bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P326: Measuring Health Equity Gaps for a Blood Pressure Control Quality Improvement Program: Results from Cook County Health
Authors: Zasadzinski Lindsay , Khan Tamkeen , Sutherland Susan , Barrett Robert , Love Kesha , Irons Sharon , Tinfang Chantal , Wozniak Gregory
Published: October 2024

Background:
High blood pressure (BP) affects nearly half of U.S. adult population and was responsible for 13.0 deaths per 100,000 in 2022, with significant differences in age-adjusted mortality rates by sex, race, and ethnicity. Previous research has also highlighted that lower BP control rates are more prominent in Hispanic and Non-Hispanic Black patients, and well as those 60 years or older. This study assesses the role of the AMA MAP™ Hypertension quality improvement (QI) program to improve potential inequities in blood pressure control at a large public health care institution.

Methods:
18,252 patients diagnosed with hypertension were identified at Cook County Health. BP values were obtained for patients in the 2 -years prior to implementation of the QI program (July 2019 to June 2021) compared to BP in the 2-years after implementation (July 2021 to July 2023). A multivariable logistic regression model of BP control status, paired t-tests, and ANCOVA analyses, stratified by race, ethnicity, sex, and age are conducted to assess SBP and measure the gaps by demographic characteristics.

Results:
Prior to the QI program, BP control (<140/<90) was significantly less for Black as compared to White patients (OR 0.82 [0.74-0.92]). The racial difference remained after the program, although it was slightly diminished (OR 0.86 [0.76 – 0.97]). Patients who were older were less likely to have controlled BP prior to the program, but these differences were no longer evident following the QI program. The QI program led to a decline in SBP in all demographic groups, including between ethnicity as shown in Figure 1 (Hispanic: -5.74 [CI:6.19- -5.29] vs Non-Hispanic -4.92 [-5.21- -4.63]), White (-5.96 [CI: -6.45- -5.47]) and Black (-4.80 [CI: -5.11- -4.49]) patients, and by age as shown in Figure 2 between 45-64 years ( -5.79 [CI: -6.12- -5.46] and 65-85 years (-4.31 [CI: -4.68- -3.94]).

Conclusion:
The results indicate an overall improvement in BP control and SBP, however, gaps persisted in SBP across ethnicity, race, and certain age groups. Quality improvement coaching and dashboards may support clinical care teams in addressing inequities in patient BP control.
Abstract P331: Simple Instruction and Provision of Literature on Low Salt Diet Ineffective in Reducing Salt Intake in Patients with Hypertension
Authors: Umanath Kausik , Sohaney Ryann , Atchison Douglas , ABRAHAM EMMY , She Ruicong , Adrianto Indra , Levin Albert , Soman Sandeep , Ortiz Pablo
Published: October 2024

Objective:
Hypertension remains poorly controlled at the population level. Reduction of salt intake via the DASH diet is effective in reducing blood pressure (BP). We enrolled a cohort of patients with hypertension to assess molecular factors that influence BP control over a follow up period of 6 months. Here we report dietary sodium intake and BP control.

Methods:
80 non-diabetic patients aged >40 with hypertension were enrolled in the study. Subjects reccieved brief instruction and a handout on the DASH diet from a study coordinator. Medications were titrated to a BP of <130/80 at enrollment, months 1, 2,3 and 6. BP was measured at each visit using an automated cuff following clinical trial methodology. 24-hour urine sodium excretion was collected at enrollment, months 3 and 6. Descriptive variables were summarized and paired t-tests were used to compare sodium excretion and BP.

Results:
Cohort characteristics are in Table 1. 73 subjects provided 24-hour urine samples and BP at enrollment and month 3 while 67 had samples at enrollment and month 6. Mean BP at enrollment was 129.9/75.3 (SD 16.6/12.5) which reduced 123/71.8 (SD 12.9/10) at month 3, p <0.001and 125.4/73.4 (SD 15.2/10.5), p=0.02. 24-hour sodium excretion was 152 mmol (SD 73.6) at enrollment. There was no difference in sodium excretion at 3- (154 mmol, SD 86.2, p=0.8) or 6 months (139 mmol, SD 60,, p=0.18).

Conclusions:
According to 24-hour urine collection, participants consumed roughly 3.5 g of sodium per day. Simple instruction and provision of literature regarding a DASH diet was ineffective in reducing sodium intake. Further study is required to determine a more effective educational delivery method and understand any social factors that may inhibit diet implementation in this urban hypertensive cohort.
Abstract P333: Predicted Nationwide Health and Economic Impacts of the AMA MAP
TM
Hypertension Program to Improve Hypertension Control
Authors: Wozniak Gregory , Dehmer Steven , Egan Brent , Hardy Blaine , Maciosek Michael , Sutherland Susan , Tsipas Stavros
Published: October 2024

Introduction:
Lack of actionable blood pressure (BP) measurements, therapeutic inertia, and suboptimal patient self-management are three key barriers to better BP control. To help address these barriers, the American Medical Association developed the Measure Accurately, Act Rapidly, and Partner with Patients Hypertension (MAP
TM
HTN) quality improvement program.

Methods:
To estimate the 10-year health and economic outcomes achieved when healthcare delivery systems adopt MAP HTN, HealthPartners Institute's ModelHealth™: Cardiovascular disease (CVD) microsimulation model was applied to conduct “what if” analyses for adopting MAP HTN nationwide and in care delivery systems of varying size. MAP HTN targets patients aged 18 to 85 years with diagnosed hypertension. To account for newly diagnosed hypertensive patients over time and outcomes that follow exposure to the program after age 85, the simulation model predicted outcomes for a dynamic cross-section of U.S. adults aged 18 to 100 years. This study was conducted from the health care sector perspective, including that of the payers for medical services and the health care delivery system that provides these services.

Risk equations to predict the incidence of CVD events were derived from Framingham Heart Study data and are based upon the following risk factors: age, sex, body mass index, systolic BP (SBP), lipid levels, smoking status, diabetes status, and CVD history. Modeled outcomes over 10 years included prevalence of SBP ≥140 mmHg; incidence of cardiovascular disease (CVD) events and CVD-related mortality; averted medical costs in 2021 U.S. dollars; and net costs.

Results:
Nationwide adoption of MAP HTN was predicted to improve mean BP control by 4.3% and prevent 601000 CVD events, with 85000 fewer myocardial infarctions, 164000 fewer strokes and 120000 fewer CVD deaths over 10 years as compared to usual care. The majority (93%) of the estimated $17.9 billion in averted costs were among Medicare beneficiaries. Total costs of implementing MAP HTN was $12.6 billion, resulting in a predicted $5.3 billion in net savings to the health care sector over 10 years. Small and large care delivery organizations could economically benefit from implementing MAP HTN at varying levels (5-50%) of shared cost savings from payers.

Conclusions:
The model demonstrates that AMA’s MAP HTN has the potential to improve population health and provide a positive business case by averting future myocardial infarctions, strokes, and CVD deaths.
Abstract P335: An innate immune component in hypertension-induced cardiac dysfunction Christoph Mora, Katherine Deck, Yunmeng Liu, Lance Benson, Tonya Rafferty, & Shengyu Mu
Authors: Mora Christoph , Deck Katherine , Liu Yunmeng , Mu Shengyu , Benson Lance , Guo Yunping
Published: October 2024

Hypertension affects nearly half of American adults, inevitably leading to cardiac dysfunction and heart failure. Cardiac fibrosis is a major factor contributing to cardiac dysfunction during hypertension progression. However, the mechanisms involved in cardio-fibrogenesis remain to be elucidated. In the past decade, studies revealed that macrophages could differentiate into professional fibrotic cells, myofibroblasts, through a process termed macrophage to myofibroblast transition (MMT), helping maintain the integrity of major organs, such as the kidney. However, it is unknown whether MMT contributes to fibrotic remodeling in hypertensive hearts. Here, we aim to identify this phenomenon in the hearts of hypertensive animals and determine the role it plays in the pathological progression from hypertension to cardiac diastolic dysfunction.

In this study we adopt the classic DOCA + Salt model of hypertension and utilized cardiac ultrasound and direct left ventricular (LV) pressure catheterization to gauge diastolic function. Heart sections from hypertensive and sham mice were stained with Masson’s trichrome to assess the extent of cardiac fibrosis. Furthermore, flow cytometry was utilized to identify MMT cells, which express both CD68 (monocytes) and α-SMA (myofibroblast) markers. These methods gave insight into the role that MMT plays in the degradation of heart function during hypertension.

Direct left ventricle pressure catheter revealed that DOCA + salt mice exhibited impaired diastolic function. This result is supported by cardiac ultrasound showing that the compliance of the heart had significantly decreased, as evidenced by the lowering of the efferent/atrial (E/A) ratio and deceleration time (DcT). In addition to this evidence of mechanical cardiac degradation, leukocytes isolated from the heart and stained with macrophage and myofibroblast markers revealed a significant increase in CD68+ & αSMA+ cells—a result reflected by increased fibrotic remodeling via Masson’s trichrome stain, in the hypertensive animals.

This study demonstrated an onset of diastolic dysfunction in the heart of DOCA + salt hypertensive mice. Moreover, we found a positive association between MMT cells and fibrosis in the hearts of hypertensive animals. Future studies will aim to parse out both the gravity of MMT in hypertensive heart dysfunction and the mechanism by which macrophages undergo this transition to find new targets against this debilitating disease.
Abstract P343: Cerebral injury and cognitive performances are correlated with immunoinflammatory markers in hypertensive patients
Authors: Carnevale Lorenzo , maffei angelo , Carnevale Daniela , Lembo Giuseppe
Published: October 2024

Immunity and inflammation play a pivotal role in hypertension onset and cardiovascular organ damage. This role has been thoroughly characterized for classical hypertension targets as the kidneys, the heart and the vasculature. Many studies have characterized this in the experimental context, however immunoinflammatory challenges links with brain injury in the clinical context of hypertension are still lacking. In this study we will characterize how immunoinflammatory mediators can be predictors of cerebral injury characterized by advanced neuroimaging in hypertensive patients.

Hypertensive patients underwent cerebral MRI and by advanced neuroimaging we characterized the microstructural injury by DTI fiber tracking. We administered the Montreal Cognitive Assessment to evaluate cognitive function, measured circulating C-reactive protein (hs-CRP) and counted circulating white blood cells (WBC).

We found a large cluster of white matter tracts whose integrity parameters were associated with immunoinflammatory biomarkers (Figure A). In particular, a cluster of tracts of the limbic system and encompassing the corpus callosum show a correlation between their loss of integrity and hs-CRP levels. Another cluster of associative tracts spanning the temporal lobe show association between their loss of integrity and the WBC. Finally, the Frontal Aslant and the Uncinate Fasciculus show association with both immunoinflammatory markers (Figure B).

In this study we performed advanced neuroimaging analyses to characterize the interplay between immunoinflammatory risk and cerebral alterations in hypertensives. Furthermore, our previous work identified that white matter damage in the Forceps Minor and Superior Longitudinal Fasciculus was a typical trait of hypertensive patients and associated to loss of cognitive functions. Our data further show the inflammatory risk association with worse cognitive functions, suggesting a clinical relevance in terms of damage evidenced by advanced MRI in hypertensive patients.
Abstract P344: APOe Genotype Modifies the Association Between Long-Term Blood Pressure Variability and Cognitive Decline/Dementia in Older Adults
Authors: Ernst Michael , Webb Katherine , Sheets Kerry , Woods Robyn , Fravel Michelle , Beilin Lawrence , Espinoza Sara , Orchard Suzanne , owen alice , Wolfe Rory , Murray Anne , Shah Raj , Polkinghorne Kevan , Reid Christopher , Lacaze Paul , Ryan Joanne
Published: October 2024

We previously reported an increased risk of cognitive decline and dementia with high visit-to-visit long-term blood pressure variability (BPV) in the ASPREE randomized trial of low-dose aspirin, conducted in 19,114 community-dwelling older adults in Australia and the USA who were initially free of significant cognitive impairment and diagnosed dementia at enrollment. Upon completion of the randomized trial phase, ASPREE participants were invited into the ASPREE-eXTension (ASPREE-XT) observational study. In this analysis, we re-examined the risks of cognitive decline and dementia using extended follow-up from ASPREE-XT, and including recently available APOe genotype as an additional covariate. Long-term BPV was estimated in each participant using standard deviation (SD) of the means of three within-visit systolic BPs obtained with a validated automated oscillometric BP monitor from the baseline and first two annual ASPREE visits. During ASPREE and continued into ASPREE-XT, participants underwent annual/biennial standardized cognitive testing (4-test battery). Incident cognitive decline was defined as >1.5 SD decline from baseline score on any cognitive test; incident dementia was a pre-specified secondary endpoint of ASPREE/ASPREE-XT and adjudicated by expert panel using DSM-IV criteria and clinical records. Participants reaching cognitive decline or dementia endpoints during the BPV estimation period were excluded from the analysis. Multivariable Cox proportional hazards regression showed the highest SD tertile of BPV, compared to the lowest SD tertile, remained associated with highest risk of cognitive decline (HR=1.16, 95% CI=1.04-1.30) and dementia (HR=1.27 (95% CI=1.02-1.59) in men, and cognitive decline (HR=1.12, 95% CI=1.01-1.24) in women (see accompanying Table), over a median follow-up of 5.8 years (for cognitive decline) and 6.5 years (for dementia). When APOe genotype was included as an additional covariate in an available subset of the cohort (81%), the presence of APOe4 allele partially attenuated the associations in both sexes, although cognitive decline remained significant in men. Our findings suggest the relationship between high long-term BPV and cognitive decline and dementia is stronger in men than women, but also modified by underlying APOe genotype.
Abstract P347: Association between Blood Pressure, Left Ventricular Structure and Cognitive Function: Evidence from a Cohort Study in Preschool-aged Children
Authors: Wang Jian , Sun Kun
Published: October 2024

Objective:
Serving as a common hypertensive target organ damage, left ventricular (LV) structure alteration has been found to be associated with cognition decline in the elderly. However, its mediating role in the association between decreased cognitive function and elevated blood pressure (BP) remains controversial, owing to several inherent confounder in adults that could distort observed associations. The study was first known conducted to examine the association between LV structure, BP and cognitive function in preschool-aged children, a population without disturbance of various cardiovascular risk factors.

Methods:
This study included 1279 children from Shanghai Birth Cohort (SBC) during 2018 to 2021. Using the Wechsler Preschool and Primary Scales of Intelligence-Fourth Edition (WPPSI-IV), children’s intelligence quotient (IQ) was evaluated at 4-year-old. Detailed anthropometrics and BP measurements and echocardiography were conducted during follow-up. Multivariable linear regression models and restricted cubic spline were applied to estimate the association between individual BP, LV structure parameters and IQ scores.

Results:
There was no significant association found between cognitive function and LV structure in preschool-aged children, while higher BP levels was found to be correlated with lower scores in cognitive function. Children in the elevated BP and non-LVH group tended to have lower full-scale IQ (FSIQ). In detail, children with elevated BP tended to have lower scores in FSIQ (β: -2.95, 95%CI: -4.65, -1.25), processing speed index (β: -1.77, 95%CI: -3.41, -0.14), working memory index (β: -2.79, 95%CI: -4.70, -0.88) and visual spatial index (β: -2.64, 95%CI: -4.74, -0.55), and these associations were independent of LV structure.

Conclusion:
Higher BP levels was related to poor cognitive development during childhood as early as four, while LV structure alteration was not. The associations between BP and children’s decreased cognitive function was independent of LV structure.
Abstract P348: Effects of Different Antihypertensive Regimens on Cognitive Function and Blood Pressure Changes in Elderly Hypertensive Patients: Network Meta-Analysis
Authors: Yan Jiao , Gao Ying
Published: October 2024

Background:
Elderly hypertensive patients with cognitive impairment not only exhibit reduced processing speed and executive function but also suffer significant deficits in memory and motor speed, adversely affecting their quality of life. This study employs a network meta-analysis to evaluate the effects of different antihypertensive regimens on cognitive function and blood pressure changes in elderly hypertensive patients.

Methods:
A comprehensive search was conducted in PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang and VIP databases for randomized controlled trials on different antihypertensive regimens for elderly hypertensive patients. Data analysis and graphing were performed using Review Manager 5.3 and Stata 16.0 software.

Results:
A total of 16 studies involving 11,694 elderly hypertensive patients and six antihypertensive regimens were included. The network meta-analysis results indicated that elderly hypertensive patients treated with angiotensin II receptor blockers (ARBs) had a greater change in cognitive function scores compared to those receiving usual care (standardized mean difference [SMD] = 0.46, 95% CI [0.23, 0.70]), angiotensin-converting enzyme inhibitors (ACEIs) (SMD = 0.33, 95% CI [0.06, 0.61]), beta-blockers (BBs) (SMD = 0.48, 95% CI [0.17, 0.78]), and diuretics (SMD = 0.32, 95% CI [0.01, 0.63]). Similarly, patients treated with calcium channel blockers (CCBs) showed greater changes in cognitive function scores compared to those receiving usual care (SMD = 0.37, 95% CI [0.04, 0.70]) and BBs (SMD = 0.38, 95% CI [0.02, 0.74]). The SUCRA rankings for changes in cognitive function scores among different antihypertensive regimens were ARB (93.6%), CCB (81.2%), diuretics (47.1%), ACEI (43.4%), usual care (17.9%), and BB (16.8%).

Conclusion:
The current evidence suggests that, compared to usual care, ACEIs, BBs, CCBs, and diuretics, ARBs might be the optimal regimen for improving cognitive function in elderly hypertensive patients.
Abstract P356: Sex-dependent Response of ATP-mediated Calcium in Renal Microvascular Smooth Muscle Cells in Ischemia-reperfusion Rats
Authors: Guan Zhengrong , Jones Clifford , Meera Samia , Zhang Shali , Inscho Edward , Feng Wenguang
Published: October 2024

Renal autoregulation is intrinsic to preglomerular microvascular smooth muscle cells (MVSMC) for maintaining stable renal blood flow and glomerular filtration rate during arterial pressure fluctuations. Our recent study suggests that renal ischemia-reperfusion (IR) leads to sex-dependent autoregulatory impairment of afferent arterioles. Renal autoregulation is linked to ATP sensitive-Ca
2+
signaling in MVSMC via activation of P2X purinoceptors (P2X). ATP vasoconstricts afferent arterioles by increasing intracellular calcium concentration ([Ca
2+
]
i
) in male rat MVSMC but female rats have not been studied. We postulate that female MVSMC exhibit highly sensitive ATP-mediated Ca
2+
responses which may protect females against IR. Blood-perfused juxtamedullary nephron experiments were performed on kidneys of Sprague-Dawley rats 24 hours after IR (60-min, bilateral renal artery clamping). ATP-induced changes in [Ca
2+
]
i
were assessed in freshly isolated MVSMC using Fura-2. Superfusion of ATP (10
-8
–10
-4
M) elicited concentration-dependent vasoconstriction in sham rats of both sexes. The maximal vasoconstriction was 68±2% of the control diameters at 10
-4
mol/L in males and 72±9% in females (n=3/group). In contrast, ATP-induced vasoconstriction was nearly abolished in both sexes 24 h post-IR. The maximal vasoconstriction only reached 91±6% and 97±3% of control diameter in male and female IR rats (n=3/group,
P
<0.05 vs. shams), respectively, indicating impaired P2X signaling in afferent arterioles post-IR. ATP exposure increased [Ca
2+
]
i
in control MVSMC of both sexes by 0.03±0.00 and 0.10±0.01 in males and 0.19±0.02 and 0.43±0.05 in females at 10
-5
and 10
-4
M ATP, respectively. The ATP-induced increase in [Ca
2+
]
i
was 4-7 fold higher in female than in male controls, suggesting that MVSMC from normal female rats exhibit a highly sensitive response to ATP stimulation versus male’s. IR suppressed ATP-induced calcium responses in MVSMC of both sexes. [Ca
2+
]
i
increased by 0.02±0.00 and 0.04±0.01 in IR males and 0.09±0.01 and 0.09±0.01 in IR females in response to 10
-5
and 10
-4
M ATP, respectively
(P
<0.05 vs control, n=60-150 cells/3-4 rats/group). Female IR MVSMC however, still possess higher reactivity to ATP than MVSMC from male shams. In conclusion, our studies suggest that MVSMC of male and female rats handle ATP-Ca
2+
signaling differently and the stronger ATP-mediated [Ca
2+
]
i
response in female MVSMC may protect females against IR-induced kidney injury.
Abstract P366: Co-Created Intervention Promotes Uptake of Low Sodium Iodized Salt Substitute to Control Hypertension: Results from a Large Community-based Quasi-Experimental Study from India
Authors: Srinivasapura Venkateshmurthy Nikhil , Dubey Manisha , Sehgal Reena , Jarhyan Prashant , Khatkar Rajesh , Konkati Shiva Prasad , Sharma Manika , Ide Nicole , Prabhakaran Dorairaj , Mohan Sailesh
Published: October 2024

Introduction:
India has a high burden of uncontrolled hypertension (28%) with low control rates (<10%). Mean dietary sodium intake (4000mg/d) is also high, which warrants implementation of population-level sodium reduction interventions, such as using low-sodium iodized salt (LSIS). Given the low awareness about LSIS, we co-created and evaluated an intervention to promote its usage.

Objective:
To estimate change from baseline to end line in proportion of households reporting LSIS use post implementation of a co-created (involving multiple stakeholders) intervention to provide education (education only arm) on LSIS and education along with subsidy to purchase LSIS (education+subsidy arm).

Methods:
The study was implemented (8 months intervention) in rural and urban sites of north and south India. In the education only arm, trained health workers provided education on LSIS to community members using pamphlets, a short video and encouraged retailers to sell LSIS to consumers by displaying point of sale posters. In the education+subsidy arm, apart from aforementioned activities, subsidy of $ 0.24/kg (~50% of the price) to purchase LSIS was provided to the distributors, who passed this on to retailers and consumers.

Results:
A total of 1,602 households and 3,108 participants were interviewed. The mean(SD) age of the participants was 46.9(14.2) years. Fifty two percent were females. At baseline, proportion of households reporting ever use of LSIS was 1.3% (95%CI: 0.9–2.1) and 2.3% (1.8–2.7) respectively, in the education and education+subsidy arms. At end line, this proportion increased to 22.6% (21.1–24.1) and 49.3% (47.5-51.2%) respectively. The odds of LSIS ever use was 2.6 (1.2-5.7) times higher in the education+subsidy arm compared to education only arm. The odds of reporting LSIS use was higher if the household had ≥ one patient with hypertension (1.7[1.3-2.3]), with graduate education (1.6[1.3-2.0]) or belonged to richest quintile (1.6[1.3-2.0]). There was no significant change in mean systolic and diastolic blood pressure, urinary sodium, and potassium between the two arms from baseline to end line.

Conclusion:
We demonstrated the possibility of increasing LSIS usage through a co-created intervention providing either education only or education+subsidy to buy LSIS with a substantially higher response for the latter. This underscores the need to make LSIS accessible, available, and affordable for regular use to reduce dietary sodium intake and control hypertension.
Abstract P382: The protective role of elevated oral microbial levels in adult hypertension: NHANES 2009-2012
Authors: Wu Di , Bing Shuang , Qiu Hongbin , Zhang Yiying , Wang Shanjie
Published: October 2024

Background and Objective:
Accumulating evidence has linked periodontal disease with hypertension, yet the relationship between the diversity of oral microbiota and blood pressure remains unclear. Our objective was to investigate the association between characteristics of oral microbiome diversity and hypertension in the general population.

Methods:
The data were extracted from the 2009-2012 National Health and Nutrition Examination Survey (NHANES), where we included participants aged 20 years or older who had indicators of hypertension. Participants with conditions such as pregnancy, periodontal disease, cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), diabetes, and cancer were excluded from the analysis. Oral microbiome α-diversity in adults was analyzed through oral rinse samples, encompassing measures such as observed amplicon sequence variants (ASVs), Faith’s Phylogenetic Diversity, the Shannon-Wiener Index, and the Simpson Index. Differences in oral microbiome α-diversity among various hypertension groups were described using weighted mean values. The association between oral microbiome α-diversity and hypertension was analyzed using multivariable logistic regression models.

Results:
Between 2009 and 2012, among 3,228 participants (weighted mean [SE] age, 36.54 [0.64] years; 1,408 males [weighted 43.62%]), there were 601 cases of hypertension (increasing to 771 when adopting the new diagnostic criteria for hypertension). Significant differences were observed in the levels of oral microbiota α-diversity among different hypertension groups. Multivariate logistic regression analyses revealed an independent association between levels of oral microbiome α-diversity and the risk of hypertension, after controlling for confounding factors. For each one-standard deviation (SD) increase in ASVs and Faith's Phylogenetic Diversity, the adjusted odds ratios (aORs) were 0.85 (95% confidence interval [CI]: 0.75-0.95) and 0.85 (95% CI: 0.75-0.95), respectively. This association persisted across varying diagnostic criteria for hypertension.

Conclusions:
Our findings indicate diverse oral microbiomes among hypertension groups, where greater α-diversity inversely correlates with hypertension risk, independent of diagnostic criteria. This implicates oral microbiota dysbiosis, potentially from environmental factors, as an additional hypertension risk factor, emphasizing the oral microbiome's potential in hypertension development.
Abstract P390: The Adipokine Chemerin Does Not Promote Activation or Cytokine Secretion by T Cells Stimulated With a Strong Polyclonal Activator
Authors: DATTMORE DEVON
Published: October 2024

High fat diet has long been implicated as a risk factor for obesity and other conditions associated with metabolic syndrome, including hypertension. The mechanism by which high fat diet increases risk of hypertension is likely multifactorial, but corresponding low-grade inflammation may play an important role. Low-grade inflammation associated with high fat diet is often accompanied by altered adipokine levels, including an increase in circulating chemerin. However, our understanding of the effects of chemerin and other adipokines on immune cells is limited. Thus, the purpose of these studies was to test the hypothesis that the adipokine chemerin promotes CD4 and CD8 T cell activation and cytokine secretion. To test this hypothesis, primary mouse splenocytes were treated with chemerin or vehicle 30 min prior to activation with a T cell-specific activator (anti-CD3/anti-CD28) for 24 h. T cell activation causes a rapid upregulation of cell surface proteins that are commonly used as experimental markers of activation. We found that chemerin did not impact the induction of the T cell activation markers, CD25, CD69, CD44, CD134, CD137 and CD154, in either CD4 or CD8 T cells. Likewise, we did not see a difference in the downregulation of CD62L, which is rapidly internalized by T cells following activation. Consistent with this, chemerin caused no difference in cytokine secretion by activated T cells. Specifically, the concentrations of IL-2, IL-17A, IFNγ, and TNFα were similar between groups. Overall, this study shows that the adipokine chemerin does not promote acute changes in activation or cytokine expression in primary mouse splenic T cells fully activated with anti-CD3/anti-CD28.
Abstract P396: A Selective Agonist of the Beta 2 Retinoic Acid Receptor Reduces Necrosis, Lipid Peroxidation, and Oxidative Stress in Doxorubicin-induced Cardiotoxicity
Authors: Varzideh Fahimeh , Jankauskas Stanislovas , Kansakar Urna , Tang Xiao-Han , Gudas Lorraine , Levi Roberto , Gambardella Jessica , Santulli Gaetano
Published: October 2024

Objective:
Doxorubicin (Doxo) is used as an antiproliferative agent to treat various cancers. However, a significant limitation of Doxo is cardiotoxicity, that can induce heart failure in patients. Mounting evidence indicates that an increased generation of reactive oxygen species (ROS), lipid peroxidation, and necrosis, are major causes of Doxo-induced heart failure. Recently, we reported that a highly selective and potent agonist of the b2 retinoic acid receptor (RARb2), improved cardiac dysfunction in mice model of myocardial infarction by inhibiting oxidative stress. In this study we investigated cardioprotective effects of RARb2 stimulation on Doxo-induced heart failure.

Methods:
We performed
in vitro
and
in vivo
experiments on an established murine model of Doxo-induced heart failure. Necrosis, oxidative stress, and lipid peroxidation were evaluated, assessing both the prevention and the rescue capacities of RARb2 stimulation.

Results:
An increased ROS production both at the mitochondrial and cellular level was observed in cardiomyocytes isolated from Doxo-treated mice. RARb2 stimulation significantly attenuated Doxo-induced ROS production. In addition, this treatment mitigated lipid peroxidation induced by Doxo in the left ventricle, marked by 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). RARb2 stimulation also mitigated the increased expression of High Mobility Group Box 1 (HMGB1), a necrosis marker, in the heart and in the serum of Doxo-treated mice.

Conclusion:
Our data demonstrate that RARb2 stimulation can attenuate necrosis, lipid peroxidation, and ROS production in a mouse model of Doxo cardiotoxicity.
Abstract P405: Integrating Self-Measured Blood Pressure Device Data Into Electronic Health Records – Barriers And Solutions
Authors: Smith Alison , Fiegel Sondi , Scales Josh , Harmon Gary , Wagner Ashley , Sanchez Eduardo
Published: October 2024

Introduction:
Despite clinical evidence supporting the use of self-measured blood pressure monitoring (SMBP)in improving blood pressure control, the infrastructure to enable data transfer from device to electronic health record (EHR) is complicated by policy, interoperability, and operational challenges. The National Hypertension Control Initiative (NHCI) engaged 350 HRSA-funded federally qualified health centers (FQHCs) to improve blood pressure control leveraging SMBP devices and integrating SMBP data into EHRs.

Hypothesis/Aims:
FQHCs could integrate SMBP device data into their EHR with financial support and training and technical assistance (T/TA).

Methods:
T/TA was provided through a curriculum to support technology infrastructure self-assessment, explore effective integration options, and implement solutions. Additionally, FQHCs were offered 1:1 consultations and EHR-specific guidance documents.

Results:
More than half (52%) of responding FQHCs reported moving through all stages of planning, preparing, piloting, scaling, and evaluating their SMBP program during the 3-year grant, while 30% reached the scaling stage. Ultimately, 27% reported full data integration and 51% reported partial integration of SMBP device data into their EHR, while 4-12% reported no to minimal integration, respectively. Based on the five most used EHRs, numerous integrations were identified with five validated SMBP devices.

Successful integration strategies included upgrading to the latest EHR version, choosing SMBP devices with verified EHR integration, utilizing EHRs with patient portal apps, and engaging with remote patient monitoring (RPM) services for pre-established integrations. Third-party integration engines emerged as complex and expensive solutions. Challenges included costly or time-consuming EHR upgrades, SMBP device purchases without prior SMBP integration assessment, limitations posed by non-cloud based EHRs or EHRs without patient portals, ability to sustain RPM subscription costs, and limited information technology expertise.

Conclusion:
SMBP device data can be integrated into EHRs, but the complexity, costs, and sustainability vary significantly. Several viable integration strategies with common EHRs and validated SMBP devices were verified. As the technology landscape evolves rapidly, the underlying need for education, strategic technology planning, and vendor collaboration remains.
Abstract P406: Transforming Clinical Practices for Blood Pressure Management in Community Health Centers through Timely Data and Technical Support
Authors: Wagner Ashley , Harmon Gary , Harrison Nekeisha , Mills Andrew , Pillai Jan , Sanchez Eduardo
Published: October 2024

Introduction:
Blood pressure (BP) control can prevent major adverse cardiac events and is monitored through various means, including the Centers for Medicare and Medicaid Services 165 metric for BP control - an annual reporting metric for community health centers (CHCs) within the Uniform Data System framework that becomes accessible 6 months after the conclusion of the reporting period. In pursuit of more immediate indicators related to BP management, the National Hypertension Control Initiative (NHCI) initiated collaboration with a population health platform to support select CHCs with rapidly available data on 19 BP-related metrics.

Hypothesis:
With technical support and regular access to data, CHCs can implement timely clinical practice and process changes.

Methods:
To support CHCs in using the population health platform, NHCI staff provided technical assistance in a rapid cycle performance improvement (RCPI) to 10 interested CHCs. This opportunity allowed CHCs to partner with NHCI staff to review BP related metrics in the population health platform and to identify opportunities for clinical process and practice changes.

Over an 8-week period from October to December 2023, 7 CHCs were actively involved in a series of 5-6 structured 30–60-minute meetings with both NHCI registered nurse and quality improvement staff. These meetings reviewed BP metrics, mapped clinical workflows for improvement, and supported data analytics. CHCs often chose 1-2 BP metrics for focus, concentrating on incremental change and short-term improvement.

Results:
Among participating CHCs that reported, they revealed successful or anticipated adjustments in team responsibilities and clinical processes, including leadership involvement and new methods. Limitations included CHC staff engagement, time, concerns with data reliability, and familiarity with the population health platform. Most reporting CHCs shared that their goals were greatly impacted by access to readily available performance data and that they plan to continue using the population health platform to affect performance moving forward.

Conclusions:
For participating CHCs, individualized guidance based on timely data may have been helpful in analyzing workflows and procedures, assessing clinical care practices, and implementing quality improvement plans. Frequent data may allow CHCs to make clinical practice and process changes to efficiently measure impact and more quickly improve BP control than standard methods.
Abstract P424: Podocyte Cell-Specific Guanylyl Cyclase/Natriuretic Peptide Receptor-A is Required for Blood Pressure and Renal Hemodynamics in Sex-Specific Manner
Authors: Ramasamy Chandramohan , Neelamegam Kandasamy , Ramachandran Samivel , Pandey Kailash
Published: October 2024

The cardiac hormones atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) that increases intracellular production of cGMP and stimulates natriuresis, diuresis, and vasorelaxant activities, thereby, reduces blood pressure (BP) and fluid volume. The role of ANP/NPRA signaling in podocytes, highly specialized epithelial cells covering the outer surfaces of renal glomerular capillaries, remains unclear. The objective of this study was to determine the effect of conditional deletion of podocyte (PD)-specific
Npr1
(encoding GC-A/NPRA) in gene-knockout (KO) male and female mice in a sex-dependent manner. Tamoxifen-treated wild-type control (PD
Npr1
f/f; WT), heterozygous (PD-Cre-
Npr1
f/+; HT), and gene-knockout (PD-Cre-
Npr1
f/-; KO) mice were fed a normal-, low-, or high-salt diet for 4 weeks. Podocytes isolated from HT and KO male and female mice showed complete absence of
Npr1
mRNA and NPRA protein compared to WT mice. On a normal-salt diet the mean arterial pressure (MAP) and heart rate (HT) were significantly greater in both male and female PD-
Npr1
KO mice compared with WT mice as measured by radiotelemetry method. On a high-salt diet, the systolic blood pressure (SBP) was significantly higher (p<0.01; p<0.001) in the PD-
Npr1
HT mice (male:108.8 ± 1.10; female: 97 ± 0.80) and KO mice (male:114.60 ± 1; female: 100.10 ± 1.10) compared with WT mice (male: 100.60 ± 0.80; female: 93.30 ± 0.80) at 4 weeks. On normal-, low-, and high-salt diets, plasma creatinine, and urinary protein were significantly increased (p<0.05; p<0.01; p<0.001), while plasma total protein and albumin were significantly reduced (p<0.05; p<0.01; p<0.001) in the
Npr1
HT and KO male and female mice compared to WT mice. These changes were significantly greater in males than females. On a normal-salt diet, the glomerular filtration rate (GFR) was significantly (p<0.05; p<0.01; p<0.001) decreased in PD
Npr1
HT mice (male: 0.67 ± 0.06; female: 0.81 ± 0.09) and KO mice (male:0.46 ± 0.04; female: 0.69 ± 0.05) compared with WT mice (male:1.1 ± 0.07; female: 1.2 ± 0.1). These observations suggest that in podocyte, ANP/NPRA/cGMP signaling may be crucial in the maintenance and regulation of GFR and hypertension and point as a biomarker of BP and renal hemodynamics in a sex-dependent manner.
Abstract P429: Stronger Association of Angiotensinogen with Mortality than Renin or Lactate in Critical Illness
Authors: Chappell Mark , Schaich Christopher , Busse Laurence , McCurdy Michael , Hinson Jeremiah , Sevransky Jonathan , Rothman Richard , Wright David , Martin Gregory Scott , Khanna Ashish
Published: October 2024

Introduction:
Sepsis and septic shock remain global healthcare issues associated with high mortality rates affecting millions every year despite best care efforts. Activation of the renin-angiotensin-system (RAS) is an early event in sepsis, and renin levels may more strongly associate with mortality than serum lactate, a widely accepted index of patient status. We postulated that reduced levels of Angiotensinogen (AGT) may reflect a dysfunctional RAS driven by high renin levels but an attenuated expression of Ang II to adequately support tissue perfusion and blood pressure. This study compared the association with mortality of AGT to serum lactate and active renin in a subset of the VICTAS (Vitamin C, Thiamine, and Steroids in Sepsis) cohort (N=103) at baseline (day 0) prior to treatment.

Methods:
Serum levels of intact AGT and active renin protein were quantified by separate ELISAs. Biomarker discrimination for all-cause 30-day mortality was compared by receiver operating characteristic (ROC) curves generated by logistic regression models adjusted for age, sex, sequential organ failure assessment (SOFA) score, systolic blood pressure, and in-hospital vasopressor support. Association of serum AGT, renin, and lactate with mortality was assessed by Kaplan-Meier curves with log rank test and hazard ratios derived from Cox regression.

Results:
Median [interquartile range] serum levels for AGT were: 114 [78.2-205.4] nM; renin: 4.9 [2.2-13.6] pM; and lactate: 2.6 [1.7-3.8] mM. ROC curves revealed better discrimination of AGT for mortality than either active renin or lactate. The area under the curve (AUC) of AGT (0.82, 95% CI: 0.70, 0.93) was greater than lactate (AUC=0.68, 95% CI: 0.57, 0.80; p=0.022). Kaplan-Meier curves and log rank test also revealed that AGT levels below 114 nM associated with reduced survival. Renin levels greater than 4.9 pM were also associated with patient mortality albeit less than that for AGT while higher lactate levels (>2.6 mM) were not associated with mortality in this cohort.

Conclusion:
AGT levels more strongly associated with 30-day mortality than renin or lactate in the VICTAS cohort. Reduced AGT may reflect increased consumption by high renin coupled with reduced expression by the liver ultimately impairing Ang II-AT
1
R tone in critically ill patients. The prospective assessment of circulating AGT may facilitate more precise therapeutic approaches treatment to restore a dysfunctional RAS and improve overall mortality in sepsis.
Abstract P436: Prorenin Increases the Firing Activity of Hypothalamic Arcuate Nucleus AgRP Neurons
Authors: Zheng Haifeng , Pan Shiyue , Chen Gang , Morton Gregory , Schwartz Michael , Feng Earley Yumei
Published: October 2024

The arcuate nucleus of the hypothalamus (ARC) serves as a key regulator of the cardiovascular and sympathetic regulating center. While neurons in the ARC expressing agouti-related peptide (AgRP) are implicated in the regulation of energy- and glucose homeostasis, our recent findings show that acute chemogenic activation of ARC
AgRP
neurons reduces blood pressure (BP), whereas inhibition of these neurons has the opposite effect. Together, these observations indicate ARC
AgRP
neuronal activity as a determinant of basal BP and suggest that tonic activity of these neurons may be required to maintain BP in the normal range. Importantly, most AgRP neurons express the (pro)renin receptor (PRR), a pivotal component of the brain renin-angiotensin system critical for BP regulation. Accordingly, we hypothesized that prorenin may regulate AgRP neuron activity through PRR, and thereby contributing to the autonomic regulation of BP. This study employed whole-cell patch clamp methodology in brain slices of ARC to investigate the effect of prorenin on AgRP neuron firing activity and understand mechanisms. Male and female mice expressing tdTomato in the AgRP neurons were used. Prorenin (2.5 nM) depolarized the resting membrane potential (-41.9 ± 8.7 mV vs. -47.2 ± 7.8 mV,
P
< 0.001) and increased the frequency of action potential (AP) (2.3 ± 1.3 Hz vs. 1.2 ± 0.8 Hz,
P
< 0.001) compared with the control (artificial cerebrospinal fluid (aCSF), n=10 neurons from 7mice). Analysis of AP waveforms revealed that prorenin decreased the amplitude of AP (61.0 ± 14.4 mV vs. 70.2 ± 14.3 mV,
P
< 0.001) and threshold potential (-31.8 ± 6.0 mV vs. -35.5 ± 4.8 mV,
P
< 0.001), and increased the rise time (2.3 ± 0.7 ms vs. 1.9 ± 0.6 ms,
P
< 0.001), decay time (2.6 ± 1.1 ms vs. 2.0 ± 0.9 ms,
P
< 0.01) and half-width (2.2 ± 0.7 ms vs. 1.8 ± 0.6 ms,
P
<0.01) compared with the control. These changes suggest that alterations in the intrinsic conductance underlying the AP waveform likely coincide with the observed decrease in resting membrane potentials, while the ion channels involved remained to be determined. In summary, prorenin increases the firing activity of the ARC
AgRP
neurons by depolarizing the resting membrane potential, implicating that activation of PRR in the ARC
AgRP
neurons may reduce BP and protect against hypertension development.
Abstract P437: Correlation between plasma CT-proET-1 and renal dysfunction in patients with resistant hypertension. A biomarker analysis of the PRECISION study.
Authors: Blattmann Peter , Iglarz Marc , Dreier Roland , Danaietash Parisa , Sassi-Sayadi Mouna , Clozel Martine
Published: October 2024

Hypothesis:
Endothelin (ET)-1 is upregulated in hypertension and especially resistant forms of hypertension. As ET-1 is a paracrine hormone involved in renal organ damage, we investigated the correlation between eGFR and activity of the ET system in the resistant hypertensive population of the PRECISION trial (NCT03541174), in which aprocitentan, a dual endothelin ET
A
/ET
B
receptor antagonist, significantly reduced blood pressure and UACR. To assess activity of the ET system, ET-1 and CT-proET-1, a stable peptide and biomarker for ET-1 production, were measured in plasma.

Methods:
From plasma collected at screening from the future randomized patients in PRECISION, ET-1 (n=688) and CT-proET-1 (n=100, randomly selected) were measured by ELISA and LC-MS-based assays respectively. Baseline levels of CT-proET-1 were determined on pooled plasma from healthy adults (n=70). Pearson correlation coefficient was determined between biomarkers of the ET system and eGFR.

Results:
CT-proET-1 concentrations measured in patients with resistant hypertension were higher than concentrations from healthy subjects (83 vs 55 pM). In patients with an eGFR≥60 mL/min/1.73m
2
, mean CT-proET-1 concentration was 75 pM [95% CI 70-81; n=77] as compared to 116 pM [95% CI 95-140 n=23] in patients with eGFR<60 mL/min/1.73m
2
. In these two subgroups, mean ET-1 concentrations were 1.90 ng/L [95% CI 1.85-1.95; n=531] and 2.10 ng/L [95% CI 1.99-2.22; n=157] for patients with an eGFR≥60 and eGFR<60 mL/min/1.73m
2
respectively. There was an inverse correlation between CT-proET-1 and eGFR (r=-0.61, p<0.0001) and a less pronounced correlation between ET-1 and eGFR (r=-0.11, p=0.0027) (see
Figure
).

Conclusions:
In patients with resistant hypertension, there was a strong inverse correlation between plasma CT-proET-1 and renal function, suggesting the role of the ET system not only in hypertension but also in renal damage. These data demonstrate that CT-proET-1 is a sensitive biomarker of the ET system, reflecting the production of ET-1.
Typification of six de Candolle names in the genus Clematis (Ranunculaceae)
Authors: MAURYA SONAM , SINGH RAGHVENDRA , PRABHUKUMAR KONICKAL MAMBETTA
Published: October 2024

The lectotypification of six names (Clematis acuminata, C. buchananiana, C. connata, C. grewiiflora, C. montana and C. napaulensis) are discussed here as per the recent ICN rules.