bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P102: Inhibition Of Mtor Decreases Angiotensin Ii-induced Steroidogenesis In Hac15 Cells
Authors: Ali Yusuf , Gomez-sanchez Elise P , Gomez-Sanchez Celso E
Published: August 2021

A recent study reported that mTOR inhibition suppressed plasma aldosterone in mice but not humans. We investigated the effects and molecular mechanisms of mTOR inhibition on steroidogenesis using the human adrenocarcinoma HAC15.

Methods:
HAC15 cells were incubated with an mTOR activator and several inhibitors including AZD8055 (AZD) at concentrations of 0 to 1000 nmol/L +/- 100 nmol/L Angiotensin II (AngII) to stimulate steroid synthesis. The raptor and rictor genes were deleted by lentiviral mediated transduction of CRISPR/gRNA. Their presence was demonstrated by Western blotting and immunocytochemical staining. Aldo and cortisol synthesis were measured by ELISA; steroidogenic enzymes, p70S6K and AKT phophorylation by western blot.

Results:
The raptor and rictor, adaptor proteins of mTOR complex 1 and 2, were demonstrated by Western blotting and IHC staining in HAC15 cells. The mTOR inhibitors decreased AngII aldosterone synthesis; AZD was the most effective. The mTOR activator MHY did not stimulate aldosterone synthesis. AZD significantly suppressed both Ang II-induced aldo and cortisol formation in a dose-dependent manner without altering cell proliferation and viability. AZD did not alter forskolin-induced aldo production, suggesting that AZD inhibition of aldo biosynthesis is adenylate cyclase-independent and is specific to the AngII signaling pathway. AZD dose-dependently suppressed AngII-induced steroidogenic enzymes including 3β-hydroxysteroid dehydrogenase-type 2, CYP17A1, StAR, and CYP11B2 protein levels. p70S6K and AKT phosphorylation levels were inhibited by AZD. As mTOR exerts its effects by forming complexes with adaptor proteins raptor and rictor, we studied the role of these individual complexes further. CRISPR/ gRNA-mediated raptor and rictor knockdown in HAC15 cells significantly decreased AngII-induced steroidogenic enzymes levels and aldo and cortisol production.

Conclusion:
These results suggest that mTOR signaling has a role in transducing the AngII signal for aldo and cortisol biosynthesis and that inhibition of mTOR is a therapeutic option for conditions associated with excessive RAS-mediated steroid synthesis.
Abstract P104: Simultaneous Treatment With Ivabradine And Spironolactone Does Not Modify Hypertension-induced Myocardial Fibrosis In Dahl Salt-sensitive Rats
Authors: Dedkov Eduard I , Milcarek Andrew T
Published: August 2021

Background:
Hypertension (HT)-induced accumulation of myocardial collagen stiffens the left ventricular (LV) wall and, hence, promotes diastolic dysfunction. Considering that a competitive aldosterone receptor antagonist spironolactone (SL) as well as a “pure” heart rate-lowering drug ivabradine (IVA) have both been proven to exert an anti-fibrotic effect during cardiac remodeling, we hypothesized that, in combination, these drugs would complement each other in alleviating HT-induced myocardial fibrosis and, therefore, could better preserve diastolic function.

Methods:
Sustained HT was induced in 7-week-old male Dahl salt-sensitive rats by feeding them a high-salt (8%) diet for 7 weeks. Then, HT rats were randomly assigned in two experimental groups: 1) IVA (10 mg/kg/day) + SL (20 mg/kg/day)-treated (HT-T) and 2) vehicle only (HT-V). The drugs and the vehicle (a mixture of 50% dimethyl sulfoxide/50% propylene glycol, v/v) were delivered IP by osmotic pumps for 8 weeks. The age-matched rats were used as normotensive controls (NT). Heart rate (HR) and blood pressure (BP) were recorded every other week using a CODA tail-cuff plethysmography system. At the end of the study, the hemodynamic parameters were assessed using a Millar pressure catheter and the hearts were collected for histology and quantitative morphometry. Statistical analysis was performed using Prism 6.

Results:
We found that during 8-week treatment period, BP had remained comparably elevated in both HT groups by ~26% (P≤0.01) on average vs. NT rats, whereas HR had been persistently reduced in HT-T group by ~38% and ~27% (P≤0.01) on average vs. HT-V and NT rats, respectively. At the end of the study period, all groups revealed a similar level of LV end-diastolic pressure, suggesting the analogous diastolic stiffness of the myocardium. At the same time, morphological examination of the hearts has confirmed that sustained HT caused significant interstitial and perivascular fibrosis (P≤0.01) in both experimental groups compared to NT rats, and that the treatment did not change the extent of fibrillar collagen accumulation as compared to HT-V rats.

Conclusions:
Taken together, our findings confirmed that a combined treatment with IVA and SL could not alleviate HT-induced myocardial fibrosis.
Abstract P117: Comparison Between Routine Clinical And Research Blood Pressure Measurements
Authors: Sanders Mark , Muntner Paul , Wei Rong , Shimbo Daichi , Schwartz Joseph E , Qian Lei , Cannavale Kimberly L , Harrison Teresa N , Lustigova Eva , Sim John J , Reynolds Kristi
Published: August 2021

Background:
Prior studies have found a large difference between blood pressure (BP) when measured routinely in the clinic compared with research studies. We aimed to compare routine clinic BP to research-grade BP in a large, integrated health care system that has initiatives to standardize clinic BP measurements.

Methods:
We identified Kaiser Permanente Southern California members ≥ 65 years old diagnosed with hypertension and taking antihypertensive medication from the Ambulatory Blood Pressure in Older Adults (AMBROSIA) study. Research-grade BPs were obtained under standardized conditions by certified research staff using a semi-automatic oscillometric device, pre-programmed to take 3 measurements at 1-minute intervals. The average of the 3 BPs was used. The most recent (prior to study enrollment) routine clinic BP from an outpatient, non-urgent clinical care encounter, measured using a semi-automatic oscillometric device, was obtained via electronic health records. If there were multiple BP readings on the same day, the first reading was used. The mean difference between clinic BP and research-grade BP was tested using paired t-tests, while the Pearson correlation and a Bland-Altman analysis were used to assess level of agreement.

Results:
We included 309 participants (mean age 75 ± 6 years; 54% female; 49% non-Hispanic white, 17% non-Hispanic Black, 17% Hispanic, 15% Asian/Pacific Islander). When measured in routine clinic practice and in the research study, the mean (SD) systolic BP (SBP) was 135 (16) mm Hg and 132 (15) mm Hg, respectively, (mean difference = - 2.7 mm Hg; 95% CI -4.6 to -0.9; limits of agreement = -36 to 30 mm Hg) and the mean diastolic BP (DBP) was 70 (10) mm Hg and 69 (10) mm Hg, respectively (mean difference = - 0.9 mm Hg; 95% CI -2.1 to 0.3; limits of agreement = -22 to 20 mm Hg). Pearson correlation analysis showed modest correlations between the two types of BP measurements (SBP r=0.40, p<0.01; DBP r=0.45, p<0.01).

Conclusion:
The difference between clinic and research-grade BP was, on average, small, but differences at the individual level were often substantial.
Abstract P124: Repeat Manual Office Blood Pressure By A Physician Is Lower Than Automated Office Blood Pressure
Authors: Rhodehouse Bryce , Shaver Courtney , Fan Jerry , Izekor Bright , Jones Clinton , Belmont De Santiago Andres , Donnelly Stephen , McNeal Michael
Published: August 2021

Introduction:
An accurate measurement of blood pressure (BP) is critical to diagnosing and treating hypertension (HTN). Manual office BP (MOBP) often results in higher readings than automated office BP (AOBP). In previous studies, a repeat MOBP by a physician resulted in a lower BP than the initial MOBP by nursing staff. We evaluated our hypothesis that a repeat MOBP by a physician is statistically equivalent to AOBP.

Methods:
In an ambulatory outpatient setting, patients were roomed and at least a 5-minute interval lapsed before an AOBP was performed using a Welch Allyn Connex Vital Signs Monitor. The physician was blinded to the AOBP. The physician then entered the room and obtained a MOBP with a manual aneroid sphygmomanometer. The difference between the AOBP and the MOBP was calculated. A Wilcoxon signed rank sum test was used to determine if a significant difference between AOBP and MOBP exists.

Results:
A total of 186 patients (112 females, 74 male) had BP measured with a mean age of 66 years. AOBP resulted in a median systolic BP (SBP) 136 mmHg (IQR 121-150 mmHg) and median diastolic BP (DBP) of 78 mmHg (IQR 72-85 mmHg). MOBP SBP had a median of 132 mmHg (IQR 120-142 mmHg) and DBP had a median of 76 mmHg (IQR 70-81 mmHg). SBP and DBP were significantly lower in the MOBP group with a mean difference between AOBP and MOBP of 4.0 and 2.7 mmHg respectively (p-value of <0.0001).

Conclusions:
Repeat MOBP performed by the physician resulted in a significantly lower BP compared to AOBP. The lower BP may be due to an overall longer interval between the AOBP measurement and MOBP measurement. MOBP may be a viable option for accurate diagnosis and treatment of HTN clinics without access to a AOBP machine.
Abstract P127: Heals Med-Tech: A Hypertension Control Program For African American Communities Using Telehealth Technologies
Authors: Clark Amanda , EL Moudden Ismail , Dodani Sunita
Published: August 2021

Background:
Cardiovascular diseases, including stroke, remain the leading cause of mortality and morbidity in the US. Hypertension (HTN) is the single most chronic condition among African-American (AA) adults with health disparities in respect to control, awareness, and compliance. HEALS Med-Tech (HMT) is a 12-month HTN management program. This abstract will present findings from the first 3 months of HMT on BP reduction in diagnosed AA adults. Primary outcomes of interest are changes in systolic BP (SBP), diastolic BP (DBP), and weight at 3, 6, and 12 months.

Methods:
HMT has 3 components: a) HEALS (Healthy Eating And Living Spiritually) a group-based, 12-month behavioral lifestyle intervention (3-months of weekly sessions followed by 9 monthly maintenance sessions) modified from the NIH-funded DASH and PREMIER programs; b) Med-component provides HTN management through medications and social support provided by PCPs; and c) Tech-component provides an interactive telehealth by mobile phone to combat barriers to healthcare access.

Results:
A total of 62 eligible AA participants were enrolled and randomized to either HEALS Med-Tech or standard care (control). The study is currently in maintenance phase. The least squares mean SBP at baseline was 144.1 mm Hg, and after 12 weeks of intervention, the SBP was 134.0 mm Hg. Similar changes were seen in DBP at 12 weeks from baseline.

Conclusion:
A multidisciplinary, community-engaged approach utilizing technology, supported by community peers, could improve HTN management in high-risk AAs. This study will contribute to understanding methods to empower AAs to increase self-care management of HTN and improve access to healthcare.
Abstract P129: Telemedicine And Relationship Of Depression Score Improvement To Hypertension Improvement Via Video Visits
Authors: Taylor Prentiss
Published: August 2021

Telemedicine and Relationship of Depression Score Improvement to Hypertension Improvement via Video Visits

Introduction:
Our group has elsewhere demonstrated effectiveness of telemedicine video visits nationwide for effective hypertension control. Here we explore associated depression scores, grouping patients into cohorts with improvement in systolic BP and patients with no improvement, over 12 months.

Hypothesis:
PHQ-9 depression scores may reveal barriers to achieving BP control via video visits.

Methods:
Quantitative analysis was performed of home video visits coded with Essential Hypertension diagnosis March 2020 through February 2021, the first 12 months of the pandemic. 569 patients with 1785 hypertension visits were in our national telemedicine practice database in the period. Serial PHQ-9 scores were available on 78 patients with multiple hypertension visits. Average percent change in PHQ-9 score was calculated as average change in score / average initial score.

Results:
Patients with reduction in BP had an average of 3.2 visits. The average number of BP measurements in the multiple visits group was 6.37. Average age of patients was 44. There were 56 patients with PHQ-9 scores with improvement in systolic BPs in the study period. Mean initial PHQ-9 score for this group was 11.79 (SEM = +/- 0.92, SD = +/- 6.87), and mean PHQ-9 score at a subsequent measurement was 7.18 (SEM = +/- 0.72, SD = +/- 5.42) . The average change in score was 4.61 (SEM = +/- 0.92, SD = +/- 6.91). These patients improved their PHQ-9 scores by an average of 39.10% (4.61 of 11.79, SEM = +/- 7.84%, SD = +/- 58.64%). There were 22 patients with PHQ-9 scores with no improvement in systolic BPs in the study period. Mean initial PHQ-9 score for this group was 13.09 (SEM = +/- 1.54, SD = +/- 7.22), and mean PHQ-9 score at a subsequent measurement was 9.5 (SEM = +/- 7.74). The average change in score was 3.59 (SEM = +/- 1.50, SD = +/- 7.01). These patients improved their PHQ-9 scores by an average of 27.40% (3.59 of 13.09, SEM = +/- 11.42%, , SD = +/- 53.58%).

Conclusions:
These results are hypothesis-generating about possible relationships between depression diagnosis, improvement in management of depression, and hypertension control. Further study of more PHQ-9 data with a larger study sample would be of interest.
Abstract P130: The Use Of A Digital Telehealth Platform To Understand The Prevalence And Control Of Hypertension In The Indian Population - A Proof Of Concept Study
Authors: Vaishnav Aditi S , Vaishnav Sudhir N
Published: August 2021

Introduction:
Despite the enormous burden of cardiovascular disease (CVD) in India, there is still lack of awareness about the importance of guideline-based risk factor (RF) management.

Objective:
Understand the feasibility & utilization pattern of an open-to-public digital health (mHealth) platform designed to assess CVD risk and RFs, and provide appropriate education and guidance.

Methods:
Data was collected over 1 month through the mHealth platform that was open to all adults aged 25-80 years. It was accessible at no cost via all web browsers on smart phones, computers & tablets with internet connectivity and in 2 languages. Platform utilization was higher in males - 93.7% (251/268) respondents. Therefore, the study population comprised 251 males (age 45.4
+
11.7 yrs). Females were not included due to the small sample size; the corresponding results will be published once adequate sample is reached.

Results:
Hypertension (HTN) was the most commonly reported RF - 152 (60.5%) of subjects. Of these, 128 (84.2%) reported taking >=1 BP lowering medications. However, BP control was poor with only 26.6% (34/128) of those on BP medications and 4.2% (1/24) of those not on medications reporting BP <130/80 mm Hg. Out of 99 subjects without history of HTN, 21.2% and 28.3% met criteria for diagnosis of HTN and high normal BP, respectively. 151 (99.3%) of subjects had at least 1 other CVD RF - 50% hyperlipidemia, 47.4% diabetes mellitus, 16.4% prediabetes, 57.2% sedentary lifestyle, 24.3% active smoking, 61.2% obesity.

Conclusion:
The use of a mHealth tool for HTN is feasible and reveals a large unmet need.
Next Steps
Assessing use of this tool to improve HTN control through lifestyle changes and compliance.
Abstract P132: Clinical Outcomes In Ischemic Stroke Patients With Uncontrolled Hypertension
Authors: Abuzaid Zahra , Almuslem Sara , Aleisa Farah
Published: August 2021

Background:
Hypertension is considered major risk factor for incidence of ischemic stroke, controlling blood pressure reduces this risk, the relationship of uncontrolled blood pressure and stroke outcomes is complex, post stroke uncontrolled blood pressure remains one of the major contributing factors for stroke recurrence and mortality, in our study we studied the long term effects of uncontrolled hypertension in modern health care setting.

Methodology:
Patients in the study were admitted to the neurology department at KFSH-D between March 2015- August 2019, we included 102 acute ischemic stroke patients whom had hypertension, all patients had follow up appointments at stroke clinic a minimum of 2 visits over 4 years. We retrospectively compared blood pressure data from stroke patients with recurrent ischemic stroke events vs. patients with initial stroke event, and recurrent stroke, also we studied blood pressure readings for different stroke severity groups, patients who had severe stroke with mRS>4, compared to milder stroke group of mRS<4.

Results:
We found 48 patients identified with recurrent stroke event, those with uncontrolled hypertension had significantly higher stroke recurrence events (P=0.002), despite acute stroke treatment, patients who had history of uncontrolled hypertension were found to have more severe stroke deficits than those who had controlled blood pressure (P=0.029). We found significant difference in the long term stroke clinical outcomes between patients who had uncontrolled blood pressure and patients who had controlled blood pressure recordings within the same hospital setting (P=0.064).

Conclusion:
Based on our findings, uncontrolled hypertension was associated with higher risk of stroke recurrence, it also increased susceptibility to worse stroke clinical outcomes up to 1 year after initial stroke event, which deserved further close attention and better blood pressure control.
Abstract P142: Factors Associated With Persistent Cardiac Organ Damage In Primary Aldosteronism After One Year Of Treatment
Authors: Aune Arleen , Kokorina Marina , Grytaas Marianne , Kringeland Ester , Midtbø Helga , Løvås kristian , Gerdts Eva
Published: August 2021

Introduction:
Adrenalectomy and medical treatment of primary aldosteronism (PA) both induce regression of left ventricle (LV) hypertrophy, while the effects on LV myocardial function are less investigated.

Hypothesis:
We hypothesized that persistent cardiac organ damage was more prevalent in medically treated PA patients.

Methods:
Eighty-four patients (57±11 years, 27% female) with PA underwent echocardiography at time of diagnosis and after 1 year of treatment (49% adrenalectomized, 51% medically treated). Persistent cardiac organ damage was identified as LV hypertrophy or low LV systolic function by midwall shortening or global longitudinal strain (GLS), both at baseline and at follow-up. LV diastolic function was assessed by left atrial enlargement and estimated LV filling pressure (E/e’). Results from logistic regression analyses are reported as odds ratio (OR) with 95% confidence intervals (CI).

Results:
After 1 year, a significant regression of LV hypertrophy was observed in adrenalectomized patients (44% vs. 22%, p=0.038), but not in medically treated patients (59% vs. 50%, p=0.206). Midwall shortening, E/e’ and prevalence of enlarged left atrium improved significantly in both treatment groups (all p<0.001), while GLS remained unchanged. In multivariable logistic regression analysis, receiving medical treatment for PA (OR 4.98 [95% CI 1.26-18.88] was a strong predictor of persistent LV hypertrophy independent of higher body mass index (OR 1.20 [95% CI 1.04-1.38]) and presence of diabetes (OR 6.48 [95% CI 1.20-34.83], all p<0.05). Important covariables of persistently low midwall shortening were persistent LV hypertrophy (OR 3.50 [95% CI 1.12-10.96]) and suppression of plasma renin activity after 1 year of treatment (OR 4.31 [1.15-16.12], both p<0.05). The strongest predictor of persistently low GLS was higher HbA
1c
(OR 2.37[95% CI 1.12-5.02], p=0.024).

Conclusions:
In PA, LV hypertrophy regression was more common in adrenalectomized patients. Persistent LV hypertrophy and impaired glucose metabolism were the major factors associated with persistent LV myocardial dysfunction independent of treatment.
Abstract P158: Endothelin Inhibits Adiponectin Production Via ETB Receptor Activation On Adipocytes
Authors: Rivera-Gonzalez Osvaldo J , Coats Laura , Speed Joshua S
Published: August 2021

Endothelin-1 has been implicated in obesity related insulin resistance. Our lab recently demonstrated that ET-1 is elevated in adipose tissue of obese mice, and blockade of ET-1 receptors improves insulin sensitivity in a mouse model of diet induced obesity. One potential mechanism by which ET-1 promotes insulin resistance is through activation of the ET-1 type B receptor (ET
B
). Blockade of ET
B
receptors improves insulin sensitivity and increases circulating adiponectin, an adipokine only released by adipose tissue. Therefore, the current hypothesis is that ET-1 causes insulin resistance and inhibits adiponectin production by adipocytes. Primary mouse adipocytes were cultured and chronically treated with ET-1 for 3 days. ET-1 treated adipocytes had significantly lower peroxisome proliferator activator gamma, a transcription factor that drive adiponectin production, and adiponectin mRNA expression and release into media. This response was attenuated by co-treatment with an ET
B
receptor antagonist (BQ-788; 57.2±2.0 vehicle, 42.5±4.5 ET-1, 59.8±1.5 ET-1+BQ788, ng/ml; p<0.05) and in adipocytes from adipocyte ET
B
receptor knockout mice. Further, expression of several genes in the insulin signaling pathway, including Glut4 and insulin receptor substrates 1 and 2 were significantly reduced in adipocytes treated with ET-1, a response that was attenuated with ET
B
receptor blockade or knockout of the ET
B
receptor. These data suggest that increased ET-1 production in adipose tissue promotes insulin resistance on adipocytes and inhibits the release of insulin sensitizing adipokines such as adiponectin, a potential mechanism by which ET-1 receptor blockade improves insulin sensitivity in obese mice.
Abstract P160: C1q/TNF-related Protein 1 Induces Obesity-related Hypertension In Mice Via Renal Na+ Retention In The Proximal Tubules
Authors: Wang Fei , Zheng Huaqing , Luo Renfei , Yang Tianxin
Published: August 2021

A recently identified adipokine C1q/TNF-related protein 1 (CTRP1) displayed a potent beneficial effect in managing metabolic disorders during type 2 diabetes and obesity. However, little is known about a potential role of CTRP1 in regulation of renal function and blood pressure (BP) in the context of obesity. Therefore, the present study aimed to determine the effect of a recombinant CTRP1 protein (termed CTRP1-His) on blood pressure in mice with diet-induced obesity (DIO). 8-mo-old male C57/B6 mice were fed a high-fat diet (60 Kcal% fat) for eight weeks and were infused with vehicle or CTRP1-His (10 ng/min/kg) via subcutaneously implanted osmotic minipump for the last seven days. BP parameters were recorded using telemetry devices. Consistent with other groups’ studies, mice infused with CTRP1-His exhibited remarkably improved multiple metabolic parameters, including hyperglycemia and hyperinsulinemia. Compared to the vehicle group, BP responses to CTRP1-His treatment developed a modest but significant increase in BP (MAP on day 7 [mmHg]: 122.3 ± 2.2 vs. 109 ± 1.73, n = 3 per each group, p < 0.01) accompanied with decreased hematocrit (Hct [%]: 43.8 ± 1.3 vs. 49 ± 1.2 %, p < 0.05), an index of plasma volume expansion. The DIO mice infused with CTRP1-His demonstrated a reduced urinary sodium excretion (U
Na
/Creatinine [mmol/mg]: 0.17 ± 0.04 vs. 0.27 ± 0.06, p = 0.07). By immunoblotting CTRP1-His infusion induced significant upregulation of renal abundances of p-NHE3, V2R, and AQP2 but suppressed obesity-induced renal abundances of p-NCC/NCC, p-NKCC2/NKCC2, and cleaved α-ENaC protein. Interestingly, CTRP1-His infusion tends to decrease albuminuria (urine albumin/Creatinine [mg/g]: 78.8 ± 7.7 vs. 120.5 ± 14, p = 0.07) in the DIO mice. Overall, our results indicated that CTRP1-His exerted a pressor effect in DIO mice via stimulating sodium-water retention through activation of NHE3 and AQP2 associated with compensatory attenuation of Na+ transporters in the distal nephron.
Abstract P168: Predictors Of Htn Remission Post-bariatric Surgery: A Contemporary Analysis
Authors: Romero Carlos Manuel , Tragesser Lauren , Haddad Abdullah , Ibrahim Kaitlyn , Soans Rohit , Vikram Eddy , McComb Joseph , Whitman Isaac R , Keane Martin G
Published: August 2021

Introduction:
The effect of bariatric surgery on improvement and remission of hypertension (HTN) is well documented. However, the factors that influence HTN remission in this population are poorly understood and have not been investigated in over a decade. We aim to describe predictors of HTN remission post-bariatric surgery in a contemporary patient population.

Methods:
All patients who underwent sleeve gastrectomy or Roux-en-Y gastric bypass from January 2014 to December 2018 at an urban academic institution were included in the analysis. Blood pressure (BP) was recorded pre-operatively, 6-month post operation, and 12-month post operation. HTN was defined as BP ≥ 140/90 or patients on anti-hypertensive medications. Remission was defined as BP < 140/90 off all blood pressure medications. Baseline characteristics of patients with and without HTN remission were described. Logistic regression analysis was performed to assess indicators of HTN remission. A p-value of 0.05 was used for all statistical analyses.

Results:
Among 844 patients who underwent bariatric surgery, 497 (58.9%) patients had HTN. Among HTN patients 167 (33.6%) had remission at 6 months and 126 (25.4%) had remission at 12 months. The major predictor of HTN remission on multivariate analysis was number of pre-operative medications at 6 months (OR 2.5, 95% CI 2.03 to 3.29) and 12 months (OR 2.6, 95% CI 1.99 to 3.56). Major predictors on univariate analysis at 12 months were CVA (OR 4.3, 95% CI 1.40 to 12.47) and HLD (OR 1.76, 95% CI 1.27 to 2.45).

Conclusion:
Number of pre-operative medications is a top predictor of HTN remission. HLD and history of stroke may be present in patients who are less likely to have HTN remission.
Abstract P174: Sex Differences In The Pro-hypertensive Effect Of Carnitine, The Precursor Of Gut-derived Metabolite TMAO
Authors: Abais-Battad Justine M , Dasinger John Henry , Mattson David L
Published: August 2021

Recent evidence reports sexually divergent mechanisms that differentially drive the severity of hypertension. Our data show that female Dahl Salt-Sensitive (SS) rats are significantly protected from salt-induced hypertension and renal injury and have stark differences in gut microbiota composition compared to males. Gut-derived metabolites are increasingly being recognized as mechanistic links between the gut microbiota and hypertension. One such metabolite is trimethylamine N-oxide (TMAO), which is derived from the bacterial metabolism of carnitine and is gaining notoriety for its role in cardiovascular disease. Metabolomics analysis in high salt-fed SS rats revealed a trend for increased TMAO (1.3-fold, p=0.11) in the serum of males compared to females (n=6). TMAO appears to be specifically derived from gut bacteria since oral antibiotic treatment nearly eliminated circulating TMAO levels in both males and females (99.3% and 88.9% reduction, respectively; p<0.001). Interestingly, antibiotic treatment reduced salt-sensitive hypertension in males but not females. There was also a corresponding increase in the TMAO precursor carnitine (1.9-fold, p<0.01) in the serum of males versus females. Thus, we hypothesized that administration of carnitine (400 mg/kg/day) in the drinking water would exacerbate salt-sensitive hypertension, renal damage, and gut inflammation in male and female SS rats challenged with high salt (4% NaCl). There was a trend for carnitine treatment to exacerbate mean arterial pressure in both males (160±9 vs 146±2 mmHg, n=4-6, p=0.22) and females (155±6 vs 139±2 mmHg, n=2, p=0.14) compared to vehicle. Despite elevated pressure in both sexes, carnitine-treated males exhibited greater increases in albuminuria (340±136 vs 194±29 mg/day, carnitine vs vehicle, p=0.28) than females (55±33 vs 26±5 mg/day). Carnitine treatment also significantly increased the number of CD3+ T cells in the colonic lamina propria (24.3±6.0 vs 2.4±0.5 x 10
6
cells/g tissue, n=5, p<0.05) of male rats compared to vehicle. Together, these data identify gut microbiota-mediated carnitine/TMAO metabolism as a potentially detrimental pathway that promotes greater salt-sensitivity, renal damage, and gut inflammation in males versus females.
Abstract P175: Discovery And Validation Of Unique Associations Of DNA Methylation Regions With 24-hour Blood Pressure Phenotypes In African Americans
Authors: Roberts Michelle L , Kotchen Theodore A , Pan Xiaoqing , Li Yingchuan , Yang Chun , Liu Pengyuan , Wang Tao , Laud Purushottam , Chelius Thomas , Munyura Yannick , Mattson David L , Liu Yong , Cowley Allen W , Kidambi Srividya , Liang Mingyu
Published: August 2021

DNA methylation, an epigenetic mark, may reflect the interactions between DNA, environment, and lifestyle. It has been implicated in the development and progression of hypertension, a risk factor for cardiovascular disease. We hypothesize that regions of DNA methylation in blood cells can explain 24h BP phenotypes in African Americans. We performed Reduced Representation Bisulfite Sequencing (RRBS) in a discovery cohort of 281 African Americans. Several DNA methylation regions (MRs) were significantly associated with continuously monitored 24-h, daytime, or nighttime SBP, DBP, PP, and MAP after adjustments for covariates age, sex, and body mass index (False Discovery Rate (FDR) = 0.013 - 0.050). Each of these MRs explained a substantial portion of 24h BP variance, ranging from 6.5% - 9.4%. After FDR adjustment, there were no MRs significantly associated with clinic BPs (FDR > 0.1374), calculated by the average of 4 resting measurements (2 per arm) by sphygmomanometer. To interrogate specific regions of DNA methylation, our lab developed a potentially clinically applicable, deep, and targeted methylation sequencing method called Bisulfite-Specific PCR ULtrapLEx Targeted Sequencing (BULLET-Seq), and tested it in two reference samples for three MRs of interest. BULLET-Seq is able to accurately quantify the 10% changes in the dilution series when methylation rates ranged from ~40% to 90% (a chr19 methylation region; R
2
= 0.95 - 0.97) and can modestly measure these changes when rates range from ~2% to 4% (a chr5 region, R
2
= 0.82), and is questionable when methylation rates are below 2% (a chr13 region, R
2
= 0.03 - 0.27). Validation of the chr19 MR in an independent cohort (n=117) was performed in a single BULLET-Seq run. After covariate adjustment, the chr19 region was significantly associated with 24h BPs (SBP, DBP, and MAP; FDR < 0.05), confirming the findings from the discovery cohort. The MR accounted for up to 1.75% of BP variance in the 24h phenotypes. In conclusion, the reported DNA MRs have potential to be excellent markers for the cumulative effect of factors that influence 24h BPs and the BULLET-Seq workflow can be applied in clinical and population settings to screen up to thousands of patients.
Abstract P176: Genes That Increase Human Lifespan By Protecting Against Risk Of Death From Cardiometabolic Diseases
Authors: Morris Brian J
Published: August 2021

Further to our
FOXO3
findings last year, we asked whether other longevity gene variants work by mitigating mortality risk from aging-related diseases. In a longitudinal study, 3,584 American men of Japanese ancestry from the Kuakini Honolulu Heart Program were followed from baseline (Exam 4, 1991-93) until Dec 31, 2019 (1% of men) or death (99%). At baseline, 2,512 subjects had either diabetes (n=1,010), hypertension (n=1,919) or coronary heart disease (CHD; n=738), and 1,072 lacked any cardiometabolic diseases (CMD). DNA samples for genotyping were obtained at baseline. Genotype frequencies of SNPs in
MAP3K5
,
PIK3R1
,
GHR, CTGF
,
EGFR
,
FLT1
,
SIRT5
and
SIRT7
were compared between subjects with and without ageing-related diseases
.
In subjects with CMD,
MAP3K5
rs2076260
longevity-associated genotypes
CC
and
CC
+
TT
were associated with longer lifespan (covariate-adjusted hazard ratio [HR] 1.23 [95% CI: 1.12-1.35,
p=
2.5x10
-5
] in a major allele homozygote model, and 1.22 [95% CI: 1.11-1.33,
p=
1.10x10
-5
] in a heterozygote disadvantage model) compared with
CT
. For diabetes, hypertension and CHD, HR
p
-values were 0.019, 0.00048, 0.093, and 0.0024, 0.00040, 0.0014, in each respective genetic model. For
PIK3R1
, subjects with cardiovascular disease (CVD) having the longevity-associated genotypes
TT
/
CC
of SNP
rs7709243
had survival curves similar to those of subjects without a CVD (HR 1.26 [95% CI, 1.14-1.39;
p
=0.0000043]). In contrast, survival curves of subjects with the
CT
genotype were significantly lower compared with survival curves of subjects without a CVD (
p
=0.0000012 compared with
TT
/
CC
, and
p
=0.0000028 compared with
CT
). For
GHR
SNP
rs4130113
, in a heterozygote disadvantage model
GG
vs longevity-associated
AG
genotype was associated with reduced mortality risk from hypertension (HR 1.23 [95% CI, 0.94-1.41;
p
=0.0041]). Men without CVD showed no association of longevity-associated genotype with lifespan. For each gene, men without the disease outlived men with disease (
p
< 10
-6
), but genotype had no effect on lifespan. In conclusion, for
MAP3K5
,
PIK3R1
and
GHR
, but not other longevity genes, longevity genotype increases lifespan only in individuals who have CMD, CVD or hypertension, likely by protection against disease-related cellular stress.
Abstract P178: Social Determinants Of Health And Preventable Hospitalization For Hypertension
Authors: Pattath Priyadarshini , Anson-Dwamena Rexford
Published: August 2021

Introduction:
Social determinants of health (SDH) can have a significant impact on the risk of hypertension related hospitalization. Understanding the drivers of potentially preventable hospitalizations for hypertension improves health outcomes and reduce associated costs. Identifying place and associated SDH has implications for tailored interventions to address disparities for high burden population for preventable hypertension hospitalization as hypertension and associated cardiovascular disease.

Methods:
County level preventable hospitalization rates for hypertension for Virginia was obtained using prevention quality indicators published by the Agency for Healthcare Research and Quality. The Health Opportunity Index (HOI), developed by the Virginia Department of Health to identify vulnerable populations is a multivariate tool that uses complex SDH indicators of a community and comprises of 13 indices - affordability, income inequality, Townsend/Material deprivation, job participation, employment access, education, air quality, segregation, food accessibility, population density, population churning, walkability, and access to care. Principal component analysis was used to develop the composite HOI and further aggregated into simple quintiles at the county level. Step-wise multiple regression analysis was performed to explore SDH and preventable hospitalization for hypertension.

Results:
Material deprivation index (
r
= -.44), affordability index (
r
= -.42) and air quality index (
r
= -.23) were found to be significantly associated with preventable hospitalization rate for hypertension. Together the model accounted for 23% of the variability in the preventable hypertension hospitalization rate (
p
> 0.05).

Conclusions:
Findings indicate that neighborhoods that spend most on housing and transportation and that are materially deprived of goods, services, amenities and resources and physical environment have higher rates of preventable hospitalization for hypertension. Areas with higher air pollution may result in hypertension. Addressing these disparities by targeted approach is one possible approach to reducing the burden of preventable hospitalization for hypertension in Virginia.
Abstract P187: Incident And Risk Factors For Hypertension Among Urban Japanese: The Suita Study
Authors: Sheerah Haytham A , Arafa Ahmed , Teramoto Masayuki , Watanabe Emi , Li Jiaqi , Sakai Yukie , Honda-Kohmo Kyoko , Kashima Rena , Nakao Yoko , Watanabe Makoto , Koga Masatoshi , Dohi Tomoharu , Kokubo Yoshihiro
Published: August 2021

Introduction:
According to the world health organization, an estimated 1.13 billion individuals worldwide have hypertension (HT). However, limited studies discussed the risk prediction for incident HT. We aim to evaluate the incidence of HT and identify its risk factors in urban Japanese residents.

Methods:
We followed up 4,314 normotensive participants at the baseline survey. Blood pressure (BP) was measured twice in the sitting position under rest. The participants have continued to visit the center every two years for regular health check-ups and all of them gave informed consent. The BP categories were defined by the ESC/ESH Guidelines. Cox regression model was used to detect HT's risks by cardiovascular risk factors.

Results:
During the mean follow-up period of 17.6 years, 25.8 per 1000 person-years of participants developed HT (optimal 16.7, normal 30.7, and elevated BPs 43.5 per 1000 person-years, respectively). The adjusted hazards ratio (HRs, 95% CIs) for developing HT for age groups in the 40s (HR=1.34, 95% CI=1.14 - 1.58), 50s (1.73, 1.47 - 2.04), 60s (2.26, 1.91 - 2.68), and 70s (2.95, 2.41 - 3.61), normal BP (2.23, 1.98 - 2.50), elevated BP (4.25, 3.78 - 4.76), smoking > 10 cig/d (1.21, 1.05 - 1.40), never drinking alcohol 1.22 (1.07 - 1.40), drinking alcohol ≥ 4 units/day 1.36 (1.15 - 1.60), parental history of HT (1.18, 1.03 - 1.34), fasting plasma glucose levels ≥ 126 mg/dL (1.39, 1.10 - 1.76), and chronic kidney disease (1.15, 1.02 -1.29) in the normotensive population.

Conclusion:
The incident and risk factors for developing HT were firstly shown in Japan. The study emphasizes the importance of controlling the risk factors for incident HT as primary prevention.
Abstract P203: Time-restricted Feeding Attenuates Hypertension In Mice
Authors: Goodlett Bethany L , Sims Braden M , Navaneethabalakrishnan Shobana , Wilcox Brooke K , Pickup Emma J , Henley Marissa R , Albee Miranda L , Arenaz Cristina M , Mitchell Brett M
Published: August 2021

Hypertension is associated with inflammation and decreased kidney function. Studies of cardiovascular function have observed that time-restricted feeding (TRF), a form of intermittent fasting, is associated with decreased blood pressure, decreased inflammation, and improved kidney function. We hypothesized that implementation of a time-restricted feeding protocol in hypertensive mice would decrease systolic blood pressure and increase kidney function. C57BL6/J mice were randomly assigned to either an L-arginine methyl ester hydrochloride (LNAME)-induced hypertension (LHTN) model, where they received LNAME in their drinking water, or a salt-sensitive hypertension (SSHTN) model, where they received a 4% high salt diet following LNAME priming and a washout period. Two days following introduction of LNAME or the high salt diet, mice were either provided food
ad libitum
or placed on a 12-hour TRF protocol, where they were only allowed to eat from 8PM to 8AM. Hypertensive mice receiving TRF treatment displayed a significantly decreased systolic blood pressure (SBP) after 4 weeks when compared to the control hypertensive groups (LHTN SBP: 164±1 vs. 149±2 mmHg, p<0.001; SSHTN SBP: 139±1 vs. 130±1 mmHg, p<0.001). When kidney function was examined in the LHTN group, TRF mice had decreased serum creatinine (Sc) levels along with decreased fractional excretion of sodium (FENa) when compared to their respective control mice (Sc: 0.19±0.01 vs. 0.13±0.01 mg/dL, p=0.007; FENa: 0.59±0.05 vs. 0.32±0.05 %, p=0.009). Glomerular filtration rate was significantly increased in TRF treated LHTN mice. Overall, these data indicate that TRF treatment reduces blood pressure in hypertensive mice, which is associated with an improvement in renal function. These findings could establish TRF as a potential therapeutic option for hypertensive patients.
Abstract P207: Sleep Hygiene As An Intervention To Improve Autonomic Function
Authors: Vazquez Michael , Yang Huan , Dang Rammy , Haack Monika , Mullington Janet
Published: August 2021

Introduction:
Insufficient sleep is associated with increased heart rate (HR) and blood pressure (BP). Exaggerated cardiovascular reactivity to the cold pressor test (CPT) has been linked to an increased incidence of hypertension. This project investigates the effects of improved sleep hygiene on autonomic function at rest and in response to CPT. We hypothesize a decrease in BP and HR at rest, and attenuated BP and HR response during CPT.

Methods:
Fifty participants (59.8 ± 1.5 years; 31 women) completed 3 overnight in-hospital stays in which they had continuous ECG and beat-to-beat BP monitoring. The first stay (S1) was a baseline control; the second stay (S2) was a 4-week wait-list control; the third stay (S3) followed an 8-week randomly assigned intervention that used sleep hygiene approaches along with scheduling to either A) stabilize sleep timing, or B) stabilize and extend the bed period. This study is still ongoing, so we are blind to the specific arm that the participants were randomized to. During each stay, autonomic testing was performed about four hours after the participant awoke, including a 5-minute resting period where breathing was controlled (BL), a 3-minute resting period where breathing was not controlled (CPT BL), and 2-minute CPT when participants then submerged their hand in 3°C water. Linear mixed models analyzing the changes in HR and systolic BP (SBP) across the three stays were used.

Results:
During the 5-minute BL, HR did not significantly decrease from S1 to S2 (p=.310) but did significantly decrease by 2 bpm from S2 to S3 (p=.006). SBP decreased by 7 mmHg from S1 to S2 (p=.022) but did not significantly decrease from S2 to S3 (p=.907). During CPT in all stays, HR and SBP significantly increased compared to CPT BL (p<0.05). There was a significant stay x test interaction effect in HR (interaction, p=.042), but not in SBP (interaction p=.361).

Conclusion:
While we are still blind to condition, both arms actively improve sleep hygiene. These preliminary data suggest that stabilization of sleep timing and possibly duration, has a positive impact on autonomic function as seen through the decreases in HR at rest and during CPT.
Abstract P209: Loss Of Rgs2 Specifically In CD4+ T Cells Decreases The Hypertensive Response To Vasopressin
Authors: Scroggins Sabrina M , Gray Gabrielle , Scroggins Douglas G , Shaw Kamara S , Santillan Donna A , Grobe Justin L , Santillan Mark K
Published: August 2021

Regulator of G protein Signaling (RGS) family members can modulate multiple cardiovascular hormones and are associated with hypertension and preeclampsia, a hypertensive disorder in pregnancy. We previously observed a 9-fold increase in RGS2 in CD4+ T cells isolated from women with preeclampsia compared to normotensive women. Further, in non-pregnant mice, we showed that loss of RGS2 in CD4+ T cells prevented angiotensin II-induced hypertension (measured via radiotelemetry) and resulted in increased levels of the anti-inflammatory cytokines interleukin 4 and transforming growth factor beta. We hypothesize that modulating RGS2 in CD4+ T cells may be a therapeutic strategy for hypertension. The objective of this study was to determine if loss of RGS2 specifically in CD4+ T cells protects against the development of arginine vasopressin-induced hypertension in mixed background CD4+ RGS2 knockout mice (CD4 RGS2
KO
). To generate mice wherein RGS2 is specifically knocked out in CD4+ T cells, CD4-Cre+ mice (C57BL/6J) were crossed with RGS2
flox/flox
mice (B6SJLF1/J). Female 8-12 week old CD4 RGS2
KO
or littermate control mice (n=5 per group) from this mixed strain were administered 24 ng/hr vasopressin for 21 days via mini-osmotic pump. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MP), and heart rate (HR) were assessed using a high throughput non-invasive blood pressure system. Prior to vasopressin infusion, KO and CTL mice showed no differences in SBP, DBP, MP, or HR. At 9-13 days of vasopressin-infusion, KO mice had a significantly lower 24-hr SBP [KO 138.7 ±4.7 vs CTL 155.9 ±3.4 mmHg, p<0.05], DBP [KO 106.9 ±4.1 vs CTL 122.8 ±2.9 mmHg, p<0.05], MP [KO 117.2 ±4.3 vs CTL 133.5 ±3.0 mmHg, p<0.05], and HR [KO 378 ±18.7 vs CTL 445 x±12.8 BPM, p<0.05] compared to CTL mice. Here, we demonstrate that in a mixed strain CD4+ RGS2 KO mouse, loss of RGS2 specifically in CD4+ T cells prevented vasopressin-induced hypertension. Therefore, RGS2 expression in CD4+ T cells may play an expanded role in the modulation of hypertension.
Abstract P212: Peroxiredoxin-4 And Dopamine D5 Receptor Interact To Reduce Oxidative Stress And Inflammation In The Kidney
Authors: Lee Hewang , Yang Sufei , Yu Peiying , Armando Ines , Zeng Chunyu , Felder Robin A , Asico Laureano D , Jose Pedro A
Published: August 2021

Peroxiredoxin-4 (PRDX4), an endoplasmic reticulum peroxiredoxin protein, plays a protective role against oxidative stress and inflammation by reducing hydrogen peroxide to water. The dopamine D5 receptor (D
5
R) is also important in protecting against oxidative stress, but the interaction between PRDX4 and D
5
R in regulating oxidative stress in the kidney is not known. In D
5
R-HEK 293 cells, fenoldopam (FEN, 25 nM/12 hr, n=4), a D1-likereceptor agonist, increased PRDX4 protein expression (1.92±0.12-fold over basal level, n=4), mainly in non-lipid rafts (LRs: 24.9±11.4%, non-LRs: 75.1±11.4%, baseline; LRs: 30.9±13.9%, non-LRs: 174.1±16.7%, FEN). FEN also increased the co-immunoprecipitation of D
5
R and PRDX4 and their colocalization, particularly in the endoplasmic reticulum. In human renal proximal tubule cells (hRPTCs), FEN (25 nM/12 hr, n=3) increased PRDX4 and D
5
R interaction in non-LRs, also. Si-RNA silencing of
PRDX4
increased reactive oxygen species (ROS) production and impaired the inhibitory effect of FEN on ROS production (scrambled siRNA: 100.0±11.6% and 65.4±5.6% for Vehicle (Veh) and FEN, respectively;
PRDX4
siRNA: 147.7±11.8% and 134.8±11.2% for Veh and FEN, respectively, n=4/group) detected by Amplex Red. In addition in both D
5
R-HEK 293 and hRPTCs, siRNA silencing of
PRDX4
increased the production of interleukin-1β (26.88±3.8 and 46.40±4.2 pg/mL [n=3, D
5
R-HEK 293]; 15.87±1.2 and 37.9±1.4 pg/mL [n=3 in hRPTCs]), tumor necrosis factor (131.7±6.5 and 271.2±18.1 pg/mL [n=4, D
5
R-HEK 293]; 108.8±11.8 and 240.1±13.7 pg/mL [n=4 in hRPTCs]), and caspase-12 (15.21±3.8 and 40.78±4.3 ng/mL [n=4,n D
5
R-HEK 293]; 8.8±1.1 and 27.9±2.0 ng/mL [n=4, hRPTCs]). Furthermore, the protein expression of D
5
R was decreased in PRDX4 siRNA-treated D
5
R-HEK293 (~41.2%, n=3) and hRPTCs (~39.6%, n=3). PRDX4 protein was also reduced in the kidney homogenates from D
5
R
-/-
mice (WT: 1.00±0.18, n=5; D
5
R
-/-
: 0.686±0.14, n=4; P<0.05). Taken together, PRDX4 interacts with D
5
R to decrease oxidative stress and inflammation in the kidney.