bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17: First-Line Beta Blocker Use Among >3.1 Million Veterans Initiating Hypertension Treatment, 2000-2022
Authors: Derington Catherine , Berchie Ransmond , Mohanty April , Jacobs Joshua , Xu Yizhe , King Jordan , Rethy Leah , Cushman William , Zickmund Susan , Ho Michael , Cohen Jordana , Bress Adam
Published: October 2024

Introduction:
It is unknown how often beta blockers (BB) are used first line for high blood pressure (BP) treatment among patients without compelling indications, despite US BP guidelines not recommending this practice since 2014.

Research Question:
How many start, and what factors influence, first line BB use among patients without compelling indications?

Methods:
Serial cross-sectional study of outpatients newly diagnosed and initiating treatment in the Veterans Health Administration, 1/1/2000–12/31/2022. We removed prevalent users, categorized drugs by class, and presented compelling indication status by initial BB use (mono- or combination therapy). Among those without compelling indications (ie, aortic aneurysm/disease, angina, atrial fibrillation/tachyarrhythmia, chronic liver disease/cirrhosis, heart failure with reduced ejection fraction, myocardial infarction, or coronary revascularization), multivariable Poisson regression estimated factors associated with BB use.

Results:
Of 3138304 Veterans (mean age 61 years, 94% male, 65% Non-Hispanic White), 774821 (25%) initiated a BB, of which the proportion without compelling indications decreased over time from 91% to 81%; the proportion with compelling indications increased from 9% to 19% (Panel A). Specific BBs used changed over time (Panel B). Among those without compelling indications, BB initiation was more likely with increasing age, females, current smokers, alcohol abuse, aspirin or statin use, each additional antihypertensive prescribed, each pre-index hospitalization, and urban setting (Panel C).

Conclusions:
Most Veterans using BB first line for high BP do not have compelling indications. Interventions are needed to align real world treatments with guidelines.
Abstract 30: Acute Effects Of Sodium Chloride Or Its Substitute Potassium Chloride On Microvascular Function In Healthy Volunteers
Authors: Stock-Schrooer Annika , Streese Lukas , Rammo Randa , Kantauskaite Marta , Rump Lars Christian , Mueller Dominik , Stegbauer Johannes
Published: October 2024

Dietary high sodium intake is a modifiable risk factors for cardiovascular (CV) diseases including vascular dysfunction and subsequently arteriosclerosis. A partial sodium substitution by potassium is associated with a lower risk of CV events and death. Our aim was to investigate the acute impact of sodium and potassium on retinal microvascular function, an established biomarker for systemic CV risk stratification.

Eighteen male and 27 female healthy individuals (mean age 31years) were randomized to eat a salty soup containing either 9g sodium chloride (high salt group), 6g sodium chloride (intermediate salt group) or 6g sodium chloride plus 3g potassium chloride (substitution group). Microvascular measurements were performed before (t0) as well as four (t4) and 24 hours (t24) after soup intake. Microvascular health was measured by investigating retinal vessel diameters. A higher arteriolar-to-venular diameter ratio (AVR) is associated with improved vascular health. Microvascular endothelial function was quantified by flickerlight-induced retinal arteriolar dilation.

The 9g (139±2mmol/l vs. 141±2mmol/l, p<0.001) and 6g salt group (140±1mmol/l vs. 141±2 mmol/l, p=0.028) had higher serum sodium concentrations at t4 compared to baseline. Serum sodium concentrations of the substitution group showed no significant difference between time points, but a significant increase in serum potassium (3.7±0.3mmol/l vs. 3.9±0.2mmol/l, p=0.019). Microvascular endothelial function was significantly decreased in the high salt group from baseline to t4 (4.5±2.2% vs. 3.7±2.2%, p=0.041), without significant changes in the other groups. In the sodium groups, there was a strong correlation between the increase in serum sodium concentration from t0 to t4 and an impaired endothelial function after t4 (R
2
=0,255, p=0,005). The substitution group showed improved microvascular health, quantified by higher AVR at t4 compared to t0 (0,83±0,07 vs. 0,86±0,07, p<0,001). An increase in serum sodium was negatively associated with AVR (R
2
=0,14, p=0,013) whereas an increase in serum potassium was positively correlated with AVR (R
2
=0,19, p=0,003).

An acute increase in serum sodium is associated with impaired microvascular endothelial function. Replacement of sodium by potassium seems to improve microvascular function already after a single potassium intake. These results might explain the beneficial effects of potassium on CV outcomes as well as the harmful effects of sodium on vascular function.
Abstract 47: Deletion of PRR in AgRP Neurons of the Arcuate Nucleus Contributes to the Development of DOCA-Salt Hypertension
Authors: Pan Shiyue , Mizuno Yuma , chen gang , Morton Gregory , Schwartz Michael , Feng Earley Yumei
Published: October 2024

Agouti-related protein (AgRP) neurons, a key neuronal population within the arcuate nucleus (ARC), are known for their pivotal roles in regulating energy- and glucose homeostasis. However, their involvement in cardiovascular regulation remains poorly understood. Using RNAscope in situ hybridization, we found that 95.4% of the ARC
AgRP
neurons express the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system that is crucial for blood pressure (BP) regulation. We therefore hypothesized that PRR signaling in the ARC
AgRP
neurons plays a regulatory role in the development of hypertension. To test this hypothesis, we selectively deleted PRR in ARC
AgRP
neurons by crossing AgRP-IRES-Cre mice with PRR
fl/fl
mice. Using RNAscope, as expected, AgRP
Cre+
PRR
fl/y
mice displayed a significantly lower PRR mRNA in the ARC
AgRP
neurons than WT mice (76.3 ± 6.1 vs. 127.7 ± 2.9 AFU,
p
< 0.05), indicating efficient ablation of PRR in ARC
AgRP
neurons. To examine the impact of PRR deletion in the ARC
AgRP
neurons on BP, the AgRP
Cre+
PRR
fl/y
and control mice were implanted with telemetry probes to monitor BP continuously. After baseline recording, mice received DOCA-salt treatment (50 mg DOCA + saline as drinking water) for two weeks. BP variability and standard time domain heart rate variability (HRV) parameters, including overall HRV (SDNN) and short-term HRV (rMSSD), were analyzed from beat-to-beat intervals (n = 2-7 mice/group). At baseline, there was no difference between the two groups in BP, BP variability, and HRV. Two weeks of DOCA-salt induced a significantly higher BP in AgRP
Cre+
PRR
fl/y
mice than the controls (156.2 ± 6 vs. 119.4 ± 3 mmHg,
p
< 0.05), while BP variability did not differ between the two groups. Noteworthy, AgRP
Cre+
PRR
fl/y
mice exhibited lower SDNN than the controls (13.3 ± 4 vs. 19.4 ± 4 ms), indicating increased sympathetic and/or reduced parasympathetic nervous activity. This lower SDNN suggests impaired cardiac autonomic function and adaptability to physiological demands in AgRP
Cre+
PRR
fl/y
mice. Concurrently, AgRP
Cre+
PRR
fl/y
mice showed a lower rMSSD (4.7 ± 0.5 vs. 10.8 ± 3.5 ms), implying reduced parasympathetic activity. In conclusion, deletion of PRR in the ARC
AgRP
neurons results in compromised cardiac autonomic function associated with the development of hypertension. Our findings underscore a novel protective role of PRR signaling in the ARC
AgRP
neurons in BP regulation.
Abstract 68: Soluble FMS-Like Tyrosine Kinase 1 induces Vascular Endothelial Dysfunction in Pregnant Female Mice
Authors: Elgazzaz Mona , Cooper Gibson , Mellott Elisabeth , Maher James , Faulkner Jessica
Published: October 2024

Preeclampsia (PE) is a hypertensive disorder of pregnancy clinically characterized by hypertension and increased risk of fetal growth restriction. Elevated levels of anti-angiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) is a well-known hallmark of PE. In addition, emerging clinical evidence indicates that vascular endothelial dysfunction is a mediator of PE. Although these two facets of PE are associated, whether sFlt-1 is a crucial mediator in endothelial dysfunction in PE is unknown. We previously showed that the placenta-derived hormone leptin, whose levels characteristically increase in PE patients, induces the features of PE in pregnant mice, notably endothelial dysfunction. Novel preliminary data also shows that sFlt-1 induces an increase in placental leptin production, however, what remains to be explored is whether this pathway mediates endothelial dysfunction in PE pregnant mice. Therefore, we hypothesize that in pregnant mice, sFlt-1 induces vascular endothelial dysfunction via increasing leptin production. We bred BALB/c female mice for timed pregnancy (12-14 wk old). On gestational day (GD)11, pregnant females were implanted with subcutaneous (sc.) minipumps containing either sFlt-1 (1.2 µg/day, n=5) or saline (n=6). Uterine artery resistance index (UARI) was measured at GD17 via Doppler ultrasound. At GD18, vascular reactivity was measured in 2nd-order mesenteric arteries by wire myography. Our data showed that sFlt-1 increased UARI compared to sham mice ([PSV-EDV]/PSV; Mean±SEM;0.61±0.01
vs.
0.45±0.01,
t
test, p=0.0007). In addition, sFlt-1 reduced endothelial-dependent relaxation to acetylcholine (concentration-response, 1nM-10µM, 2-way ANOVA w/RM, p<0.0001), indicating endothelial dysfunction. sFlt-1 also reduced smooth muscle relaxation responses to sodium nitroprusside (p<0.05). To test whether sFlt-1 induces leptin production, we bred BALB/c mice as described above. At GD12, mice were treated with either sFlt-1 (sc.10 µg) or saline (n=6/group). After 24 h, mice were euthanized, and plasma and subcutaneous adipose tissue were collected. Our data showed an increase in plasma leptin in sFlt-1 group (ng/mL;5.0 ±0.2
vs.
2.9±0.1,
t
test, p<0.0001) and an upregulation in placental leptin gene expression (normalized to 18S; fold change to control; 7.8±1.8
vs.
1.1±0.3,
t
test, p<0.05). In conclusion, our data indicates that sFlt-1 induces vascular endothelial dysfunction and increases leptin plasma levels and gene expression in preeclampsia.
Abstract MP07: Efficacy and safety of aprocitentan in patients with resistant hypertension and elevated NT-proBNP
Authors: Weber Michael , Bakris George , Gimona Alberto , Narkiewicz Krzysztof , Schlaich Markus , Sassi-Sayadi Mouna , Wang Jiguang , Flack John
Published: October 2024

Background and Objectives:
The endothelin ETA/ETB receptor antagonist aprocitentan (APRO) decreased blood pressure (BP) in patients with confirmed resistant hypertension (RHT) in the PRECISION study. 19.6% of the overall population (143 subjects) had a reported history of Heart Failure (HF). It is well known that in subjects with RHT, HF is often underdiagnosed. In PRECISION, NT-proBNP (a marker of HF) was measured. Here we report the efficacy and safety of APRO in patients with increased NT-proBNP.

Methods:
730 patients with RHT were switched to a standardized fixed-dose combination of amlodipine/valsartan/hydrochlorothiazide from their existing anti-hypertensive and diuretic medication and then randomized to APRO (12.5 mg or 25 mg) or placebo in PRECISION. This analysis considers subjects with baseline blood levels of NT-proBNP >125 pg/mL. Change in BP, incident cases of edema/fluid retention and change in body weight were assessed. Descriptive statistics are presented.

Results:
236 enrolled subjects (32.3%) had NT-proBNP levels from 125–1125 pg/mL. At Week 4, APRO 12.5 mg decreased trough sitting systolic BP (SiSBP) by mean (SD) 14.2 (16.7) mm/Hg, APRO 25 mg by 15.8 (13.5) mm/Hg and placebo by 9.9 (18.0) mm/Hg, confirming that the effect was greater for APRO than placebo with no apparent difference between 12.5 and 25 mg, as observed in the overall population enrolled in PRECISION. The effect was maintained with APRO 25 mg at Week 36 with a decrease of 18.4 (15.2) mm/Hg versus baseline.

Adverse events of edema/fluid retention were reported with an incidence of 13.4%, 25.7% and 1.2% in the 12.5 mg, 25 mg and placebo group, respectively, at Week 4. During the SB part up to 36 weeks edema/fluid retention was reported by 26.1% of subjects with 25 mg. Body weight change at Week 4 was +0.5, +0.7 and -0.2 Kg with 12.5 mg, 25mg and placebo, respectively. This weight increase was reversible: a subsequent decrease resulted in a difference versus baseline of 0.4 kg at Week 36. NT-proBNP ratio vs baseline (geometric mean) was 0.94, 0.86 and 0.78 with 12.5 mg, 25 mg and placebo, respectively, at Week 4. There was no increase over time, the ratio vs baseline was still below 1 (0.91) at Week 36.

Conclusion:
Aprocitentan is effective in patients with RHT and elevated NT-proBNP. Edema and fluid retention are more common in this sub-group compared with the overall population included in PRECISION, but it is not linked to significant weight gain or increase of NT-proBNP.
Abstract P100: TRPM7 deficiency amplifies aldosterone signalling cardiac fibroblasts
Authors: Rios Francisco , Camargo Livia , Montezano Augusto , Touyz Rhian
Published: October 2024

Introduction:
Transient Receptor Potential Melastatin 7 (TRPM7) channel is a channel bound to a kinase domain that influences cellular Mg
2+
with an important role in inflammatory response and cell metabolism. TRPM7 is regulated by aldosterone. Here, we investigated the importance of TRPM7-Mg2+ in pro-fibrotic responses and oxidative stress in cardiac fibroblasts (CF) in the context of hypertension and organ damage induced by aldosterone.

Methods:
Wild-type (WT) and TRPM7-deficient (M7+/Δ) mice were treated with aldosterone (600µg/Kg/day) plus NaCl (1% drinking water), 4 weeks. Mechanisms were investigated in primary culture of CF. Ca
2+
and Mg
2+
influx was assessed by fluorescence microscopy and flow cytometry. Gene and protein expression was assessed by real-time PCR and immunoblotting. Proteomic analysis was performed in two-dimensional liquid chromatography and mass spectrometry (LC/LC-MS/MS).

Results:
M7+/Δ mice exhibited reduced tissue [Mg
2+
] (28%) and increased cardiac collagen deposition (2-fold). Aldosterone-induced fibrosis and hypertension were enhanced in M7+/Δ. CF M7+/Δ had reduced aldosterone-induced calcium influx (136±6 vs WT:166±7) and Mg
2+
influx (1.05±0.05 vs WT 1.14±0.02). CF M7+/Δ exhibit increased expression of calpain-1(300%), α-SMA(80%), collagen-1 (50%), mineralocorticoid receptor target proteins ENaC(70%) and SGK1(30%) and reduced proliferation(33%) vs WT(p<0.05). Aldosterone reduced TRPM7 (44%) and increased expression of ENaC (150%) and collagen-1 (93%) in CF WT to similar levels observed in CF M7+/Δ. CF M7+/Δ exhibit increased Nox2(70%), Nox4(120%) and ROS production (1,362 vs WT: 899 RLU/mg protein). Increased mRNA for the antioxidant catalase, NQO1 and Prdx1 (1.7-2.6-fold) was found in M7+/Δ CF. Mg
2+
supplementation normalised Ca
2+
and Mg
2+
influx, proliferation and expression of SGK1, Nox4, catalase and NQO1, whereas other effects might be mediated by the kinase domain. Proteomic analysis showed that CF M7+/Δ exhibit reduced expression of proteins related to cell migration and proliferation (Tnc, Cdcc80, Crip1, Ggt5) cell cycle and differentiation (AnxA8, Rpl22, Prickle2) and cell metabolism (Marcks, Mtab, Ces1d, Serpina3n, Afap1l1).

Conclusion:
Our findings demonstrate that in aldosterone-treated mice TRPM7 expression and tissue Mg
2+
levels are decreased. These processes are associated with cardiac fibrosis and oxidative stress. Our findings suggest a cardio-protective role for TRPM7/Mg2+ in aldosterone-induced hypertension.
Abstract P124: Prognostic Significance of Free Triiodothyronine Levels in Patients with Heart Failure with Preserved Ejection Fraction and Hypertrophic Cardiomyopathy: A Multicenter Retrospective Analysis
Authors: Zhang Kuo
Published: October 2024

Objective:
This study aimed to identify key prognostic factors in patients with hypertrophic cardiomyopathy (HCM) presenting heart failure with preserved ejection fraction (HFpEF), with a special focus on the role of Free Triiodothyronine (FT3) levels.

Methods:
A retrospective cohort study was conducted, comprising HFpEF patients admitted to two medical centers from 2009 to 2019. Data collection included demographic and clinical parameters, particularly FT3 levels. Univariate and multivariate Cox analyses, Kaplan-Meier (KM) survival curve analysis, and Restricted Cubic Spline (RCS) curve analysis were employed to identify prognostic factors and to assess the non-linear predictive value of FT3.

Results:
The analysis revealed that age, atrial fibrillation, and NT-proBNP levels significantly influenced prognosis in heart failure patients. Additionally, FT3 levels emerged as a significant independent predictor of both all-cause mortality and cardiac transplantation. Patients with lower FT3 levels exhibited poorer long-term prognoses, with 2.885 identified as the critical FT3 value.

Conclusions:
These findings underscore the importance of FT3 levels as a crucial prognostic factor in patients with heart failure, warranting consideration in patient outcomes assessments. Clinicians are recommended to monitor FT3 levels and contemplate interventions aimed at maintaining or enhancing thyroid function in these patients to improve outcomes.
Abstract P185: Patient Portal Access, Health Literacy, Patient Trust in Health System, and Shared Decision Making Among US Adults with Hypertension: A National Cross-Sectional Study
Authors: Chen Yuling , Spaulding Erin , Slone Sarah , Kruahong Suratsawadee , Commodore-Mensah Yvonne , Dennison Himmelfarb Cheryl
Published: October 2024

Background:
Shared decision-making (SDM) is increasingly recognized as central to delivering patient-centered care and improving hypertension control. However, there is limited understanding of the association between patients' access to patient portals, health literacy, trust in the health system, and involvement in SDM.

Objectives:
This study investigated the associations between patients' access to patient portals, health literacy, trust in the health system, and patients’ involvement in SDM among adults with hypertension in the United States (US).

Methods:
This cross-sectional study utilized data from the 2022 Health Information National Trends Survey (HINTS 6) conducted among US adults. The exposure variables were patient portal use, health literacy, patients' trust in health systems, and whether the participant was offered access to patient portals by healthcare providers. The outcome of interest was whether patients were always involved in SDM (Yes/No) during the past 12 months. Analyses were weighted according to HINTS 6 methodology. We performed three weighted sequential multivariable logistic regression models (Fig. 1, Models 1-3). The fully adjusted model included demographics, clinical characteristics, and social determinants of health and resources for implementing SDM and was stratified by age (<65 and ≥65 years).

Results:
We included 1703 adults with hypertension (mean age of 61.6, SD 13.9 years; 52.5% male; and 64.9% White adults). About 86.4% of participants were offered online access to patient portals by their healthcare providers. In the fully adjusted model (Fig. 1, Model 3), adults who were offered access to patient portals (adjusted odds ratio [aOR] 1.90, 95% CI 1.03-3.49), with higher health literacy levels (aOR 2.18, 95% CI 1.42-3.34), and with higher trust in health systems (aOR 3.08, 95% CI 2.26-4.21) were more likely to engage in SDM than their counterparts. These associations were similar among adults <65 years (Fig. 2). However, among adults ≥65 years, offering online access to patient portals was not associated with involvement in SDM; while those who used the patient portal 6-9 times during the past 12 months were more likely to engage in SDM than those who never used it (aOR 2.26, 95% CI 1.06-4.83).

Conclusion:
Offering access to patient portals may enhance SDM among US adults with hypertension, especially for adults with higher health literacy levels and greater trust in health systems. These associations differed by age.
Abstract P188: Prevalence of AHA Pediatric Risk Categories in Youth with Hypertension Disorders: a SUPERHERO Analysis
Authors: Vincent Carol , Harry Giya , Murphy Margaret , Onugha Elizabeth , South Andrew
Published: October 2024

Background:
Cardiovascular (CV) risk factors in childhood contribute to the development of CV disease (CVD) later in life. In higher risk groups of youth, increased risk of CV events begins early in adulthood. The American Heart Association (AHA) 2019 CV Risk Reduction in High-Risk Pediatric Patients scientific statement uses medical diagnoses and CV health factors to classify patients into High, Moderate, and At-risk categories. The prevalence of these risk categories in youth with hypertension (HTN) disorders is unknown.

Methods:
Cross-sectional analysis of baseline electronic health record data from youth referred for HTN disorders in the multisite retrospective SUPERHERO Registry. Inclusion criteria were age <19 years and index subspecialty clinic visit for a HTN disorder by ICD-10 codes from 1/1/2015–12/31/2023. Exclusion criteria were kidney failure on dialysis, kidney transplantation, or pregnancy by ICD-10 codes. We report prevalence of AHA Pediatric Risk Category (High, Moderate, At-risk). We used clinic BP and 2017 AAP Clinical Practice Guidelines to define HTN, clinic BMI percentile to define obesity, and ICD-10 codes to define other risk category medical diagnoses. We report frequencies and proportions in this descriptive analysis.

Results:
Of 9356 participants, 3544 (37.9%) were female and 5464 (58.4%) were ≥13 years. At the index visit, 5563 participants (63.5%) were hypertensive. A total of 634 participants (6.8%) were classified as High risk, 6100 participants (65.2%) as Moderate risk, and 1034 participants (11.1%) were in the At-risk group. There were 1588 participants (17.0%) not classified into a risk category with available data.

Conclusions:
In a large cohort of youth with HTN disorders, we found that over 80% of participants were in an AHA pediatric risk category with 63.5% of participants having either primary or secondary HTN. Our findings suggest that if only HTN is used to identify youth at early CV risk, we will miss youth who may benefit from early CV health factor intervention. Next steps include confirming our findings using laboratory and prescription data in defining risk categories and investigating the association of AHA pediatric risk category with target organ injury using laboratory and echocardiogram data.
Abstract P193: Adoptive transfer of placental CD4+ T Cells from preeclamptic patients with a history of COVID-19 causes hypertension and cognitive dysfunction postpartum in a pregnant rat model of preeclampsia
Authors: Deer Evangeline , Simmons Kimberly , Herrock Owen , Campbell Nathan , Roman Richard , Zheng Baoying , Morris Rachael , Lamarca Babbette
Published: October 2024

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with activated CD4+ T cells, impaired cognitive function, and changes in cerebral blood flow (CBF) autoregulation. Previously, PE women have been shown to develop neurovascular and cardiovascular disorders earlier in life than those that had uneventful pregnancy. COVID-19 (CV) during pregnancy is associated with an increase incidence of the PE phenotype and is also associated with chronic neurovascular and cardiovascular consequences. Previously, we showed adoptive transfer of placental CD4+ T cells from PE women into athymic nude pregnant rats causes a PE phenotype, however we don’t know the role of CD4+ T cells to cause long-term neurovascular or cardiovascular consequences in PE in the presence or absence of a history (Hx) of COVID-19 during pregnancy. Therefore, we hypothesize that CD4+ T cells from PE patients with and without a Hx of CV causes hypertension and neurovascular dysfunction compared to CD4+ T cells from normotensive patients. One million placental CD4+ T cells from Normotensive (NT), CV Hx NT, and PE patients with or without a CV Hx were isolated and injected interperitoneally (i.p.) into pregnant nude athymic rats on gestational day (GD) 12. Dams were allowed to deliver and aged 12-weeks after delivery. At 12-weeks postpartum, blood pressure (MAP) was measured; CBF autoregulation was measured by laser Doppler flowmetry. The Barnes maze and the novel object recognition behavioral assays were used to assess cognitive function 12-weeks postpartum. A two-way ANOVA was used for statistical analysis. At 12-weeks postpartum, MAP increased in CV Hx PE (153±6, n=7, p<0.05) and PE (150±5 mmHg, n=5, p<0.05) compared to CV Hx NT (121±6, n=6) and NT (116±6 mmHg, n=6), respectively. Behavioral analysis showed CV Hx PE and PE exhibited impaired memory and learning (P<0.05) compared to either NT group. Our findings indicate that rat recipients of CD4+ T cells from PE patients in the presence or absence of CV Hx have HTN and cognitive dysfunction in the postpartum period compared to recipients of control CD4 + T cells. These data indicate the importance of CD4+ T cells in long-term consequences of PE and COVID infection during pregnancy.
Abstract P203: Nicotine Exposure: A Catalyst for Nitrosative and Oxidative Stress in Glomerular Podocytes and Renal Impairment
Authors: Jones Adam , Semenikhina Marharyta , Fedoriuk Mykhailo , Stefanenko Mariia , Cherezova Alena , Spires Denisha , Veit Acosta Martina , Stadler Krisztian , Ilatovskaya Daria , Palygin Oleg
Published: October 2024

Introduction:
Nicotine consumption through vaping, cigarettes, or nicotine replacement therapy poses major risks for renal health, especially in individuals with hypertension or kidney disease. Nicotine induces oxidative stress and nitric oxide synthase (NOS) remodeling in endothelial cells, but a gap in knowledge persists regarding its impact on glomerular epithelial cells, particularly podocytes. We hypothesize that nicotine promotes nitrosative stress in podocytes, generating peroxynitrite (ONOO
-
), causing mitochondrial damage, and glomerular impairment.

Methods:
We performed confocal imaging on human cultured podocytes to detect ONOO
-
, Ca
2+
, and nitric oxide (NO) in response to nicotine. We used Seahorse assay (Agilent XFe24) to test mitochondrial respiration. Nicotine was then chronically infused in Dahl SS rats (0.2 mg/kg/day s.c., 0.4% NaCl diet) for 21 days, and recorded blood pressure with telemetry. Glomerular damage was evaluated, and electron microscopy was employed to assess mitochondrial ultrastructure. Electron paramagnetic resonance (EPR) spectroscopy was used to access the NO levels in cultured podocytes and
in vivo
. OriginPro was used for statistical analysis.

Results:
Acute application of nicotine promoted intracellular Ca
2+
and ONOO
-
transients in podocytes. The ONOO
-
response was blocked in the presence of SOD, indicating that ONOO
-
production requires superoxide. The application of specific α7, α4β2, α2β4, α4β4, and α3β4 nicotinic acetylcholine receptor (nAChR) agonists elicited Ca
2+
transients but did not produce ONOO
-
, suggesting that nitrosative stress occurs independently from nAChR activation. Incubation with nicotine (12 hrs) resulted in a decrease in podocytes’ mitochondrial respiration (two-sample t-test, p<0.05).
In vivo
, nicotine infusion did not affect blood pressure but promoted mitochondrial damage in podocytes, which exhibited swelling, loss of cristae, and mitophagy (t-test, p<0.05). Histopathological assessment showed higher glomerular damage in nicotine-exposed rats (t-test, p<0.05). Both EPR and confocal approaches demonstrated nicotine-mediated changes in NO bioavailability and an increase in NOS2 activity (t-test, p<0.05).

Conclusion:
Nicotine products promote NOS uncoupling in podocytes, leading to ONOO
-
formation, redox stress, mitochondrial impairment, and glomerular damage. Understanding nicotine's impact on podocytes is crucial for preventing or developing therapies against smoking and vaping-related pathologies.
Abstract P207: Regulation of Fetal-Placental ACE and ACE2 in COVID-19 Exposed Pregnancies Compared to Hypertensive and Healthy Pregnancies
Authors: aji narjiss , Fregeau Genevieve , cruz Nayara , St-Gelais Lea , Vachon Isabelle , Gagnon Sonia , Casarini Dulce , Bertagnolli Mariane
Published: October 2024

Introduction:
Higher risks of preterm birth and fetal growth restriction are observed in COVID-19 pregnancies. The infection mechanism, linked to a potential depletion of the cardioprotective protein ACE2, which serves as a receptor for SARS-CoV-2, could pose additional risks for mothers and fetuses. An ACE2/ACE imbalance, favoring ACE, has been seen in hypertensive (HT) pregnancies and is linked to poor outcomes, including pre-eclampsia. This study aims to assess whether similar changes in ACE and ACE2 regulation in placentas and umbilical cord blood occur in COVID-19 compared to HT and healthy (Ctrl) pregnancies, and whether this imbalance is associated with impaired vascular structure.

Methods:
A retrospective cohort study recruited 77 pregnancies (25 COVID-19, 16 HT, 36 Ctrl) at Montreal Hospital Sacré-Coeur. Placental infarction was assessed in histological sections, umbilical cord fibrosis by Masson's trichrome staining, and placental ACE2 content by immunohistochemistry. ACE and ACE2 activity were measured by fluorometric assay in umbilical cord plasma. Data are presented as mean 95% CI. Linear regression was used for correlations, Kruskal-Wallis and Mann-Whitney tests for group comparisons.

Results:
Maternal age, gestational age, and the proportion of male/female fetuses were similar between groups. Ctrl group had lower rates of C-section delivery, obesity, and gestational diabetes compared to COVID-19 and HT pregnancies. Although ACE2 content in placentas was reduced in HT pregnancies, the COVID-19 group had significantly higher content compared to HT and Ctrl pregnancies (23.4 CI=20.4-26.4 vs. 15.5 CI=9.7-21.3 and 17.6 CI=15.1-20.1, respectively, p<0.01). The ACE2/ACE activity ratio in cord blood was significantly reduced in COVID-19 and HT groups compared to Ctrl (3.1 CI=2.4-3.6, 2.5 CI=1.7-3.1, and 4.1 CI=3.5-4.8, p<0.01), indicating an imbalance favoring ACE activity in HT and COVID-19 groups. The ACE2/ACE ratio negatively correlated with umbilical cord fibrosis (slope=-3.1 CI= -6.1 to -0.1, p=0.04) and was significantly lower in placentas with tissue infarction (2.5 CI=1.2-3.8 vs. 4.6 CI=3.8-5.3, p<0.01).

Conclusion:
HT pregnancies have reduced ACE2 content and an ACE2/ACE activity imbalance in cord blood. COVID-19 pregnancies show a similar imbalance in cord blood but significantly higher ACE2 content in the placenta. This imbalance is associated with structural changes in fetal-placental vessels, suggesting a link to poor pregnancy outcomes.
Abstract P308: High Prevalence of Secondary Hypertension with Prospective Systematic Screening
Authors: Bagordo Domenico , Shagjaa Tungalagtamir , ROSSI FEDERICO BERNARDO , Pintus Giovanni , Zanon Chiara , Bertoli Eleonora , Byiringiro Clement , Seccia Teresa , ROSSI Gian Paolo
Published: October 2024

Introduction:
A systematic screening of hypertensive patients for secondary arterial hypertension (SHT) is generally held to be not justified by the low prevalence of SHT but improved knowledge and diagnostic tools might change this view.

Hypothesis:
To challenge the notion that the prevalence of SHT is low, we prospectively submitted consenting hypertensive patients presenting between 2017 and 2023 to a systematic search for SHT.

Methods:
The systematic search for SHT entailed, besides history and full physical examination, renal Doppler ultrasound assessment, a sleep questionnaire, and measurement of serum Na
+
, K
+
, ionized Ca
2+
, plasma active renin (DRC), aldosterone concentration (PAC), the aldosterone-renin ratio (ARR), PTH, TSH, and 24-h urinary/plasma Na
+
, K
+
, Ca
2+
, phosphate, and metanephrine and normetanephrine excretion. Cure or prominent improvement of hypertension after target treatment was used to confirm SHT.

Results:
In 494 consecutive patients (median age 62 years, 50% women) who completed the work-up, we found that 11.5% of these patients had isolated systolic hypertension. The overall prevalence of SHT among those with systo-diastolic HT was 72.3%: 25.5% had primary aldosteronism; 13.4% obstructive sleep apnea, 7.9% hypothyroidism, 6.5% renovascular hypertension and 19.0% rarer causes of SHT. Of all patients, only 14% were referred by their general practitioner or other specialists and 85% were self-presenting.

Conclusions:
Only a small minority of consecutive hypertensive patients seen in a specialized center were referred by their doctors, thus calling for implementation of broad strategies to increase the awareness of SHT. The fact that a systematic screening showed that SHT is far more common than currently believed supports this conclusion.
Abstract P329: Mycophenolate Mofetil Enhances Short-Term Blood Pressure Variability During Recovery in Salt-Sensitive Hypertensive African Americans
Authors: McNeil John , Altvater Michelle
Published: October 2024

Elevated blood pressure variability (BPV) is an independent risk factor for cardiovascular disease (CVD), kidney disease, dementia, and stroke. High BPV is thought to be caused by arterial stiffness, vascular remodeling, inflammatory cascades, and neurohormonal mechanisms. This study aims to investigate the potential impact of mycophenolate mofetil (MMF) on short-term BPV in the context of salt-sensitive hypertension among African Americans (AA). MMF’s anti-inflammatory properties hold promise as a potential intervention for hypertension management by modulating short-term BPV.

AA participants,18-50 years, normotensive, not pregnant, and not on prescription medications were recruited. In this crossover study, 51 participants received either MMF or a placebo daily. Physiological parameters were monitored every 15 minutes during a 3-hour psychosocial stressor assessment with rest, stress, and recovery periods. BPV was assessed using coefficient of variation (CV), standard deviation (SD), and average real variability (ARV).

The treatment group showed a significant decrease in SBP CV (p < 0.05) during stress. During recovery, SBP SD (p, 0.05) and SBP ARV (p < 0.05) significantly increased in individuals receiving MMF treatment. Age-stratified analysis maintained significant effects of MMF on BPV during stress. Gender did not significantly alter the observed effects of MMF on BPV.

Our study highlights the effectiveness of MMF in reducing BPV during acute stress, potentially lowering adverse cardiovascular events. MMF-treated groups showed increased BPV during recovery, indicating a quicker BP recovery to baseline. While a decrease in BPV during the stress period was observed, it was supported only by CV. The significant increase in BPV in the treatment group during recovery indicates MMF's ability to expedite the inflammatory stress response. The observed decrease in BPV during stress suggests a swifter return to baseline BP, potentially offering benefits for non-stress baseline physiology. Further research is warranted to clarify the mechanisms and clinical significance of these findings, impacting hypertension assessment and management.

MMF treatment induces distinct changes in BPV during recovery, suggesting that MMF may positively influence BP regulation through a variety of inflammatory pathways. The alterations in SBP BPV underscore MMF's therapeutic potential for managing BPV and reducing cardiovascular risk in salt-sensitive, hypertensive AAs.
Abstract P336: The Diagnostic Value of Magnetocardiography for Left Ventricular Remodeling in Patients with Hypertension
Authors: Zhang Jianfeng , Jiang Yufeng , Zhang Junyi , Zhou Yafeng
Published: October 2024

Background:
Left ventricular remodeling, commonly observed in the development of cardiovascular diseases, entails structural and functional changes in the heart and stands as an independent risk factor for cardiovascular events. In recent years, magnetocardiography (MCG), as a non-invasive detection method, can capture the weak magnetic field generated by the electrical activity of the heart, and can detect the electrophysiological activity of the heart with high spatiotemporal resolution regardless of the interference of human tissues, and can objectively reflect the changes in cardiac structure and electrophysiology.

Method:
Through the inclusion and exclusion criteria, the patients were divided into hypertension combined with left ventricular remodeling group and hypertensive non-left ventricular remodeling group according to the results of echocardiography（ECHO）. The MCG examination is completed to collect parameters that can reflect ventricular diastolic function. The correlation analysis of ECHO and MCG related parameters was carried out, and the diagnostic efficacy of MCG in the diagnosis of left ventricular remodeling was evaluated.

Outcome:
A total of 220 patients were included in this study, of whom 113 (51%) were males and 107 (49%) were females. There were 115 cases (52%) in the hypertensive and left ventricular remodeling group and 105 cases (48%) in the hypertensive non-left ventricular remodeling group.

Among the 15 MCG parameters, the QRS_Integral, QRS_MCM, R_MCM, R_CA, R_FMA, R_CA, QRS_CA and QRS_FMA were 0.694, 0.771, 0.739, 0.691, 0.691, 0.578, 0.711, 0.739 and 0.757, respectively. The sensitivities were 0.443, 0.617, 0.626, 0.667, 0.348, 0.609, 0.757 and 0.835, and the specificities were 0.924, 0.886, 0.81, 0.722, 0.857, 0.8, 0.59 and 0.6, respectively. QRS_FMA QRS_CA R_CA QRS_MCM The AUC=0.887, sensitivity 0.843, specificity, positive predictive value 0.874, negative predictive value 0.835, and Youden index were 0.71.

Conclusion:
Some of the parameters of MCG are related to cardiac hyperparameters, which can objectively reflect changes in cardiac structure and electrophysiology, and may help to combine ventricular remodeling and "electrical remodeling".

Key words:
Nine-channel low-temperature superconducting magnetocardiography; left ventricular remodeling; hypertension; sensitivity; specificity
Abstract P362: The Associations of Neighborhood Social and Built Environments with Ambulatory Blood Pressures in Young Adults of the Georgia Stress and Heart Cohort
Authors: Dong Yanbin , Altvater Michelle , Howerton Silas , Zhu Haidong , weeks charles , Cheng Jie , Li Wenjun
Published: October 2024

Ambulatory blood pressure monitoring (ABPM) is an assessment method in which BP measurements are taken at regular intervals when individuals are awake and asleep, during a typical 24-hour period. Thus, ABPM is an accurate and effective way to measure BP. Neighborhood social and built environments play an important role in health, which were previously associated with cardiovascular risk factors. However, the effects of neighborhood social and built environments on ABPM is understudied, particularly among young adults and African Americans. The current study aimed to investigate the cross-sectional associations between neighborhood social and built environments and ABPM in our Georgia Stress and Heart Cohort consisting of 543 participants, aged 29.1 ± 3.6 years, 49.7% African American and 51.2% female. There were found to be consistent positive associations of neighborhood social and built environments with 24-hour systolic BP (SBP), 24-hour diastolic BP (DBP), daytime SBP, daytime DBP, nighttime SBP, and nighttime DBP (
p
≤0.01, respectively), after the adjustment for age, race and sex. Neighborhood factors such as Median Household Income and College Graduation held the negative associations with measurements of 24-hour SBP, 24-hour DBP daytime SBP, daytime DBP, nighttime SBP, nighttime DBP, and 24-hour SBP (
p
≤0.01, respectively). This study is one of the first to report the relationship between neighborhood social and built environments and ABP, particularly in young adults and African Americans residing in the US southeastern region. Future longitudinal studies are warranted to further support the findings of the current study.
Abstract P365: Prevalence of Hypertension in Minnesota Adults in 2023 Using Data from a Statewide Electronic Health Record Consortium
Authors: Margolis Karen , Chamberlain Alanna , Drawz Paul
Published: October 2024

Background:
Data on prevalence of hypertension in the United States come primarily from in-person data collected by the National Health and Nutrition Examination Survey and self-reports in the Behavioral Risk Factor Surveillance Survey. Electronic phenotypic algorithms for hypertension that include diagnosis codes, blood pressure values, and antihypertensive treatment have been proposed and tested.

Objective:
To describe prevalence of hypertension in Minnesota adults using data from a statewide electronic health record (EHR) consortium, the Minnesota EHR Consortium (MNEHRC).

Methods:
Data from 11 health systems participating in the MNEHRC were standardized to a common data model allowing for distributed querying of EHR data. Data were de-duplicated using a one-way hash algorithm. Preliminary prevalence of hypertension in 2023 was estimated in Minnesota residents with ≥ 1 encounter in the past 3 years who had ≥1 diagnosis of hypertension in the past 5 years. Medicaid insurance status was determined via linkage with state enrollment files. Residential addresses of patients were geocoded to census tracts and social vulnerability index (SVI) of census tracts was determined.

Results:
Among 4,369,470 Minnesotan age 18 and older in 2023, 23.6% had hypertension based on ≥1 diagnosis code. Prevalence increased with age, was higher in men (26% vs. 22% in women), and adjusted for age and sex was highest in Black (30%) and Native American (27%) compared with White (23%) and Hispanic (21%) Minnesotans. Within each race/ethnic group, those insured by Medicaid had a higher adjusted hypertension prevalence than those with other insurance types. The prevalence of hypertension in census tracts with moderate to high SVI ranged from 3% to 43%, but on average was similar to the statewide prevalence of 24% (see image 1). Prevalence of hypertension in race/ethnicity, sex, and age subgroups in higher SVI census tracts was similar to the statewide prevalence in those subgroups.

Conclusions:
The prevalence of hypertension in Minnesota was described in detail by demographic characteristics, geography and social vulnerability. Future work will expand the electronic hypertension phenotype and examine quality of care.
Abstract P368: The Impact of Obesity on Patients Admitted for Hypertensive Emergency.
Authors: Amoah Joseph , Fatuyi Michael , Somoza-Cano Francisco , Amoah Nana Nyarko , Dekowski Sammir , Asafu-Adjaye Frempong
Published: October 2024

Objectives:
Obesity is associated with a spectrum of metabolic and cardiovascular disorders, including hypertension. We will examine the hospital outcomes of hypertensive emergency in obese patients.

Methods:
Using the National Inpatient Sample Database (NIS) of 2020, patients admitted for hypertensive emergency as the principal diagnosis were identified using ICD-10 codes. The primary outcome was inpatient mortality with the secondary outcomes being acute kidney injury (AKI), cerebrovascular accident (CVA), myocardial infarction (MI), length of hospital stays, and charges between groups. (Patients with body mass index (BMI) greater than 30 and patients with body mass index lesser than 30).

Results:
A total of 59,690 patients were admitted for hypertensive emergency. Of those, 21% had a BMI>30. Patients with BMI> 30 were younger (53 years, 95% CI 53 – 54 VS 61 years, 95% CI 61 – 62). Patients with BMI > 30 had reduced inpatient mortality (p=0.0420), CVA (p=0.0248), acute hypoxic respiratory failure (p=0.0033), and total hospital charges ($ 46,314, 95% CI $44,000.75 - $48,627.93 VS $47,248.7 95% CI $45,709.43 - $48,787.97). There was no difference in length of hospital stay between groups (4 days, 95% CI 3 – 4 VS 4 days, 95% CI 4 – 4). Patients with a BMI greater than 30 had increased acute kidney injury (p=0.0026).

Conclusion:
Per this study, obesity does not increase mortality in patients admitted for a hypertensive emergency.
Abstract P380: ISG15 is responsible for endothelial inflammation and vascular disfunction induced by Spike protein 1 of SARS-CoV-2.
Authors: Rios Francisco , Montezano Augusto , Camargo Livia , Lopes Rheure , Garcia Ana , ARANDAY-CORTES ELIHU , Briones Ana , McLauchlan John , Touyz Rhian
Published: October 2024

Introduction:
COVID19-associated immunopathology is associated with increased production of interferon (IFN)-alpha (IFNα) and lambda3 (IFNL3). Effects of IFNs are mediated by interferon-stimulated genes (ISGs) and influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFNs and may be important in vascular dysfunction associated with hypertension.

Methods:
Human microvascular ECs (MEC) were stimulated with S1P (1µg/mL), IFNα (100ng/mL) or IFNL3 (100IU/mL). Because ACE2, metalloproteinase domain-17 (ADAM17) and type-II transmembrane serine protease (TMPRSS2) are important for SARS-CoV-2 infection, we used inhibitors of ADAM17 (marimastat), ACE2 (MLN4760), and TMPRSS2 (camostat). Gene and protein expression was investigated by real-time PCR and immunoblotting. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive mice and in ISG15KO mice.

Results:
MEC stimulated with S1P increased expression of IFNα (3-fold), IFNL3 (4-fold) and ISGs (2-fold) (p<0.05). IFNα and IFNλ3 increased protein expression of TMPRSS2 and ADAM17, but not ACE2. MEC exhibited higher responses to IFNα (ISG15: 16-fold) than to IFNL3 (ISG15: 1.7-fold) (p<0.05). ISG15 was also increased by S1P, effects that were enhanced by MLN4760 (2-fold) and reduced by marimastat (50%). S1P increased IL-6 mRNA (1.3-fold), TNFα (6.2-fold) and IL-1β (3.3-fold). These responses were increased by by IFNs. IL-6 was increased by IFNα (1,230pg/mL) and IFNL3 (1,124pg/mL) vs control (591pg/mL). This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). Nitric oxide production and eNOS phosphorylation (Ser1177) were reduced by IFNα and (40%) and IFNL3 (40%). Reduced endothelium-relaxation maximal response (%Emax) was observed in vessels from WT-mice stimulated with IFNα (67%) and IFNL3 (71%) vs control (82%) (p<0.05) but not in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNα (9.1±0.5mN vs control: 7.3±0.3mN, p<0.05).

Conclusions:
In ECs, S1P, IFNα and IFNL3 increased ISG15 and IL-6, processes that involve ADAM17 and are independent on ACE2. Inflammation induced by S1P was amplified by IFNs. IFNs induce vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension.