bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P308: Leucine Rich Repeat Containing 8A Anion Channels Modulate Vasodilation In Angiotensin II-induced Hypertensive Mice
Authors: Choi Hyehun , Nguyen Hong N , Lamb Fred S
Published: October 2023

Leucine Rich Repeat Containing 8 (LRRC8) family proteins (LRRC8A, B, C, D and E) comprise Volume-regulated anion channels (VRACs) which are activated by tumor necrosis factor alpha (TNFα) and angiotensin II (AngII). We have previously investigated vascular reactivity in mesenteric arteries from male wild type (WT) and smooth muscle-specific LRRC8A knockout (KO) mice. KO vessels displayed enhanced responsiveness to both endothelium-dependent (acetylcholine, ACh), and independent (sodium nitroprusside, SNP) vasodilators. We hypothesized that LRRC8A KO mice would be protected from AngII-induced hypertension. Blood pressure (BP) was measured by radiotelemetry. Resting BP was unaltered compared to WT and AngII infusion by osmotic minipump (alzet, 90 ng/min for 14 days) induced a similar degree of hypertension in awake mice (nighttime) but the difference between day and night pressures was significantly larger in KO mice. Mesenteric arteries were isolated from WT and KO mice after 14 days and vascular reactivity was quantified by wire myograph. Relaxation responses to both ACh and SNP relaxation were impaired in AngII hypertensive compared to normotensive WT mice. However, KO vessels relaxed better to both vasodilators in rings from both vehicle and AngII-treated mice (ACh LogEC
50
, WT+AngII -5.3 ± 0.27 vs. KO+AngII -6.5 ± 0.19,
p
< 0.05, n=4-6; SNP LogEC
50
, WT+AngII -7.4 ± 0.10 vs. KO+AngII -8.1 ± 0.10,
p
< 0.05, n=3-6). These results demonstrate a dissociation between elevated blood pressure and impaired vasodilator function. The data suggest that LRRC8A anion channels play a complex role in the development of AngII-induced hypertension.
Abstract P314: Sex-specific Role For The Circadian Clock Protein PER1 In Aortic Stiffness
Authors: Sharma Ravindra K , Gomes Joshua , Mckee Annalisse , Cheng Kit-Yan Thomas , Costello Hannah M , Mohandas Rajesh , Gumz Michelle L
Published: October 2023

Background:
Increased aortic stiffness is independently associated with an increased risk of cardiovascular events and improvement in aortic stiffness positively correlates with better survival. Period 1 (PER1) is a core circadian clock protein and previous studies have shown that global or kidney-specific knockout (KO) of PER1 results in salt-sensitive hypertension, but the role of PER1 in the vasculature remains unknown. The goal of the present study was to test the hypothesis that loss of PER1 would lead to increased aortic stiffness.

Methods:
Male and female C57BL/6J (16-18 weeks old) mice with global or vascular smooth muscle cell (VSMC)-specific PER1 KO (n=7-10) and control mice (WT) were subjected to echocardiographic measurement of pulse wave velocity (PWV) to evaluate aortic stiffness. We further investigated if treatment with high salt diet plus an aldosterone analog (HS-DOCP, deoxycorticosterone pivalate) has any additional effect on aortic stiffness in male VSMCs-specific PER1 KO mice.

Results:
In mice on a normal diet, global KO of PER1 resulted in increased PWV in males (WT: 202±8, PER1 KO: 287±27 cm/s, p<0.01) but not in female mice (WT:219±14, PER1 KO: 225 ± 23 cm/s, p<0.80) compared to age-matched wild type. Further, morphometric analysis of the aorta showed increased adventitia thickness in male global PER1 KO mice (WT: 41.7±2.3, PER1 KO: 54.6±2.4 um, (p<0.01). These data led us to generate VSMC PER1 KO mice by crossing Tagln Cre mice with floxed PER1 mice. VSMC KO was confirmed by recombination PCR. PWV was not different between male VSMC PER1 KO and Cre negative littermate control (CNTL) mice on normal diet, however, it was increased in VSMC PER1 KO mice after treatment with HS-DOCP (CNTL: HS-DOCP: 241 ±12, PER1 KO: HS-DOCP: 307±18 cm/s, p<0.01). PWV in female VSMCs PER1 KO mice was not statistically significant compared to littermate CNTL mice (CNTL: 247±12, VSMC PER1 KO: 233 ± 25 cm/s, p<0.50).

Conclusion:
Our findings indicate that loss of the clock protein PER1 increases aortic stiffness in male but not in female mice suggesting a sex specific role for the circadian clock in the pathology of aortic stiffness. Further studies are warranted to identify the potential mechanisms involved in the pathogenesis of PER1-dependent aortic stiffness.
Abstract P318: INDOLE-3 ACETIC ACID: A NOVEL DUAL-ACTION INHIBITOR OF THE ENDOTHELIN SYSTEM FOR TREATING HYPERTENSION
Authors: Hasan Raquibul , Ezewudo Emmanuella , Zerin Farzana , Menon Sreelakshmi , Simon Nimi , Moniri Nader , Nguyen Tro Thien , Chougule Mahavir Bhupal , Rahman Taufiq
Published: October 2023

Elevated levels of endothelin-1 (ET-1) stimulate potent vasoconstriction, free radical production, oxidative stress, and vascular inflammation, which are often present in salt-sensitive hypertension, pulmonary hypertension, drug-resistant hypertension, and hypertension among African Americans. There is currently no known drug that simultaneously targets both ET-1 receptors (ETRs) and the ET-1 synthesizing enzyme ECE-1, even though dual targeting of the ET system could lead to a new generation of drug molecules with improved therapeutic outcome. Using an integrated in vitro, in vivo and in silico approaches, here we report the discovery of indole-3 acetic acid (IAA) as an inhibitor of both ET-1 receptors and ECE-1. IAA is produced in the human body via tryptophan metabolism by gut microbiota. Our data demonstrates that IAA concentration-dependently inhibits ET-1-evoked vasoconstriction in rat resistance mesenteric arteries and ET-1-stimulated reactive oxygen species (ROS) production in smooth muscle cells (SMCs). Furthermore, IAA suppresses ET-1-induced endothelial cell (EC) activation, adhesion molecule overexpression, and leukocyte adhesion. IAA inhibits ET-1-stimulated, ET
A
R- and ET
B
R-mediated increases in [Ca
2+
]
i
. Intriguingly, IAA produces a concentration-dependent inhibition of purified human ECE-1. Treatment of Dahl salt-sensitive (DSS) hypertensive rats, a model of augmented ET-1 signaling, with an oral extended-release formulation of IAA significantly inhibits blood pressure elevation in high-salt diet-fed (HSD) DSS rats. IAA-treated DSS arteries show intact acetylcholine- and sodium nitroprusside-induced vasodilation, suggesting that IAA preserves endothelial and smooth muscle function, respectively. IAA treatment also prevents arterial remodeling, oxidative stress, and kidney dysfunction in HSD DSS rats. Overall, our study identifies IAA as the first-in-class dual-action inhibitor of ETRs and ECE-1, which produces profound antihypertensive effect in vivo. IAA could also be therapeutically useful for other cardiovascular diseases in which ET-1 signaling is implicated.
Abstract P319: Eliminating Cardiotoxicity In Alpha1-adrenergic Receptor Antagonists
Authors: Healy Chastity L , Puccini Sara J , Aragon Ingrid R , Dodda Vasudeva , Muthyala Ramaiah , Sham Yuk , O'Connell Timothy D
Published: October 2023

Introduction:
Alpha-1 adrenergic receptor (α1-AR) antagonists (α1-blockers) are efficacious antihypertensives, but ALLHAT found that doxazosin (Dzn) doubled the risk of heart failure (HF). We previously demonstrated that α1-ARs, specifically the α1A-AR, protect the heart, explaining the worse outcomes with Dzn in ALLHAT. Interestingly, α1-ARs localize to and signal at the nucleus in cardiac myocytes (CM), whereas α1-ARs localize to the sarcolemma in smooth muscle (SM).

Hypothesis:
We hypothesize that a membrane impermeant α1-blocker would inhibit α1-ARs in SM, reducing blood pressure, but preserve protective α1-signaling in CMs, preventing HF.

Methods:
We developed an α1A-AR homology model to define the structural basis of α1-blocker binding and modified existing α1-blocker structure to reduce cardiotoxicity. Using this model, we designed 30 compounds, synthesized 9 in gram quantities, and tested 2 compounds.

Results and Conclusions:
Binding assays identified 2 novel high affinity α1-ligands; α1705 (IC50 = 5.2 [CI:3.5,7.6] nM, n=3) and α1707 (5.8 [CI:4.2,8.1] nM, n=3) (Dzn: 7.7 [CI:6.3,9.2] nM, n=6). Uptake assays in cultured CM indicated uptake of Prazosin (10 μM Prz: 230 nM in CMs detected by mass spectrometry), whereas α1705 and α1707 were not detected. In HEK cells expressing α1A-AR at the cell surface, Prz, α1705, and α1707 (all 2 μM) inhibited Ca2+ transients (90%, 76%, 88%) induced by the α1A agonist A61603 (20 μM). In CM, A61603 increased ERK phosphorylation (1.55±0.04 fold, n=7, P<0.0001), a survival signal, which was blocked by Prz (1.21±0.06 fold, n=7, P=NS), but not α1705 (1.72±0.13 fold, n=7, P<0.001). Further, A61603 (20 μM) inhibited H202-induced CM death (-17.4±7.6%, n=5), which was reversed by Prz (30.9±15.4%, n=5, P=0.035), but not α1705 (-0.94±11.6%, n=5, P=NS). In DOCA-salt hypertensive mice, infusion of Prz or α1705 (2 mg/kg/d, 3 d) lowered systolic pressure (Cont: +18.9 mmHg, n=1; Prz: 6.4±3.2 mmHg, n=3, α1705: -6.1±5.6 mmHg, n=3), and while Prz was detected in CMs following 4 d, α1705 was not. In conclusion, we have developed a novel membrane impermeant α1-blocker with reduced cardiotoxicity that could improve hypertension outcomes, especially in patients suffering from chronic kidney disease or benign prostatic hyperplasia.
Abstract P335: Patient Preferences For Renal Denervation In Uncontrolled Hypertension: The RADIANCE PREFER Study
Authors: Fisher Naomi D , Schmieder Roland E , Seo Jaein , Augustin Dimitri A , Coleman Leslie A , Reeve-Stoffer Helen , Trapali Myrto , Marsh Kevin
Published: October 2023

Objective:
Blood pressure control is a challenge for patients for reasons including adherence, medication side effects, poor access to healthcare, and inconvenience of long-term treatment. Renal denervation is a treatment option that lowers blood pressure in combination with lifestyle modifications and medications, but it requires a minimally invasive procedure. This study assessed how patients make choices between treatments, and quantified their willingness to undergo renal denervation.

Methods:
An online discrete choice experiment (DCE) was completed by US adults with uncontrolled hypertension despite being prescribed ≥1 medication. In 10 DCE tasks, participants chose between two hypothetical treatments defined by the 10-year cardiovascular (CV) risk, current treatments (procedure/number of pills per day), durability/need for future treatments (additional procedure or pills), and risks of mild-to-moderate and serious adverse events. The attributes were developed through a targeted literature review, 10 qualitative interviews, and FDA feedback, and were refined through 5 cognitive pilot interviews. DCE data were analyzed using mixed logit models which were used to simulate treatment uptake in different scenarios.

Results:
Participants (n=258) were 62% female, 40% non-white, and from multiple regions of the US, with a majority from the South (63%). Mean (SD) age was 53 (12) years and BMI was 33 (10) kg/m
2
. All participants were currently taking ≥1 pill/day. Participants put the most weight on CV risk when deciding between treatment options. Given the same number of pills, 42% would choose an interventional treatment if it reduced their 10-year CV risk by 5% more than medication alone. In addition, 42% of patients would prefer a one-time invasive procedure versus taking an additional pill if the procedure had the same effect on CV risk as medication alone.

Conclusions:
A substantial number of patients taking medication for hypertension would be willing to undergo renal denervation to reduce their CV risk or to avoid an increase in their pill burden.
Abstract P337: Blood Pressure And Retina Responses Of Malignant Hypertension Patients In The Rice Diet Program
Authors: Lin Pao-Hwa , Lopez David A , La Jong , Li Yi-Ju , Luft Friedrich C , Neelon Francis , Klemmer Philip , Kuo Anthony , Sanoff Scott
Published: October 2023

Introduction:
The residential Rice Diet Program at Duke (RDP) has been shown to be effective in treating patients with malignant hypertension (MH) using a low salt (5 meq/d), low protein (5% kcal), and low fat (5% kcal) diet with no anti-hypertensive medications. Our team examined the RDP medical records and further clarified the identification of 710 MH patients by limiting the criteria of an averaged systolic blood pressure (SBP)>170 mmHg to be met ±7 and a documented non-diabetic hemorrhrage and/or papilledema to be met ± 30 days of starting RDP, respectively.

Methods:
Wilcoxon ranked-sum was used to compare baseline and week-4 blood pressures (BPs), weight, and urine chloride (uCl, a measure of low-salt diet adherence). Linear regression was used to examine the association between baseline age, gender, SBP, last weight measure and uCl change with SBP change at week-4. Retina evaluation were compared between baseline and last measure using Chi-Square and Fisher’s Exact tests.

Results:
Male patients (p=.048) and those with a greater change in uCl (p=.001) had a greater reduction in SBP at week-4 (
Table
). Those with a higher baseline SBP had a lower reduction in SBP (p<.001), while baseline age and last weight measure had no effect. The proportion of MH patients with either hemorrhage alone, papilledema alone or both, reduced during RDP participation (p<.001).

Conclusion:
The RDP significantly lowered BPs, weight and uCl in MH patients within 4-week of starting RDP. The proportion of patients with documented retinal hemorrhage and/or papilledema also reduced significantly during participation in RDP. The mechanisms of the diet’s impact merit further investigation.
Abstract P338: ASSOCIATION OF HYPERTENSION AND FOOD INSECURITY WITH DIETARY SODIUM AND POTASSIUM IN ADULTS
Authors: Onugha Elizabeth , Banerjee Ankona , Vimalajeewa Horahenage Dixon , Dave Jayna , Racette Susan B
Published: October 2023

Food insecurity (FIS), the lack of consistent access to nutritious food is a risk factor for HTN and leads to poorer health outcomes. Although studies show a higher prevalence of HTN in patients living with FIS, there is limited data exploring the underlying mechanism. Using dietary recall data, we sought to evaluate the relationship between HTN and FIS.

We performed a cross-sectional analysis of 16,703 adults aged between 18 and 65 years who participated in the National Health and Nutrition Examination Survey between 2011 and 2018. We excluded pregnant participants. We examined the association between FIS, HTN, and dietary sodium and potassium levels using univariate and multivariate analysis.

Adults who reported FIS were more likely to have HTN (aOR=1.22, 95% CI: 1.02-1.46, p=0.029). Non-Hispanic Blacks participants were more likely to have HTN than Non-Hispanic Whites (aOR=1.74, 95% CI: 1.54-1.96, p<0.001) while Hispanic participants were more likely to have lower BP (aOR=0.82, 95% CI: 0.71-0.94, p=0.007). The prevalence of FIS was higher among Non-Hispanic Black (28.8%) (aOR= 1.28, 95% CI= 1.02-1.61, p<0.01) and Hispanic participants (33.5%) (aOR= 1.67, 95% CI= 1.33-2.09, p<0.01) compared to Non-Hispanic White. Individuals living in food-insecure households had a higher prevalence of obesity (23.7%) compared to adults who lived in food secure households. (18.4% for normal weight and 17.9% for overweight; p < 0.01). The prevalence of hypertension increased with age, peaking in the 60-65 age group (p<0.001). Individuals who reported FIS had a significantly lower mean intake of sodium (3.57 ± 0.04 gm) and potassium (2.5 ± 0.03 gm) compared to individuals living in food secure households (3.69 ± 0.02 gm and 2.74 ± 0.02 gm, respectively; p < 0.01 for both). We found that for every 1 gm increase in dietary sodium, the odds of HTN increased by 1% (p<0.01). For every 1 gm increase in dietary potassium the odds of HTN decreased by 9% and the odds of living in a food insecure household decreased by 16%.

Adults with a lower dietary potassium intake were more likely to report FIS and have HTN. Increasing assess to healthy foods, particularly foods rich in sources of potassium, for individuals living with FIS, may reduce the prevalence of HTN and lead to better cardiovascular outcomes.
Abstract P343: A Correlational Study On Spiritual And Religious Well-being, Social Determinants Of Health, And Self-efficacy For Appropriate Medication Use Among African- American Women With Hypertension
Authors: Augusta Tracie L , Mary Annapoorna , Sohye Lee , Mzayek Fawaz , Woodbury-Moore Christy
Published: October 2023

Background:
African American (AA) women are disproportionately affected by hypertension and are less likely to adhere to their medication regimen when compared to White and Hispanic women. Very little is known about social factors associated with medication adherence among AA women. Spiritual well-being (SWB), religious well-being (RWB), and social determinants of health (SDOH) may be associated with self-efficacy for appropriate medication use (SEAM).

Purpose:
The purpose of the study is to: (1) examine the relationships among SDOH, namely age, education level, household income, and marital and insurance status, and SWB and RWB; (2) examine the relationships between SDOH and SEAM; and (3) assess the potential associations of SWB and RWB with SEAM.

Methods:
The study employed a cross-sectional correlational design. An online survey was used to collect data. A purposive sample of 187 AA women with hypertension diagnosis over 1 year was recruited. SWB and RWB were measured using the Spiritual Well-Being Scale, and SEAM was measured using the Self-Efficacy for Appropriate Medication Use Scale. SDOH were adopted from Healthy People 2030. Linear regression analysis was conducted to assess the adjusted association of SWB and RWB with SEAM, and
p
< .05 was considered significant.

Results:
The women of the study were middle aged (M = 57.34 years, SD = 12.89) and had moderate SWB and RWB scores. Only age and education were positively associated with SEAM (
p
< .001 and
p
= .025, respectively). There was no association of SWB or RWB with SEAM.

Discussion and Conclusion:
SWB and RWB scores did not predict SEAM in this sample of AA women with hypertension. However, this could be due to lack of power due to a small sample size. Older age and higher education level were associated with higher self-efficacy. Interventions to improve adherence to antihypertension drug treatments aimed at younger AA women with lower educational attainment could help in improving care and reducing disparities in health outcomes for this population.
Abstract P345: CONCOMITANT HYPERTESION AND DYSLIPIDEMIA PATIENTS TREATED BBY EITHER FIXED-DOSE OR FREE-COMBINATION AMLODIPINE AND ATORVASTATIN
Authors: Chu Pao Hsien H , Lin Chia-Pin
Published: October 2023

In this study, we analyzed three groups of patients: those receiving a fixed-dose regimen of amlodipine 5 mg/atorvastatin 10 mg (Caduet 10), those receiving a fixed-dose regimen of amlodipine 5 mg/atorvastatin 20 mg (Caduet 20), and those receiving a free-combination regimen. We obtained data from the National Health Insurance Research Database (NHIRD) of Taiwan from January 1, 2016, to December 31, 2019, to conduct our analysis. After excluding some patients, we included 9,095 eligible patients for further analysis, including 3,313 patients in the Caduet 10 group and 2,658 patients in the Caduet 20 group. The primary endpoint of our study was major adverse cardiovascular events. We found that each component of the primary endpoint was significantly lower in the Caduet 20 group compared to the other two groups (Figure). Additionally, the incidence of newly diagnosed diabetes mellitus (DM) was significantly lower in the Caduet 10 group than in the other two groups . This finding is consistent with previous studies indicating that a higher statin strength may be associated with a higher incidence of newly onset DM.
Abstract P357: Hypertension At Rural Worksites - An Ongoing Problem
Authors: Bolin Linda P , Burch Ashley , Lee Elisabeth , Shackelford Paul , Bolin Paul
Published: October 2023

Introduction:
The objective of this study is to determine the prevalence of undiagnosed or uncontrolled hypertension in participants through worksite-based health screening assessments in rural areas. It is estimated that, in rural communities, the prevalence of hypertension is 10% higher than urban areas. Through our SERVIRE Outreach Screening Program (
S
topping
E
arly
R
eversible
V
ital organ damage
I
n
R
ural
E
astern North Carolina) we provide worksite-based health screenings for low-wage workers throughout eastern North Carolina. These screenings include assessment for hypertension and other associated comorbidities.

Hypothesis:
There are elevated rates of hypertension among those working in rural worksites in Eastern North Carolina.

Methods:
Rural worksites were identified for health screenings that included a series of questionnaires and biometrics. Screenings concluded with a one-on-one provider meeting to discuss attitudes about preventative care, screening results, and referrals as needed.

Results:
A total of 1132 individuals (45.2% Black) (56.2% male) participated in our ongoing screening clinics. Nearly seventy percent (68.1%) of participants reported seeing a healthcare professional within the previous year. Undiagnosed hypertension (SBP ≥140) was found in 259 (23.4%) participants and 185 (16.7%) participants had diagnosed but uncontrolled hypertension. Blood samples were obtained from 974 participants; elevated serum creatinine was found in 101 (9.6%) individuals.

Conclusion:
In conclusion, nearly half of the health screening participants had uncontrolled or undiagnosed hypertension. These high rates of hypertension were evident despite the majority of participants reporting having visited a healthcare provider within the previous year. Among screened patients, nearly one in ten had elevated serum creatinine, a marker of end organ damage. Future screenings will implement on site retinal exams as an additional tool to assess end organ damage. Our SERVIRE program provides convenient, worksite-based health screening to identify untreated hypertension among low-wage, rural workers in eastern North Carolina.
Abstract P359: Resident Management Of Hypertensive Urgency
Authors: Lee Paul Y , Shah Kajol , Selvakumar Tharakeswari , Plosker Aaron , Viswanathan Rohan , Saad Kyrollos , MATASSA DANIEL
Published: October 2023

Objective:
Hypertensive urgency is generally defined as a severely elevated blood pressure without evidence of end-organ damage. Consensus statements do not recommend the acute lowering of blood pressure nor referral to the emergency room. Rapid lowering of blood pressure in patients who are chronically hypertensive carries the risk of hypoperfusion and therefore ischemia to vital organs. The objective of this study was to assess residents’ perception of the management of hypertensive urgency.

Methods:
An anonymous survey was sent via email to all active resident physicians of an academic internal medicine residency program. It comprised of 8 questions regarding the outpatient and inpatient treatment of hypertensive urgency.

Results:
A total of 47 residents responded to the survey. Most respondents (44 of 47) knew that evaluating for reversible causes of elevated blood pressure is the first step of management. Fewer residents (37 of 47) said the next course of action would be to up-titrate the oral blood pressure regimen. When asked about real life practice, 35 of 47 attested to conservative management with 12 of 47 respondents regularly using IV antihypertensives to treat hypertensive urgency. The most common contributing reason (25 of 47) to pushing IV antihypertensives was pressure from colleagues and staff, with only 2 residents denying ever administering IV antihypertensives.

Residents were also aggressive in the management of hypertensive urgency in the outpatient setting with 15 of 47 respondents reporting most commonly referring patients to the ER for blood pressure lowering (31.91%) and 5 of 47 reporting administering clonidine in the office for quick blood pressure lowering.

Conclusion:
Resident physicians in our program should be less aggressive in treating hypertensive urgency, especially in the outpatient setting. We suspect that the notion that hypertensive urgency warrants immediate blood pressure lowering is prevalent as pressure from staff/colleagues was the largest cited reason to giving IV antihypertensives in urgency. Further efforts should be pursued to educate residents about the current guidelines regarding hypertensive urgency.
Abstract P372: Global Burden Of Chronic Kidney Disease Due To Hypertension In 38 Oecd Countries: A Benchmarking Analysis For The Global Burden Of Disease Study 2019
Authors: Dhanani Maulik , Kamani Yashkumar G , Vanodia Mihir , Dhawan Arushi , Kyada Sumit , Lakkimsetti Mohit , AMIN VISHRANT P , Gajjar Rohan , Marsool Mohammed Dheyaa Marsool , DESAI HARDIK D
Published: October 2023

Background:
Chronic Kidney Disease (CKD) due to hypertension (HTN) ranks as the leading cause of death among all types of CKD in Organization for Economic Cooperation and Development (OECD) countries.

Method:
Using the Global Burden of Disease methodology, CKD due to HTN prevalence, incidence, deaths, Disability adjusted life years were analyzed by age, sex, year across the 38 OECD countries between 1990-2019.

Results:
Total prevalence of CKD due to HTN doubled from 4933515 (95%UI4543,520-5382155) in 1990 to 10871399 (95%UI10055175-11754447) in 2019. Age-standardized incidence rate (ASIR) increased from 21/100000 in 1990 to 25/100000 in 2019. The highest ASMR was observed in Mexico (16/100000), ASIR in Turkey (36/100000) in 2019. The highest annual percentage of change (APC) increased in ASMR observed in Estonia 341% (0.8-3.6) per 100000 from 1990-2019.

Conclusion:
CKD due to HTN has remained a leading cause of deaths in OECD countries. The escalating prevalence of CKD due to HTN underscores the urgency for proactive strategies aimed at prevention, early detection, and effective management of HTN.
Abstract P389: Prevalence Of Hypertension In A Stemi-activated Subset Of Patients From 2019 To 2021
Authors: Lantz Rebekah , Hefner Dylan , Walk Casey , Sadhu Srikanth
Published: October 2023

Background:
About 47% of US adults have hypertension (HTN) per the 2017 guideline. Prevalence is worse in certain distributions of the country with top quartile in the Southeastern pocket. In a subset of patients who present with ST-segment elevated myocardial infarction (STEMI), the prevalence is 30-40%. An interesting further subset of patients are those who presented during COVID-19 pandemic. COVID-19 wreaked havoc on the world with its first confirmed case 9 January 2020. International followed by national transport became limited, followed by announcement of a pandemic. Quarantines and lockdowns were set in place, especially in March 2020, to prevent epidemiologic spread.

Hypothesis:
We were interested to observe if STEMI-alert patients during this period presented with worse background disease compared to years 2019 and 2021, years before and after COVID-lockdown and peak, including if the prevalence of HTN increased in the population.

Methods:
We evaluated 1001 adults who were STEMI-activated from 1 January 2019 to 31 December 2021 at 5 sites in Southwest Ohio. We obtained patient demographics and risk factors and performed multinomial logistic regression to compare years 2019 and 2021 to 2020. Statistical analysis was with SAS 9.4. Results. For 1001 STEMI-alert patients, 244 patients (72.6%) had HTN in 2019, 250 (78.9%) in 2020 and 261 (75.0%) in 2021. Overall prevalence over the three years was 755 (75.4%). Compared to 2020, 2019 prevalence was not significant (p=0.12) (OR 0.72) (CI 0.47,1.09). Neither was 2021 (p=0.25) (OR 0.78) (CI 0.51,1.19).

Conclusion:
STEMI-alert patients at our institution appeared to have higher overall prevalence of HTN than reported nationally by the Centers for Disease Control (CDC), 75.4% versus 40%. These may have self-selected for disease severity by STEMI-alert activation status. HTN may also be of higher prevalence in this region, be associated with poor disease detection or there may be patient compliance issues when antihypertensives are prescribed by a healthcare provider. HTN prevalence did not have statistical significance across the three observed years despite our hypothesis that patients would present with more background cardiac comorbidities such as HTN.
Abstract P406: Aprocitentan, A Novel Endothelin Receptor Antanognist, In Older Patients With Difficult-to-control Hypertension
Authors: Weber Michael A , Narkiewicz Krzysztof , Bakris George L , Wang Jiguang , Flack John M , Danaietash Parisa , Flamion Bruno , Haskell Lloyd P , Schlaich Markus P
Published: October 2023

Background:
In older adults, hypertension (HTN) control can be difficult despite multiple therapies, especially in those with altered kidney function. The PRECISION study showed that aprocitentan (APRO), a dual endothelin receptor antagonist12.5 or 25 mg daily decreases blood pressure (BP) in patients (Pts) with resistant HTN. We evaluated APRO BP lowering in Pts aged ≥ 65 years.

Methods:
Pts had sitting unattended automated office systolic BP (SBP) ≥ 140 mmHg after switching their antihypertensives (anti-HTN) (except beta-blockers) to a standardized therapy (ST) of amlodipine, valsartan and HCTZ. Reductions in office and ambulatory BP; and safety were assessed in 3 sequential parts over a 48-week period as follows: 4-week double-blind (DB) APRO 12.5 mg, APRO 25 mg, PBO; 32-week single-blind APRO 25 mg; and 12-week DB withdrawal APRO 25 mg, PBO.

Results:
In PRECISION, 321 Pts were aged ≥ 65 years. Of those, 202 (63%) were obese, 115 (36%) had chronic kidney disease stage 3-4, and 209 (65%) were on ≥ 4 anti-HTN prior switching to ST.At Week 4, APRO reduced office SBP, PBO adjusted SBP is: APRO 12.5 mg -5.64 and APRO 25 mg -4.63 mmHg in Pts 65–< 75 years; and APRO 12.5 mg -6.75 and APRO 25 mg -12.85 mmHg in Pts ≥ 75 years. APRO 25 mg maintained BP reduction over 32 weeks but this disappeared at Week 40 in those randomized to PBO at Week 36, PBO adjusted SBP is +5.70 mmHg in Pts 65–< 75 years; +3.51 mmHg in Pts ≥ 75 years. Ambulatory BP confirmed office BP reductions with both APRO doses, particularly with APRO 25 mg on nighttime SBP at Week 4 in Pts ≥ 75 years: 12.5 mg: -8.8; 25 mg: -14.8; PBO +1.0 mmHg. At Week 4, the most frequent adverse event (AE) was peripheral edema: 7.7%, 12.9%, and 2.3% in Pts 65–< 75 years, and 18.2%, 22.7%, and 3.6% in Pts ≥ 75 years, with APRO 12.5 mg, APRO 25 mg, and PBO, respectively. Edema was managed with additional diuretics. 4 Pts discontinued due to edema; none had received additional diuretics. 7 Pts (APRO 25 mg) were hospitalized for heart failure; 4 of them had switched from loop or more than one diuretic to HCTZ.No orthostatic hypotension events occurred.

Conclusion:
In older resistant HTN Pts, APRO added to ≥ 3 anti-HTN substantially decreased office and ambulatory BP. The most frequent AE was peripheral edema, which rarely led to treatment discontinuation.
Abstract P409: Angiotensin Ii Activates At1a Receptors In Sfo-pvn-dmv To Modulate The Autonomic Nervous System And Immune System In Hypertension
Authors: Perrotta Marialuisa , Carnevale Lorenzo , Pallante Fabio , Migliaccio Agnese , Perrotta Sara , LEMBO GIUSEPPE , Carnevale Daniela
Published: October 2023

Angiotensin II (AngII) modulates the autonomic nervous system (ANS) and we have previously found that it activates a vagal-splenic reflex that in turn promotes lymphocytes priming and blood pressure increase. AngII binds type 1a receptors (AT1aR) expressed in the neuronal centers of the cardiovascular control, among which the dorsal motor nucleus of the vagus nerve (DMV). Here we hypothesize that AngII signaling in the DMV activates the vagal-splenic pathway elicited by hypertension. To investigate whether circulating AngII targets the DMV, we intravenously injected fluorescent AngII in mice implanted with osmotic minipumps (AngII or veh), finding it in the DMV complex of AngII mice . To target DMV AT1aR signaling, we utilized AT1aRflox crossed with mice expressing cre-recombinase in PHOX2B neurons. We verified gene deletion by RNAscope and infused AngII, finding no protection from HTN (SBP 147±4 vs 146±2 mmHg in AT1aR-KO-DMV vs WT, p=0.797). Hence we investigated whether upstream brain areas relevant for AngII signaling, the paraventricular nucleus of the hypothalamus (PVN) and the subfornical organ (SFO), modulate DMV complex. Interestingly, AngII was able to cross BBB of PVN and SFO of hypertensive mice. Mechanistically, we targeted AT1aR gene in PVN and SFO, finding protection from AngII-HTN in both cases (SBP 109±1 vs 144±1 mmHg in AT1aR-KO-PVNvsWT, p<0.001; SBP 140±2 vs 160±2 mmHg, in AT1aR-KO-SFOvsWT, p<0.001). Consequently, to test whether the SFO might be the first sensor of hypertension-induced vagus-splenic activity, we measured the SSNA in AT1aR- SFO KO finding it significantly reduced (107±10vs323±57 in AngII AT1aR-SFO KOvsWT, as number of spikes by microneurography, p<0.01), as immune cell egression was (splenic CD3+area 120±10 vs 64±7 mm
2
*10
3
in AngII AT1aR-SFO KOvsWT, p<0.001). These results suggest that AT1aRs in the SFO-PVN axis modulates the DMV function and in turn the vagal-splenic reflex in HTN.
Abstract P414: Cytomegalovirus, Hypertension, And Oxidative Stress: Is There A Connection?
Authors: Gonçalves Elioelsio , Oliveira Helen M , De Paula Guilherme O , Lira Cleberson , Sinhorin Valéria D G , Priviero Fernanda , Webb R Clinton , Bomfim Gisele F
Published: October 2023

Cytomegalovirus (CMV) infection is associated with various chronic inflammatory conditions, including cardiovascular disease. Hypertension is characterized by increased levels of reactive oxygen species in various tissues and blood, and oxidative stress is thought to contribute to organ damage in this disease. In view of this, the aim of this study was to assess the association between CMV infection, blood pressure, and oxidative stress in hypertensive patients. A total of 89 patients with normal or high blood pressure participated in the study. Patients with systolic blood pressure > 130 mmHg or diastolic blood pressure > 90 mmHg or using anti-hypertensive drugs were included in hypertensive group. Blood samples were collected to measure IgG CMV and indirect markers of oxidative stress. In the hypertensive group, 61 patients were included, 45 women and 16 men, with a mean age of 60.8 years. In normotensive group, 228 patients were included, 20 women and 8 men, with a mean age of 47.4 years. The normotensive group showed higher levels of IgG CMV (180.5 ± 20.7 RU/mL) and catalase (1.34 ± 1 μmol/min/mg) compared with the hypertensive group (155.4 ± 57 RU/mL and 1.01 ± 0.74 μmol/min/mg, respectively). In addition, serum carbonylated proteins (13.16 ± 2.6) were higher in the hypertensive than the normotensive group (11.24 ± 2.4). No differences were observed in glutathione S-transferase between groups. A Pearson correlation analysis revealed a positive correlation between IgG CMV concentration (0.236, p=0.026) and catalase (0.217, p=0.041) in the normotensive group. However, IgG CMV was not associate with the levels of systolic (-0.108) or diastolic (-0.052) blood pressure. Based on these data, we suggest that CMV may play a role in the oxidative process.
Abstract P418: Antigen-presenting Cell-specific MAP-kinase Signaling Contributes To Inflammation And Salt-sensitivity Of Blood Pressure In Humans
Authors: Saleem Mohammad , Ertuglu Lale , Pitzer Mutchler Ashley , Laffer Cheryl L , Kirabo Annet
Published: October 2023

Salt-sensitivity of blood pressure (SSBP) is defined by the changes in blood pressure in concert with salt intake/depletion. SSBP affects 50 percent of hypertensive and 25 percent of normotensive individuals and is an independent risk for stroke and cardiovascular death in both groups. We recently found that phosphorylation of STAT3 and SMAD3 in antigen-presenting cells plays an important role in developing SSBP. We hypothesized that mitogen-activated protein kinases (MAPKs) signaling plays an important role in activating/phosphorylating JAK-STAT-SMAD and contributes to salt-sensitivity of blood pressure. We isolated monocytes from eleven healthy individuals and treated them with either normal salt (NS) or high salt (HS) and performed bulk-RNA-sequencing. The bulk-RNA transcriptomic data analysis suggested that out of 21 members of the MAPK family, eighteen were upregulated (1.7-fold) in monocytes exposed to high salt. Among these, MAPK7 (NS:818.18±54.96; HS:1473.18±151.50) and MAPKAPK2 (NS:3977.81±286.67; HS:6222.63±440.32) were significantly upregulated. In additional experiments, we enrolled eleven hypertensive patients and phenotyped them for salt-sensitivity using a rapid salt-load and depletion inpatient protocol. Blood was collected at baseline, after salt loading, and depletion, and CITE-Seq was performed on isolated PBMCs. The data analysis showed that MAPK7 and MAPKAPK2 expressions mirror the blood pressure changes following salt loading and depletion in salt-sensitive but not in salt-resistant patients. Moreover, we found a positive correlation between MAPKAPK2 expression and the pulse pressure ((PP) r=0.52, p=0.033) after salt-load. Epoxyeicosatrienoic acid (EET) has been shown to activate MAPKs resulting in inhibiting ENAC activity. The data showed a strong positive correlation between MAPK7 expression and levels of EETs in plasma (r=0.70, p=0.036), and urine (r=0.68, p=0.045) after salt-load. These results from bulk-RNA and single-cell CITE-Seq data indicate that MAPKs play an important role in human SSBP.
Abstract P424: Postpartum Blood Pressure Trajectories After Hypertensive Disorders Of Pregnancy
Authors: Mujic Ema , Petersen Julie , Nelson Kerrie , Chestnut Idalis , Yarrington Christina , Parker Samantha
Published: October 2023

Background:
Following a hypertensive disorder during pregnancy, blood pressure (BP) generally decreases rapidly in the first three weeks postpartum followed by a period of stabilization. Little is known about patterns of deviation from this trend.

Methods:
Patients with hypertension during pregnancy (chronic, gestational, or during delivery hospitalization) were enrolled in a remote BP monitoring program and provided with a cell-enabled cuff to take daily BP measurements during their first six weeks postpartum. Measurements were transmitted to a portal and integrated with their electronic medical record. Patients delivering between January 2021 and December 2022 with ≥2 BP measures at an urban safety net hospital were included (n=1,571). Quadratic group-based trajectory models were used to identify latent patterns of postpartum systolic BP (SBP) and diastolic BP (DBP) over time, a method that can be used to capture clinically distinct sub-groups of patients. Patients were grouped into one of four trajectories based on posterior probabilities. Demographic and reproductive characteristics of each trajectory group were examined.

Results:
Based on 1,571 patients with an average of 15 postpartum BP measurements per patient, the group trajectory model identified 4 trajectories of SBP and DBP (labeled as starting BP value-rate of BP decline): (1) low-steep (SBP 123, DBP 78), (2) moderate-steep (SBP 134, DBP 87), (3) high-gradual (SBP 143, DBP 93), and (4) high-flat (SBP 146, DBP 95). The percent of patients falling into each SBP trajectory group were (1)22.6 (n=346), (2)38.0 (n=611), (3)28.6 (n=451), (4)10.8 (n=163), and for DBP were (1)18.2 (n=288), (2)35.4 (n=557), (3)31.9 (n=508), and (4)14.4 (n=218). Key demographic and pregnancy characteristics varied across SBP and DBP trajectory groups. The high-flat groups were most likely to be older (≥36 years) and non-Hispanic Black. The high-flat SBP and DBP groups had the highest percentage of preterm births (26.4%, 43 out of 163; 20.6%, 45 out of 218, respectively).

Conclusion:
In this on-going observational study, we characterized 4 distinct group trajectories of SBP and DBP in the 6-weeks postpartum. These data may aid in the identification of patients at risk of persistent postpartum hypertension.
Abstract P425: Peripartum Cardiomyopathy And Other Cardiac Events In Pregnant And Postpartum Patients With Mood Disorders
Authors: Harrison Rachel , Neuburg Blake , Palatnik Anna
Published: October 2023

Background:
Evidence suggests a link between depression and adverse cardiac events. We sought to understand whether mood disorders are associated with peripartum cardiomyopathy (PPCM) and other cardiac events in pregnancy and postpartum.

Methods:
Retrospective cohort study utilizing the National Inpatient Sample (HCUP) of pregnant and postpartum patients from 2017-2019. Subjects were separated into two groups based on ICD10 coding for presence or absence of mood disorder (depression, bipolar, anxiety, or other mood diagnosis). The primary outcome was diagnosis of PPCM. Secondary outcomes included a composite of acute cardiac events and maternal death. Groups were compared via t-tests, chi-squared analysis, and logistic regression that included all variables that differed between groups with p<0.05.

Results:
Over 2.2 million subjects were analyzed and approximately 168,000 (7.4%) had an ICD10 diagnosis of mood disorder. Those with mood disorders were more likely to be non-Hispanic white, obese, tobacco user, publicly insured, have comorbidities, and deliver at a large, private, non-profit hospital (all p<0.05). They delivered earlier in pregnancy and were also more likely to undergo cesarean (37.0±4.6 vs 37.8±3.7 weeks and 35.8% vs 31.8%, respectively, p<0.001). The primary outcome of PPCM was more than twice as common in those with mood disorder (0.12% vs 0.05%, p<0.001) as were other cardiac events, include the composite of adverse cardiac events (0.36% vs 0.14%, p<0.001). Maternal death was the same in both groups (p=0.253). After controlling for confounders, PPCM remained independently associated with diagnosis of mood disorders (aOR 1.36, 95%CI 1.03-1.80) as did the composite of adverse cardiac events (aOR 1.57, 95%CI 1.37-1.81).

Conclusion:
Mood disorders in pregnancy and postpartum are associated with increased rates of PPCM and other cardiac events.
Abstract P426: Novel Peptide B7-33 Demonstrates Efficacy In Rat Models Of Preeclampsia
Authors: Pantho Ahmed F , Amaral Lorena , Afroze Syeda , Vora Niraj , Kuehl Thomas J , Zawieja David C , LaMarca Birdie B , Uddin Mohammad N
Published: October 2023

Background:
Preeclampsia (PreE) is a hypertensive pregnancy disorder, which occurs in approximately 10% of all gestations. The literature suggests potential therapeutic role of H2 relaxin in PreE. Due to the complex insulin-like structure of relaxin (A- and B- chains, 53 amino acids, 3 disulfide bonds), a novel H2 relaxin B-chain-only peptide variant B7-33 (27 amino acids without any disulfide bonds) has recently been developed.

Objective:
This single-chain peptide displayed equivalent efficacy to the natural H2 relaxin in several functional assays both
in vitro
and
in vivo
. The Aim of this study is to evaluate whether B7-33 attenuates preE syndrome in rat models of PreE.

Methods:
Rat Model 1. The efficacy of B7-33 was evaluated in the Reduction of Uterine Perfusion Pressure (RUPP) model as described previously. RUPP rats are randomly assigned to 4 groups (N=8/group): 1) vehicle, 2) B733; 3) B733-Fc; and 4) B733-HSA. Rats are dosed twice weekly (i.v.) from GD10 to GD 20. Rat Model 2. Timed-pregnant rats are used, and the model is conducted as previously described. DOCA and saline administration begin at approximately GD2. Three groups of animals are studied (n=8 per group). 1) normal pregnant rats; 2) pregnant animals injected (i.p.) initially with 12.5 mg of DOCA, followed by a weekly injection of 6.5 mg, and whose drinking water was replaced with 0.9% saline; 3) rats administered DOCA and saline as for Group 2, and given B733 35 ug i.p. biweekly from GD10-20. BP, proteinuria and inflammatory markers were evaluated. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test.

Results:
RUPP rats have increased MAP, plasma TNF-α, and plasma sFlt-1 along with decreased NO index compared to normal pregnancy. Treatment with B733 and B7-33 fusion proteins lowers MAP, TNF-α, and sFlt-1 back to that of normal pregnancy. B7-33 data are consistent with earlier data with serelaxin in the RUPP model. All fusions tested ameliorate hypertension in the RUPP animals. B7-33 normalizes BP and proteinuria in the DOCA rat model of preE.

Conclusion:
Both B7-33 and B7-33 fusion proteins attenuate preE syndrome in RUPP and DOCA rat models of PreE. We conclude that B7-33 is an ideal candidate for development as a novel therapeutic in preE.
Reporting LDL cholesterol results by clinical biochemistry laboratories in Czechia and Slovakia to improve the detection rate of familial hypercholesterolemia
Authors: Vrablík Michal , Šálková Veronika , Vecka Marek , Soška Vladimír , Budina Marek , Šálek Tomáš
Published: October 2023

IntroductionThis survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations.
Materials and methodsThe web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults.
ResultsA total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a).
ConclusionsOnly a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.
Brothers in Arms? The Selection and Prioritisation of Core International Crimes and Terrorism in the Netherlands
Authors: Verhagen Giel
Published: October 2023

Since 2019, the Dutch Public Prosecutor has tried four cases in which the accused has been cumulatively charged with a terrorism-related crime as well as a core international crime. This article examines the Dutch selection and prioritisation process of these charges when they are combined, comparing it to cases that solely include a core international crime charge and solely include terrorism-related charges. The findings suggest that, as a result of the suspect-driven approach and limited universal jurisdiction in the Netherlands, the available evidence is the most important criterion in the selection and prioritisation process in cases that include core international crimes. Moreover, resources can also be identified as an influential factor, whereas this aspect features less prominently in cases that only include terrorism-related charges. The influence of other criteria, such as gravity, remains ambiguous.
Plague and the Leviathan
Authors: Kapust Daniel J.
Published: October 2023

Building on a number of recent studies that have turned to Hobbes in light of covid-19, I explore the context of Hobbes’ own encounters with plague while at Oxford, along with efforts to mitigate plague by the regime of James I. I then explore what role his encounters with plague may have played as he wrote his philosophical masterpiece, Leviathan.