bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P235: Relationship Between Skin Sympathetic Nerve Activity And Nocturnal Non-dipping Blood Pressure In Patients With Postural Orthostatic Tachycardia Syndrome
Authors: Liu Xiao , Rosenberg Carine , Reaso Jewel N , Li Xiaochun , Rader Florian , Chen Peng-Sheng
Published: September 2022

Background:
Patients with postural orthostatic tachycardia syndrome (POTS) have a high incidence of nocturnal non-dipping of blood pressure (BP).

Objective:
To test the hypothesis that non-dipping of BP is associated with persistently elevated nocturnal skin sympathetic nerve activity (SKNA) in patients with POTS.

Methods:
We used Bittium Faros 180 ECG monitor to simultaneously record electrocardiogram (ECG) and SKNA, and SpaceLab OnTrak arterial BP monitor (ABPM) over 24-hr in 55 POTS patients (51 women, 36±10 years-old). The Faros signals were high pass filtered at 300 Hz to display the SKNA. The same original signals were bandpass filtered 0.05-150 Hz to display ECG. BP was measured every 30-min when awake (7 AM to 9 PM) and hourly at night (9 PM to 7 AM).

Results:
The overall successful ABPM measurement was 71±18%. Nocturnal dipping of BP was presented in 40 patients with an average dipping% of 15.5±4.8%. Nocturnal non-dipping of BP was present in 15 patients with an average dipping% of 3.9±3.7% (p<0.001).
Figure A
shows hourly averaged SKNA. A mixed effect model was used to compare the log (SKNA) values of two groups of patients at all time points, with patient as a random effect. The non-dipping group had higher SKNA from midnight of day 1 to 4 am of day 2 (indicated by the red bars, p=0.0118, 0.0223, 0.0402, 0.0382, 0.0424). The difference between awake time and sleep time (determined by patients’ diary) average SKNA was 0.155±0.106 μV in dipping group and 0.076± 0.101 μV in the non-dipping group (p=0.017,
Figure B
).

Conclusion:
Nocturnal non-dipping of BP is associated with non-dipping of SKNA in patients with POTS suggesting sympathetic nerve activity plays an important mechanistic role.
Abstract P243: Innovative Care Team Design: An Original Approach To Optimize Patient Outcomes With Our RN-pharmacist Led Hypertension Clinic
Authors: Overstreet Jordan , Clausen Sonja , Comer Keven J , Jennings Angela
Published: September 2022

Background:
Bozeman Health (BH) Primary Care provides care to >8000 patients with a diagnosis of hypertension (HTN). In 2019, less than half of these patients had their blood pressure (BP) controlled. The State of Montana Board of Pharmacy grants pharmacists the ability to have collaborative practice agreement(s) with providers. This allows the pharmacist to act as an intermediary to the provider and a ‘safety net’ for the nurses working off protocol. Utilizing evidence-based medication protocols, registered nurses (RNs) with clinical pharmacy collaboration, began treating HTN patients utilizing motivational interviewing, shared decision making, lifestyle modification, risk assessment tools, medication titration and regular follow-up. The program is initiated with a primary care provider (PCP) referral.

Methods:
The RN-Pharmacist led HTN Clinic was implemented in January 2019 after a 3-month pilot program which showed 90% (35 of 39) of enrolled patients achieved BP goal within 9 weeks or less. Ambulatory care RNs completed a 12-week intensive educational program on HTN. Upon completion of education, RNs managed patient appointments (including telemedicine appointments), charted and worked off medication protocol algorithms. Office notes were sent to the pharmacist to sign prescriptions and subsequently to the PCP for general information. Patients were seen in follow-up every 2-4 weeks with the HTN RN until their BP and personal goals were met. The primary objective of this project was to have 75% of patients referred to the hypertension clinic at goal within 12 weeks. Secondary outcomes included: secondary cause risk assessment, decrease in BMI, and high patient satisfaction scores.

Results to date:
•Enrolled 607 patients, 74% (237 of 321) at BP goal within 12 weeks •Average decrease in systolic BP - 8.4mmHg and diastolic BP - 5.5mmHg •Net decrease of 0.12kg/m2 in BMI upon graduation •Patient program satisfaction surveys 4.8/5; 5 being “very satisfied”

Conclusions:
The RN-Pharmacist Led HTN Clinic is an innovative, collaborative, multidisciplinary approach to hypertension management that allows care team members to practice at the top of licensure while improving HTN outcomes and achieving high patient satisfaction.
Abstract P244: Tubular Sites Of Mtorc2 Inhibition Of Sodium Transport In Dahl Salt-sensitive Rats.
Authors: Cowley Allen W , Yang Chun , Isaeva Olena , Shimada Satoshi , Kurth Terry , Stumpf Megan , Kriegel Alison J , Dash Ranjan K
Published: September 2022

Background:
There is evidence that the mTOR signaling pathway plays an important role in salt induced hypertension in the Dahl salt-sensitive (SS) rat via regulation of Na
+
excretion. PP242 inhibition of mTORC1-2 prevented hypertension in SS rats and intrarenal PP242 produced a 4-fold increase of Na
+
excretion while selective inhibition of mTORC1 with rapamycin had no effect. The goal of the present study was to identify the renal tubular Na
+
transporters regulated by the mTORC2 pathway.

Methods:
Natriuretic effectors of mTORC2 were deduced from the differences of Na
+
excreted with PP242 treatment beyond that observed by the natriuretic actions of benzamil (B; ENaC inhibitor), furosemide (F; NKCC2 inhibitor), hydrochlorothiazide (H; NCC inhibitor) and in combination (B+F+H). Unanesthetized SS rats were first administered B, F, H or B+F+H (i.p.) and 2 days later with co-administration of PP242 with these same reagents. Rats were studied when fed 0.4% NaCl (LS) and then following 3 weeks of a 4.0% NaCl (HS) diet. The effect of PP242 on ENaC activity in freshly isolated cortical collecting ducts was also examined using cell-attached patch clamp electrophysiology.

Results:
Urine Na
+
excretion rates determined at 20 min. intervals over 80 minutes increased nearly 2-fold with administration of PP242 + B, compared to B alone [0.10
+
0.02 vs. 0.04
+
0.01 mmol/100gbw (n=8; P<0.05)] and similarly in the F and H comparisons [F: 0.20
+
0.02 vs. 0.10
+
0.02 mmol/100gbw (n=8; P<0.05); H: 0.05
+
0.01 vs. 0.03
+
0.01 mmol/100gbw (n=8; P=0.06)]. PP242 given in the presence of F+B+H did not further enhance the overall natriuretic response. Rats fed HS showed little enhancement of natriuresis when PP242 was administered with any of the drugs. Minimum changes in K
+
excretion were observed with PP242 in LS or HS studies. Patch clamp studies found that PP242 reduced ENaC activity through reduction of the open channel probability (Po) in both LS and HS fed rats. Western blot data indicated that PP242 reduced pNCC T53 and phosphorylation of SGK1.

Conclusion:
Together, these studies found evidence that the natriuretic actions of PP242 are a consequence of inhibitory actions on the ENaC and NCC transporters in the distal nephron segments.
Abstract P248: Estrogen Replacement Mitigated Blood Pressure Elevation Via Suppression Of Sodium Cotransporter In Angiotensin Ii-infused Ovariectomized Female Rats
Authors: Kim Yang Gyun , Cho Minhae , Moon Ju Young , Lee Sang Ho
Published: September 2022

Introduction:
Female rats with lower proximal sodium transporters are known to excrete natriuresis faster than male rats. However, it is not sure whether the protective effect would be conserved in menopausal rats.

Hypothesis:
We assessed the hypothesis that ovariectomy would change renal sodium transporters in female rats and the estrogen supplementation could reverse angiotensin II (ANGII)-induced changes in renal sodium transporters and natriuresis.

Methods:
Six-week female Sprague Dawley rats (n=22) were ovariectomized, and half of them (n=11) were treated with estradiol 2 weeks later for 4 weeks, and then ANGII (n=14) or vehicle (n=8) was infused via osmotic minipumps for 2 weeks. Blood pressure (BP) was measured by the tail-cuff sphygmomanometer. Blood, urine, and kidney samples were collected.

Results:
The ANGII induced significant BP elevation in ovariectomized (OVX) and OVX with estradiol (OVX+E) rats. OVX affected elevating BP even in the sham rats. Albuminuria significantly increased in ANGII-infused OVX rats and did not change in ANGII-infused OVX+E rats. Urine sodium was significantly decreased in ANGII-infused OVX rats, while it increased in ANGII-infused OVX+E rats. Sodium transporters in the proximal tubule (sodium-hydrogen exchange 3, sodium phosphate cotransporter) were not different between OVX and OVX+E irrespective of ANGII infusion. Among the distal tubule transporters (α/β/γ-epithelial sodium channel (α/β/γENaC), sodium chloride cotransporter (NCC), phosphorylated NCC (pNCC)), pNCC were markedly augmented in ANGII-infused OVX rats, whereas not changed in ANGII-infused OVX+E rats. ANGII infusion affected increasing ANGII type 2 receptor (AT
2
R) in OVX+E rats but did not influence AT
2
R levels in OVX rats.

Conclusions:
Estradiol has the protective effect from elevating BP in ANGII-infused OVX rats. It was achieved via augmentation of natriuresis, which was connected to the suppression of NCC.
Abstract P250: Targeting The Thrombospondin-CD47 Axis Attenuates Blood Pressure And Renal Injury In Female Hypertensive (mRen2)27 Rats
Authors: Mackert Jessica , Wilson Adam , Cruz-Diaz Nildris , Melo Ana C , Chappell Mark C , Soto-Pantoja David
Published: September 2022

Alterations in the extracellular matrix (ECM) can influence vascular stiffness and compromise organ function contributing to hypertension. A key component of the ECM is the type I integral membrane receptor CD47 that regulates the ECM by binding to the matricellular protein thrombospondin-1(TSP1). Increased circulating levels of TSP1 and CD47 activation are associated with cardiac and renal pathologies. Thus, the objective of the current study determined the efficacy of targeting CD47 with an anti-sense morpholinos to reduce blood pressure and renal injury in 20-week old hypertensive (mRen2)27 female rats. The CD47 morpholino (Morph) or the missense probe (Control) were dissolved in sterile PBS and administered by tail vein injection twice weekly for 6 weeks. Systolic blood pressures (SBPs) were monitored in conscious rats by a tail cuff auscultation and expression of RAS components assessed by RT-qPCR; all data are means ± SEM with n=8-10 per group. Prior to treatment, the baseline SBPs did not differ between the Control and Morph groups [196 ± 5 vs.197 ± 4 mmHg; p=0.87]. However, as early as one week of treatment, the CD47 Morph group exhibited a significant reduction in SBPs compared to the Control transgenics [185 ± 5 vs. 204 ± 3 mmHg; p<0.01]. At the end of the 6 week treatment period, SBPs remained significantly lower in the CD47 Morph group compared to the Controls [185 ± 4 vs.199 ± 3 mmHg; p<0.02]. In addition, CD47 blockade was associated with reduced proteinuria in the CD47 Morph compared to Controls [7 ± 1 vs. 26 ± 7 mg protein/24 hr excretion; p<0.05]. Regarding the mechanism of CD47 blockade to reduce blood pressure and proteinuria, mRNA analysis revealed lower renal renin mRNA levels in the CD47 Morph versus the Control group [0.54 ± 0.11 vs.1.04 ± 0.11; p<0.01]. Moreover, CD47 Morph treatment significantly reduced the mRNA levels of renal ACE [0.78 ± 0.13 vs.1.05 ± 0.14; p<0.05] and the renal AT1A receptor [0.74 ± 0.07 vs.1.05 ± 0.12; p<0.05], however, renal angiotensinogen mRNA levels were not different among the CD47 Morph and Controls [1.04.± 0.10 vs. 1.16 ± 0.20, p=0.83]. We conclude that silencing CD47 attenuates hypertension and renal injury in the female (mRen2)27 potentially by reducing expression of the renin-ACE-AT1 receptor axis within the kidney.
Abstract P252: Differential Expression Of ACE2, Neprilysin And ACE In Extracellular Vesicles Isolated From Human Urine
Authors: Chappell Mark C , Yamaleyeva Liliya M
Published: September 2022

The Ang II convertase ACE2 is present in urine and may correlate with various renal pathologies. We reported functional ACE2 in urinary exosomes and now extend our studies to distinguish exosomes (EXOs) and microvesicles (MVs) containing ACE2, as well as neprilysin (NEP) and ACE. EXO purification was modified by an intermediate centrifugation step (20k xg, 60 mins) to pellet MVs followed by 100k xg to pellet EXOs. The MV, EXO, and 100k supernatant (soluble, SOL) fractions were assessed for ACE2 activity with MCA-APK-DNP, and NEP and ACE activities with MCA-RPPGFSAFK-Dnp with selective inhibitors. Peptidase activities were expressed as relative fluorescent units (RFU x10
6
/min/mL), and data are means ± SEM (*P<0.05; **P<0.01, N=4). Morning collections from male subjects [51 to 65 years of age, non-smokers] were collected, treated with Cibacron blue to bind albumin, 0.2 μM filtration, and 100 kDa Amicon concentration prior to high speed and ultracentrifugation steps. ACE2 activity was >3-fold higher in the EXO versus the MV fractions with minor activity in the SOL fraction. In contrast, NEP activity was highest in the MV fraction [~2-fold > EXO] while endopeptidase activity was barely detectable in the SOL fraction. ACE activity was similar in MVs and EXOs, but NEP activity was 40-fold higher than ACE in both the MV and EXO fractions. Differential centrifugation of the 100-kDa urine concentrate reveals a unique profile of ACE2, NEP and ACE expression in MVs and EXOs. The functional significance of these peptidase activities in different vesicular populations is currently unknown; however, their origin may reflect the distinct regulation and release of ACE2 and NEP/ACE in urinary vesicles.
Abstract P253: Delta And Omicron Variants Of SARS-Cov-2 Do Not Stimulate ACE2 Conversion Of Ang II To Ang-(1-7)
Authors: Chappell Mark C
Published: September 2022

The Spike domain of SARS-COV-2 binds ACE2 and induces peptidase internalization removing a key regulatory site within the renin-angiotensin system that may exacerbate the effects of SARS-COV-2. However, a recent study finds that an early Beta variant (D614G) of the SARS-COV-2 Spike protein and its receptor-binding domain (RBD) markedly stimulated ACE2 activity using fluorescent substrates. The more dominant forms of SARS-COV-2 include the Delta and Omicron variants and we determined whether these new variants activate ACE2. Delta (B.1.617.1) and Omicron (B.1.1.529) RBDs, and Beta Spike (B1.351) were incubated with human soluble ACE2 for 10 mins at 37°C followed by Ang II [2 μM] and 125I-Ang II [0.5 nM] for up to 20 mins, and the Ang-(1-7)/Ang II ratio quantified by HPLC-γ detection. Ang-(1-7)/Ang II increased linearly over time and doubled with 10 ng of ACE2 (*P<0.01 vs 5 ng; N=4); however, the Delta or Omicron RBD proteins (1 μM) failed to stimulate ACE2 activity at any time point (A). Varying concentrations of the Delta or Omicron RBDs, as well as Spike protein also failed to stimulate ACE2 activity (5 ng), although 200 nM Omicron RBD was inhibitory (B). The newer Spike variants may not activate ACE2; however, the Spike D614G variant also failed to activate ACE2, which questions whether SARS-COV-2 enhances ACE2 activity to metabolize Ang II. We conclude that Delta and Omicron variants do not stimulate the metabolism of Ang II to Ang-(1-7). Moreover, alterations in circulating ACE2 activity in COVID-19 patients likely reflect changes in protein content through shedding of the peptidase, although the interaction of ACE2 autoantibodies to influence peptidase activity is also possible.
Abstract P302: Efficacy Of A Digital Hypertension Self-management And Lifestyle Coaching Program In Reducing Blood Pressure Across Sex, Language And Racial Groups
Authors: Roberts Jenn , Roach Brian , Gazit Tomer , Mark Shirley , Aggarwal Sanjeev
Published: September 2022

Introduction:
Hypertension affects nearly half of adults in the U.S. and is more prevalent in non-Hispanic black and Hispanic people than other groups. HEDIS now includes blood pressure readings from remote monitoring devices that are digitally stored and transmitted to the provider. Digital interventions used to support self-management of hypertension are effective in reducing blood pressure. Healthcare policies that support adoption of innovative digital interventions can positively impact groups with greater health disparities.

Hypothesis:
We tested the hypothesis that systolic blood pressure (SBP) change observed after 6 months in a smartphone-based hypertension self-management program would demonstrate similar outcomes across subgroups and not be impacted by known health inequities based on sex, language or race.

Methods:
A cohort study of individuals who enrolled in a digital-only hypertension self-management program without live coaching was used to evaluate SBP change at 6 months and its association with age, sex, language (English/Spanish), and race. Because race information was only available in a subset of the cohort who shared electronic medical records, the largest sub-groups (432 white and 127 non-Hispanic black adults) were compared.

Results:
15,361 (age 57 ± .8y, 37% female) people uploaded SBP data at both time points. A reduction in SBP was observed (t = 15.1, p<.01), and the majority (62.3%) reduced SBP. 83.6% (4139 of 4947) of those with stage 2 hypertension (SBP ≥ 140 mm Hg) at program start reduced SBP, with an average reduction of 16.6 ± 0.18 mm Hg. No difference in SBP change was found based on age, race, or preferred language (all ps > .05). Females had a greater reduction in SBP than males (1.5 ± 0.19 mm Hg, p<.01).

Conclusions:
This study supports the use of a smartphone-based hypertension program incorporating AI driven, digital-only self-management and lifestyle coaching to reduce SBP similarly across age, race, and preferred language groups. Results indicate that digital self-management tools have the potential to bridge health inequity gaps. Future studies could assess whether digital behavioral change coaching leads to reduced SBP across disadvantaged groups based on Area of Deprivation Index (ADI).
Abstract P305: MACHINE LEARNING DETECTS ASSOCIATIONS BETWEEN RETINA FEATURES AND BLOOD PRESSURE STATUS IN RICE DIET PROGRAM PATIENTS
Authors: Sommerfeld Romeo , Lorenz Cedric , Lopez David , Kuo Anthony , Bergner Benjamin , Luft Friedrich Cameron C , Lippert Christoph , Daubechies Ingrid , Neelon Francis , Klemmer Philip , Sanoff Scott , Lin Pao-Hwa
Published: September 2022

The retina provides direct evidence of target-organ damage, and in hypertension, it may reflect vascular disease status in conjunction with clinical measurement of blood pressure (BP). However, outcomes of the examination of the retina varies from one clinician to another due to various reasons. Machine learning methods have been used as a supportive tool in identifying deep retina features objectively and consistently. The Kempner Rice Diet Program, developed in the early 1940s, used a low-salt and low-protein diet intervention (Rice Diet) to treat patients with severe hypertension before effective drug treatment was available. The meticulously documented medical records of the Rice Diet Program patients and their retina photographs provide a rare opportunity to examine the association of BP trajectories and target-organ damage as reflected in the retina. We trained a deep neural network on systolic BP and funduscopic changes from the UK Biobank Project. We achieved an R
2
value of 0.36 on 16,357 validation retina images from the UK Biobank. Our model predicts BP values for specific retinal areas by producing heatmaps of higher or lower hypertensive findings. We then applied the model on 975 retina photographs of 165 patients of the Rice Diet Program. We observed a significant correlation between retina features and systolic BP (Correlation= 0.35, p = 2*10
-29
), showing that the model generalizes to patients with hypertension and images taken under a variety of conditions between 1944-1971. We suggest that deep-learning-based predictions for retinal analysis could be useful in monitoring treatment progress and recovery from hypertension-induced target-organ damage. This assessment serves as an adjunct to point-of-care BP measurements in the subset of 165 patients. Our findings underscore the potential utility of machine learning in hypertension evaluation and treatment. Further, it may allow us to elucidate individual responses to hypertension treatment beyond BP measurement alone. Findings from this first-step analysis may promote development of more effective BP control strategies.
Abstract P307: A Case Of Dual Tachycardia Presenting With Heart Failure Exacerbation
Authors: Osman Abdul-Fatawu , Ezeh Ebubechukwu , Jamal Shakeel Muhammad , Sheikh Ali
Published: September 2022

Dual tachycardia (DT) is the occurrence of simultaneous supraventricular tachycardia and ventricular tachycardia/fibrillation (VT/VF). With increasing interest in this uncommon arrhythmia due to difficulties with diagnosis and complexity of management, DT is identified in about 9% of double-chamber ICD interrogation. An 81 year old male with history of hypertension, ischemic cardiomyopathy status-post BiV AICD presented to ED with worsening exertional dyspnea, orthopnea and pedal edema. He was tachycardic (140 bpm) with bibasilar rales. BNP 655 pg/mL, cardiomegaly and pulmonary edema on chest x-ray. EKG revealed atrial fibrillation (AF) with rapid ventricular response. Echocardiogram revealed a reduced left ventricular ejection fraction <20%. He was diuresed with furosemide, diltiazem infusion for rate control and heparin for anticoagulation. During admission, he developed two episodes of monomorphic VT in VF zone and was successfully cardioverted. During the initial episode, he was in AF and had a VT triggered by PVC which was successfully cardioverted to BiV Paced rhythm. However, he remained in AF which was converted to sinus rhythm after a second cardioversion. A repeat EKG revealed sinus rhythm with BiV paced rhythm. He was later transitioned to oral metoprolol, amiodarone to maintain rhythm control and apixaban.

Dual tachyarrhythmia can be managed with medical therapy and/or catheter ablation. The termination of the trigger AF/PVC has been shown to reduce the recurrence of VT/VF episodes. Rhythm control for AF with antiarrhythmic therapy can reduce AF and PVC burden, improve BiV pacing, prevent ICD shocks and help reduce heart failure exacerbation.
Abstract P310: Defining Systolic Blood Pressure Normative Values In Hospitalized Pediatric Patients
Authors: Uber Amanda M , Han Jialin , Montez-Rath Maria E , Chaudhuri Abanti
Published: September 2022

Background:
Hypertension (HTN) has been recognized as an evolving problem in the pediatric population with concern for increasing incidence. Normative values of blood pressure (BP) in children and definition of HTN in the outpatient setting exist, which cannot be reliably used for inpatient treatment and therapy initiation, because of several factors unique to the inpatient setting. No normative exists to describe HTN in hospitalized pediatric populations. We aimed to produce normative BP values for hospitalized pediatric patients in the acute care setting.

Methods:
We conducted a cross sectional observational study among all children hospitalized on the acute care floors, ≥ 2 and < 18 years of age, at Stanford Children’s Hospital, from Jan-01-2014 to Dec-31-2018. Our cohort included 4112 patients with a total of 118,423 automated, oscillometric, BPs measured in the upper extremity during a hospitalization of >24 hours.

Results:
In our cohort the overall prevalence of HTN, defined by outpatient guidelines, was 14-41% in boys and 7-34% in girls. Centile curves (Figure 1) were derived from the data set and demonstrated an overall higher BP reading for hospitalized patients when compared to the outpatient setting.

Conclusion:
Higher blood pressures are anticipated during hospitalization compared to patients in the ambulatory setting, hence outpatient 2017 clinical practice guidelines cannot be reliably used for inpatient treatment and therapy initiation. The thresholds provided by the centile curves may provide the clinician with some guidance how to manage hospitalized pediatric patients based on clinical circumstances.
Abstract P312: High Potassium Intake Aggravates Cardiovascular Damage Accompanied By Premature Senescence In Hypertensive Apolipoproteine-ko Mice Under High Salt Diet
Authors: Arifaj Denada , Lang Alexander , Yakoub Mina , Argov Doron , Rahman Masudur , Hering Lydia , Temme Sebastian , Rump Lars Christian , Gerdes Norbert , Stegbauer Johannes
Published: September 2022

Increased sodium intake aggravates cardiovascular diseases. Salt substitute containing potassium chlorideimproves cardiovascular outcome in hypertensive patients with high cardiovascular risk, however it isunknown whether it is attributed to potassium (K+) supplementation or sodium reduction. Here, weinvestigate the role of high K+ intake on the development of hypertensive cardiac damage in the presenceor absence of high salt diet. 8-10 weeks old apolipoproteinE-deficient mice (apoE-KO) were fed a normalK+ (0,55%) or high K+ (5%) diet throughout the experiment. Two weeks after diet start,mice were infusedwith angiotensin (Ang)II (500ng/kg/min) for 28 days. Cardiac function was assessed by MRI. High K+ dietincreased serum K+ levels compared to mice fed a normal K+ diet (5.3±1.2 vs. 3.9±0.4mmol/L, p<0.05).Interestingly, high K+ diet did not affect blood pressure or cardiac function. As expected, aldosteroneexcretion was increased in high K+ diet group compared to normal K+ diet (132±20 vs 8±18 ng/24h,p<0.01). To evaluate the consequence of K+ mediated aldosterone secretion for hypertensivecardiovascular damage, we additionally treated our high K+ group with high salt diet (1%NaCl) in thedrinking water. High K+ induced aldosterone production in the presence of high NaCl intake aggravatedhypertensive cardiac damage characterized by higher left ventricular mass, more cardiac fibrosis andinflammation compared to mice fed a high K+ or a high NaCl diet solely. Furthermore, the simultaneousintake of high K+/NaCl diet, induced higher mitochondrial ROS production in cardiac endothelial cellscompared to high K+ or high NaCl diet alone. As a consequence, cellular senescence markers such as p16and p21 were significantly higher in mice fed a high K+ / NaCl diet. Of note, co-treatment withspironolactone (50mg/kg/day), significantly attenuated cellular senescence and cardiovascular damage inmice fed a high K+/NaCl diet. High K+ diet compared to normal K+ diet does not have a beneficial effecton hypertensive cardiac damage in apoE-KO mice. Moreover, the present study indicates that potassium-induced aldosterone production aggravates the detrimental effect of high salt intake on cardiac health inhypertension by influencing cardiac senescence.
Abstract P314: Loss Of Set7 Prevents Isoproterenol-induced Heart Dysfunction
Authors: Lunardon Guilherme , de Oliveira Silva Tábatha , Lino Caroline , Lu Yao Wei , Miranda Juliane , Asprino Paula , Irigoyen Maria Claudia , Takano Ana Paula , Barreto-Chaves Maria Luiza , Wang Da-Zhi , De Almeida Silva Amanda , Diniz Gabriela P
Published: September 2022

Recent studies have revealed the influence of histone-modifying enzymes in cardiac remodeling and dysfunction. The Set7 methyltransferase regulates the expression of several genes through methylation of histones and modulates the activity of non-histone proteins. However, the role of Set7 in heart dysfunction remains unknown. To answer this question, wild type (WT) and Set7 knockout (KO) male mice were injected with isoproterenol (iso) or saline (s) subcutaneously for 14 days. The WTiso mice displayed decreased Set7 activity in the heart compared to WTs mice (Table 1). Both WTiso and KOiso mice exhibited increased heart weight to tibia length ratio (HW/TL) and cardiomyocyte area. However, KOiso mice had higher HW/TL and cardiomyocyte area compared to WTiso mice. Sirius Red staining revealed that both WT and KO mice injected with iso had increased myocardial fibrosis compared to their controls. Nonetheless, loss of Set7 attenuated iso-induced myocardial fibrosis. Echocardiogram showed that WTiso mice had lower ejection fraction (EF) and fractional shortening (FS), and higher E/A ratio compared to WTs mice. Conversely, KOiso mice did not show alteration on these parameters compared to their controls. RNA sequencing analysis revealed that biological processes related to oxidant detoxication, cellular respiration, and anti-inflammatory response were enriched in the heart of KOiso mice compared to WTiso mice. On the other hand, biological processes related to cell aging, interferon production, and immune response were downregulated in the heart of KOiso mice compared to WTiso mice. Collectively, our data suggest that Set7 deletion prevents iso-induced heart dysfunction.
Abstract P315: Nogo-a Reduces Ceramide
De Novo
Biosynthesis To Protect From Heart Failure
Authors: Sasset Linda , Manzo Onorina , Zhang Yi , Marino Alice , Rubinelli Luisa , Riemma Maria Antonietta , Chalasani Madhavi Latha S. , Dasoveanu Dragos C. , Roviezzo Fiorentina , Jankauskas Stanislovas , Santulli Gaetano , Bucci Mariarosaria , Lu Theresa , Di Lorenzo Annarita
Published: September 2022

Growing evidence correlate the accrual of the sphingolipid ceramide in plasma and cardiac tissue with heart failure (HF). Regulation of sphingolipid metabolism in the heart and the pathological impact of its derangement remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of endoplasmic reticulum, abundant in the vascular wall, down-regulates the sphingolipid
de novo
biosynthesis, via serine palmitoyltransferase (SPT), first and rate liming enzyme, to impact vascular functions and blood pressure. Nogo-A, a splice isoform of Nogo, is transiently expressed in cardiomyocyte (CM) following pressure overload. Cardiac Nogo is upregulated in dilated and ischemic cardiomyopathies in animals and humans. However, its biological function in the heart remains unknown.We discovered that Nogo-A is a negative regulator of SPT activity and refrains ceramide
de novo
biosynthesis in CM exposed to hemodynamic stress, hence limiting ceramide accrual. At 7 days following transverse aortic constriction (TAC), SPT activity was significantly upregulated in CM lacking Nogo-A and correlated with ceramide accrual, particularly very long chain ceramides, which are the most abundant in CM, resulting in the suppression of “beneficial” autophagy. At 3 months post-TAC, mice lacking Nogo-A in CM showed worse pathological cardiac hypertrophy and dysfunction, with 50% mortality rate. Mechanistically, Nogo-A refrains ceramides from accrual, therefore preserves the “beneficial” autophagy, mitochondrial function, and metabolic gene expression, limiting the progression to HF under sustained stress.
Abstract P318: Blood Pressure And Cardiovascular Disease Mortality Among US Adults, 1999-2019
Authors: Elfassy Tali , Tremblay Julien , German Charles A , Drexler Yelena , Yang Eugene , Contreras Gabriel
Published: September 2022

Introduction:
Elevated blood pressure (BP) is recognized as the leading risk factor for cardiovascular disease (CVD). Low BP values are also markers of concurrent CVD. Our objective was to determine the association between systolic BP (SBP) and diastolic BP (DBP) with CVD mortality, comparing different BP ranges in a contemporaneous population.

Methods:
The National Health and Nutrition Examination Survey is a nationally representative survey of the US population. Our sample included data from 53,561 adult participants of the 1999-2018 cycles, with measured BP and mortality data available through 2019 linked from the National Death Index. BP was measured three times with a standardized sphygmomanometer and averaged. CVD mortality was defined through ICD-10 codes as diseases of the heart or cerebrovascular disease. We used age adjusted Poisson regression models to estimate incidence densities ratios (IDRs) for CVD mortality. All analyses accounted for the complex survey design.

Results:
The population was comprised of 51% women with a mean age of 46 years. After an average follow-up of 9.9 years, 7,825 (10.5%) died of any cause and 2,451 (3.1%) died of CVD. Compared with SBP 110 - < 120mmHg, CVD mortality did not differ at SBP 100-<100mmHg or 120-<130 mmHg, but was significantly higher by: 56% with SBP <100mmHg (IDR: 1.56, 95% CI: 1.15, 2.10), 21% with SBP 130 – < 140mmHg (IDR: 1.21, 95% CI: 1.04, 1.42), 36% with SBP 140 – < 160mmHg (IDR: 1.36, 95% CI: 1.14, 1.64), and 77% with SBP ≥160mmHg (IDR: 1.77, 95% CI: 1.47, 2.14). Compared with DBP 70 - < 80mmHg, CVD mortality was significantly higher by 64% with DBP < 50mmHg (IDR: 1.64, 95% CI: 1.38, 1.94), 46% with DBP 50 - < 60mmHg (IDR: 1.46, 95% CI: 1.26, 1.670), 24% with DBP 60 – < 70 mmHg (IDR: 1.24, 95% CI: 1.09, 1.41), 36% with DBP 80 – < 90mmHg (IDR: 1.36, 95% CI: 1.15, 1.61), 54% with DBP 90 – < 100mmHg (IDR: 1.54, 95% CI: 1.20, 1.97), and 182% with DBP ≥100mmHg (IDR: 2.82, 95% CI: 1.90, 4.19).

Conclusion:
Among US adults, we found a J shaped association between both SBP and DBP with CVD mortality. Lowest risk of CVD mortality was found at SBP 110 - < 120mmHg, with higher risk at levels below 100mmHg or at or above 130mmHg. For DBP, lowest risk of CVD mortality was found at DBP 70 - < 80mmHg, with higher risk at levels below 70mmHg or at or above 80mmHg.
Abstract P319: Genetic Interactions Between Novel Genes
Arhgef11
And
Cgnl1
Are Involved In Hypertensive Chronic Kidney Disease
Authors: Attipoe Esinam , Johnson Ashley C , Chandran Agata , Wu Wenjie , Garrett Michael R
Published: September 2022

Patients with hypertension are at higher risk for developing chronic kidney disease (CKD) and ultimately kidney failure. Previous genetic studies involving the Dahl salt-sensitive (SS) rat, a well-established model of hypertensive CKD, identified multiple regions linked to kidney injury. Extensive work on Chr.2 identified and characterized the role of
Arhgef11
in the onset and progression of CKD using SS-
Arhgef11
-/-
rats. The identification of
Arhgef11
and mechanism (regulation of actin cytoskeleton components) has provided an opportunity to expedite gene identification on other chromosomes based on known genetic interactions between loci, such as with Chr. 8. The effect of the Chr. 8 locus on kidney injury was previously validated using a congenic strain [S.SHR(8)]. Bioinformatics analysis of genes residing within the confidence interval, and those mechanistically linked with
Arhgef11
, identified cingulin-like 1 (
Cgnl1
) as a candidate.
Cgnl1
plays a role in the regulation of cell-cell contacts via adherens and tight junctions through several interacting proteins [e.g. ZO-1 and PLEKHA7 (linked with hypertension by GWAS and an SS-
Plekha7
mutant model)]. Recent studies using a novel model (SS-

Cgnl1
-/-

) demonstrates that knockout of
Cgnl1
leads to loss of salt-sensitive blood pressure and reduced renal injury compared to wildtype SS, supporting the congenic studies. Using multi-omics approaches incorporating bulk RNAseq, single nuclei RNAseq, spatial transcriptomics, small RNAseq, and mass spectrometry discovery proteomics, a putative mechanism connecting proximal tubule injury to alterations in sodium solute transporters and hypertension was established. The direct physiological interaction between
Arhgef11
and
Cgnl1
on hypertension and CKD is currently underway using a double knockout model (SS-
Arhgef11
-/-

Cgnl1
-/-

). In addition, to better elucidate the impact of loss of
Arhgef11
,
Cgnl1
, or both genes together, gene-edited cell lines using CRISPR technology has been generated and are also being studied. It is anticipated that completion of this work will lead to a better understanding of the role of genetics in hypertensive CKD, the influence of factors that complicate kidney disease, and potential new therapeutic targets.
Abstract P322: 2-year Morbidity And Mortality Due To Hypertensive Crisis In A Predominantly African American Population
Authors: Waldron Frederick A , Benenson Irina , Hinfey Patrick , Zinzuwadia Shreni , Jones-Dillon Shelley , Dort Jochena
Published: September 2022

Title: 2-Year Morbidity and Mortality due to Hypertensive Crisis in a Predominantly African American Population
Hypertensive crisis (HTNC) is a complication of Hypertension with a prevalence of 1-2%. HTNC is defined by a sudden and unpredictable increase in systolic blood pressure of ≥180 mmHg or diastolic blood pressure of ≥120 mmHg. HTNC may present as hypertensive urgency (HTNU) if asymptomatic, or hypertensive emergency (HTNE) if there are signs of end organ damage (EOD) eg: stroke (CVA), congestive heart failure (CHF), acute kidney injury (AKI), acute myocardial infarction (AMI) and death. A 2y retrospective cohort study of 1100 participants: 550 cases and 550 hypertensive controls BP >140/90) but < 200/120, matched for race, sex, and age, was conducted to determine the incidence of EOD, and the 2year mortality. The population was: Blacks 481/550 (87.4%), White 18/550 (3.3%), Asian 2/550 (0.4%) and other 49 /550 (8.9%). The mean SBP for cases was SBP 209.7 (SD=23.1), controls 147.8(SD=22.8) p=0.239; DBP cases 115.5 (SD=22.4), controls 84.2 (SD=14.1) p<.001. The incidence of new EOD for CHF: HTNE=39/440 (9.8%), HTNU=8/150 (5.3%), controls=6/550 (1.1%), p<.001; AKI HTNE=27/400 (6.8%), HTNU=5/150 (6.7 %), controls=17/550 (3.1%) p<0.001; AMI HTNE=6.5% and HTNU=2.7% controls=6/550 (1.1%) p<.001. There was no significant difference in the incidence of hemorrhagic and ischemic CVA, but the trend was higher in HTNE and HTNC for ischemic CVA: HTNE=4/400 (1%), HTNU=1/150 (0.7%), controls=(0.2%) p=.234. The 2y mortality for HTNE=82/400 (20.5%), HTNU=16/150 (10.6%), controls= 36/550 (6.5 %). The odds of dying was 3.5 times greater in the HTNU (OR 3.5, 95% CI 1.78-6.98), p<.001) and 4.3 times in the HTNE population (OR 4.3, 95% CI 2.65-7.01), p<.001). The study reveals a high morbidity and mortality associated with hypertensive crisis, with 1/5 of the population of HTNE dying in two years, mostly from related cardiovascular disease and renal failure.
Abstract P327: Cardiovascular Risk In People Living With Hiv With Less Than 5 Years Of Use Of Antiretrovirals
Authors: Araujo Edjane Silva , Arrais Claudia , Pires Nilviane , Barros Allan Kardec , Lima Pereira Cindy , Sousa Junior Carlos Magno , Santana Ewaldo , Luz Aldicléya Lima
Published: September 2022

Introduction:
People living with HIV/AIDS (PLHIV) are at high cardiovascular risk (CVR) due to chronic immune activation by the virus, generating a persistent inflammatory state, and the use of antiretrovirals (ARVs).

Hypothesis:
Factors specific to PLHIV, such as viral load (CV), TCD4 (CD4) cell count, ARV class and duration of use, are related to higher CVR in this population.

Methods:
This is a quantitative cross-sectional observational study, composed of 276 PLHIV on ARV therapy, treated at the Center for Attention to Sexually Transmitted Infections/AIDS, from July to October 2018, in a municipality in the interior of the state of Maranhão - Brazil. The variables analyzed were: sex, VC, CD4, ARV classes and duration of use and Framingham risk score (FRS). The ERF was used to stratify the CVR and the data were analyzed using the Statistical Package for Social Science (SPSS) software, version 19.0. Results were considered significant if p<0.05. This study was approved by the ethics and research committee of the Federal University of Maranhão, according to number. 2.781.461/2018.

Results:
Among the study participants, 44.4% (N=122) were women and 55.6% (N=153) were men. Regarding the classes of ARV in use, 47.6% (N=131) used NRTI/tNRTI, 26.2% (N=72) NNRTI, 2.5% (N=7) IP and 23.6% ( 65) other classes. Of the sample, 93.82% (N=258) had low CVR, according to the ERF, and 6.18% (N=17) had moderate and high CVR. Male sex (94.1%, N=16, p=0.001), duration of ARV use less than 5 years (33.3%, N=6), between 5 and 10 years were associated with moderate and high CVR. (17.6%, N=3) and over 10 years (47.1%, N=8), with p=0.025.

Conclusions:
In the sample of this study, there was a significant association between moderate and high CVR with male gender and ARV use for less than 5 years.
Abstract P328: Statin Reduces Long-term All-cause Mortality In Dialysis Patients With Atherosclerotic Cardiovascular Disease
Authors: Lee Myunhee , Kim Dae-Won
Published: September 2022

Introduction:
Statin therapy is essential for secondary prevention in patients with ASCVD (Atherosclerotic cardiovascular disease). ASCVD is the major contributor to morbidity and mortality in dialysis patients. However, the effects of statin therapy in dialysis patients remain uncertain.

Hypothesis:
We aimed to assess the hypothesis that statin therapy might decrease long-term mortality in dialysis patients with ASCVD.

Method:
Patients receiving maintenance dialysis aged ≥ 18 years who had a first-time ASCVD event between 2013 to 2018 were included from the Korean National Health Insurance Service data. Association of statin use with long-term mortality was examined using Cox proportional hazards regression model adjusted for demographics and comorbidities.

Results:
Among 17,242 dialysis patients, 9,611 (55.7%) patients were prescribed statin after a first-time ASCVD event. Of statin users, moderate-intensity statin accounted for 7,376 (76.7%). During mean follow-up of 32.6 ± 20.9 months, statin use was associated with a decrease in the risk of all-cause mortality than statin non-use after adjusting confounding factors (Hazard ratio [HR]:0.92, 95% confidence interval [CI]:0.88-0.97, p=0.0009). Regarding statin intensity, moderate-intensity statin therapy was associated with a lower risk of all-cause mortality than no statin therapy (HR:0.91, 95% CI:0.87-0.96, p=0.0002).

Conclusions:
Despite a lack of evidence, more than half of dialysis patients have been prescribed statins after an ASCVD event. In dialysis patients with ASCVD, moderate-intensity statin therapy significantly reduced long-term mortality risk. Statin therapy might be beneficial for secondary prevention in dialysis patients.
Abstract P337: Valsalva Maneuver And Detection Of Late-onset Orthostatic Hypotension
Authors: Park Jin-Woo , Okamoto Luis E , Kim Seong-Hwan , Baek Seol-Hee , Sung Joo Hye , Gamboa Alfredo , Shibao Cyndya A , Diedrich Andre , Kim Byung-Jo , Biaggioni Italo
Published: September 2022

Delayed orthostatic hypotension (dOH) is defined as OH occurring ≥3 minutes of standing. Standard autonomic testing now includes a 10 min head-up tilt (HUT) and detects “early” dOH, but “late” onset dOH (occurring ≥10 min of standing) remains a diagnostic challenge. To determine if the Valsalva maneuver (VM) can identify patients that would require a prolonged HUT (>10 min) to diagnose late dOH, we analyzed a database of 2,498 patients who underwent autonomic function tests (AFTs) in Korea University Anam Hospital between 2016-2022. Patients with diagnosis of OH (onset of OH <3 min; n=176), early dOH (OH between 3-10 min; n=68) and late dOH (n=32) were included in the analysis. A normal autonomic function test group (n=114) with a composite autonomic scoring scale of 0 and normal HUT, was used as a control group. VM parameters, including changes from baseline in systolic BP at late phase 2 (ΔSBP
VM2
) and in heart rate at phase 3 (ΔHR
VM3
), pressure recovery time at phase 4 (PRT), Valsalva ratio (VR) and baroreflex sensitivity (BRSa and BRSv), were compared among groups. We found that ΔSBP
VM2
, ΔHR
VM3
and VR were lower in late dOH patients compared to controls (P<0.01) but were higher than those of early dOH and OH. PRT was longer in late dOH compared to controls, but shorter than that of early dOH and OH. When compared late dOH patients with age and gender matched controls, only the differences in PRT and ΔHR
VM3
remained significant. A receiver operating characteristic analysis revealed that cut-offs values of PRT ≥2.14 sec and ΔHR
VM3
≤15 bpm distinguished late dOH from an age and gender matched controls (P<0.01). A multivariate logistic regression analysis showed that patients with longer PRT (odds ratio [OR]=3.448 [1.360-8.739]) and lower ΔHR
VM3
(OR=0.149 [0.056-0.398]) were more likely to have late dOH. In conclusion, our results in late dOH patients showed that PRT and ΔHR
VM3
differ from those of controls, early dOH and OH, suggesting a milder form of autonomic dysfunction. These VM parameters could be used to identify patients who need prolonged >10min HUT to diagnose late-onset OH.
Abstract P340: Associations Of Life’S Simple 7 And 10-year Change In Load-dependent Arterial Stiffness: The Multi-ethnic Study Of Atherosclerosis (mesa)
Authors: Pewowaruk Ryan , Korcarz Claudia E , Szklo Moyses , Greenland Philip , Tedla Yacob , Gepner Adam
Published: September 2022

Introduction:
Arterial stiffness can be separated into two main mechanisms: 1) load-dependent (LD) stiffening from higher blood pressure (BP) and (2) structural stiffening due to changes in the vessel wall. Structural stiffening is strongly associated with advancing age. LD stiffening is highly variable and is more strongly associated with CVD.

Hypothesis:
Optimal Life’s Simple 7 factors will be associated with a slower rate of increase in LD stiffness.

Methods:
MESA participants with carotid ultrasound at Exam 1 and Exam 5 (year 10) were included (n=2557). Peterson’s elastic modulus (PEM) was calculated to represent total stiffness. Structural stiffness was PEM adjusted to a standard BP of 120/80 mmHg using participant-specific models. LD stiffness was the difference between total and structural stiffness. Changes in stiffness mechanisms over 10 years for poor versus optimal Life’s Simple 7 (LSF) factors were compared with linear models adjusted for age, sex, race/ethnicity, study site, education, BP and lipid medication, C-reactive protein, Interleukin-6, and baseline stiffness.

Results:
No LS7 factors was associated with increased LD stiffening for the whole cohort. For the bottom quartile of baseline LD stiffness, smoking (2.55±1.23 kPa, p=0.039) was associated with increased LD stiffening. For the highest quartile of baseline LD stiffness, no LS7 factors were significantly associated with stiffening.

Conclusion:
Smoking was associated with increased LD stiffening in those with low baseline stiffness. Smoking cessation and prevention may be especially important in these individuals to promote healthy vascular aging.
Abstract P341: BLOOD PRESSURE RESPONSES OF RICE DIET PROGRAM PATIENTS WITH MALIGNANT HYPERTENSION
Authors: Lin Pao-Hwa , Lopez David , Li Yi-Ju , Luft Friedrich Cameron C , Neelon Francis , Klemmer Philip , Kuo Anthony , Sanoff Scott
Published: September 2022

Introduction:
Prior to the availability of effective anti-hypertensive medications, patients with malignant hypertension (MH) had a poor prognosis with a median survival of ~eight months. During this era, MH patients came to Durham NC to enroll in the residential Rice Diet Program at Duke (RDP), where they were placed on a low salt (5 meq/d), low protein (5% kcal), and low fat (5% kcal) diet with no anti-hypertensive medications. Examining the medical records of >16,000 RDP patients, we identified 298 patients with MH, which we define as those with documented papilledema, no documented diabetes or pseudotumor cerebri, and with a systolic BP >170 mmHg.

Methods:
Age at entry, gender, duration in RDP, BP and urine chloride (a measure of low-salt diet adherence) response were compared between those who stayed < vs. ≥ median duration (207.5 days) by Wilcoxon and within each group by paired t test. Linear regression was used to examine the association between these factors with the BP response from entry to weeks 4, 8, and 13, for those with continuous BP data during each period.

Results:
BPs and urine chloride reduced significantly in both groups and the reductions were significantly greater among those with ≥ median duration (
Table
). Age at entry had no effect on BP change except at 4 weeks. Weight had no effect while male gender, higher baseline systolic BP, and greater reduction in urine chloride were all associated with a greater BP reduction (all p<0.05). This finding was consistent at all three time points.

Conclusion:
A low-salt, low-protein, and low-fat diet was effective in lowering BP in those with MH. Sodium loss may be a key mechanism, but other components of the diet should also be examined.div>