bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P221: Cardiovascular Outcomes In Hypertensive Patients Who Discontinue Study Medication In A Large Outcome Trial. The Life Study.
Authors: Wachtell Kristian , Julius Stevo , Okin Peter M , Greve Anders M , Devereux Richard B , Oparil Suzanne , Kjeldsen Sverre E , Boman Kurt
Published: September 2022

Objective:
Patient discontinuation of study medication during a hypertension outcome trial has implications for study power. We aimed to assess patient characteristics and outcomes in patients with hypertension and left ventricular hypertrophy (LVH) who discontinued the study drug but otherwise remained in the study until the end of follow-up.

Methods:
In patients who discontinued vs. those continuing, Cox proportional hazards models identified baseline variables that had a significant impact on the occurrence of the primary composite endpoint (cardiovascular death, stroke, and myocardial infarction) in 9,193 hypertensive patients and LVH in the LIFE study.

Results:
During a mean follow-up of 4.8 years, 3,281 patients (35.7%) discontinued one or more days, not counting death as a reason for discontinuation. The distribution of days to discontinuation was highly skewed towards the first part of the study; the 25
th
percentile was at day 161, and the median was at day 669. Reasons for discontinuation were a clinical adverse event (50%), a secondary study endpoint (19%), required study therapy (11%), withdrawal (2%), administrative (18%), and lost to follow-up (0.2%). Those who discontinued were older, more often male, had slightly lower body mass index, higher systolic and lower diastolic pressure, higher Framingham Risk Score (FRS), and more ECG LVH determined by either Cornell product or Sokolow-Lyon criteria. Patients randomized to losartan discontinued less than those randomized to atenolol. Multivariate analyses showed that older age, male gender, FRS, Sokolow-Lyon criteria, atenolol treatment as well as a history of pre-study myocardial infarction, cerebral vascular disease, peripheral vascular disease, and atrial fibrillation as well as lower levels of hemoglobin, higher serum creatinine and lower cholesterol independently predicted discontinuation.

Conclusions:
Patients discontinued during the first part of the study mainly due to a clinical adverse event. Patients who discontinued the study drug had, on average, more previous and concurrent cardiovascular disease than those who continued until the study ended. Thus, too high risk in an outcome study implies early drug discontinuation and thus reduction in the study power.
Abstract P225: Dahl Salt-sensitive And Salt-resistant Rats Exhibit Highly Disparate Blood Pressure Responses To Lifetime High Fat Diet Feeding
Authors: Fink Gregory , Xu Hui , Fernandes Roxanne , Garver Hannah , Lauver Adam A , Watts Stephanie W
Published: September 2022

In an effort to understand obesity associated hypertension, we and others are using Dahl salt-sensitive (SS) rats fed a high fat diet as an experimental model. One reason for choosing this rat strain is that it is well-known that SS rats exhibit accelerated hypertension development not just in response to high salt intake but to numerous other stimuli as well, when compared to Dahl salt resistant (SR) rats. However, it is not known whether this general dichotomous sensitivity to hypertension development in SS and SR rats also extends to the impact of high fat feeding. Therefore, in the present study we tested the hypothesis that high fat feeding would cause a smaller increase in blood pressure in SR rats versus SS rats in both females and males (n=8 each). To explore possible strain differences in the mechanisms known to contribute to obesity associated hypertension, we also compared the activity of the renin angiotensin and sympathetic nervous systems in SS and SR rats. Rats were fed a high fat diet (60% kcal fat) from weaning. Blood pressure was measured by telemetry starting at 12 weeks of age. At 12 weeks, mean arterial pressures (MAP, mmHg) were 109±8 and 158±6 in male SR and SS rats, and 108±1 and 150±5 in female SR and SS rats, respectively. By 18 weeks MAP were 109±7 and 175±4 in male SR and SS rats, and 108±1 and 180±4 in female SR and SS rats, respectively. In males, plasma renin was lower, and aldosterone the same, in SS rats than SR rats. However, SS rats showed larger falls in blood pressure during week-long ACE inhibitor treatment and to acute sympathoinhibition with hexamethonium than did SR rats. In females, plasma renin and aldosterone both were higher in SS rats than SR rats. Female SS rats also showed larger falls in blood pressure to chronic ACE inhibition and acute ganglion blockade than did SR rats. These results confirm that both male and female SR rats are highly resistant to obesity associated hypertension, and that less robust activation by high fat diet of the renin angiotensin and sympathetic nervous systems may be a causative factor.
Abstract P236: Role Of Axl In Target Organ Inflammation And Damage Due To Hypertensive Aortic Remodeling
Authors: Chen Wei , Van Beusecum Justin P , Xiao Liang , Patrick David , Ao Mingfang , Zhao Shilin , Cavinato Cristina , Caulk Alexander W , Humphrey Jay D , Harrison David G
Published: September 2022

Background:
Aortic remodeling enhances arterial pulsatility in the microcirculation and we have shown that excessive endothelial stretch increases release of Growth Arrest Specific 6 (GAS6), which activates Axl on monocytes causing immune activation and inflammation.

Hypothesis:
GAS6/Axl blockade reduces renal and vascular inflammation and lessens renal dysfunction caused by aortic remodeling.

Methods and Results:
Three month old male C57Bl/6 mice received osmotic minipumps containing vehicle or ang II for 2 weeks and the pumps removed. Aortas demonstrated increased collagen and an 80% loss of Windkessel function that persisted for 6 months following ang II. Renal function studies showed reduced ability to excrete a volume load, a progressive increase in albuminuria and tubular damage as estimated by Periodic Acid Schiff staining. Treatment with the Axl inhibitor R428 beginning 2 months after ang II had minimal effect on aortic remodeling 2 months later, but reduced aortic and renal infiltration of T cells, gamma/delta T cells and macrophages as measured by flow cytometry (Figure). R428 also improved renal excretory capacity, decreased urinary NGAL, reduced albuminuria, and attenuated renal tubular damage. Interestingly, macrophage/T cell complexes were present in aortas of mice previously exposed to hypertension, and were reduced by R428.

Conclusion:
Brief episodes of hypertension induce chronic aortic remodeling which increases Axl signaling and transformation of monocytes to inflammatory antigen presenting cells that activate T cells. Axl blockade might serve as a therapeutic option to improve end-organ damage after an episode of hypertension.
Abstract P237: Mitochondrial GCN5L1 Promotes CypD Acetylation, Oxidative Stress, Endothelial Dysfunction And Hypertension
Authors: Dikalov Sergey , Tkachuk Liliya , Ao Mingfang , Fehrenbach Daniel , Sack Michael , Dikalova Anna
Published: September 2022

Nearly half of adult population has hypertension which is a main risk factor for cardiovascular disease. Mitochondrial dysfunction contributes to hypertension and targeting mitochondria can potentially improve treatment of hypertension. We found hyperacetylation of mitochondrial Cyclophilin D (CypD) in essential hypertension and proposed that CypD acetylation can promote endothelial dysfunction and hypertension. CypD acetylation can be regulated by general control of amino acid synthesis 5 like 1 (GCN5L1) protein, therefore, we GCN5L1 can potentially promote endothelial dysfunction and hypertension. Western blot of aortic mitochondria showed an increased GCN5L1 level in hypertensive mice which was coupled with the reduction of Sirt3 deacetylase level resulting in 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. We reported pathogenic role of mitochondrial lipid oxidation products isolevuglandins (isoLGs) and scavenging of isoLGs with mitochondria-targeted mito2HOBA reduces mitochondrial acetylation. We tested if mitochondrial isoLGs contributes to acetylase/deacetylase imbalance driving CypD acetylation. It was found that mito2HOBA supplementation improves Sirt3 expression and reduces GCN5L1 level leading to normalization of GCN5L1/Sirt3 ratio and reduced CypD acetylation. To define the pathophysiological role of GCN5L1 in endothelial cells we tested if GCN5L1 depletion prevents cytokine-induced of mitochondrial oxidative stress. Indeed, treatment of human aortic endothelial cells with AngII+TNFα induces mitochondrial O
2
.
-, however, GCN5L1 depletion using siRNA completely abrogated the cytokine-induced mitochondrial oxidative stress. To define the role GNC5L1 in pathogenesis of endothelial dysfunction we have developed new tamoxifen-inducible endothelial specific GNC5L1 knockout mice (Ec
GNC5L1KO
). It was found that depletion of endothelial GCN5L1 reduces vascular production of mitochondrial O
2
.
-, prevents inactivation of endothelial nitric oxide and preserves endothelial dependent relaxation in angiotensin II-infused Ec
GNC5L1KO
mice compared with wild-type littermates. These data support the pathogenic role of GNC5L1 in CypD acetylation and development of endothelial dysfunction.
Abstract P239: Angiotensin II-Induced Memory Gamma Delta T Cells Sensitize Mice To A Mild Hypertensive Stimulus
Authors: Paradis Pierre , Comeau Kevin , Schiffrin Ernesto L
Published: September 2022

Hypothesis:
We hypothesize that memory γδ T cells form after a hypertensive challenge, and that they sensitize mice to develop hypertension to mild hypertensive stimuli.

Methods:
Ten-12-week-old C57BL/6J mice were exposed or not to a pressor dose of angiotensin II (490 ng/kg/min, SC) for two weeks, followed by a two-week washout period, and then infused with a subpressor dose of angiotensin II (140 ng/kg/min, SC) for two weeks. Blood pressure (BP) was measured by telemetry and memory γδ T cells profiled by flow cytometry. A subset of mice was injected IP with 400 μg of anti-T cell receptor γδ-depleting or isotype control antibodies 1 day before and 6 days after the initiation of second hypertensive challenge. A final subset was injected IV with 2.5x10
5
γδ T cells isolated from hypertensive or normotensive mice, and then exposed to a subpressor dose of angiotensin II as above.

Results:
Repeated hypertensive challenges yielded a higher systolic BP than one mild hypertensive stimulus (154±4 vs 120±3 mm Hg,
P
<0.01). Two-week pressor dose angiotensin II increased effector memory γδ T cells in mesenteric artery perivascular adipose tissue (1.25±0.37% vs. 0.24±0.12%, P<0.05) and mesenteric lymph nodes (1.49±0.03% vs 0.82±0.15%, P<0.05). γδ T cell depletion reduced systolic BP elevation from day 8 (135±5 vs 150±5 mm Hg,
P
<0.05) to day 13 of the second hypertensive challenge (150±5 vs 163±2 mm Hg,
P
<0.05). Adoptive transfer of γδ T cells isolated from hypertensive compared to normotensive mice caused a greater systolic BP elevation in response to a subpressor dose of angiotensin II (159±3 vs 142±6 mm Hg,
P
<0.01).

Conclusion:
Memory γδ T cells develop after a hypertensive challenge and sensitize mice to mild hypertensive stimuli. Memory γδ T cells may represent a novel therapeutic target to treat hypertensive humans.
Abstract P245: Catheter-based Radiofrequency Renal Denervation In Normotensive Pigs Leads To Long-term Pathological Changes In Renal Nerves
Authors: Lee David P , Kandzari David E , Tunev Stefan , Schlaich Markus P , Finn Aloke , TRUDEL Julie , Sharp Andrew
Published: September 2022

Objective:
Pre-clinical data of renal nerve regrowth following radiofrequency (RF) renal denervation (RDN) are lacking. In this analysis of RF RDN in normotensive pigs, we assessed the specificity and durability of RF ablation to the perivascular tissues around the renal arteries.

Design and Method:
RF ablations were delivered to the renal arteries in pigs. To assess specificity, serial tissue samples were harvested from 6 pigs at day 7, and 8 pigs at day 28. Surrounding tissues (ureter, kidney, lymph nodes, skeletal muscle, adrenal glands, and renal nerves) were evaluated with a semi-quantitative scoring system (
Figure
). To assess durability, RF RDN was performed in a separate group of pigs with an additional control group. Serial tissue examination at day 7 (n=6 animals per group) and day 180 (n=8 per group) included quantification of cortical norepinephrine (NE) levels and renal cortical axon density, and evaluation for fibrosis, necrosis, and nerve fiber atrophy.

Results:
Disruption to non-target perivascular tissues was rare, whereas artery nerve disruption and axonal loss were sustained through 28 days (
Figure
). At 180 days, there was nerve atrophy from axonal destruction around the ablation regions. Necrosis was evident at day 7 but not day 180. Fibrosis was confined to the ablated regions. Renal cortical axon density and cortical NE levels were significantly reduced at 7 and 180 days in the RDN group vs. control.

Conclusion:
RF RDN specifically disrupted the renal nerves leading to axonal loss. Cortical axon density, NE reduction, and nerve atrophy were sustained through 180 days. These results support the existing clinical evidence of the specificity and durability of RF RDN.
Abstract P251: Assay Performance And System Compatibility For RAAS Triple-A Analysis In Hypertension Profiling
Authors: Poglitsch Marko , Mengozzi Giulio , Stanley Scott , Hedge Michael , Domenig Oliver , Schmidt Uwe , Nonnato Antonello , Settanni Fabio , Ponzetto Federico , Shoemaker Robin C
Published: September 2022

Recent studies revealed major concerns related to the accuracy of widely used clinical assays for aldosterone and renin, fueling the need for alternative and more robust bio-analytical solutions for assessment of the Renin-Angiotensin-Aldosterone-System (RAAS) in clinical samples. RAAS Triple-A profiling is a high-throughput mass-spectrometry based assay for quantification of Angiotensin I (Ang I), Angiotensin II (Ang II) and Aldosterone in serum samples. Quantified hormone levels are used to calculate markers for plasma-renin-activity (PRA-S), plasma angiotensin-converting-enzyme activity (ACE-S) and adrenal aldosterone secretion (AA2-Ratio), which can be used for clinical profiling in patients with uncontrolled hypertension. A RAAS Triple-A LC-MS/MS kit was recently launched as an In Vitro Diagnostic (IVD) device in Europe for hypertension profiling. In the current study, a comparative approach was used to assess analytical performance of the RAAS Triple-A assay on three different LC-MS/MS systems, Altis+ (Thermo Scientific), Xevo TQ-S (Waters), and Triple Quad 6500+ (Sciex) located in three different laboratories. RAAS Triple-A kits (96-well format) were used to analyze one set of n=50 triplicate human serum samples at each location. At each site, samples were sample preparation and LC-MS/MS analysis according to the RAAS Triple-A kit manual. Analytical validation of assay linearity, precision, and accuracy were evaluated at each site, and Bland-Altman-Analysis was used to test for quantification bias between sites. Results demonstrate the measured concentrations for each analyte, Ang I, Ang II, and aldosterone, were strongly correlated between sites (R
2
= Ang I: 0.996; Ang II: 0.991; Aldo: 0.983). Performance characteristics of all target analytes were in compliance with European Medical Agency (EMA) standards for bio-analytical assays on each instrument. Robust assay performance across laboratories and different LC-MS/MS systems allows for a broad clinical application of RAAS Triple-A profiling potentially improving treatment efficacy in hypertension by supporting treatment decisions with individual RAAS Triple-A profiles.
Abstract P300: Patterns Of Adherence To Home Blood Pressure Monitoring Among Men And Women In The Electronic Framingham Heart Study
Authors: Paul Tenes J , Soni Apurv , Pathiravasan Chathurangi H , Asaker Jean-Claude , Mehawej Jordy , Filippaios Andreas , Zhang Yuankai , Sadaniantz Katherine , Wang Ziyue , Benjamin Emelia J , Liu Chunyu , Lin Honghuang , Murabito Joanne M , McManus David D , Kovell Lara
Published: September 2022

Blood pressure (BP) measures in women more sharply increase with age compared with men, with a widening disparity in older women. The use of home blood pressure monitoring (HBPM) among women may improve this inequity. However, sex-related differences in adherence to HBPM are not well understood.

We analyzed data from electronic Framingham Heart Study participants who were given a Withings digital BP cuff and instructed to perform HBPM weekly for 1 year. Adherence was defined as ≥1 BP measurement per week, averaged over 4-week segments. HTN status was self-reported. Group-based trajectory modeling (GBTM) was used to identify trajectory patterns of adherence. We investigated the association of 3 adherence patterns with HTN status stratified by sex using multinomial logistic models adjusting for age group, marital status, education, employment status, income, non-BP cardiac medication use, subjective health, depression and anxiety.

Among 1,048 participants (59% female, mean age 53±9 years, 25% with HTN), we identified 3 trajectory groups corresponding to distinct patterns of HBPM adherence: early discontinuation (N = 458, 58% female, 21% HTN), gradual decrease (N = 360, 60% female, 27% HTN), and high adherence (N = 230, 57% female, 31% HTN,
Figure 1
). Women with HTN compared to women without HTN had 80% higher odds of being in the high adherence group versus early discontinuation group (aOR 1.80; 95% CI 1.02-3.17). This pattern was not observed for men (aOR 1.12; 95% CI 0.68-1.63).

In this middle-aged eCohort, HTN was associated with high adherence to HBPM in women but not men. The targeted prescription of HBPM for woman should be studied to see if it can reduce sex disparities in BP control.
Abstract P306: A Specific 3-month Nursing Program After Laboratory Detection Of Non-adherence To Medication In Uncontrolled Hypertension Improves Adherence And Blood Pressure Control (ATHAN Trial)
Authors: Oliveras Anna , Vazquez Susana , Camps Carme , Vega Victoria , Vinyoles Ernest , Fontdevila Laia , Faura Anna , Crespo Marta , Pascual Julio , Hernández Juan José
Published: September 2022

Non-adherence to treatment is a known factor for uncontrolled hypertension. We hypothesized that the detection of non-adherence to antihypertensive treatment plus the implementation of a specific nursing program would ameliorate treatment adherence and blood pressure (BP) control.An interventional, prospective, randomized, study of 44 consecutively attended patients (age 58.1±12.9yr, 30 men/14 women) with 24h-BP ≥130/80 mmHg while receiving ≥2 antihypertensive drugs was performed. Partially or fully non-adherent patients (confirmed by urine determination of antihypertensives) were randomized (1:1) to receive a specific 3 month nursing program (group I) to improve adherence - evaluation of knowledge on BP goals, complications of high BP, indicated treatment; detection of causes of non-compliance and proposal of measures to improve it, with fortnightly follow-up -, or to routine follow-up (group C). Urine antihypertensives and 24h-BP were determined at baseline, 3 and 12 months. Baseline office SBP/DBP (mmHg) was 150.4±16.3 / 91.1±15.5, and the number of prescribed non-detected drugs was 2±1.4. Between-groups differences in variation (Δ) of BP at 3 and 12 months are shown (Table). In addition, at 3 months, the percentage of patients with controlled BP was 50%( 11 of 22) and 18.2% (4 of 22) in the I and C groups, respectively (p=0.026), and at 12 months was 60% (12 of 20) and 26.3% (5 of 19), respectively (p=0.034).In conclusion, a specific 3 month nursing intervention improves control of BP in patients with uncontrolled hypertension and inadequate therapeutic compliance. Both the BP decrease and the improvement in therapeutic adherence were maintained at 12 months.
Abstract P308: Comparative Cost-effectiveness Of Hypertension Treatment Guidelines In US Adults
Authors: Penko Joanne , Bellows Brandon K , Hennessy Susan , Kazi Dhruv S , Coxson Pamela , Bibbins-Domingo Kirsten , Moran Andrew E
Published: September 2022

Introduction:
The 2017 ACC/AHA guidelines lowered blood pressure (BP) thresholds for hypertension diagnosis and treatment compared to the 2003 JNC7. We compared cost-effectiveness of treating to ACC/AHA and JNC7 over 10 years in untreated hypertensive adults 35-84 years of age.

Methods:
The Cardiovascular Disease (CVD) Policy Model simulates CVD events, deaths, and costs in US adults. Inputs are estimated from national datasets, cohort studies, and literature. We simulated three treatment strategies: (1) no pharmacological treatment; (2) full JNC7; or (3) full ACC/AHA. Base-case analyses targeted all treatment-eligible adults. Secondary analyses stratified treatment by baseline BP (130-139/80-89 vs. ≥140/90 mmHg) and indicators of high CVD risk (diabetes, CKD, CVD, or 10-yr risk ≥10%).

Results:
Twenty-four million untreated adults could be treated under JNC7 and 29 million under ACC/AHA, preventing 1.2 million and 1.5 million CVD events at 10 years, respectively. Treating to JNC7 compared to no treatment and ACC/AHA compared to JNC7 was cost-effective (<$50,000 per quality-adjusted life year gained) (Table). JNC7 or ACC/AHA was cost-saving for high-risk adults with BP ≥140/90 mmHg and cost-effective for high-risk adults with BP 130-139/80-89 mmHg (JNC7: $103,000/QALY; ACC/AHA: $90,000/QALY). Both JNC7 and ACC/AHA cost >$150,000 per QALY gained for treating lower risk adults.

Conclusion:
Treating according to either JNC7 or ACC/AHA guidelines is a cost-effective way to prevent CVD. At ten years, regardless of guideline, treating high-risk hypertensive patients is either cost-saving or cost-effective; treating lower-risk patients is relatively low value.
Abstract P321: Hypertension-related Cardiovascular Mortality In Asian American Subgroups
Authors: Shah Nilay S , Shimbo Daichi , Muntner Paul , Huffman Mark D , Kandula Namratha , Mefford Matthew , Lloyd-Jones Donald , Khan Sadiya
Published: September 2022

Introduction:
Cardiovascular disease (CVD) mortality rates are heterogenous among Asian American subgroups. To inform more precise prevention strategies, we identified patterns of hypertension-related CVD mortality in Asian American subgroups.

Methods:
Among deaths with CVD (ICD-10: I00-I99) as the underlying cause and hypertensive disease (ICD-10: I10-I15) as underlying or contributing cause in 2018-2021 mortality data from CDC WONDER with concurrent population estimates from the IPUMS Current Population Survey, we calculated age standardized mortality rates (ASMR) and proportional mortality for non-Hispanic Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Hispanic adults, with non-Hispanic White as the reference.

Results:
There were 37,746, 95,404, and 867,599 deaths in non-Hispanic Asian, Hispanic and non-Hispanic White groups, respectively. Among non-Hispanic Asian females, ASMR ranged from 41.6 (95% CI 40.0-43.3) per 100,000 population in Japanese to 52.6 (51.0-54.2) per 100,000 in Filipina women. Among non-Hispanic Asian males, ASMR ranged from 45.8 (43.3-48.2) per 100,000 in Korean to 81.0 (78.5-83.5) in Filipino men (Table). Proportional mortality was higher for all Asian American subgroups vs. non-Hispanic White individuals. Proportional mortality ratios ranged from 1.11 (Korean males) to 1.38 (Filipino males; Chinese and Filipina females), vs. non-Hispanic White individuals.

Conclusions:
There was substantial variation in hypertension-related cardiovascular mortality among Asian American subgroups. All Asian subgroups had higher proportional mortality compared with non-Hispanic White individuals.
Abstract P329: Moderate Dietary Sodium Restriction Does Not Alter Insulin Sensitivity Or Secretion In Metabolic Syndrome
Authors: Mustapha Taopheeq A , Manning Robert , Luther James M
Published: September 2022

We previously demonstrated that maximal dietary sodium restriction (10mmol/d) decreases insulin secretion and impairs insulin secretion. It is unclear if dietary changes other than NaCL account for this and if more moderate sodium restriction reflecting clinically achievable ranges would alter glucose metabolism. We therefore hypothesized that moderate diet-induced stimulation of the renin-angiotensin-aldosterone system would impair insulin secretion in participants with the metabolic syndrome. We conducted a randomized, double-blind cross-over study in 29 volunteers in which we provided a standardized 50mmol Na/day diet for 7 days. Participants were provided encapsulated NaCl 150 mEq/d (High Sodium, HS) or matching placebo capsule (Low Sodium, LS) for 7 days. Insulin sensitivity was assessed with hyperinsulinemic clamp and insulin secretion was assessed with hyperglycemic clamp at 5 and 7 days of diet, respectively. LS diet increased plasma aldosterone compared to HS diet (15.2±6.2 vs 10.8±3.2;
P
<0.001) but did alter blood pressure (126.5±13.6 vs 128.7±13.9 mmHg;
P
=0.49). Fasting glucose and insulin were similar during LS diet. As assessed by hyperinsulinemic clamps, insulin sensitivity was similar (0.2756 ± 0.0771 vs 0.2917 ± 0.0722 mg/kg/min per uU/mL Insulin;
P
=0.49). Insulin clearance tended to decrease during the LS period (980 ± 410 vs 1127 ± 366; P=0.10). There was no difference in glucose-stimulated insulin secretion assessed by hyperglycemic clamp (55.3 ± 47.7 vs 50.0 ± 36.7 uU/ml; P=0.7). Dietary sodium restriction achievable dose not alter glucose and insulin metabolism in the short term.
Abstract P332: The Hypertension Induced By Clozapine Is Related With Increased Renal Sodium Transporters In Mice
Authors: Ren Zhiyun , Wang Weiwan , Zhang Chenyang , Wang Xiaoyan
Published: September 2022

Introduction:
Hypertension is caused by multi-factors, and the pathogenesis is linked to, generally, the increases in the protein expressions and functions of renal sodium transport proteins along the nephron. One of the major side effects of clozapine (common antipsychotic drug) is hypertension. The mechanism is unknown.

Hypothesis:
the pathogenesis of the clozapine-induced hypertension is associated with increases of renal sodium transport proteins.

Methods:
we examined the blood pressures (BP) and protein expressions of major sodium transport proteins profiled along the renal tubules in the C57Bl6/J male mice (9 weeks old, n=4-5/group) treated with clozapine at three doses of 5,10 and 20 mg/ kg for 1 week via intraperitoneal injection.

Result:
blood pressures (tail-cuff, BP98A, softron, Japan) were higher in clozapine at 20mg/kg/day than vehicle (SBP: 130±1.64 vs 109±1.39, DBP: 87 ±4.12 vs 69±2.10 mmHg, n=5/group) and not altered at 5 & 10 mg/kg/day. There were no differences in BW, serum/urine creatinine and electrolytes except for a slight increase in serum sodium at dose of 20 mg/kg (152.8±0.71 vs 150.6±0.40, mmol/L).In renal homogenates, total protein abundance of NaPi2 (western blotting,199±26% of vehicle) NKCC2(184±20), NCC(213±14),and ENaC-α(217±47),were higher at 20 mg/kg than vehicle. No increases were found in protein expressions of NHE3, αNKA, ENaC-β and ENaC-γ. The expressions of renin, AT1R and ACE at 20mg/kg were similar between groups while ACE2 was decreased (42±10). No increases were found in protein expressions of pNKCC2 in 5&10mg/kg(100±50,45±15); NCC was increased at 5 mg/kg (175±9); α NKA was increased in 5mg/kg (216±5) and 10mg/kg (163±2) groups.In plasma membrane enriched fraction (17k), NKCC2(204±43) and ENaC-α(381±28)were higher at 20 mg/kg than vehicle. In intracellular membrane enriched fraction (200k), NKCC2(521±127) was higher than vehicle. Phosphorylated NKCC2 was increased in renal homogenates(331±35),17k(427±87) 200k(521±127) but WNK4 was not changed.

Conclusions:
increases of renal sodium transport proteins, mainly pNKCC2 and NKCC2, contribute to the dose-related increase of BP in mice treated with clozapine and may play an important role in the pathogenesis of the clozapine-induced hypertension.
Abstract P338: High Sodium Intake - Effects On Afferent Renal Nerve Activity
Authors: Rodionova Kristina , Ditting Tilmann , Linz Peter , Hilgers Karl F , Ott Christian , Schmieder Roland E , Schiffer Mario , Amann Kerstin , Veelken Roland
Published: September 2022

Previous work of ours suggests that the sensitivity of renal afferent neurons is decreased under pathological conditions. Here we tested the hypothesis that pathologically decreased sensitivity of renal afferent neurons due to high salt diet is normalized after renal denervation. 6 male Sprague Dawley (SD) rats were put on high salt diet (HS; 8% NaCl) for 10 days. In another group of 18 rats on high salt diet (HS) left kidneys were denervated (DNX) 7 days prior to examination. 17 rats on standard diet with and without DNX were used as controls. Dorsal root ganglion neurons with renal afferents were investigated in primary neuronal cell culture using current clamp mode to assess action potential generation during current injection. Neurons were characterized as tonic highly active (> 5 action potentials, AP) and phasic less active neurons (≤ 5 AP upon stimulation)In renal neurons from rats on HS the relation of tonic to phasic neurons shifted towards less active phasic units (62% tonic neurons in control vs. 42% on HS, p<0.05, z-test). Denervation (DNX) of the left kidney in rats on high salt diet (HS-DNX) led to a recovery of afferent renal DRG neurons remaining vital after denervation. They regained their electrophysiological property of mainly tonic firing (42% tonic neurons in HS vs. 71% HS-DNX, p<0.05, z-test).In rats on high salt diet the proportion of highly active tonic neurons with renal afferents decreased at the expense of less active phasic neurons. This HS effect could be abolished by DNX.
Abstract P342: Virtual Cardiac Rehabilitation For Heart Failure - Real World Experience Of Medication Adherence, Blood Pressure Control And Exercise Tolerance
Authors: SIGAMANI ALBEN , Singh Pallav
Published: September 2022

Introduction:
India has a high burden of young-onset heart failure owing to an increased incidence of ischemic heart disease(IHD) in young and older adults (<60 years). Hypertension affects 207 million adults in India; less than 20% have controlled blood pressure. Cardiac rehabilitation (CR) effectively improves outcomes in patients with heart failure but is very scarce; there is only one spot for every 360 IHD patients/year, with more than 3 million CR spaces needed each year.

Methods:
Virtual cardiac rehabilitation is administered via a mobile application, Numen Health. This is a physician-led program delivered by a multi-disciplinary team of experts. The experts provide multi-faceted interventions for IHD patients, targeting increased medication adherence, behavior changes, reinforced lifestyle modification, blood pressure control through diet, exercise, and building mental resilience with continued care post-hospital discharge.

Results:
Between April 2021 and March 2022, 42 patients with low ejection fraction (LVEF<45%) heart failure registered on the program. They represented nearly 10% of 426 IHD patients who had joined the program. Over a median duration of 90 days, target blood pressure control was achieved in 39/42 (93%). Zero hospital re-admissions were encountered; 17/42(40%) achieved improved cardiac and exercise tolerance compared to baseline exercise tolerance time. It had increased from 15 minutes to 30 minutes, 200% from baseline. The median MET score on day 90 was 13 (9-17). Physical activity duration per week increased; to 90 minutes on average; It had risen from the ability to do for <5 minutes at baseline. Medication adherence and clinical follow-up were 100% of the prescribed. A self-rated satisfaction scale scored the program at 90 - 95 /100 on day 30 by all.

Conclusions:
Virtual Cardiac Rehabilitation in India is feasible and possibly effective in delivering integrated CR services at home. Numen health shows promise in bridging the gap of negligent CR services across India.
Abstract P355: Involvement Of Nlrp3 Inflammasome In Vascular Injury-induced Neointimal Formation And PDGF-BB Stimulated Monocyte Retention And Pyroptosis In Arterial Smooth Muscle Cells
Authors: Wang Yunting , Zhang Yang , Li Xiang
Published: September 2022

Intimal hyperplasia due to pathological vascular remodeling is a common feature of cardiovascular diseases such as atherosclerosis and restenosis after angioplasty. Nlrp3 inflammasome has been reported to trigger endothelial injury leading to pathological vascular remodeling in metabolic diseases. This study aimed to elucidate whether the Nlrp3 inflammasome in smooth muscle cells (SMCs)
per se
is involved in their phenotypic regulation and thereby contributes to pathological vascular remodeling. The ligation injury-induced neointimal hyperplasia model was established in hypercholesterolemic mice. Mice received a single intravenous injection of AAV encoding mutant mPCSK9 (rAAV8-D377Y-mPCSK9). Then mice received partial ligation surgery in left carotid artery (LCA) and consumed a high fat, high cholesterol diet for 4 weeks. The neointimal formation and various markers related to synthetic phenotype and Nlrp3 inflammasome pathways were assessed in ligated LCA. The collateral un-ligated right carotid artery (RCA) served as controls. Our data revealed that ligation injury induced neointimal formation in Nlrp3
+/+
mice, which was markedly attenuated in Nlrp3
-/-
mice (intima area: Nlrp3
+/+
15.97±4.07 μm
2
vs.
Nlrp3
-/-
4.31±1.27 μm
2
). Ligation injury drastically increased Nlrp3 inflammasome activation, monocyte adhesion, pyroptosis, and synthetic phenotype trans-differentiation in LCAs of Nlrp3
+/+
mice. These changes were largely limited in the SMC-enriched neointimal region and abrogated in Nlrp3
-/-
mice. PDGF-BB, a ligation injury-associated factor promoting SMC synthetic phenotype transition, activated Nlrp3 inflammasomes in cultured SMCs. Inhibition of inflammasome-dependent caspase-1 by Ac-YVAD-cmk attenuated PDGF-BB-induced SMC-monocyte interaction and pyroptosis, whereas proliferation and migration of SMCs were unaffected. Together, these results suggest that in arterial SMCs, activation of Nlrp3 inflammasomes and subsequent events including induction of pyroptosis and adhesion of monocytes are essential for ligation injury-induced neointimal formation. These results provide new insight into the mechanisms of Nlrp3 inflammasome action in SMCs in pathological vascular remodeling in hypercholesterolemia.
Angiotensinogen Suppression: A New Tool to Treat Cardiovascular and Renal Disease
Authors: Cruz-López Edwyn O. , Ye Dien , Wu Congqing , Lu Hong S. , Uijl Estrellita , Mirabito Colafella Katrina M. , Danser A.H. Jan
Published: September 2022

Multiple types of renin-angiotensin system (RAS) blockers exist, allowing interference with the system at the level of renin, angiotensin-converting enzyme, or the angiotensin II receptor. Yet, in particular, for the treatment of hypertension, the number of patients with uncontrolled hypertension continues to rise, either due to patient noncompliance or because of the significant renin rises that may, at least partially, overcome the effect of RAS blockade (RAS escape). New approaches to target the RAS are either direct antisense oligonucleotides that inhibit angiotensinogen RNA translation, or small interfering RNA (siRNA) that function via the RNA interference pathway. Since all angiotensins stem from angiotensinogen, lowering angiotensinogen has the potential to circumvent the RAS escape phenomenon. Moreover, antisense oligonucleotides and small interfering RNA require injections only every few weeks to months, which might reduce noncompliance. Of course, angiotensinogen suppression also poses a threat in situations where the RAS is acutely needed, for instance in women becoming pregnant during treatment, or in cases of emergency, when severe hypotension occurs. This review discusses all preclinical data on angiotensinogen suppression, as well as the limited clinical data that are currently available. It concludes that it is an exciting new tool to target the RAS with high specificity and a low side effect profile. Its long-term action might revolutionize pharmacotherapy, as it could overcome compliance problems. Preclinical and clinical programs are now carefully investigating its efficacy and safety profile, allowing an optimal introduction as a novel drug to treat cardiovascular and renal diseases in due time.
Reservoir Pressure Integral Is Independently Associated With the Reduction in Renal Function in Older Adults
Authors: Aizawa Kunihiko , Hughes Alun D. , Casanova Francesco , Gates Phillip E. , Mawson David M. , Gooding Kim M. , Gilchrist Mark , Goncalves Isabel , Nilsson Jan , Khan Faisel , Colhoun Helen M. , Palombo Carlo , Parker Kim H. , Shore Angela C
Published: September 2022

Background:

Arterial hemodynamic parameters derived from reservoir-excess pressure analysis exhibit prognostic utility. Reservoir-excess pressure analysis may provide useful information about an influence of altered hemodynamics on target organ such as the kidneys. We determined whether the parameters derived from the reservoir-excess pressure analysis were associated with the reduction in estimated glomerular filtration rate in 542 older adults (69.4±7.9 years, 194 females) at baseline and after 3 years.

Methods:

Reservoir-excess pressure parameters, including reservoir pressure integral, excess pressure integral, systolic, and diastolic rate constants, were obtained by radial artery tonometry.

Results:

After 3 years, and in a group of 94 individuals (72.4±7.6 years, 26 females), there was an estimated glomerular filtration rate reduction of >5% per year (median reduction of 20.5% over 3 years). A multivariable logistic regression analysis revealed that higher baseline reservoir pressure integral was independently associated with a smaller reduction in estimated glomerular filtration rate after accounting for conventional cardiovascular risk factors and study centers (odds ratio: 0.660 [95% CIs, 0.494–0.883];
P
=0.005). The association remained unchanged after further adjustments for potential confounders and baseline renal function (odds ratio: 0.528 [95% CIs, 0.351–0.794];
P
=0.002). No other reservoir-excess pressure parameters exhibited associations with the reduction in renal function.

Conclusions:

This study demonstrates that baseline reservoir pressure integral was associated with the decline in renal function in older adults at 3-year follow-up, independently of conventional cardiovascular risk factors. This suggests that reservoir pressure integral may play a role in the functional decline of the kidneys.
Meetings: The Operation of Grassroots Political Power in the Northwest Shanxi Anti-Japanese Base Area
Authors: Yue (岳靖芝) Jingzhi
Published: September 2022

Grassroot communities are critical fields of governance. To enhance the development of local government and to mobilize, organize, and arm the people to fight against the Japanese invaders, the Communist Party employed a number of methods in the base areas during the Anti-Japanese war. Among them, holding meetings was an effective method to get the work done and to forge leadership in local governance in the base areas, and it built a space of power that incorporated and displayed both group and individual experiences. Though the endless rounds of meetings can be seen as a kind of formalism, they provide a pivotal angle to observe the operation of power in the Northwest Shanxi Anti-Japanese Base Area. For the Communist Party, whose purpose was to reshape the countryside, the implementation of policies was far more important than their formulation. The villages were the critical places where the Party interacted with the people, where most of the meetings occurred, and where most of the policy directives were implemented. Grassroot meetings in the base areas revealed directly the willingness of the people to participate as well as their on-site performance, and indirectly the response of the people toward the Party’s policies and how the Party dealt with that response. Making decisions, mobilizing and organizing the people, and implementing policies were the basic functions of meetings. The establishment of the institution of meetings and the twists and turns of its practice reflected the gaps between the Party’s ideal and practice, and between the Party and the people.
What Does “Environmental Populism” Mean?
Authors: Sconfienza Umberto Mario
Published: September 2022

The current article brings together and reviews the literature on “environmental populism”; that is, environmental issues that could be explored through a populist frame. The article reviews four different cases of environmental populism: (i) right-wing populism and climate denial, (ii) resource populism, (iii) eco-populism, and (iv) the populism of environmental movements. For each case, the article analyzes how different theories of populism explain the environmental issues under consideration and how the environment is constructed. Lastly, the article argues that these four different cases only share very abstract features between them, and greater clarity would be gained by dropping the “environmental populism” label altogether in favor of “environmental populisms,” in the plural.
Taxonomic review of Manulea (M.) tienmushanica (Daniel), comb. nov., and its allies with descriptions of two new species from mainland China (Lepidoptera: Erebidae: Arctiinae)
Authors: VOLYNKIN ANTON V. , SALDAITIS AIDAS , HUANG SI-YAO
Published: September 2022

The Manulea tienmushanica (Daniel, 1954) species group is established, characterised and reviewed. Two new species are described: Manulea (M.) salweena sp. n. (China: Yunnan), and Manulea (M.) diaforetica sp. n. (China: Yunnan). Two new combinations are established: Manulea (M.) tienmushanica (Daniel, 1954), comb. n. and Manulea (M.) nigripuncta (Fang, 2000), comb. n. Adults, male and female genitalia are illustrated.
North China Spring Rainfall and Its Linkage with SST and Atmospheric Circulation
Authors: Shang Lin , Li Wenhong
Published: September 2022

Spring rainfall is important for agriculture and economics in North China (NC). Thus, there is an imperative need for accurate seasonal prediction of the spring precipitation. This study implements a novel rainfall framework to improve understanding of NC spring rainfall. The framework is built based on a three-cluster normal mixture model. Distribution parameters are sampled using Bayesian inference and a Markov chain Monte Carlo algorithm. The probability behaviors of light, moderate, and heavy rainfall events can be reflected by the three rainfall clusters, respectively. Analysis of 61-yr data indicates that moderate rainfall makes the largest contribution (67%) to the total rainfall amount. The moderate rainfall intensity is mainly influenced by the sea surface temperature anomaly (SSTA) in the previous season over the equatorial eastern Pacific, and rainfall frequency is influenced by geopotential height anomaly in the mid- to high latitudes in spring. It is also found that more extreme precipitation events can be observed in the spring following an eastern Pacific El Niño event in the previous autumn and winter. Based on these relationships, we develop a multiple linear regression model. Hindcasts for spring precipitation using the model indicates that its anomaly correlation is 0.48, significant at the 99% confidence level. The result suggests that the newly developed model can well predict spring rainfall amount in NC.
Intertwined Crises: California’s Public Universities’ Responses to COVID-19 and Anti-Asian Animus, January 2020 to June 2021
Authors: Castro Samayoa Andrés , Nguyen Bach Mai Dolly , Lally Marisa , Pemberton Brittney
Published: September 2022

COVID-19 ravaged everyday life for individuals across the globe, but its impact was especially harmful to Asian Americans who suffered both a notably high risk of infection and hospitalization, as well as a sharp rise in anti-Asian racism. In this article, we take these intertwined issues—a synergistic interaction between a novel virus and the deeply rooted racism rendering Asian Americans as perennial foreigners—to interrogate whether and how organizations’ early responses to COVID-evidenced communicative strategies that acknowledged the crises that unraveled throughout 2020. Through the framings of Situational Crisis Communication Theory and Racialized Organizations, this study considers what repertoire of crisis communication strategies do public institutions employ to address COVID-19 and what do these responses reveal about racialized inequality in higher education? The findings draw from an original archive of 2,723 public community messages across 31 public institutions in the University of California and California State University systems and demonstrate a deprioritization of responsiveness to anti-Asian animus amid the multiple issues emergent from COVID-19; rather than taking the opportunity to foreground universities’ capacity to respond to this crisis, institutions often redirected their responsibility. Such evidence reveals that universities are racialized organizations that employ management strategies that remain ill-prepared to not only manage racialized inequality throughout the crises of the COVID-19 syndemic but also to interrupt racism’s durability.
Traumatic Gallbladder Rupture in a Pediatric Patient Misdiagnosed as Acute Appendicitis
Authors: Ferenczy Allison , Glenn Joshua
Published: September 2022

We present an 8-year-old male with a history liver surgery as a neonate who presented to the emergency department with a chief complaint of abdominal pain. A computed tomography scan (CT) showed ascites with dilated loops of small bowel and the appendix was not visualized. The pediatric surgery team was consulted for possible perforated appendicitis. Patient was initially treated with conservative management. The patient became peritoneal and was taken for diagnostic laparoscopy. A laceration of the dome of his gallbladder was visualized and a cholecystectomy was performed. Traumatic gallbladder rupture is a rare entity and occurs in 2% of all blunt abdominal injuries. The diagnosis can be difficult to make due to nonspecific symptoms. While an avulsion to the gallbladder may be diagnosed on CT scan, gallbladder lacerations can be difficult to visualize on imaging. The practitioner must have a suspicion for gallbladder injury to aid in the diagnosis.
Experiences of Community Resilience and Inequity Among LGBTQ+ People: A Person-Centered Analysis
Authors: Parmenter Joshua G. , Galliher Renee V.
Published: September 2022

A diverse sample of LGBTQ+ people ( N = 527) was recruited to explore sexual and gender diverse peoples’ co-occurring experiences with community resilience resources and inequity within the LGBTQ+ community. Using latent profile analysis, four distinctive latent profiles emerged: Marginalized, Ambivalent, Disengaged, and Embedded. Beta regression analyses suggested that identity centrality played a pivotal role in a participants’ membership to a given profile. Additionally, plurisexual and gender diverse identities may be associated with less likelihood of membership in profiles that were high in LGBTQ+ community resilience resources. Profile membership was also associated with mental health, internalized minority stress, and LGBTQ+ identity affirmation. The present study assists in expanding the understanding of co-occurring processes (i.e., community resilience resources and inequity within the LGBTQ+ community) and how they link to mental health, internalized minority stress, and positive LGBTQ+ identity outcomes for sexual and gender diverse people. We discuss implications for practice, education, training, and research.