bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 25: The Blood Pressure Effects of a Just-in-time-adaptive Intervention for Physical Activity and Diet in Patients with Hypertension: A Randomized Controlled Trial
Authors: Dorsch Michael , Golbus Jessica , Basu Tanima , Luff Evan , Warden Kimberly , Giacalone Michael , Bailey Sarah , VanAken Gabriella , Mishra Sonali , Klasnja Predrag , Newman Mark , Skolarus Lesli , Nallamothu Brahmajee
Published: October 2024

Background:
Emerging data suggest mobile health interventions are a promising approach for managing hypertension, but large-scale studies are lacking. The myBPmyLife mobile application is a just-in-time adaptive intervention incorporating behavioral change strategies such as goal setting, prompts, visualizations, and feedback to encourage increased physical activity and lower-sodium food choices.

Methods:
The study was a prospective, randomized-controlled trial that enrolled patients with hypertension from the University of Michigan Health in Ann Arbor, MI, and the Hamilton Community Health Network, a series of federally qualified health center clinics, in Flint, MI. Participants were randomized 1:1 to either the intervention group receiving the myBPmyLife mobile application or the control group and followed for 6 months. Participants in both groups received a smartwatch and a Bluetooth blood pressure (BP) monitor and were prompted to perform BP measurements once weekly. The primary outcome was systolic BP (SBP) change from baseline to 6 months. Secondary outcomes included change from baseline to 6 months in mean daily step count assessed by smartwatch and mean daily sodium intake assessed by the Block sodium screener.

Results:
The study enrolled 602 participants between December 2021 and July 2023. Mean age was 59.6 years (SD 14), with 74.4% self-identifying as White and 51.7% as men. Baseline estimated sodium intake was 3089 mg (SD 1078) per day, mean step count was 7618 (SD 3778) steps per day, SBP was 132 (SD 15) mmHg, and diastolic blood pressure (DBP) was 82 (SD 10) mmHg. Change in SBP from baseline to 6 months was -5.2 (SD 15) mmHg in the intervention and -5.7 (SD 15) mmHg in the control group (Table; p=0.76). Change in DBP from baseline to 6 months was -3.0 (SD 9) mmHg in the intervention and -3.6 (SD 10) mmHg in the control group (p=0.52). From baseline to 6 months, estimated daily sodium intake decreased by 1145 mg (SD 1023) in the intervention and 860 mg (SD 1001) in the control group (p=0.002), while mean daily step count increased by 170 steps (SD 2690) in the intervention and decreased by 319 steps (SD 2612) in the control group (p=0.040).

Conclusion:
A mobile health intervention, myBPmyLife, promoting lifestyle modification in hypertensive patients did not change SBP over 6 months compared to the control group despite significantly improving daily sodium intake and step count over that period.
Abstract 27: A Randomized Clinical Trial for Asymptomatic Elevated Blood Pressure in Patients Discharged from Emergency Department
Authors: prendergast heather , Kitsiou Spyros , Petzel Gimbar Renee , Freels Sally , Sanders Anissa , Daviglus Martha , Carter Barry , Del Rios Marina , Heinert Sara , Khosla Shaveta
Published: October 2024

Introduction:
Hypertension is a prevalent condition that is often asymptomatic. Emergency Department (ED) patients commonly present with underlying and undiagnosed hypertension. As EDs serve as critical access points for healthcare, they present a unique opportunity for hypertension screening and intervention, and ED-based interventions could target patients who are often missed in other healthcare settings.

Hypothesis:
We hypothesize that an Education and mHealth Empowerment intervention would be effective when compared to standard discharge instructions in reducing systolic blood pressure by 6-month follow-up among patients with asymptomatic elevated blood pressure discharged from the ED.

Methods:
A randomized clinical trial was designed to enroll patients with asymptomatic elevated blood pressure (> 140/90 mm Hg and ≤ 180/110 mm Hg) discharged from an urban academic ED that predominantly serves patients from minoritized racial and ethnic groups. Patients were randomized to either usual care (standard discharge with outpatient follow-up referral) or the intervention arm (education and mHealth Empowerment intervention at discharge – the intervention included a consultation with a clinical pharmacist or an advanced practice nurse, and use of mHealth to educate on and facilitate self-monitoring and behavior change along with a primary care referral, and follow-up visits at 3 and 6 months).

Results:
Of the 574 enrolled, 289 were randomized to the intervention group. The mean age of the sample was 51.1 (±12.5) years, and 57% were female, 72% were Black, and 20% Hispanic. There were no statistically significant differences between the two arms by demographics or mean blood pressure at baseline. At 6 months follow up, the intervention arm showed a greater reduction in systolic blood pressure compared to the usual care group, and the difference was statistically significant (mean difference: 4.9 mm Hg, 95% CI [0.8, 9.0], p=0.02).

Conclusions:
The Education and mHealth Empowerment intervention was more effective than standard discharge instructions in reducing systolic blood pressure in a predominantly Black and Latino patient population with elevated blood pressure discharged from the ED. This intervention, and other similar ED-based interventions could be a viable and scalable strategy for blood pressure control in asymptomatic patients for preventing secondary cardiovascular complications due to uncontrolled hypertension.
Abstract 43: PAR1 Inhibition with Vorapaxar Enhances Renal Function and Modulates Inflammation Mediators in Diabetic Nephropathy
Authors: Bohovyk Ruslan , Kravtsova Olha , Lowe Melissa , Upadhyay Gunjan , Levchenko Vladislav , Halade Ganesh , Palygin Oleg , Staruschenko Alexander
Published: October 2024

Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, and hypertension is a comorbidity in about 90% of all cases. Characteristics of pathological changes of DN include severe albuminuria, renal hyperfiltration, glomerular basement membrane thickening, and glomerulosclerosis. Identifying the molecular mechanisms underlying DN is critical for developing more effective therapeutic approaches. Thus, interventions targeting podocytes have become a major focus for diseases like DN due to their crucial role in regulating glomerular permeability and maintaining glomerular structures. Our previous studies have demonstrated that serine proteases and Protease-activated receptor 1 (PAR1) are involved in developing DN through TRPC6-mediated calcium signaling in podocytes. Utilizing a PAR1 heterozygous knockout rat model with a type 2 diabetic background, we showed that reducing PAR1 expression decreases microalbuminuria and glomerular damage. This study aims to define the effects and potential mechanisms of pharmacological blockade of PAR1 on the development of DN. To achieve this, 16-week-old T2DN rats were treated with a potent and selective PAR1 antagonist (vorapaxar (SCH 530348), 10 mg/kg of diet) for 16 weeks to determine the effect of PAR1 inhibition. We found improvements in glomerular filtration rate (GFR) in treated animals compared to control after 16 weeks of treatment (0.8 ± 0.2 vs 1.2 ± 0.2 mL/min/100g b.w., p=0.029, N≥4). We observed a trend toward differences in basal intracellular calcium concentration in podocytes between the control and treated groups, although these changes were not statistically significant (202 ± 95 vs 152 ± 75 nM, p=0.19, n≥10, N=3). Additionally, inhibition of PAR1 caused modulation in the inflammation-resolution mediators in the kidney with significant upregulation of Maresins Conjugates in Tissue Regeneration (MCTR1) and downregulation of hydroxy-docosahexaenoic acids (7-,14-,17-HDHA). Changes in GFR may be linked to reduced glomerular damage, indicating that the structural integrity of the glomeruli is better maintained in treated animals. Alterations in the lipidomic profile could indicate a reduction in the inflammatory processes typically associated with DN. Overall, our data indicates that vorapaxar improves glomerular filtration rate and modulates lipid mediators in a type 2 diabetic rat model. This suggests that targeting PAR1 could be a promising therapeutic strategy for diabetic nephropathy.
Abstract 53: Chronic Angiotensin-(1-7) Treatment May Enhance GABAergic Neurotransmission onto Melanocortin-4 Receptor Neurons in The Hypothalamic Paraventricular Nucleus in a Sex-Specific Manner
Authors: Vernail Victoria , Bingaman Sarah , Silberman Yuval , Arnold Amy
Published: October 2024

Angiotensin (Ang)-(1-7) is a protective hormone of the renin-angiotensin system that lowers blood pressure in animal models of cardiovascular disease; however, the precise mechanisms remain incompletely understood. Recent data from our laboratory suggests that blood pressure lowering effects of Ang-(1-7) may involve the arcuate nucleus of the hypothalamus (ARC). We have shown that Ang-(1-7) activates proopiomelanocortin (POMC)-containing neurons in the ARC. While ARC POMC neuron activation canonically increases blood pressure by stimulating melanocortin-4 receptors (MC4R) in the hypothalamic paraventricular nucleus (PVN), these neurons also release the inhibitory neurotransmitter GABA. Selective activation of these GABAergic POMC neurons could serve as a novel mechanism to lower blood pressure. In this study, we hypothesized that Ang-(1-7) treatment inhibits PVN MC4R neuron activity via enhanced GABAergic function. To test this, male and female MC4R-GFP mice were implanted with osmotic mini pumps at 14 weeks of age and treated chronically with either Ang-(1-7) (400 ng/kg/min) or saline. After six weeks of drug administration, action potential firing of PVN MC4R-expressing neurons was examined using cell attached electrophysiology. To assess GABAergic function, changes in action potential firing frequency following bath application of the GABA
A
receptor antagonist bicuculline (10 μm) were compared between Ang-(1-7) and saline treated animals (n=4-6 mice/group). While Ang-(1-7) did not alter baseline firing frequency of MC4R PVN neurons in male mice (1.5±0.6 vs. 1.1±0.3 Hz saline; p=0.630, unpaired t-test), it enhanced bicuculline responsiveness as indicated by a greater peak increase in action potential firing frequency (156.9±18.0 vs. 106.2±6.8 % saline; p=0.013). In female mice, Ang-(1-7) increased baseline action potential firing frequency of PVN MC4R neurons (1.5±0.4 vs. 0.3±0.1 Hz saline; p=0.026) but did not alter bicuculline responsiveness (111.0±5.3 vs. 143.2±25.3 % saline; p=0.241). Overall, our data suggest that Ang-(1-7) enhances GABAergic neurotransmission onto PVN MC4R neurons in a sex-specific manner. These data provide new insight into the neural mechanisms of Ang-(1-7), which could have implications for understanding the beneficial cardiovascular effects of this hormone. Additional studies are needed to examine this inhibitory neurocircuit in the context of hypertension as well as precise mechanisms underlying the observed sex differences.
Abstract 62: Notch3 and the Vascular-Adipose Interactome in the Regulation of Adiponectin and Vascular Contraction
Authors: Montezano Augusto , Sarafian Raquel , Rao Prashant , He Ying , Rios Francisco , Camargo Livia , Chen Zsu-Zsu , Barber Jacob , Gerszten Robert , Touyz Rhian
Published: October 2024

Notch3, a cell-cell interaction receptor expressed in VSMCs, is important in vascular function. Notch3 mutations cause CADASIL and aberrant Notch3 signaling is associated with vascular dysfunction/remodeling of resistance arteries, similar to the vascular phenotype in hypertension. Recent evidence suggests that Notch receptors, including Notch3, also play a role in adipose biology. Based on our previous findings that aberrant Notch3 signaling leads to vascular injury, and that perivascular adipose tissue influences vascular function we investigated a potential role for Notch3 in the vascular-adipose interactome. We characterized adipose tissue (AT) [brown AT (BAT) and white AT (WAT)] and vascular function in mice overexpressing Notch3 (N3) and in mice harboring the R169C gain of function Notch3 mutation (RC). We evaluated expression of Notch3, and its target transcription factors, BAT markers (UCP-1, OTOP-1), and production of adiponectin and IL-6. Isolated arteries from control mice were exposed to BAT conditioned medium (CM) and vascular function assessed by myography. We did not observe any changes in body weight, but BAT (N3: 115.4±7.1; RC: 115.3±8.2; WT: 154±12.1 mg, p<0.05) and WAT (N3: 309.7±39; RC: 370.4±41; WT: 618.1±73 mg, p<0.05) were decreased in N3 and RC mice. Expression of Notch3 target genes (Heyl, Hes5) was increased in BAT from N3 and RC mice. This was associated with increased production of adiponectin (N3: 25.1±0.4; RC: 25.8±0.6; WT: 23.6±0.4 pg/µg of tissue, p<0.05) and IL-6 (N3: 45.3±5.6; RC: 51.6±5.1; WT: 33.7±2.1 pg/µg of tissue, p<0.05) (by ELISA). UCP-1 expression was increased in WAT from Notch3 mice versus wildtype. Vascular contraction to U46619 was reduced by BAT CM from WT mice (EMax: 158.5±9.7% vs control 183.6±6%). This effect was enhanced with BAT CM from Notch3 (N3 and RC) mice. WAT CM from N3 and RC mice reduced vascular sensitivity to contraction (logEC50: N3=7.2±0.17M; RC=7.2±0.1M; WT: 7.7±0.1M, p<0.05). In summary, at the molecular level, Notch3 regulates adipose tissue, with increased production of adiponectin in BAT and increased expression of browning markers in WAT. Functionally BAT from Notch3 mice attenuates vasoconstriction in WT mice. Our data suggest a putative role for Notch3 in the vasoprotective effects of BAT. These novel findings suggest an important role for Notch3 in the vascular:adipose interactome. Notch3 activation may influence vascular function, in part, by regulating perivascular BAT/WAT.
Abstract 64: Smooth Muscle Cullin-3 Regulates the Renal Baroreceptor Mechanism: a Link Between CUL3 and Integrin β1
Authors: Golosova Daria , Kumar Gaurav , Lu Ko-Ting , Chaihongsa Nisita , Brozoski Daniel , Muskus Veitia Patricia , Reho John , Nakagawa Pablo , Sigmund Curt
Published: October 2024

Cullin-3 (CUL3) is a critical component of the CUL3-Ring-Ligase (CRL) ubiquitin ligase complex. CUL3 mutants in smooth muscle cells (SMCs) cause vascular dysfunction, arterial stiffness, and severe hypertension (HTN). We hypothesized that conditional deletion of CUL3 in SMCs (S-CUL3KO) led to HTN via 1) a renin-angiotensin system (RAS)-dependent mechanism, and 2) impaired renal baroreceptor mechanism regulating renin expression. CUL3
Flox
mice were bred to mice carrying tamoxifen-inducible CRE-recombinase under a smooth muscle promoter (ISM-CRE, control). S-CUL3KO mice exhibited augmented systolic blood pressure (SBP) (ISM-CRE: 124±1 vs. S-CUL3KO: 167±3 mmHg, p<0.05) 3-weeks post tamoxifen. Once HTN was established we used an angiotensin-converting enzyme inhibitor (captopril, 10 mg/kg/day in drinking water) for 1 week to reverse HTN. We observed a greater depressor effect in S-CUL3KO (ΔSBP -49±3 mmHg) compared to ISM-CRE (ΔSBP -33±1 mmHg, p<0.05). A similar effect was identified following angiotensin II type I receptor blocker (ARB, candesartan, 100 mg/kg/day in drinking water) treatment (ΔSBP, ISM-CRE: -27±2 vs. S-CUL3KO: -37±2, p<0.05). We prevented HTN in S-CUL3KO by administering ARB before tamoxifen injection (SBP 120±5 mmHg). Mesenteric arteries exhibited augmented Ang-II induced vasoconstriction, which was prevented with ARB, suggesting that HTN in S-CUL3KO is RAS-dependent and AT
1
R-mediated. Despite severe HTN, S-CUL3KO did not suppress renin mRNA expression in kidneys. We hypothesize that S-CUL3KO exhibits a defective renal baroreceptor mechanism causing impaired suppression of renin expression. We propose that CUL3 participates in the degradation of integrin β1, the key mechanosensory of the renal baroreceptor, via Rab-mediated trafficking and lysosomal fusion. Supporting this, HEK293 cells lacking CUL3 exhibited lower integrin β1 protein expression (0.51±0.08 vs. 0.09±0.01 normalized RFU, p<0.05) concomitant with increased Rab5 and Rab7 expression (3.6±0.3 vs. 1.9±0.1 and 0.95±0.12 vs. 0.37±0.04 normalized RFU). S-CUL3KO demonstrated severely impaired morphological distribution of integrin β1 protein in the juxtaglomerular apparatus. In conclusion, our findings support the hypothesis that 1) CUL3 regulates RAS via the renal baroreceptor, and 2) Rab proteins regulating integrin β1 expression are potential targets for the CRL3 pathway. Understanding CUL3 target proteins might contribute to the development of new strategies to treat HTN.
Abstract 65: Postpartum Alterations of Middle Cerebral Artery Reactivity and Hemodynamics in a Transgenic Rat Model of Preeclampsia
Authors: Pulgar Victor , Ray Jonathan , Sun Xuming , Yamaleyeva Liliya
Published: October 2024

Evidence suggests that cerebrovascular disease is a leading cause of morbidity and mortality in women with preeclampsia (PE), however the mechanisms are unknown. In a transgenic rat displaying PE-like syndrome (TGA-PE: female transgenic for angiotensinogen mated to male transgenic for renin), we have shown postpartum alterations in cerebrovascular hemodynamics suggesting dysfunctional autoregulation. We hypothesize that impaired middle cerebral artery (MCA) reactivity contributes to the cerebrovascular dysfunction in this model. High frequency ultrasound was used to determine the pulsatility index (PI) of left MCA (LMCA). Vascular responses were studied in isolated segments of LMCA from SD (n= 12) and TGA-PE (n=8) two months post-delivery. Arteries were mounted on a Multi-Wire Myograph for determination of isometric force (USA-DMT). The contractile responses to K
+
75 mM and endothelin-1 (ET-1, 10
-11
-10
-7
M) were measured in basal tone. Vasodilatory responses to acetylcholine (ACh, 10
-11
-10
-4
M) were determined in arteries pre-constricted with the thromboxane agonist U46619 (10
-7
M); the maximal response (

R
MAX

) and sensitivity (pD
2
=-Log[EC
50
]) were analyzed. Our data show that systolic blood pressures were elevated in TGA-PE versus SD at 2 months post-delivery (144.9±2.7
vs.
118.4±2.5, p<0.05; n=10-19). However, the PI was lower in TGA-PE
vs.
SD (0.96±0.05
vs.
1.31±0.06; p<0.05, n=8-13). No differences in basal tone of MCA segments were observed, whereas TGA-PE arteries displayed a lower optimal diameter (175±4 μm
vs.
217±4 μm; p<0.05) and a lower response to K
+
(0.85±0.11
vs.
1.29±0.1 mN/mm; p<0.05) compared to SD. Vasodilatation to acetylcholine was similar (ACh
MAX
: 79±8
vs.
70±9%) with a lower sensitivity (pD
2
: 5.2±0.1
vs.
6.7±0.4; p<0.05) in TGA-PE. The contractile response to ET-1 was increased in TGA-PE arteries (ET-1
MAX
:
159±7
vs.
129±6 % K
MAX
; p<0.05) with no differences in sensitivity (pD
2
: 8.8±0.1
vs.
8.9±0.1). Our data demonstrate structural and functional differences in MCA from TGA-PE vs. SD at 2 months postpartum. In addition to a smaller functional diameter, a lower non-receptor dependent contraction may explain the lower resistance of MCA observed in the preeclamptic model. We conclude that attenuated vasodilatory and increased contractile responses of MCA could promote cerebrovascular dysfunction in this model, and that these adaptations may contribute to cerebrovascular pathology in postpartum preeclamptic state. Supported by NIH 1R01HL155420
Abstract 67: Cardiac Biomarkers in Pregnancies with and without Hypertension – a Case Control Study
Authors: Kovell Lara , Denu Mawulorm , Shao Cassie , Meyerovitz Claire , Moinul Sheikh , Essa Angela , Wilkie Gianna , Moore Simas Tiffany , Juraschek Stephen
Published: October 2024

Background:
There is ongoing debate about hypertension (HTN) management during pregnancy with a range of recommended targets. Whether HTN is related to subclinical cardiac injury during pregnancy is unclear.

Objective:
To determine the relationship between HTN with subclinical cardiac injury during and immediately after pregnancy, measured via high sensitivity troponin I (hs-cTnI).

Methods:
In a prospective, 1:1 case-control design, we enrolled pregnant women with and without HTN between 24-32 weeks gestation (2019-2022). HTN cases were defined by a clinician diagnosis at <20 weeks gestation or a baseline blood pressure (BP) ≥140/90 mm Hg. The control group (no HTN) had a systolic BP <120 mm Hg. Hs-cTnI was collected at baseline, the delivery admission, and postpartum day 1. We used mixed effects tobit models to compare the groups on log-transformed hs-cTnI, adjusted for age and BMI.

Results:
The mean age of the HTN group (N=38) was 33.6 (SD 5.4) vs. 30.3 (5.8) years for the no HTN group (N=38). Mean (SD) baseline BP was 131.1 (14.7)/88.2 (13.5) for the HTN group and 110.1 (7.2)/70.9 (8.2) mm Hg for no HTN. At baseline, hs-cTnI was 1.3 (0.2) in the HTN group and 0.6 (0.1) ng/L in the no HTN group (
Figure
). Compared to baseline, hs-cTnI increased 89.1% (95% CI: 27.3-180.8%) and 322% (192-511%) for the HTN group, and 101.6% (41.0-188.3%) and 165.2% (88.6-272.9%) for no HTN at delivery and postpartum, respectively. Across all time points, the HTN group had a higher hs-cTnI of 1.05 (0.07-2.03) ng/L compared to the control group.

Discussion:
HTN was associated with subclinical cardiac injury during and immediately postpartum. These findings support recommendations to control HTN throughout pregnancy to reduce cardiac injury.
Abstract MP03: Perineuronal nets in the paraventricular nucleus of the hypothalamus are altered during DOCA-salt hypertension
Authors: Blanco Ismary , Chen Sichu , Yeo Erin , Santisteban Monica
Published: October 2024

The paraventricular nucleus of the hypothalamus (PVN) is critical to integrate peripheral signals to modulate neurohumoral and sympathetic output. During hypertension, overactivation of the PVN contributes to neurohumoral dysregulation and increased sympathetic tone. Perineuronal nets (PNNs) are lattice-like extracellular structures that surround the soma and proximal dendrites of neurons and modulate neuronal firing and circuit plasticity. These structures are expressed throughout the brain, including the hypothalamus and PVN, and are of particular interest because changes in their deposition have been associated with multiple neurological disorders including stress, PTSD, and depression. Here, we explore changes in PNNs in the PVN during DOCA-salt hypertension, a model of neurogenic hypertension, specifically testing the hypothesis that PNNs deposition would be decreased in the PVN. 5-month old male C57BL6 mice were implanted with a s.c. deoxycorticosterone acetate (DOCA) pellet and received 0.9% NaCl in the drinking water. Blood pressure was monitored twice weekly by tail-cuff plethysmography. After 21-days of DOCA-salt (n=3) and sham control (n=4), mice were perfused with 2% paraformaldehyde to quantify PNNs using the marker N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA). We found a trend towards less WFA+ neurons in the PVN in DOCA-salt vs control (42.29 ± 7.93 neurons/mm
2
in DOCA vs 68.97 ± 10.80 in control; p=0.1231), but observed no difference in the overall PVN area that was positive for WFA+ staining (26.53 ±0.80 % in DOCA vs 29.75 ± 2.02 % in control). Next, we quantified WFA intensity (PMID 28713865) and observed a decrease in individual PNN intensity in the PVN of DOCA-salt mice (40.08 ± 7.46 vs 67.39 ± 7.42 a.u. in control), as well as a decrease in total WFA+ intensity in the PVN (26.04 ± 3.48 vs 33.80 ± 0.29 a.u. in control; p=0.0458). We conclude that PNN deposition is decreased in the PVN during DOCA-salt hypertension, a potentially important mechanism which has been previously unexplored. PNN intensity has been previously associated with neuronal firing; therefore, ongoing studies are investigating the contribution of PNNs in the PVN to sympathetic tone and blood pressure regulation during DOCA-salt hypertension.
Abstract MP10: A Remote Pharmacist Intervention for Monitoring and Treating Hypertension for Patients Living in Rural Areas
Authors: Carter Barry , Simmering Jacob , Francis Shelby , Sewell Daniel , Finkelstein Rachel , Ernst Michael , Polgreen Philip , Polgreen Linnea
Published: October 2024

Background:
Hypertension is a significant, but modifiable, cause of morbidity. Many people are unaware that they have hypertension, and of those with a diagnosis, many do not have controlled blood pressure (BP). Undertreatment may be especially problematic in medically unserved rural areas with reduced access to medical care. The goal of this study was to evaluate whether a remote pharmacist-based intervention improves BP management for patients in rural areas.

Methods:
We recruited English- and Spanish-speaking rural adults from University of Iowa Health Care with at least 2 previous clinically measured BP values > 145 mmHg systolic or > 95 mmHg diastolic, for a 12-month study. Patients submitted up to 14 home BP measurements via text messaging pre-randomization. They had one conversation with the research pharmacist, and then they were randomized to the intervention or control group. The control group received only usual care for the rest of the study period. The intervention group received calls as often as once a month from a remote pharmacist who reviewed their home BP, gave medication recommendations to patients’ providers through the electronic medical record, and provided lifestyle recommendations. Research BPs and antihypertensive medication use were measured at baseline, 6 months, and 12 months. At the end of the study, patients were asked about their experiences with the remote pharmacist and the study in general.

Results:
There were 211 patients in the control group, and 209 in the intervention group. Average age was 58 years. Four percent of participants were Black, and 23% were Hispanic. Average BMI was 33, and 29% had diabetes. The decrease in systolic BP in the intervention group was 9.5 mmHg lower than the control group at 6 months (p<0.001), and 4.8 mmHg lower than the control group at 12 months (p=0.019). There were no changes in the probability of being treated, but the intervention group had 75% more medication changes in the first 6 months compared to the control group (p<0.001). Many patients commented about the ease of participation and were interested in continuing communications with the pharmacists and reporting home BP readings after the study finished.

Conclusions:
Our bi-directional texting and remote pharmacist intervention successfully lowered BP levels. Future work will expand this study to other populations and examine this study’s cost effectiveness.
Abstract MP16: Expression of an AT
1
R Receptor Mutant which Genetically Biases Gαq Specifically in Vascular Smooth Muscle Cell Causes Hypertension and Enhanced Vascular Contraction
Authors: Chaihongsa Nisita , Lu Ko-Ting , Reho John , Brozoski Daniel , Muskus Veitia Patricia , Nakagawa Pablo , Grobe Justin , Sigmund Curt
Published: October 2024

Angiotensin II (ANG) type 1 receptor (AT
1
R) belongs to the 7-membrane superfamily of G protein-coupled receptors (GPCR) which have the largest class of drug targets. AT
1
Rs can adopt different conformations that can bias G-protein coupling (particularly Gaq) or b-arrestin signaling. The b-arrestin pathway is reported to be cardioprotective while the canonical Gaq-dependent pathway is typically associated with the detrimental effects of ANG. We hypothesize that selective and inducible activation of the AT
1
R Gaq pathway in the absence of b-arrestin signaling in vascular smooth muscle (SMC) results in hypertension and vascular dysfunction via an AT
1
R-dependent mechanism. We generated an AT
1
R mutant (AT
1
R
TSTS-AAAA
) which ablates the phosphorylation sites for GPCR kinases (GRK) in the C-terminal to impair b-arrestin recruitment and to induce a Gaq bias. Transgenic mice were made with a construct that induces both AT
1
R
TSTS-AAAA
and tdTomato expression in response to Cre-recombinase. Primary fibroblasts cultured from AT
1
R
TSTS-AAAA
mice exhibited a Cre-induced expression of tdTomato and marked increase in phosphorylated-extracellular signal-regulated kinase (P-ERK) in response to ANG when compared to mice cells expressing wildtype AT
1
R. Mice carrying inducible AT
1
R
TSTS-AAAA
were bred with tamoxifen-inducible SMC-specific CRE (SMC
CreERT2
, S-TSTS) mice. Transgene expression in S-TSTS mice was successfully activated by tamoxifen as measured by the expression of the embedded tdTomato reporter in the aorta SMC. S-TSTS mice exhibited a trend of increased systolic blood pressure (SBP) 1 week after tamoxifen injection (147.76 ± 13.21 vs. 108.85 ± 4.58 mmHg). Candesartan (10 mg/kg/day in drinking water) was then administered to S-TSTS mice once hypertension was established. Candesartan treatment for 1 week reversed the hypertension in S-TSTS mice (100.00 ± 2.88 mmHg). Interestingly, 2 weeks after ending candesartan treatment, SBP was once again elevated in S-TSTS mice (142.01 ± 7.65 vs. 90.35 ± 1.14 mmHg, p<0.05). In addition, mesenteric arteries from transgenic mice exhibited a robust increase in ANG-induced constriction when compared to control mice (ANG, max constriction 60.25 ± 4.78% vs. 14.12 ± 4.72%, p<0.05). Our findings support the hypothesis that signaling through the Gaq-dependent pathway in SMC leads to increased vasoconstriction and hypertension through an AT
1
R-dependent mechanism.
Abstract MP19: Hypertension Prevalence Among Youth aged 8–19 years in a National Survey — United States, 2017–2020
Authors: Sekkarie Ahlia , Zhou Wen , Lundeen Elizabeth , Imoisili Omoye , Jackson Sandra , Kumar Ashutosh , He Siran , Loustalot Fleetwood
Published: October 2024

Hypertension in youth tracks into adulthood and has long-term negative health effects. In 2017, the American Academy of Pediatrics released new Clinical Practice Guidelines on pediatric hypertension. The guidelines updated blood pressure (BP) thresholds and age-sex-height percentile references for youth 1–17 years. Pediatric hypertension prevalence estimates since the new guideline are lacking.

This study aims to provide the latest nationally representative prevalence estimates of elevated BP and hypertension in youth aged 8–19 years, total and stratified by age group, sex, race and ethnicity, and body mass index (BMI) category. For adolescents aged 13–17 years, both percentile-based thresholds and adult BP thresholds are available in the guidelines. We therefore compared adult BP thresholds for elevated BP (120–129/<80 mmHg) and hypertension (≥130/≥80 mmHg) with percentile thresholds in adolescents.

We used data from 2017–March 2020 National Health and Nutrition Examination Survey to obtain a sample of 2600 youth after excluding those with no BMI or BP measures. Prevalence estimates of elevated BP and hypertension were 8.7% (95% CI: 6.9-10.6) and 5.4% (95% CI: 4.0-6.7), respectively. Estimates were higher among males and increased with age (Table). Youth with severe obesity had the highest prevalence of hypertension. Hispanic youth had the lowest prevalence of elevated BP. In adolescents, elevated BP prevalence was similar using percentile thresholds (11.9%, 95% CI: 9.3-15.1) and the adult threshold (10.8%, 95% CI: 8.5-13.7). Hypertension prevalence in adolescents was also similar for percentile thresholds (4.8%, 95% CI: 3.1-7.6) and the adult threshold (4.8%, 95% CI: 2.0-7.5).

Our findings suggest ongoing concern of elevated BP and hypertension among youth in the US. Either percentile or adult based thresholds for determining high BP could be used among adolescents by researchers. Knowledge of current national estimates can inform policies and interventions to support cardiovascular health in youth.
Abstract MP21: Hypertension in Young Adults: Social Determinants of Prevalence, Awareness, Treatment, and Control
Authors: Alexander Thomas , Gauen Abigail , Petito Lucia , Kohli-Lynch Ciaran , Carton Thomas , Smith Steven , Merritt Greg , Ahmad Faraz , Allen Norrina
Published: October 2024

Introduction:
Hypertension (HTN) is the leading modifiable risk factor for CVD and a major cause of preventable deaths in the US. Social determinants of health (SDoH) impact HTN management.

Methods:
HTN prevalence, awareness, treatment, and control were assessed in NHANES 2017-2020 among young (18-39 years), middle-aged (40-64 years), and older adults (≥65 years). Exposures included 5 social needs: low education, low income, no health insurance, food insecurity, and no/limited employment. Sample included participants with SDoH measures and HTN as defined per 2017 ACC/AHA guidelines or use of BP lowering medications (N=3720, representing 89 million adults). Multinomial regression estimated the association of number of social needs (0, 1, or ≥2) with HTN status including aware, treated (among aware) and controlled (among treated), adjusted for age, sex, and race/ethnicity. NHANES weights were used in analyses.

Results:
HTN prevalence was 22.7% among young adults. Young adults were more likely than middle-aged and older adults to be unaware or untreated compared to controlled for HTN (P<0.001). Young adults with HTN were more likely to be uninsured, food insecure, and low income compared to older adults (Figure). Adults with HTN and ≥2 social needs were more likely than adults with no social needs to be untreated (OR 1.79; 95% CI 1.15- 2.78; P=0.009) or uncontrolled (OR 1.71; 95% CI 1.27-2.32; P<0.001) compared to having controlled HTN.

Conclusions:
SDoH strongly associate with HTN screening and management. Treatment and control are less common among adults with multiple social needs, particularly for younger individuals. Improving insurance coverage, employment, and food security for young adults could improve HTN management.
Abstract MP25: Buprenorphine pharmacotherapy reduces somatic signs of withdrawal in neonates but may not prevent cardiovascular risk in adult offspring with prenatal fentanyl exposure
Authors: Ahmed Nermin , Dalmasso Carolina , Lamb Jennifer , Ravasi Camila , Ortinski Pavel , PAUTASSI RICARDO MARCOS , Loria Analia
Published: October 2024

Long-term effects on the cardiovascular system of offspring exposed to fentanyl
in utero
are one of the understudied aspects of the opioid crisis. Previously, we have shown that offspring exposed to opioids
in utero
display exacerbated somatic signs of withdrawal compared to vehicle-exposed offspring. We also showed that prenatal opioid exposure induce long lasting effects increasing blood pressure (BP) in the adult offspring. Buprenorphine (BUP) is one of the most effective FDA-approved standard-of-care therapies used to treat mothers with opioid use disorder and their newborns with neonatal opioid withdrawal syndrome (NOWS). Yet, long-term effects of BUP in the pediatric population is limited. This study aimed to determine the efficacy of BUP in reducing somatic signs of withdrawal in rat neonates and the long-term effects on BP control. Female Sprague-Dawley rat breeders were implanted with a chronic jugular vein catheter and subjected to 2-hr self-administration (SA) sessions of vehicle (VEH, 0.9% NaCl, n=3) or fentanyl (FEN, 2.5 μg/kg/infusion/lever press, n=3). After rats developed dependence, they were paired during proestrus with males for breeding. SA sessions continued until delivery. There were no changes in maternal weight gain and pup weights at birth. At postnatal day 1, a subset of FEN-SA pups was treated with BUP for 5 consecutive days (1 mg/kg, sc). Video recording was performed daily to quantify somatic signs of withdrawal, including body curls, head movements, and spasms. FEN-SA increased withdrawal at postnatal days 1-3. This effect was attenuated in FEN-SA offspring treated with BUP (p<0.05).14-week-old male offspring were implanted with radiotelemetry (n=4 per group). Compared to VEH-SA, FEN-SA offspring showed: 1) increased BP in response to phenylephrine (PE, 40 µg/kg ip), 2) tachycardic response to 1-hour restraint stress followed by impaired BP recovery (p<0.05, respectively), 3) similar acute responses to AngII (30 µg/kg, sc), 4) exacerbated BP and delayed heart rate recovery in response to acute FEN (20 µg/kg, sc, p<0.05), although plasma clearance was similar between groups. BUP treatment in FEN-SA offspring did not influence acute changes in BP or heart rate to different hypertensive stimuli. Taken together our data suggests that an opioid-based therapy effectively reduced somatic signs of withdrawal; however, it does not seem effective in attenuating the acute and chronic BP responses in prenatal fentanyl-exposed offspring.
Abstract MP28: Advanced Lipid Status Parameters in Women With Preeclampsia
Authors: Gojkovic Tamara , Ardalic Daniela , Antonic Tamara , Banjac Gorica , Zeljkovic Aleksandra , Vekic Jelena , Miljkovic Trailovic Milica , Munjas Jelena , Jovicic Snezana , Saric Matutinovic Marija , Ivanisevic Jasmina , Vladimirov Sandra , Spasojevic Kalimanovska Vesna , Mikovic Zeljko , Stefanovic Aleksandra
Published: October 2024

Preeclampsia (PE) is a hypertensive disorder associated with pregnancy, usually occurring after the 20th week of gestation, followed by proteinuria or signs of end-organ dysfunction. Early-onset preeclampsia is associated with placental dysfunction, while late-onset preeclampsia is recognized as a maternal disorder, influenced by risk factors like maternal obesity, diabetes mellitus, or chronic hypertension. During physiological pregnancy, lipid metabolism changes to adequately supply the fetoplacental unit with nutrients and energy, consequently changing the composition of LDL and HDL particles. However, in preeclampsia, these changes become atherogenic. The study aimed to examine changes in advanced lipid status parameter concentrations and the dominant diameter of LDL and HDL particles during pregnancies affected by PE. In this study, 92 pregnant women at high risk for complication development were followed longitudinally throughout the first (T1), second (T2), and third (T3) trimesters. They were classified into high-risk (HR) (72 women) and PE (20 women) groups based on pregnancy outcomes. Total cholesterol (TC), HDL-C, triglycerides (TG), apoAI, and apoB concentrations were measured using commercial kits, while LDL-C concentrations and the atherogenic index of plasma (AIP) were calculated using established equations. Dominant LDL and HDL particle sizes were determined by gradient gel electrophoresis. TG levels were significantly higher in the PE group compared to the HR group across all trimesters (p<0.05; p<0.05; p<0.01), while AIP was significantly elevated in T2 (p<0.01) and T3 (p<0.01). HDL-C levels were lower in the PE group than in the HR group in T2 (p<0.05). In the HR group during pregnancy, concentrations of TC, TG, LDL-C, apoB, as well as HDL-C increased significantly (p<0.05 for all parameters), while the dominant LDL diameter decreased markedly (p<0.001) between all trimesters, without changes in the dominant HDL diameter. There were no changes in HDL-C concentration during pregnancy in the PE group. In contrast, TG concentrations increased significantly (p<0.01), accompanied by a significant decrease in dominant LDL particle diameter (p<0.05). In conclusion, pregnant women with PE exhibit atherogenic changes in lipid status parameters, including no increase in HDL-C concentration, potentially leading to a loss of HDL's protective effect.
Abstract MP30: The Role of CD20+ B cells in Mediating Hypertension in Preeclampsia during Pregnancy
Authors: Campbell Nathan , Hankins Miriam , Zheng Baoying , Demesa Alexandra , Turner Ty , Deer Evangeline , Amaral Lorena , Morris Rachael , Lamarca Babbette
Published: October 2024

Pre-eclampsia (PE), new-onset hypertension after the 20
th
week of pregnancy alongside other organ dysfunction, endothelial dysfunction, and immune activation. We have previously shown that CD19+ B cell adoptive transfer causes a PE phenotype in athymic nude rats. CD19 is present on all B cells including plasma cells. CD20 is absent from plasma cells but is present on mature B2 and memory B cells. The objective of this study was to determine if CD20+ B cells, excluding plasma cells, cause maternal hypertension, fetal growth restriction, and endothelial dysfunction.

Three hundred thousand placental CD20+ B Cells from normal pregnant (NP) or PE patients were isolated by magnetic separation and injected i.p. into nude athymic rats on gestational day (GD) 12. On GD18, carotid catheters were inserted. On GD19, mean arterial pressure (MAP) was measured and blood and tissues were collected. Preproendothelin (PPET) expression was quantified in kidney and placental tissues using RT-PCR. A student’s t-test was used for statistical analysis.

Participants whose placental B cells were used in this study had similar age, pre-pregnancy BMI, and diastolic BP on admission. PE participants had elevated systolic BP at admission (135±4 vs 120±4 mmHg) and delivery (139±6 vs 124±3 mmHg) as well as diastolic BP at delivery (79±4 vs 68±2 mmHg). PE participants also had trending decreases in fetal weight (2621±323 vs 3202±102 g) and gestational age (36±1 vs 39±0 weeks) at delivery.

MAP increased from 107±4 mmHg (n=8) in the NP recipient rats to 123±2 mmHg (n=8, p<0.01) in the PE recipient rats. Pup and placental weights were unchanged following adoptive transfer. Renal PPET expression increased by 2.595±0.61 fold (ΔΔct) in PE recipient rats (n=7, p<0.05) compared to NP recipient rats (n=7). Placental PPET expression was unchanged following adoptive transfer.

CD20+ B cells from women with PE contribute to hypertension and endothelial dysfunction during pregnancy. This data supports the important role of B cells in the development of PE and improves our understanding of the population of B cells responsible for contribution to the disease.
Abstract MP31: The effect of dual SGLT1/2 inhibition on the progression of salt-sensitive hypertension
Authors: Kravtsova Olha , Levchenko Vladislav , Bohovyk Ruslan , Staruschenko Alexander
Published: October 2024

The dual inhibition of sodium-glucose co-transporter 1 and 2 (SGLT1/SGLT2) presents a novel therapeutic approach to cardiovascular diseases. The FDA recently approved the dual SGLT1/2 inhibitor sotagliflozin (Sota) for treating heart failure regardless of ejection fraction. However, our understanding of the effects and mechanisms of SGLT2 and dual SGLT1/2 inhibitors in salt-sensitive hypertension (SS HTN) remains limited. Thus, additional studies are needed to reveal the role and mechanism(s) of SGLTi in SS hypertension. In our previous studies, we demonstrated the beneficial effect of SGLT2i dapagliflozin (Dapa) on SS HTN in male and female Dahl SS rats on blood pressure (MAP after 3 weeks on high salt diet were: Dapa vs. vehicle: 136 ± 3 vs. 156 ± 6 mmHg in males and 140 ± 5 vs. 160±9 mmHg in females). This study aims to define the effects and potential mechanisms of dual SGLT1/2 inhibition in managing SS HTN. Dual SGLT1/2 inhibition with Sota (30 mg/kg/day) prevented the development of SS HTN in Dahl SS in both sexes without changes in heart rate. By the 21
st
day of the high-salt challenge, MAP was lower more than 30 mmHg in treated groups (Sota vs. vehicle: male rats 126 ± 2 vs 157 ± 5 mmHg (N=7, p=0.0002); female rats 126 ± 3 vs 167 ± 10 mmHg (N=6, p=0.0095). Under Sota treatment, rats had significantly increased diuresis (Sota vs. vehicle: males 69 ± 3 vs 35 ± 2 ml and females 48 ± 5 vs 31 ± 2 ml on day 21), glucose and sodium excretion. In both sexes, Sota treatment resulted in a lower heart-to-body weight ratio, and kidney weight was not changed. Also, Sota attenuated kidney fibrosis and protein cast formation (Sota vs. vehicle: cortex fibrosis in males 2.3 ± 0.4 vs 4.6 ± 0.5 % and females 2.0 ± 0.2 vs 4.0 ± 0.7 %, outer medullary protein casts in males 2.5 ± 0.2 vs 16.0 ± 2.6 % and 1.9 ± 0.3 vs 7.5 ± 0.9 % in females) without changes in albuminuria in both sexes. However, no changes in glomerular filtration rate or creatine clearance were detected. Based on our data, it can be inferred that dual SGLT1/2 inhibition prevents the development of SS HTN and kidney damage. Potential mechanisms underlying those beneficial effects of SGLT1/2 inhibition will be further explored.
Abstract P108: Correlations of attended and unattended office blood pressure measurements with Left Ventricular Mass in untreated hypertensives.
Authors: IYEKU Akinwale , Jalaludeen Navazh , Mukhtar Omar , McEniery Carmel , Ojji Dike , Cheriyan Joseph , Wilkinson Ian
Published: October 2024

Introduction:
Unattended (UA) office blood pressure (BP) measurements have been proposed as better substitutes for attended (AT) BP readings for the diagnosis and monitoring of patients with hypertension (HTN). A superior correlation of UA over AT BP measurements with Left Ventricular Hypertrophy (LVH), an early marker of hypertensive organ damage has not been conclusively demonstrated. We hypothesized that in a group with untreated HTN, UA BP would correlate more strongly with left ventricular hypertrophy than AT BP.

Methods:
Newly diagnosed untreated patients with HTN presenting newly to an outpatient clinic in Nigeria were consented as part of a larger study. Three sets of AT and UA seated BP readings were carried out using a validated device followed by same-day echocardiographic assessment of their Left Ventricular Mass Indexed to Body surface area (LVMI). Pearson’s coefficient (r) was determined and a 2-tailed significance was defined by a two-tailed P value (P) less than 0.05. Coefficients were compared using Fisher r to z transformation.

Results:
A total of 49 participants (female=25) were recruited with a mean age of 46.2 +/- 9 years. The mean of the AT BP in the cohort (mAT) was 157.1 +/- 13.5mmHg, while the mean of the UA BP was 151.9 +/- 15.7 with no significant difference in both (P=0.085). The mean LVMI of the cohort was 102.3 +/- 28.7 mg/m2. Both the mAT BP (r= 0.304, P= 0.034) and the mUA BP (r=0.354, P=0.013) positively correlated with LVMI, with no significant difference in the strength of both correlations with r to z transformation (z=0.27, P=0.394 ).

Conclusion:
In a small cohort of newly diagnosed Nigerian hypertensives, both attended and unattended systolic office blood pressure readings correlated positively with left ventricular mass indexed to body surface area, with no significant difference in the strength of their correlation. Having failed to demonstrate a superior correlation of unattended blood pressure readings with LVH, our findings support the continued use of attended office blood pressure readings for clinical monitoring in busy time-constrained office settings where unattended office blood pressure monitoring may not be feasible. Larger studies are however required to confirm these findings.