bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P328: Regression to the Mean: Do confirmatory measurements influence the effect?
Authors: Barrett Robert , Sutherland Susan , Riesser Benjamin , Rakotz Michael , Egan Brent
Published: October 2024

Background:
Regression to the mean (RTM) in blood pressure (BP) is a well-established phenomenon wherein a group of individuals selected for high or low BP values will regress toward mean values over time. The influence of confirmatory measurements (CM) of BP, a metric captured within the AMA MAP™ Hypertension (HTN) program, has not been studied within large populations of patients in usual care settings. We compared consecutive outpatient systolic blood pressure (SBP) readings of adults with HTN to further characterize the influence of CM on RTM.

Methods:
A patient cohort (N= 197,819) comprised of adults with previously diagnosed HTN from 6 diverse healthcare organizations engaged in the AMA’s quality improvement program, was identified for analysis. Outpatient visits with no treatment adjustments, and with a subsequent outpatient visit at participating sites, were evaluated for change in SBP. Each SBP was identified as having derived from a repeat measurement (confirmatory) or a single reading. The analysis was restricted to paired observations of sequential visit BPs with the same measurement method, CM or single. Linear regression was used to evaluate SBP change, controlling for organization, race, sex, age, initial visit SBP, and days between visits, stratified by measurement type.

Results:
A cohort of 197,819 patients with HTN was identified, mean age of 62.2 ± 13.9, initial SBP 131.3 ± 15.2 mmHg. The figure shows the median and interquartile range for change in SBP by 10 mmHg increments of initial SBP, stratified by CM presence. Regression modeling demonstrated that RTM, measured as mmHg fall/mmHg initial, was statistically significantly lower with CM (0.55, 95% CI [0.54 – 0.56]) vs. without (0.59, 95% CI [0.58 – 0.59]). This difference translates to a roughly 5 mmHg decreased effect in RTM for visit pairings with an initial SBP of 140 mmHg.

Conclusion:
RTM remains a powerful influence on follow-up SBP, which complicates assessment of response to antihypertensive interventions. Confirmatory BP measurements reduce RTM and may improve assessment of the patient’s true BP and responses to clinical interventions.
Abstract P330: Next-Gen Hypertension Control: Integrating Clinical Pharmacists And Cutting-Edge EPIC Electronic Medical Record For Quality And Result Driven Approaches at Federally Qualified Health Centers
Authors: Mikhataykina Maria , Agrawal Neha
Published: October 2024

Hypertension management in Federally Qualified Health Centers (FQHCs) requires innovative and comprehensive strategies beyond traditional methods. This study explores a collaborative approach by integrating clinical pharmacists into the healthcare team and utilizing the EPIC Electronic Medical Record (EMR) system. The model addresses medical and non-medical health determinants, offering comprehensive treatment for underserved communities regardless of their ability to pay.

We hypothesized that integrating clinical pharmacists would improve and sustain blood pressure control, resulting in more patients achieving their target health outcomes. As part of multidisciplinary teams, clinical pharmacists identify, track, and analyze patient data, manage medication therapies under collaborative practice agreements, and coordinate with other healthcare providers to ensure continuous care. By leveraging EPIC EMR’s data management and patient monitoring capabilities, clinical pharmacists use real-time data to tailor medication regimens, ensure timely interventions, and conduct follow-ups every 2 to 4 weeks via telemedicine or in-clinic visits until patients reach their goals. This approach enhances patient engagement and medication adherence, which is crucial for adequate blood pressure control and cost management. It also supports personalized care addressing medical needs, lifestyle, and socioeconomic factors affecting patient health. The study, initiated in January 2024, involves adult patients with hypertension at one of the largest FQHC in Houston, TX. Key performance indicators include the percentage of patients achieving target blood pressure levels, medication adherence rates, and the frequency of follow-up visits. Preliminary data from quarter 1, 2024, shows that out of 327 patients, 58% have had at least 2 consultations with a clinical pharmacist. Out of those patients, 46% reached blood pressure control below 140/90 mmHg, while 27% showed improvement toward their goal.

This quality and result-driven approach elevates hypertension management standards, reduces health disparities, and enhances healthcare delivery within FQHCs. Clinical pharmacists have proven to be indispensable members of the healthcare team. This session aims to provide practical insights and strategies for healthcare professionals to implement similar models, paving the way for the future of hypertension care.
Abstract P334: Association Between Arthritis and Heart Failure Among People with Hypertension in United States
Authors: KOOKANOK Chutawat , Poochanasri Methavee , Kulthamrongsri Narathorn , Kanthajan Tatchaya , Bhuriveth Varathpavee , Wareesawetsuwan Nicha , Sodsri Tulaton , Sripusanapan Adivitch , Siramongkholkarn Smuch , Lertsakulbunlue Sethapong , Wanichwecharungruang Nisha , Rochanaroon Voramol , Rodsom Kamonluk , Tantisattamo Ekamol
Published: October 2024

Background:
Hypertension is well known for its association with cardiovascular events and arthritis. However, epidemiological data on the direct relationship between heart failure and arthritis in hypertensive patients is limited. This study examines the hypothesis that arthritis increases the risk of heart failure among patients with hypertension. Additionally, the effect of gender on these outcomes was assessed.

Method:
In our study, we analyzed data from 6,789 adults with hypertension aged 18 to 80 years, sourced from the National Health and Nutrition Examination Survey (NHANES) for the years 2017-2018. Arthritis was defined based on participants’ self-reported diagnosis by a doctor. We utilized logistic regression to explore the relationship between arthritis and the presence of heart failure across three different models. The first model included heart failure alone, the second model included age, gender, education, race, body mass index (BMI), smoking, and drinking, and the third model additionally included coronary artery disease and stroke.

Result:
The prevalence of heart failure among individuals with both arthritis and hypertension stands at 6.0%. Investigation into gender reveals a notable prevalence in males at 8.2% compared to 4.5% in females [Fig 1]. The analysis revealed a positive correlation between the two conditions across the entire population, with correlation coefficients of 2.38 (95% CI: 1.68-3.37), 1.61 (95% CI: 1.11-2.34), and 1.51 (95% CI: 1.01-2.25) for the three models, respectively. Specifically, in males, there was a notably increased association in the first and second models, with correlation coefficients of 2.77 (95% CI: 1.76-4.35) and 1.69 (95% CI: 1.05-2.74), respectively. Conversely, among females, a significant association was observed only in the first model, with a correlation coefficient of 2.24 (95% CI: 1.29-3.89) [Fig 2].

Conclusion:
A robust positive correlation between arthritis and heart failure was observed in hypertensive U.S. patients. Gender was found to be a factor influencing this relationship, with males having a higher risk and prevalence of heart failure compared to the overall population.
Abstract P338: Impaired Endothelial-Dependent Vasorelaxation and Myogenic Response in Renal Afferent Arterioles of Diabetic mice: Role of Endothelial NOX1, and New Gene Pathways.
Authors: Wang Hong , Wu Andrew , Ortiz Pablo , Mendez Mariela
Published: October 2024

Diabetes increases the risk of cardiovascular disease and hypertension, in part, by decreasing arterial vasodilation through decreased NO bioavailability and increased superoxide. In the kidney, type 1 diabetes induces a decrease in renal filtration, proteinuria, inflammation, and fibrosis, increasing the incidence of kidney disease. In diabetic rats and rabbits, prone to renal disease, diabetes blunts acetylcholine (Ach)-induced vasorelaxation of afferent arterioles, in part, by enhancing endothelial superoxide. However, it is unclear whether diabetes affects afferent arteriole vasodilation and myogenic response in mice. We hypothesize that diabetes increases endothelial NOX1 mediated superoxide production in mouse afferent arterioles, decreasing Ach-induced vasodilation. We dissected and perfused afferent arterioles from male diabetic Akita mice 12-14 weeks of age and measured the effect Ach (10
-7
-10
-5
M) on luminal diameter after pre-constriction with norepinephrine. Diabetic Akita mice had a largely reduced Ach-induced dilation at all doses of Ach (80±6% average inhibition in dilation, p<0.025, n=6). To study the role of NOX1, we used the inhibitor ML171 (5µM). When added to the endothelial lumen, NOX1 inhibition completely restored Ach-induced dilation of diabetic Akita mice, which was not different from WT controls. In Control C57 mice, ML171 did not change Ach-induced dilation in Aff-Art (n=6). We then examined the myogenic response in diabetic mice by measuring lumen diameter after step increases in perfusion pressure (60-140 mmHg). Afferent arterioles of diabetic Akita mice did not constrict when pressure was increased, even at 140 mmHg, whereas WT mice showed normal myogenic response (delta constriction 60-140 mmHg WT: 2.15±0.41 vs Akita: 0.37±0.32 µm, WT p<0.01 from baseline, Akita n.s from baseline). To understand the mechanisms behind these effects we performed RNAseq in manually micro-dissected afferent arterioles from 12-week-old Akita and WT mice. Bioinformatics analysis showed 530 DEGs (FDR pAdj<0.05, n=6). Most of the DEGs are involved in endothelial cell function/metabolism, smooth muscle cell contractility, activated inflammatory pathways, and free radical/NO production. We conclude that early diabetes has a large effect on renal afferent arteriole reactivity by affecting the expression of hundreds of genes. These effects are likely involved in hypertension and kidney damage progression in type 1 diabetes.
Abstract P350: Circulating Endothelial microRNAs in Patients with INOCA and Diabetes Mellitus
Authors: Mone Pasquale , Ferrone Marco , Ciccarelli Michele , Varzideh Fahimeh , Gambardella Jessica , Tesorio Tullio , Santulli Gaetano
Published: October 2024

Ischemia with no obstructive coronary artery (INOCA) is a common cause of hospitalizations, resulting in poor outcomes and diminished quality of life. A key element in the pathophysiology of INOCA is endothelial dysfunction, which leads to myocardial ischemia despite the absence of significant coronary artery obstruction. Effective management of endothelial dysfunction is essential for alleviating symptoms and preventing cardiovascular events in INOCA patients. Recent studies have highlighted diabetes mellitus (DM) as a significant contributor to INOCA complications by exacerbating endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs), which are known to regulate gene expression, have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, there is a lack of research evaluating miRNA biomarkers specifically in INOCA patients. In our study, we examined a panel of circulating miRNAs associated with the regulation of endothelial function in INOCA patients with and without DM. Using RT-qPCR, we analyzed miRNA expression in a cohort of consecutive patients undergoing percutaneous coronary intervention (PCI) who were confirmed to have INOCA. We measured the expression levels of a previously validated panel of miRNAs in INOCA patients with DM compared to those without DM. Specifically, we observed an increased expression of several miRNAs previously associated with endothelial dysfunction and decreased expression of miRNAs known to protect endothelial function. Further analyses revealed that among these miRNAs, miR-363-5p was significantly downregulated (P<0.001) and miR-92a-3p was significantly upregulated (P<0.001) in INOCA patients with DM compared to those without DM, as illustrated in the volcano plot in
Figure 1
. Taken together, our findings demonstrated significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their potential role as biomarkers for endothelial dysfunction in INOCA.
Abstract P353: Sexual dimorphism of blood pressure responses to angiotensin II in rats subjected to early life circadian stress
Authors: Aponso Hiruni , Latimer Mary , Rhoads Megan , Pollock David
Published: October 2024

Various forms of early life stress (ELS) lead to a greater risk of hypertension, but no studies have examined stress produced by circadian disruption. We hypothesize that circadian stress during adolescence will increase sensitivity to a hypertensive stimulus in adulthood recapitulating other models of early life stress (ELS). We exposed male and female rats 1-2 weeks post-weaning to 6-hour phase advances (shifts) in the light/dark cycle each week for 4 weeks. To assess whether the molecular clock contributes to the response to ELS, we performed these studies in both Bmal1 knockout (KO) rats and littermate wildtype (WT) controls, Bmal1 is a core circadian clock transcription factor. At 10-12 weeks of age, baseline mean arterial pressure (MAP) was measured (telemetry) followed by a 2-wk angiotensin II (AngII) infusion (250 ng/kg/min, s.c.). At baseline, non-ELS KO rats of both sexes had lower MAP compared to WT littermates, but this genotype effect was lost in ELS rats. Thus, exposure to circadian stress early in life has only a modest effect on baseline blood pressure in rats lacking Bmal1. AngII increased MAP in all groups but was significantly attenuated in male ELS rats compared to non-ELS controls of both genotypes (p
stress
= 0.039, p
genotype
=0.979, p
SxG
=0.917, 2-way ANOVA), but this attenuation was not evident in female rats (p
stress
= 0.497, p
genotype
=0.041, p
SxG
=0.772). We also observed a significant phase advance in peak MAP in male non-ELS rats of both genotypes that was absent in ELS males (p
Genotype
=0.030, p
AngII
<0.001, p
AngIIxGT
=0.025). In contrast, there were no significant differences in peak MAP time in any female rats. The response to AngII was attenuated in ELS male, but not female rats. These data do not support our original hypothesis that exposure to circadian stress during adolescence induces hypersensitization to Ang II in rats but does reveal an impact on the timing of peak MAP in male rats. We propose that the attenuated MAP response to AngII seen in male rats following exposure to specific types of circadian stress during the post-weaning period may pre-condition rats against a subsequent hypertensive stimulus.
Abstract P354: Endothelial Sirt3 deficiency and SOD2 acetylation voids female protection from hypertension
Authors: Dikalova Anna , Ao Mingfang , Gius David , Dikalov Sergey
Published: October 2024

The prevalence of hypertension in early adulthood among women is 3-times lower than in men; but with aging hypertension rate increases in women much steeper, and hypertensive vascular and kidney damage is significantly higher in women. Gender-specific aspects of hypertension are poorly understood and clinical studies did not show protection by estrogen hormone therapy. We found that human hypertension is linked to hyperacetylation of critical antioxidant and metabolic mitochondrial enzymes superoxide dismutase (SOD2) and long-chain acyl dehydrogenase (LCAD) due to vascular deficiency of mitochondrial deacetylase Sirt3. We hypothesized that endothelial Sirt3 depletion leads to the loss of female protective cardiovascular phenotype and exacerbates hypertension in female compared with male mice due to hyperacetylation of mitochondrial proteins. Indeed, infusion of angiotensin II in wild-type female mice showed protection of vascular metabolism, endothelial nitric oxide and lower blood pressure compared with male littermates which was coupled with reduced acetylation of mitochondrial LCAD and SOD2 in female mice. Endothelial specific Sirt3 knockout female mice showed increased mitochondrial acetylation, exacerbated angiotensin II-induced hypertension and higher blood pressure compared with male mice which models human hypertension. Hypertension is linked to SOD2 acetylation (Circ Res. 2020;126(4):439-452) which leads to SOD2 inactivation and vascular oxidative stress. We found that endothelial specific acetylation mimetic SOD2-K68Q knock-in female mice lost antihypertensive phenotype and had higher blood pressure compared with angiotensin II-infused male mice. These studies demonstrate critical role of mitochondrial acetylation in endothelial dysfunction and hypertension suggesting that female antihypertensive phenotype can be associated with reduced mitochondrial acetylation protecting mitochondrial and endothelial functions. It is conceivable that pharmacological targeting of mitochondrial metabolism and acetylation can rescue female cardiovascular protection and improve treatment of endothelial dysfunction and hypertension.
Abstract P363: Prevelance of Hypertension in Kidney Transplant Recepients as Determined by Ambulatory BP Monitoring (ABPM)
Authors: Hommos Musab , Alasfar Sami , Quillen Jaxon , Buras Matthew , Abu Jawdeh Bassam
Published: October 2024

Background:
Cardiovascular disease remains the most common cause of death among kidney transplant recipients, with hypertension being one of the most prevalent risk factors. Understanding the current prevalence of hypertension in this population is critical to help shape post-transplant care policies and guidelines and ensure proper management of CVD risk.

Methods:
We included all kidney transplant recipients who received their transplant between 2019 and 2023 at our center and who completed 24-hour ABPM at 12 months post-transplant. We reported data in mean (SD) unless noted otherwise. BP was categorized per AHA guidelines. This study was deemed exempt by the IRB.

Results:
A total of 940 patients were included in this study. Detailed results are seen in Figure 1 and Table 1. Notable to mention that 60% of the patients had blood pressure > 130/80 mmHg at 12 months post kidney transplant, with the majority being stage 1. Patients with more severe hypertension tended to be older, had lower eGFR, and had more comorbidities. They also had lower diastolic blood pressure than stage 1 HTN patients, consistent with older age. Night-time BP was significantly higher among stage 2 HTN patients.

Conclusion:
Hypertension remains a prevalent condition post-kidney transplant despite the majority of patients having satisfactory kidney allograft function. Ongoing BP monitoring and assessment of out-of-office BP post-kidney transplantation is critical to ensure control of this important cardiovascular risk factor. 24-hour ABPM has several advantages in this group, including accurate measurement of out-of-office BP and detection of nocturnal hypertension, an independent risk factor for cardiovascular events. Additional studies are needed to describe the hypertension subphenotypes (e.g., sustained vs. masked) and to identify predictors of severe uncontrolled hypertension in this patient population.
Abstract P391: Role of Renal Dopamine D2 Receptor in Inverse Salt Sensitivity and Salt Sensitivity of Blood Pressure: Insights from Nephron Segment-Specific Deletion Models
Authors: Feranil Jun , Campisi Cadme Raisha , Moore Shaun , Armando Ines , Jose Pedro
Published: October 2024

The renal dopamine D2 receptor (D2R) is essential in renal and blood pressure (BP) homeostasis. In mice, global
Drd2
deletion or renal-selective
Drd2
silencing increases the renal expression of proinflammatory factors, renal injury markers, and BP. The D2R is expressed in several nephron segments, including the proximal and distal convoluted tubules. To study the differential effects of D2R in these segments, we generated two mouse models: one with
Drd2
deletion only in the
S1 and S2
segments of the proximal tubule

P
SGLT2
::Cre+ Drd2
fl/fl

(
Sglt2 cKO
) and their littermates as controls, P
SGLT2
::Cre-

Drd2
fl/fl

(Sglt2 WT) and another with deletion of the receptor in the
whole nephron

P
CDHR16
::Cre+ Drd2
fl/fl

(
Cdhr16 cKO
) and their littermates as controls,

P
CDHR16
::Cre- Drd2
fl/fl

(Cdhr16 WT). In male Sglt2 cKO mice, compared with Sglt2 WT mice, D2R expression in the renal cortex was decreased by 25% (P<0.05, n=5-6/group). In Cdhr16 cKO mice, compared with Cdhr16 WT mice, D2R expression was decreased by 30% (P<0.05; n=3/group). In Sglt2 cKO mice, tubular lumen expansion, an indication of tubular damage, was higher on low salt (0.09%NaCl; LS) than on normal salt (0.4%NaCl; NS) (25.5±.8 vs. 11.4±.0.3; P<0.001) diet. In Cdhr16 cKO mice tubular lumen expansion was also higher on LS than NS (13.9±0.4 vs 8.7±0.2; P<0.001) diet. In Sglt2 cKO mice, BP (carotid artery under anesthesia) was higher on LS (130±2 mm Hg) than on NS (107±2 mm Hg) or HS (4% NaCl) (100±3 mm Hg) (n=10/group) (P<0.05) diet. In Cdhr16 cKO mice, BP (tail cuff, CODA under anesthesia, confirmed by telemetry) was higher on LS (110±8 mm Hg, P<0.02; n=4-5/group) and HS (119±9 mm Hg, P<0.05; n=4/group) diets than on NS diet (84±5 mmHg). On LS diet, UNaV was lower in Sglt2 cKO than Sglt2 WT (1±0.3 vs 7±2 µEq/24h; P< 0.05; n=4-6/group) mice. On LS diet, UNaV was also lower in Cdhr16 cKO than Cdhr16 WT (5±0.9 vs 34±14 µEq/24h; P<0.05; n=3-4/group) mice. These results indicate that a decrease in D2R expression only in the proximal tubule results in inverse salt sensitivity of BP, i.e., BP higher on LS than NS or HS diets, while downregulation of its expression in the whole nephron results in inverse salt sensitivity, as well as salt sensitivity.
Abstract P393: Isolevuglandins Regulate Chromatin Accessibility in Hypertensive Human Monocytes
Authors: Krishnan Jaya , Phung Johnson , de la Visitacion Nestor , Patrick David
Published: October 2024

Background:
Isolevuglandins (isoLGs) are products of lipid peroxidation that are formed in the presence of reactive oxygen species. IsoLGs are increased in circulating CD14
+
monocytes in patients with hypertension and contribute to inflammatory activation. When adducted to histones, isoLGs prevent nucleosome assembly. Moreover, isoLGs induce disassembly of pre-formed nucleosomes. IsoLGs can be induced in cell culture with tert-butyl hydroperoxide (tBHP) and are efficiently scavenged by ethyl-2-hydroxybenzylamine (Et-2HOBA). We hypothesized that isoLGs regulate chromatin accessibility in hypertensive (HTN) monocytes.

Methods:
Human CD14
+
monocytes were isolated from 3 normotensive (NT) and 5 HTN subjects. HTN monocytes were treated with vehicle. NT monocytes were treated with vehicle, tBHP, or co-treated with tBHP and Et-2HOBA. Cells were cultured for 24 hours and submitted for bulk ATAC sequencing to assess regions of open chromatin across the genome. Data were analyzed using Partek Flow software. Reads were aligned to the GRCh38 human genome. Differences in chromatin accessibility were determined by DESeq2 analysis and were considered significant at an adjusted P-value of 0.05 and fold change of 1.5. Reads were filtered to focus on accessible chromatin at transcription start sites (TSS). First, chromatin accessibility of HTN monocytes was compared to NT monocytes. Second, to determine chromatin regions with isoLG-regulated accessibility that are associated with hypertension, we compared control and tBHP+Et2HOBA treated cells to a combined HTN and tBHP treated group.

Results:
HTN monocytes exhibited increased chromatin accessibility at 131 TSS and decreased accessibility at 56 TSS compared to NT monocytes. Chromatin accessibility was increased at 205 TSS and decreased at 183 TSS in response to both hypertension and isoLGs. Gene set enrichment revealed a significant increase in chromatin accessibility in genes regulating chemokine signaling, RAS signaling, lysosomal activity, and focal adhesion.

Conclusions:
We determined that significant differences in chromatin accessibility are present in HTN monocytes compared to NT monocytes. IsoLGs regulate chromatin accessibility in HTN monocytes. Moreover, isoLGs regulate accessibility of the TSS of genes involved in inflammation and cell migration. These findings implicate isoLGs as novel post-translational histone modifications that regulate chromatin accessibility and contribute to inflammation in hypertension.
Abstract P398: The effects of care by hypertension specialists on cardiovascular outcome, blood pressure control and cost-effectiveness among uncontrolled hypertensive patients
Authors: Cai Li , Yao Ling , Zhu Qing , Liu Shasha , Wang Duolao , Hong Jing , Heizhati Muralbek , Li Nanfang
Published: October 2024

Background:
Studies suggested that physician specialty had an impact on patient outcomes of cardiovascular disease. However, the effects of care by hypertension specialists on clinical outcomes and financial burden among uncontrolled hypertensive patients are unknown.

Objective:
This study was to assess the effects of care by hypertension specialists on risk of cardiovascular outcomes, blood pressure (BP) control, and cost-effectiveness among patients with uncontrolled hypertension.

Methods:
A retrospective cohort study was conducted of patients aged 45-79 years who were admitted to the People’s Hospital of Xinjiang Uygur Autonomous Region, China, for uncontrolled hypertension between 2015 and 2019. We assessed the relationship between care by hypertension specialists and major adverse cardiovascular events (MACE), BP control, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) by the Cox regression, the generalized estimating equations (GEE) model, and the Markov model, respectively.

Results:
A total of 10680 patients with uncontrolled hypertension were followed up for a median of 4.0 years. Among them, 5646 (52.9%) patients received care by hypertension specialists and had fewer MACE than the non-specialists group (21.5 vs 39.7 per 1000-person-years; hazard ratio 0.67; 95% CI: 0.57 to 0.79) according to multiple Cox regression after stabilized inverse probability of treatment weighting. At 4 years, the odds ratio for BP control between the hypertension specialist group and the non-specialist group was 0.83 (95% CI: 0.79 to 0.86). Odds ratios with declining trend were observed at 1, 2, and 3 years. Over a lifetime horizon, the ICERs of the hypertension specialists group was USD 6295.37 per QALY gained compared with the non-specialists group.

Conclusions:
This study provided some evidence that care by hypertension specialists was associated with reduced risk of MACE and improved BP control in patients with uncontrolled hypertension, and was cost-effective.
Abstract P399: Defining A Negative Space: A Scoping Review of Hypertension
Authors: Degtyar Aleksandra , Wilder Marcee , Souffront Kimberly
Published: October 2024

Study Objectives:
This scoping review seeks to examine the existing body of literature to reveal consensus or absence thereof regarding the definition and management strategies for asymptomatic hypertension.

Methods:
The review was conducted using Joanna Briggs Institute guidelines. We searched the CINAHL (EBSCO), Scopus, Ovid EMBASE, and PubMed (MEDLINE) databases using keywords and index terms (“hypertension”, “high blood pressure”, “elevated blood pressure”, “asymptomatic”, “symptomless”, “symptom free”, “emergenc*”, “urgent”) to identify adult patients with hypertension in an emergency or outpatient setting. After review and quality assessment, we retained 35 texts for inclusion.

Results:
The definition of “asymptomatic hypertension” varied widely between the texts. There was significant variation in which society or academic guideline served as the reference and what the blood pressure cut offs were; all specified a lack of end-organ damage. A majority included a definition for hypertensive urgency, most commonly based on elevated blood pressure with vague symptoms. End-organ damage was poorly defined – studies instead described the absence of hypertensive emergency. The most common emergencies mentioned were myocardial infarction, renal failure, and hypertensive encephalopathy. Of the texts which provided recommendations, all recommended a thorough history and physical examination. Only one study recommended additional testing for asymptomatic patients – an ECG and creatinine test. Treatment recommendations for asymptomatic patients relied predominantly on ACEP clinical policy, with a majority of studies advocating for gradual reduction of blood pressure rather than an immediate one, as well as referral for outpatient management.

Conclusion:
There is a need for unified guidelines on the definition and management of asymptomatic hypertension to ensure effective and consistent patient care. Additionally, there is no consensus for further diagnostic testing in patients with a negative history and physical exam, and there is strong agreement that rapid blood pressure decrease in asymptomatic patients can be detrimental. Addressing this gap in guideline consistency and evidence base could enhance clinical outcomes and streamline healthcare processes across different settings. Future research should focus on establishing consensus and developing management strategies that are adaptable to both emergency and primary care environments.
Abstract P404: Using Target: BP™ Initiative Resources and Awards To Improve Evidence-Based Practice Adoption And Blood Pressure Control
Authors: Smith Alison , Overton Katherine , Montgomery Liz , Yang Jianing , Wozniak Gregory , Rakotz Michael , Bolles Michele , Sanchez Eduardo
Published: October 2024

Target:
BP™ is a national initiative created by the American Heart Association and the American Medical Association in 2017 in response to the high prevalence of uncontrolled blood pressure (BP). Committed to advancing health equity, Target: BP supports health care organizations to improve blood pressure control by leveraging AHA guidelines and scientific statements and the AMA MAP
™
framework; assists health care organizations in their journeys to improve and sustain BP control with professional education and resources; and recognizes health care organizations annually with achievement awards.

Target:
BP recognizes organizations that commit to improvement, adopt evidence-based BP activities, and achieve BP control rates ≥70 percent, currently defined as SBP<140 and DBP<90 mmHg in CMS Controlling High Blood Pressure #236. Evidence-based BP activities include 1) calibrating BP measurement devices, 2) checking to see if devices are validated, 3) training and, 4) testing care team members in BP measurement every 6-12 months, 5) using a protocol to measure and confirm BP measurements, and 6) posting a positioning graphic (job aid) next to every place where BP is measured.

Since adding evidence-based activity award criteria, self-attested achievement levels have improved from 2021 to 2023 for device calibration from 47.9% to 65.3%, for team training from 67.6% to 85.5%, for team testing from 67.0% to 86.2%, for measurement protocol use from 83.3% to 94.4%, and for job-aid posting from 54.8% to 69.6%. For each activity, Target: BP provides no-cost education and resources to help achieve the criteria. Overall participation has grown from 330 to 1806 organizations since 2017, now caring for 8.6 million patients with hypertension. In 2023, 866 organizations reported BP control rates ≥70 percent and 1489 reported the adoption of ≥4 of 6 evidence-based BP activities.

Future expansion of the evidenced-based activity criteria will address treatment intensification, lifestyle risk factors, self-measured blood pressure monitoring, and equitable health outcomes. In a 2023 survey of participating organizations, 85.2% of 230 respondents reported “improving patient outcomes” as their primary reason for participating in Target: BP. Among respondents, 95.7% agree or strongly agree that expanded criteria will help to focus QI priorities.

Award incentives appear to play a positive role in encouraging organizations to adopt evidence-based practices and improve blood pressure control.
Abstract P418: Placental small-RNA sequencing reveals a distinct microRNA signature and its functional relevance in a preeclamptic rat model
Authors: Vaka Ramana , Amaral Lorena , Chambers Christy , Campbell Nathan , Zheng Baoying , Lamarca Babbette
Published: October 2024

Introduction:
Despite considerable research over the last few decades, molecular mechanisms that govern preeclamptic (PE) pathogenesis are poorly understood. Recent studies focussed on mechanistic exploration documented that microRNAs (miRNAs) regulate critical processes (endothelial dysfunction, inflammation, oxidative stress) pertinent to PE pathology. However, to the best of our knowledge, a complete placental miRNA expression profiling has not been undertaken. Given the complexity surrounding miRNA biology, a comprehensive miRNA profiling would greatly aid our efforts in better understanding PE pathology.

Objective:
The objective of the current study was to perform a comprehensive profiling of placental miRNAs in PE rat (reduced perfusion pressure;RUPP) model, and identify their functional relevance.

Methods:
RUPP surgery was performed on gestational day (GD)14. Blood pressures (carotid catheterization) were collected on GD19, and placenta (~5mg) was used to isolate miRNA (Qiagen’s miRNeasy Micro Kit). Small RNA sequencing (s-RNA seq) was performed by Illumina sequencer(NEXTFLEX Kit). Enrichment analysis was performed using Cytoscape(BINGO, overrepresentation, p=0.05). Functional associations were retrieved using TAM2.0.

Results:
RUPP rats showed higher MAP (123.8±1.51 vs.98.70±1.53 mmHg, n=10, p<0.0001) vs.control rats. S-RNA seq revealed a total of 142 (40 up and 102 down) differentially regulated (diff-reg) miRNAs in RUPPs. Of these, the top 5 diff-reg miRNAs were; miR-211-3p, miR-628, miR-6324, miR-363-5p, miR-6329 (up) and miR-3587, miR-29b-3p, miR-3556a, miR-29a-3p, miR-21-3p (down). Interestingly, TAM2.0 revealed that these miRNAs are involved in immune response (miR-363, miR-21, miR-29), B-cell differentiation (miR-628), T-cell activation (miR-21), adipogenesis, lipid metabolism (miR-211, miR-29, miR-21), and angiogenesis (miR-363, miR-21) all of which are relevant to PE. Further, enrichment analysis revealed that the top 10 significantly enriched terms include, regulation of transport, cell-cell signaling, calcium ion-dependent exocytosis (BP); synaptic vesicle, perinuclear region of cytoplasm, membrane bound/clathrin-coated vesicle (CC); glycoprotein binding, protein dimerization activity, myosin head/neck binding (MF).

Conclusions:
Our findings demonstrate that dysregulated placental miRNAs may be involved in PE pathogenesis. Future studies building on these preliminary findings may help identify candidate miRNA for therapeutic manipulation.
Abstract P419: Left Ventricular Diastolic Dysfunction in Preeclamptic Patients: A Systematic Review and Meta-Analysis
Authors: Vaka Ramana , Booz George , Adcock Sarah , Hinton Elizabeth , Lamarca Babbette
Published: October 2024

Introduction:
Preeclamptic (PE) patients are at a 4-fold higher risk for developing heart failure later in life. Pathological cardiac remodeling, and the ensuing left ventricular (LV) dysfunction during hypertensive pregnancy are thought to precede heart failure in these patients. Specifically, several observational studies employing echocardiography demonstrate exaggerated LV diastolic function alterations in PE patients suggestive of diastolic dysfunction.

Objective:
Thus, to consolidate the evidence supporting diastolic dysfunction in preeclampsia, we sought to systematically review the clinical literature, and conduct a meta-analysis on the pooled data pertaining to LV diastolic function.

Methods:
Three databases, MEDLINE (Ovid), Embase (Elsevier), and Scopus (Elsevier) were searched from inception to January 26, 2024 and the search results were uploaded to Covidence for screening. The diastolic function data—early diastole mitral flow to annulus velocity ratio (E/e’), isovolumic relaxation time (IVRT), early to late diastole mitral flow velocity ratio (E/A), and E wave deceleration time (DT)—were extracted, and subsequently used to perform meta-analysis using Cochrane’s RevMan Web (Mean Difference, MD; random effects models with inverse variance weighting).

Results:
A total of 63 from 5013 screened studies were eligible for inclusion and of these, only the studies reporting E/e’ (34/63), IVRT (18/63), E/A (38/63), and DT (16/63) were included in the meta-analysis. Our analysis showed that E/e’ is increased (MD of 2.33 [95% CI, 1.77 to 2.89], p<0.00001) in PE patients when compared to healthy pregnant women indicating elevated LV filling pressures. Further, PE patients exhibited significantly higher IVRT (MD of 8.88 msec [95% CI, 6.07 to 11.68], p<0.00001) and lower E/A (MD of -0.16 [95% CI, -0.25 to -0.06], p=0.001), collectively suggesting that the myocardial relaxation is impaired in preeclampsia. Interestingly, DT (MD of 3.10 msec [95% CI, -5.43 to 11.62], p=0.48) was not found to be different between the groups.

Conclusions:
Our findings demonstrate that PE patients develop LV diastolic dysfunction during pregnancy which may be mediated by hypertension caused pressure overload. Given that diastolic dysfunction is a hallmark characteristic of heart failure with preserved ejection fraction (HFpEF), future longitudinal studies examining cardiac function during pregnancy and postpartum will help determine if PE patients are destined to develop HFpEF.
Abstract P422: Neuropeptide FF and Its Receptor NPFFR2 Decrease Renal Sodium Excretion and Increase Blood Pressure in Mice
Authors: Feranil Jun , Asico Laureano , Armando Ines , Felder Robin , Jose Pedro , Lee Hewang
Published: October 2024

The kidney is critical in the overall regulation of fluid and electrolyte balance and blood pressure. Neuropeptide FF (NPFF), a morphine-modulating peptide, regulates cardiovascular function through its interaction with two receptors, NPFFR1 and NPFFR2. We now report that NPFF and its receptors, mainly NPFFR2, are expressed in the kidney. NPFF (9.25 mmol, 0.5 mL/hr, 0.05 nmol/day, 7 days) chronically infused underneath the renal capsule, decreased renal sodium excretion (UNaV) from 0.68±0.07 mEq/day, n=5 to 0.43±0.06 mEq/day (n=6/group) in conscious C57BL/6 mice. This was accompanied by an increase in systolic blood pressure (SBP, 114.5±5.0 mm Hg, n=4); the infusion of vehicle (saline) did not affect the blood pressure (96.4±3.0 mm Hg, n=4). The renal subcapsular injection of a single dose (10 µg in 100 µL) of NPFF also increased SBP within 15-35 min (NPFF: 105.5±3.44 mm Hg, n=6); saline injection did not affect SBP (82.6±5.65 mm Hg, n=4). RF-9 (10 µg in 100 µL), an antagonist of NPFF receptors prevented the NPFF-mediated increase in SBP (NPFF alone: 105.5±3.44 mm Hg, n=6; RF+NPFF: 88.5±5.90 mm Hg, n=5), whereas RF-9, alone, had no effect (Baseline: 97.6±2.70 mmHg; RF-9: 90.9±4.70 mm Hg, n=5). The renal subcapsular injection of scrambled peptide (10 µg in 100 µL) had no effect on SBP (86.1±1.83 mm Hg, n=4). However, SBP was decreased by the renal subcapsular infusion of
Npffr2
siRNA (98±4 vs 113±3 mmHg; P < 0.05; n=3-5/group) in C57Bl/6 mice fed with a high salt diet (4% NaCl). Furthermore, the SBP of conventional germline
Npffr2
knockout (KO) mice fed a high salt (4% NaCl) diet was lower than the SBP of wild-type (WT) littermates (WT: 105.6±2.9 mm Hg, n=5; KO: 90.5±5.5 mm Hg, n=4, P < 0.05). By contrast, in mice fed normal salt (0.8% NaCl) diet, SBP was not different between
Npffr2
KO mice and WT littermates (WT: 96.5±4.5 mm Hg, n=5; KO: 98.7±11.7 mm Hg, n=4, P > 0.05). Taken together, NPFF and its receptor, NPFFR2, in the kidney cause salt-sensitive hypertension in mice. Uncovering the functional relevance of renal NPFF in the dynamic regulation of renal sodium transport will lead to a better understanding of blood pressure homeostasis.
Abstract P423: Blood Pressure and Renal Function Outcomes After Revascularization of Renal Artery Stenosis in Patients from 3 Different Clinical Settings
Authors: Martinez Juan Luis , Clara Albert , Vazquez Susana , Galceran Isabel , Marcos Lidia , Perez Saez Maria Jose , Crespo Marta , Oliveras Anna
Published: October 2024

The effects of renal percutaneous transluminal angioplasty (rPTA) of renal artery stenosis (RAS) on BP and renal function are controversial. We aim to search for possible differences in these outcomes in different clinical settings.

We conducted an observational analysis of effects of rPTA in patients with RAS diagnosed as a result of: screening patients with peripheral artery disease (Vascular Dpt.; G1, n = 20), patients with resistant hypertension or with clinical suspicion of RAS (Hypertension Unit; G2, n = 28) or kidney transplant patients with renal function impairment and/or elevation of BP (Transplantation Unit; G.3, n = 21). RAS is defined as a reduction of ≥70% of the renal artery lumen.

Sixty-nine patients were examined (mean age 67±12yr, 64% male). Overall, mean±S.D. baseline SBP/DBP (mmHg) was 147.4±20.6 and 75.7±1.8, and the estimated glomerular filtration rate (eGFR) was 48.7±27.0 mL/min/1.73m
2
. G.1 exhibited a higher prevalence of smoking patients (90%) and patients with past major vascular events (100%), lower DBP (70.0±9.8 mmHg) and better renal function (eGFR: 62.5±23.2 mL/min/1.73m
2
), compared to G.2 and G.3.

Twelve months after rPTA, BP decreased only in patients in G.2 and G.3: variation of (Δ) SBP(mmHg): mean (95%CI)= -18.9 (-26.7 to -11.0) and -20.0 (-29.8 to -10.1), respectively; p<0.001 for both; ΔDBP (mmHg): mean (95%CI)= -6.6 (-10.7 to -2.4), p=0.003 and -6.3 (-11.7 to -0.8), p=0.027, respectively. Regarding renal function, it only improved in G.3: ΔeGFR (mL/min/1.73m
2
): mean (95%CI)= 8.9 (1.5 to 16.4), p=0.022. ΔSBP was associated with baseline SBP (r= -0.709, p<0.001) and the origin group (Rho = -0.362, p = 0.003); ΔeGFR was associated with baseline eGFR (r= -0.508, p<0.001) and the origin group (Rho = 0.356, p = 0.004). Overall, median ΔSBP was -11 mmHg, and median ΔeGFR was +1.0 mL/min/1.73m
2
. An ANOVA analyzed factors associated with these changes. After adjusting for confounders, ΔSBP was dependent on baseline SBP and group of origin (both p<0.05; adjusted R
2
0.340). ΔeGFR was dependent on baseline eGFR and diabetes (both p<0.05; adjusted R
2
0.123).

Blood pressure decreased in patients with suspected RAS because of resistant hypertension 12 months after rPTA. Both BP and renal function improved after rPTA in kidney transplant patients with diagnosis of RAS. Higher BP levels and lower eGFR correlated with better results. Patients with peripheral artery disease screened for RAS showed no change in BP or renal function after rPTA.
Abstract P427: Novel SNVs of NBCe1, D405E and I803M mutants, reduced cell-surface expression and transport activity.
Authors: Yamazaki Osamu , Fujii Wataru , Yakuwa Yumika , Chonan Atsuro , Furukawa Taiji , Kozuma Ken , Fujigaki Yoshihide , Shibata Shigeru
Published: October 2024

Introduction:
The electrogenic Na
+
/HCO
3
-
cotransporter NBCe1 is mainly expressed in proximal renal tubule, and regulate pH homeostasis and plasma volume. NBCe1 homozygous mutation causes many symptoms, including severe hypotension, proximal renal tubular acidosis (RTA), and extrarenal phenotype (migraine, mental retardation, mineral bone disorder and ocular abnormalities).

Hypothesis:
Undetermined single nucleotide variants (SNVs) in NBCe1 will be crucial role of sodium and bicarbonate transport.

Methods:
We identified the missense mutations (D405E and I803M) in NBCe1 variant A (kidney type) from the NCBI database. We conducted a comparative analysis of cellular localization and cell protein expression using confocal microscopy and western blotting. Furthermore, we performed functional analysis in D405E and I803M SNVs using two-electrode voltage clamp method.

Results:
Immunofluorescence analysis with confocal microscopy revealed that the D405E and I803M variants were present predominantly in the cell-surface in HEK293 cells. Western blotting in HEK293 cells confirmed that the D405E and I803M variants were significantly reduced protein expression level (25% in D405E and 57% in I803M) compared with WT, respectively.

Moreover, electrophysiological analysis revealed that D405E and I803M variants were significantly reduced transport activity. These consisting data suggest that cell-expression level and transport activity are comparable.

Conclusion:
These data illustrate the diverse physiological consequences of distinct SNVs and underscore the importance of functional characterization in membrane transport proteins.
Abstract P428: Angiotensin II vascular abnormalities in 32.5% of 3322 patients with essential hypertension(EH): Use of angiotensin II analogue, saralasin.
Authors: Anderson Gunnar
Published: October 2024

Introduction:
Renin-AII abnormalities in EH were documented by infusing saralasin
,
the AII analogue:patients with a abnormal fall in mean BP(<=-8mmHg) indicating a “angiotensinogenic” component to their hypertension and those with a abnormal rise in mean BP(>=8mmHg) indicating, as previously reported, an increased AII vascular sensitivity.

Methods:
Pa
tients
tested for secondary HBP in a 1-day BP study with recumbent BP by Arteriosonde, infusion of Lasix, recumbent for 1 hr, stand for 2 hours, measure renin(ng/ml/hr), recumbent for 1/2 hr, infusion of saralasin for 1/2 hr, infusion of 2 l of 0.9%NS over 4 hr and measurement of plasma aldosterone and cortisol. Patients with secondary causes of hypertension, those age<18, those with renal insufficiency, vascular abnormalities (eg diabetes, ASHD) were excluded. Data is now stored using excel 365. Linear regression was calculated using GraphPad Prism version 10.0.0 for Windows, www.graphpad.com.

Results:
3691 adults(mean age = 43.4±0.2, 46.3% female) with EH of whom 3322 received saralasin: “Angiotensinogenic” HBP occurred in 12.9% of EH and they were younger[p=.0012,t=3.2]than the EH group, and had a high renin(nl:1.7-6.6). The saralasin-induced fall in BP was -15.6±.6/-13.0±.3. Saralasin increased the % of SBP that was <=130 from 28.1% to 54.7%. Saralasin induced an abnormal BP rise in 19.6% of patients who were older with low renin. There was a significant linear correlation with log
10
of renin for 3322 patients with EH for Δ Mean BP with saralasin[ΔMBP = -9.3*(log renin) + 4.3] (p<.0001,f=1056, r=-.50). Results were similar in 1463 patients on no BP meds. [ΔMBP=-9.5*(log renin) +4.46](p<0.0001,f=470,r=-.50). 12.5% were "angiotensinogenic", 16.7% pressor responders.

Conclusions:
EH has a significant “angiotensingenic” component (12.9%) and increased AII vascular sensitivity(19.6%), both of which may contribute to their HBP.

table:
three saralasin groups(BP fall, rise,no Δ) as in abstract(data are mean+se)

Change in

mean BP to
------------

#(%)

--------

initial BP

-------

post lasix BP

----

saralasin BP

--

Age(yr)

-

renin

i
nfusion of

saralasin

(1)<= -8 mmHg
----
430(12.9%)
--
160±2*/99±1*
---
147±1*/96±1*
----
132±1*/83±1*
---
41.1±.7*
---8.1±.4*

(2)>=+8 mmHg----
651(19.6%)
--
170±1
&
/103+1
&
-
142±1
&
/90±1
ns1
160±1
&
/101±1
&
-

50.2±.5
&

---

1.5±.1
&

(3)>8,<-8 mmHg-2241(67.5%)
-

155±1
@
/98±1
!

---
137±1
@
/

90±1
@

-

138±1
@
/90±1
@

-

41.3±.9
ns2

-
3.4±.1
@

___________________________________________

*p<.00001(1v2),
&
p<.0001(2v3),
@
p<.0001(1v3),
!
p=ns(1v3),
ns1
(2v3),
ns2
(1v3)