bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P002: Mechanism Of Mesenteric Artery Vasodilation And Blood Pressure Regulation By Statins
Authors: Zerin Farzana , Hasan Ahasanul , Hasan Raquibul
Published: September 2022

Purpose:
Statins are the world’s most prescribed drugs with a wide variety of cholesterol-dependent and -independent cardiovascular effects. Pre-clinical and clinical data suggest that statins lower blood pressure (BP) in some patients but have no effect in others. However, the underlying mechanism for such differences remain unclear. By studying the direct vascular effects of therapeutically relevant concentrations of statins in resistance mesenteric arteries from normotensive Sprague Dawley (SD) rats and Spontaneously Hypertensive (SHR) rats, we sought to determine the mechanism of differential BP regulation by statins.

Methods:
Pressurized arterial myography, phosphodiesterase (PDE) activity assay, ELISA-based cGMP measurement, blood pressure measurement with tail-cuff.

Results:
Our pressure myography data revealed that statins induce rapid vasodilation in resistance mesenteric arteries. Endothelium denudation, inhibition of endothelial nitric oxide (NO) synthase (eNOS) with L-NNA, smooth muscle cell (SMC) guanylyl cyclase (sGC) inhibition with ODQ, or the inhibition of protein kinase G (PKG) with KT5823 each abolished statin-evoked vasodilation, demonstrating a critical role of endothelium and NO signaling in this process. However, contrary to previous reports, mevalonate application had no effect on vasodilation. Statins selectively inhibited PDE1A in SMCs, elevated [cGMP]
i
, which could potentiate NO-GC-cGMP-PKG signaling, leading to vasodilation. Statin-evoked vasodilation is attenuated in SHR rat mesenteric arteries that have reduced eNOS expression and impaired NO signaling. Consistent with the vasodilatory action, acute statin treatment lowered systolic and diastolic BP in healthy SD rats. In contrast, acute statin treatment failed to lower systemic BP in SHR rats with reduced eNOS expression.

Conclusion:
Statins are endothelium-dependent vasodilator, and selective inhibitor of PDE1A in resistance mesenteric arteries. Intact endothelial function and NO production are essential for statin-induced vasodilation and the reduction of BP. Our study could provide explanation to the anti-hypertensive and BP neutral effects of statins.
Abstract P004: Chronic Nebivolol And Metoprolol Treatment Reduce Circulating Endothelial Cell-Derived Microvesicles In Adults With Hypertension
Authors: Fandl Hannah K , DeSouza Christian S , Garcia Vinicius P , Greiner Jared J , Stauffer Brian L , Desouza Christopher A
Published: September 2022

Nebivolol and metoprolol are effective blood pressure medications that also reduce risk of cardiovascular and cerebrovascular events. Endothelial cell-derived microvesicles (EMVs) are small anucleoid, extracellular vesicles released in response to a myriad of stimuli that trigger cell activation or apoptosis. Clinical interest in EMVs has increased due, in part, to their role in the development and progression of cardiovascular and cerebrovascular disease as well as their prognostic value. Circulating EMVs are elevated with hypertension and contribute to vascular dysfunction. The aim of this study was to determine the independent effects of nebivolol and metoprolol treatment on circulating EMVs in adult humans with hypertension. Thirty-eight middle-aged adults with elevated blood pressure completed a 3-month double-blind, randomized, placebo-controlled trial: 14 received nebivolol (N: 8M/6F; 5 mg/d; age: 58±2 yr; BP: 142/86±2/2 mmHg), 15 received metoprolol succinate (M: 9M/6F; 100 mg/d; 57±2 yr; 139/87±2/2 mmHg), and 9 received placebo (P: 5M/4F; 1 gelatin capsule/d; 55±3 yr; 136/84±2/2 mmHg). Blood pressure was lowered (P<0.05) to a similar extent by both N (124/76
+
3/2 mmHg) and M (125/79
+
3/2 mmHg) but unchanged by P (133/80
+
3/2 mmHg). EMV phenotype was determined using markers indicative of endothelial activation (CD62e
+
) or apoptosis (CD31
+
/CD42b
-
) by flow cytometry. Circulating activation- and apoptosis-derived EMVs were significantly lower (~25%) after N (activation-EMVs: 68±7 to 48±6 EMV/μL; apoptosis-EMVs: 129±2 to 103±9 EMV/μl) and M (activation-EMVs: 57±5 to 39±3 EMVs/μL; apoptosis-EMVs: 125±4 to 96±9 EMV/μL) treatment. Placebo had no significant effect on EMVs (activation-EMVs: 61±7 to 57±6 EMV/μL; apoptosis-EMVs: 131
+
3 to 124
+
8 EMV/μL). There was no significant correlation between the reduction in either EMV phenotype and changes in blood pressure in the N or M group. These results demonstrate that both N and M treatment reduce circulating EMVs, and the reduction appears to be independent of changes in blood pressure. Lower circulating EMVs may contribute to the reduced risk of cardiovascular and cerebrovascular events associated with chronic N and M therapy.
Abstract P011: Usefulness Of Standing Office Blood Pressure In Detecting Hypertension In Untreated Adults
Authors: Giacona John M , Khan Ghazi , Wang Jijia , Pittman Danielle , Smith Scott A , Vongpatanasin Wanpen
Published: September 2022

Clinical guidelines recommend office blood pressures (BP) to be taken in a seated position. However, the accuracy of standing BP measurements for diagnosing hypertension (HTN) has not been investigated. We assessed BP in both seated and standing positions in 125 healthy adults not on anti-HTN medications. HTN 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 diagnosing HTN. 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 diagnosing HTN was derived using cut-off points derived from Youden’s Index. Our cohort’s mean age was 49 ± 17 years, with 62% female (77 of 125), and 24% Black (30 of 125). Prevalence of HTN was 33.6% (42 of 125). Sensitivity and specificity of seated SBP was 43% and 92%, respectively. Optimal cutoffs selected by Youden’s index for standing SBP/DBP was 124/81 mmHg. Sensitivity and specificity of standing SBP was 74% and 65%, respectively. The AUROC of standing SBP was significantly higher than seated SBP (BF =11.8), when HTN was defined as 24-Hr SBP ≥ 125 mmHg (Fig 1). Similarly, when HTN was defined as 24-Hr DBP ≥ 75 mmHg or daytime DBP ≥ 80 mmHg, the AUROC of standing DBP was higher than seated DBP (all BF >3). The addition of standing to seated BP improved HTN detection than seated BP alone based on 24-Hr SBP/DBP ≥ 125/75 mmHg or daytime SBP/DBP ≥ 130/80 mmHg (all BF >3). In conclusion, standing office BPs both alone and in combination with seated BPs, outperformed seated BPs in diagnosing hypertension in untreated adults.
Abstract P015: Characteristics And Care Of Inpatients With Orthostatic Hypotension
Authors: Wagner Benjamin A , Strauss Adam , Anderson Timothy , Juraschek Stephen P
Published: September 2022

Background:
Orthostatic hypotension (OH) contributes to over 80,000 hospitalizations annually, yet most studies of OH are conducted in outpatient settings. We sought to better characterize the causes, care, and course of OH in hospitalized patients in a large academic center.

Methods:
In this observational study, we reviewed 101 electronic medical records of adults with OH during admission to Beth Israel Deaconess Medical Center in Boston between January 1, 2017 and June 30, 2021, extracting details related to symptoms, etiology, interventions, blood pressure (BP), and post-hospital follow-up. OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mm Hg, respectively.

Results:
Of these patients (39.6% female, 9.9% Black, mean length of stay of 6.8 days), 30.7% had evidence of OH on initial presentation
(Table)
. While dizziness (32.7%) and lightheadedness (29.7%) were common, 19.8% of patients were asymptomatic. Volume resuscitation (64.4%), medication changes (53.5%), and physical therapy (24.8%) were the most frequent interventions. Among medication changes, reductions in beta blockers (37.0%) and loop diuretics (27.8%) were most common. On average, orthostatic systolic and diastolic BP improved by 7.9 and 3.0 mm Hg, respectively, and OH improved or resolved in 64.3% of patients. Within six months of discharge, 24.8% of patients had a subsequent encounter for OH.

Conclusion:
This study identifies important foci for further study of inpatient OH, including detection among asymptomatic patients, clinical practices focused on BP augmentation strategies (volume resuscitation, down-titration of beta blockers and loop diuretics), and high recurrence rates.
Abstract P018: A Little Goes A Long Way: Improving Blood Pressure Control Through A Loaner BP Cuff Program
Authors: Norwich Diana , Hatheway Clark , Chang Grace , Schafhalter-Zoppoth Ingeborg
Published: September 2022

Introduction:
Out-of-office blood pressure (BP) measurement is key to diagnosing and improving hypertension (HTN). Effective out-of-office BP measurements depend on owning a home BP device. By loaning BP cuffs to patients with HTN, we aimed to improve rates of BP control at our residency clinic by 10% in 12 months.

Methods:
Root Cause Analysis identified barriers to out-of-office BP testing. BP cuffs obtained via a QI grant were loaned to patients through our Hypertension Clinic. We also provided education on proper technique, lifestyle, and medication management. Patients were referred by residents and attendings, or recruited via telephone outreach targeting those with BP > 160 mmHg. Patients of the HTN clinic served as our experimental cohort. Workflows and outreach were revised via PDSA cycles. Resident engagement was assessed by survey.

Results:
In our experimental cohort, BP control for severe hypertension (<160 mmHg) improved from 76% to 84% and overall BP control (< 140 mmHg) from 47% to 54% at 5 months. For the whole clinic, BP control for severe hypertension improved from 85% to 91% at 1 month and 87% at 5 months; overall blood pressure control decreased from 75% to 67%. Surveyed residents reported regular follow up, medication titration and getting a BP cuff loaner as top reasons for referral.

Conclusions:
We successfully implemented a BP cuff loaner program within a hypertension clinic. Initial data shows improvement of severe and overall BP control for enrolled patients. The program was well-received by involved providers and patients. Providing BP cuff loaners is an effective low-cost intervention that improved BP control and decreases disparity for low-income patients.
Abstract P027: Yamaguchi Syndrome Presenting With Atrial Fibrillation And Heart Failure Diagnosed With Contrast Echocardiography
Authors: Osman Abdul-Fatawu , Jamal Shakeel Muhammad , Banga Sandeep , Baloch Zulfiqar , Sheikh Ali
Published: September 2022

Yamaguchi syndrome or apical hypertrophic cardiomyopathy (ApHCM), is a rare variant of hypertrophic cardiomyopathy (HCM), prevalence of about 3% among HCM population in the United States. Generally considered a benign condition but can be potentially life-threatening.

A 84 year old female with history of mitral regurgitation with mitra-clip, paroxysmal atrial fibrillation (pAF) presented to ED with dyspnea and leg swelling. She was tachypneic with bibasilar rales, jugular venous distention. BNP 1,086 pg/l with cardiomegaly and pulmonary edema on chest x-ray.

She was managed for acute decompensated cardiac failure (NYHA class III) using IV furosemide with symptom improvement. EKG revealed AF with abnormal deep T-wave inversion most prominent in precordial leads (V4-V6). Contrast echocardiogram revealed ApHCM, missed on prior echocardiograms. Patient’s dose of metoprolol was doubled, and outpatient follow-up was scheduled.

Conclusion:
ApHCM commonly presents with heart failure symptoms, chest pain, palpitation, or syncope. Undiagnosed/untreated ApHCM can lead to complications including diastolic dysfunction, left atrial enlargement causing atrial fibrillation, apical clots formation with subsequent thromboembolism, ventricular wall aneurysm, arrhythmias, and myocardial infarction. In our case, contrast echocardiogram was able to diagnose ApHCM. A presentation of heart failure symptoms at NYHA class II or higher is a known predictor of poor prognosis in patients with ApHCM. Missing diagnosis on normal echocardiogram without use of ultrasound contrast is very common. Diagnosing with proper use of modality can help to improve outcomes in these patients.
Abstract P037: Impact Of Protein Energy Malnutrition On Inpatient Outcomes Of Hypertensives Emergencies : Insight From The National Inpatient Sample
Authors: Khanal Smriti , Kannayairam Sandhya , Karki Sadichhya , Poudyal Abhushan , Park Dae Yong
Published: September 2022

Introduction:
Protein energy malnutrition (PEM) is associated with adverse clinical outcomes for various cardiac diseases, but its effect on outcomes of hypertensive emergencies (HTNE) has not been studied. We examined the impact of PEM on in-hospital outcomes of HTNE using the largest inpatient database in the United States.

Methods:
We reviewed the National Inpatient Database from 2017 to 2018 to identify admissions for HTNE and stratified them to those with PEM (PEM+) and without PEM (PEM-). Multivariable logistic regression was used to compare categorical and continuous variables after adjusting for confounders. Primary outcome included in-hospital mortality. Secondary outcomes included mean length of stay (LOS), total hospital charge (THC), and acute kidney injury (AKI).

Results:
Of 749,115 admissions with HTNE, 34,555(4.6 %) had PEM. A total of 27,855 (3.72%) deaths were observed inpatient for HTNE. Among PEM + cohort, 2,310 of 34,555 (6.68 %) died compared with 25,545 of 714,560 (3.57 %) among PEM- cohort [AOR 1.29, 95% CI 1.17-1.45, p<0.001]. Both LOS (7 days,95% CI [6.63]-7.38, p<0.001) and THC ($86,928, 95% CI [61,632]-74,831, p<0.001) were significantly higher in PEM + cohort. PEM + cohort also had higher odds of AKI [5360 of 35,555(44.5%) vs 22,950 of 714,560 (31.12%);(AOR 1.39, 95% CI 1.31-1.46, p<0.001)].

Conclusion:
Concomitant diagnosis of PEM in HTNE is associated with higher odds of in-hospital mortality and AKI . It also increases burden on healthcare.Higher vigilance and early risk stratification may be important for better outcomes in HTNE admissions with PEM. Further prospective studies are required to evaluate the measures to mitigate negative outcomes.
Abstract P044: Associations Between Depression And Hypertension Among Women And Men Veterans
Authors: Chang Tiffany E , Gaffey Allison E , Brandt Cynthia , Lichtman Judith H
Published: September 2022

Background:
Hypertension increases the risk of cardiovascular disease. Literature describing associations between depression and blood pressure is inconsistent, potentially due to differing associations by sex. Veterans have high burdens of both depression and hypertension, respectively, and thus are a critical population in which to understand possible individual differences. Thus, among Veterans, we estimated the association between depression and hypertension and determined if this differs by sex.

Methods:
We used 2001-2017 nationwide Veterans Health Administration data from Veterans who served in support of conflicts in Afghanistan and Iraq. Major depressive disorder (MDD), mild depression, or no depression (reference group) were defined based on ICD-9/ICD-10-CM codes. Multivariable logistic regression models tested if depression status (independent variable) affected the risk of hypertension (dependent variable; defined as ≥2 blood pressure readings ≥140 systolic or ≥90 diastolic), controlling for sociodemographic factors, smoking, and comorbid mental health conditions. The adjusted model was also stratified by sex.

Results:
Among 761,627 Veterans (13.0% women; median age [interquartile range]= 29.5 [25.2-39.2] years), 24.1% had MDD, 18.8% mild depression, and 57.1% no depression. MDD was more prevalent for women than men (32.4% vs. 22.8%;
p
<0.001). Hypertension was more common among Veterans with MDD (48.6%), compared to those with mild depression (40.7%) or no depression (28.0%;
p
<0.001). In adjusted analyses, those with MDD had a 2.46xgreater risk of hypertension (95% CI, 2.43-2.49) and those with mild depression had 1.76xgreater risk (95% CI, 1.73-1.78) vs. those with no depression. In sex-stratified analyses, adjusted odds ratios were similar for women and men (MDD: 2.43 for women, 2.46 for men; mild depression: 1.74 for women, 1.75 for men).

Conclusion:
Both major and minor depression are associated with an increased risk of hypertension, with similar risk observed for women and men. Given the high burden of both depression and hypertension in this younger population, the potential long-term health implications of these conditions may warrant targeted intervention to prevent cardiovascular disease.
Abstract P046: The Association Of Sex And Gender With Disordered Eating Behavior In Youth With Hypertension
Authors: Borra Gagana , Perrin Ella , Ravi Hanna , South Andrew M
Published: September 2022

Background:
DEB (disordered eating behavior) prevalence in adolescents has been increasing steadily. Females generally have a higher prevalence compared to males in the general population, but data do not exist in adolescents with HTN, a condition that requires lifestyle counseling and is more common in males. Finally, the difference in the risk of DEB conferred between sex, a biological construct, and gender, a self-identified construct, is characterized poorly, especially in youth with HTN.

Objective:
Determine the association of sex and gender with DEB prevalence in adolescents with HTN disorders.

Hypothesis:
Females will have a higher prevalence of screening positive for DEB compared to males regardless of if defined by sex or gender.

Design/Methods:
This was a secondary analysis of a prospective cross-sectional study of adolescents aged 11-18 years with HTN disorders. We excluded patients with diabetes mellitus, kidney failure or transplantation, or gastrostomy tube dependence. We collected data via electronic health record abstraction and surveys, including the validated SCOFF DEB screening questionnaire, with a score ≥2/5 as positive, as well as self-reported sex, defined as assigned at birth, and gender, defined as that with which the participant identifies. We compared DEB prevalence by sex and gender using bivariate generalized linear models; our directed acyclic graph identified no variables in the adjustment set.

Results:
Of 74 participants, 59% (44/74) identified as male and 41% (30/74) identified as female. One participant whose sex was male declined to answer the gender question. DEB prevalence overall was 28% (21/74); it was 20% (9/45) in males and 41% (12/29) in females by both sex and gender. Females had double the risk of DEB compared to males, when defined by sex (adjusted RR 2.07, 95% CL 0.9996 to 4.28), or gender (adjusted RR 2.02, 95% CL 0.98 to 4.18). However, our findings did not meet statistical significance at
p
<0.05.

Conclusions:
Among adolescents with HTN disorders, females had double the risk of screening positive for DEB compared to males by both sex and gender. Adolescents with HTN may benefit from routine DEB screening, especially those that identify as female.
Abstract P050: Loss-of-function Cyp4a11 Variants Are Associated With Apparent Treatment Resistant Hypertension Identified In Electronic Medical Records; In The VA Million Veteran’s Program And Vanderbilt’s BioVU
Authors: Shuey Megan M , Hellwege Jacklyn , Hung Adriana M , Edwards Todd L , Brown Nancy
Published: September 2022

Excessive dietary salt intake is common in patients with and salt-sensitivity contributes to the pathophysiology of resistant hypertension. Dietary salt intake regulates the excretion of 20-HETE and patients with salt-sensitive hypertension have a disrupted relationship between 20-HETE and sodium excretion. We hypothesized that rs1126742, a loss-of-function variant in the gene
CYP4A11
encoding the enzyme responsible for the formation of 20-HETE, as well as a more common variant rs3890011, in partial linkage disequilibrium with rs1126742, would be associated with apparent-treatment resistant hypertension (ATRH). To test this hypothesis, we used the Department of Veteran Affairs Million Veterans Program dataset derived from electronic medical records. Patients with ATRH (cases, n=16,833), defined as uncontrolled BP of at least 140/90 mmHg despite the concurrent use of three antihypertensive medications including a thiazide diuretic or patients on four or more antihypertensive medications including a thiazide diuretic, and patients with controlled BP (controls, n=53,931) less than 135/90 mmHg on one or two antihypertensive medications were identified from the dataset using electronic algorithms. Within this population we found that there was a significant association between both rs1126742 and rs3890011 and ATRH (β=0.04, p=0.02; β=0.05, p<0.001, respectively). When we stratified the population by race, rs3890011 was significantly associated with ATRH in both whites and blacks (β=0.04, p<0.001 and β=0.06, p=0.02, respectively) while rs1126742 was associated with ATRH in blacks (β=0.07, p=0.01) but not whites. To validate these findings, we sought replication in an independent site, the Vanderbilt University Medical Center’s BioVU, a DNA databank linked with electronic medical records. We identified white patients with ATRH (n=2,998) and controlled hypertension (n=934), defined as patients with BP controlled to less than 140/90 mmHg by a single antihypertensive medication. The previous associations in whites were replicated; rs3890011 (β=0.43, p=0.02) was significantly associated with resistant hypertension while rs1126742 was not. Our findings support an association between these
CYP4A11
loss-of-function variants and ATRH.
Abstract P051: Hypertension Is Associated With All-cause Mortality In Caucasians But Not African Americans With Suspected Cardiac Amyloidosis
Authors: Manjunath Sonakshi , Deych Elena , Lenihan Daniel , Zhang Kathleen
Published: September 2022

Background:
Diagnostic delay is common among patients with cardiac amyloidosis. Hypertensive heart disease is a known echocardiographic mimic of cardiac amyloidosis, with greater prevalence among African Americans than among Caucasians. The association between hypertension and clinical outcomes in patients with suspected cardiac amyloidosis is not known.

Objective:
We sought to determine the association between a known diagnosis of hypertension and all-cause mortality in African Americans and Caucasians with suspected cardiac amyloidosis.

Methods:
We identified 230 patients who underwent cardiac biopsy for suspected cardiac amyloidosis at our institution between 2000-2018. Clinical and demographic data were obtained from the medical record. Echocardiograms performed at the time of cardiac biopsy were interpreted by study personnel. All-cause mortality was assessed using the Social Security Death Index.

Results:
Among 230 patients with suspected cardiac amyloidosis, hypertension was more common among African Americans (71 of 91, 78%) than among Caucasians (73 of 139, 52%). Over a median follow-up period of 4.5 months, the all-cause mortality rate was higher among Caucasians with hypertension (67%) than Caucasians without hypertension (42%, p= 0.048). There was no difference in all-cause mortality rate among African Americans with and without hypertension (47.8% vs. 50%, p=0.903). Among Caucasians, those with hypertension had increased posterior wall thickness, relative wall thickness, and interventricular septal thickness as compared to those without hypertension (p<0.01 for all). There were no significant differences in these parameters among African Americans with and without hypertension (p>0.05).

Conclusions:
Hypertension and the hypertensive echocardiographic phenotype are associated with all-cause mortality in Caucasians but not African Americans with suspected cardiac amyloidosis. Additional study is needed to understand the differential effects of hypertension on clinical outcomes by racial category in patients with suspected cardiac amyloidosis.
Abstract P053: Causes And Predictors Of Readmission In Hypertensive Emergency - A Nationwide Inpatient Analysis
Authors: Ahmed Ibrahim , Amoateng Richard
Published: September 2022

Introduction:
Hypertensive emergency (HE) is a common medical emergency requiring inpatient admission. Our aim was to characterize HE patient demographics and analyze the factors that increases the likelihood for HE readmissions.

Methods:
This was a retrospective cohort study using the 2019 Nationwide Readmissions Database to identify admissions in adults with a diagnosis HE. Regression models were used. Primary outcome was all-cause 30-day readmission rate, mortality rate, causes and predictors for readmission.

Results:
Out of a total of 56,648 admissions with HE, 7,753 were readmitted, with a readmission rate of 13.72%. The most common causes for readmissions were CHF exacerbation in setting of CKD stage 1-5 11.51% (892 of 7753), hypertensive emergency 11.48% (890 of 7753), hypertensive urgency 7.92% (614 of 7753), AKI 4.67% (362 of 7753), Sepsis 3.12% (241 of 7753), NSTEMI 2.44% (189 of 7753), and ischemic CVA 1.79% (139 of 7753). Compared to index admissions, readmissions had higher mortality rate (1.39% vs 0.35%), LOS (5.13 days vs 3.65 days), and total charge ($58,172.50 vs $42,273.43). See table 1 for index admission group demographics. The top predictors for readmissions were, reported in odds ratio, ESRD 3.43, hypertension 2.30, discharged AMA 2.29, diabetes mellitus 1.92, transfer to nursing facility 1.5, drug abuse 1.40, depression 1.28.

Conclusion:
HE has a high readmission rate of 13.72% with the most common cause for readmission being CHF exacerbation, followed by recurrence of HE, AKI, sepsis, NSTEMI, and ischemic CVA. The best predictor for HE readmission was ESRD, followed by hypertension, discharged AMA, and diabetes mellitus.
Abstract P057: Adipocyte Progenitor Cells In Perivascular Adipose Tissues: The Effect Of Sex And Anatomical Location
Authors: Rendon Mora Cristian J , Flood Emma D , Watts Stephanie W , Contreras G A
Published: September 2022

Perivascular adipose tissue (PVAT) modifies vascular function due to its capacity to synthesize vasoactive products and its mechanical properties. During cardiovascular diseases (CVD), changes in adipocyte populations affect PVAT function. In obesity, expansion of adipose tissue (AT) differs between sex in rodents and humans in a site-dependent manner. Consequently, men are more susceptible to obesity-associated hypertension. However, how adipocyte progenitors (APC) contribute to those differences in PVAT depots is currently unknown. Our objective was to evaluate the distribution of APCs among different AT sites in both sexes under normotensive conditions using a genetic lineage tracing mouse model. We hypothesize that APC population distribution is affected by sex and anatomical location. PVAT from abdominal (abPVAT) and thoracic (atPVAT) aorta, mesenteric arteries (mesPVAT), and non-PVAT subscapular (BAT), perigonadal (GON), and subcutaneous (SCAT) were collected from 30-week-old female and male double transgenic mice (
PDGFRa
-CreER
T2
/R26-LSL-tdTomato; n=13). In this model, tamoxifen administration (5d, 150 mg/kg) induces
PDGFRa
+
cells well-defined APC populations, to express the fluorescent tdTomato reporter. To harvest APC, AT was minced, digested [Liberase™ (50μg/ml)] for 1hr at 37°C, and then filtered with a 40μm cell strainer. The cell suspension was incubated with conjugated antibodies anti CD45, and CD31. Zombie NIR was used to exclude dead cells. Next, flow cytometry was performed to determine APC population distribution defined as CD45
-
, CD31
-
, and tdTomato
+
; results are shown as % APC±SEM. PDGFRα
+
are present in all AT tissues. Among PVAT sites, abPVAT had fewer APC (1.17±0.25) compared with GON (5.6±0.25; P<0.05). APC populations in BAT (5.61±0.23), atPVAT (2.74±0.23), MesPVAT (3.72±0.25), and SCAT (2.65±0.25) did not differ. There were no sex differences in APC populations in PVAT; however, in GON, males (1.28±0.75; n=4) had fewer APC compared to females (9.92±0.31; n=9) (P<0.01). These data show that APC is in a lower proportion in abPVAT than in other depots, which can clarify the underlying process of differences in PVAT expansion; our future experiments will study how APC can be affected by hypertensive conditions.
Abstract P059: Carotid Artery Stiffness Is Elevated In Young Hypertensive Rats Relative To Age-matched Normotensive Rats
Authors: Brown Elili , Graham Wayne , Diz Debra I , Cruz-Diaz Nildris
Published: September 2022

Hypertension has a bidirectional relationship with arterial stiffening, a hallmark feature that reduces vascular compliance, resulting in increased blood velocity, disruptions to laminar flow, and target organ injury. Our prior studies in transgenic hypertensive (mRen2)27 rats document age-related sex differences in cardiac dysfunction associated with cerebrovascular changes that develop earlier in males than females. Both sexes develop cardiac dysfunction and cerebrovascular damage by 1 year of age. The current objective was to determine systolic blood pressure (SBP) and arterial stiffness (AS) in both the carotid artery and aortic arch in young adult male and female (mRen2)27 versus normotensive Sprague Dawley (SD) rats. SBP was measured at 20 weeks of age via tail-cuff, to which rats were acclimated prior to measurements. AS data was obtained from transthoracic echocardiograms using the Vevo 2100 LAZR ultrasound. Data are presented as mean ± SEM; t- tests were conducted using GraphPad Prism 8 (p<0.05 considered significant). SBP was higher in both male (182 ± 3 mm Hg) and female (184 ± 7 mm Hg) (mRen2)27 rats compared with male (136 ± 5 mm Hg) and female (121 ± 5 mm Hg) SD rats. AS was significantly higher in the aortic arch of female (mRen2)27 rats: 5.9 ± 0.6 mm/ms compared with 2.8 ± 0.6 mm/ms for SD female rats. In male (mRen2)27 rats, aortic arch stiffness was 5.1 ± 0.5 compared with 3.5 ± 0.1 for SD male rats. The carotid artery was significantly stiffer in both male and female (mRen2)27 rats versus the SD control rats: female (mRen2)27, 6.9 ± 0.6 mm/ms, versus female SD, 2.6 ± 0.5 mm/ms; male (mRen2)27, 4.1 ± 0.2 mm/ms, versus male SD rats, 3.0 ± 0.2 mm/ms. Our findings suggest that young adult hypertensive rats, regardless of sex, exhibit greater AS relative to normotensive rats. While the increased carotid stiffness could contribute to cerebrovascular damage, further studies at different time points in both sexes are necessary to understand the mechanisms involved in the development of AS and the relationship, if any, to the sex differences in progression of cerebrovascular disease.
Abstract P062: Interaction Of Cytochrome P450 1B1 And 12/15 Lipoxygenase In Paraventricular Nucleus In The Regulation Of Angiotensin II-induced Hypertension In Female Mice
Authors: Dutta Shubha R , Singh Purnima , Song Chi Young , Shin Ji Soo , Malik Kafait U
Published: September 2022

Recently, we showed that 17β-estradiol (E2)-cytochrome P450 (CYP) 1B1-generated metabolite 2-methoxyestradiol (2-ME) in the paraventricular nucleus (PVN) protects from angiotensin (Ang) II-induced hypertension. Moreover, we showed that 2-ME produces this action by inhibiting the cytosolic phospholipase (cPLA)
2
α/arachidonic acid (AA)-cyclooxygenase (COX)-generated metabolites prostaglandin (PG)E
2
and thromboxane (TX)A
2
exerting prohypertensive effects via prostanoid receptors EP1, EP3, and TP, respectively, in female mice. 12/15 lipoxygenase (ALOX15), which also metabolizes AA, is present in the brain in neural tissue, endothelial cells, microglia, and astrocytes. This study was conducted to determine the contribution of central 12/15 lipoxygenase (ALOX15) and its relationship to CYP1B1 in Ang II-induced hypertension in the female mice. ALOX15 knockdown in the PVN by transduction with adenovirus (Ad)-ALOX15-short hairpin (sh)RNA (200 nL, bilaterally 7.04х10
11
pfu/mL) but not its control Ad-scrambled (Scr)-shRNA (6.4х10
11
pfu/mL) produced a greater reduction in systolic blood pressure (SBP, mmHg) measured by tail-cuff in response to Ang II (700 ng/kg/min, subcutaneous, osmotic pump, two weeks) in intact
Cyp1b1
knockout (KO, E2 present but lacking 2-ME) than wild-type (WT, endogenous E2 and 2-ME present) female mice (Day 12: 177±4 vs 143±1 and 133±3 vs 124±1, respectively, P<0.05, n=4/group). Moreover, administration of ALOX15-generated AA metabolite 12(S)-hydroxyeicosatetraenoic acid (HETE) in a dose (50 ng/ 2 μL/ every 3rd day, intracerebroventricularly) that did not alter the mean arterial pressure (MAP) alone produced a greater increase in MAP in response to Ang II in ovariectomized (both E2 and 2-ME are lacking) than intact
Alox15
KO female mice (Day 0 vs Day 12: 103±4 vs 167±2 and 103±2 vs 128±1, respectively, P<0.05, n=4/group). These results suggest that E2, via its CYP1B1-derived metabolite 2-ME, inhibits the generation of ALOX15/AA metabolite 12(S)-HETE in the brain to protect against Ang II-induced hypertension in female mice. Thus, 2-ME and/or ALOX15/12(S)-HETE inhibitors could be useful for treating hypertension and its pathogenesis in females.
Abstract P064: Anatomical Substrate For Leptin Control Of Central Autonomic Network Regulating Cardiovascular And Metabolic Functions
Authors: Williams Paul , Guo Deng-Fu , Olson Alexis , Rahmouni Kamal
Published: September 2022

Leptin, a hormone secreted by adipose tissue, is a critical signal influencing energy balance and blood pressure through modulation of the autonomic nervous system. However, the anatomical substrates for leptin regulation of the central autonomic network underlying cardiovascular and metabolic functions remains unknown. Here, we used a retrograde pseudorabies virus encoding a green fluorescent protein (PRV-GFP) in mice expressing a red fluorescent (td-Tomato) in leptin receptor (LepR) neurons to map the LepR neurons that project polysynaptically to the kidneys, the left lobe of the liver, or the interscapular brown adipose tissue (iBAT). The animals were sacrificed at 5-, 6-, or 7-days post-PRV injection, the brain imaged using confocal microscopy, and co-localization quantified. We identified approximately 100 nuclei containing LepR neurons and more than 60 nuclei expressing GFP after PRV-GFP inoculation of the kidney, liver, or iBAT. Interestingly, 42 nuclei that express LepR neurons (tdTomato) also express GFP after PRV-GFP inoculation of either kidney, liver, or iBAT. Of these shared nuclei, we observed co-expression of tdTomato and GFP in only a few nuclei. After inoculation of PRV-GFP into kidneys, 25% of GFP expressing neurons in the preoptic (PO) nucleus co-localized with tdTomato while 3% co-localization was noted in the lateral hypothalamus (LH), and 1% in the nucleus of the solitary tract (nTS). For the liver, 35% co-localization was observed in the PO and 2.5% in the LH. For the iBAT, 20% co-localization was seen in the PO, 1.5% in the LH, and 8% in the nTS. Co-localization was also observed in other areas such as the septal nucleus, arcuate nucleus, dorsal and ventral medial hypothalamus, periaqueductal gray, and ventral tegmental area. In summary, LepR neurons projecting to the kidney, liver, or iBAT are present in specific regions such as the preoptic nuclei, some hypothalamic areas, and the nTS with the level of co-localization dependent on the organ. Our data suggest that although LepR neurons are distributed throughout the brain, those associated with the autonomic networks controlling cardiovascular and metabolic functions reside in specific regions of the brain.
Abstract P081: Early Life Stress (ELS) Induces Greater Aortic Pulse Wave Velocity (PWV) Through Reactive Oxygen Species (ROS)
Authors: Kellum Cailin E , Cruz-Ojeda Felix , He Lihao , Xie Min , Pollock Jennifer
Published: September 2022

ELS, such as verbal and physical abuse or maltreatment, is linked to a greater risk ofcardiovascular disease (CVD) in adulthood. Aortic stiffness, an independent predictor of CVD,has been suggested as a prognostic tool for early detection and intervention in at-riskpopulations. Several human studies have shown that aortic stiffness (assessed by PWV) isincreased in both adults and adolescents with ELS. ELS mouse models, such as maternalseparation with early weaning (MSEW), show aortic endothelial dysfunction with increasedsuperoxide and systemic inflammation, which are both present in humans with ELS exposureand contribute to aortic stiffness. We hypothesized that MSEW mice develop aortic stiffness in aROS-dependent manner at an early age. The MSEW protocol entails separating pups from thedam 4h/day (postnatal, PD 2 to 5) and 8h/day (PD 6 to 16) followed by weaning at PD17.Normally-reared (NR) litters remain with the dam and are weaned at PD21. Female and maleMSEW and NR mice were treated for 2 weeks with the ROS scavenger, TEMPOL (30mg/kg/day; drinking water) from 8 weeks of age. PWV was assessed prior to and after TEMPOLtreatment. PWV was significantly increased in MSEW mice at baseline (NR: 1.95 mm/sec ±0.15, MSEW: 2.60 mm/sec ± 0.17, p=0.009) in both sexes similarly. PWV was not significantlydifferent between MSEW and NR mice after TEMPOL treatment (NR: 1.78 mm/sec ± 0.06,MSEW: 1.97 mm/sec ± 0.12, p<0.05). MSEW mice had significantly more aorticCD11b
+
Ly6C
+
CX3CR1
+
inflammatory monocytes compared to NR mice (NR: .9% ± 0.31,MSEW 1.5% ± 0.25, p=0.014) at baseline, however TEMPOL did not affect this. TEMPOLtreatment significantly decreased CD11b
+
F4/80
+
MHCII
hi
inflammatory resident macrophages inMSEW mice compared to NR mice (Median Fluorescent Intensity; NR: 1,235,274 ± 54413,MSEW : 944,446 ±11728, p=0.007). In conclusion, ELS induces increased aortic stiffness in aROS-specific manner at an early age. Inflammatory resident macrophages may contribute to theELS-specific ROS-dependent mechanism. The mechanisms identified in this work arepotentially powerful tools for preventative therapeutics to reduce CVD burden in ELS-populations.
Abstract P087: Metformin Treatment Decreases Blood Pressure But Does Not Ameliorate Hypertensive Cardio-Renal Damage In A Double Transgenic Rat Model
Authors: Wimmer Moritz I , Bartolomaeus Hendrik , Chen Chia-Yu , Kedziora Sarah , Vecera Valentin , Potapenko Olena , Bartolomaeus Theda , Jarquindiaz Victor H , Loeber Ulrike , Haase Nadine , Forslund Sofia Kirke , Mueller Dominik N , Wilck Nicola
Published: September 2022

Introduction:
Metformin (Met) is used as a first-line treatment in type II diabetes, reduces the cardiovascular (CV) risk in diabetes and may lead to decreased CV mortality independent of diabetes status. Met treatment has been shown to induce gut microbiome changes leading to enhanced production of protective short-chain fatty acids and potentially harmful metabolites (LPS). Our study aims to examine the effects of Met in a model of RAAS-mediated hypertension with cardio-renal damage.

Methods:
Four-week-old double transgenic rats (dTGR, transgenic for human renin and angiotensinogen) received oral Metformin (Met) or Vehicle (Veh) for 3 weeks. SD rats served as healthy controls. Flow cytometry (n=10 per group), echocardiography (n=14), radiotelemetric blood pressure (BP) measurements (n=5), clinical chemistry and gene expression analyses (n=14) were used to assess damage to kidney and heart.

Results:
Met treatment did not influence survival nor lead to lactate acidosis. Met treatment lowered BP significantly (systolic BP: Met: 218±5 mmHg, Veh: 237±3 mmHg). Interestingly, the decreased BP was accompanied by increased cardiac hypertrophy (heart weight to tibia length, SD: 34±1 g/m, Met: 40±1 g/m, Veh: 37±1 g/m). Echocardiographic systolic and diastolic function was deteriorated (EF: Met: 64±2 %, Veh: 68±4 %; E/A: Met: 0.75±0.1, Veh: 0.93±0.1). Plasma BNP and cardiac ß-to-α MHC ratio were higher in Met-treated dTGR. Intestines, spleens, kidneys and hearts of dTGR showed a strong pro-inflammatory phenotype with increased adaptive (e.g. cardiac T cells % of leucocytes: (SD: 10±0.003 %, Met: 15±0.01 %, Veh: 13±0.01 %) and innate (e.g. cardiac monocytes % of leucocytes: (SD: 2±0.001 %, Met: 3±0.004 %, Veh: 5±0.02 %) immune cell subsets in comparison to SD rats; with almost no differences between Met- and Veh-treated dTGR. Fecal metagenomic shotgun sequencing showed no large-scale taxonomic shifts between Veh- and Met-treated dTGR.

Conclusion:
dTGR display a pronounced pro-inflammatory immunophenotype across several organs. Met did not ameliorate hypertensive target organ damage in dTGR despite the BP lowering effect. These findings could help to understand the effects of Met on the microbiome, immunome and organ damage in the context of hypertension.
Abstract P094: Prevalence Of Polycystic Ovary Syndrome In Youth With Hypertension Disorders
Authors: Costa Claudia , Patel Paula , Constantacos Cathrine , Hunter Janel , South Andrew M
Published: September 2022

Introduction:
While Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among adolescent females, it continues to be underdiagnosed and understudied. In particular, it is unknown whether youth with HTN may have a greater undiagnosed burden of PCOS compared to the general adolescent population. Patients with PCOS are at an increased risk for reproductive morbidities, hormone-dependent cancer, and metabolic and cardiovascular diseases. Furthermore, the relationships between metabolic syndrome (MBS) or obesity and PCOS in patients with HTN have not been fully investigated.

Objectives:
To estimate the prevalence of PCOS in adolescent females with HTN and investigate whether MBS and obesity increase this risk.

Methods:
This is an ongoing prospective cross-sectional study that has enrolled 12 of 40 participants to date. Inclusion criteria are females 10-18 years with HTN disorders of any cause and menarche for ≥2 years. Exclusion criteria are CAH, ovarian or pituitary cancer, Cushing syndrome, pregnancy, and a diagnosis of PCOS prior to HTN diagnosis. Data are collected via EHR abstraction and administered questionnaires, and include demographics, past medical, menstrual, and fertility histories, blood pressure, and physical characteristics including height, weight, and waist circumference. Our power and sample size calculations, made a priori, are based on estimating the difference in our population’s hypothesized PCOS prevalence (p1=0.25) with that of the general adolescent female population (p0=0.1) using the one-sample z-test of proportions. We will also use multivariable generalized linear models to estimate the risk of PCOS due to MBS or obesity.

Results:
The median systolic and diastolic blood pressures are 122.7 mmHg [113.8, 128.0] and 72.5 mmHg [68.8, 76.6]. The median waist circumference is 80.7 cm [76.5, 95.6]. The prevalence of PCOS is 17% (2/12), while 8% (1/12) have MBS and 58% (7/12) have obesity.

Discussion:
We are continuing to enroll new participants to reach our target enrollment of 40. Our results have the potential to educate clinicians to consider screening for PCOS in adolescent females who present with HTN to allow for prevention of the comorbidities associated with PCOS and to guide HTN treatment.
Abstract P095: Arginine Vasopressin Infusion Is Sufficient To Cause Pregnancy-specific Cardiac Hypertrophy
Authors: Schickling Brandon M , Gumusoglu Serena , Santillan Donna A , Santillan Mark K
Published: September 2022

Preeclampsia is a prevalent gestational disorder characterized by hypertension, proteinuria, and renal damage. Mothers with a history of preeclampsia (PE) are at increased risk of future cardiovascular disease (CVD). Yet, the mechanism by which preeclampsia predisposes patients to future CVD is unknown. Previously published data demonstrated that arginine vasopressin (AVP) infusion in mice recapitulates clinical features of PE including pregnancy-specific hypertension. We hypothesized that chronic AVP infusion in pregnant mice would cause cardiac hypertrophy. C57Bl6/J mice were implanted with an osmotic minipump to deliver 24ng/hr of AVP throughout gestation until necropsy on gestational day 18. Blood pressures were monitored by tail cuff plethysmography and showed no increase in mean arterial pressure (MAP) in nonpregnant mice. However in pregnant mice, an increase of 18.8 ± 7.4 mmHg (82.1 vs 100.8, p=0.05) in MAP was observed in AVP-infused mice compared to saline-infused pregnant mice. Similarly, there was pregnancy-specific 13.4 ± 0.9 mg (93.6 vs 106.9, p=0.0001) increase in the heart weight of AVP-infused mice. Plasma levels of NT-ProBNP were measured by ELISA and showed a significant 163.6 ± 61.00 pg/ml (426.0 vs 589.6, p=0.01) increase in pregnant AVP-infused mice. Human 3rd trimester maternal plasma samples were obtained from the Iowa Maternal Fetal Tissue Bank (IRB# 200910784) for a case control study. In plasma samples from preeclamptic patients there was a significant 264.6 ± 79.72 pg/ml (185.1 vs 449.8, p=0.001) and a 27.9 ± 11.5 pg/ml (64.6, n=32 vs 92.5, n=66, p=0.02) increase in NT-ProBNP and MR-proANP respectively compared to normal pregnancy plasma. H9C2 rat cardiomyocytes treated with pooled plasma from preeclamptic patients showed a 6.6 and 1.8 fold increase in rat ANP and BNP expression respectively. These data suggest that AVP infusion in mice specifically during pregnancy is sufficient to cause cardiac hypertrophy beyond typical hypertrophy seen in a normal pregnancy and that unknown circulating factors in preeclamptics may contribute to the development of hypertrophy. Importantly, these data support using AVP-infusion as a novel mouse model of pregnancy-specific cardiac hypertrophy to study postpartum cardiomyopathies.
Abstract P098: Association Between Postpartum Sleep Characteristics And Twenty-four Hour Blood Pressure Patterns In Women With And Without A History Of Preeclampsia
Authors: Nuckols Virginia , Guerrero Mariah , Stroud Amy , Santillan Mark K , Pierce Gary L
Published: September 2022

Introduction:
Women with a history of preeclampsia (hxPE), a hypertensive pregnancy disorder, are at a four-fold elevated risk of chronic hypertension postpartum compared with healthy pregnancy. The postpartum period is particularly vulnerable to adverse sleep characteristics such as poor sleep quality and frequent sleep disturbances, which are associated with hypertension risk. However, the relation between postpartum sleep characteristics, nighttime blood pressure (BP) and diurnal BP variation assessed by twenty-four hour ambulatory BP monitoring is not well-studied.

Methods:
Women with a hxPE (N=13, age 37 ± 5 years) and healthy pregnancy controls (N=12, 36 ± 3 years) without history of sleep disorders were enrolled between 1-5 years postpartum (2.9 ± 1.3 years). Subjective sleep characteristics were reported using the Pittsburgh Sleep Quality Index (PSQI). Ambulatory BP monitoring was conducted to measure 24-hour, day and night BP as well as nocturnal BP dipping and morning BP surge quantified by sleep-trough surge.

Results:
Women with a hxPE tended to report poorer global sleep quality (7 ± 3 vs 5 ± 3 PSQI score, P=0.09) related to more frequent sleep disturbance (8 ± 4 vs 5 ± 3 score, P=0.053) without differences in habitual sleep duration (7 ± 1 vs 7 ± 1 hours, P=0.37) or sleep latency (18 ± 11 vs 17 ± 9 min, P=0.89). In the entire group, frequency of sleep disturbance was associated with greater 24-hour BP (systolic: r = 0.42, P=0.046; diastolic: r = 0.43, P=0.04) but not night BP (systolic: r = 0.19, P=0.40; diastolic: r = 0.19, P=0.40). Only sleep latency was related to blunted nocturnal BP dipping % (r = -0.38, P=0.08), and no sleep characteristics were associated with augmented morning BP surge.

Conclusions:
Women with a hxPE reported poorer overall sleep quality compared with healthy pregnancy controls 1-5 years postpartum, particularly frequent sleep disturbances. Frequency of sleep disturbance was associated with elevated 24-hour BP, but not higher nighttime BP or attenuated nocturnal BP dipping, indicating that the impact of postpartum sleep characteristics on BP is not attributable to diurnal BP variation.