bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP09: Effect Of Western Diet On Renal Transcriptome Of Hypertensive Mice Overexpressing Human Angiotensin Receptor Type 1
Authors: Ketkar Harshada , Tang Samantha , Jain Sudhir
Published: August 2021

Over-expression of human angiotensin-II receptor type1 (hAT1R) may cause pathological outcomes due to overactivation of renin-angiotensin system. Transgenic (TG) mice containing Hap-I (hypertensive genotype) of human hAT1R gene are more prone to develop metabolic syndrome disorders as compared to TG mice with Hap-II (normotensive genotype). This gene variant associated risk of hypertension together with Western diet and aging may lead to renal disorders. However, mechanisms underlying this process are not well examined. For this purpose, we studied the renal gene expression alterations in aged TG mice containing either Hap-I or Hap-II of hAT1R gene. Aged mice (20-24 months of age) were maintained on a regular diet or high fat diet with 2% NaCl (Western diet, WD) for 16 weeks. On a regular diet, aged Hap-I mice presented higher (~9 mmHg) systolic blood pressure with respect to age-matched Hap-II animals. Following administration of Western diet, blood pressure increased in both groups of mice, but to a larger extent in Hap-I animals (~15 mmHg in comparison to ~7 mmHg in Hap-II). Aged Hap-I mice on Western diet showed increased renal fibrosis. RNA-seq data from renal tissue of Hap-I aged mice revealed that WD significantly altered the expression of >400 genes (p-adj. <0.05). Bioinformatics analysis (Qiagen IPA software) identified major alterations in main canonical pathways involved in renal function and oxidative damage. These changes in turn resulted in kidney failure, renal tubular injury, and renal proliferation. In addition, post WD treatment, RNA seq. analysis from Hap-I and Hap-II kidneys also reveals haplotype specific regulation of genes associated with blood pressure regulation and kidney disorders. Overall, these results indicate that Western diet promotes hypertension and fibrosis in the kidneys of aged mice. These alterations are paralleled by perturbation of renal transcriptional profile. Overall, these studies will assist in the identification of novel mechanisms and molecules involved in hypertension and associated kidney pathophysiology.
Abstract MP43: Knockout Of ACE-N Facilitates Improved Cardiac Function After Myocardial Infarction
Authors: SUHAIL HAMID , Peng Hongmei , Sarkar Sarah , Xu Jiang , Bernstein Kenneth E , Liao Tang-Dong , Ortiz Pablo A , Rhaleb Nour-Eddine
Published: August 2021

Angiotensin-converting enzyme (ACE) hydrolyzes N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) into inactive fragments through its N-terminal domain (ACE-N). We reported that cardioprotective effects of ACE inhibitor in angiotensin II-induced hypertension were partially mediated through increased Ac-SDKP bioavailability. Whether increased endogenous Ac-SDKP by knocking out ACE-N leads to improved cardiac function in myocardial infarction (MI) is unknown. Wild-type (WT) and ACE-N knockout (ACE-N
-/-
) mice were subjected to MI induced by ligating the left anterior descending artery and treated with either vehicle or Ac-SDKP (1.6 mg/kg/day, s.c.) for 5 weeks. Echocardiography was performed on awake mice at the end of experiment and left ventricles (LV) were harvested for histology and molecular biology studies.

ACE-N-/- mice showed increased plasma Ac-SDKP level in Sham or MI group compared to WT. Exogenous Ac-SDKP further increased Ac-SDKP level in both WT and ACE-N-/-. SF and EF were significantly decreased in both WT and ACE-N-/- mice post-MI, . Exogenous Ac-SDKP further increased EF and SF post-MI only in WT, but not in ACE-N-/- mice. Sarcoendoplasmic reticulum calcium transport ATPase 2 (SERCA2), a marker of cardiac calcium homeostatsis, significantly decreased in WT post-MI was rescued with Ac-SDKP, whereas ACE-N-/- mice displayed less reduction in SERCA2 expression. These results demonstrate that gene deletion of ACE-N improves cardiac function in mice post-MI, which was associated with increased Ac-SDKP level and minimally reduced expression of SERCA2.Therefore,this study illustrates that endogenous Ac-SDKP results in cardioprotective role in MI.
Abstract MP44: A Novel And 2 Known Differentially Expressed MicroRNAs Were Identified In Peripheral Blood Mononuclear Cells Of Patients With Hypertension Associated With Metabolic Syndrome
Authors: Berillo Olga , Huo Kugeng , Fraulob-Aquino Julio C , Richer Chantal , Li Na , Briet Marie B , Lipman Mark L , Sinnett Daniel , Paradis Pierre , Schiffrin Ernesto L
Published: August 2021

Background:
Hypertension (HTN) is associated with subclinical target organ damage including cardiac, vascular and kidney injury. The immune system plays a role in hypertension and target organ damage. Activation of T cells has been reported among peripheral blood mononuclear cells (PBMCs) of patients with HTN. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune cells. Whether miRNAs play a role in the activation of immune cells in hypertension complicated by target organ damage in humans remains unknown. We aimed to address this question by identifying differentially expressed (DE) miRNAs and their mRNA targets in PBMCs of patients with hypertension complicated or not with metabolic syndrome (MetS) or chronic kidney disease (CKD).

Methods:
Normotensive subjects and patients with hypertension (HTN) associated or not with at least 2 other features of MetS or CKD were studied (n=15-16). PBMCs were isolated from blood, RNA extracted for small and total RNA sequencing (RNA-seq) using Illumina HiSeq-2500 and data were analyzed using a systems biology approach. MiRDeep2 was used for novel miRNAs prediction, miRNA annotation and counting. TargetScan 7.07 was used to predict DE miRNA targets with weighted context score percentile >50%. DE genes miRNAs and mRNAs were identified with fold change (FC) >1.5 and
P
<0.005. DE miRNAs with FC>2 and mean read count number (MRCM) >500, and with predicted targets with MRCM>300 were validated by reverse transcription-quantitative PCR (RT-qPCR).

Results:
DE miRNAs, mRNAs and non-coding RNAs were identified in HTN (22, 19 and 0), MetS (57, 401 and 11) and CKD (6, 26 and 2) compared to NTN. TargetScan predicted that 7 miRNAs target 3 mRNAs in NTN, 57 miRNAs target 55 mRNAs in MetS and 3 miRNAs target 2 mRNAs in CKD. DE miR-409-5p (FC: 0.54±0.10 vs 1.00±0.09,
P
<0.05), miR-411-5p (FC: 0.40±0.06, vs 1.00±0.11,
P
<0.001) and the novel miR-pl-86 (FC: 1.96±0.17 vs 1.00±0.15,
P
<0.05) in MetS vs NTN were validated by RT-qPCR. RNA-seq data were correlated with RT-qPCR for miR-409-5p (R
2
=0.40,
P
<2.4E-07, n=55), miR-411-5p (R
2
=0.55,
P
<1.1E-10, n=55), miR-pl-86 (R
2
=0.37,
P
<5.5E-07, n=56).

Conclusion:
This study showed that DE miR-409-5p, miR-411-5p and miR-pl-86 may play a role in HTN associated with MetS.
Abstract MP51: Isolevuglandins In Antigen-presenting Cells, A Biomarker For Salt Sensitivity Of Blood Pressure In Humans?
Authors: Ertuglu Lale , Elijovich Fernando , Sahinoz Melis , Laffer Cheryl L , Pitzer Ashley , Ikizler Alp , Kirabo Annet
Published: August 2021

Background:
High Na+ stimulates antigen-presenting cells (APCs) in an ENaC dependent manner, with formation of isolevuglandin (isoLG) adducts (neoantigen peptides) that promote T cell activation and salt sensitive (SS) hypertension in rodents.

Methods:
We studied this pathway in 9 subjects with essential hypertension who discontinued anti-hypertensive therapy for 2 weeks. Their SS was assessed by 24-hrs of salt loading (460 mmoL) and salt depletion (10 mmoL/24 hr, plus furosemide 40 mg x 3). Muscle and skin Na
+
were measured at baseline (BA) by
23
Na magnetic resonance imaging (NaMRI). The % of APCs containing isoLG adducts (flow cytometry), urine and serum electrolytes and epoxyeicosatrienoic acids (EETs 8-9, 11-12 and 14-15) were measured at BA, after salt-loading (HI) and after salt-depletion (LO).

Results:
Age was 54 years (48-56), with 23% female, BMI 30 kg/m
2
(28-40) and screening SBP 136 mmHg (120-144), and DBP 85 mmHg (75-99). BA 24-hr urine Na
+
excretion was 178 (143-212) mmoL, Hi 392 (229-421) and LO 27 (25-29). SBP response to salt-depletion varied from -13.8 to +5.6 mmHg. Muscle Na+ correlated with duration of hypertension (r=0.73, p<0.03) and with SBP, DBP and mean arterial pressure (MAP) during BA, HI and LO (r=0.66 to 0.87). Mean %isoLGs in APCs were not different among the three stages of the protocol but ΔisoLGs due to HI or LO had positive correlations with ΔSBP, ΔDBP and ΔMAP produced by the same interventions (r=0.46 to 0.70). A 10% change in dendritic cell isoLGs predicted a 1.45 mmHg change of SBP in the same direction. Urine (not plasma) EETs (sum of three isoforms) showed negative correlations with isoLGs on the three phases of the protocol (r=0.57 to 0.69), and ΔEETs by HI and LO correlated negatively with ΔisoLGs produced by the same interventions (r=0.58 to 0.77).

Conclusions:
Muscle Na+ increases with duration of hypertension and correlates with severity of BP elevation. Changes in APC isoLGs due to Na+ loading or depletion seem to be a biomarker of SS of BP in humans. Relations between urine EETs and ΔEETs with APC isoLGs and ΔisoLGs suggest that EETs might be inhibitors of APC ENaC as they are of renal ENaC. Relationships between isoLGs and urine but not plasma EETs suggest that activation of APCs by high salt may occur in the hyperosmolar renal medulla.
Abstract MP52: Hypertensive Stimuli Indirectly Stimulate Mouse Mesometrial Lymphangiogenesis Through Immune Cells
Authors: Wilcox Brooke K , Navaneethabalakrishnan Shobana , Martinez Karina A , Pournouri Anil , Henley Marissa R , Goodlett Bethany L , Lopez Alexandra H , Chakraborty Sanjukta , Mitchell Brett M
Published: August 2021

We previously reported increased renal lymphatic density in multiple mouse models of hypertension, and further augmenting renal lymphatics lowers blood pressure. However, whether interstitial levels of hypertensive stimuli have a direct effect on lymphatics or an indirect effect through secreted immune cell factors has not been examined. We hypothesized that hypertensive stimuli directly increases lymphatic endothelial cell (LEC) proliferation and increases sprouting of mouse mesometrial lymphatic vessels. Murine LECs were cultured and treated with angiotensin II (angII), salt, and asymmetric dimethylarginine (ADMA) for 24 hours. To mimic the
in vivo
environment, a lymphatic-specific reporter mouse (Prox1-tdTomato) mesometrium tissue explant was treated with either the same hypertensive stimuli or with hypertensive conditioned media for 8 days. Mesometrial vascular beds were cultured in DMEM supplemented with 20% fetal bovine serum to induce lymphatic sprouting and this was replenished every day. The conditioned media was made by treating murine splenocytes for 24 hours with the same hypertensive stimuli. These stimuli had no effect on murine LEC proliferation. Hypertensive stimuli significantly decreased mesometrial lymphatic vessel sprout length (SL) and sprout number (SN) compared to controls (control SL in pixels by ImageJ analysis: 34.0 ± 2.6, angII: 3.7 ± 2.6, salt: 2.67 ± 2.18, ADMA: 9.06 ± 5.12, all p<0.05; control SN: 7 ± 3, angII: 0 ± 0, salt: 0 ± 0, ADMA: 1 ± 1, all p<0.05). Conditioned media treatment normalized SL and SN by day 8 for all hypertensive stimuli except salt. In conclusion, hypertensive stimuli directly inhibit mesometrial lymphangiogenesis, but this was mitigated by hypertensive stimuli induced immune cell secreted factors.
Abstract MP53: A Role Of Anti-isolevuglandin-adduct Antibody Production In Hypertension
Authors: de la Visitacion Nestor , Chen Wei , Krishnan Jaya , Harrison David G , Patrick David M
Published: August 2021

Isolevuglandins (isoLG) are products of lipid oxidation that covalently ligate self-proteins and contribute to immune activation in hypertension. We hypothesized that these are recognized as “non-self” elicit an antibody response. To determine the presence of anti-isoLG adduct antibodies in humans, immunoblots were performed using endogenous antibodies present in plasma of healthy and hypertensive subjects against human proteins artificially adducted with isoLG. Protein-G HRP was used to visualize the binding of IgG antibodies. We found that humans with hypertension possess IgG antibodies that bind isoLG protein adducts to a greater extent compared to unadducted protein. To identify unique monoclonal antibodies to isoLG adducts C57Bl/6 mice were made hypertensive via angiotensin II infusion for two weeks and then boosted with kidney protein that was adducted with isoLG. Boosted mice were then sacrificed and splenic B-cells were fused with a myeloma cell line. Individual colonies were screened for reactivity with isoLG adducts identifying 11 monoclonal antibody clones with a high specificity for isoLG adducts. Four clones were chosen for further analysis that exhibited 1.5 to 6-fold affinity to adducted vs unadducted mouse proteins. Western blots of normotensive and hypertensive kidney, bone marrow, and heart protein lysate using one of our monoclonal antibodies (clone 2B11) revealed a 90 kDa protein that is increased in bone marrow of hypertensive mice. We conclude that hypertension results in the production of anti-isoLG adduct antibodies in mice and humans. Identification of unique monoclonal antibodies that react with isoLG adducts suggests clonal expansion of anti-isoLG antibody producing cells. Finally, a hypertensive antigen is recognized by the 2B11 clone. Future studies will utilize these antibodies to identify peptide antigens that drive immune activation in hypertension.
Abstract MP54: Pro-resolving Lipid Mediators Ameliorate Endothelium Dysfunction In Arteries From Hypertensive Rats
Authors: Edwards Jonnelle M , Waigi Emily W , Bearss Nicole , Joe Bina , McCarthy Cameron G , Wenceslau Camilla F
Published: August 2021

Resolution of inflammation is an active phenomenon to switch off the inflammatory processes andfacilitate the return to homeostasis. Increasing the levels of pro-resolving lipid mediators topromote the resolution of inflammation is emerging as a novel therapeutic approach. Arachidonicacid (AA) and docosahexaenoic acid (DHA) are substrates to produce the pro-resolving lipidmediators lipoxin A4 (LXA4) and resolvin D1 (RvD1), respectively. However, it is unknown if thesemediators can ameliorate dysfunction in arteries from hypertensive animals. Therefore, wehypothesized that pro-resolving lipid mediators decrease acetylcholine-induced contractions inarteries from spontaneously hypertensive rats (SHR). Mesenteric resistance arteries from maleSHR and Wistar Kyoto (WKY) (14-weeks old, n=6-8) were used for vascular function via wiremyograph. MRA were incubated with either RvD1 or LXA4 (10 nM, 1 hour) or vehicle prior toconcentration response curves to acetylcholine or phenylephrine (1 nM - 3 μM). We alsoperformed lipidomic analysis on plasma from WKY and SHR. As expected, low concentrations (≤100 nM) of acetylcholine induced relaxation in arteries from both groups, however highconcentrations (≥ 1 μM) of acetylcholine induced contraction in arteries from SHR, but not in WKY[Relaxation to acetylcholine [Area Under the curve (AUC)]: WKY: 396.6 ± 17.7 vs. SHR-control:296.0 ± 26.7*, t-test *vs. WKY, p=0.03). Treatment with the mediators did not change relaxationin arteries from WKY (AUC: Vehicle: 396.6 ±17.7 vs. RvD1: 402.8 ± 18.0; LXA4: 399.0 ± 18.4,p>0.05). However, incubation with RvD1 or LXA4 reduced acetylcholine induced-contraction inarteries from SHR (AUC: Vehicle: 296.0 ± 26.7 vs. RvD1: 372.5 ± 18.5*; LXA4: 376.8 ± 23.6*, t-test *vs. vehicle, p<0.05). Lipidomic analysis showed that precursors for pro-resolving lipidmediators are decreased in SHR [DHA (pmol/mL): WKY: 5637.5 ± 275.3 vs. SHR: 4509.2 ±453.9*, AA: WKY:16018.3 ± 351.3 vs. SHR: 13928.5 ± 959.5 *vs. WKY, p<0.05]. Overall, theseresults suggest that resolution of inflammation and the pro-resolving lipid mediators, RvD1 orLXA4, may be used as a new therapeutic tool to improve vascular function in hypertension.
Abstract MP68: The Correlation Between Left Atrial-left Ventricular-arterial Coupling And Circadian Rhythm Of Blood Pressure In Hypertension
Authors: Liu Yan , Sun Qiaobing , Zhao Yixiao , Jiang Yinong
Published: August 2021

The Correlation between Left Atrial-Left Ventricular-Arterial Coupling and Circadian Rhythm of Blood Pressure in Hypertension

Objective:
Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and arterial stiffness increased. In this study, we further investigated the association between LA-LV-arterial coupling and circadian rhythm of blood pressure (BP) in essential hypertension (HT).

Design and Methods:
We enrolled 289 HT patients which were evaluated by 2 dimensional speckle tracking echocardiography (2D-STE), ambulatory 24-hour BP monitoring (ABPM) and carotid-femoral pulse wave velocity (PWV). According to BP patterns, these patients were divided into two groups, which included dippers (n=109), patients with a >10% reduction in BP at nighttime; non-dippers (n=180), patients with a <10% reduction in BP at nighttime. 2D-STE based LA and LV strains were studied and the following parameters were measured, LV global longitudinal strain (GLS), LA reservoir strain (LA
S-S
), LA conduit strain (LA
S-E
), and LA booster pump strain (LA
S-A
). LA stiffness index (LASI) defined as the ratio of E/e' to LA
S-S
, and PWV-to-GLS ratio (PWV/GLS) were calculated to reflect LA-LV-arterial coupling. Furthermore, we also explored the correlation between LASI (or PWV/GLS) and ambulatory blood pressure indexes. The related factors were evaluated by multivariate linear regression analysis to find the independent factors.

Results:
LASI was significantly higher in non-dippers (0.35±0.24) than dippers (0.29±0.12) (
p
<0.05). PWV/GLS was significantly higher in non-dippers (-90.30±34.13) than dippers (-79.62±25.84) (
p
<0.05). LA
S-S
, LA
S-A
and LV GLS were significantly lower in non-dippers than dippers (
p
<0.05). Multivariate linear regression analysis revealed that LV mass index (LVMI), PWV/GLS, nighttime mean SBP (n-SBP) and nighttime mean DBP (n-DBP) were independently correlated with LASI; LASI and n-SBP were independently correlated with PWV/GLS.

Conclusions:
LA and LV myocardial mechanics, and LA-LV-arterial coupling were associated with circadian rhythm of BP. Nocturnal systolic BP was the independent risk factor of abnormal LA-LV-arterial coupling in HT.
Abstract P106: Development Of An Oral Drug Delivery System For The Cardio-protective Neuropeptide Alpha-calcitonin Gene Related Peptide
Authors: Kumar Ambrish , Williamson Maelee G , Hess Andrew , DiPette Donald J , Potts Jay D
Published: August 2021

Alpha-calcitonin gene related peptide (α-CGRP) is a promising neuropeptide for the treatment of cardiovascular disease. We have developed an alginate biomaterial-based delivery system which increases the peptide’s bioavailability and have shown that subcutaneous delivery of alginate-CGRP microcapsules significantly improved cardiac function in pressure overload-induced heart failure in mice. The goal of this study is to develop efficient alginate microcapsule formulations for oral delivery of α-CGRP. An electrospray method was used to prepare four different formulations of alginate-CGRP microcapsules all of 200 μm diameter- i)- alginate-CGRP microcapsules, ii)- alginate-CGRP microcapsules with UV-light exposure, iii)- poly-L-ornithine (PLO) coated alginate-CGRP microcapsules, and iv)- PLO alginate-CGRP microcapsules with UV-light exposure. The stability of the microcapsules in the digestive tract was evaluated in deionized water, simulated gastric fluid (SGF; pH 1.2), and simulated intestinal fluid (SIF; pH 6.8). Over time, the size of all four microcapsule formulations remained almost unchanged in SGF, however all four of the microcapsule formulations swelled in presence of SIF. Compared to deionized water, the size of alginate-CGRP microcapsules after 6 h incubation in SIF increased by 1.7 fold. Since all four formulations yielded similar results, we chose to further study the alginate-CGRP microcapsules
in vivo
. To determine the bioactive nature of the released peptide, alginate microcapsules containing α-CGRP in doses of 1, 3, and 10 (mg/kg b.wt) were fed to male C57BL/6 mice via oral gavage. Systolic blood pressure (SBP) was subsequently measured by a tail-cuff method. α-CGRP microcapsules reduced SBP in a time-dependent manner. Alginate-CGRP at 1 and 3 mg/kg lowered the SBP by 25 mmHg for up to 4 h and 48 h, respectively. However, 10 mg/kg alginate-CGRP initially reduced SBP to undetectable levels which ultimately returned to baseline level by day 7. These studies indicate that alginate microcapsules can withstand the low pH of the stomach and the release of the peptide is bioactive
in vivo
. Thus, alginate microcapsules may provide an ideal formulation to deliver α-CGRP orally for the long-term treatment of cardiac diseases.
Abstract P107: Anti- Mir-510 In The Treatment Of Essential Hypertension By Using Hypertensive Rats
Authors: K Auxzilia Preethi , J.S Sushmaa Chandralekha , sekar Durairaj
Published: August 2021

Introduction:
Hypertension (HTN) is one of the major public health complications throughout the world. Although progress has been made in HTN research, early diagnosis and treatment of HTN are yet to be flourished. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in many diseases including HTN. According to our previous report, there is direct evidence showing that miR-510 is involved in HTN.

Hypothesis:
We assessed the hypothesis that to decipher the critical pathways of miR-510 and PTEN in regulation of PI3K/AKT Pathways, so it can be used as a therapeutic pathway as well as biomarker. Finally, we intend to study how anti-miR-510 reduces the HTN in the hypertensive induced rat model.

Methodology:
Proliferation, migration, invasion and apoptosis capacity of miR-510, Anti-miR-510, PTEN and eNOS were evaluated in HUVEC Cells. The expression pattern of miR-510, anti-miR-510 and eNOS, PTEN are analyzed by qPCR and western blot The relationship between miR-510, Anti-miR-510 and PTEN are investigated by luciferase assay Deoxycorticosterone acetate (DOCA) of 70mg/kg and 1% NaCl salt induced hypertension model (Sprague Dawley rats) was used in this study. According to the dose dependent study, anti-miR-510 was administered intravenously. Histological analyses are performed to examine the hypertrophy by using cardiac tissues fixed in 1% paraformaldehyde.

Results and conclusion:
Our results suggested that miR-510 can directly influence the PTEN expressions in HUVEC cells. Furthermore, the in vitro experiments clearly indicated that miR-510/PI3K/AKT/PTEN axis involved in HTN. Anti-miR-510 delivery can reduce the progression of HTN in the hypertensive induced rat model. Though miR-510 is involved in HTN, but its molecular mechanism is almost unknown. So, these analyses suggested that the correlation between miR-510, PTEN, anti-miR-510 are the critical step in gene expression and regulations. Thus, all these analyses could lead in identification of therapeutic target and non-invasive biomarker for HTN. Our in vivo experiments suggesting that anti-miR-510 may act as a novel therapeutic molecule for HTN treatment.
Abstract P108: Side Effects Of Initial Combination Versus Monotherapy For Patients With Hypertension
Authors: An Jaejin , Mefford Matthew , Ni Liang , Wei Rong , Zhou Hui , Harrison Teresa N , Brettler Jeff , Muntner Paul , Reynolds Kristi
Published: August 2021

Clinical guidelines recommend initiating combination antihypertensive therapy for many patients with hypertension. However, data on the risk of side effects are limited. We evaluated side effects associated with initiating combination therapy versus monotherapy among patients with hypertension from Kaiser Permanente Southern California between 2008-2014. Patient characteristics, antihypertensive medication use, and possible side effects were collected using electronic health records. We examined the association of initial combination therapy and incidence of side effects including acute kidney injury, hypotension, injurious fall, hyperkalemia, hypokalemia, hyponatremia, or hyperuricemia using multivariable Cox Proportional hazards models. Of 164,805 patients, 44% initiated combination therapy (34% angiotensin converting enzyme inhibitor (ACEI)-thiazide diuretics (TD); 10% other combinations) and 56% initiated monotherapy (22% ACEIs; 16% TD; 11% beta blockers (BB); 7% calcium channel blockers). Incidence rates of side effects were between 3.8 for hyperkalemia to 55.5 for hypokalemia per 1000 person-yrs during median follow-up of 0.27-0.45 yrs. Initiation of ACEI-TD combination therapy was associated with a lower risk of hyperkalemia than ACEI monotherapy and a lower risk of hypokalemia than TD monotherapy (
Table
). Initiation of ACEI-TD combination therapy was associated with a higher risk of hyponatremia, hyperuricemia, and hypotension, but not associated with injurious falls when compared with other monotherapy groups. Monitoring for side effects following initiation of antihypertensive medication with combination therapy may be useful.
Abstract P115: Feasibility Of Implementing A Remote Blood Pressure Monitoring And Management Program
Authors: Gupta Aditi
Published: August 2021

Introduction:
Hypertension guidelines recommend remote monitoring of blood pressure (BP) but widespread implementation is lacking due to several multi-level barriers.

Hypothesis:
Barriers to remote monitoring and management of hypertension are largely surmountable by reorganization of the current model of hypertension management and leveraging new technology, implementation science, and team-based system-wide processes.

Methods:
We conducted a NIH funded multi-disciplinary pragmatic type 1 hybrid effectiveness implementation pilot study to lower BP in patients ≥65 years old, combining evidence-based strategies and incorporating them in the clinic flow. We used the electronic health record for real time identification of patients with poorly controlled hypertension and approached them for enrollment. Enrolled participants were randomized to either the virtual collaborative care clinic (vCCC) where trained pharmacists monitored and managed BP through telehealth or to usual care with education. All patients were provided with electronic BP cuffs. The entire study was conducted remotely due to the COVID-19 pandemic. We used surveys and interviews to assess feasibility, acceptability, and satisfaction scores.

Results:
There was a high enrollment rate with 31 of the 93 potentially eligible patients participating in the 12-week feasibility study. Twenty-nine patients have completed the study: 15 in the vCCC and 14 in the usual care group. SBP decline was 13.7 ± 18.6 mmHg in the vCCC group compared to 4.3 ± 20.5 mmHg in the usual care. Additionally, patients in the vCCC group used their home BP monitors more often, with mean usage 6.3 times per week compared to 0.6 times in the usual care group. The vCCC program had high patient, pharmacist, and physician satisfaction scores. Provider acceptability and feasibility was also high.

Conclusion:
The vCCC program may be an effective strategy to manage hypertension in the future. The program had high acceptability and satisfaction, along with better reduction in SBP. These data support a larger health system wide study using the vCCC for hypertension management.
Abstract P120: Feasibility Of An Asynchronous, Semi-Automated Remote Patient Monitoring Blood Pressure Management System
Authors: Sarraju Ashish , Babakhanian Meg , Szeto Irvin , Seninger Clark , Chang Tara I , Bhalla Vivek , Downing Lance , Rodriguez Fatima , Turakhia Mintu , Wang Paul J
Published: August 2021

Introduction:
While remote patient monitoring (RPM) for hypertension (HTN) continues to grow in the United States, most systems are third party, employer-directed, or do not directly lead to changes in medication management. Systems that address these issues may reduce therapeutic inertia and lead to more rapid control of blood pressure (BP). We developed a clinician-facing HTN RPM system with evidence-based customizable medication titration protocols that integrate with a patient mobile app and Bluetooth®-connected BP cuff. We report interim results from the pilot implementation of this system.

Hypothesis:
In a pilot study, an RPM system with patient and clinician-facing platforms and a semi-automated protocol will achieve high engagement with actionable user feedback.

Methods:
We performed a single arm, single center study with five clinicians from primary care (3) and cardiology (2). Eligible patients had essential hypertension (BP >130/80 mmHg) and a smartphone (iPhone, Android). Patients used a Bluetooth®-connected cuff that sent readings to a patient app and a clinician dashboard. Based on BP and comorbidities, a protocol provided medication titration recommendations for clinicians. In this 12-week study, we assessed feasibility through user feedback, user engagement (defined as the number of BP measurements), and changes in systolic (SBP, mmHg) and diastolic BP (DBP, mmHg).

Results:
We enrolled 18 patients (age 51
+
11y; 94% male; 29% White). Baseline SBP was 133
+
7.8 and DBP was 87
+
7.1. At a mean follow-up of 4.7 weeks, there were 15
+
11 weekly BP measurements per patient. Mean per-patient decreases in SBP and DBP were 12 (95% CI 5.8-18, p<0.001) and 7.1 (95% CI 3.1-11, p = 0.002), respectively. A total of 77.8% (14/18) patients continued BP measurements without attrition. Key feedback included improved cuff-mobile app connectivity (patients) and increased medication choices in protocols (clinicians).

Conclusions:
In interim results of a pilot study, an RPM HTN system was implemented with high engagement, evidence of BP reduction, and actionable feedback. Complete results including medication and BP changes are anticipated by September 2020 and will guide a planned, funded, large, multicenter cluster randomized trial.
Abstract P147: Association Between Lipid Transfer To HDL-c And Arterial Stiffness In Patients With Ischemic Stroke Due To Hypertensive Emergency
Authors: Oliveira-Andrade Days , Freitas Fatima , Aguiar Franciana , Mansor Ana Luiza , Cosenso-Martin Luciana , Souza Doroteia R , Maranhao Raul C , Vilela-Martin Jose F
Published: August 2021

Objective:
To evaluate arterial stiffness (AS) and lipids transfer to high density lipoprotein cholesterol (HDL-c) in ischemic stroke due to hypertensive emergency (IS-HE).

Methods:
Thirty and one patients with IS-HE, 33 individuals with ischemic stroke without hypertensive emergency (IS), 31 controlled hypertensive (CHT) and 33 normotensive (NT) individuals were studied. AS was assessed by analyzing the pulse wave velocity (PWV),
augmentation index
and central blood pressure. The lipids transfer to HDL-c was evaluated after incubation of the plasma with an artificial radiolabeled nanoparticle, used as a donor of esterified and non-esterified cholesterol. Cholesterol transfer was measured in the HDL-c fraction, after chemical precipitation of lipoproteins containing apolipoprotein B.

Results:
Systolic (SBP) and diastolic (DBP) blood pressure were significantly higher in the IS-HE compared to IS, CHT and NT groups (190/110 mmHg vs 140/87, 128/69 and 129/80 mmHg, respectively; p<0.05). Similarly, central SBP and DBP were higher in patients with IS-HE compared to IS, CHT and NT (147/101 mmHg vs 128/90, 118/71 and 120/83 mmHg, respectively; p<0.05). PWV was significantly higher in the groups IS-HE and IS, compared to NT group (9.7 and 10.6 vs 7.8 m/s, respectively; p<0.05). The esterified cholesterol transfer was reduced in the IS-HE and IS groups in relation to the CHT and NT groups (4.19 and 3.76 vs 4.5 and 4.75, respectively; p<0.05). The non-esterified cholesterol transfer was also markedly decreased in IS-HE e IS groups compared to CHT and NT groups (4.57 and 4.06 vs 5.47 and 5.71, respectively; p<0.05). A negative correlation was observed between non-esterified cholesterol transfer and PWV in the IS-HE group.

Conclusion:
This study provides evidence that high blood pressure levels are associated to arterial stiffness and a marked decrease in the lipids transfer to HDL-c in patients with ischemic stroke due to hypertensive emergency, which indicates that changes in the HDL-c fraction can contribute to atherogenesis in these patients. These considerations contribute to the concept that determining HDL-c functionality with dynamic assays can be relevant for predicting the cardiovascular disease risk.
Abstract P150: Sex Differences In Augmentation Index And Aortic Pulse Pressure Among Patients Diagnosed With Acute Primary Intracerebral Hemorrhage
Authors: Ryalat Fatima , Shaltout Hossam A , DIZ Debra I , Wolfe Stacey Q
Published: August 2021

Introduction:
Intracerebral hemorrhage (ICH) is the second most common subtype of stroke. Hypertension is a major cause of primary spontaneous ICH. However, sex difference in blood pressure (BP) and arterial stiffness among ICH patients is not well characterized.

Methods:
A prospective pilot study to investigate the feasibility of measuring arterial stiffness in acute primary ICH patients was approved by the institutional research board at Wake Forest Baptist Health. Eligible subjects with primary ICH were enrolled in the study within 7 days of onset. Non-invasive measurements of brachial BP, aortic BP, augmentation index at heart rate of 75 beats per minute (AIx75), and carotid-femoral pulse wave velocity (cf-PWV) were measured at the patient’s bedside, using the SphygmoCor XCEL System v1 (AtCor Medical Pty Ltd., Sydney, Australia).

Results:
A total of 20 patients have been enrolled in the study over 5 months. Over half the patients enrolled were female (55%, n = 11), including 82% (n = 9) White, 9% (n = 1) Asian and 9% (n = 1) Hispanic. There was increased diversity in the male patients (45%, n = 9) including 44% (n = 4) Black, 22% (n = 2) White, 22% (n = 2) Hispanic, and 11% (n = 1) Asian. Men were significantly younger than women (57 ± 5 years vs 74 ± 3 years, respectively, P = 0.009). There were no significant differences in BMI or ICH score. At the time of measurement, there were no significant sex differences in brachial or aortic blood pressures (systolic and diastolic), however, females had significantly higher AIx75 (35 ± 4 vs 20 ± 6, P = 0.036) and aortic PP (53 ± 2 mm Hg vs 42 ± 4 mm Hg, P = 0.020) than males. Sex difference in cf-PWV was not statistically significant (p = 0.054).

Conclusion:
In the current feasibility pilot study, preliminary data show that females had higher arterial stiffness measured as AIx75 and aortic PP than males in the acute setting of ICH. Further study will be required to ascertain whether this is related to higher age at presentation in females. Whether sex differences in arterial stiffness predict differences in the outcome among ICH patients is not well characterized; thus, assessment of 30-day functional and neurological outcomes will be performed with NIHSS and modified Rankin Scores.
Abstract P151: Cardiovascular Effects Of Peritoneal Dialysis In The 5/6 Nephrectomy Rat Model
Authors: Nasci Victoria , Kriegel Alison J
Published: August 2021

In the US more than 130,000 people are diagnosed with end stage renal disease (ESRD) each year. Of those only 3% receive a kidney transplant while the remaining 97% are reliant on dialysis for survival. Among dialysis patients, cardiovascular (CV) related events are the leading cause of death. Despite therapeutic advancements the continued CVD following the onset of dialysis poses an interesting clinical challenge that necessitates studies into the effects and effectiveness of dialysis. Furthermore, home dialysis, particularly peritoneal dialysis (PD), has been utilized increasingly in ESRD care (up 10% in 2018) thus the need to understand PD effects on the CV system is urgent. Based on clinical outcomes, we hypothesized that PD would have no effect on CV outcomes in chronic kidney disease (CKD). To study CKD, we performed 5/6 nephrectomy (5/6Nx) or sham surgery, on 10 week old male Sprague-Dawley rats. Peritoneal catheters were then implanted 6 weeks post-surgery and PD was initiated 2 days later in some of the 5/6Nx and sham animals (15ml [Baxter PD-2 2.5%] 1-hour dwell 3x/day for 9 days). Echocardiography was performed at baseline, 6-, and 7-weeks post-surgery. At week 7 pressure volume analysis was performed prior to serum and tissue collection. Statistical significance was determined by two-way ANOVA. 5/6Nx increased heart weight (5/6Nx 0.43±0.02 vs. Sham 0.34±0.01; p<0.05). PD had no effect on heart weight in sham rats, but attenuated the increase in 5/6Nx rats (5/6Nx 0.43±0.02 vs. 5/6Nx PD 0.40±0.01; p<0.05). 5/6Nx increased systolic blood pressure (5/6Nx 133.6±5.6 vs. Sham 111.1±5.9; p<0.05). PD had no effect on blood pressure in either sham or 5/6Nx rats. 5/6Nx increased cholesterol (5/6Nx 134.9±8.3 vs. Sham 104.3±11; p<0.05), but PD attenuated the rise in cholesterol in 5/6Nx rats (5/6Nx 134.9±8.3 vs. 5/6Nx PD 115.7±9; p<0.05), and greatly increased triglycerides (5/6Nx 65.6±11 vs. 5/6Nx PD 165.5±11.9; p<0.05). CV echocardiography parameters in sham animals and in 5/6Nx were unchanged by PD. These data combined suggests that PD may have little to no effects on some CV parameters while worsening others. These findings indicate more studies focused on the CV effects of dialysis are necessary to help improve outcomes in the ESRD population.
Abstract P152: Low Memory Recall And High Common Carotid Artery Flow Pulsatility In Non-Dialysis Chronic Kidney Disease Patients
Authors: Shenouda Ninette , Chouramanis Nicholas , Cohen Matthew , Townsend Raymond R , Edwards David G
Published: August 2021

A significant proportion of patients with non-dialysis chronic kidney disease (CKD) present with mild-to-moderate deficits in the cognitive domains of executive function and episodic memory. Excess blood flow pulsatility is damaging to the microvasculature of high-flow, low-resistance organs like the brain and may contribute to the cognitive deficits prevalent among CKD patients. We tested the hypothesis that patients with moderate-to-severe non-dialysis CKD have excess flow pulsatility along their carotid and cerebral vasculature that is associated with deficits in executive function and episodic memory. We recruited 10 non-dialysis CKD patients (age=68±8 yrs; estimated glomerular filtration rate, eGFR=36±18 mL/min/1.73 m
2
) and 7 healthy age-matched adults (age=65±5 yrs; eGFR=81±17 mL/min/1.73 m
2
). Global cognitive function was assessed with the Montreal Cognitive Assessment (MoCA). Executive function and episodic memory were assessed using the NIH Toolbox Flanker Inhibitory Control and Attention Test and California Verbal Learning Test III, respectively, and reported as standardized scores (mean=100, SD=15). Pulsatility index [(systolic blood velocity - diastolic blood velocity)/ mean blood velocity] was measured in the common carotid (CCA), internal carotid (ICA), and middle cerebral arteries (MCA) via Doppler and transcranial Doppler ultrasound. Compared to healthy adults, CKD patients did not differ in total brain blood flow (p=0.42) but had lower MoCA (CKD=26±3, Healthy=29±1; p=0.01) and memory recall scores (CKD=92±21, Healthy=110±9; p=0.05). CKD patients did not differ from our healthy control group in executive function (CKD=91±10, Healthy=90±11; p=0.80) but did produce a mean score that was 0.6 SD lower than the NIH Toolbox reference sample. CKD patients had a higher pulsatility index in the CCA (CKD=2.3±0.5, Healthy=1.9±0.3; p=0.05) but not in the ICA (p=0.68) or MCA (p=0.57). CCA pulsatility index was strongly and inversely associated with episodic memory recall scores (r=-0.64, p<0.01, n=17). This data suggests that although the higher CCA flow pulsatility in non-dialysis CKD patients does not appear to be transmitted to the cerebrovasculature, it nevertheless may still be contributing to memory impairments.
Abstract P153: Heart Rate And Systolic Hypertension At Early Post-kidney Transplant Period
Authors: Tantisattamo Ekamol , Mutirangura Pornthira , Polpichai Natchaya , Saowapa Sakditad , Eguchi Natsuki
Published: August 2021

Introduction:
Sympathetic nervous system activation may be assessed by increased heart rate, which is associated with worsened cardiovascular and renal outcomes in general population. We aim to examine association between heart rate and blood pressure in kidney transplant recipients.

Methods:
A single center retrospective cohort study examines association of average successive heart rate (ASHR), which was defined as the average heart rate between successive office heart rate, with systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 12-, 24-, 36-, and 48-weeks post-transplant by using multiple linear regression. Association of the ASHR with systolic hypertension (SHTN) and diastolic hypertension (DHTN) defined as SBP ≥130 and DBP ≥80 mmHg, respectively, were tested by multiple logistic regression.

Results:
Of all 105 kidney transplant recipients, mean age±SD was 54±12 years old and 61% was female. ASHR were 80±9, 79±10, 78±11, 76±11 beats/minutes at 12, 24, 36, and 48 weeks, respectively (p 0.509); therefore, ASHR was categorized into low and high ASHR groups (<80 and ≥80 beats/minute). The corresponding SBP were 136±17, 135±19, 132±16, 133±16 mmHg (p 0.356) and DBP were 80±11, 80±12, 78±11, 71±11 mmHg, respectively (p 0.644). With adjustment for age, gender, body mass index, type of kidney transplant, and induction immunosuppressive medications, at 24-week post-transplant, every 10 beats/minute increase in ASHR was associated with 4.4 mmHg decrease in SBP (β
adjusted
-0.440; p 0.016; 95%CI -0.796, -0.084) and high ASHR group was associated with 0.32-time lower odds of developing SHTN (OR
adjusted
0.324; p 0.022; 95%CI 0.124, 0.852). There was no statistically significant association between ASHR and SBP at other post-transplant periods as well as between ASHR and DBP.

Conclusions:
Increased or high heart rate is associated with lower SBP or SHTN, but not DBP or DHTN at early post-transplant period. This association in an opposite direction among kidney transplant recipients may indicate different effects of sympathetic nervous system activation on blood pressure. Changes in immunological and non-immunological factors may contribute to the findings at different post-transplant periods.
Abstract P156: Negative Interaction Of Fatty Liver And Hypertension On Cardiovascular Mortality In Non-diabetic Men
Authors: Ould Setti Mounir , Voutilainen Ari , Tajik Behnam , Niskanen Leo , Tuomainen Tomi-Pekka
Published: August 2021

Fatty liver disease (FLD) and hypertension are separately associated with cardiovascular (CV) mortality. While the two conditions are established as separate predictors of CV outcomes, FLD and hypertension are interrelated in multiple ways. A biological interaction in respect to CV disease outcomes could exist between FLD and hypertension. In this study, we investigated the joint effect and interaction of FLD and hypertension regarding CV mortality using an interaction framework. Using a population-based cohort, we followed 1,569 middle-aged non-diabetic Finnish men for 34 years. We computed the fatty liver index and considered values ≥60 as indicative of FLD. We defined hypertension as either i) self-reported hypertension and a confirmed use of antihypertension medication, or ii) a mean systolic ≥160 or diastolic ≥105 blood pressure on baseline examination. The choice of the blood pressure measurement threshold to define hypertension was based on a sensitivity analysis. With adjustment for age, body mass index, smoking, and alcohol consumption, separate and combined effects of FLD and hypertension and their interaction at the multiplicative and additive scales regarding all-cause and CV death were assessed using Cox proportional hazards models. Among the men, 372 had FLD and 342 had hypertension. FLD and hypertension coexisted in 134 men. FLD and hypertension associated, independently and combined, with an increased hazard of all-cause and CV deaths. Non-cardiovascular mortality associated with FLD, but not with hypertension. We found a negative interaction between FLD and hypertension regarding the hazard of all-cause (relative excess risk due to interaction [RERI], -0.97; 95% confidence interval [CI], -1.65 to -0.28) and CV mortality (RERI, -1.74; 95% CI, -2.98 to -0.50). The interaction was also found on a multiplicative scale. We found evidence of a negative interaction between FLD and hypertension in respect to CV mortality. Our findings were robust to different definitions of hypertension but were more relevant at high blood pressure thresholds. We thus recommend adjusting for FLD or hypertension when studying the effect of the other condition on mortality or CV diseases in middle-aged men and call for further research on the topic.
Abstract P159: Moderate To Severe Obstructive Sleep Apnea Is Independently Associated With Inter-arm Systolic Blood Pressure Difference: Tokyo Sleep Heart Study
Authors: Shiina Kazuki , Tomiyama Hirofumi , Nakano Hiroki , Masatsune Fujii , Chikamori Taishiro
Published: August 2021

Objective:
Obstructive sleep apnea (OSA) is recognized as an independent risk factor for cardiovascular disease. On the other hand, inter-arm systolic blood pressure difference (IAD), inter-ankle systolic blood pressure difference (IAND), and ankle-brachial index (ABI) are all known predictors of cardiovascular events. The aim of the present study was to investigate the association between OSA and four-limb blood pressure differences.

Methods:
We conducted this cross-sectional study in a large sleep cohort from Tokyo Sleep Heart Study. In 2643 consecutive patients who visited our sleep clinic for polysomnography between 2005 and 2017; all the subjects underwent blood pressure measurement simultaneously in all the four limbs by oscillometric methods.

Results:
The prevalence rate of IAD ≥ 10 mm Hg was significantly higher in the severe OSA (apnea-hypopnea index ≥ 30) group (4.6%) than in the no/mild (apnea-hypopnea index < 15) OSA group (1.6%). Multivariate logistic regression analysis also identified moderate to severe OSA as being significantly associated with IAD ≥ 10 mm Hg, even after adjustments for confounding variables [moderate OSA; odds ratio (OR): 3.627, 95% confidence interval (CI): 1.056-12.465,
P
= 0.041. Severe OSA; OR: 3.778, 95% CI: 1.113-12.595,
P
= 0.031]. However, there were no significant associations of the OSA severity with IAND ≥ 15 mm Hg or ABI < 0.9.

Conclusions:
Moderate to severe OSA was independently associated with the IAD, not but with the IAND or ABI. The plausible explanation is that the negative intrathoracic pressure caused by OSA may exert an adverse impact on the structural properties of the thoracic aorta. Our findings emphasized that physicians should be careful of IAD, easily applied clinical tool, to evaluate subclinical cardiovascular damage and cardiovascular risk in patients with OSA.