bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 120: Greater 24-hour Blood Pressure Variability Is Associated With Higher Retinal Microvascular Resistance And Smaller Lumen Diameter In Healthy Normotensive Adults
Authors: Gimblet Colin , Ernst Jackson , Holwerda Seth , Kardon Randy , Hashimoto Ryuya , Dubose Lyndsey E , Fiedorowicz Jess , Pierce Gary L
Published: October 2023

Introduction:
Elevated blood pressure (BP) is associated with damage to high flow, low resistance target organs such as the retina. Recent evidence suggests that 24-hour BP variability (BPV) is a novel risk factor for cardiovascular disease, independent of 24-hour average BP. However, whether 24-hour BPV is related to concentric retinal arteriole remodeling in healthy adults is unknown. Thus, the purpose of our study was to determine the degree to which 24-hour BPV is associated with retinal lumen diameter and vascular resistance in healthy young/middle-aged adults, independent of 24-hour average BP.

Methods:
Healthy, normotensive adults aged 25 to 60 years (n=40; 50% female) underwent measurements of retinal arteriole diameter and flow using laser speckle flowgraphy. 24-hour brachial BP was determined using ambulatory BP monitoring. BPV was calculated as the standard deviation of all BP recordings for systolic and diastolic BP. Retinal vascular resistance was calculated as ocular perfusion pressure divided by mean retinal flow across 4 arterioles. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV).

Results:
Higher 24-hour systolic and diastolic average BP were associated with smaller retinal lumen diameter and elevated vascular resistance (P<0.05). Although both systolic BPV (r=0.391, P=0.012) and diastolic BPV (r=0.315, P=0.048) were associated with higher retinal vascular resistance, only diastolic BPV was associated with smaller retinal arteriole lumen diameter (r=-0.393, P=0.012). The association of greater diastolic BPV with smaller retinal arteriole lumen diameter (β=-0.363, P=0.01) and higher retinal vascular resistance (β=0.395, P=0.007) remained after adjusting for age, body mass index, cfPWV, and 24-hour average diastolic BP.

Conclusion:
Higher diastolic BPV may contribute to adverse remodeling of retinal arterioles in healthy normotensive adults independent of arterial stiffness and traditional cardiovascular disease risk factors. Future studies could utilize local metabolic vasodilation via diffuse luminance flicker to examine whether retinal arteriole autoregulatory mechanisms are impaired in individuals with higher BPV.
Abstract 121: A Cell Atlas Of The Dahl SS Thoracic Aortic Perivascular Adipose Tissue: Delving Into Single-Cell Data
Authors: Terrian Leah , Thompson Janice , Contreras Andres , Rockwell Cheryl , Watts Stephanie W , Bhattacharya Sudin , Nault Rance
Published: October 2023

Nearly every blood vessel is surrounded by a layer of fat aptly named perivascular adipose tissue (PVAT). PVAT is an important regulator of vascular tone known largely for its anti-contractile secretions. Recently, however, new PVAT functions have been discovered. These findings include mechanosensing and immune cell regulating capabilities. Further research would be facilitated by the existence of a map of the cells that make up PVAT and showing how they differ from the cells in other types of adipose tissue. Here, we build this map using single-nucleus RNA-sequencing (snRNA-seq) to construct a thoracic aorta PVAT (tPVAT) cell atlas. We then test our hypothesis that cell populations, cell-type proportions, and gene expression patterns differ between tPVAT and brown adipose tissue (BAT). To accomplish this, snRNA-seq was performed on two samples of both tPVAT and BAT that were collected from male Dahl SS rats fed a normal diet. The resulting sequencing files were quality controlled and processed using standard snRNA-seq pipelines. A total of 30,352 and 29,813 nuclei were profiled in tPVAT and BAT respectively. Both tissues were primarily represented by adipocytes, smooth muscle cells, and endothelial cells with a few differences in proportions (Fig. 1). Notably, there is a population of white adipocytes representing 0.3% (89/30352) of nuclei in tPVAT that are absent in BAT. We also find many genes that are differentially expressed in each cell type between the two tissues. This cell atlas provides valuable information to understand the cells that participate in recognized and newly discovered mechanisms of PVAT.
Abstract 126: Nlrp3 Chromatin Availability And Isolg-adducted Histones In Salt-sensitivity Of Blood Pressure
Authors: Pitzer Mutchler Ashley , Ertuglu Lale , Jamison Sydney , Laffer Cheryl L , Kirabo Annet
Published: October 2023

Salt-sensitivity of blood pressure puts both normotensive and hypertensive individuals at a higher risk for cardiovascular morbidity and mortality. Isolevuglandins (IsoLGs) are increased in multiple oxidative-stress associated diseases, including salt sensitive hypertension. Scavenging of IsoLGs using 2-HOBA in a mouse model of salt-sensitive hypertension blocked NLRP3 inflammasome in dendritic cells (DCs) and abolished salt-induced hypertensive response. IsoLGs adduct to histones, specifically H4. We tested the hypothesis that elevated sodium in antigen-presenting cells leads to IsoLG-adducted H4 histones and increased chromatin availability to NLRP3 inflammasome components contributing to salt-sensitive hypertension.
In vivo
studies were performed on 19 hypertensive subjects enrolled in an acute inpatient protocol to assess response to salt loading (460 mmoL/24 hrs) and salt depletion (10 mmoL/24 hrs, and furosemide 40 mg x 3). Isolated PBMCs from salt sensitive subject (δ;SBP
SD-SL
= -12.9) and a salt resistant subject (δ;SBP
SD-SL
= 0.35) were analyzed by ATACseq.
In vitro
studies were performed on isolated CD11c+ dendritic cells treated with either normal salt (150mM) or high salt (190mM) and histone protein extraction isolated for western blot and blotted for D11, an ScFv specific to IsoLG-adducted proteins. Additional
in vitro
studies were performed on isolated monocytes from 11 individuals treated with either normal or high salt and submitted for RNA sequencing. RNAseq data of isolated monocytes demonstrated an overall upregulation in differentially expressed histone modification genes after high salt visualized in a heatmap and PCA plot, specifically, upregulation of gene
HIST4H4
encoding the Histone H4 (25.4 ± 4.6 vs 65.5 ± 6.5, [n=11, q=1.5 x 10
-3
]). Changes in chromatin availability inflammasome component NLRP3 were more salt responsive in DCs of the salt-sensitive subject versus the salt-resistant subject after salt depletion. Additionally, high salt increased IsoLG-histone adduction in CD11c+ DCs. Our results suggest the high sodium environment increase in IsoLG-adducts may epigenetically regulate NLRP3 inflammasome components in SSBP.
Abstract 137: Trends In Primary Aldosteronism Screening - An Underutilized Test In Hypertension
Authors: Kositanurit Weerapat , Giacona John M , Xie Donglu , Hoeting Natalie , Navar Ann M , Vongpatanasin Wanpen
Published: October 2023

Previous studies have shown low screening rates for primary aldosteronism (PA) in at-risk hypertensive (HTN) patients. However, the impact of recent HTN guidelines on screening has not been thoroughly evaluated. Therefore, we retrospectively reviewed adults with new diagnosis of HTN seen in outpatient clinics between 1/1/2015 and 12/31/2020. We included patients with BP ≥140/90 mmHg for 2 consecutive visits or had HTN ICD codes. Patients were categorized into Stage-2 HTN or greater (BP ≥140/90 mmHg) and apparent resistant HTN (aRHTN) defined as uncontrolled BP (≥130/80 mmHg) on 3 anti-HTN drugs including a diuretic or controlled BP on ≥4 drugs based on 2018 ACC/AHA resistant HTN guidelines. A total of 34,384 patients were included with mean age 61±14 years, 53% (18,384) women, 17% (5,693) Black individuals, with 2.5 years of median follow-up. As shown in Figure 1, the PA screening rates over time ranged 1-2% and 4-6% in Stage-2 HTN or greater (A), and aRHTN (B), respectively. Moreover, rates of PA screening index by year were not increased after the launch of the 2018 ACC/AHA guidelines, for both categories. Interestingly, the proportion of PA screening did not change during the COVID-19 pandemic despite the reduction in number of patients seen in 2020. In conclusion, the rate of PA screening has not increased in the hypertensive population even after the guidelines demonstrate the need for screening in these at-risk patients. These findings highlight the underutilization of PA screening and calls for increased awareness of the disease in at-risk populations.
Abstract P103: Higher Preoperative Plasma Aldosterone Concentrations Are Associated With Elevated Risk Of Atrial Fibrillation After Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Wan Jindong , Liu Sen , Yang Yi , Wang Dan , Wang Xinquan , Zhou Peng , Wang Peijian
Published: October 2023

Background:
Postoperative atrial fibrillation (POAF) is associated with poor outcomes in patients with coronary chronic total occlusions (CTO). Aldosterone is a steroid hormone that regulates fluid and electrolyte homeostasis and is known to increase the risk of proarrhythmia. This study aimed to explore the additional value of preoperative plasma aldosterone levels for predicting POAF after CTO percutaneous coronary intervention (PCI).

Methods:
We conducted a prospective cohort study involving consecutive patients with a left ventricular ejection fraction (LVEF) greater than 50% requiring CTO-PCI in the First Affiliated Hospital of Chengdu Medical College. Patients were excluded if they had a history of AF, preoperative endocarditis and/or a ventricular assist device. Plasma aldosterone levels, echocardiography and transforming growth factor beta1 (TGF-β1) examination were assessed before percutaneous recanalization. The primary endpoint was the occurrence of POAF within 30 days after percutaneous recanalization. New-onset POAF after CTO-PCI was defined as any episode detected via continuous in-hospital electrocardiogram/telemetry monitoring and documented by a physician in the chart, regardless of duration or need for treatment.

Results:
Thirty-eight of 268 (14.2%) patients had POAF. Compared with controls, patients experiencing POAF were significantly older, had a higher body mass index, had diabetes and hypertension, and had higher preoperative plasma aldosterone levels. In logistic regression analysis, higher plasma aldosterone levels exhibited 1.75-fold higher odds (95% confidence interval [CI], 1.15-2.32, P=0.004) for the presence of POAF, which was significant in the adjusted model (odds ratio [OR], 1.82 [95% CI, 1.21-2.45], P=0.007). Reverse transcriptase PCR analysis performed on the left atrial appendage and plasma examination revealed that TGF-β1 was activated in POAF patients.

Conclusion:
Higher plasma aldosterone levels are associated with increased odds for POAF in patients with CTO-PCI, even in the absence of primary aldosteronism, implying that plasma aldosterone levels might be a target for POAF risk stratification after CTO-PCI.
Abstract P106: High-throughput Sequence Symmetry Analysis To Detect Angiotensin-receptor Blockers (arb) Induced Prescribing Cascades.
Authors: Smith Kayla , Morris Earl , Ndai Asinamai , Keshwani Shailina , Kulkarni Priyanka , Schmidt Stephan , Pepine Carl , Vouri Scott , Smith Steven M
Published: October 2023

Introduction:
ARBs are considered first-line antiHTN therapy, but side effects may prompt additional therapy resulting in prescribing cascades. We sought to screen for potential ARB-induced prescribing cascades during real-world use via high-throughput sequence symmetry analysis.

Methods:
Using claims from 5% (2011-15) and 15% (2016-20) samples of Medicare fee-for-service beneficiaries we identified new ARB users aged ≥66 years who had continuous enrollment for ≥360 days pre- and ≥180 days post-ARB initiation. We screened for initiation of 446 other ‘marker’ drug classes (based on WHO Anatomical Therapeutic Classification level 4 codes) within ±90 days of ARB initiation, generating sequence ratios (SRs) representing proportions of ARB initiators starting the marker class after, compared to before, the ARB. Adjusted SRs (aSRs), accounting for prescribing trends over time, were calculated with 95% CIs >1 considered statistically significant.

Results:
We identified 278,586 ARB initiators (mean ± SD age, 76.3 ± 7.3 years; 63% women, 92% hypertension). Of 446 ‘marker’ classes studied, and excluding other antihypertensive classes, we discovered 49 statistically significant signals indicative of potential prescribing cascades. The 30 strongest prescribing cascade signals by aSR are summarized (Figure), and included iron trivalent medications and
H. pylori
treatments.

Conclusion:
We identified potential prescribing cascade signals reflecting known as well as potentially underrecognized ARB adverse events in this Medicare cohort. Future work is needed to assess biologic plausibility and determine impact of these cascades on patient outcomes.
Abstract P112: Association Between Plasma Aldosterone Concentration And Ambulatory Blood Pressure Profile In Patients With Primary Aldosteronism
Authors: Morita Ryutaro , Azushima Kengo , Wakui Hiromichi , Tamura Kouichi
Published: October 2023

Background:
Patients with primary aldosteronism (PA) have a higher risk of cardiovascular disease (CVD) than essential hypertension due to underlying hyperaldosteronism. Although an altered circadian blood pressure (BP) rhythm estimated by ambulatory blood pressure monitoring (ABPM) has been highlighted as a major contributor of CVD in essential hypertension, there would be very few reports investigating clinical significance of ABPM in PA patients. Therefore, we aimed to examine a possible association between plasma aldosterone concentration (PAC) and ABPM profile in PA patients.

Methods:
Consecutive 40 PA patients, who had been diagnosed by the functional tests and underwent adrenal venous sampling (AVS) from April 2015 to July 2022, were included in this study. The clinical parameters were measured during hospitalization for AVS. The dietary salt intake of hospitalized patients was controlled at 6 g/day. The 24-h ABPM was performed from the first day of hospitalization to the next day, and AVS was performed on the third day in the morning. During AVS, blood samples were collected from the inferior vena cava before and 1 hour after adrenocorticotropic hormone (ACTH) stimulation to measure the PACs.

Results:
We firstly analyzed a correlation between PAC and ABPM profile and found that post-stimulation PAC was negatively correlated with nocturnal dipping rate in both systolic and diastolic BPs (
R
=-0.387,
p
=0.020, and
R
=-0.341,
p
=0.042, respectively), while pre-stimulation PAC was not. Thus, according to the median of post-stimulation PAC, we divided participants into high PAC and low PAC groups and compared clinical characteristics between the two groups. The nocturnal BP dipping rates were significantly lower in the high PAC group than low PAC group (
p
= 0.009). Multiple regression analysis revealed that high PAC was an independent factor contributing to low nocturnal BP dipping rates (
β
= –0.316,
p
= 0.038).

Conclusions:
In this cross-sectional study, we revealed that higher PAC was significantly associated with a non-dipper circadian BP profile characterized by lower nocturnal BP dipping rates in PA patients. Additionally, ACTH stimulation may improve the sensitivity of PAC as a clinical indicator of nocturnal hypertension.
Abstract P113: Variations In 24 Hour Ambulatory Blood Pressure Coverage Across Canada And The United States
Authors: Pasricha Sachin Vidur , Padwal Raj , Ringrose Jennifer , Dubrofsky Lisa
Published: October 2023

Introduction:
The gold standard for diagnosis hypertension is a 24-hour ambulatory blood pressure monitor (ABPM). In-office blood pressure may be falsely high in 30% of individuals (white coat hypertension) or falsely normal in 20% of individuals (masked hypertension). We hypothesize that ABPM funding varies across Canada and the U.S, and sought to investigate this hypothesis.

Methods:
We reviewed the fee schedules in 14 jurisdictions: 10 Canadian Provinces, three Canadian Territories, and the U.S. Centre for Medicare and Medicaid Services - CMS. We collected data on a) if ABPM is funded, b) indications approved for funding, and c) the reimbursement amount. We summarized this data descriptively.

Results:
Five jurisdictions (Alberta, Saskatchewan, Quebec, New Brunswick, the U.S. CMS) cover ABPM. The U.S CMS has specific indications for use and limits frequency to one annually, while Saskatchewan limits it to five annually (Table 1). Reimbursement amounts vary widely, from $14.70 to $81.16 (CAD), as do reimbursement components. Prior research using IBM’s MarketScan commercial claims database identified a median ABPM reimbursement by U.S private insurers of $89 (USD).

Conclusion:
ABPM coverage across Canada and the U.S. fluctuates. There is also variation in reimbursement amount and indications among jurisdictions providing coverage. Further studies should seek to measure if this variation corresponds with a variation in ABPM use, diagnostic rates of masked and white coat hypertension, or antihypertensive spending per capita. We would advocate for jurisdictions that do not currently fund ABPM to consider coverage in light of this geographic variability.
Abstract P121: Medical Treatment And Outcomes In Adults With Co-occurring Hypertrophic Cardiomyopathy And Hypertension: A Scoping Review
Authors: Montgomery Sophie , Nicolas Barnaby , Pleasure Mitchell , Reuter Maria , Collins Maxine , Massera Daniele , Shimbo Daichi , Sherrid Mark , Arabadjian Milla E
Published: October 2023

Background:
Over 50% of adults with hypertrophic cardiomyopathy (HCM) have co-occurring hypertension (HTN). Therapeutic management poses a clinical challenge as first and second-line antihypertensive medications (AHM) can worsen obstructive HCM (OHCM), which comprises ~70% of all HCM. Treatment and clinical course in adults with HCM+HTN are underexplored. With this scoping review, we sought to 1) characterize the literature on the management and outcomes of HCM+HTN, and 2) identify knowledge gaps to inform future research directions.

Methods:
We searched 5 databases (PubMed, CINAHL, Scopus, Embase, Web of Science) to identify and review eligible articles: 1) peer-reviewed; 2) English-language; 3) cohorts with an established HCM diagnosis; 4) data on management, and/or outcomes related to co-occurring HTN; 5) published 2011 - 2023. We reviewed reference lists of eligible articles to find other relevant studies. The review was conducted according to PRISMA ScR guidelines, with 2 independent reviewers at each stage of review.

Results:
We extracted data from 12 articles (of 966 results); all were retrospective observational. Five defined HTN (JNC7 criteria and/or AHM). One study examined HTN in adults with apical HCM, 2 in adults with OHCM, and 9 did not differentiate HCM phenotype. Only 1 study described a medication strategy for treating HCM+HTN, showing that prioritizing β1 selective blockers and verapamil over direct vasodilators led to improvement in functional (NYHA) class and lower blood pressure. There was notable heterogeneity in definitions and analytic methods related to outcomes. Four studies showed worse renal function in those with HCM+HTN versus HCM alone, but results were equivocal in other outcomes, including stroke, cardiovascular disease, atrial fibrillation, surgical interventions for HCM, and sudden death. All-cause mortality was similar between those with HCM+HTN and HCM alone.

Conclusions:
To our knowledge, this is the first scoping review to examine the literature on the clinical course and outcomes of patients with HCM+HTN. Our results highlight the critical need for further research to improve understanding of co-occurring HCM and HTN, with particular focus on medical management to optimize clinical course and outcomes.
Abstract P124: Piezo1 Mediates Vasodilation Induced By Acute Hyperglycemia In Mouse Renal Arteries And Microvessels
Authors: fei lingyan , Xu Minze , Wang Honghong , jiang shan , Patzak Andreas , khedkar Pratik , Zheng Zhihua
Published: October 2023

Background:
Acute hyperglycemia (HG) is a risk factor for developing acute kidney injury and poor renal outcome in critically ill patients. The role of renal vasculature in this context is not clear. We hypothesize that HG-associated hyperosmolarity facilitates vasodilation through Piezo1-mediated eNOS activation.

Methods:
Vasoreactivity of isolated mouse mesenteric (MA) and renal interlobar (ILA) arteries were analyzed using wire myography and that of renal afferent (AA) and efferent (EA) arterioles, and vasa recta (VR) using microvascular perfusion. Immunofluorescence and western blot were used for molecular analyses of isolated mouse blood vessels as well HUVECs.

Results:
Pre-treatment with HG (44 mmol L
-1
glucose; 4 h) increased acetylcholine (ACh)-induced relaxation in ILA and MA, which was prevented by eNOS inhibition using L-NAME. Hyperosmotic mannitol solution had a similar effect. HG induced an immediate, L-NAME-inhibitable dilation in AA, EA, and VR, whereby stronger dilation in AA compared to EA. HG also increased glomerular filtration rate in mice. In HUVECs, HG and the Piezo1 activator Yoda1 increased levels of Piezo1 protein, phosphorylated CaMKII (p-CaMKII), Akt, and p-eNOS. The HG-effect could be prevented by inhibiting Piezo1 using GsMTx4 and CaMKII using KN93. Furthermore, in arteries and microvessels, inhibition of Piezo1 using GsMTx4 prevented the HG-effect, while Yoda1 caused relaxation and dilation, respectively.

Conclusion:
Results reveal that Piezo1 mediates renal vasodilation induced by hyperosmolarity in acute HG. This mechanism may contribute to the pathogenesis of renal damage by acute HG.
Abstract P137: Lack Of Atrial Natriuretic Peptide Aggravates Glomerular Disease In Type 1 Diabetic Nephropathy
Authors: Spires Denisha R , Cherezova Alena , Ilatovskaya Daria
Published: October 2023

Introduction:
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and DKD patients have a significantly higher risk of developing cardiovascular disease. Some studies have suggested the role of the Atrial Natriuretic Peptide (ANP) in DKD development. ANP is a cardiac hormone that regulates renal salt/water homeostasis and plays a major role in renal hemodynamics. We hypothesized here that ANP plays a critical role in T1DKD, playing a potential protective role in podocytes of the glomeruli.

Methods:
We used the ANP knock-out (SS
NPPA-/-
) rat on the Dahl Salt-Sensitive (Dahl SS) background injected with streptozotocin (STZ; 75mg/kg) as a model of T1DKD. At 9-10 weeks of age, male SS
NPPA-/-
and Dahl SS wild-type (SS
WT
) rats were
i.p.
injected with either STZ or vehicle. Baseline, midpoint, and endpoint blood glucose, urine, and body weights were collected. Glomerular filtration rate (GFR) was assessed before animals were. Glomerular injury was scored blindly on a scale from 0-4 (0 = healthy glomerulus, 4 = severely sclerosed) in Masson Trichrome stained kidneys. One-way ANOVA through Origin 2019b was used for statistical analysis.

Results:
STZ- SS
WT
and STZ-SS
NPPA-/-
groups exhibited similar body weight (237.8 ± 18.9 vs. 234.5 ± 10.03 g, respectively), two-kidney weight to body weight ratio (32.1 ± 1.6 vs. 29.4 ± 1.6 mg/g, respectively), and endpoint blood glucose levels (>650 mg/dL). Interestingly, we observed a significantly higher heart to body weight ratio for the STZ-SS
NPPA-/-
vs STZ- SS
WT
rats (7.0 ± 0.33 vs. 5.1 ± 0.07 mg/g, respectively, p<0.05). STZ- SS
WT
and STZ-SS
NPPA-/-
had similar diuresis (54.4 ± 2.8 vs. 52.5 ± 4.01 mL/24hr/100gTBW, respectively). Importantly, histological analysis displayed a more profound glomerular injury in the STZ-SS
NPPA-/-
when they were compared to STZ- SS
WT
(3.4 ± 0.02 vs. 3.2 ± 0.03 au, respectively, p<0.05).

Conclusion:
Thus far the data suggest that lack of ANP has a detrimental impact on DKD-related renal tissue damage, specifically, glomerular disease progression. Future studies will provide mechanistic insight into the role of ANP in oxidative stress and assess the role of ANP in nitric oxide production and calcium transients in the podocyte.
Abstract P144: Association Of Hypertension With Reasons For Admission In Young Hospitalized Patients
Authors: Seok Minji , Muhyieddeen Amer , Gulati Martha
Published: October 2023

Background:
Early onset of hypertension can contribute to harmful impacts on cardiovascular and brain health, which may manifest as coronary artery disease and strokes. In this analysis, we examined the most common reasons for hospitalization among patients with coexisting diagnoses of hypertension and compared lists among different age groups.

Methods:
We scrutinized the 2020 National Inpatient Sample dataset to locate all patients with a history of hypertension. We assessed the 10 most frequent diagnoses for hospital admission among hypertensive patients across age categories.

Results:
For the year 2020, there were a total of 8,661,206 hospitalizations for patients with a history of hypertension. Of these, 559,513 cases (6.5%), were in patients under 40 years of age. Within this group, the top ten admission reasons did not include NSTEMI or cerebral infarction compared to the quartiles of patients greater than the age of 40 (Figure 1).

Conclusion:
Younger patients were a small minority among hospitalized patients with hypertension. The top ten reasons for hospitalization in younger patients did not include diseases that are frequently associated with hypertension such as cerebral infarction and NSTEMI; conversely, these were frequent reasons for hospital admission in middle and older aged patients. Further studies are needed to characterize the severity of hypertension in each age category as well as the degree to which it influences the top reasons for admission.
Abstract P147: Cumulative Diastolic Blood Pressure Burden In Normal Systolic Blood Pressure And Cardiovascular Disease
Authors: Cho So Mi J , Lee Hokyou , Koyama Satoshi , Schuermans Art , Ganesh Shriienidhie , Hornsby Whitney , Honigberg Michael C , Natarajan Pradeep
Published: October 2023

Introduction:
The clinical significance of isolated diastolic hypertension defined by the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) Guideline remains controversial. We examined whether long-term diastolic burden independently predicts the first major adverse cardiovascular event (MACE) in participants with sustained untreated normal systolic BP.

Methods:
We identified 18,181 Mass General Brigham Biobank participants aged 18 to 64 years with untreated systolic BP <130 mmHg. Cumulative diastolic burden was determined as the area under curve for diastolic BP (DBP) ≥80 mmHg over a 5-year period prior to enrollment. Hazard ratio (HR) between cumulative diastolic burden and MACE was estimated using Cox proportional hazards regression. Prognostic value of enrollment and cumulative DBP was compared.

Results:
Of the 18,181 participants, mean [SD] age at enrollment was 47.6 [14.3] years, 13,574 [74.7%] were female, and 2853 (15.7%) MACE occurred over a median [IQR] follow-up of 3.5 [1.9-5.3] years. Each SD increase in cumulative DBP was associated with HR (95% CI) of 1.07 (1.03-1.11), adjusting for age, sex, race, body mass index, systolic BP, lipids, diabetes, smoking, statin, and antihypertensives initiation during follow-up. In addition to traditional risk factors, cumulative DBP improved the discrimination C index (95% CI) from 0.732 (0.724-0.742) to 0.739 (0.732-0.748) (Likelihood ratio test
P
=0.021), whereas inclusion of enrollment DBP did not improve prognosis.

Conclusions:
Among individuals with normal systolic BP, cumulative DBP may augment risk stratification beyond a single DBP measure and other traditional risk factors.
Abstract P148: Association Of Hypertension With Cardiovascular Disease In The United States
Authors: Grobman Ben , Turkson-Ocran Ruth-Alma , Larbi Kwapong Fredrick , Juraschek Stephen P
Published: October 2023

Background:
Hypertension is strongly associated with cardiovascular disease (CVD). Nevertheless, its relative importance compared with other established CVD risk factors among U.S. adults is unclear.

Objective:
To determine the prevalence of CVD risk factors and compare their association with CVD in a large U.S. population.

Methods:
The 2017 and 2019 Behavioral Risk Factor Surveillance System queried a representative sample of U.S. adults about hypertension (HTN), diabetes, and high cholesterol based on health professional diagnosis, obesity (BMI ≥30 from self-reported weight and height), smoking, and physical inactivity. We used logistic regression to examine the association between risk factors and CVD (nonfatal stroke and/or nonfatal myocardial infarction). Coefficients were compared using Wald tests. Models were also examined across sex (male vs. female), race (Black vs. White), and age (≥ 65 and <65), using interaction terms.

Results:
The weighted sample was 21.0% age ≥65 years, 51.3% female, 70.0% Non-Hispanic White, and 11.6% Non-Hispanic Black. While all risk factors were associated with CVD, HTN was most strongly associated with CVD in the fully adjusted model (OR = 2.26;
P
-values comparing to other coefficients were all <0.001). There was no evidence of effect modification across sex and race (all
P
-interaction values >0.05), the association between hypertension and CVD was stronger for age <65 years (
P
<0.001). Nevertheless, hypertension was still the strongest risk factor among both age groups.

Conclusion:
In this large U.S. sample, hypertension was the most prevalent and strongest CVD risk factor and should be a primary focus of policy focused on CVD prevention.
Abstract P160: Orthostatic Hypotension During Hospitalization: A Retrospective Observational Study
Authors: Rose Emily , Wagner Benjamin A , Strauss Adam , Anderson Timothy , Juraschek Stephen P
Published: October 2023

Background:
During hospital admissions, orthostatic hypotension (OH) is often considered a consequence of hypertension treatment, but the impact of reducing antihypertensive agents on OH response is unknown.

Objective:
To examine the association between inpatient antihypertensive medication changes and OH response.

Methods:
In this retrospective observational study, we reviewed electronic medical records of adult patients who experienced OH during their admission to Beth Israel Deaconess Medical Center between 2015 and 2021. Antihypertensive classes were categorized as not prescribed, no change, or decrease. OH improvement was assessed using vital sign flow sheets at presentation and discharge. We used logistic regression models adjusted for age, sex, and Black race to assess the association between antihypertensive categories and OH improvement.

Results:
Among 399 included patients (mean age: 69.9 years, 44% female, 10% Black), beta blockers (45%) were the most common antihypertensive class prescribed, followed by loop diuretics (23%), alpha blockers (21%), ACE inhibitors (20%), dihydropyridines (16%), ARBs (12%), thiazide diuretics (10%), and non-dihydropyridines (4%). Not being prescribed a dihydropyridine was associated with OH improvement (OR =2.37, 95% CI: 1.16-4.84), while decreasing a loop diuretic was associated with OH improvement (OR = 3.49, 95% CI: 1.46-8.36)
(Table)
. Changes to other classes were not associated with OH improvement.

Conclusion:
This study suggests that neither continuation nor reduction of most antihypertensives is associated with OH improvement. These findings should be tested in a prospective randomized trial.
Abstract P175: Benefits Of Gardening For Self-management Of Hypertension Among African-American Men: A Mixed-Methods Analysis
Authors: McCoy Carrie , Morgan Katherine , Brewer LaPrincess C
Published: October 2023

Background:
African American men are disproportionately affected by hypertension compared to other racial/ethnic groups. Self-management practices such as following a diet rich in fruits and vegetables can lead to improved hypertension control. However, healthy options may be inaccessible for some African American men, Gardening may provide easy access to fruits and vegetables.

Methods:
We conducted a mixed-methods study exploring African American men’s experiences with hypertension from Tennessee who regularly engaged in personal or community gardening and their gardening benefits (diet, physical activity, stress management), preferred diets and food selection. Participants completed semi-structured interviews and the Dietary Approaches to Stop Hypertension (DASH) diet questionnaire which was compared to the U.S. Department of Agriculture (USDA) MyPlate.

Results:
Participants (N=9, mean age 65 [SD 5.4] years) reported that gardening improved their regular physical activity, stress management, and satisfaction with providing for others. Several themes emerged including that participants preferred to manage their hypertension through diet modification by alternating traditional diets (high fat/sodium) with heart-healthy (low fat/sodium) meals and that they recognized the continuous nature of healthy food selection. Diet questionnaire responses revealed mean daily fruit (2.9 [SD 1.7]) and vegetable (2.8 [SD 1.1]) servings were below DASH diet recommendations but above MyPlate guidelines. Further, mean daily meat/protein (3.7[SD 1.1]) and fat/oil intake (6.4 [SD 7.2]) servings exceeded both recommendations.

Conclusion:
Our study suggests that personal and community gardening may provide a means for African American men to improve hypertension self-management practices through physical activity, stress relief, and healthy food access. Further studies of gardening interventions on blood pressure control among this group are warranted.
Abstract P181: Tcell Derived Hiv Proteins Promote Oxidative Stress, Endothelial Dysfunction And Hypertension Via Interleukin 1a-mediated Mechanisms In Mice.
Authors: Kress Taylor , Kovacs Laszlo , Barris Candee , MacArthur Roger , Kennard Simone , Pacholczyk Rafal , Belin De Chantemele Eric J
Published: October 2023

Antiretroviral therapy (ART) has markedly extended the life of people living with HIV (PLWH). However, PLWH now experience accelerated development of hypertension and cardiovascular disease (CVD), the etiology of which, including the individual contributions of ART and repressed viral infection, remain ill-defined. While ART prevents viral replication, viral reservoirs persist, and viral proteins remain in the circulation leading us to hypothesize that Tcell-derived HIV proteins contribute to endothelial dysfunction and hypertension. We utilized the Tg26 transgenic mouse model which ubiquitously express 7/9 viral proteins and reported increased blood pressure (BP) and impaired endothelium-dependent relaxation (EDR) in aorta and mesenteric arteries in both sexes. Bone marrow transplant (BMT) from Tg26 mice into WT (Tg26->WT) increased BP (WT->WT: 141.6 Tg26->WT 160.3 mmHg; P<0.05) and impaired EDR in conduit and resistance vessels (P<0.05). To determine whether Tcells, the main target of HIV, are responsible for CVD in Tg26 mice, thoracic aortas from WT male and female mice were co-cultured with either WT or Tg26 primary CD3+ Tcells, and yielded endothelial dysfunction. Moreover, inhibition of Tcell activation via Abatacept treatment in intact Tg26 mice lowered BP, restored vasorelaxation and reduced sympatho-activation to WT levels in Tg26 mice (P<0.05). A cytokine panel revealed increased production of interleukin 1α (IL-1α) in Tg26 CD3+ Tcells and plasma of Tg26->WT BMT (P<0.05). Abatacept decreased plasma IL-1α levels in intact Tg26 mice (P<0.05). Treatment with anti-IL-1α antibody abolished Tcell-mediated endothelial dysfunction and primary human microvascular endothelial cells (hMVEC) treated with IL-1α for 24 hours increased ROS mediated DNA damage (8-OHdG). IL-1α exposed hMVEC displayed increases in NOX1, NOXO1, and NOX4 while BMT aortas showed increased NOX1, NOXO1, and NOXA1. Inhibition of NOX1 via GKT771
ex vivo
restored vasorelaxation. Additionally, anti-IL-1α restored vasorelaxation and BP in intact Tg26 mice. Ultimately, we found that Tcells expressing viral proteins produce high IL-1α levels which increase endothelial NOX1 expression and ROS production, leading to endothelial dysfunction and hypertension
Abstract P189.2: Aberrant Trafficking Of Intestinal Immune Cells In Salt-sensitive Hypertension
Authors: Rauch Ariana , Bartolomaeus Hendrik , Yarritu Alex , Stuerzbecher Lucas , Vecera Valentin , Anders Wibke , Anandakumar Harithaa , Wilck Nicola
Published: October 2023

Hypertension is characterized by an inflammatory response, which precedes the clinical detection of organ damage. Yet, the activation and origin of target organ infiltrating immune cells are not fully understood. This study takes a systems view on inflammation in experimental hypertension and aims to investigate the extent to which the gut-associated immune cells contribute to the immune response in salt-sensitive hypertension.

Immune cell trafficking from the intestine to hypertensive target organs was analyzed using
in vivo
labelling of intestinal immune cells via targeted UV-photoconversion in
Kaede
-transgenic mice. Salt-sensitive hypertension was induced in 8-10 week old male mice by oral N-nitro-L-arginine methylester (L-NAME) pretreatment (0.5 mg/ml) and two 3-week high-salt feedings (HSD, 4% NaCl-diet, 1% drinking water), separated by a 2-week normal-salt (NSD, 0.5% NaCl-diet) interval. Hypertensive organ damage and photolabelled immune cells (5d post photoconversion) were analyzed.

HSD-fed mice displayed target organ damage as indicated by upregulation of mRNA-expression of markers of kidney damage (
Ngal
), inflammation (
Ccl2
) and fibrosis (
Col3a1
) (2^-ddCT Sham vs HTN: 1.5±1.3 vs 5.5±3.1, 1.2±0.8 vs 2.7±1.4, 1.0±0.3 vs 2.2±0.7, respectively). Intestinal immune cell trafficking was observed both in homeostasis (NSD) and disease (HSD). Infiltration of photolabelled
Kaede
red
(
Kred+
)
intestinal immune cells was detected in various organs, namely the mesenteric lymph nodes, spleen, blood and bone marrow, as well as target organs of hypertension, namely the kidney, heart and eye. In the kidney, B-cells (39.9 ± 24.2% (NSD), 66.8 ± 5.8% (HSD) of CD45+ Kred+ cells) and T-cells (32.5 ± 18.3% (NSD), 10.1 ± 4.4% (HSD) of CD45+ Kred+ cells) were among the major migrating populations. Salt-sensitive hypertension was characterized by a dysregulation of the intestinal-renal immune cell axis.

Immune cells originating from the intestine migrate and populate various organs, both in physiological homeostasis and in an aberrant manner in salt-sensitive hypertension. Our findings provide insight into mechanisms underlying hypertension-induced organ damage and could argue for interventions targeting intestinal immune cells.
Abstract P191: Health Services Availability And Readiness For Management Of Hypertension And Diabetes In Primary Level Healthcare Facilities In Ghana
Authors: Hinneh Thomas , Ogungbe Oluwabunmi V , Metlock Faith , Abeiku Mensah Bernard , Commodore-Mensah Yvonne
Published: October 2023

Background:
Hypertension (HTN) and diabetes (DM) are the leading cause of adult morbidity and mortality in Ghana and other African countries. We explored the service availability (SA) and readiness (SR) of health systems for managing HTN and DM in the Bono Region, Ghana.

Methods:
We conducted a multi-center cross-sectional study of four primary health facilities between June 2022 and July 2022. We modified the World Health Organization (WHO) Service Availability and Readiness Assessment tool to focus on management of HTN and DM. We computed composite scores for SR based on domains of functional equipment, diagnostic capacity, medications, and clinical guidelines & protocols; SA based on service-specific domains and stratified by facility ownership (Mission vs Government). At a cutoff value of 70%, services were considered "available" or facility "ready" to manage HTN and DM based on previous studies.

Results:
The median number of HCWs was 7 (IQR 2-7). The overall average SR and SA scores were 75.5% and 63% respectively (Fig A & B). SR scores were higher at mission hospitals (84.5%) than at government hospitals. SA scores were generally lower than SR Scores for both Mission and Government facilities. Half of the health facilities had guidelines and had CVD training in the last 2 years (n = 2; 50%), and all (n=4,100%) had received supervisory visits regarding CVD care in the last three months.

Conclusion:
There are gaps in diagnostic capacity, basic equipment, clinical guidelines, and a limited number of physicians accounting for low scores, particularly in government facilities. Improving resource allocation and implementing a team-based care policy may enhance HTN and DM care in Ghana .
Abstract P212: NMDA Receptor Glutn2c Deficient Mouse Associates With Hypertension
Authors: Jeon Sihyun , Almada Andrea , Romero Cesar A
Published: October 2023

Introduction:
N-methyl-D-Aspartate (NMDA) receptors are glutamate receptors located in the CNS and peripheral tissues. We previously showed that kidney NMDA receptors in the connecting/collecting ducts (CNT/CCD) participate in renal autoregulation and kidney vasodilation. We also showed that the use of non-specific NMDA inhibitors increases blood pressure. This work aims to identify which NMDA receptor subtypes are associated with hypertension.

Methods:
We simultaneously evaluated the expression of GluN2C and 2D in the CNT/CCD by using in-situ hybridization (RNA scope) with the presence of CNT/CCD marker AQP-2 using immunofluorescence. Blood pressure was evaluated in C57B mice and global genetic ablated mice on C57B background: GluN2C-KO or GluN2D-KO. Blood pressure was measured using the tail-cuff method three times a week for two weeks after three sesión training. We used both male and female mice. Animals were fed on regular and high salt diets (4%).

Results:
RNA expression of NMDA subunits 2C and 2D were found to be present in AQP2-positive regions from mouse kidneys, compatible with CNT/CCD regions. The average systolic blood pressure (SBP) for C57B control mice was 105.6±10.5 mmHg; on GluN2C-KO mice, SBP was 114.6±7.3 mmHg, significantly elevated compared to the matched C57B control mice (p<0.01), and GluN2D mice’s SBP was 111.6±10.4 mmHg with no significant differences from the matched control (111.1±4.6 mmHg; p=0.93). No difference was observed between male and female mice in both genetically ablated mice. After a challenge with a high salt diet, blood pressure did not change in all three groups.

Conclusion:
NMDA receptors subunits GluN2C and GluN2D are expressed in the CNT/CCD region. The genetic absence of GlutN2C is associated with high blood pressure; however, the lack of GLUN2D did not change SBP. No salt sensitivity was observed in any of the genetically ablated mice. Future work will explore the role of renal hemodynamics in these blood pressure phenotypes.
Abstract P234: High-fat Diet Reduces Beneficial Effect Of Perivascular Adipose Tissue On Arterial Stiffness
Authors: McClintock Dillon , Bush Sydney , Flood Emma D , Watts Stephanie W , Tykocki Nathan R , Roccabianca Sara
Published: October 2023

Perivascular adipose tissue (PVAT) is has been shown to significantly contribute to arterial mechanics in health. Our previous results showed that, when including PVAT arterial stiffness is significantly reduced in the thoracic aorta. In this study, we aim to quantify the effect of PVAT on arterial stiffness in an animal model of adiposity driven hypertension. Our model was the thoracic aorta of Dahl Salt-Sensitive rats 8 weeks old on control (CON, n=2) and high-fat (HF, n=2) diets. Uniaxial mechanical tests for aorta + PVAT (+PVAT) and aorta - PVAT (-PVAT) were performed on a custom mechanical stretcher. The data reported is the low-stress stiffness calculated from the Cauchy stress-stretch curve. Blood pressure was also recorded for these animals. As expected, +PVAT samples’ stiffness appear to be lower than -PVAT samples. Including PVAT results in a 61% reduction of stiffness in the animals on CON diet. However, in animals fed a HF diet, the beneficial effect of PVAT is reduced to 21%. Surprisingly, while animals on HF diet had higher blood pressure compered to animals on CON diet, the stiffness recorded for -PVAT samples was lower in animals fed a HF vs CON diet. This could be due to an early remodeling mechanism which increases the cross-sectional area of the vessel, resulting in a lower values of stress for comparable values of stretch. Another possibility is that the collagen fibers in the tissue were not fully engaged during the test, due to the low level of deformation applied. Finally, more tests are required to confirm these initial observations. In conclusion, HF diet appears to decrease the beneficial effect of PVAT on the stiffness of the thoracic aorta.
Abstract P301: Predicting Complete Resolution Of Hypertension After Adrenalectomy In Primary Aldosteronism: A Systematic Review And Meta-analysis Of Prognostic Models.
Surgical Outcome of PRimary Aldosteronism progNostic mOdels (SOPRANO) Study
Authors: Marzano Luigi , Kazory Amir , Husain-Syed Faeq , Ronco Claudio
Published: October 2023

Background:
Unilateral primary aldosteronism (PA) is the most common surgically curable form of hypertension, despite complete clinical success after adrenalectomy being far from certain. Several presurgical factors were associated with complete resolution of hypertension (CRH). However, it remains unclear which of the available prognostic models combining those factors can be used in clinical practice to predict blood pressure-related outcomes after surgery for PA.

Objectives:
To identify, describe and appraise all prognostic models developed to predict CRH, and meta-analyse their predictive performances.

Methods:
We searched MEDLINE, Embase, and Web of Science, for development and validation studies of prognostic models according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The quality assessment used adapted TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) and PROBAST (Prediction model Risk Of Bias ASsessment Tool) criteria. After selection, we extracted descriptive statistics and aggregated area under the receiver operator curve (AUC) using meta-analysis.

Results:
From 25 eligible studies, we identified 12 prognostic models used for predicting CRH after total adrenalectomy in PA. We report the results for three models that had available data from at least three external validation studies: the Primary Aldosteronism Surgical Outcome (PASO) score (AUC: 0.81; 95% confidence interval [CI]: 0.74–0.86; 95% predictive interval [PI]: 0.04–1.00), Utsumi nomogram (AUC: 0.79; 95% CI: 0.72–0.85; 95% PI: 0.03–1.00), and the Aldosteronoma Resolution Score (ARS) model (AUC: 0.77; 95% CI: 0.74–0.80; 95% PI: 0.59–0.86 for all studies and AUC: 0.80; 95% CI: 0.75–0.85; 95% PI: 0.57–0.93 for the studies with the same adrenal vein sampling-guided adrenalectomy rate compared to the models meta-analyzed).

Conclusions:
The PASO score, Utsumi nomogram, and ARS model showed good and comparable discrimination performance to predict CRH after unilateral adrenalectomy in PA. However, unlike the ARS model, the number of external validation studies for the PASO score and the Utsumi nomogram was relatively low to draw definite conclusions.