bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P049: Blood Pressure Polygenic Risk Score Stratifies Individuals With High Risk Of Hypertension In Different Ancestries
Authors: Teixeira Samantha K , Souza Vinicius , Horta Bernardo , Pereira Alexandre , Krieger Jose E
Published: September 2022

The heritability of arterial hypertension ranges from 25 to 68%, but the underlying genetic determinants remain elusive. Thousands of variants with small effects on systolic blood pressure (SBP) from European Ancestry Genome-Wide Association Studies have been used to derive genetic risk scores, whose predictive power in samples from diverse ancestries has yet to be determined. We used the LDPred2 algorithm and 423 thousand genetic variants from UK Biobank that were common to an admixed sample population from Brazil to derive SBP polygenic risk scores (PRS). We selected the best model that displayed a score with hyper-parameters ρ = 0.056, h
2
= 0.0739 and without sparsity, which presented the highest correlation coefficient with observed SBP (0.206) and SBP change per standard deviation increase (4.04mmHg) in a different set of data from the UK Biobank prior to test its predictive power on SBP and hypertension in a third set of the UK Biobank and two admixed Brazilian population samples. All three populations displayed similar normal distribution of PRS, with the UK Biobank PRS distribution slightly shifted to the right, presenting higher PRS average (7.8 vs. 5.6 and 6.4 in Baependi and Pelotas, respectively), but with similar standard deviation (3.3 vs. 3.2 for both Baependi and Pelotas). We used the PRS deciles to stratify the populations and observed a significant difference on SBP average between the top and bottom deciles in all three populations (14.43 mmHg, 9.34 mmHg and 7.51 mmHg for the UK Biobank, Baependi and Pelotas, respectively). We then compared the top 10% PRS versus the remaining 90% of the PRS distribution, and observed that high PRS is associated with 1.8, 2 to 3 and 3 to 4-fold increase in prehypertension, hypertension stage I and hypertension stage II risk, respectively, demonstrating that the increased risk is independently of age and ancestry. Considering the highly admixed nature of the Brazilian population, we provide evidence for the generalization of PRS between populations with different genetic structure.
Abstract P052: Recurrent Major Depressive Disorder And Hypertension - A Nationwide Analysis Of Patient Demographics And In-hospital Outcomes
Authors: Ahmed Ibrahim , Amoateng Richard , Gadani Mrudula
Published: September 2022

Introduction:
Hypertension (HTN) is a condition that contributes significantly cardiovascular disease. Little is known about the effect of recurrent major depressive disorder (rMDD) on HTN.

Methods:
This was a retrospective cohort study using the Nationwide Inpatient Sample database to identify admissions in adults with a diagnosis of HTN and rMDD in 2019. Regression models were adjusted for demographic variables and hospital characteristics. Primary outcome was all-cause mortality, and secondary outcomes were length of stay (LOS) and total charge in USD.

Results:
Out of 9,582,450 admissions with hypertension, 114,480 had rMDD. Compared to Non-rMDD-HTN cohort, rMDD-HTN cohort had more females, younger age, White, Medicaid, private insured, self-pay, median household income, and fewer Black, Hispanic, API , highest household income. rMDD-HTN cohort had more AIDS, alcohol abuse, drug abuse, chronic pulmonary disease, and less arthropathies, dementia, PVD, and diabetes mellitus. rMDD-HTN cohort had lower all-cause mortality rate (0.40% vs 1.70%,p<0.001), all-cause lower mortality OR 0.38 (95%CI 0.30-0.47,p<0.001), longer mean LOS of 1.90 days (95%CI 1.74-2.05,p<0.001) with mean LOS of 6.73 days vs 4.63 days, and total hospitalization charge -$15,428.93 (95%CI -$16,964.47- -$13,893.38,p<0.001).

Conclusion:
In patients admitted with HTN, the presence of rMDD was associated with a lower all-cause mortality rate, lower odds of all-cause mortality, longer LOS, and lower total hospitalization charge. rMDD was associated with more female, younger age, White, Medicaid as well as higher prevalence of AIDS, alcohol abuse, drug abuse and chronic pulmonary disease.
Abstract P054: Loss Of The Smooth-muscle-cell-angiotensin Ii-sensitive Lncrna Leads To Smc Hypertrophic And Hypertensive Remodeling Due To Cell Cycle Dysregulation.
Authors: Espinosa-Diez Cristina , Liu Mingjun , Wei Jianxin , Mahan Sidney , Du Mingyuan , An Wenxi , Hahn Scott , Bruder-Nascimento Thiago , Straub Adam C , Shiva Sruti , Gomez Delphine A
Published: September 2022

Vascular smooth muscle cells (SMC) responses to increased levels of Ang II during hypertensive remodeling included enhanced vasoconstriction and hypertrophy due to the enlargement of the SMC on the vessel wall. Hypertrophic SMC usually present defects in cell division and cell polyploidy. However, the molecular mechanisms controlling SMC hypertrophy and polyploidy vs. hyperplasia are still not fully understood. Long-non-coding-RNAs (LncRNAs) are epigenetic regulators of gene expression influencing biological processes, including cell division fidelity. We discovered a novel lncRNA decreased in dedifferentiated SMC, the SMC-Ang II-Sensitive (SAS) lncRNA, which expression is reduced in response to Ang-II in cultured SMC and the aorta of hypertensive mice, suggesting a role in mediating hypertension-induced SMC hypertrophy. Publicly available transcriptional datasets revealed that SAS is preferentially expressed in SMC-rich tissues, including the aorta and renal artery, in humans and mice. Yet, the functional relevance of SAS in SMC has never been investigated. Knockdown of SAS reduces proliferation and migration in SMC treated with Platelet-Derived Growth Factor (PDGF-BB). SAS knockdown was also associated with distinct SMC hypertrophic morphological changes, including enlargement in cell size and polynucleation in vitro. We have generated a SAS KO mouse, and aortas from these mice present a higher number of polynucleated medial SMC than their WT littermates. These data correlate with a cell cycle arrest in G1 and senescence phenotype that SAS deficient SMC present due to dysregulation in cyclins expression. Furthermore, SAS defective cells show mitochondria hyperfusion and increased oxygen consumption that correlates with the observed senescence and arrest on the G1/S checkpoint, and it is exacerbated by treatment with Ang-II. Interestingly, treatment with Losartan, an Ang-II receptor inhibitor, rescues SAS expression on Ang-II treated SMC and diminishes SMC hypertrophy. Together, these observations suggest that a decrease in SAS causes SMC hypertrophy due to defects in cell cycle completion. SAS is a potent regulator of SMC morphology and is required for proper cell division and mitochondria organization.
Abstract P055: Standing Blood Pressure And Risk Of Falls, Syncope, Cardiovascular Disease, And Mortality
Authors: Kondo Jordan , Wood Julia , Kendrick Karla , Turkson-Ocran Ruth-Alma , Ngo Long , Cluett Jennifer , Lipsitz Lewis , Mukamal Ken , Selvin Elizabeth , Lutsey Pamela , Coresh Josef , Windham B. Gwen , Malek Natalie , Juraschek Stephen
Published: September 2022

Background:
ACC/AHA guidelines recommend screening for low standing BP prior to initiating antihypertensive medications based on the exclusion of adults with a standing SBP <110 mm Hg in SPRINT. However, the prevalence and implications of low standing SBP on adverse events are unknown.

Objectives:
To determine the prevalence of low standing SBP and its relation to adverse events among middle-aged adults.

Methods:
We examined the association between lower standing SBP (<110 mmHg) and falls, syncope, CVD, and mortality in the Atherosclerosis Risk in Communities Study, a prospective cohort study of community-dwelling, middle-aged, Black and White adults. Supine and standing SBP were measured at visit 1 (1987-1989). Adverse events were ascertained by hospital claims for falls and syncope and adjudicated outcomes for CVD and mortality. We used Cox models adjusted for risk factors of falls, syncope, and CVD events.

Results:
Among 12,558 adults followed >20 years (mean age 54.1±5.8 yrs, 55% women, 26% Black), 3018 (24%) had a standing SBP <110 mm Hg, and 544 (4%) had orthostatic hypotension. Higher standing SBP was associated with higher risks of CVD and mortality, but not other outcomes (
Figure
). In contrast, a standing SBP <110 mm Hg was not associated with falls, syncope, CVD, or mortality (HR 1.06 [95% CI 0.96, 1.18], 1.09 [0.99, 1.21], 0.92 [0.83, 1.01], 0.94 [0.87, 1.01], respectively).

Conclusions:
In this population, lower standing SBP was common and not associated with falls or syncope, whereas higher standing SBP was associated with higher risk of CVD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events.
Abstract P068: Dietary Sodium Restriction Prevents Vascular Endothelial Growth Factor Inhibitor-Induced Hypertension
Authors: van Doorn Leni , Visser Wesley J , Van Dorst Daan C , Mirabito Colafella Katrina M , Koolen Stijn L , van Emond-de Mik Anneke , Garrelds Ingrid , Bovee Dominique , Oomen-de Hoop Esther , Bins Sander , Eskens Ferry A , Hoorn Ewout , Danser Jan H , Mathijssen Ron , Versmissen Jorie
Published: September 2022

Vascular endothelial growth factor tyrosine kinase inhibitors (VEGFIs) are effective anti-cancer agents which often induce hypertension. VEGFI-induced hypertension was demonstrated to be sodium-sensitive in preclinical studies, but the sodium sensitivity in humans and its potential as a preventive antihypertensive strategy in the clinical situation remains unknown. Therefore, the efficacy of dietary sodium restriction (DSR) to prevent VEGFI-induced hypertension was studied in patients with cancer.

To this end, patients with cancer who developed VEGFI-induced hypertension (defined as daytime systolic blood pressure (SBP) > 135 mmHg and/or diastolic blood pressure (DBP) > 85 mmHg or a rise in SBP/DBP of ≥ 20 mmHg) were treated with DSR under supervision of a specialized dietician (aiming at < 4 g salt/day). The primary endpoint was the difference in daytime mean arterial blood pressure (MAP) increase between the VEGFI treatment cycle with and without concomitant DSR.

Of the forty-nine screened patients, twenty (41%) patients were eligible for the DSR intervention based on their VEGFI-induced blood pressure rise, of whom sixteen successfully completed the intervention. During the first VEGFI treatment cycle without DSR, mean daytime MAP increased from 95 mmHg to 110 mmHg. During the subsequent treatment cycle with concomitant DSR, mean daytime MAP increased from 94 mmHg to 102 mmHg. Therefore, DSR attenuated the increase in mean daytime MAP by 7 mmHg (95% CI 1.3 to 12.0,
P
= 0.009). DSR prevented the rise in the endothelin-1/renin ratio that normally accompanies VEGFI-induced hypertension (
P
= 0.020) and slightly prevented the onset of proteinuria: 0.15 (0.10-0.25) g/24h with DSR versus 0.19 (0.11-0.32) g/24h without DSR;
P
= 0.005. For two patients, proteinuria decreased from common terminology criteria of adverse events (CTCAE) grade and 3 during the treatment cycle without DSR to grade 1 and grade 2 during DSR, respectively.

In conclusion, DSR significantly attenuated the VEGFI-induced BP rise, the increase in the endothelin-1/renin ratio and the onset of proteinuria. Therefore, DSR is an effective and attractive non-pharmacological intervention for patients with VEGFI-induced hypertension and its sequelae.
Abstract P079: Leptin And Risk Of Incident Hypertension In The Reasons For Geographic And Racial Differences In Stroke (REGARDS) Cohort Study
Authors: Sherman Sarah E , Stoutenburg Eric , Long Leann , Juraschek Stephen P , Cushman Mary , Howard Virginia J , Tracy Russell P , Judd Suzanne E , Kamin Mukaz Debora , Zakai Neil A , Plante Tim B
Published: September 2022

Background:
Leptin is an anorexigenic and sympathoexcitatory adipokine strongly associated with obesity and associated with hypertension in animal models. Whether leptin is associated with hypertension incidence independent of obesity is unclear.

Methods:
REGARDS recruited 30,239 Black or White adults aged ≥45 years recruited from 48 US contiguous states in 2003-07 with a second visit in 2013-16. Baseline serum leptin was measured by ELISA in a sex- and race-stratified sample of 4,400 REGARDS participants. Modified Poisson regression estimated relative risk (RR) of incident hypertension (140/90 mm Hg threshold or use of antihypertensives) per higher leptin tertile, stratified by a BMI of 30 kg/m
2
, adjusting for known confounders.

Results:
Among the 1,834 participants without prevalent hypertension (mean [SD] age 62, 56% women, 25% Black adults), median follow-up was 9 years. Incident hypertension developed in 35%. BMI significantly modified the relationship between leptin and incident hypertension (P-interaction <0.001) such that higher leptin was associated with greater hypertension risk in the crude model among those with BMI <30, but not ≥30, kg/m
2
(
Figure
). This association was fully attenuated when adjusting for waist circumference and BMI.

Conclusions:
Leptin is associated with hypertension among normal weight but not obese adults in REGARDS. Adiposity may be on the causal pathway between leptin levels and obesity.
Abstract P082: Exposure To Excess Albumin Causes Inflammatory Activation Of The Proximal Tubule.
Authors: Almutlaq Rawan , Dayton Alex , Ross Jaryd , Srisomboon Yotesawee , O'Grady Scott , Evans Louise C
Published: September 2022

In previous studies, we used chronic servo control experiments to show that renal inflammation is a secondary event in salt-sensitive hypertension, with pressure amplifying renal immune cell infiltration in Dahl salt-sensitive (SS) rats. In contrast, albuminuria occurs early in the development of hypertension and facilitates its progression. In this study, we tested the hypothesis that albuminuria causes release of pro-inflammatory cytokines in the proximal tubule, which in turn may initiate renal inflammation.We exposed the apical membrane of human proximal tubule cell monolayers (RPTEC-TERT1) to human serum albumin (HSA, 10 mg/ml, n=8) for 24 and 48hrs. Control cells were kept in standard media without HSA (n=8). The concentrations of 47 cytokines were measured in the basolateral (BM) and apical (AM) media using Luminex assays. After 24hrs we found that 18 cytokines were significantly higher in the BM and 14 in the AM relative to controls. At 48hrs, 17 cytokines were significantly higher in the BM and 15 in the AM. Notably, we found significant increases in basolateral release of several chemokines, including CCL2 (24hrs: 6.1±0.9 vs. 40.6±8.9, 48hrs: 20.1±4.5 vs. 85.8±15.6 pg/mg), CXCL1 (24hrs: 1.3±0.3 vs. 39.5±12.2, 48hrs: 3.4±1.1 vs. 94.2±41.4 pg/mg), and IL-8 (24hrs: 1.3±0.4 vs. 11.6±3.7, 48hrs: 2.1±0.5 vs. 10.1±3 pg/mg). We propose that HSA-induced chemokine secretion facilitates immune cell recruitment and the initiation of renal inflammation. To track the progression of albuminuria and proximal tubule injury in SS rats we performed daily urine collections in rats fed either a high-salt (HS, 4.0% NaCl, n=6) or a control-salt (CS, 0.4% NaCl, n=5) diet for 7-days. In SS rats fed HS, albuminuria preceded proximal tubule injury. Urinary albumin was elevated after 2-days of HS (22.6±6.5 vs. 61.1±18.7 mg/day) whereas Kidney Injury Molecule-1 (KIM-1) was increased after 5-days of HS (15.5±1.5 vs. 31.3±5.6 ng/day).To conclude,
in vitro
exposure to excess albumin causes significant increases in the levels of multiple cytokines involved in the initiation of inflammation. In SS rats fed HS, albuminuria precedes proximal tubule injury. Together these data suggest that albuminuria may facilitate hypertension through the initiation of renal inflammation.
Abstract P086: Blood Pressure And Salt Differentially Regulate Testicular Immune Cell Populations In Hypertensive Mice
Authors: Navaneethabalakrishnan Shobana , Goodlett Bethany , Smith Hannah , Mitchell Brett M
Published: September 2022

We recently reported that increased proinflammatory (M1) macrophages, inflammation, and inflammation-associated lymphangiogenesis is associated with reproductive dysfunction in mice with salt-sensitive HTN (SSHTN). However, it is unknown whether these effects are primarily due to increased systemic pressure and/or salt. We hypothesized that artificial lowering of blood pressure may not reverse the inflammatory environment within the testes, that is associated with SSHTN. Male C57BL6/J mice were made hypertensive by providing L-NAME (0.5 mg/mL) in the drinking water for 2 weeks, followed by a 2-week washout period, and a subsequent 3-week 4% high salt diet (SSHTN). In another group, mice received L-NAME 2 weeks, followed by a 2-week washout period and a subsequent 3-week 4% high salt diet along with hydralazine (250mg/L) in their drinking water (SSHTN+HDZ). Control (C) mice received L-NAME for 2 weeks and then tap water and normal diet. Systolic blood pressure in SSHTN mice (141±1 mm Hg) was significantly increased when compared to C mice (102±3 mm Hg), but the pressure decreased to 119±1 mm Hg (p<0.05) in SSHTN+HDZ mice. Flow cytometry analysis revealed a significant decrease in M2 macrophages in the testes of SSHTN and SSHTN+HDZ mice when compared to control mice (C: 15.8%±1, SSHTN: 9.8%±2, SSHTN+HDZ: 8.4%±2; p<0.05). There was an increase in Th1 T cells in the testes of SSHTN and SSHTN+HDZ mice when compared to control mice (C:4.8%±1, SSHTN:11.4%±1, SSHTN+HDZ: 10.1%±1; p<0.05), whereas Th17 T cells (C:13.6%±2, SSHTN:19.5%±1, SSHTN+HDZ: 14.8%±1; p<0.05), CD4+TNFa+ (C:8.2%±2, SSHTN:12.5%±1, SSHTN+HDZ: 9%±2; p<0.05) and gamma-delta T cells (C:73%±4, SSHTN:83.5%±1, SSHTN+HDZ: 80%±2; p<0.05) were significantly increased in SSHTN mice but were decreased significantly in SSHTN+HDZ mice. These data demonstrate that high systemic pressure and salt together act on some immune cell populations while others are only altered by salt. Further investigations on the effect of lowering blood pressure on inflammatory markers, lymphatics, and testicular function might help in better understanding the mechanisms behind the differential regulation of immune cells.
Abstract P090: Prevalence And Risk Factors Of Disordered Eating Behavior In Youth With Hypertension
Authors: Perrin Ella C , Ravi Hanna , South Andrew M
Published: September 2022

Background:
Eating disorders in adolescents are increasing in prevalence and have adverse health consequences, but remain underdiagnosed. Patients with medical conditions that require lifestyle management, such as obesity and diabetes mellitus, have higher disordered eating behavior (DEB) risk (20–39%) than the general adolescent population (10%). Patients with CKD might also be at increased DEB risk. In youth with other conditions requiring lifestyle counseling—such as HTN—DEB prevalence and associated risk factors are unknown.

Objective:
Estimate DEB prevalence in youth with HTN compared to the general adolescent population and investigate whether obesity, CKD, or less specialized lifestyle counseling source are associated with higher DEB risk.

Design/Methods:
Prospective cross-sectional study of youth aged 11–18 years with HTN. We excluded patients with diabetes mellitus, kidney failure or transplantation, or gastrostomy tube dependence. We collected data via surveys and electronic health record abstraction. We administered the validated SCOFF DEB screening questionnaire wherein a score ≥2/5 is positive. We compared DEB prevalence using a one-sample z-test of proportions (p
0
=0.1) and estimated DEB risk by obesity, CKD, or lifestyle counseling using multivariable generalized linear models.

Results:
Of 74 participants, 59% (44/74) identified as male gender, 22% (16/74) as Black or African American, and 36% (27/74) as Hispanic; 58% (43/74) had obesity and 26% (19/74) had CKD. DEB prevalence was 28% (95% CI 18–39%,
p
<0.001). CKD was associated with higher DEB prevalence (adjusted RR 2.17, 95% CL 1.09 to 4.32), but obesity and lifestyle counseling source were not.

Conclusions:
DEB prevalence is higher in youth with HTN and comparable to that reported in other conditions requiring lifestyle counseling. Concurrent CKD is associated with more than double the risk of DEB in this population. Youth with HTN may benefit from routine DEB screening.
Abstract P107: Adam 10 & 17 Double-knockout Impairs Renal And Vascular Functions And Induces Hypertension By Altering The Renal Proteomic Profiles
Authors: Aung Lynn-Htet-Htet , Sun Zhongjie
Published: September 2022

Background:
ADAM 10 & 17, the two most well-known members of disintegrin and metalloproteinases (ADAMs), are responsible for the cleavage of diverse transmembrane proteins into bioactive molecules in the renal tubular cells.

Objective:
The purpose of this study is to understand the effects of ADAM 10 & 17 double-knockout (DKO) on renal and vascular functions using the renal tubular cell-specific ADAM 10 & 17 DKO mice.

Results:
We tested the renal and vascular functions in three groups (n=10-15 per group) of male and female wild-type (WT), vehicle, and DKO mice. The urine output (
P
< 0.05) and glomerular filtration rate (
P
< 0.01) of DKO mice were significantly lower than those of WT and vehicle control groups. The urinary sodium (
P
< 0.0001) and potassium (
P
< 0.01) excretion in DKO mice were also significantly reduced. Consistently, we found a significant decrease in urea (
P
< 0.0001) and creatinine (
P
< 0.0001) clearance in DKO mice, suggesting that the renal function is impaired when both ADAM 10 & 17 are depleted. In addition, the pulse wave velocity (
P
< 0.0001), and blood pressure including systolic blood pressure (
P
-value < 0.0001), diastolic blood pressure (
P
< 0.0001), and mean blood pressure (
P
< 0.0001) levels of DKO mice were significantly higher than those of WT and vehicle controls, indicating that ADAM 10 & 17 depletion impairs renal and vascular functions and causes hypertension. This phenomenon is further supported by the evidence that DKO mice showed a slower relaxation response to acetylcholine, compared to WTs. Next, to understand the changes in proteomic profiles in DKO kidneys, we performed proteomic analysis of WT and DKO kidney tissues and identified ~100 differentially expressed proteins (DEPs). These DEPs are highly enriched in drug metabolism, metabolic pathways, and TGF-beta signaling, PPAR-signaling and AGE-RAGE signaling pathways, suggesting that ADAM 10 & 17 may play a role in renal cellular metabolism, cell growth, differentiation, and apoptosis.

Conclusions:
The depletion of ADAM 10 & 17 impairs the renal and vascular functions likely
via
disrupting the cellular metabolism and homeostasis.
Abstract P109: A Novel Murine Model Of Diet-induced Cholemia For Studies On The Gut-liver-kidney Axis In Blood Pressure Regulation
Authors: Yeoh Beng San , Saha Piu , Golonka Rachel M , Abokor Ahmed A , Joe Bina , Vijay-Kumar Matam
Published: September 2022

Bile acids (BA) are classically viewed as emulsifiers produced by the liver for aiding the absorption of fats in the gut. Accumulating evidence now recognizes BA as vasoactive agents capable of lowering blood pressure (BP). However, it remains unclear whether the ensuing hypotension can be associated with end-organ damage. To delineate the pathogenic role of BA in the gut-liver-kidney axis, we leveraged our prior finding that a subset of C57BL/6 mice developed cholemia (
i.e.
, high circulating BA) when fed a diet supplemented with 7.5% inulin. Briefly, we challenged 4-week-old male mice (n=50) with the inulin diet for one week and identified the subset that developed cholemia (B6
BA
; n=6). Non-cholemic mice (B6; n=6) were maintained as control. Assessment on BP at 6 months of inulin feeding indicated that B6
BA
mice (systolic BP: 107.6 ± 2.2 mmHg; diastolic BP: 78.6 ± 3.1 mmHg) are hypotensive relative to non-cholemic B6 mice (systolic BP: 139.8 ± 5.6 mmHg; diastolic BP: 109.0 ± 3.8 mmHg), which was accompanied by polydipsia (7.0 ± 0.4 ml/day in B6
BA
vs 4.3 ± 0.2 ml/day water intake in B6), polyuria (2.5 ± 0.1 ml/day in B6
BA
vs 1.2 ± 0.1 ml/day urine output in B6), and elevated urinary BA (28.5 ± 1.7 μM in B6
BA
vs 3.3 ± 0.6 μM in B6) in B6
BA
mice. B6
BA
mice also excreted more urinary creatinine (50.4 ± 3.4 mg/dl in B6
BA
vs 25.6 ± 1.3 mg/dl in B6), sodium (271.8 ± 20.1 μmol/day in B6
BA
vs 103.0 ± 11.0 μmol/day in B6) and potassium (349.2 ± 16.7 μmol/day in B6
BA
vs 128.7 ± 7.7 μmol/day in B6), which could be, in part, explained by their higher glomerular filtration rate (1209.0 ± 121.0 in B6
BA
vs 681.2 ± 148.7 μl/min/100 g body weight in B6). Of note, B6
BA
mice displayed renomegaly, interstitial nephritis, and bile casts in urine, as well as elevated renal transcripts (>2-fold increase relative to B6) for lipocalin 2, kidney injury molecule-1, tumor necrosis factor alpha, collagen type I α1 and endothelin-1. Taken together, these findings demonstrate that our mouse model of diet-induced cholemia presents with low BP and renal pathology. We envision that this model has notable advantages (
e.g.
, ease in inducing cholemia, no early morbidity and tractable for long-term study),
in lieu
of the conventional bile duct ligation approach, for studying how BA regulate BP.
Abstract P112: Evidence Of Renin Expression And Function In The Brainstem
Authors: Nakagawa Pablo , Gomez Javier , Fekete Eva M , Brozoski Daniel , Grobe Justin L , Sigmund Curt D
Published: September 2022

The role of the brain renin-angiotensin system (RAS) in blood pressure (BP) and autonomic control isrecognized. However, the lack of the precise source of renin in the brain is one of the main barrierstowards a complete understanding of how the brain RAS operates. Here, we hypothesized that renin isexpressed in brain regions involved in sympathetic control such as the rostroventral lateral medulla(RVLM). We employed RNAscope, a highly sensitive and specific
in
situ
hybridization technology.Surprisingly, the renin positive signals were absent in the RVLM, but we identified renin transcripts inthe nucleus ambiguus (NA), a site in the vicinity of the RVLM that contains cardiac vagal motoneurons.There was no signal in this region with the negative control scrambled probe. The signal strength wasgreater than that observed in other regions of the brain classically associated with the brain RAS. Wealso observed that the NA contains other necessary RAS components to produce angiotensin.Interestingly, renin was colocalized with cells expressing choline acetyltransferase (ChAT), suggesting itspossible role in cholinergic neurotransmission. Therefore, we generated mice lacking renin specifically incholinergic neurons (Ren-a
ChAT-null
). Because we previously identified an alternative brain-specific reninisoform (ren-b) that elicits cardioprotective roles, we also generated mice lacking ren-b in cholinergicneurons (Ren-b
ChAT-null
). At baseline, Ren-a
ChAT-null
exhibited a trend towards decreased BP, while Ren-b
ChAT-null
exhibited higher BP, although these differences were not statistically significant. Importantly,Ren-a
ChAT-null
exhibited an attenuated tachycardiac and pressor responses to atropine (p<0.005 andp<0.05, respectively; n=4-7), indicating a lower parasympathetic tone in these mice. Conversely, Ren-b
ChAT-null
exhibited an augmented pressor response to atropine (p<0.005; n=7) suggesting an elevatedparasympathetic tone. These data suggest that the activation of the brain RAS in the NA might play arole in cholinergic neurotransmission, and it defines the NA as a potential source of endogenous renin inthe brainstem. Studies to understand the differential contribution of Ren-a and Ren-b in the NA to BPare in progress.
Abstract P134: Tnfα Impairs Endothelial Calcium Signaling And Elevates Blood Pressure In Obesity.
Authors: Kuppusamy Maniselvan , Ottolini Matteo , Daneva Zdravka , Chen Yen-Lin , Sonkusare Swapnil K
Published: September 2022

Endothelial dysfunction in small arteries is a hallmark of obesity-induced hypertension. Recent studies show that endothelial upregulation of inducible nitric oxide synthase (iNOS) and NADPH oxidase 1 (NOX1) plays a critical role in obesity-induced endothelial dysfunction. Endothelial upregulation of iNOS and NOX1 results in excessive formation of peroxynitrite, a reactive nitrogen species, which impairs endothelium-dependent vasodilation. It is well-known that inflammatory mediators elevate cellular iNOS, NOX1, and peroxynitrite levels. In this regard, tumor necrosis factor-alpha (TNFα) signaling has been proposed as a critical contributor to endothelial dysfunction in obesity. Notably, vascular SMCs TNFα levels were increased in heart failure and diabetes. Therefore, we hypothesized that vascular wall-derived TNFα acts locally to impair endothelial function in obesity. Flow cytometry studies showed an increase in TNFα levels in freshly isolated SMCs from small mesenteric arteries (MAs) of high-fat diet-fed obese mice compared to normal chow-fed control mice. However, TNFα levels in ECs from obese mice were not different from those in ECs from control mice. The pro-inflammatory effects of TNFα are mediated mainly through TNFα receptor I activation. Treating the obese mice with a selective inhibitor of TNFα receptor I signaling reduced the blood pressure to normal levels in obese mice but did not affect blood pressure in control mice. Treatment with R7050 also abolished the obesity-induced increase in iNOS and NOX1 expression in endothelial cells. Further, R7050 administration restored acetylcholine-induced, endothelium-dependent vasodilation of MAs in pressure myography experiments. Previous studies showed a decrease in Ca
2+
influx through endothelial TRPV4 channels contributes to blood pressure elevation in obese mice. Notably, R7050 administration restored the Ca
2+
influx signals through endothelial TRPV4 channels in MAs, as studied using high-speed confocal Ca
2+
imaging. Our findings collectively indicate that TNFα signaling contributes to the impairment of endothelial calcium signaling and blood pressure elevation in obesity and highlights the role of SMCs as a source of TNFα in obesity
Abstract P207: The Feasibility Of A 6-week, Pharmacist-Led, Self-Monitored Blood Pressure Treatment Program
Authors: Ishak Anthony M , Cluett Jennifer , Wood Julia , Vyavahare Medha , Mukamal Ken J , Juraschek Stephen P
Published: September 2022

Background:
Guidelines recommend concomitant out-of-office blood pressure (BP) measurements with telehealth counseling for titration. While high quality home BP measurement coupled with pharmacist care reduces the time needed to achieve BP goal, it remains unclear how rapidly BP titrations can be applied in clinical practice.

Objective:
To examine the impact of home BP monitoring coupled with a rapid, biweekly, pharmacist-led BP medication titration program on BP control and patient safety.

Methods:
Forty patients were referred if BP ≥140/90, using ≤2 anti-hypertensive medications, and failed a trial of lifestyle modification. The initial visit with the pharmacist included validation of home BP monitor compared with an Omron HEM-907XL. Patients monitored BP twice daily in the morning and evening for a week then had their medication regimen adjusted every 2 weeks until reaching their goal or completing a 6-week follow-up period.

Results:
Of the 29 patients completing the program, mean enrollment SBP/DBP was 155.2 (SD, 15.8)/89.7 (SD, 11.5) mm Hg. The completion SBP/DBP was 132.1 (SD, 10.9)/ 77.6 (SD, 10). The number of HTN medications prescribed increased by an average of 0.3 (from 1.3 to 1.6) over the follow-up period. There were no incidences of falls or hypotension. One patient had a clinically significant electrolyte change requiring medication adjustment. Two patients had a clinically significant change in serum creatinine, but both stabilized after altering their hypertension medication regimen.

Conclusion:
A 6-week, pharmacist-led, home BP monitoring program with rapid titration had high retention and increased the percentage of patients achieving BP goals without safety concerns.
Abstract P208: Utility Of Standing Office Blood Pressure In Assessing Blood Pressure Control In Patients With Autonomic Failure
Authors: Khan Ghazi , Giacona John , Pittman Danielle , Wang Jijia , Vongpatanasin Wanpen
Published: September 2022

Current guidelines recommend blood pressure (BP) target based on office BP taken in a seated position for hypertensive patients. However, the accuracy of standing BP measurements for determining blood pressure control in patients with autonomic (ATF) is unknown.We measured BP in seated and standing positions in 47 hypertensive and normotensive adults with ATF. Office BP was measured in the seated position 3 times and after standing for 3 minutes. Adequate BP control was defined by 24-hour ambulatory SBP/DBP of < 125/75 mmHg. Area under receiver operator characteristic curve (AUROC) was calculated to determine accuracy of seated and standing BP in assessing BP control. Bayes factor (BF) was used to assess the significance of the difference between AUROC of seated and standing BP. Sensitivity and specificity of standing BP in determining blood pressure control was derived using cut-off points derived from Youden’s Index.Prevalence of HTN was 72% (34/47) and the mean age was 71 ± 11 years. Sensitivity and specificity of seated SBP was 65% and 73%, respectively. Optimal cutoffs selected by Youden’s index for standing SBP/DBP was 104/83 mmHg. Sensitivity and specificity of standing SBP was 96% and 64%, respectively. The AUROC of standing SBP was significantly higher when compared to seated SBP alone, when controlled SBP was defined as 24-Hr SBP < 125 mmHg (BF > 3). Similarly, when controlled SBP was defined as daytime SBP < 130 mmHg, the AUROC of 3
rd
standing was significantly higher when compared to seated SBP alone or in combination (BF > 3).In conclusion, standing SBP is more useful than seated SBP in assessing BP control in patients with ATF.
Abstract P215: Evidence Of Terminal Digit Preference In Veterans Affairs Midwest Region Primary Care Clinics
Authors: O'Halloran Meghan , Kramer Holly , Hughes Ashley , Weaver Frances , Kale Ibuola , Huo Zhiping , Stroupe Kevin , Tarlov Elizabeth
Published: September 2022

Objective:
This study examined terminal digit preference (TDP) and its association with BP control in Veterans Affairs Midwest region clinics.

Methods:
TDP was examined in 517,668 BP values from 202,781 Veterans age 18 to 85 years during primary care visits from January 1, 2019 to March 1, 2020 across eight Midwest region sites. Presence of TDP was examined using a goodness of fit test with 10 bins. BP control (<140/90 mmHg or <130/80 mmHg) was assessed in 98,433 Veterans with diagnosed hypertension based on last clinic visit vital signs. Spearman correlation coefficients examined the association of TDP with BP control.

Results:
Mean age was 65.9 (standard deviation [SD]15.7) years, 93.9% (188, 586/202,781) were male; race was White in 78.1% (153,372/202,781), Black or African American in 16.3% (33, 053/202,781), and Asian in 0.5% (1,014/202, 781). For SBP measurements, significant TDP (P<0.001) for digit 8 was noted in all 8 sites ranging from 12.6% (6,839/54,279) to 21.2% (18,124/85,493). For DBP measurements, significant TDP was noted (P<0.001) for digit 0 ranging from 13.5% (7,327/54,276) to 32.7% (27,956/85,493). Among the 8 sites, BP control rates (<140/90 mmHg) ranged from 72.2% (5,947/8,237) to 81.0% (15,405/19,019) while BP < 130/80 mmHg among Veterans with high CVD risk (n=179, 074) ranged from 33.6% (4,960/14,762) to 45.5% (8,204/18,233). Both SBP TDP for digit 8 (r=0.80; P<0.05) and DBP TDP for digit 0 (r=0.73; p < 0.05) were significantly and positively correlated with BP control.

Conclusion:
Our data show presence of BP TDP in the Midwest region VA sites. The correlation of TDP with BP control rates raises concerns about ability to accurately assess BP control in these sites.
Abstract P222: Effectiveness Of A Multicomponent Implementation Strategy On Increasing Uptake Of USPSTF Hypertension Screening Recommendations In A Primary Care Network: The Embrace Cluster Randomized Trial
Authors: Kronish Ian M , Phillips Erica , Carter Eileen , Alcantara Carmela , Schwartz Joseph E , Razon Dominic T , Serafini Maria A , Flatow James , Sanchez Jose , Shimbo Daichi , Moise Nathalie
Published: September 2022

Background:
In 2015, the US Preventive Services Task Force (USPSTF) updated its primary care screening guidelines to recommend out-of-office BP testing with ABPM or HBPM for confirming the diagnosis of hypertension (HTN) in adult patients with high office BP.

Methods:
We applied the Behavior Change Wheel framework to develop a theory-informed strategy for increasing the uptake of the USPSTF HTN screening guideline. We then conducted a 2-arm cluster randomized trial in which 8 primary care practices (154 clinicians) in an ambulatory care network serving vulnerable communities in New York City were randomized to receive the implementation strategy (4 practices) or a wait-list control (4 practices). The strategy was implemented from October 2017 to March 2018, and consisted of: 1) clinician education about HTN screening recommendations; 2) clinician information on how to order ABPM and HPBM; 3) patient information on ABPM and HBPM; 4) nurse training on how to teach patients to conduct HBPM; 5) access to an ABPM testing service; 6) clinician feedback on out-of-office BP test ordering; and 7) embedded tools in the EHR to facilitate ABPM and HBPM ordering. The primary outcome was change in the proportion of patients completing ABPM or HBPM in the year before versus year after implementation.

Results:
There were 1069 eligible patients (mean age 53±16 years, 67% women) with high office BP but no diagnosis or treatment for HTN. In implementation practices, the proportion of patients with out-of-office BP test ordering increased from 0.5% in the year before implementation to 4.0% in the year after implementation (p<.001) whereas test ordering did not change in control practices (3.1% to 2.8%, p=0.66); p<.001 for interaction. Similarly, out-of-office BP test completion increased from 0.5% to 3.0% (p<.001) in implementation practices whereas test completion did not change in control practices (2.2% to 2.0%, p=0.76); p<.001 for interaction.

Conclusions:
A theory-informed implementation strategy increased out-of-office BP testing in adult primary care patients being screened for HTN. Yet, out-of-office BP testing in the context of HTN screening remained low in both implementation and control practices, suggesting a need for more potent implementation strategies.
Abstract P231: Prevalence Of Comorbid Hypertension Among Hospitalized Patients With Cancer: Results From U.s. Population-based Inpatient Database
Authors: Park Chanhyun , Han Sola , Litten Kathryn , Ng Boon
Published: September 2022

Background:
Hypertension (HTN) is the most common comorbidity in patients with cancer. Age and race/ethnicity affect the morbidity and mortality of HTN and cancer. We investigated the status of comorbid HTN stratified by age and race/ethnicity among hospitalized patients with cancer in the U.S.

Methods:
Using 2016-2018 National Inpatient Sample data, we included hospitalized adults with a primary diagnosis of cancer and classified them by diagnosis of HTN. Patients were further grouped by age (18-54, 55-64, 65-74, 75+ years), race/ethnicity (white, black, Hispanic, Asian, and others). The top 12 most common cancers were selected, including kidney cancer. Multivariate logistic regression was used to obtain the odds ratios (ORs) and the predicted percentages of HTN by cancer type, age, and race/ethnicity.

Results:
Among 956,601 hospitalized cancer patients, 56.4% (n=539,978) had HTN. The mean age was 64.5 (SE=0.068) years, and 70.4% (n=673,640) was white patients. The predicted percentages of having HTN were higher in black (67.5%, OR=2.02, p<0.001), Hispanic (56.0%, OR=1.08, p<0.001), and Asian (57.0%, OR=1.14, p<0.001) patients than white patients (54.5%). Compared to patients aged 18-54 years (41.4%), the percentages of having HTN were higher in those aged 55-64 (55.1%, OR=1.98, p<0.001), those aged 65-74 (60.4%, OR=2.57, p<0.001) and those aged 75+ (67.6%, OR=3.73, p<0.001). The percentages of HTN were the highest in kidney cancer patients across all age and race/ethnicity groups (Table).

Conclusions:
HTN is highly prevalent among hospitalized cancer patients, especially kidney cancer. This study provides evidence for improving care in patients with cancer and HTN.
Abstract P240: Nearly Half Of Participants In A Rural, Worksite-based Health Assessments Have Undiagnosed Or Uncontrolled Hypertension
Authors: Bolin Linda P , Burch Ashley , Shackelford Paul , Lee Elisabeth , Bolin Paul
Published: September 2022

Introduction:
Untreated hypertension can result in stroke, heart failure, and kidney damage. Recent reports suggest the prevalence of hypertension is 10% higher in rural areas compared to urban centers.Identifying rural residents with uncontrolled hypertension is the first step to initiating treatment and preventing end organ damage. The objective of this study is to determine the prevalence of elevated blood pressure readings or uncontrolled hypertension in participants living in a rural area through worksite-based assessments.

Hypothesis
We assessed the hypothesis that there are elevated rates of hypertension among those living in rural areas with limited access to health care providers or systems.

Methods:
Rural worksites were identified for free screenings that include a series of questionnaires and bio-metrics. Screenings conclude with a one-on-one provider meeting to discuss results and referrals as needed.

Results/Conclusions:
A total of 654 individuals (46.3% Black) (57.2% male) participated in our screening clinics. When asked about health insurance coverage, 526 (88.7%) reported having insurance. Nearly seventy percent (66.9%) of participants had seen a healthcare professional within the previous year. Undiagnosed hypertension (SBP ≥140) was found in 169 (26.1%) participants and 114 (17.6%)participants had diagnosed but uncontrolled hypertension. In conclusion, nearly half of participants had uncontrolled/undiagnosed hypertension. Our worksite-based health screening clinics provided a convenient, walk-in service, immediate results, and provider consultation as a bridge to accessing ongoing care.
Abstract P242: Psychological Distress Related To Hypertension Diagnostic Testing And Diagnosis
Authors: Green Beverly B , Anderson Melissa L , Margolis Karen L , McClure Jennifer B
Published: September 2022

Background:
Little information is available as to whether undergoing hypertension diagnostic testing or receiving a new diagnosis of hypertension leads to psychological distress.

Design, Setting, and Participants:
BP CHECK was a randomized diagnostic study of 510 adults aged 18-85. Participants had elevated BP in clinic at baseline but no previously diagnosed hypertension. The trial was conducted from 2017 to 2019 in primary care centers of an integrated healthcare system. Participants were randomized to one of three diagnostic regimens: (1) Clinic BP, (2) Home BP, or (3) Kiosk BP. All participants completed 24-hour ambulatory blood pressure monitoring (ABPM) at 3 weeks. ABPM results were sent to participants and their primary care providers and uploaded into the electronic health record. This analysis includes a subset of participants (n=255) who completed psychological distress questionnaires at baseline, and at least one follow-up (after completing their diagnostic regimen and 6 months after randomization)

Main Outcomes and Measures:
The primary outcomes were within-person change in psychological distress (impact of events and state anxiety scales, BP worry Likert 5-point scale) comparing baseline to 3 weeks and 6 months post-enrollment.

Results:
Participants were half female (127/255), mostly
>
age 50 (78%), and White race (83%). Baseline mean BP was 150 mmHg systolic and 80 mmHg diastolic; 63.9% had hypertension on ABPM (daytime average
>
135/85 mmHg). There was no significant change in impact of events or state anxiety at either follow-up. BP worry was significantly increased at 3 weeks (mean change 0.22 (0.13-0.30), but not at 6 months. Six month outcomes were not influenced by ABPM test results or receiving a hypertension diagnosis.

Conclusion and Relevance:
The hypertension diagnostic process increased hypertension worry short term, but not longer-term. It had little impact on other measures of psychologic distress. The risk of psychologic distress after hypertension diagnostic testing and receipt of a hypertension diagnosis appears to be low, reinforcing the importance of timely hypertension diagnoses. Additional studies with more diverse patient populations are needed.
Abstract P247: Altered Renal Sodium Transporters Expression Is Associated With Cholinergic-mediated Salt Sensitive Hypertension In Young Spontaneously Hypertensive Rats
Authors: Raikwar Nandita , Maiers Trever , Harwani Sailesh
Published: September 2022

High sodium diet is a major contributing factor and has been associated with inflammation in patients suffering from hypertension. Systemic infusion of nicotine induces renal inflammation and the development of premature hypertension in young spontaneously hypertensive rats (SHR) and leads to enhanced expression of the renal Na-K-Cl cotransporter (NKCC2). Sodium sensitivity also plays a role in the development of cholinergic hypertension. We hypothesized that these findings were related to alterations in renal sodium transporters expression. We continuously infused SHR and Wistar Kyoto (WKY, normotensive control) rats with saline or nicotine (15mg/kg/day) and fed either a low-salt (LSD, 0.01% NaCl) or high-salt (HSD, 4% NaCl) diet for 2 weeks. Renal homogenates were assessed by western blot for the presence of the epithelial sodium channel (ENaC), NKCC2, Na-Cl co-transporter (NCC) and Serum and glucocorticoid regulated kinase 1 (SGK-1). Nicotine infusion in WKY induced 1.9-fold increase (p=0.003) in renal expression of SGK-1 under LSD, compared to saline-infused controls. The sharp increase in SGK-1 in nicotine-infused WKY on LSD was accompanied by a 1.9-fold increase in NCC (p=0.004), a 1.3-fold increase in the cleaved alpha ENaC, a 1.2-fold increase in the uncleaved alpha ENaC, and a 1.5-fold increase in the beta-ENaC (p=0.02). Both saline and nicotine infused WKY showed very little expression of renal NKCC2 in either LSD or HSD. There was no effect of either diet or nicotine infusion on expression of SGK-1, NCC, or ENaC subunits in SHR. Nicotine had no effect on NKCC2 expression in SHR on LSD, but HSD alone induced a 2.25-fold increase in renal NKCC2 expression compared to LSD in saline infused SHR (p=0.006). Nicotine infusion further induced a 58% increase in renal NKCC2 expression for SHR fed HSD (p=0.004). Here we show an effect of nicotine to appropriately increase the expression of NCC and ENaC in WKY under LSD and a trend towards decreased expression under HSD. In contrast, nicotine not only has no effect on NCC and ENaC under LSD in SHR but leads to a paradoxical increase in NKCC2 under HSD. We conclude that inappropriate regulation of renal sodium transporters likely plays a role in cholinergic-mediated renal inflammation and hypertension.