bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P296: High Salt (NaCl) Induces Metabolic Modifications and Affects Classic and Alternative Macrophage Activation
Authors: Geisberger Sabrina Yasmin , Zasada Christin , Jantsch Jonathan , Dechend Ralf , Kempa Stefan , Mueller Dominik N
Published: December 2018

High intake of dietary sodium is a risk factor for cardiovascular disease. Previously, we have shown that an increase in extracellular hypertonic sodium (+40 mM Na
+
; HS) inhibits alternatively-activated M2 macrophage (M(IL4+IL13)) gene signature and function, while boosting classic M1 macrophage polarization (M(LPS)) and bacterial killing capacity. M1 macrophages predominantly rely on glycolysis, whereas M2 macrophages use oxidative phosphorylation, fueled by the oxidation of fatty acids, at a late phase of activation (24 h). The aim of this study was to elucidate the role of HS on the metabolic signature of M1 and M2 macrophages. Therefore, we quantified
13
C incorporation into intermediates of central carbon metabolism via GC-MS based pulsed stable isotope resolved metabolomics (pSIRM), and performed Seahorse analyses at varying time points during M1/M2-activation. After 24 h, LPS-induced increase in basal ECAR (extracellular acidification as surrogate parameter for glycolysis) and lactate production were further boosted under HS compared to isotonic salt conditions (NS), whereas mitochondrial respiration (OCR) was not affected. On the other hand, IL4+IL13-induced increase in OCR was decreased under HS compared to NS, while ECAR was not affected at this stage. Regarding TCA-cycle, we have found an early (1 h and 3 h post-stimulation) increase in citrate levels in M1 and M2 macrophages independent of HS, which further increased after 24 h in M1 and M1+HS. Interestingly, both in early and late phase of activation, glucose-derived
13
C incorporation into citrate was lower in HS-treated compared to NS-treated M0, M1 and M2 macrophages, suggesting an alternative replenishing source. Consistently, other TCA-cycle intermediates increased after 24h (especially in M1 and even further in M1+HS), whereas glucose-derived
13
C incorporation was minimal. Our data suggests that under hypertonic sodium macrophages re-direct TCA-cycle intermediates into the production of pro-inflammatory mediators (as described for late-phase M1 macrophages), whereas TCA-cycle itself is replenished by other alternative metabolic substrates. These HS-induced metabolic modifications might play an important role for macrophage activation and function.
Abstract P297: Hypertensive Crisis in an Inner-City Population: A Retrospective Case Control Study
Authors: Waldron Frederick , Benenson Irina
Published: December 2018

Hypertensive crisis (HTNC) is a potentially life-threatening condition that can develop de novo or as a complication of hypertension. HTNC is characterized by a severe and an acute increase in blood pressure (BP) ≥ 180/120 mmHg, which may progress to end organ damage (EOD), and premature death. HTNC is divided into hypertensive emergency (HTNE), in which there is evidence of EOD, and hypertensive urgency (HTNU) with no EOD. We conducted a 3-year retrospective case controlled study, to determine the prevalence and the risk factors for HTNE and HTNU in an inner city population. Cases (1784) were adult patients visiting the ER with a BP ≥ 200/120 mmHg. Controls had a diagnosis of HTN defined by a BP >140/90, but < 200/120 mmHg. Controls were matched 1:1 for age, gender and race using the SAS program. The total population of subjects with a diagnosis of hypertension was 15631. African Americans accounted for 89% (1585/1784) of the cases, other races for 9% (159/1784) and Caucasians for 2% (40/1784). The prevalence of HTNC was 11.4 % (1784/15631) and HTNE 3.2 % (505/15631). Twenty eight percent (28%) of the cases (505/1784) had EOD. Cases had significantly increased odds of developing the following EOD: acute kidney injury (OR 1.54, p=0.022), acute or worsening congestive heart failure (OR 4.91, p<0.0001), non ST elevation myocardial infarction (OR 2.39, p<0.0001), ischemic stroke (OR 3.27, p<0.0001), hemorrhagic stroke (OR 4.55, p<0.001). The predictors for EOD were: age > 65, male gender, anemia, chronic kidney disease and a history of stroke and cardiovascular comorbidities (hyperlipidemia, coronary artery disease, congestive heart failure). Insurance status and access to primary care were not associated with an increased odds of EOD. The study highlights the high morbidity of poorly controlled HTN, and the disparity in the prevalence of HTNC in the African American community, which is 5 times the national average.
Abstract P300: Countries’ Geographic Latitude And Their Populations’ Cholesterol And Blood Pressure
Authors: Liu Yuhao , Brook Robert D , Liu Xuefeng , Byrd James B
Published: December 2018

Background:
Sunlight has been hypothesized to play a role in variation in cardiovascular disease according to geographic latitude.

Objectives:
To evaluate the plausibility of sunlight as a factor in populations' average cholesterol and BP.

Methods:
We analyzed 180 or more countries' age-standardized average cholesterol, age-standardized mean systolic BP, and age-standardized prevalence of raised BP, by latitude, over decades. We also performed analysis by ultraviolet B light (UVB) exposure.

Results:
Mean cholesterol increases with distance from the Equator. This relationship has changed very little since 1980. Similarly, in 1975, mean systolic BP and prevalence of raised BP were higher farther from the Equator. However, the relationship between latitude and BP has changed dramatically (
Figure
); by 2015, the opposite pattern was observed in women. Countries' UVB exposure has a stable relationship with cholesterol over decades, but a changing relationship with BP.

Conclusions:
Since sunlight exposure in a country is relatively fixed and its relationship with BP has changed dramatically in recent decades, countries' average sunlight exposure is an unlikely explanation for contemporary country-level variation in BP. However, our findings are consistent with a putative effect of sunlight on countries' average cholesterol, as well as a no longer detectable effect on BP decades ago. A parsimonious potential explanation for the relationship is that 7-dehydrocholesterol can be converted to cholesterol, or in the presence of ultraviolet light, can instead be converted to vitamin D. This work is archived in unrefereed preprint form: https://doi.org/10.1101/308726.

Figure.
Abstract P301: Heart Rate Variability is Associated with Future Global Cognitive Performance: the Multi-Ethnic Study of Atherosclerosis
Authors: Schaich Chris , Malaver Diego , Shaltout Hossam A , Zeki Al Hazzouri Adina , Herrington David M , Hughes Timothy M
Published: December 2018

Background:
Low heart rate variability (HRV) is associated with major vascular risk factors for cognitive decline, including hypertension and cardiovascular disease (CVD). Therefore, we hypothesized that higher HRV during mid- to late-life is associated with better cognitive performance.

Methods:
In a subset of participants from the Multi-Ethnic Study of Atherosclerosis (N = 2,961; aged 45-84 years; 55% female; 40% white, 22% African-American, 25% Hispanic, and 13% Chinese-American), we used multivariate linear regression to study the relationship of short-term HRV to global cognitive performance as measured by the Cognitive Abilities Screening Instrument (CASI; score range 0-100). Two measures of HRV, the standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD), were computed at Exam 1 (2000-2002) and Exam 5 (2010-2012). CASI was administered at Exam 5.

Results:
In age-, race-, sex- and education-adjusted models, Exam 1 SDNN was significantly associated with performance on the CASI (
β
= 0.74 ± 0.22;
P
< 0.001). This association remained significant after adjustment for cardiovascular risk factors, including prevalent CVD, medication use, and
APOE
ε4 allele carriage (
β
= 0.53 ± 0.23;
P
= 0.019). Furthermore, participants with highest quartile Exam 1 SDNN scored better than the adjusted mean CASI score (0.61 ± 0.22 points higher;
P
= 0.022), and 0.81 ± 0.29 points higher than other quartiles (
P
= 0.006); participants in other Exam 1 SDNN quartiles scored similarly to each other and to the adjusted mean. In contrast, there were no associations between CASI score and Exam 5 SDNN, Exam 1 RMSSD, or Exam 5 RMSSD after adjustment for cardiovascular risk factors, and no interactions between HRV and race or
APOE
were present.

Conclusions:
Highest quartile 10-year antecedent SDNN is associated with better global cognitive performance in a multi-ethnic population of middle-aged and elderly adults, independent of sociodemographic factors, traditional cardiovascular risk factors,
APOE
status, and prevalent CVD. These results suggest that mid- to late-life HRV may be an early predictor of future cognitive ability.
Abstract P304: Sex Differences in Mechanisms of Adiposity-Associated Hypertension in Dahl S Rats
Authors: Fink Gregory D , Garver Hannah
Published: December 2018

In humans, excessive accumulation of visceral adipose tissue is often associated with hypertension, but there is evidence that the
mechanisms
responsible may differ between men and women. Dahl S rats fed a high fat diet (HFD) from weaning gain visceral fat and develop a progressively higher arterial pressure compared to Dahl S rats fed a control diet (CD). We previously showed that the
magnitude
of this effect is similar in males and females. Here we used pharmacological interventions to compare in males and females the contributions of brain prostanoids, the renin-angiotensin system and the sympathetic nervous system to the development of hypertension in this rat model. Dahl S rats were placed on CD or HFD at weaning. All rats received telemetry implants at 15-16 weeks of age to measure arterial pressure, heart rate, and activity. Studies were conducted from 19-23 weeks of age, a time when hypertension is still developing. Drug interventions were separated by at least a week. Mean arterial pressure (MAP) was significantly higher in male HFD (156.0+/- 6.5 mmHg) versus male CD (133.3+/-1.6 mmHg) rats, and in female HFD (140+/-2.6 mmHg) versus female CD (131.4+/-1.2 mmHg) rats during the experimental period. Treatment for one week with the ACE inhibitor enalapril (250 mg/L in the drinking water) lowered MAP significantly more in male HFD (-38.3+/-5.9 mmHg) than in male CD (-23.9+/-1.6 mmHg) rats, but female HFD (-33.2+/-2.2 mmHg) and CD (-28.4+/-1.5 mmHg) rats responded similarly. Treatment for one week with the centrally acting sympatholytic clonidine (2 mg/L in the drinking water) reduced MAP more in females than males, but there were no differences between CD and HFD groups. One week treatment with the prostanglandin D synthase inhibitor AT56 (5.8 nmol/hr sc) caused only a slight fall in MAP (~3 mmHg) that was similar in all groups. Finally, a single injection of the ganglion blocker hexamethonium (30 mg/kg, ip) caused a short-term depressor response that was not significantly different in magnitude among the groups. We conclude that the renin-angiotensin system may have a greater role in adiposity-associated hypertension in Dahl S males versus females, but that sympathetic overactivity or prostaglandin D are not factors in either sex in the age range studied here.
Abstract P309: Aberrant Corin and PCSK6 in the Placenta of Hyperinsulinemic Dams
Authors: Abassi Zaid , Kinaneh Safa , Skarzinski Galina , Cinnamon Einat , Smith Yoav , Ariel Ilana , Bursztyn Michael
Published: December 2018

Introduction:
Corin, a serine protease converts pro-atrial natriuretic peptide (pro-ANP) and pro-brain natriuretic peptide (pro-BNP) to the mature respective peptides. There is evidence that the pregnant uterus produces ANP, where it promotes spiral artery remodelling, essential for adequate blood supply to the developing conceptus.

Aim:
Here we examine corin and PCSK6, a key enzyme in the conversion of pro-corin to corin, in the placenta of hyperinsulinemic dams (HD) in comparison to normal pregnant dams (NPD).

Materials and Methods:
Female Wistar rats were rendered hyperinsulinemic by subcutaneous insulin pellet, mated and followed to day 21 of pregnancy. Both groups were then sacrificed and their placentas were dissected together with the implantation site designated mesometrial triangle (MT). Placentas and MT were sectioned from the maternal through the fetal surface to the base of the MT. For western blot (WB) the placentas and MT were separated, snap frozen in liquid nitrogen and stored at –80°C. RNA expression of corin was carried out by
in-situ
hybridization in 5 NPD and 6 HD with
corin
probe (RNAscope® Assay 2.5 Detection Reagent, Cat No. 507231) and image analysis was performed.

Results:
As previously described, HD (n=20) developed hypertension as compared with in NPD (n=16). Moreover, HD exhibited lower placental and foetal weights. Corin and PCSK6 mRNA and immunoreactive peptide were detected in the mesometrial tissues. Corin abundance as determined by western blot was significantly decreased in the placenta/ mesometrial triangle by ~40% (P<0.02), as was PCSK6 immunoreactivity. Corin and PCSK6 mRNAs displayed similar pattern of alterations as protein abundance, where
in-situ
hybridization for corin mRNA revealed a 50% (P<0.001) expression reduction. Corin mRNA was specifically expressed by cytotrophoblasts in the labyrinth. Concomitant with the downregulation of corin/PCSK6, ANP levels decreased in the MT of HD.

Summary and Conclusion:
Corin, PCSK6 and ANP are all expressed in the placenta of NPD but declined in dams with chronic hyperinsulinemia, suggesting a role of corin/PCSK6 pathway in the prevention of pregnancy-induced hypertension and intrauterine growth restriction, in this setting.
Abstract P333: Effect of Autonomous Cortisol Secretion on Cerebrovasuclular Events in Patients With Primary Aldosteronism
Authors: Kudo Masataka , Mugikura Shunji , Morimoto Ryo , Tezuka Yuta , Omata Kei , Shiratori Beata , Igarashi Yasuhiro , Seiji Kazumasa , Takase Kei , Ito Sadayoshi , Satoh Fumitoshi
Published: December 2018

Background:
Primary aldosteronism (PA) display a higher risk of cerebrovascular events (CVE) compared with essential hypertension (EH).On the one hand, it was also reported that the PA patients associated with autonomous cortisol secretion had high incidence of CVE.

Objective:
Our objective was to investigate the effect of autonomous cortisol secretion on the prevalence of CVE in the patients with PA and/or Cushing syndrome (CS).

Design and Setting:
This was a retrospective cross-sectional study from Tohoku University Hospital between 2008 and 2017.

Patient:
291 patients were analyzed. In the patients with PA, the recent continuous cases performed adrenal venous sampling (AVS) were extracted. They were divided into four groups. Group A: 32 CS patients, Group B: 34 PA patients with autonomous cortisol secretion, Group C:121 PA patients with aldosterone producing adenoma (APA) and Group D: 104 PA patients with idiopathic hyperaldosteronism (IHA). They were also performed and analyzed MRI brain scans during a hospitalization and examined 1-mg dexamethasone suppression test . The patients in Group A, B and C were underwent adrenalectomy.

Results:
In Group A and Group B, the female-to-male ratio was significantly high (about 4:1). The prevalence of symptomatic stroke prevalence of symptomatic stroke before the confirmed diagnosis in each group were as follows: Group A:2/32, Group B: 0/34, Group C:13/121 and Group D: 3/104. The unruptured cerebral aneurysms were detected in Group A:1/32, Group B: 0/34,Group C:2/121 and Group D: 3/104. Aside from this results, 3 patients underwent surgical clipping for unruptured cerebral aneurysms. During this follow-up period, 5 patients had new onset of CVE(cerebral infarction: 1, cerebellar hemorrhage: 4) in Group C albeit carried out adrenalectomy. In comparison with MRI findings between Group A and B, we found no significant difference in the prevalence of Cerebral microbleeds (CMBs:5.8-9.3%) and High grade white matter hyperintensities (HWHs:43-50%).

Conclusion:
In this study, we could not demonstrate that the patients with PA associated with autonomous cortisol secretion had high incidence of CVE. Nevertheless, we demonstrate that the patients with APA had relatively high incidence of CVE.
Abstract P336: Efficacy and Safety of Vasodilator Beta-Blocker in Elderly Hypertensive Patients: Result From BEFIT-KOERA Study
Authors: Cho Eun Joo , Hong Geu-Ru , Koh YoungYoup , Jeon Dong Woon , Jung In Hyun , Kang Min Kyoung , Yang Young Mo , Park SangWon , Kim Jae Hyung
Published: December 2018

Purpose:
Beta-blockers are efficacious in young hypertensive patients with sympathetic activation. Elderly patients have been known to be at higher risk of hypotension, bradycardia, and other side-effects of beta-blockers when compared with younger patients. This study was to evaluate efficacy and safety of vasodilator beta-blocker in elderly hypertensive patients.

Methods:
BENEFIT-KOREA study (BEnefits after 24 weeks of NEbivolol administration For essential hypertensIon patients wiTh various co-morbidities and treatment environments in KOREA) was a open labeled non-controlled, prospective, multicenter observational study enrolled total 3,140 subjects [1,871 male(59.6%), mean age=63.5±12.9 years old]. We evaluated efficacy and safety of vasodilator beta-blocker in elderly patients.

Results:
Subjects of more than 65 years old [n=1,655, 839 male (49.3%), mean age=73.6±5.8] were analyzed. Table shows that vasodilator beta-blocker is effective in reduction of blood pressure, mean arterial pressure and pulse pressure in elderly patients regardless of add-on or switched to beta-blocker. Adverse drug reaction rate was not different between age group (n=19, 1.15% vs. n=17, 1.15%). Table shows lipid profile and body mass index were not aggravated after 24-week treatment of vasodilator beta-blocker.

Conclusion:
Vasodilator beta-blocker is efficacious and safe without metabolic derangement in elderly patients regardless of prescription patterns. These drug effects in elderly are comparable to in younger patients.
Abstract P340: Variable Pressor and Sympathetic Responsiveness Reflects Neurotransmitter Imbalance in the Paraventricular Nucleus that is Prevented by Loss of Renal Sensory Nerves
Authors: Knuepfer Mark M , Zheng Hong , Liu Xuefei , Sharma Neeru M , Patel Kaushik P
Published: December 2018

The paraventricular nucleus of the hypothalamus (PVN), a key regulator of sympathetic activity, is dependent on a balance of excitatory (NMDA) and inhibitory (nNOS) neurotransmission. Ischemic heart failure (HF), hypertension and renal disease are associated with excessive NMDA and reduced nNOS in the PVN. Individuals with essential hypertension have greater sympathetic tone and exaggerated pressor responsiveness to acute behavioral stress. We observed variable pressor responsiveness in Sprague-Dawley and Borderline Hypertensive rats (SDR and BHR). We hypothesized that those SDR or BHR with greater pressor responses to stress have greater NMDA and/or reduced nNOS activity in PVN. We proposed that renal denervation (RDN) or deafferentation resolves the difference in stress responses and the PVN imbalance. We recorded arterial pressure (AP), and, in some rats, cardiac output and sympathetic nerve activity. After recovery, SDR and BHR were exposed to acute stress (1 cm deep cold water) repeatedly. Average AP responses were greater in male BHR compared to SDR (X=60±2 vs 49±1 mmHg). Responses were divided between those with AP responses greater or lesser than these means. SDR with larger pressor responses (LP), had elevated NMDA NR1 mRNA and protein levels in the PVN and reduced nNOS mRNA (p<0.05). Likewise, in female BHR, larger AP responses (X=57±3 mmHg) LP had greater NMDA NR1 mRNA and protein in the PVN and reduced nNOS protein. Therefore, the imbalance in PVN exists in normotensive rats and correlates with greater AP and sympathetic responses predisposing an individual to cardiovascular disease. In related studies in male SDR and BHR, we examined the effects of RDN on acute stress responses to cold water and to air jet. In both rat strains, RDN or selective renal deafferentation with capsaicin or resiniferatoxin selectively prevented the exaggerated AP responses only in LP rats. Finally, RDN or deafferentation reversed the HF-induced increase in sympathetic nerve activity and the increase NADPH-diaphorase and nNOS staining and protein levels in the PVN. These data suggest that renal sensory nerves are responsible for variable excitatory and inhibitory influences in the PVN that contribute to the predisposition to cardiovascular disease.
Abstract P341: Melanocortin Receptor 4 Activation Mediates Leptin-Induced Sensitization of the Angiotensin II-Elicited Hypertensive Response in Mice
Authors: Xue Baojian , Beltz Terry G , Guo Fang , Johnson Alan K
Published: December 2018

Obesity has been shown to promote the renin-angiotensin system (RAS) activity and inflammation in the hypothalamus that increase BP and sympathetic activity. Our previous studies using an
Induction-Delay-Expression
(IND-DEL-EXP) experimental design demonstrated that in the rats high-fat diet (HFD) or central leptin pretreatment resulted in an enhanced hypertensive response to subsequent treatment with angiotensin (ANG) II. The present study tested whether the leptin sensitization of ANG II-induced hypertension is mediated by activation of brain melanocortin receptor 4 (MC4R) in mice. The animals pretreated with either 3-week HFD or systemic leptin during IND responded with enhanced hypertension to ANG II (1000 ng/kg/min, sc.; HFD, Δ44.0±2.1 mmHg vs. Δ29.4±3.2 mmHg; leptin, Δ43.0±1.7 mmHg vs. Δ29.4±2.0 mmHg). This sensitized ANG II hypertensive response produced by systemic leptin given during IND was blocked by co-administration of icv SHU9119, a MCR4 antagonist (Δ24.0±2.9 mmHg). Moreover, a similar sensitization of the ANG II-induced hypertensive response was produced by icv pretreatment with MT II, a MC4R agonist (Δ39.6±2.1 mmHg). The results indicate that leptin-induced sensitization of ANG II-elicited hypertension is mediated by activation of brain MC4R.
Abstract P352: The Quality of Blood Pressure Measurement in the Hemodialysis Unit
Authors: Bittman Jesse , Pham Thuy , Sarian Mari , Tobe Sheldon
Published: December 2018

Objectives:
The association of intradialytic blood pressure with interdialytic blood pressure and clinic outcomes is inconsistent. Poor technique of routine blood pressure measurement in the hemodialysis unit may contribute to this inconsistency. We aim to assess adherence to current blood pressure measurement standards in the hemodialysis unit.

Methods:
We assessed a convenience sample of 79 hemodialysis unit patient visits for adherence to five blood pressure measurements standards, per Hypertension Canada guidelines. The frequency of errors in blood pressure measurement was assessed by descriptive statistics.

Results:
In 79 blood pressure measurements only 6% had no errors in measurement technique across the five standards we assessed. The most common errors were cuff position (29% correct) and patient position (29% correct), while the upper arm was appropriately chosen in 94% of patients.

Conclusion:
Errors in blood pressure measurement technique were common and may contribute to inaccuracy in blood pressure measurement.
Abstract P356: Community Hypertensive Control is Improved by Pharmacists in a Closed-Loop Digital Healthcare Ecosystem: A Real World Study of Large Samples
Authors: Li Yingjie , Chen Ying , Li Dongxing , Wang Zhen , Zhang Hongguang , Liu Kai
Published: December 2018

Objective:
To evaluate the effects of pharmacist-led digital care for hypertension management at retail pharmacies in China.

Methods:
For the past 3.5 years we have been developing and operating a digital healthcare ecosystem that formed a closed-loop of healthcare delivery by pharmacists to hypertensive patients at drug stores. The system included a set of BP tele-monitor, an App and a cloud engine that ran 5 proprietary algorithms to support personalized lifestyle coaching and medication guidance. Between Jan 1
st
2015 and Apr 30
th
2018, we served 2,683,865 walk-in patients in 8,730 pharmacies in 199 cities, and 54,032 of them were selected in this report following 4 inclusion criteria: 1) baseline BP was hypertensive (≥ 140/90 mm Hg), 2) the frequency of in-store hypertensive care was ≥ 1 time per month, 3) the intervention duration between the first- and last-time hypertensive care was ≥ 1 month, and 4) baseline characteristics were complete.

Results:
The study population demonstrated an average reduction of SBP by 12.2 mm Hg (baseline: 152.0 ± 14.4 mm Hg, last time: 139.8 ± 19.2 mm Hg, P< 0.001) and of DBP by 6.8 mm Hg (baseline: 89.7 ± 11.7 mm Hg, last time: 82.9 ± 12.7 mm Hg, P<0.001). Among them, 31,493 (58.3%) patients had improved hypertension stages with 24,326 (45.0%) of them returning to the normal BP range. The first time health intervention had the strongest BP control effect, accounting for 81.6% reduction of SBP and 78.0% reduction of DBP over time. Linear simulation revealed descending relationship of both SBP and DBP to time, and the concentration distributions were moving towards the normal BP level. The linear fitting functions were: SBP, y=141.222+9.613x
-1
-0.025x (R
2
=0.835); DBP, y = 83.450+5.419x
-1/2
-0.015x (R
2
=0.911).

Conclusion:
Pharmacists are valuable resources in a closed-loop digital healthcare setup to improve community hypertensive control.
Abstract P362: Change of P Wave Parameters After Switching Anti-Hypertensive Agent From Free Drug Combination Into Fixed Dose Combination
Authors: Ki Young Jae , Chung Joong Wha , Seo Young Uk
Published: December 2018

Background:
In hypertensive patients, it is well-known that PWD (P wave dispersion = maximal P wave duration - minimal P wave duration) is associated with the level of BP and the level of PWD correlates with the prevalence of arrhythmias and left atrial enlargement in previous studies. Fixed-dose combination(FDC) of anti-hypertensive agents effectively lower BP compared with free-drug combination. There have been some studies comparing the effect of anti-hypertensive agents on P-wave parameters. However, there have been no studies assessing the change of PWD after switching anti-hypertensive agents from free drug combination into fixed-dose combination

Objective:
The aim of this study was to assess the change of PWD after switching anti-hypertensive agents from free drug combination of angiotensin II receptor blocker(ARB)/Calcium channel blocker(CCB) into fixed-dose combination

Design and Method:
This study included 20 patients who changed anti-hypertensive agents from free drug combination of ARB/CCB into same dosage fixed-dose combinations (FDCs) of ARB/CCB during 2011 to 2014. The maximal P wave duration(maxPWD), minimal P wave duration(minPWD), P wave dispersion(PWD), cPWD(corrected by heart rate, i.e. corrected P wave dispersion) measured by 12-lead electrocardiogram(ECG) at a paper speed of 50mm/s and 20mm/mV

Results:
The PWD was reduced non-statically after changed into fixed dose combination (54.45±13.14ms) compared with free drug combination (56.73±11.90ms, p=0.070). The cPWD was reduced statically after changed into fixed dose combination (56.72±11.90ms) compared with free drug combination (60.02±12.28ms, p=0.003).

Conclusions:
The cPWD significantly reduced after switching anti-hypertensive agents from free drug combination into fixed dose combination
Abstract P371: The Effects of Omega-3 Fatty Acid Ethyl Esters on QT Dispersion and Corrected QT Dispersion in Hypertensive Patients With Left Ventricular Hypertrophy
Authors: Ki YoungJae , Chung Joong Wha , Seo Young Uk
Published: December 2018

Background:
Left ventricular hypertrophy (LVH) leads to arrhythmia such as atrial fibrillation, ventricular arrhythmias and known risk factor of sudden cardiac death. Recent study suggests that Omega-3 fatty acid ethyl esters have anti-arrhythmic effects and reduce sudden cardiac death among survivor of myocardial infarction. QT dispersion(QTD) reflects ventricular repolarization heterogeneity and prolonged QTD has been associated with the risk of arrhythmic death in coronary artery disease patients. However, no study has done to prove the effects of Omega-3 fatty acid ethyl esters on QTD and corrected QTD(cQTD) in hypertensive patients with LVH Objective: We tried to evaluate the effects of Omega-3 fatty acid ethyl esters on QTD and cQTD in hypertensive patients with LVH

Design and Method:
This study included 30 hypertensive patients who confirmed LVH by ECG voltage criteria. The patients were evaluated with 12-leads electrocardiography before and 3~6 months after treatment of Omega-3 fatty acid ethyl esters(1g/day). We measured QTD (maximal QT interval - minimal QT interval) and cQTD (maximal corrected QT interval - minimal corrected QT interval) by Bazett’s formula using electronic caliper before and after treatment.

Results:
QTD (before: 60.86±14, after: 51.84±13.95 P=0.003) and cQTD (before: 63.83±14.18, after: 51.83±13.94 P<0.001) was significantly reduced after treatment of Omega-3 fatty acid ethyl esters

Conclusions:
The QTD and cQTD significantly reduced after treatment of Omega-3 fatty acid ethyl esters in hypertensive patients with LVH. It may partially explain the anti-arrhythmic effect of Omega-3 fatty acid ethyl esters.
Abstract P376: The Monitoring by a Pharmacist Facilitator, of Side Effect, is Useful to Report Adverse Reactions Associated With Antihypertensive Agents in Practical Clinic in South Italy
Authors: Maretta Alessia , Fersini Giuseppina , Salerno Valentina , Saullo Francesca , Virno Roberta , Spagnuolo Vitaliano
Published: December 2018

Adverse Drug Reactions (ADRs) are a serious health related problem, which can limit the treatment options, compliance and even leads to discontinuation of therapy. Unfortunately not in all countries, the reporting reaches standard levels set by the WHO. As well, in our region (Calabria), located in south of Italy, only few reports are usually reported. For these reasons, the Italian Agency of the Drugs (AIFA) has been promoting and financing regional projects with multidisciplinary groups to increase spontaneous reporting. From first January 2018, we started a survey program finalized to report all adverse events from antihypertensive drugs observed in our Cardiovascular Prevention Clinic. We evaluated all of the 250 outpatients (≥18 years), consecutively visited in our clinic, from 1 January 2018 to 30 April 2018. All of these were in antihypertensive treatment (monotherapy or multiple drugs therapy). A total of 20 ADRs were observed. Of the 20 ADRs, 19 were non-serious events; a serious event required hospitalization (atrial-ventricular complete block). Causality assessment has been estimated with the Naranjo algorithm; the results indicated n=19 possible ADRs and n=1 probable. Incidence of ADRs was found to be higher in the age group between 45 and 54 years old (6 of 20) and males experienced more ADRs than females (35%, 7 of 20). ADRs were more frequently associated with combination therapy (65%, 13 of 20) versus monotherapy. Calcium channel-blockers were found to be the most frequently associated drugs with ADRs (n=8), followed by angiotensin receptor blockers (n=4). We compared our reports with the reports, of the same period, available for our region obtained from National Pharmacovigilance Network. During this period were reported 27 side effect reactions in all our region (5 reports in the 2017). In conclusion, in the last 4 months, regional projects, with the creation of a multidisciplinary group composed of Medical and Pharmacists Facilitator, was useful in improving and increase quality and quantity of spontaneous reports in Calabria.
Abstract P378: Dahl Salt-Sensitive Rats Exhibit Aberrant Renal Hemodynamic Responses to a High Salt Diet and Salt-Sensitive Hypertension as Compared to Consomic SS.BN1 Rats
Authors: Polichnowski Aaron J , Potter Jacqueline , Allen Shannon , Dykes Rhesa , Duffourc Michelle , Williamson Geoffrey A
Published: December 2018

Altered renal vascular responses to a high salt diet have been proposed to contribute to salt-sensitive (SS) hypertension. The goals of this study were to assess: 1) SS hypertension and renal injury in Dahl SS vs. Brown-Norway (BN) and consomic SS.BN1 rats and 2) renal hemodynamics in conscious SS vs. SS.BN1 rats during consumption of a low and high salt diet. Systolic BP (24 hrs/day via telemetry), proteinuria and renal injury were assessed in 10 week old SS (n=9), BN (n=8) and SS.BN1 (n=8) rats during a 0.4% NaCl diet and for 3 weeks during a 4.0% NaCl diet. On a 0.4% NaCl diet, BP was different (P<0.05) among SS, BN and SS.BN1 rats (160±1 vs. 115±2 vs. 141±2 mmHg) while proteinuria was higher (P<0.05) in SS vs. BN and SS.BN1 rats (87±14 vs. 22±3 and 30±5 mg/day). A 4% NaCl diet exacerbated differences (P<0.05) in BP (188±3 vs. 122±2 vs. 150±1 mmHg) and proteinuria (259±29 vs. 29±5 vs. 68±15 mg/day) between SS vs. BN and SS.BN1 rats. Abundant uromodulin (UMOD) positive protein casts were only observed in SS rats. Interestingly, strikingly low levels of UMOD, located on chromosome 1, were found in the urine of SS vs. BN and SS.BN1 rats at baseline. Mean arterial BP (MAP, mmHg, via telemetry), renal vascular resistance (RVR, mmHg/ml/min) and renal blood flow (RBF, ml/min, via Transonic flow probe) were assessed in conscious 10 week old SS (n=5) vs. SS.BN1 (n=5) rats for 2-3 hrs/day over 3 days of 0.4% NaCl feeding and over days 3-7 of 4.0% NaCl feeding. While MAP was higher during a 0.4% NaCl diet in SS vs. SS.BN1 rats (137±3 vs. 121±3), interestingly, RVR was lower (16±2 vs. 20±2, P<0.05) and RBF higher (9±1 vs. 6±1, P<0.05) in SS vs. SS.BN1 rats. During 4.0% NaCl feeding, RVR decreased (17±2, P<0.05), RBF increased (8±1, P<0.05) and MAP remained unchanged (122±3) in SS.BN1 rats whereas RVR increased (19±3, P<0.05), RBF remained unchanged (8±1) and MAP increased (146±4, P<0.05) in SS rats. In conclusion, SS hypertension is abolished in SS.BN1 rats. Dahl SS rats exhibit an unexpected low RVR and high RBF when fed a 0.4% NaCl diet vs. SS.BN1 rats. Yet, SS rats display an impaired ability to lower RVR during a high salt diet as compared to SS.BN1 rats. These data warrant future investigations into the role that UMOD may play in altering renal hemodynamics, SS hypertension and CKD in Dahl SS rats.
Abstract P384: Conditional knockout of Acid Ceramidase in Renal Collecting Ducts Induced Sodium Retention in Mice
Authors: Wang Weili , Li Pin-Lan , Ritter Joseph , Li Ningjun
Published: December 2018

We have previously shown that renal sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite formed by phosphorylation of sphingosine, increases sodium excretion through inhibition of epithelial sodium channel (ENaC) via S1P receptor 1, which is mainly localized in the collecting ducts. However, the role of S1P-producing enzyme in renal sodium excretion remains unknown. The immediate substrate for S1P generation, sphingosine, is formed from the hydrolysis of ceramide by ceramidase, which is a rate-limiting step for S1P production. Acid ceramidase (AC) is the major form of ceramidase in collecting duct. The present study was to test the hypothesis that deletion of AC in the collecting ducts impacts renal sodium handling. Mice with collecting duct-specific AC knockout (CD-AC-KO) were generated by crossing AC floxed mice with Aquoporin 2-Cre mice. The specific knockout of AC in renal collecting ducts was confirmed by immunohistochemistry and Western blot analyses. Functionally, urinary sodium excretion was decreased by 40% in CD-AC-KO mice compared with control mice (Ctrl) after acute IV sodium loading (2.19±0.32 vs. 1.3±0.18 μmole/min.g kwt in Ctrl vs. KO, P<0.05). Furthermore, the natriuretic response to elevated renal perfusion pressure (pressure natriuresis) was severely impaired in CD-AD-KO mice compared with control mice (5.3±0.54 vs. 3.0±0.25 μmole/min.g kwt in Ctrl vs. KO, P<0.05). Moreover, chronic high salt-induced sodium retention was remarkably enhanced in CD-AC-KO mice compared with control animals (2.9±0.21 vs. 5.0±0.30 mmole/100g bw. 24h in Ctrl vs. KO, P<0.05). These results suggest that AC in renal collecting ducts plays an important role in the regulation of renal sodium excretion and that modulation of AC function in the kidneys could be a therapeutic approach for salt-sensitive hypertension.
Abstract P389: Lowered Blood Pressure With Hypertension Management Model in a West African Population: Increased Efficiency and Implications for Improved Outcomes
Authors: Kofi Owusu Isaac , Adomako-Boateng Fred , Kueffer Fred , Guy Molly , Lang'at Chemuttaai , Whitman Teri , Hettrick Douglas , Keith Holloman , Opare-Sem K.O.
Published: December 2018

Objective:
A novel locally appropriate hypertension management model of care was developed and tested in the Republic of Ghana to address specific socioeconomic and community-related barriers to blood pressure (BP) control.

Design and Methods:
Patients with a history of hypertension were enrolled and each agreed to visit a participating nearby community pharmacy at least once per week for 6 months for a BP check, symptom review, and medication monitoring. Weekly pharmacy visit data were manually logged into a mobile application by the pharmacy staff. Guideline based logic in the application provided immediate feedback to the patient and transmitted data to the primary physician. Electronic prescriptions, from the primary physician, were accessible to participating pharmacies. Clinic blood pressure from the prior 6 months was also retrieved from patient records.

Results:
Compliance with weekly BP assessments in the 150 enrolled patients (57± 8 years; 73% Female) was 61% and 2705 total pharmacy BP assessments were conducted. Improvement in overall health awareness was reported in 82% of the patients and 95% indicated a desire to continue using the model of care in the future. During the 6-month voluntary program period, the number of scheduled office visits decreased by 60% compared to standard monthly visits. Despite fewer in clinic visits, average systolic BP decreased significantly from the 6-month pre-trial period baseline (137.4±14.0 to 129.8± 16.3 mmHg, p<0.01). The proportion of patients with blood pressure below target (140 mmHg) for least 75% of all readings increased from 41% in the 6 months prior to enrollment to 62% during the study follow up period (p<0.01). This improvement was associated with potential cardiovascular risk reduction of 5-21% based on previous randomized trials. The proportion of patients with > 75% controlled BP also improved in the subset of patients with BP below target at enrollment from 52% to 76% (p<0.01), implying potential risk benefits even in “well controlled” patients.

Conclusions:
The care model applied in this hypertensive West African resulted in fewer clinic visits and high patient and clinician satisfaction as well decreased systolic blood pressure and increased proportion of time with controlled blood pressure.
Abstract P392: Ambulatory Arterial Stiffness Index Among Children With Chronic Kidney Disease
Authors: Halbach Susan M , Carroll Megan , Ng Derek K , Flynn Joseph T , Samuels Joshua , Furth Susan L , Warady Bradley A
Published: December 2018

The ambulatory arterial stiffness index (AASI) is a non-invasive measure of arterial stiffness derived from ambulatory blood pressure monitoring (ABPM) data. Studies in children have shown higher AASI is associated with obesity and hypertension, but there are no data examining AASI in children with chronic kidney disease (CKD). We used data from the Chronic Kidney Disease in Children (CKiD) Cohort Study to evaluate the association between AASI and hypertensive status on ABPM, and to identify predictors of AASI, including BMI, proteinuria, mineral metabolism and BP parameters from ABPM. Of 639 CKiD participants at their first successful ABPM visit, the mean age was 12 years, 60% (382/639) were male, 15% (96/639) were obese and the mean eGFR was 52 ml/min/1.73m
2
. Approximately two-thirds reported antihypertensive therapy use (66%, 422/639) yet 58% (368/639) met criteria for abnormal ABPM (elevated mean awake/sleep DBP/SBP or awake/sleep load >25%). Participants who met criteria for abnormal ambulatory BP had a higher mean AASI than those with a normal ambulatory BP (0.337 and 0.307, respectively, p=0.008). Masked hypertension (MH) was common (42.4%, 284/639) and those subjects had a significantly higher AASI compared to normotensive children (Table). Male sex, age and BMI category were all positively associated with AASI, but presence of proteinuria, abnormal serum calcium or phosphate were not. AASI is associated with hypertensive status and BMI in children with CKD and may be a useful non-invasive measure of vascular stiffness in this population. The relationship of AASI to other measures of vascular stiffness such as pulse wave velocity requires further study.
Stroke Outcomes With Vorapaxar Versus Placebo in Patients With Acute Coronary Syndromes: Insights From the TRACER Trial
Authors: Ungar Leo , Clare Robert M. , Rodriguez Fatima , Kolls Bradley J. , Armstrong Paul W. , Aylward Philip , Held Claes , Moliterno David J. , Strony John , Van de Werf Frans , Wallentin Lars , White Harvey D. , Tricoci Pierluigi , Harrington Robert A. , Mahaffey Kenneth W. , Melloni Chiara
Published: December 2018

Background

Vorapaxar, a protease‐activated receptor‐1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage.

Methods and Results

TRACER
(Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow‐up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan‐Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22–6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58–1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71–1.24]).

Conclusions

Stroke occurred in <2% of patients. Vorapaxar‐assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.
A new species of Chaunax (Lophiiformes: Chaunacidae) from the western South Pacific, with comment on C. latipunctatus
Authors: HO HSUAN-CHING , SHAO KWANG-TSAO
Published: December 2018

A new species of anglerfish, Chaunax nudiventer, is described on the basis of 35 specimens from the western South Pacific Ocean. It is characterized by large spots on the dorsal surface; a largely naked area on abdomen; a relatively short head and long tail, both reflected in the elongated body; slender and simple spines on body surface; numerous broad flaps on lateral side of body; and higher number of lateral line neuromasts: mainly 41–43 in lateral line proper, 4 in the upper peropercular series, and 16–17 in the pectoral series. Comments on a similar species, C. latipunctatus from the eastern South Pacific Ocean, is provided.
Nomenclatural changes in North American Phymatodes Mulsant (Coleoptera: Cerambycidae)
Authors: SWIFT IAN P. , RAY ANN M.
Published: December 2018

The following nomenclatural changes to the genus Phymatodes Mulsant, 1839 are proposed: P. juglandis Leng, 1890 = P. decussatus (LeConte, 1857); P. mohavensis Linsley and Chemsak, 1963 = P. nitidus LeConte, 1874; P. lecontei Linsley, 1938 (a replacement name) = P. grandis Casey, 1912; P. oregonensis Chemsak, 1963 = P. nigrescens Hardy and Preece, 1927; P. blandus picipes Linsley, 1934 and P. blandus propinquus Linsley, 1934 = P. blandus (LeConte, 1859); P. hirtellus densipennis Casey, 1912 and P. ursae Knull, 1940 = P. hirtellus (LeConte, 1873); P. decussatus australis Chemsak, 1963 and P. decussatus posticus Van Dyke, 1920 = P. obliquus Casey, 1891; P. frosti Casey, 1924, a valid name which has not previously been mentioned in the literature = P. dimidiatus (Kirby in Richardson, 1837); P. concolor Linsley, 1934 is afforded full species status; P. lividus (Rossi, 1794) is formally recorded as established in North America. A key and diagnoses for all native and introduced North American species are provided, which include the more recently described species, P. tysoni Linsley and Chemsak, 1984, and P. shareeae Cope, 1984, in addition to the introduced species P. lividus.
Chinese Paracladius Hirvenoja, with the description of P. ovatus sp. n. (Chironomidae: Orthocladiinae)
Authors: FU YUE , WANG XINHUA , ANDERSEN TROND
Published: December 2018

Six species of Paracladius Hirvenoja, 1973 are recorded from China. One of these, P. ovatus sp. n. from Oriental China is described and illustrated as male. Two species, P. akansextus Sasa et Kamimura, 1987 and P. quadrinodosus Hirvenoja, 1973 are recorded from China for the first time and Chinese material of P. alpicola (Zetterstedt, 1850), P. antennarius Yan et Wang, 2005 and P. conversus (Walker, 1856) are reexamined. A key to the males of Paracladius is presented.
The Effect of Land Surface Heterogeneity and Background Wind on Shallow Cumulus Clouds and the Transition to Deeper Convection
Authors: Lee Jungmin M. , Zhang Yunyan , Klein Stephen A.
Published: December 2018

Idealized large-eddy simulations (LESs) with prescribed heterogeneous land surface heat fluxes are performed to study the impact of the heterogeneity length scale and background wind speed on the development of shallow cumulus and the subsequent transition to congestus/deep convection. We study the impact of land surface heterogeneity in an atmosphere that favors shallow convection but is also conditionally unstable with respect to deeper convection. We find that before the convection transition, larger and thicker shallow cumulus clouds are attached to moisture pools near the PBL top over patches with low evaporative fraction (referred to as “DRY”). This feature is attributable to a surface-induced secondary circulation whose development depends on the heterogeneity size and the background wind speed. With large patches (≥5 km) under zero ambient wind, the secondary mesoscale circulation promotes the vertical transport of moisture forming a moisture pool over DRY patches, while with smaller patches, no such circulation develops. The influence of the background wind on the secondary circulation is strong such that any wind stronger than 2 m s−1 effectively eliminates the impact of surface heterogeneity on the PBL and brings no secondary circulation. This is because the triggered secondary circulation is not strong enough to withstand the imposed background wind. Based on these, we propose two criteria for the convection transition, namely, that the heterogeneity length scale is greater than 5 km and that the background wind speed is less than Uc0, where Uc0 is the near-surface cross-patch wind speed of the secondary circulation under zero background wind for a given patch size and is about 1.5 m s−1 in our cases.