andrew M , Nixon Patricia A , Chappell Mark C , Diz Debra I , Jensen Elizabeth T , Shaltout Hossam A , Washburn Lisa K
Published: December 2018

Introduction:
Cardiovascular disease (CVD) is the leading cause of mortality and hypertension (HTN) is a major risk factor for CVD. Preterm birth is an emerging risk factor for both CVD and HTN, but the underlying mechanisms are poorly described. The renin-angiotensin system (RAS) plays a key role in HTN and CVD, and adolescents born preterm have higher blood pressure (BP) with a shift in the balance of the classical and alternative pathways of the RAS exhibited as increased angiotensin II and reduced angiotensin-(1-7) as compared to term-born adolescents. Although numerous factors influence the expression of angiotensins, the precursor protein angiotensinogen in the kidney is implicated in the development of HTN and CVD and may contribute to higher angiotensin II. As the status of renal angiotensinogen in individuals born preterm is unknown, we hypothesized that urinary angiotensinogen is increased in young adults born preterm as compared to their term-born peers.

Methods:
We compared urinary excretion of angiotensinogen corrected for urine creatinine and systolic and diastolic BP in 142 young adults (mean age 19.9 years) born preterm with very low birth weight (<1500 g) to 32 young adults born term using Wilcoxon Rank-Sum test and t-test. We used generalized linear models to compare the ln(x) urinary angiotensinogen between the preterm and term groups adjusted for the potentially confounding factors race, maternal hypertensive pregnancy, and maternal smoking during pregnancy.

Results:
Compared to term, subjects born preterm had higher median urinary angiotensinogen (0.02 μg/g, IQR 0.01 to 0.04 vs. 0.01 μg/g, IQR 0.004 to 0.01,
p
< 0.001) and higher mean systolic BP (111 mmHg, SD 11 vs. 106 mmHg, SD 10,
p
= 0.03). On crude and adjusted analyses urinary angiotensinogen was associated positively with preterm birth (crude
β
: 0.82, 95% CI 0.47 to 1.16; adjusted
β
: 0.79, 95% CI 0.39 to 1.18).

Discussion:
In addition to higher BP, young adults born preterm demonstrated increased urinary angiotensinogen as compared to their term-born peers. Preterm birth may induce programming of the renal RAS leading to higher angiotensinogen and a higher angiotensin-to-angiotensin-(1-7) ratio, potentially contributing to the increased risk of HTN in individuals born preterm.
Abstract P311: Static Urine Osmolality With Elevated First Trimester Urine Copeptin in Human Preeclampsia
Authors: Santillan Donna A , Scroggins Sabrina M , Ray Alyssa T , Zhang Shao Y , Sigmund Curt D , Pierce Gary L , Grobe Justin L , Santillan Mark K
Published: December 2018

We have previously shown that maternal plasma copeptin (CPP), as a marker of vasopressin, is highly predictive of preeclampsia (PE) in the first trimester and remains elevated throughout pregnancy. Furthermore, in maternal urine samples we demonstrated that CPP was also significantly elevated in the first trimester in women who later developed PE. Because a urine dipstick test could be easily used in the clinic, we sought to validate this finding in a new and expanded cohort of samples and to determine whether these changes persist throughout pregnancy. In addition, to begin to address the mechanism for this difference, we also assessed urine osmolality to further probe renal function. In a case-control study (IRB# 2015038355), banked maternal urine samples and clinical data from each trimester from women who developed PE (N=117) and controls (N=593) were obtained from the University of Iowa Maternal Fetal Tissue Bank (MFTB) (IRB# 200910784). CPP concentrations were measured by ELISA. Osmolality was determined by freezing point depression. Differences between groups were detected by Chi square, Student’s T Test, or ANOVA as appropriate. Using a validation cohort and a different ELISA (USCN vs Phoenix Pharmaceuticals), we validated our earlier findings. We again find a significant increase in the concentration of urine CPP in the first trimester in women who developed preeclampsia compared to women who did not (0.304 ± 0.03 vs 0.223 ± 0.01 pg/ml,
P
=0.03). No significant differences in copeptin were observed in urine CPP in the 2nd and 3rd trimesters from PE and control women (2
nd
tri: 0.205 ± 0.04 vs 0.213 ± 0.02; 3
rd
tri: 0.290 ± 0.03 vs 0.336 ± 0.02 pg/ml
P
>0.05 in 2
nd
and 3
rd
trimesters). In this cohort, we did not detect differences in urine osmolality between preeclamptics and controls in any trimester (1
st
tri: 606.09 ± 50.16 vs 604.28 ± 16.72; 2
nd
tri 582.10 ± 36.30 vs 596.96 ± 16.98; 3
rd
tri: 479.63 ± 58.81 vs 583.75 ± 19.61 mOsm/kg H
2
O). We conclude that (i) PE is associated with increased maternal urinary CPP in the 1st trimester, (ii) this increase does not correlate with expected increases in urine osmolality. Future work will focus on understanding the mechanisms involved in the elevation in urinary CPP such as early immunologic changes or renal concentrating responses.
Abstract P316: Effects of Paternal Contribution of a Null Allele of Regulator of G Protein Signaling-2 (
Rgs2
) upon the Placental Transcriptome of C57BL/6J Mice
Authors: Perschbacher Katherine J , Deng Guorui , Walsh John W , Santillan Donna A , Devor Eric J , Pierce Gary L , Sigmund Curt D , Fisher Rory A , Gibson-Corley Katherine N , Santillan Mark K , Grobe Justin L
Published: December 2018

Preeclampsia (PreE), a cardiovascular disorder of pregnancy, remains a major cause of maternal and fetal mortality worldwide. The early etiology of the disorder is unclear, though increased G protein-coupled receptor signaling has been implicated. Regulator of G protein Signaling-2 (RGS2) is a negative regulator of G protein signaling, and mutations of
RGS2
have been associated with increased risk for PreE in humans. Our ongoing work has demonstrated that breeding wildtype C57BL/6J dams with
Rgs2
-deficient (
Rgs2
-KO; B6.129P2-

Rgs2
tm1Dgen

/Mmnc) sires is sufficient to cause ~50% reduced placental expression of
Rgs2
mRNA, and to induce hypertension, renal and placental morphological phenotypes typical of PreE in the wildtype dams. To test the hypothesis that reduced RGS2 (via paternal contribution of an
Rgs2
-null allele) is sufficient to cause molecular changes within the placenta that are typical of PreE, we performed RNA sequencing on placentas collected on gestational day 12.5 from C57BL/6J dams mated with either
Rgs2
-KO sires or wildtype littermates of these sires. RNA was isolated and sequenced using an Illumina HiSeq 4000. Transcript counts were quantified and aligned to the mouse genome (UCSC genome browser) using Kallisto, followed by differential gene expression analysis using DEseq2 (FDR = 0.1). 726 genes were differentially expressed (479 up, 247 down), including some (
Hsd11b2
(up),
Adm
(down)), that are similarly changed in human PreE placenta (PMID: 28618048 & 26268791). Ingenuity Pathway Analysis indicated that reduced placental
Rgs2
expression was associated with mitochondrial dysfunction, unfolded protein response, and oxidative stress (all p < 1e-3), which also parallels findings in human PreE placenta. Collectively these data support the conclusion that reduced
Rgs2
expression in the feto-placental unit is sufficient to induce transcriptomic changes within the placenta that are typical of PreE.
Abstract P332: Hesperidin in Citrus Fruit Juice Plays a Role in Preventing Cognitive Impairment Induced by Ischemic Brain Damage
Authors: Kawakami Moe , Iwanami Jun , Tsukuda Kana , Higaki Akinori , Min Li-Juan , Mogi Masaki , Horiuchi Masatsugu
Published: December 2018

Recently we reported that drinking
Citrus iyo
juice (CI) inhibited more effectively vascular remodeling in the inflammation-induced vascular injury mouse model than
Citrus unshiu
juice (CU). These results led us to explore the possibility that citrus fruits juice drinking could attenuate cognitive decline in transient cerebral ischemia mouse model, focusing on the effects of flavanone, hesperidin, which is more abundantly contained in CI compared with CU and has antioxidant activity. Eight-week-old male C57BL/6 mice were administrated 10 % CI or CU in drinking water or 100 mg/kg/day hesperidin orally by gavage. Two weeks after administration, brain ischemia was induced by bilateral common carotid artery occlusion (BCCAO) for 18 minutes. The Y maze task was performed 2 weeks after BCCAO operation. After cognitive task, cerebral blood flow (CBF) was measured by a laser speckle flowmetry. Morphological changes in the hippocampus were examined. Administration of CI, CU or hesperidin did not influence systolic blood pressure, body weight and brain weight. Cognitive function was significantly impaired (sham, 71% (16 of 23) vs BCCAO, 55% (14 of 27) in Y maze) with the increase in superoxide anion production after BCCAO. The cognitive impairment was more effectively attenuated by the administration of CI than CU (CI, 66% (13 of 23); CU, 61% (17 of 27)) with the significant increase in CBF. Interestingly, we also observed that the treatment with hesperidin significantly prevented cognitive decline (67% (13 of 21)) after BCCAO. The increase in superoxide anion production 24 hours after BCCAO (expressed as fold-increase compared to sham) was attenuated by CI or hesperidin, not by CU (BCCAO, 4.0; CI, 1.2; hesperidin, 1.1; CU, 3.0). The fold-increase in TNF-α mRNA in the hippocampus 24 hours after BCCAO was prevented by hesperidin (BCCAO 5.0; hesperidin, 2.8). Cell number in CA1 region of hippocampus decreased in BCCAO-operated mice. Hesperidin treatment attenuated this decrease (sham, 163±5; BCCAO, 136±4; hesperidin, 154±4). These results suggest that the intake of hesperidin in citrus fruits juice should prevent cognitive decline after brain ischemia at least in part due to reduction of oxidative stress, inflammatory cytokine and an increase in CBF.
Abstract P334: Demographic, Risk Factors and Knowledge Profile of the Participants From a Vascular Disease Prevention Campaign - Red September
Authors: Mendes Junior Maurício M , Angelim Abraão Iuri M , Neno Ana Carolina L , da Cunha Lais F , Almeida Lívia P , da Costa Lílian S
Published: December 2018

Introduction:
Studies have suggested beneficial effect of the continuous educational work in the prevention of chronic degenerative diseases.

Objective:
To describe the demographic, risk factors (RF) profile and knowledge of the participants of a Vascular Disease (VD) Prevention Campaign - Red September.

Method:
A cross-sectional descriptive analysis of data collected through a form with questions about RF associated with VD and the subject’s knowledgement about them.

Results:
In a total of 572 subjects (55% female), with a mean age of 43.7±16.4 years, the prevalence of RF for women and men respectively, was 29.1% x 28.3% for arterial hypertension (AH); 11.2% x 8.3% for diabetes mellitus; 15.5% x 13.3% for dyslipidemia; 55% x 65.1% for self-reports of anxiety and/or depression (A/D); 26.8% x 33.1% for family history of early VD and 7.6% x 6.7% of previous cardiovascular (CV) event. Dividing women by age group, the prevalence of AH, spontaneous report of A/D and insufficient physical activity found was, respectively, 5%, 36% and 63% for the group between 18-50 y/o; 50%, 52% and 65.5% for 51-70 y/o group, and 82.4%, 76.5% and 88.2% for women above 71 y/o. The participants' knowledge results reveal that 72% had a satisfactory answer on "what is an artery?", only 25% knew the doctor specialized in the care of VD, and 70.5% of the women and 84.4% of the men are unaware that fatigue may be a symptom. When questioned about which RFs are most related to VD, the first, second and third responses were, respectively: fatty diet (36.9%), inadequate diet (18.1 %) and sedentarism (19.3%). Despite of the knowledge of the causality of VD and CV presence, these RFs are significantly present in this population.

Conclusion:
The need for better strategies to reduce the discrepancy found in this sample is notorious, aimed at reducing the high percentage of modifiable RF that were evidenced in the analyzed population and have been already seen and published in previous studies.
Abstract P337: Src Signaling and Toll-like Receptor 4 (TLR4) are Involved in Ouabain-induced Endothelial Cell Inflammation
Authors: Zhang Yemin , McCarthy Cameron , Beraldi Calmasini Fabiano , Ferreira Wenceslau Camilla , Ogbi Safia , Martinez Quinones Patricia , webb R. Clinton
Published: December 2018

Controversial evidence indicates that endogenous ouabain, a cardiotonic steroid can be synthesized in the adrenal cortex and hypothalamus and secreted as a hormone reaching nanomolar concentrations in the blood. The steroid has pathophysiological significance since its blood levels are positively correlated with blood pressure elevation. Inflammation of the vascular wall and endothelial dysfunction contribute to vascular stiffening in hypertension and it has been proposed that the endothelium is a site of action of ouabain. We hypothesized that ouabain would increase pro-inflammatory events in the endothelium. We observed that a low concentration ouabain (10nM; 24hr) sharply increased mRNA levels of the pro-inflammatory cytokines compared to control group (vehicle; 24h), TNF-α (59.9 fold vs con), IL-1β (3.23 fold vs con), COX2 (309.08 fold vs con), IL-6 (5.76 fold vs con) in cultured, human aortic endothelial cell (HAEC) and increased cyclooxygenase (COX2) expression (1.78 fold vs con). Simultaneously, a burst of nitric oxide (NO) was produced (1.2 fold vs con). Thus, low nanomolar concentrations of ouabain induced endothelial cell inflammation and dysfunction. Additionally, we observed that ouabain (10nM; 24hr) decreased mRNA expression of epidermal growth factor receptor (EGFR) (0.31 fold decrease vs con), and decreased the protein expression of EGFR (0.23 fold decrease vs con). But we found that ouabain induced the expression of non-receptor tyrosine kinase Src (2.27 fold vs con) and Toll-like receptor 4 (TLR4) (2.03 fold vs con), and activated the downstream signaling molecules, Myd88 (1.69 fold vs con), Akt (P-AKT/AKT, 4.31 fold vs con). Overall, the results provide a mechanism for ouabain-induced endothelial cell inflammation involving the inhibition of EGFR and the activation of Src and TLR4 to induce Akt signaling leading to secretion of pro-inflammatory cytokines.
Abstract P343: Utility of Autonomic Testing for the Diagnosis of Neurogenic Orthostatic Hypotension and Subsequent Management With Droxidopa
Authors: Alam Sami B , Almardini Waiel , Suleman Amer
Published: December 2018

A 62-year-old man with a history of Hodgkin lymphoma, lupus, type 2 diabetes mellitus, neuropathy, hypercholesterolemia, hypothyroidism, and orthostatic hypotension who was taking gabapentin, saxagliptin, pravastatin, levothyroxine sodium, omeprazole, prednisone, midodrine, and fludrocortisone was evaluated for syncope, collapse, and fluctuating blood pressure (BP). He reported a 2-year history of syncope, with progressive worsening over a 3-month period. Initially, his episodes of syncope were preceded by dizziness and nausea, but began to occur without warning. He also reported a 5-year history of orthostatic hypotension, with supine BP of 100/60 mmHg and standing BP of 50-60/40 mmHg. Treatment with midodrine (10 mg three times daily) and fludrocortisone (0.1 mg twice daily [BID]) did not relieve his symptoms. Initial cardiac evaluation revealed a systolic murmur, but was otherwise unremarkable. Autonomic function tests, including continuous electrocardiography, BP and heart rate monitoring at 2-min intervals, and transcranial Doppler, were performed in the supine and 80° head-up tilt positions. A BP drop from 112/68 mmHg to 76/60 mmHg occurred within 2 min of tilt, accompanied by dizziness and presyncope. Heart rate with deep breathing revealed a depressed baseline autonomic tone, and a Valsalva maneuver test showed a depressed Valsalva response (Valsalva ratio: 1.15). Taken together, these results indicated a diagnosis of neurogenic orthostatic hypotension (nOH). Treatment with droxidopa (100 mg BID) was initiated; this dose was titrated to 100 mg once daily due to hypertension, for which, a nitroglycerin patch (0.2 mg nightly) was prescribed. All other medications were continued. Treatment with droxidopa significantly improved his symptoms; he no longer loses consciousness upon positional change, but still experiences some symptoms of presyncope (eg, slight lightheadedness, dizziness). This has allowed greater integration into activities of daily living and a less strenuous routine for the patient and his caretakers
.
In conclusion, autonomic function testing in this patient effectively led to a timely diagnosis of nOH which, in turn, allowed for implementation of appropriate pharmacologic intervention to manage symptoms.
Abstract P344: Vascular Purinergic Neurotransmission is Not Altered in High Fat-Fed Dahl S Hypertension
Authors: Sangsiri Sutheera , Galligan James J
Published: December 2018

Mesenteric arteries (MAs) are supplied densely by sympathetic nerves releasing NE and ATP to increase vascular tone. Increased neuronal ATP/NE storage and release and impaired clearance cause hypertension. Our previous studies of DOCA-salt hypertensive rats showed that 1) impairment of the prejunctional autoreceptors regulating ATP and NE release contributes to elevated sympathetic neurotransmission, and 2) purinergic neurotransmission was impaired due to decreased ATP bioavailability in sympathetic nerves. As hyperactivity of sympathetic nerves occurs in obesity-related hypertension, we investigated alterations in purinergic transmission in high fat-fed (HF) Dahl S rats. MAs maintained
in vitro
were stimulated focally. Intracellular recording of excitatory junction potential (EJP) from smooth muscle cells was obtained from male and female, control and HF rats. EJP amplitude, facilitation and rundown were assessed. EJPs from all groups were abolished by tetrodotoxin (300 nM), a Na
+
channel blocker, and P2X receptor antagonist, PPADS (10 μM), indicating EJPs were neurogenic and purinergic. At 17 weeks, we found that 1) frequency (0.5-10Hz) response curves from control and HF were similar in male and female arteries. 2) When using short trains of stimulation (0.5Hz; 5 pulses), UK14304 (0.0001-1μM)-, an α2-adrenergic receptor agonist, blocked EJPs response equally well in arteries from control and HF rats. Moreover, the α-adrenergic receptor antagonist, yohimbine (1 μM), potentiated EJPs similarly in control and HF groups. 3) There were no differences in EJP rundown caused by trains of stimulation (10Hz, 50 pulses) in MA from control and HF fed rats. Differential facilitation of purinergic neurotransmission was detected in male
vs
female. In the presence of yohimbine, degree of EJP facilitation was higher in female arteries compared to male control arteries (2.69±0.26
vs
1.96±0.09 N=4, p<0.05) indicating higher prejunctional ATP storage in female nerves. However, HF did not affect the degree of facilitation. These data suggested that sympathetic neurovascular function is not affected in HF Dahl S rats. Elevated blood pressure in this animal model is not dependent on altered sympathetic neurovascular function.
Abstract P355: Is Knowledge of Proper Technique a Barrier to Accurate Blood Pressure Measurement in the Hemodialysis Unit?
Authors: Bittman Jesse , Pham Thuy , Sarian Mari , Tobe Sheldon
Published: December 2018

Objectives:
Hypertension and hypotension are associated with adverse outcomes in hemodialysis patients. However, routine blood pressure measurement in the hemodialysis unit has poor correlation with interdialytic blood pressure and clinical outcomes. Poor measurement technique in routine practice may contribute to this poor correlation. We aim to assess hemodialysis unit nurses’ knowledge of proper blood pressure measurement technique.

Methods:
All hemodialysis unit nurses were asked to anonymously answer 12 multiple-choice questions on proper blood pressure measurement technique, based on Hypertension Canada guidelines. Frequency of incorrect responses were used to gauge gaps in knowledge.

Results:
73 hemodialysis nurses completed the survey with an average score of 9.5/12 (SD 1.4). Only four respondents answered all questions correctly. The most frequent errors were regarding patient position during measurement. 96% of respondents graded their confidence in their blood pressure measurement technique as ≥4/5.

Conclusion:
Despite routine use and high confidence, there are gaps in knowledge of proper blood pressure measurement technique.
Abstract P359: Management of Hypertension and Diabetes Comorbidity by Pharmacists in a Digital Setup
Authors: Wang Wei , Wang Zhen , Zhang Hongguang , Chen Ying , Li Yingjie , Li Dongxing , Liu Kai , Cao Jiumei
Published: December 2018

Objective:
To identify the health outcomes of using a digital approach to manage patients of hypertension and diabetes comorbidity in China.

Methods:
We developed and promoted a digital solution that consisted of BP and blood glucose (BG) tele-monitors, an App, and a cloud engine with 5 proprietary algorithms for personalized care in 1,150 drug stores in 101 cities. During Jun 1
st
2015 and Apr 30
th
2018, a total of 4,775 patients of both uncontrolled BP and BG received monthly pharmacy services of: 1) BP and BG tele-monitoring, 2) App-assisted lifestyle coaching for meal plans and exercises, and 3) App-guided medication consultation.

Results:
The study population had an average age of 65.7 ± 10.4, BMI of 24.4 ± 3.3, and male of 47.5%. SBP and DBP were reduced on average by 9.3 mm Hg (baseline: 154.4 ± 14.7 mm Hg, last time: 145.1 ± 18.5 mm Hg, P< 0.001) and 5.0 mm Hg (baseline: 86.7 ± 11.2 mm Hg, last time: 81.7 ± 11.7 mm Hg, P<0.001). Their fasting blood glucose (FBG) and random blood glucose (RBG) were reduced by 0.8 mM (baseline: 9.1 ± 2.2 mM, last time: 8.3 ± 2.3 mM, P<0.001) and 3.1 mM (baseline: 14.5 ± 3.3 mM, last time: 11.4 ± 4.0 mM, P<0.001). The percentage of patients who had controlled BP or BG or both measurements were 36.0% (n=1,717, P<0.001), 28.8% (n=1,376, P<0.001) and 11.4% (n=542, P<0.001) by the time of this analysis. Patients in general felt comfortable about data sharing with pharmacists and were satisfied with this interventional approach that provided easy data access to them and their close relatives who in many cases played an important role in helping the patients achieve better compliance. The health outcomes were not associated with geographic differences except for RBG (r=0.1, P<0.001) or economic status of the site.

Conclusion:
Patients of hypertension and diabetes comorbidity can be effectively managed by pharmacists when digital tools were integrated into the interventional approach.
Abstract P361: Single Pill Combination Therapy is Not Superior to Free Combination Therapy for Controlling Hypertension
Authors: Rock Wasseem , Dabbah Shereen , Rimbrot Sofia , Vered Shiraz , Grossman Ehud , Sharabi Yehonatan
Published: December 2018

Introduction:
The 2017 AHA guidelines advocate the use of ambulatory blood pressure monitoring (ABPM) for assessing the response to anti-hypertensive therapy and favor the use of single pill combination therapy for patients on multiple drugs. We aimed to investigate whether single pill combination therapy was superior to free pill combination therapy for attainment of goal blood pressure.

Methods:
We used data from 1074 consecutive ABPM studies performed between February 2017 and March 2018 to identify patients who received the following drug combinations as either single pill or free pills: ACEI/HCTZ, ARB/HCTZ, ACEI/CCB, ARB/CCB. Goal blood pressure was defined as an average awake blood pressure below 130/80 mmHg.

Results:
There were 193 patients in the single pill combination group and 136 patients in the free pill combination group. There was no difference between the groups regarding age, gender, number of antihypertensive drugs, and previous cardiovascular disease except for previous stroke which was more common in the free pill combination group. Compared to single pill combination, free pill combination showed a trend to superiority in the rate of blood pressure control in all drug combinations, with statistical significance reached only when comparing pooled groups (see table).

Conclusions:
Single pill combination therapy was not superior to free pill combination therapy for attainment of goal blood pressure.
Abstract P367: Adherence Assessment Via Comprehensive Identification and Quantitation of Circulating Medications with Significant Correlation to Lower Blood Pressure Observed in Hypertensive Patients
Authors: Daniels J S , Morrison Ryan D , Milne Stephen B , McNaughton Candace D , Sutherland Jeffrey J
Published: December 2018

Employing a novel and proprietary comprehensive precision medicine clinical tool that is a LC/MS/MS-based platform (PrecisCMQ™), we analyzed the serum of HTN patients seeking emergency care (n=293) for the presence and quantity of 42 antihypertensive and cardiovascular medications. Patient self-reported adherence correlated with clinical tool-based adherence. Among patients prescribed
>
3 medications, clinical tool-based adherence in patients (n=74) who indicate they never miss a dose was 74%, versus 60% in patients (n=69) who reported missed doses (p = 0.009, two-sided t-test; median prescribed medications = 3.5). Patients were considered adherent when 80% of prescribed medications were detected and categorized as nonadherent otherwise. Among patients with
>
3 prescribed medications, we found adherent patients had lower SBP (9.7 mm Hg; 95% CI 1.8 - 17.6; p = 0.02) and lower DBP (6.9 mm Hg; 95% CI 1.9 - 12.1; p = 0.007) after adjusting for age, sex, BMI, and patient-reported adherence. No significant difference in BP was observed in patients prescribed < 3 medications. By comparing medication clinical tool-based detections to prescribed medications listed in the EHR, 12% of the detected medications (68/549) were not recorded in the patients’ EHR. After accounting for the above covariates and the number of medications in the EHR, we observed that the total number of detected medications, including prescriptions not in the EHR, significantly correlated with both SBP (attributed to 4.8% of variation; p = 0.01) and DBP (patients prescribed
>
3medications; explaining 2.5% of BP variation; p = 0.05). Additionally, to assess whether patients with higher systemic medication concentrations had lower BP, we compared SBP and DBP to medication concentrations normalized to published reference ranges. After accounting for the above covariates and the number of detected medications, we observed a relationship between medication(s) concentration(s) and BP across all patients. Together, these results support the utility of clinical tool-based medication monitoring for assessing adherence and improving BP control in HTN patients.
Abstract P377: Effect of Salt Diet on Haplotype Specific Expression of Human Angiotensinogen Gene
Authors: Sivankutty Indu , Mopidevi Brahmaraju , Perla Sravan , Jain Sudhir , Kumar Ashok
Published: December 2018

Human Angiotensinogen gene (hAGT) is an important component of the Renin- Angiotensin System. The 2.5 Kb promoter of the hAGT gene has ten polymorphisms that form two haplotype (Hap) blocks. Hap-I containing -6A, -20A, -217A, -532T, -793A, -1074T, -1178G, -1561T, -1562C, and -1670A is associated with increased blood pressure whereas Hap-II containing -6G, -20A, -217G, -532C, -793G, -1074G, -1178A, -1561G, -1562G, and -1670G is associated with normal blood pressure in human subjects. In order to understand the role of these SNPs in the transcriptional regulation, we have generated novel transgenic mice with the hAGT gene, targeted to the mHPRT locus with either Hap I or II variants. In the present study, we have examined the effect of high salt diet on the hAGT gene expression and transcriptional regulation in the 8 weeks old male transgenic mice containing these two haplotypes. Quantitative real time PCR analysis revealed an increase in hAGT expression in the liver of Hap-I as compared to Hap-II in basal condition (4.09 fold), Hap-I high salt vs Hap-I basal (2.15 fold), Hap-II high salt vs Hap-II basal (1.9 fold) and Hap-I high salt vs Hap-II high salt (2.47 fold) with p<0.05 in these transgenic mice. Immunoblot analysis also indicated the upregulation of the hAGT in plasma in all the study groups, viz; Hap-I compared to that of Hap-II (2.5 fold), Hap-I high salt vs Hap-I basal (1.9 fold) and Hap-II high salt vs Hap-II basal (1.7 fold) with p<0.05. Our studies show that the transgenic mice fed high salt diet have increased mRNA levels in the liver for the transcription factors HNF1, FOXO1, FOXA1 and MR (4, 3.13, 3.93 and 5.4 fold increase respectively; p<0.05). CHIP assay also complements the above observations. Our results strongly suggest that SNPs in Hap-I promote increased transcription and expression of the hAGT gene in multiple tissues, with resultant elevation of plasma hAGT levels. Our studies would provide new insights into the susceptibility of individuals to salt induced hypertension and explain the novel paradigm in salt induced transcriptional regulation of human angiotensinogen gene.
Abstract P379: Paradoxical Natriuretic Peptide Resetting in Astronauts
Authors: Frings-Meuthen Petra , Jordan Jens , Lichtinghagen Ralf , Smith Scott , Heer Martina
Published: December 2018

Human studies in space provide unique and often unexpected findings regarding the role of terrestrial gravity for human cardiovascular and renal regulation. While vascular volume is shifted towards the head, which would be expected to increase natriuretic peptide (NP) release, preliminary observations suggested the opposite. Therefore, we assessed natriuretic peptide regulation on different controlled sodium diets in space and on Earth. Eight male astronauts (50±2.8 yrs.) ingested higher (5.5 g/day) and low sodium (2g/day) diets for five days each on Earth and on the International Space Station (ISS) in alternating order. Dietary nutrient intake was individually tailored and kept constant. At day five of each intervention, midregional-pro atrial NP (MRproANP), N-terminal pro B-type NP (NTproBNP), and aldosterone in blood, urinary sodium excretion, and body mass were measured. On Earth, MRproANP was 71.86±4.39 pmol/L on moderately high and 65.13±6.71 pmol/L on low sodium intake. In space, MRproANP was 44.61±4.26 pmol/L on high and 31.37±4.02 pmol/L on low sodium intake (p<0.001 between sodium intakes, p<0.01 between Earth and space). Similarly, NTproBNP responded to changes in sodium intake (p<0.001) and was regulated at lower levels in space (p=0.008). Serum aldosterone concentrations decreased on higher sodium intake but did not differ between space and Earth (p<0.001 between sodium intakes, p=0.95 between Earth and space). Body mass did not differ between low and high sodium intake, either on Earth or in space (space: low sodium 83.7±3.1 kg, higher sodium 84.4±3.1 kg, Earth: low sodium 87.1±3.6 kg, higher sodium 87.2±3.2 kg). In conclusion, NP release while responding to changes in sodium intake is paradoxically reset to lower levels in space. The mechanisms may have implications for volume regulation and cardiovascular health during long-term space travel.
Abstract P388: Lifestyle Interventions Reduce the Need for Guideline-Directed Antihypertensive Medication
Authors: Hinderliter Alan , Smith Patrick , Sherwood Andrew , Blumenthal James
Published: December 2018

Introduction:
The 2017 ACC-AHA Hypertension Guideline recommends lifestyle modification in the initial treatment of hypertension, and therapy with medications based on a threshold blood pressure determined by overall cardiovascular risk. In this secondary analysis of the ENCORE trial, we examined the effects of the DASH diet alone and in combination with weight loss and aerobic exercise on the indications for antihypertensive medication.

Methods:
Participants included 129 overweight or obese (BMI=25-40 kg/m
2
) men and women between the ages of 40 and 80 years who had blood pressure 130-160/80-99 mmHg and who were not being treated with antihypertensive medications. Participants were randomized to 16 weeks of DASH diet plus behavioral weight management (consisting of nutritional counseling and a behavioral weight management program; DASH+WM), DASH diet alone (consisting of nutritional counseling without exercise or caloric restriction; DASH), or usual care controls (maintenance of usual exercise and dietary habits; UC).

Results:
The participants averaged 53.5±8.8 years of age; 68% (88 of 129) were female, and 60% (77 of 129) were white. Nineteen had an estimated 10-year atherosclerotic cardiovascular disease risk ≥ 10% by the Pooled Cohort Equations, and 1 had diabetes. Blood pressure averaged 138±9/86±6 mmHg. Criteria for treatment with antihypertensive medications, as defined in the 2017 ACC-AHA Hypertension Guideline, were present in 53% (68 of 129). Blood pressure fell by 16/10 mmHg in DASH+WM, 11/8 mmHg in DASH, and 3/4 mmHg in UC. The percentage of subjects with indications for antihypertensive medical therapy fell from 54% (25 of 46) to 15% (7 of 46) in the DASH+WM group and from 51% (20 of 39) to 23% (9 of 39) in the DASH group; and did not significantly change (55% [24 of 44] to 48% [21 of 44]) in the UC group (p = 0.001 for active treatments vs UC; p = 0.011 for DASH+WM vs DASH alone).

Conclusions:
In overweight or obese men and women with hypertension, lifestyle interventions dramatically decrease the number of individuals for whom guideline-directed antihypertensive medication is indicated.
Abstract P391: Ambulatory Blood Pressure Phenotypes and Cardiovascular Target Organ Damage in Adolescents: The SHIP AHOY Study
Authors: Hamdani Gilad , Urbina Elaine M , Lande Marc , Meyers Kevin , Samuels Joshua , Flynn Joseph T
Published: December 2018

Hypertensive target organ damage (TOD) is associated with increased risk for cardiovascular (CV) events. Ambulatory blood pressure (ABP) allows better prediction of TOD than clinic BP in adults, but data in youth are lacking. We aimed to determine if BP phenotype, based on a combination of clinic BP and ABP, predicts underlying CV TOD in otherwise healthy adolescents. We evaluated clinic BP (mean of 6 auscultatory BP’s), ABP (Spacelabs OnTrak), left ventricular mass index (LVMI), pulse wave velocity (PWV), diastolic function (E/e’), and systolic function (longitudinal strain) in 244 adolescents (median age 15.7 yrs, 63% white, 54% male). Clinic HTN was defined according to pediatric guidelines, and ambulatory HTN was defined as wake systolic BP
>
95
th
percentile for sex and height. General linear models were used to evaluate associations between BP phenotype and TOD. Normal BP phenotype was found in 162 participants (66%), while 44 (18%), 16 (7%), and 22 (9%) had white coat (WCH), masked (MH), and ambulatory (AH) HTN, respectively. Participants with an abnormal BP phenotype had higher LVMI and PWV compared to those with normal BP (table). Participants with AH also had significantly higher PWV than those with WCH or MH. Adolescents with MH or AH had worse diastolic function (higher E/e’) compared to those with normal BP or WCH. Only participants with AH had significantly worse systolic function (less negative strain) compared to those with normal BP; there was no significant difference in strain among subjects with normal BP, WCH and MH. In conclusion, ABPM improves TOD risk stratification in adolescents evaluated for HTN.
Abstract P394: Ace Activity and Its Expression as a Hypertension Biomarker in the Urine of Pediatric Renal Transplant Recipients
Authors: Pignatari Maria Cecilia , Ronchi Fernanda Aparecida , Ribeiro Amanda Aparecida , Carvalhaes João Tomás de Abreu , Miranda Larissa , Nogueira Paulo Cesar Koch , Casarini Dulce Elena
Published: December 2018

Pediatric hypertension is a risk factor for hypertension in adults. Primary hypertension results from genetic, environmental, and behavioral factors. Renin Angiotensin System is important to control cardiovascular and renal functions. Angiotensin Converting Enzyme (ACE) has isoforms: somatic (130-190 kDa) and testicular (90-110 kDa). Casarini et al. described the N-domain isoform of 90kDa, in urine of hypertensive humans as a possible hypertension biomarker.

Objective:
Analyze ACE isoform in urine of pediatric renal transplant recipients before and after transplantation and urine of donor, to verify the 90 kDa isoform transmission and correlating with hypertension.

Methods:
30 pediatric recipients with living donors; ACE activity was performed before, 1, 3 and 6 months post transplantation using ZPhe and HHL as substrates and its ratio.

Results:
69% had pre-transplant hypertension and 85.7% family history. After 6 months 25% remained. From the pre-transplant until the sixth month after, ACE activity was reduced. In the model of linear regression between ACE activity and variables, including pre-transplantation for the substrates ZPhe-HL remained significant, time and uropathy (0.023 more); with HHL, time and uropathy with higher activity of ACE (0.019 more) and for weight, reduction of ACE activity ( 0.00038 at 1 kg increase in weight). At post-transplant only time and weight remained significant with ZPhe-HL, and for HHL uropathy, proteinuria (0.010 more ACE activity) and weight. Recipients before transplantation had higher urinary ACE activity when compared to controls. Western blotting data showed that all recipients without ACE 90KDa when received a kidney from the donor that had this isoform, started to express it.

Conclusions:
Increased ACE activity in uropathies may be associated with renal injury or intra-renal production. Proteinuria, a marker of renal injury, can be associated with increase on ACE activity. With nutritional recovery and a healthy kidney after transplantation, patients can reverse the degree of renal damage and decrease the production of ACE.
Abstract P402: A New Oral Salt Tolerance Test has Acceptable Consistency for its First Volunteer
Authors: MA Zhiyi , CHEN Yuanyuan , ZENG Zhechun , SUN Ningling
Published: December 2018

Objectives:
One of the cores of salt restriction is to keep balance of salt intake and excretion. There is still no method to identify salt tolerance based on salt intake and excretion. In order to evaluate the ability to absorb and excrete salt, we established a new method Oral Salt Tolerance Test (OSTT). We firstly evaluated its consistency for one person among repeated tests.

Methods:
After signing informed consent, the 40-year-old healthy woman volunteer was asked to keep fasting after 9PM and empty bladder before sleep on the day before test. On the morning for test, she emptied bladder firstly and then drank 500ml 0.9% saline in 15 minutes. Urine volume and urine samples for sodium test were collected at 30min, 60min, 120min and 180min time points. This test was repeated twice on the other two days.

Results:
1. According to sodium concentration and urine volume at each timepoints, we calculated equal sodium chloride amount. The baseline urine sodium concentration before test 1 is higher than those before test 2 and test 3. Accordingly, the 30min sodium concentration and urine volume are lower and higher respectively than those of the other two tests, while the 30min equal sodium chloride amounts are similar among the three tests. 2. The Intraclass Correlation Coefficient for equal sodium chloride amount among the three tests is 0.94 (95% Confidence Interval 0.6810 to 0.9958) and this indicates that the consistency among the three tests is acceptable.

Conclusion:
The acceptable consistency makes this new OSTT possible to screen more subjects with various clinical conditions. In the future, we hope this new method would give us a novel insight for hypertension or renal diseases patients.
Wienhausen Hs 80: Überlegungen zu Kontext und Performanz des Objekts
Authors: Dauven-van Knippenberg Carla , Meyer Elisabeth
Published: December 2018

The former Cistercian convent of Wienhausen in Lower Saxony contains a unique collection of miniature-manuscripts from the 14th till 16th century. These little and on first sight unimpressive booklets – most of them comprise no more than a few folia – have drawn little scholarly attention as a group. When studied, scholars were mainly interested in their content (prayers etc.), but less in their material distinctiveness, namely the very small size and the fact that a relatively large number of these booklets has been preserved. Most of these booklets contain Latin texts, demonstrating the high educational level of the cloistered women, but also showing that Latin is the language of divine vicinity. Using the example of the Wienhäuser Manuscript 80 we suggest that the women made those little booklets from the blank folia-margins of discarded larger parchment manuscripts. The use of scraps probably offered a possibility for the women to produce booklets for their very personal use and belongings aside from all other manuscripts for daily devotional practices. We suggest that the meaning of the small booklets lays not only or primarily in the texts, but also in the objects themselves, their tininess and the fact that the women made and owned them. A future dna-analysis could throw light on the relation between these tiny scrap booklets and other preserved manuscripts from the convent.
A new species of Apolysis Loew, 1860 from China (Diptera: Bombyliidae, Usiinae, Apolysini)
Authors: YAO GANG , YANG DING , EVENHUIS NEAL L. , GHARALI BABAK
Published: December 2018

The genus Apolysis Loew, 1860 is a moderately species-rich bee fly genus with 116 decribed species in the world; 14 species in the Palaearctic, and one species in the Oriental. A new species from China is described: Apolysis galba sp. nov. and Apolysis beijingensis (Yang & Yang), comb. nov., is redescribed. A key to the genera of the subfamily Usiinae in China is presented.
Character evidence for the monophyly of the Microdesminae, with comments on relationships to Schindleria (Teleostei: Gobioidei: Gobiidae)
Authors: GILL ANTHONY C. , MOOI RANDALL D.
Published: December 2018

The composition of the Microdesminae has been inconsistently reported in recent molecular studies. A monophyletic Microdesminae consisting of both Indo-Pacific and New World/Atlantic genera is diagnosed here by the following synapomorphies: maxilla with elongate projection extending anteriorly over ascending processes of premaxilla; palatine medial process absent; single dorsal process on cleithrum; supracleithrum oriented vertically and closely applied to cleithrum; posttemporal with elongate posteroventral process; body slender and elongate, with associated increase in number of vertebrae and median fin rays (total vertebrae 42–66 with 19 or more precaudal vertebrae, total dorsal-fin rays 42–78, anal-fin rays 27–43), slender pelvis with anterior extensions of the pelvic intercleithral cartilage, and decrease in number of pelvic-fin rays (with a spine and 2–4 segmented rays); single dorsal fin; dorsal-fin spines usually 12 or more; predominantly 1:1 relationship between interneural spaces and anterior dorsal-fin pterygiophores; and first (supernumerary) ray on first anal pterygiophore a bilaterally paired, segmented ray. Several of these characters (particularly single dorsal process on cleithrum, posttemporal with elongate posteroventral process) support a possible relationship between microdesmines and Schindleria, as does dorsal gill-arch morphology.