bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP46: Mutagenesis Of PRR Cleavage Site In Mice Attenuates Angiotensin II-induced Hypertension And Suppresses Renin Expression
Authors: Wang Fei , Chen Yanting , Zou Chang-jiang , Luo Renfei , Yang Tianxin
Published: August 2021

It is well demonstrated that activation of renal (pro)renin receptor (PRR) contributes to AngII-induced hypertension. Relatively, less is known about involvement of soluble PRR (sPRR), the extracellular domain of PRR, primarily generated by site-1 protease(S1P) and furin. Moreover, the relationship between PRR/sPRR and the renin-angiotensin system (RAS) has been debated. In the present study, we used CRISPR/Cas9 strategy to generate mice with mutagenesis of the overlapping cleavage site for both proteases in PRR (termed as PRR
R279V/L282V
) to examine the phenotype during angiotensin II (AngII) infusion with particular emphasis on circulating and intrarenal renin status. PRR
R279V/L282V
mice exhibited a reduction of sPRR level in plasma by ~53% and in the kidney by ~82%, were fertile, and had no gross developmental abnormalities. At basal condition, PRR
R279V/L282V
mice had drastically suppressed renin levels from plasma (plasma total prorenin/renin content [ng/ml]: 9.3 ± 0.7 in PRR
R279V/L282V
mice vs. 12.8 ± 0.9 in WT mice, n = 5, p < 0.05), urine (urinary total prorenin/renin excretion [ng/24h]: 0.54 ± 0.11 in PRR
R279V/L282V
mice vs. 1.05 ± 0.15 in WT mice, n = 5, p < 0.05), and the kidney as compared to wild-type controls (WT). By telemetry, the hypertensive response of PRR
R279V/L282V
to AngII infusion (300 ng/min/kg) was blunted (MAP [mmHg] in Day 10: 125.9 ± 4.6 in PRR
R279V/L282V
mice vs. 138.5 ± 2.8 in WT mice, n = 8 for each group, p < 0.05) in parallel with attenuated response of intrarenal renin and renal medullary α-ENaC expression. We further examined the direct role of sPRR in renin regulation in As4.1 cells, a renin-expressing cell line isolated from mouse renal tumor and M-1 cells, a mouse cell line derived from the collecting duct. The exposure to sPRR-His in both cell types consistently elevated renin activity, and renin expression at both protein and mRNA levels, all of which were sensitive to inhibition by ICG-001, a β-catenin signaling inhibitor. Together, these results represent strong evidence favoring sPRR as a mediator of AngII-induced hypertension and a master regulator of renin expression at systemic and local levels. Therefore, PRR should be considered as an integrative member of the RAS.
Abstract MP47: Rho-related BTB Domain-containing Protein 1 (RhoBTB1) Attenuates Established Arterial Stiffness In Ang-ii-treated Mice
Authors: Fang Shi , Wu Jing , Reho John J , Brozoski Daniel , Donato Silva Sebastiao , Lu Ko-Ting , Sigmund Curt D
Published: August 2021

RhoBTB1 is a transcription target of PPARγ but its function remains unclear. Restoration ofRhoBTB1 by genetic complementation in S-P467L mice expressing dominant negative PPARγmutation reversed hypertension, arterial stiffness, and vascular dysfunction. Here, we asked ifrestoring RhoBTB1 can reverse Ang-II-mediated hypertension and arterial stiffness.To test this hypothesis, S-RhoBTB1 mice, which expressed smooth muscle-specific, tamoxifen(Tx)-inducible RhoBTB1, were implanted with minipumps which released Ang-II (490ng/kg/min, 6weeks) or vehicle. Concurrently, littermate ISM-Cre mice, which expressed smooth muscle-specific, Tx-inducible Cre (but not RhoBTB1), were used as control. Transgenes were induced by5 daily Tx injections 2 weeks after Ang-II pump implantation, and tissue was harvested 2 weeksafter Tx. Measurements were made during a 1 week baseline period, 2 weeks of Ang-II, and 2weeks after transgene activation.Aortic RhoBTB1 expression was decreased in Ang-II-treated ISM-Cre mice (ISM-Cre, Ang-II vs.ISM-Cre, vehicle dCT: 13.6±0.1 vs. 12.4±0.1, n=10), and restored to normal in Ang-II-treated S-RhoBTB1 mice (S-RhoBTB1, Ang-II vs. ISM-Cre, vehicle dCT: 12.8±0.2 vs. 12.4±0.1, n=10-12).Interestingly, pulse-wave velocity, a clinical indicator of arterial stiffness, was significantlydecreased upon RhoBTB1 restoration in Ang-II-treated mice (S-RhoBTB1 vs. ISM-Cre: 2.9±0.1vs. 3.8±0.2, n=22-26). Concomitantly, measures of both pressure-diameter and stress-strainshowed that aortic compliance was improved by RhoBTB1 restoration in Ang-II-treated mice.Interestingly, restoring RhoBTB1 was insufficient to attenuate Ang-II-mediated hypertension (S-RhoBTB1, Ang-II vs. ISM-Cre, Ang-II vs. ISM-Cre, vehicle SBP: 152.1±1.7 vs. 148.0±3.7 vs.115.4± 0.7 mmHg n=12, 8, 6). Currently, we are investigating the mechanism by which RhoBTB1attenuates arterial stiffness.In summary, RhoBTB1 restoration ameliorated Ang-II-mediated arterial stiffness but nothypertension, suggesting that arterial stiffness is not merely a consequence of hypertension butcan be independently regulated from blood pressure. Moreover, there may be novel targets ofRhoBTB1 that can regulate aortic stiffness and be therapeutic.
Abstract MP48: Crispr/cas9 Trpv1 Deletion In Rats Does Not Impair Mechano- And Chemo-sensory Renal Afferent Nerve Responses
Authors: DeLalio Leon J , Stocker Sean D
Published: August 2021

Elevated renal afferent nerve activity (ARNA) or dysfunctional renal reflexes contributes to hypertension and chronic kidney disease. The transient receptor potential vanilloid type-1 (TRPV1) channel is expressed in renal sensory nerves, and intrarenal administration of the TRPV1 agonist capsaicin increases ARNA. Nonselective denervation of renal sensory nerves using high-concentration capsaicin reduces arterial blood pressure (ABP) in experimental models of hypertension. However, the role of TRPV1 channels in ARNA responses to chemo- and mechano-sensitive stimuli has not been directly tested.

To test this hypothesis, we generated a novel TRPV1 rat knockout model (TRPV1
-/-
) using CRISPR/CAS9 to delete exon 3

. ARNA multifiber recordings were performed in male and female TRPV1
-/-
and wild-type littermates (250-400g) after decerebration or Inactin anesthesia (data combined). Wild-type and TRPV1
-/-
rats had no significant differences in baseline mean ABP (126±4 mmHg vs 138±5 mmHg, respectively; n=8-10) or heart rate (451±25 bpm vs 432±24 bpm, respectively; n=8-10). Baseline ARNA was not different between wild-type and TRPV1
-/-
rats (16±3 Hz vs 28±6 Hz, respectively; n=8-10). Intrarenal artery infusion of the TRPV1 agonist capsaicin (0.1-10μM, 50μL per 15s) significantly increased ipsilateral ARNA in wild-type but not TRPV1
-/-
rats (Δ discharge with 10μM: 65±3 Hz vs 6±1 Hz, respectively; n=5-7). As a second chemosensitive stimulus, intrarenal artery infusion of bradykinin (0.1-10μM, 50μL per 15s) produced similar increases in ipsilateral ARNA between wild-type and TRPV1
-/-
rats (Δ discharge with 10μM: 52±6 Hz vs 73±18 Hz, respectively; n=5-6). Finally, elevated renal pelvic pressures (0-20mmHg; 30s) significantly increased ipsilateral ARNA in both wild-type and TRPV1
-/-
rats; however, the ARNA response was significantly greater in TRPV1
-/-
versus wild-type rats (Δ discharge with 20mmHg: 47±14 Hz versus 18±6 Hz, respectively; n=5-8). In conclusion, mechanosensitive and chemosensitive ARNA responses remain intact in TRPV1
-/-
rats. The mechanisms responsible for renal sensory nerve activation remain unidentified and the impact of TRPV1 deletion in rat models of hypertension and kidney disease remains to be tested.
Abstract MP49: Single Cell Multiplex Immunophenotyping Using Mass Cytometry And CITE-Seq Reveals Decreases In Circulating PD-1
+
CD8
+
Memory T Cells With Features Of Exhaustion In Human Hypertension
Authors: Alexander Matthew R , Smart Charles D , Dale Bethany L , Elijovich Fernando , Wogsland Cara , Barone Sierra , Irish Jonathan , Madhur Meena S
Published: August 2021

Emerging evidence from animal models has demonstrated the importance of multiple innate and adaptive immune cells in hypertension. We hypothesized that the abundance and phenotype of circulating immune cell subsets are altered in human hypertension. To test this, we performed high dimensional single cell profiling of human peripheral blood mononuclear cells using mass cytometry. Unsupervised computational analysis revealed a 40% decrease in CD8
+
memory T cells in hypertensive individuals. Using Phenograph to identify subsets of these cells revealed a selective 60% decrease in PD-1
+
CD8
+
memory T cells in hypertension. This observation was confirmed in a validation cohort using flow cytometry in which PD-1
+
CD8
+
memory T cells were significantly decreased 44% in hypertensive compared to control individuals. To determine the phenotype of these PD-1
+
CD8
+
memory T cells, we performed Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) on four control and four hypertensive individuals. Using antibodies to identify PD-1
+
and PD-1
-
CD8
+
memory T cells, gene set enrichment analysis of the coordinate single cell transcriptomic data revealed that PD-1
+
cells exhibit over-representation of features of both immunologically active effector T cells and hypofunctional exhausted T cells. Thus, clustering analysis of PD-1
+
CD8
+
memory T cells was performed which demonstrated 4 distinct subclusters. One of these subclusters was decreased in hypertension and exhibited selective expression of multiple inhibitory receptors characteristic of exhausted T cells. At the protein level, this subcluster was marked by expression of the inhibitory receptor LAG3 and low levels of CD57. Combining these markers to identify PD-1
+
LAG3
+
CD57
-
CD8
+
memory T cells permitted identification of exhausted cells which demonstrated a significant 35% decrease in hypertensive compared to control individuals using flow cytometry. Taken together, these results demonstrate novel and reproducible decreases in circulating PD-1
+
CD8
+
memory T cells with features of exhaustion in human hypertension. These findings provide new insights into the pathogenesis of human hypertension including loss and/or re-invigoration of exhausted T cells.
Abstract MP50: Time Restricted Feeding Reduces Interleukin 17a Production Associated With Western Diets
Authors: Davis Gwendolyn K , Fehrenbach Daniel , Smart Charles D , Edell Claudia , Pollock Jennifer , Madhur Meena S
Published: August 2021

Circadian rhythms govern our daily physiological processes. However, disruption of circadian rhythms, as can occur with
ad libitum
Western diets, disrupt these processes leading to cardiometabolic diseases. Our lab and others have shown that Th17 cells, which produce interleukin 17A (IL-17A), are implicated in the development of cardiovascular and renal end-organ damage associated with high fat and/or high salt diets. Th17 cell differentiation and trafficking is regulated by the circadian clock and influenced by light-dark cycles. However, whether feeding-fasting rhythms influence Th17 cell responses is poorly understood. We tested the hypothesis that limiting food intake to the 12-hr active period (time-restricted feeding, TRF) mitigates high fat and high salt (HF/HS) diet induced T cell IL-17A production and target organ damage. Beginning at 8 weeks of age, male C57Bl/6J mice were placed on either a normal chow/normal salt (NC/NS) or a HF/HS diet for 20 weeks, with TRF intervention occurring during the last two weeks in the HF/HS + TRF group. Body weight was similarly significantly increased in the HF/HS and HF/HS + TRF groups in comparison to the NC/NS group. Th17 cells were significantly increased (2.6-fold increase, p = 0.02) in the Peyer’s patches (lymphoid aggregates found in the small intestines) of mice on HF/HS diet in comparison to those on NC/NS. Importantly, TRF abolished this increase. Renal CD4
+
T cell IL-17A production, as measured by flow cytometry, was increased by HF/HS diet compared to NC/NS (3-fold increase, p = 0.02). Similarly, TRF abolished this increase. This study highlights how Western diets exacerbate intestinal and renal IL-17A production and the potential beneficial impact of a behavioral intervention, TRF, to mitigate the Th17 mediated inflammation associated with diet-induced obesity.
Abstract MP60: Down-regulated Mir-338-3p In Subcutaneous Small Arteries Of Hypertensive Patients With Chronic Kidney Disease Targets Protein Tyrosine Phosphatase Receptor Type S And Glutathione Peroxidase 3
Authors: Berillo Olga , Huo Kugeng , Richer Chantal , Fraulob-Aquino Julio C , Briet Marie B , Boutouyrie Pierre , Lipman Mark L , Sinnett Daniel , Paradis Pierre , Schiffrin Ernesto L
Published: August 2021

Background:
Hypertension (HTN) causes vascular injury identified by endothelial dysfunction, vascular stiffening, and remodeling, which contributes to kidney damage leading to chronic kidney disease (CKD). MicroRNAs (miRNAs) repress/degrade target mRNAs. Their role in vascular injury in HTN remains unclear. We aimed to identify differentially expressed (DE) miRNAs in gluteal subcutaneous arteries of patients with HTN associated or not with CKD to shed light on the pathophysiological molecular mechanisms.

Methods:
Normotensive subjects and patients with HTN associated or not with CKD grades 3-4 were studied (n=15-16). Small arteries were isolated from gluteal subcutaneous biopsies, RNA extracted and small and total RNA sequencing performed by Illumina HiSeq-2500. DE genes were identified with a
P
<0.05 and fold change (FC) >1.3. Top 3 DE miRNAs (
P
<0.001, FC>2, mean read count number (MRCN) >3,000 in all groups and having predicted mRNA targets) were selected for validation by reverse transcription-quantitative PCR (RT-qPCR). The mRNA targets of the top selected miRNA were predicted by TargetScan with
P
<0.01, FC>1.5 and MRCN>150 and the top 9 targets were validated by RT-qPCR using gain- and loss-of-function in human aortic endothelial cells (HAECs). Gene ontology enrichment analysis (GOEA) was done in Cytoscape.

Results:
DE miRNAs and mRNAs were identified uniquely associated with HTN (miRNAs: 10, mRNAs: 68), CKD (miRNAs: 68, mRNAs: 395), and in both groups (miRNAs: 2, mRNAs: 32). miR-338-3p presented the best correlation between RNA sequencing and RT-qPCR (R
2
=0.328,
P
<0.001) among the top 3 DE miRNAs. Two of the selected top 9 miR-338-3p predicted targets were validated in HAECs. Protein tyrosine phosphatase receptor type S (
PTPRS
, FC: 0.80±0.08 vs 1.00±0.00) and glutathione peroxidase 3 (
GPX3
, FC: 0.88±0.04 vs 1.00±0.00) were down-regulated in HAECs transfected with miR-338-3p mimics (
P
<0.05). GOEA showed association of
GPX3
with oxidative stress detoxification (
q
<0.05), and of
PTPRS
with the immune system, neuronal system and developmental process (
q
<0.001).

Conclusion:
Down-regulated miR-338-3p in gluteal subcutaneous small arteries of hypertensive patients with CKD targets
PTPRS
and
GPX3
that may play a role in vascular injury in HTN.
Abstract MP62: Sars-cov-2 Spike Protein Regulation Of Angiotensin Converting Enzyme 2 And Tissue Renin-angiotensin Systems: Influence Of Biologic Sex
Authors: Cassis Lisa A , Waters Christopher M , Shoemaker Robin C , Sturgill Jamie , AlSiraj Yasir , Ensor Mark
Published: August 2021

Angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor and an enzyme of the renin-angiotensin system (RAS), is on the X chromosome and stimulated by estrogen. Male sex is a risk factor for SARS-CoV-2 severity. Previous investigators demonstrated that the SARs-CoV-2 Spike (S) protein decreases tissue ACE2 by protein internalization or shedding. This study defined sex differences in tissue ACE2 expression and their impact on SARS-CoV-2 S protein regulation of ACE2 activity and AngII levels. Male and female intact or gonadectomized (GDX) low density lipoprotein receptor deficient (

Ldlr
-/-

) mice, and Four Core Genotype (FCG) male (XY or XX) or female (XX or XY) mice were fed a Western diet for 4 months. In lung, ACE2 mRNA abundance was similar in male and female mice and reduced by GDX (Male XY intact: 1.04 ± 0.15; Female XX intact: 1.13 ± 0.13; Male XY GDX: 0.11 ± 0.03; Female XX GDX: 0.18 ± 0.04 ΔΔCt; P<0.05). Lungs from XX mice had higher ACE2 mRNA abundance than XY mice regardless of gonadal sex (P<0.05), and GDX reduced ACE2 mRNA abundance in lungs of XX, but not XY females (XX Female GDX: 0.18 ± 0.04; XY Female GDX: 0.38 ± 0.09; P<0.05). In adipose, XX females had higher ACE2 mRNA abundance than XY males (XX female: 5.4 ± 0.7; XY male: 1.0 ± 0.1; P<0.05), regardless of gonadal sex (XY females: 3.3 ± 0.7; XX males: 1.5 ± 0.3; P<0.05). Male XY and female XX

Ldlr
-/-

mice were administered vehicle or SARS-CoV-2 S protein (2 nmol/kg, ip, 3 doses) with tissue harvest six hours later. In lung, AngII levels were increased by S protein in male, but not female mice (Male, vehicle: 12.3 ± 2.3; Male, S protein: 33.6 ± 7.1; Female, vehicle: 16.1 ± 2.0; Female, S protein: 20.2 ± 1.3 pg/μg protein; P<0.05). In adipose, ACE2 activity was reduced by S protein in male, but not female mice (Male, vehicle: 63.6 ± 13.9; Male, S protein: 26.1 ± 1.9; Female, vehicle: 32.5 ± 1.9; Female, S protein: 25.1 ± 1.3 RFU/hr/mg tissue; P<0.05). SARS-CoV-2 S protein (35 nM) decreased ACE2 activity in type II lung alveolar cells (Vehicle: 2.0 x 10
4
; S protein: 1.2 x 10
4
RFU/10
6
cells) and 3T3-L1 adipocytes (Vehicle: 2.1 x 10
4
± 0.3 x 10
4
; S protein: 1.1 x 10
4
± 0.8 x 10
3
RFU/10
5
cells; P<0.05). Biologic sex regulation of ACE2 may protect females from SARS-CoV-2 S protein-mediated ACE2 reductions and activation of the local RAS.
Abstract MP71: Impact Of 30 Versus 60 Second Time Interval Between Automated Office Blood Pressure Measurements On Measured Blood Pressure
Authors: Cluett Jennifer L , Juraschek Stephen P , Mukamal Kenneth J , Ishak Anthony , Wood Julia
Published: August 2021

Background:
Guidelines advocate for the use of automated office-based blood pressure (AOBP) measurement to improve accuracy of blood pressure (BP) measurement in the outpatient clinical setting. Current recommendations include a 5-minute period of quiet rest prior to obtaining 3 readings, each separated by 1-2 minutes. As a result, AOBP requires a minimum of 7 minutes of rest time in addition to proper patient positioning plus cuff inflation and deflation, adding nearly 10 minutes to an office visit. Reducing this by even 1 minute has broad implications for the widespread use of AOBP.

Methods:
Patients from a single hypertension center underwent a 3-day evaluation that included a 24-hour ambulatory BP monitor (ABPM) and one of two, non-randomized, unattended AOBP protocols. Half of patients underwent 3 BP measurements separated by 30 seconds and the other half underwent 3 BP measurements separated by 60 seconds. All measurements were compared to the average awake-time BP from ABPM as well as the first AOBP measurement.

Results:
Among 102 patients, the average awake-time BP was 128.6±13.6/76.5±12.5 mmHg for the 30-second protocol and 132.5±15.6/77.7±12.2 mmHg among those who underwent the 60-second protocol . Mean BP was lower with the 2nd and 3rd AOBP measurement by -0.5/-1.7 mmHg and -1.0/-2.3 mmHg for the 60-second protocol versus -0.8/-2.0 mmHg and -0.7/-2.7 mmHg for the 30-second protocol (
Figure
). Differences between AOBP measurements (1st, 2nd, or 3rd) and awake-time ABPM were nearly identical across protocols.

Conclusion:
A 30-second interval between AOBP measurements was as accurate and reliable as a 60-second interval.
Abstract MP72: Remote Monitoring Reduces Blood Pressure And Crisis Hypertension In Post-acute Transitions Of Care For Medicare Patients
Authors: Sanchez Jorge , Adams Don , Smith Bert , Shah Nirav H
Published: August 2021

Introduction:
The major benefits of remote physiologic monitoring (RPM) of blood pressure are usually observed in high-risk patients. Readmissions, return to acute care (RTA), is an undesirable outcome for post-acute care facilities (PACs). Transitions from PACS to ambulatory care have a high risk of RTA. We assessed RPM for hypertension (HTN) patients discharged from PACs.

Hypothesis:
We hypothesized that PAC discharged patients would benefit from RPM and it would lead to less hypertension during their transition to ambulatory care.

Methods:
Patients were enrolled in Medicare’s (CMS) RPM program that were being discharged from PACs in Tennessee. HTN RPM began at discharge from PACs. Blood pressure (BP) was measured with cellular-connected devices and a mobile-could application (Alertive, Seattle WA). Data was equally divided into 24-hour windows, classified to JNC8 hypertension classes. Results were reported to PAC and ambulatory clinicians on a monthly basis. Immediate alerts were delivered to physicians for patients with systolic BP > 180 mmHg for timely intervention. Events such as ED visits and hospital readmissions were tracked by the nursing team during their calls per CMS RPM criteria. Patients were telephoned once a month, coached on their BP data, adherence to medications, and upcoming medical visits. Mean comparison of BP data before and after RPM was performed using paired t-test.

Results:
BP readings from 20 patients (mean age=78.3 ±8.4) were collected between March and May, 2021. A total of 758 readings were analyzed. Twelve hypertensive crises in 6 unique patients were observed. Nine hypotensive instances in 5 patients were observed. Events led to intervention in all unique patients. One patient was hospitalized, and another was referred to the ED for abdominal pain vs 8 patients readmitted in the prior 90 days. Overall, there was a significant decrease in mean systolic BP (144.7 ± 23.1 mmHg at start of RPM vs. 135.2 ± 15.9 mmHg, post RPM; p=0.018) with a mean reduction of 9.5 mmHg at end of the program.

Conclusions:
After discharge from PAC’s patients monitored by CMS’ RPM achieved a significant reduction in BP. PAC hypotension is an area to evaluate in cardiovascular and renal patients. Future work to demonstrate reduction in RTA is merited.
Abstract P110: Intravenous Hydralazine Effect On Blood Pressure Following Severe Inpatient Hypertension Development
Authors: Ghazi Lama , Li Fan , Chen Eric , SIMONOV MICHAEL , Yamamoto Yu , Biswas Aditya , Hanna Jonathan , Shah Tayyab , Peixoto Aldo J , Wilson F. Perry
Published: August 2021

Background:
BP elevations in the hospital are commonly treated with intravenous medications, specifically hydralazine. However, treatment guidelines are lacking. Our goal is to assess the effect of intravenous hydralazine on BP following severe inpatient HTN development.

Methods:
This is a cohort study of adults admitted for reasons other than HTN and developed severe HTN within a single healthcare system. We defined severe inpatient HTN as the first documentation of BP elevation (>180 systolic or >110 diastolic) at least 1 hour after admission. Pregnant women were excluded. Mixed-effects models with nonlinear time trend were used to assess and visualize the time-dependent effect of intravenous hydralazine on BP within 6 hours of BP elevation.

Results:
Of the 23,147 inpatients who developed severe HTN, 13,753 were untreated and 9,166 were treated of which 12% received intravenous hydralazine. Of the treated and untreated patients, 57 and 46% had a severe MAP reduction (drop ≥30%) (p-value<0.01). Risk factors for severe MAP drop include older age, history of drug and alcohol abuse, and higher BP on admission. Compared to inpatients with severe HTN who did not receive antihypertensives, those treated with intravenous hydralazine had a -12 [-14, -10], -19 [-22, -17], -8[-10, -7] mmHg greater reduction in MAP, SBP, and DBP after adjustment for demographic and clinical characteristics. Moreover, intravenous hydralazine resulted in acute BP reduction (
Figure 1
).

Conclusion:
Severe MAP reduction is observed in both treated and untreated inpatients with severe HTN, however adjusted absolute decrease in MAP is greater in inpatients treated with intravenous hydralazine.
Abstract P111: Comparative Efficacy Of Bisoprolol Compared To Other Selective Beta-1 Blockers In Patients With Hypertension - A Systematic Review And Meta-analysis Of Observational Studies
Authors: Jadhav Uday M , Nair Tiny , BANSAL SANDEEP , Ray Saumitra
Published: August 2021

Introduction:
Selective beta-1 blockers (s-BBs) are used in the management of hypertension (HT) in specific subsets. Studies comparing the potency of blood pressure (BP) lowering with different s-BBs are sparse. The objective of this meta-analysis was to evaluate the efficacy of bisoprolol compared to other s-BBs (Atenolol, Betaxolol, Esmolol, Acebutolol, Metoprolol, Nebivolol) in HT patients by examining their effect on BP, heart rate (HR) and metabolic derangements, by examining the evidences reported in observational studies.

Methods:
Electronic databases like PubMed, EMBASE, Cochrane Library, Clinicaltrials.gov, Surveillance, Epidemiology and End Results Program and 12 PV databases were systematically searched from inception to October 2019. Observational studies that compared bisoprolol with other s-BBs in patients with HT were evaluated in accordance with the PRISMA guidelines. Pooled data were calculated using random-effects model for meta-analysis in terms of mean difference (MD) and 95% confidence interval (95% CI) for each outcome. Outcomes of interest were BP, HR and lipid profile.

Results:
Four observational studies which compared bisoprolol with other s-BBs (nebivolol and atenolol) were included in this meta-analysis. Significant reduction was observed in office diastolic BP [MD: -1.70; 95% CI: -2.68,-0.72;
P
<0.01] among arterial HT patients treated with bisoprolol for 26 weeks (w) compared to those treated with other s-BBs. HT patients treated with bisoprolol for 26 w showed significant reduction in HR [MD: -2.20; 95% CI: -3.57,-0.65;
P
<0.01] and office HR [MD: -2.55; 95% CI: -3.57,-1.53;
P
<0.01] than other s-BBs. HDL cholesterol levels increased significantly in essential HT patients treated with bisoprolol at 26 w [MD: 7.17; 95% CI: 1.90,12.45;
P
<0.01], 78 w [MD: 11.70; 95% CI: 4.49,18.91;
P
<0.01] and 104 w [MD: 10.20, 95% CI: 4.49,18.91;
P
<0.01] compared to other s-BBs.

Conclusion:
Our results suggests that bisoprolol is superior to other s-BBs in reducing BP and HR. Bisoprolol also had a favourable effect on lipid profile shown by increase in HDL cholesterol. This meta-analysis emphasizes the efficacy of bisoprolol over other s-BBs, which aids clinical decision making in treatment of patients with HT.
Abstract P112: Orthostatic Hypotension, Orthostatic Hypertension And Ambulatory Blood Pressure In Patients With Chronic Kidney Disease: Findings From The Chronic Renal Insufficiency Cohort Study
Authors: Ghazi Lama , Cohen Jordana , Townsend Raymond R , Drawz Paul , Rahman Mahboob , Pradhan Nishigandha , Cohen Debbie L , Weir Matthew R , Rincon-choles Hernan , Juraschek Stephen P
Published: August 2021

Background:
We recently demonstrated how orthostatic hypotension might be used to identify out-of-office blood pressure phenotypes, including white coat effects and nocturnal non-dipping patterns. However, these findings have not been replicated in a population with chronic kidney disease (CKD).

Objective:
To examine the association between orthostatic hypotension (OH) or hypertension (OHTN) with ambulatory BP in adults with CKD.

Methods:
CRIC is a prospective multicenter observation cohort study of participants with CKD. Standing BP at 1 minute and ABPM were obtained on 1467 participants. OH was defined as a 20mmHg drop in systolic BP (SBP) or 10 mmHg drop in diastolic BP (DBP) when changing from seated to standing positions. OHTN was defined as a 20 mmHg or 10mmHg rise in SBP or DBP respectively when changing from seated to standing position. White coat effects, based on ABPM, was defined as the difference between seated clinic and ambulatory BP. Systolic and diastolic night to day ratio was also calculated.

Results:
Of the 1467 participants (age: 58 ± 10 yrs, 44% female, 39% black) 73 had OH and 165 had OHTN). OH was positively associated with systolic and diastolic white coat effect (β=5.9 [0.9, 10.9] and 4.2 [1.3, 7.1]). OHTN was negatively associated with diastolic white coat effect (-4.9 [-6.9, -3]). OH was positively associated with systolic and diastolic night-to-day ratio (0.03 [0.01, 0.05] and 0.03 [0.01, 0.06] respectively).

Conclusions:
Clinic-based assessments of OH and OHTN may be useful for identifying BP phenotypes often missed with seated office BP measurements in CKD patients.
Abstract P113: IMPACT OF ARTERIAL SITE AND PRESSURE WAVE ACQUISITION METHOD ON ARTERIAL FORM FACTOR AND MEAN AND CENTRAL ARTERIAL PRESSURE
Authors: Mukhopadhyay Debduti , Nagpal Sagar , Osmond Peter , Izzo Joseph L
Published: August 2021

Accurate mean arterial pressure (MAP) measurement requires an integrated arterial pressure waveform but MAP is often estimated from systolic (S) and diastolic (D) BP using a fixed form factor (FF, usually 0.33): MAP = DBP + FF*pulse pressure (PP), also solvable for FF if MAP is known. MAP is constant in the arterial tree but central (c) PP is lower than peripheral (p) PP, so cFF should be higher than pFF, and MAP and FF values should be similar among devices. We tested these principles for 2 transfer function-dependent devices: SphygmoCor (SPG), which generates high fidelity radial arterial tonometry waveforms and integrates MAP, and Mobil-O-Graph (MOB), a 24-hour ambulatory oscillometric brachial pulse wave analysis system that reports a proprietary MAP. SPG data were obtained after 5-10 minutes of rest and MOB values were obtained at 20 min intervals. For SPG (n =371) [mean(SD)]: pBP 140(28)/80(15) and cBP 126(28)/81(15) mmHg, age 48(20) yr, BMI 28(6.6), 54% women, 17% black. SPG-pFF was lower than cFF [0.34(.056) vs 0.44(.049), p<0.000]; SPG-pFF and cFF were correlated (r
2
= 0.23, p<0.000); and on stepwise multiple regression, pFF was related to MAP > gender > age (multiple-r
2
= 0.37, p<0.000; BMI and race excluded). For MOB (n = 157): pBP 135(18)/81(12) and cBP 123(16)/83(12) mmHg, age 59(16) yr, BMI 30(6), 52% women, 24% black. MOB-pFF was a fixed value [0.46(0.00098)] that was lower than cFF [0.57(0.048), p<0.000] and MOB-cFF was not correlated with MAP or any other characteristic. To compare SPG and MOB directly, 101 pairs were matched precisely (SPSS software) for pSBP and pDBP (130.9/78.7 mmHg for each device group); SPG-MAP was lower than MOB-MAP [96.3 vs 102.6 mmHg (p<0.000)] and SPG-cSBP was lower than MOB-cSBP [117.5 (18.0) vs 119.7(14.6), p=.015], with respective FF’s similar to the full groups. We conclude that: 1) FF varies within-subjects by arterial location and (at constant MAP) cFF > pFF; 2) SPG-pFF (but not MOB-pFF) varies between-subjects and is affected by MAP, gender, and age; 3) the proprietary MOB-pFF is fixed and much higher than traditional FF or SPG-pFF; and 4) compared to SPG, MOB overestimates MAP by about 5% and underestimates cSBP by about 2%. These findings have implications for FF methods and proprietary devices such as Mobil-O-Graph.
Abstract P121: Automated Messaging Program To Facilitate Systematic Home Blood Pressure Monitoring: A Qualitative Analysis Of Provider Interviews
Authors: Murphy Andrew R , Einhorn Julian , Rogal Shari , Burton Danielle , Suffoletto Brian P , Rollman Bruce L , Forman Daniel E , Irizarry Taya , Muldoon Matthew F
Published: August 2021

Introduction:
Hypertension is a leading cause of morbidity worldwide. Home blood pressure monitoring (HBPM) has been shown to lower blood pressure (BP) if paired with co-interventions but such programs are not routinely used in clinical care. MyBP is an automated bi-directional text messaging HBPM program that assists lowering of BP, but how to best implement within clinical care remains unknown. Therefore, in this study, we sought stakeholder input from care providers.

Methods:
We conducted semi-structured interviews (average recorded duration 28 minutes) with physicians, nurses, and medical assistants from primary care settings, most of whom had participated in a feasibility trial of MyBP. The interview was designed around constructs from the Consolidated Framework for Implementation Research. Interviews were transcribed verbatim and analyzed using inductive coding to organize meaningful excerpts and identify salient themes.

Results:
Subjects were physicians (n = 11) and nurses/medical assistants (n = 6). Care providers felt that patients benefitted from MyBP’s positive influence on BP measurement adherence, psychological factors (such as health literacy and patient empowerment), and perceived patient usability of the program. They reported that the program data aided in clinical diagnosis and management of HTN with a practical user interface for providers. Barriers to implementation included lack of integration into the electronic medical record and difficulty in training office staff in its use.

Conclusion:
In this qualitative analysis of care provider stakeholders, MyBP was seen as a pragmatic and effective way to empower patients in BP self-management and tangibly aid providers. Future research will need to focus on strategies to overcome implementation barriers to facilitate integration in to the clinical and digital environment.
Abstract P128: Direct Observed Therapy In Suspected Resistant Hypertension Is Safe
Authors: Hiremath Swapnil , Ruzicka Marcel
Published: August 2021

Introduction:
Direct observed therapy (DOT) has emerged as a method for assessment of adherence, particularly in patients with apparent treatment-resistant hypertension (ATRH), in clinical care as well as research. We have previously demonstrated that direct observed therapy resulted in controlled hypertension in 30% of patients with ATRH. In this study we report on the safety of DOT in terms of change in blood pressure (BP) and hypotensive symptoms.

Methods:
Patients with ATRH were enrolled in a prospective study of DOT, which was followed by ambulatory blood pressure monitoring on the same day and at one month. DOT was performed by administering all prescribed BP lowering drugs, supervised by a nurse in an outpatient clinic setting. BP and vitals were measured at baseline and every 30 minutes until BP plateau based on two consecutive BP readings. All BP measurements during DOT were performed using an automated oscillometric BP device. In this study, we report the change in BP during DOT, with incidence of orthostatic symptoms, and decrease in systolic BP > 20 mm Hg as outcomes of interest.

Results:
50 patients underwent DOT, 32 men, mean age 62 years on median 4 BP lowering drugs (range 3 to 7). The mean baseline BP was 146/77 mm Hg , and the lowest BP during DOT was 129/68 mm Hg. The median decrease in systolic BP was 14 mm Hg (range 0 to 60) and diastolic BP was 8 mm Hg (range 0 to 37). 5 patients (10%) developed orthostatic symptoms during DOT, none of which required any interventions, and resolved with continued observation. A decrease of > 20 mm Hg in systolic BP was seen in 19 patients (38%), and a systolic BP of
<
110 mm Hg was seen in only 6 patients (12%).

Conclusions:
DOT caused decrease in BP by >20 mmHg in about 40% of patients. While these large acute decreases in BP were largely asymptomatic, close observation of BP is required until peak BP lowering effect wanes. As decrease in BP is driven by the degree of non-adherence and number of prescribed BP lowering drugs, our safety record has limitation dictated by the number of subjects enrolled, and relatively small number of patients with more than 5 BP lowering drugs.
Abstract P131: RISK FACTORS AND WAYS OF INFLUENCING MASKED UNCONTROLLED HYPERTENSION
Authors: Shalimova Anna
Published: August 2021

Purpose:
to establish risk factors of masked uncontrolled hypertension (MUCH) and clarify how fixed combinations can affect blood pressure (BP) control.

Methods:
We examined 70 patients with hypertension. The initial assessment of the effectiveness of antihypertensive therapy was carried out 3 months after its appointment. Of the 70 patients, 63 were able to reach essential office BP reduction point (these patients were additionally scheduled for ABPM).

Results:
Among 63 patients in whom hypertension was controlled according to office BP data, 58.7% had insufficient BP control according to ABPM data. Among patients with insufficient control of out-of-office BP, there were significantly more patients with circadian rhythm disorders (p=0.000). An assessment of possible factors for the development of MUCH showed that elderly age occurred in 78.4%, male sex - in 59.5%, smoking - in 70.3%, stress - in 78.4%, various sleep disorders - in 45.9%, diabetes mellitus (DM) - in 56.8%, obesity - in 67.6%, insulin resistance (IR) - in 73%, chronic kidney disease (CKD) - in 35.1% patients with MUCH. Analysis of patient therapy showed that out of 37 patients with MUCH, 7 patients received monotherapy, 9 patients - free dual combinations, and 21 patients - fixed dual combinations. For patients with MUCH, antihypertensive therapy was strengthened: patients who had previously received monotherapy or free combinations were transferred to double fixed combinations (both drugs acted for 24 hours), and those patients who received double fixed combinations were transferred to triple fixed combinations. Evaluation of therapy after 3 months showed that of 37 patients with initially established MUCH, complete BP control was achieved in 86.5% (in the remaining 13.5%, despite sufficient office BP control, MUCH was maintained according to ABPM data).

Conclusions:
In inadequate control of out-of-office BP, disturbances of the circadian rhythm are more common than with complete BP control. MUCH is associated with such risk factors as elderly age, male gender, smoking, stress, sleep disturbances, DM, obesity, IR, and CKD. Strengthening antihypertensive therapy contributed to the achievement of both office and out-of-office BP in 86.5% of patients with previously established MUCH.
Abstract P134: Selected Social Determinants Of Health And Hypertension For Patients Of An Urban Community Primary Care Clinic
Authors: Echols Melvin R , Pollard-Thomas Paula , Nuss Henry , Egwuogu Heartley , Hobbs Kristen , Hall Laura Lee , Ferdinand Keith
Published: August 2021

Background:
Hypertension (HTN) is the most potent cardiovascular disease worldwide and a major public health concern in the U.S. Although Social Determinants of Health (SDoH) are associated with HTN, it is unclear whether these indicators are routinely captured in the primary care setting. We sought to examine the prevalence of any HTN and its association with captured SDoH for new patients (pts) presenting to an urban community primary care clinic for 2019 and 2020.

Methods and Results:
We identified a cohort-based, cross-sectional sample of 2,577 new pts ≥ 18 years of age in a community clinic in Atlanta, GA, between Jan 2019 and Dec 2020. Electronic health records were reviewed to determine the rate of selected SDoH indicators (financial strain, transportation, medical transportation, and food insecurity) captured at any time and the presenting blood pressure for all new patients. Blood pressure was classified as follows: normal, systolic BP/diastolic BP (SBP/DBP) ≤120/80 mmHg, elevated SBP 120-129mmHg and DBP<80mm, stage 1 SBP 130-139mmHg or DBP 80-90mmHg, and stage 2 SBP ≥ 140mmHg+ or DBP 90mmHg+. Likelihood-ratio Chi-square tests were analyzed to detect an association between SDOH and stages of HTN. Of the 2,577 pts seen, 93% were African American, 72% were female, 59% were single, 77% had BMI ≥ 25, and 85% were insured. Only 41% (n=1062) pts had information of at least one SDoH measure in the entire cohort. Of the SDoH domains evaluated, financial strain and food insecurity were more likely in new pts with stage 1 HTN or higher (χ2= 16.0, df=8, p=0.04; χ2= 27.7, df=12, p=0.006).

Conclusion:
Routine assessments of SDoH for African American pts presenting for new pt visits are suboptimal in the primary care setting. However, financial strain and food insecurity are significantly associated with stage 1 and 2 HTN in this population. Standardization of intake processes is essential to increase the collection of SDoH indicators and may ultimately guide secondary prevention strategies for HTN interventions.
Abstract P135: The Role Of Digital Health In The Management Of Hypertension
Authors: Kesiena Onoriode , Seffah Kofi , Kumar Navin , Hama Eunice
Published: August 2021

Introduction:
Digital health involves the use of technology to delivery health care. It is associated with improved clinical outcomes in various populations. We assessed its role in medication adherence in adults with hypertension.

Methods:
Data from the 2018 National Health Interview Survey data was used. We analyzed 8,224 respondents with hypertension representing about 69 million United States adults. The independent variables were: Use of the internet to (1) to look up health information (2) to fill a prescription and (3) to schedule a medical appointment and use of an email (4) to communicate with a healthcare provider. The dependent variable was anti-hypertensive medication adherence. Chi-square analysis was used to identify group differences and a logistic regression was used to analyze the association between digital health utilization and anti-hypertensive medication adherence.

Results:
Of the study population, 7,387/8,224 (89.8%) of the respondents reported adherence to anti-hypertensive medications. Those who were adherent were predominantly > 65 years of age, 4141/7387 (47.8%) and earned > $75,000/yearly, 580/2581 (25.2%). The use of internet to look up health information as compared to those who do not, was associated with 30% reduced odds of medication adherence [OR 0.71, 95% CI 0.59, 0.86, p=<.001]. However, this was insignificant after adjusting for covariates [AOR 0.92, 95% CI 0.89, 1.22, p=0.551]. Using the internet to fill up prescription as compared to those who do not, was associated with 47% odds of medication adherence [OR 1.47, CI 1.14,1.90, p=0.003]. This odd increased further after adjusting for covariates [AOR 1.95, CI 1.37,2.78, p=<.001]. No significant association was found in the relationship between medication adherence and scheduling a medical appointment with the internet or communicating with a provider via email even after adjusting for covariates.

Conclusion:
Increase adherence to anti-hypertensive medications is associated with online refill of prescriptions. This means that the use of digital health technologies in hypertensive populations can lead to better health outcomes. Future studies should evaluate other aspects of digital health use in hypertensive populations.
Abstract P136: Reference Ranges And Cut-Off Values For Simultaneous Monitoring Of RAS-Blocker Efficacy And Screening For Secondary Hypertension Using RAAS Triple-A Profiling
Authors: Poglitsch Marko , Foco Luisa , Gögele Martin , Pramstaller Peter P , Pattaro Cristian
Published: August 2021

Uncontrolled hypertension is caused by various factors including compliance issues, patient specific drug uptake and elimination profiles or secondary forms of hypertension, resulting in blood pressure control rates of less that 50%. RAAS Triple-A profiling is a high-throughput mass-spectrometry based assay for Angiotensin I (Ang I), Angiotensin II (Ang II) and Aldosterone in serum samples. Hormone levels are used to calculate markers for plasma-renin-activity (PRA-S), plasma angiotensin-converting-enzyme activity (ACE-S) and adrenal aldosterone secretion (AA2-Ratio). The integrated analysis of these molecular markers together with drug prescription information allows to identify the underlying cause of uncontrolled hypertension, including primary aldosteronism and insufficiency in drug adherence or dosing for ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs). 500 participants with prescribed antihypertensive drugs were selected from the “Cooperative Health Research in South Tyrol” (CHRIS) study, a population-based study from an Alpine rural environment. Five age- and sex-matched groups (N=100 each) selected were individuals on single therapy with ARBs, ACEi or beta blockers, and on single pill dual therapy of ACEi or ARBs in combination with diuretics. Three age and sex-matched control groups of 100 participants each were included, being normotensive, hypertensive (treated with non-antihypertensive drugs) and hypertensive participants without any prescribed medication. RAAS Triple-A analysis was performed in all individuals and reference values for Ang I, Ang II, Aldosterone, PRA-S, ACE-S and AA2-Ratio were established in appropriate sub-populations. Drug monitoring by LC-MS/MS based quantification of anti-hypertensive drugs in serum was used as a gold standard to determine cut-off values for compliance with ARB and ACEi therapy and ROC analysis was performed using angiotensin-based biomarkers.
Abstract P138: Long-term Effects Of Severe Caloric Restriction To The Heart Function
Authors: De Souza Aline M , Almeida Jonathas , Shults Nataliia , Ji Hong , Sandberg Kathryn
Published: August 2021

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT)
ad libitum
or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received
ad libitum
chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet (
data not shown
) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.