bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P330: Customization of Low-sodium Diet and Its Efficacy
Authors: Kidambi Srividya , Moosreiner Andrea , Rubens Merrill , Obi Brittaney , Widlansky Michael , Tyagi Sudhi , Puppala Venkata , Beyer Andreas , Cowley Allen , Mattson David , Kotchen Theodore , Liang Mingyu
Published: March 2022

Introduction:
Lack of adherence with a low-sodium (Na) diet remains a challenge for many patients. Most research studies use standardized diets for subjects which may decrease adherence and hence result in sub-optimal lowering of blood pressure (BP). We hypothesized that adoption of a customized low-Na diet will result in high rates of adherence, lower BP, and improve vascular function.

Methods:
Post-menopausal women (50-65 years) and men (30-65 years) with baseline BP ≥ 130/80 mm Hg or history of HTN were recruited. Subjects were placed on a 2-week 1200mg Na/day diet (after a 3-day run-in period during which subjects were given 2400 mg of Na/day in addition to their regular diet). Subjects were off all BP medications 1 week prior to the start of the diet and during 2 weeks of study diet. All food was prepared by a bio-nutritionist with a customized menu according to food logs kept by the subjects. Two 24h urine Na measurements were taken to ensure compliance with the diet. In addition to BPs, conduit (brachial artery flow-mediated dilation (FMD)) and micro (~ 200 μm extracted from gluteal adipose tissue biopsies) vessel functions were evaluated before and after the diet period to assess in vivo and in vitro vascular function respectively.

Results:
Seventeen subjects (9 African-American, 7 Caucasian, and 1 Hispanic) with mean BPs of 145 ± 14/87 ± 6 mm Hg (± SD) before starting the low-Na diet were recruited. During the diet period, subjects consumed an average of 1000 mg of Na/day (66% reduction from baseline Na intake). Excluding 2 subjects in whom the 24h urine Na did not drop (instead increased) after 2-weeks indicating non-adherence, the average SBP/DBP reductions were -11 ± 14 (-7%, p=0.06)/-8 ± 10 mm Hg (-9%, p=0.04). Average urine Na levels were 230 ± 83 (before) and 71 ± 82 (after) mmol/24hr. Brachial artery FMD improved from 7.3 ± 3.2 to 9.6 ± 2.3 % (p=0.04) after 2 weeks. Maximal Arteriolar FMD (endothelial dependent) trended toward an increase from 54 ± 18 to 77 ± 13 % and smooth muscle dependent dilation to papaverine was not effected.

Conclusions:
The adoption of a customized low-Na diet can result in high rates of dietary adherence (88% in the current study) and lower BPs. In addition, vascular function improves within 2 weeks on a low-Na diet.
Abstract P333: Repeated Measurementof Casual Urine Na/K Ratio May Provide Useful Information to Screen Early Stage Chronic Kidney Disease Patients With Higher Sodium and Lower Potassium Intake
Authors: Okuyama Yuka , Uchida Haruhito A , Iwahori Toshiyuki , Umebayashi Ryoko , Kato Ayako , Miura Katsuyuki , Ueshima Hirotsugu , Wada Jun
Published: March 2022

Objective:
Lowering sodium-to-potassium ratio has been reported to benefit people for hypertension prevention and control in epidemiological studies. Four to seven repeated measurements of casual urine sodium-to-potassium ratio is known to provide high correlation and good agreement quality with less bias to estimate 7-day 24-hour urinary Na/K ratio in normotensive and hypertensive individuals. However, little is known about urinary Na/K ratio in patients with chronic kidney disease (CKD). The aim of this study was to clarify the relationship of the repeated measurement of casual and 24-hour urinary sodium-to-potassium ratio in patients with CKD.

Design and Method:
A total of 61 inpatients with CKD, 31 in stage 1-3 (eGFR ≥ 30 ml/min/1.73m
2
) and 30 in stage 4-5 (eGFR < 30 ml/min/1.73m
2
), aged 20 to 85 under low-sodium diet (NaCl 6 g/day) were recruited in Okayama University hospital. Sodium-to-potassium ratio in casual urine at 4 points/day (first void after rising, each urine after breakfast, lunch or dinner) for 2 days and 2-day 24-hr urine at the same day were measured. Correlation and the quality of agreement by Bland and Altman between casual urine and 24-hour urine samples were analyzed.

Results:
Mean 24-hour Na and K excretion was lower in participants in stage 4-5 (Na: 87.5 mmol/24h, K: 18.8 mmol/24h) than in participants in stage 1-3 (Na: 99.0 mmol/24h, K: 26.1 mmol/24h), whereas mean 24-hour urine Na/K ratio was higher in participants in stage 4-5 (5.1) than in participants in stage 1-3 (4.1). Casual urine Na/K ratio was strongly correlated with 2-day 24-hour urinary Na/K ratio by sampling 2 casual urine specimens per day for 2 days in participants in stage 1-3 (r = 0.69-0.78), but not in stage 4-5 (r = 0.12-0.19). The bias for mean Na/K ratio between 2-day 24-hour urine and sampling 2 casual urine per day for 2 days in participants in stage 1-3 ranged from -0.86 to 0.16, and the quality of agreement for the mean of this casual urine sampling was similar to that of all 8 points of casual urine samples for estimating 2-day 24-hour values.

Conclusion:
Repeated casual urine Na/K ratio measurement may provide good estimate of 24-hour urine Na/K ratio, in stage 1-3 CKD patients as well as normotensive and hypertensive people; however, not in stage 4-5 CKD patients.
Abstract P334: Persistent Adrenomedullin Derivative Inhibits Development of Hypertension
Authors: Nagata Sayaka , Yamasaki Motoo , Kitamura Kazuo
Published: March 2022

Human adrenomedullin (hAM) consists of a 52 amino acid peptide that is amidated and has a disulfide bond. The bioactive peptide hAM has a variety of physiological functions, such as vasodilatation, hormone secretion, neurotransmission, embryogenesis, wound healing and immunoregulation. hAM has shown several therapeutic effects in experimental models of various diseases, including ischemic heart disease, inflammatory bowel disease, stroke and retinochoroidal disease. However, these therapies required continuous administration of hAM as the half-life of native hAM is quite short in blood. To resolve these issues, the aim of this study was to synthesize novel hAM derivative, and to examine its effect in spontaneously hypertensive rats (SHR). First, we conjugated the hAM N-terminal with 60kDa polyethylene glycol (PEG) (60 kDa PEG-hAM). To demonstrate that PEG binds covalently to α-amino residue of the N-terminal tyrosine of hAM, 60 kDa PEG-hAM was digested with cyanogen bromide and the AM(6-52) thus obtained was confirmed by ion exchange chromatography and MALDI-MS. Next, to determine plasma hAM concentrations, either 60 kDa PEG-hAM (10 nmol/kg) or native hAM was administrated subcutaneously with Wistar rat. We compared hAM concentrations in the peripheral blood of rats after injection with either 60 kDa PEG-hAM or native hAM. The hAM concentrations in the 60 kDa PEG-hAM group after 1, 7 and 10 days were 2600, 740 and 280 pM, respectively. In contrast, the hAM concentrations in the native hAM group after 1 day was 6.7pM, not detect 7 and 10 days. In addition, 60kDa PEG-hAM stimulated cAMP production in cultured human embryonic kidney cells expressing a specific AM receptor. Finally, we compared blood pressor after administrated subcutaneously with either 60 kDa PEG-hAM (20 nmol/kg) or saline in SHR with high salt diet. After 9 days, a single subcutaneous administration of 60 kDa PEG-hAM inhibited development of hypertension with SHR. In summary, the plasma half-life of 60 kDa PEG-hAM was much longer than native hAM, and subcutaneous injection of 60 kDa PEG-hAM in a single dose inhibited development of hypertension with SHR. Therefore, these results suggest that 60 kDa PEG-hAM is a possible therapeutic agent for the treatment of hypertension.
Abstract P336: Excreted Living Renal Proximal Tubule Cells (RPTC) Demonstrate Increased Sodium and Bicarbonate Transport in Inverse Salt Sensitive Individuals Using a Patch Clamp Instrument
Authors: Xu Peng , Schiermeyer Katherine A , Gildea John J , Tran Hanh T , Carey Robert M , Felder Robin A
Published: March 2022

In our previous clinical studies of salt sensitivity of blood pressure, we have demonstrated that approximately 11% of study participants have a paradoxical increase in ≥7mm of Hg blood pressure on a low NaCl diet (5 meq/day) vs a high NaCl diet (300 meq/day). We define these participants as having inverse salt sensitivity (ISS) while salt resistant (SR) participants demonstrate ≤7mm Hg. RPTCs from 2 ISS and 2 salt resistance (SR) participants were patch clamped and ramp currents were recorded using a voltage ramp protocol from -100 to +45 mV within 200 ms in at least 5 experiments for each cell line. Activity of sodium transporters was probed by exchanging an 80 mM Na
+
with a 140 mM Na
+
buffer. Na
+
transport was significantly increased during the low salt to high salt exchange (ISS1: 80mM Na+ 90.6 ± 17.78 pA VS 140 mM Na, 192.8 ± 47.67 pA, n=9, P<0.05 paired t-test; ISS2: 126.5 ± 41.14 pA VS 198.3 ± 47.45 pA, n=6 P<0.05 paired t-test). The fold change in current from 80 to 140 mm Na
+
buffer in ISS cells was significantly increased when compared to salt resistant (SR) (normal) participants indicating ISS cells have more sodium channel activity than SR cells (ISS 2.07 ± 0.01, n=2 VS SR 1.3 ± 0.1, n=2, P<0.05, t-test). Activity of bicarbonate transporters was probed by exchanging 25mM Na gluconate with 25mM NaHCO3. A similar trend was found for bicarbonate transport which showed increased current when we exchanged the Na
+
gluconate to NaHCO3, while SR cells didn’t show any difference when switching Na
+
gluconate to NaHCO3 (ISS1: Gluconate 461.5 ± 226.6 pA VS 1932 ± 658.7 pA, n=8, P<0.05 paired t-test; ISS2: 284.1 ± 83.02 pA VS 1102 ± 295.4 pA, n=6, P<0.05 paired t-test; SR1: 144.1 ± 20.93 pA VS 164.7 ± 27.22 pA, n=12; SR2: 256.5 ± 38.67 pA VS 277.8 ± 38.16 pA, n=5). Comparing bicarbonate
/
gluconate ratios, ISS cells demonstrated an increased ratio over the SR cells (ISS 8.65 ± 2.35, n=2 VS SR 1.11 ± 0.01, n=2, p=0.08) indicating a sodium bicarbonate transporter is hyperactive in ISS cells. Many transporters can be contribute to ISS, therefore we will selectively silence the sodium and bicarbonate transporters to determine which one(s) contribute to the etiology of ISS which then could be targeted for therapeutic intervention.
Abstract P344: Nuclear Factor E2-related Factor 2 (nrf2) Causes Early Microvascular Endothelial Dysfunction and Increased Adma by Activation of the Cox2/tp Receptor Pathway in Mice Infused With Angiotensin II for Three Days
Authors: Wang Dan , Hao Xueqin , Wang Cheng , Welch William J , Tomlinson James , James James , Wilcox Christopher S
Published: March 2022

Background:
Activation of Nrf2 by tert-buthylhydroquinone (tBHQ) prevents hypertension, oxidative stress, endothelial dysfunction and ADMA in mice infused with angiotensin II (Ang II) for 12 days. However, Nrf2 activation with bardoxolone methyl increased cardiovascular events in diabetic patients within one week. Since we found that tBHQ activated cyclooxygenase (COX)-2 within 3 days, we tested the hypothesis that short-term tBHQ administration to Ang II infused mice increases microvascular dysfunction via COX dependent of PGs and TxA
2
that activate thromboxane-prostanoid receptors (TP-Rs).

Methods:
Mesenteric resistance arterioles(MRAs)were isolated from mice infused for 3 days with ANG II (400 ng/kg/min) or vehicle and given oral tBHQ (0.1% of water) or vehicle (n=6 mice/group). Endothelial derived relaxation factor (EDRF) was assessed by a myograph and NO and ROS by RatioMaster
TM
.

Results:
Compared to vehicle, Ang II infused mice given tBHQ had increased (P<0.05) conscious mean arterial pressure (135±6 vs 115±7 mmHg), urinary 8-Iso prostane (1.5±0.4 vs 1.1±0.2ng/mg creatinine), and decreased EDRF (17± 3 vs 23± 2%) and NO (0.23 ± 0.02 vs 0.35 ± 0.02 Δunits), and enhanced ( P<0.05, ) cellular ROS (0.27 ± 0.02 vs 0.12 ± 0.03 Δunits), mitochondria ROS (0.24 ± 0.02 vs 0.1 ± 0.02 Δunit) and microvascular asymmetric dimethylarginine (ADMA, 77 ± 6 vs 55 ± 7 nmol/mg protein). All these effects of tBHQ were prevented in COX-1 knockout mice drinking parecoxib (COX-2 inhibitor) and in TPR and Nrf2 knockout mice.

Conclusions:
Activation of Nrf2 increases short term Ang II-induced increases in BP, oxidative stress, ADMA and endothelial dysfunction. These depend on signaling via COX 1 + 2 and TP receptors. Our studies reveal novel dual effects of Nrf2 in Ang II infused mice: increased BP, ROS, ADMA and endothelial dysfunction within 3 days secondary to activation of COX/TPR signaling follow by the opposite effects of Nrf2 on BP, ADMA and vascular function within 12 days. Therefore, blockade of COX-2/TPRs pathway during initiation of Nrf2 therapy may prevent the devastating early adverse effects that have prevented its use in hypertension or diabetes.
Abstract P349: Plasma Corin Levels Reflect Dynamic Changes in Cardiac Expression Induced by Experimental Acute Myocardial Infarction
Authors: Wang Dong , Gladysheva Inna P , Sullivan Ryan D , Fan Tai-hwang M , Mehta Radhika M , Tripathi Ranjana , Sun Yao , Reed Guy L
Published: March 2022

Introduction:
Corin is a cardiac membrane protease that activates pro-ANP and pro-BNP. Changes in circulating corin levels have been linked to poor clinical outcomes following acute myocardial infarction (AMI) in some, but not all studies and the pathophysiologic mechanisms responsible for these changes are not understood.

Hypothesis:
We examined the hypothesis that plasma corin levels are closely correlated with alterations in cardiac corin expression related to acute ischemic injury.

Methods:
AMI was induced by left anterior descending coronary artery ligation. Hearts and plasma were assessed at 3 hrs, 24 hrs and 3 days post AMI. We measured plasma corin, troponin T levels, cardiac corin, infarct size, ANP and BNP expression by ELISA, qRT-PCR and histology staining. Cardiac function was assessed by echocardiography. Data represent means ± SE of n = 7-9 mice per group.

Results:
Plasma corin levels were significantly increased at 3 hrs (1090±237.50 pg/ml, P<0.05), 24 hrs (1666±214.50 pg/ml, P<0.001), and 3 days (1221±185.90 pg/ml, P<0.01P<0.01) post-AMI with a “rise-and-fall” pattern similar as troponin T when compared to non-MI group (553.9±96.13 pg/ml). In contrast, at the same time-points, cardiac corin expression dropped by 5% (P>0.05), 69% (P<0.001) and 65% (P<0.001) as measured by real time PCR and 30% (P<0.05), 76% (P<0.001) and 75% (P<0.001) by immunohistology. Transcript levels of pro-ANP increased at 24 hrs (20%) and 3 days (3.8-fold, P<0.001) vs. non-MI mice. Transcript levels of pro-BNP also increased 3.2-fold at 24 hrs (P<0.001) and 1.8-fold at 3 days (P<0.01) post MI. EF% and FS% consistently dropped by 36% (P<0.01), 60% (P<0.001) and 68% (P<0.001) and 42% (P<0.01), 63% (P<0.001) and 72% (P<0.001) respectively. Plasma corin levels were negatively correlated with cardiac corin (P<0.01), EF% and FS% (P<0.05) and positively correlated with infarct sizes (P<0.01).

Conclusions:
Plasma corin levels markedly increase and then decline following AMI, reflecting dynamic changes of cardiac corin expression related to acute cardiomyocyte injury. As such, plasma corin levels may serve as a valuable marker to indicate the severity of acute myocardial injury and, over a longer term, expression by the remaining viable cardiomyocyte mass.
Abstract P353: Attenuation of Cardiac Fibrosis, Hypertrophy and Myopathy by AT2R Agonist NP-6A4
Authors: Pulakat Lakshmi , Gavini Madhavi , Mahmood Abuzar , Belechia Anthony , Toedebusch Ryan , Beauparlant Paige , DeMarco Vincent , Kumar Senthil , Ardhanari Sivakumar
Published: March 2022

Adverse cardiac remodeling (hypertrophy, fibrosis and myopathy) underlies cardiac dysfunction and heart failure. Male Zucker obese (ZO:fa/fa) rat that suffers from cardiac dysfunction, adverse remodeling, and heart failure with preserved ejection fraction is a useful model to study the effects of cardioprotective drugs. We reported that NP-6A4 (Novopyxis Inc. Cambridge, MA), a peptide agonist of the Angiotensin II Type 2 Receptor (AT2R), protected mouse cardiomyoblast HL-1 cells and human coronary artery vascular smooth muscle cells (hCAVSMCs) from acute nutrient serum deficiency stress better than β-AR-Blockers, ARBs, and AT2R agonist CGP42112A. This effect was inhibited by AT2R-specific antagonist PD123319, confirming that NP-6A4 acts through AT2R. AT2R is a cardiac and vascular reparative molecule that protects the heart and vasculature from structural damage and fibrosis. No current drugs increase AT2R expression. We report that NP-6A4 treatment (1μM) increased AT2R mRNA (up to 4 fold; p≤0.05) in hCAVSMCs and human coronary artery endothelial cells (up to 8 fold; p≤0.05). This effect was inhibited by PD123319 (10 μM). Treatment of 11-week old male ZO rats with heart disease with NP-6A4 (1.8mg/kg/day in saline, delivered once daily subcutaneously; N=7) increased cardiac AT2R expression and mitigated cardiac dysfunction and adverse remodeling. Quantitative RT-PCR and immunohistochemistry analysis showed that 2 weeks of NP-6A4 treatment increased cardiac AT2R mRNA (up to 9 fold) and protein (1.5-3 fold) compared to controls (N=6) receiving saline (p<0.01). NP-6A4 treatment improved cardiac parameters; endocardial circumferential strain (p≤0.05), myocardial performance index (MPI) (p≤0.005), and E/E’ ratio (p≤0.002). NP-6A4 treatment also increased cardiac capillary density (118% compared to saline treatedl; p≤0.002), and reduced interstitial fibrosis (77% compared to saline treated; p≤0.039.) At 19-weeks (after 8 weeks of treatment), cardiac tissues from 5 out of 6 control rats exhibited regions of myopathy. Only 2 out 7 NP-6A4 treated rats exhibited similar levels of myopathy in the heart. We propose that NP-6A4 attenuates adverse remodeling and improves cardiac function by increasing AT2R expression in cardiac cells.
Abstract P358: Central BP Variability is Increased in Hypertensive-related Target Organ Damage
Authors: De La Sierra Alejandro , Pareja Julia , Yun Sergi , Acosta Eva , Aiello Francesco , Oliveras Anna , Vazquez Susana , Armario Pedro , Blanch Pere , Sierra Cristina , Calero Francesca , Fernandez LLama Patricia
Published: March 2022

Peripheral BP variability (BPV) has been found to be increased in hypertensives with target organ damage (TOD). It is unknown if central BP variability follows the same pattern. We aimed to evaluate short-term BPV in a group of hypertensive subjects classified as having or not cardiac, renal, or vascular TOD.

A total of 178 hypertensives (33% women; age 57±12) were evaluated. TOD was defined by the presence of left ventricular hypertrophy (LVH) on echocardiography, renal alterations (urinary albumin excretion >30mg/g or eGFR < 60 ml/min/1.73m
2
) or aortic stiffness (aortic pulse wave velocity > 10 m/s). BPV was estimated by 24-hour peripheral and central BP monitoring. Parameters evaluated included: night-to-day ratios (NDR), standard deviation (SD) and coefficient of variation (CV) for 24 hours, day and night, weighted standard deviation (WSD) and average real variability (ARV).

Ninety-two patients (51.7%) had TOD, distributed as follows: 66 (37.1%) had LVH, 47 (26.4%) had renal alterations, and 37 (20.8%) increased aortic stiffness. Systolic and diastolic night-to-day ratios and systolic BPV were increased in patients with TOD with respect to those without (table). No differences were observed in diastolic BPV. The increase in systolic BPV was also observed when comparing groups with or without LVH, renal damage or aortic stiffness. Brachial BPV exhibited the same increased variability as central BPV.

We conclude that the presence of hypertensive cardiac, renal or vascular organ damage is associated with increased systolic central BPV and reduced systolic and diastolic nocturnal fall in BP. Central BPV follows the same pattern as observed with peripheral BPV.
Abstract P360: Diagnostic Accuracy Provided by Different Approaches to Office Blood Pressure Measurement: How Many Readings Are Enough?
Authors: Kronish Ian M , Edmondson Donald , Shimbo Daichi , Shaffer Jonathan , Krakoff Lawrence , Schwartz Joseph
Published: March 2022

Importance:
Guidelines lack consensus about the optimal approach to measuring office blood pressure (BP) when screening for hypertension.

Objective:
To compare the accuracy provided by different office BP measurement approaches that differ based on number of office BP readings within a visit, number of visits, and assessment method.

Design:
Cross-sectional

Setting:
Primary care.

Participants:
707 employees without prior diagnosis of hypertension or cardiovascular disease and with screening BP <160/105 mmHg.

Measures:
Six standardized BP readings were taken during each of 3 office visits at least 1 week apart, using 2 assessment methods (mercury sphygmomanometer and BpTRU oscillometric device) for a total of 12,645 readings. Confirmatory factor analysis was used to develop a model from which estimates of the probability of correctly classifying an individual’s office BP status using differing numbers and types of office BP readings were generated.

Results:
A single systolic BP reading correctly classified an individual as having BP above or below the cutpoint for elevated office BP (i.e. 140 mmHg) when the reading was <129 mmHg or >155 mmHg, respectively. Averaging three systolic BP readings across two visits correctly classified an individual 95% of the time if the averaged reading was <134 mmHg or >148 mmHg. There was more confidence gained by increasing the number of visits than the number of readings within a visit. There was no clinically significant confidence gained by dropping the first reading versus averaging all readings, nor by measuring with a manual mercury device versus with an automated oscillometric device.

Limitations:
Only evaluated research quality BP readings. Similar probabilities may not apply to BP measured in routine clinical practice.

Conclusions and Relevance:
Averaging BP readings across two or more office visits might best balance increased confidence in BP status with efficiency of BP measurement, though the preferred measurement strategy may vary with the clinical context. Patients with average readings modestly below the 140/90 mmHg cutpoint (e.g., 134-139 mmHg) might be appropriate for referral to out-of-office BP testing as one cannot gain strong confidence that their “true” office BP is below goal.
Abstract P362: What is the Cost of Measuring a Blood Pressure?
Authors: Yarows Steven A
Published: March 2022

Importance:
Blood pressure (BP) measurement has transitioned to the oscillometric method in most hospitals in the United States, however out-patient offices mainly use the auscultatory technique.

Objective:
Is the Welch Allen oscillometric Connex Vital Signs Monitor time and cost-saving in out-patient Primary Care Offices compared to the auscultatory technique?

Design:
An analysis to determine the time to measure BP in consecutive office patients. The Welch Allen Connex Vital Signs Monitor (WA) was initially used and subsequently the standard wall-mounted ausculatory monitor (Manual) method.

Setting:
A single Family and Internal Medicine practice.

Participants:
Patients presenting for an office visit.

Main Outcome(s) and Measure(s):
The patient demographics were recorded (birthdate, gender, BMI, and date of measurement) and the time of measurement of each technique was recorded.

Results:
The average time to manually measure BP was 58.6±13.9 seconds, whereas the WA average was 39.8±23.0 seconds, 18.8 seconds faster (p<0.05). There was an improvement with experience only with the WA device. The last 1/3 of measurements showed significant improvement (p<0.05) in the speed of measurement for WA (29.3 seconds) vs. Manual (57.5 seconds), which did not significantly change between the first 1/3 and last 1/3 of measurements (p=0.25). The average MA cost to measure a single BP using the Manual method was $0.35 vs. the WA method was $0.24, or a saving with the WA method of $0.11 per measurement. After the proper oscillometric technique was mastered, the cost of the last 1/3 of measurements for the Manual was virtually the same at $0.34, however the WA method decreased to $0.17, a saving of $0.17 per measurement.

Conclusions and Relevance:
The oscilliometric Welch Allen Connex Vital Signs Monitor saved 17 cents per measurement in our out-patient primary care practice which potentially saves $1,119 per year.
Abstract P369: Ambulatory Blood Pressure Monitoring Profile as a Useful Tool - Assessment of an Adult Population in the Real World
Authors: Prado Yasmin S , Rodrigues Livia F , Lopes Patricia d , Rocha Ligia d , Lucci Maria A , dos Santos Mariella P , Almeida Paulo E , Costa Lílian S
Published: March 2022

Introduction:
The pattern of therapeutic and diagnostic control of arterial hypertension (AH) has been better evaluated with the use of Ambulatory Blood Pressure Monitoring (ABPM) in clinical practice.

Objective:
The purpose of the study was to evaluate the blood pressure (BP) profile through data obtained in an adult population (18-59 years), and to further determine the differences of BP readings between users (G1) and non-users (G2) antihypertensive drugs.

Method:
In a cohort of 2222 non-elderly subjects, both genders, mean 43 years (56.8% female), referred for ABPM from an outpatient set-up, we studied 24-hour ABPM patterns.

Results:
Of 2222 adults, 1324 (59.6%) were off antihypertensive medications (G2) and of the remaining, 751 (33.8%) used one or two drugs and 6.6% used three or more drugs. Analysis of variance was applied for a comparative study of therapeutic control between groups, with a significance level of
p
less than 0.05. From the G2, 898 subjects (67,8%) had 24-hour BP within normal limits (119x71mmHg) and, 426 (32,2%) had an elevated mean 24-hour BP (139x87mmHg). Of the G1, subjects in monotherapy, double or triple or more antihypertensive therapies presented satisfactory control in 68% (118x71mmHg), 72% (117x70mmHg) and 66% (119x71mmHg) respectively, with no statistically significant difference between groups. The mean nocturnal drop expressed in percentage for the SBP and DBP in G2, was 11.9±2.03 and 18.4±7.19 in normotensive subjects, and 11.1±4.05 and 16.8±8.02 in hypertensive subjects, with no significant difference between different gender groups (p=0.6). Irrespective of normal nocturnal drop values in G1, we observed a significant attenuation in the subgroup using three or more drugs (percentage of 10.1±6.02 and 14.8±6.13) compared to those with monotherapy or double therapy (11.0±4 and 16.6±4.08), both with similar pattern in their dipping profile.

Conclusion:
The percentage diagnosis of AH by ABPM (32%) is similar to the reported papers in the literature. The pattern of nocturnal drop may help the identification of target organ damages and help in determination of therapeutic adjustments, corroborating literature data, which emphasize the use of ABPM study in the diagnostic and therapeutic evaluation.
Abstract P373: A Cohort Study in Elderly Population - Differences Between Older and Very Older Subjects
Authors: Rodrigues Livia F , Lopes Patricia d , Prado Yasmin S , dos Santos Mariella P , Lucci Maria A , Rocha Ligia d , Almeida Paulo E , Costa Lílian S
Published: March 2022

Introduction:
It is known that isolated systolic hypertension (ISH) and elevated pulse pressure (PP) play an important role in the development of cerebrovascular disease, congestive heart failure, and coronary heart disease, which are the major causes of cardiovascular morbidity and mortality in the population aged older than 65 years. The systolic blood pressure (BP) has been proven to be a stronger predictor of cardiovascular diseases than diastolic BP and a correlation between mortality and high BP has been extensively proven for those in late life until around the age of 80 years.

Objective:
To evaluate BP profile on 24-hour, daytime and night time periods, pulse pressure (PP), riser BP pattern and systolic and diastolic nocturnal drop in an elderly population, referred to be clinically healthy with no prior history of CV disease and off CV medications.

Methods:
We analyzed a cohort of 1300 elderly patients aged over 65 years and compared the ambulatory blood pressure data of elderly individuals (G1) aged 65-79 years (1020 subjects, mean 67.16 years, 64.7% female) and very elderly individuals (G2) aged over 80 years (280subjects, mean 83.89 years, 69.3% female).

Results:
Differing trends for systolic and diastolic BP between groups resulted in large differences in ambulatory PP, it being significantly greater (
p
= 0.001) throughout the entire 24-hour in G2, even after correcting for age (24-hour, daytime and night time periods being 55,07 x 66,76mmHg, 55,31 x 67,03mmHg and 54,55 x 65,95mmHg , respectively in G1 and G2). The prevalence of non-dipping was not significantly higher in G2. Largest difference between groups was in the prevalence of the riser BP pattern, asleep systolic BP mean greater than awake SBP mean (18,7% vs. 6,5% in patients G2 and G1, respectively; p 0.001).

Conclusions:
There is a growing recognition of the importance of the systolic component of BP. About 65% of hypertension in the elderly is ISH, and CVD risk increases with PP, which is not simply a marker for stiff diseased arteries; elevated PP and asleep systolic BP mean was the major basis for the diagnosis and stratification of ISH.
Abstract P375: Community Based Wireless Blood Pressure Monitoring Improves Patient Centeredness
Authors: Moran Ryan J , Narezkina Anna , Patrick Kevin
Published: March 2022

Objective:
Studies exploring wireless-based systems to monitor patients in underinsured communities are lacking. We evaluated blood pressure (BP) control with wireless vs. conventional home-based BP machines in a pilot study nested within a larger trial in San Diego County focusing on optimizing cardiovascular risk reduction.

Methods:
Patients with a new diagnosis of hypertension (HTN), or those with BP above 140/90 on a current regimen were enrolled from three federally qualified healthcare center systems in low-income communities. Participants were randomized to conventional automated BP cuff (CBP) or a wireless cloud-based system (WBP), and followed with a clinical visit at 3, and 6 months. Exit surveys were conducted to evaluate patterns of use.

Results:
At the time of this analysis complete clinical data are available for 151 participants (71 WBP; 80 CBP). Baseline BPs did not differ between treatment arms (systolic: 149.9 mmHg WBP; 151 mmHg CBP; P=0.72; diastolic: 83.5mmHg WBP; 81.3 CBP; P=0.23). BP decreased significantly in both arms by the end of the pilot (Figure 1). No differences were seen between groups for both net change of BP (P=0.79) or for end mean systolic BP (P=0.96). Of 60 participants in WBP arm who completed the exit survey, those with BP still not at goal (N=20) were more likely to report “Strongly Agree” or “Agree” that the wireless system helped them feel more engaged in their clinical care (P=0.02).

Discussion:
Both wireless and conventional BP monitoring had a clinically significant impact on BP control among underinsured individuals in this study, and the wireless system appears to improve engagement in care.
Abstract P377: Real World of Ambulatory Arterial Stiffness Index and Central Aortic Pressures of Hypertensive Patients Treated by Their Primary Care Physicians
Authors: Cabrera-Sole Ricardo , Urrera Rivera Liliana , Turpin Lucas Caridad , Garcia Ruiz Santiago
Published: March 2022

Background:
THE AMBULATORY ARTERIAL RIGIDITY INDEX (aasi) is a good method to measure the vascular risk of patients with hypertension. However, in a few cases this index is taken into account when treating patients at high risk. In this paper, we present our experience on AASI levels in patients with AHT (PHTT) and high cardiovascular risk referred by their primary care physicians (PCP)

Objectives:
to evaluate the AASI in patients with hypertension who received previous treatment and to correlate these values with central arterial pressures.

Materials and Methods:
We studied 256 PHTAs (100 women and 156 men, (69 + 8 years old) treated by their PCP, who underwent a 24-hr ABPM study, and arterial stiffness was measured by AASI, , as well as the central arterial pressures and the simple or combined drugs that were used at the beginning and the end of the 16-week follow-up after modifying the treatment and evaluating them by telephone at least once a month. The details are described in the following table:

* Means p values less than 0.05.

Conclusions:
In the real world, PHTTs are not well controlled despite taking more than two drugs, requiring adjustment and closer follow-up to obtain desired results in the control of hypertension and in improving parameters of arterial stiffness measured by AASI as well as central pressures and consequently decrease cardiovascular risk. For follow-up, telephone follow-up may be useful for better control of these patients.
Abstract P383: Pharmacist-led Digital Care Improved Community Hypertension Control by Increasing Medication Adherence in China
Authors: Qu Wenhao , Wang Hongwei , Yang Zhifang , Wang Zhen , Liu Kai
Published: March 2022

Objective:
To identify the correlation between medication adherence and community hypertension control when a digital solution was introduced to assist retail pharmacists in a randomized controlled trial (RCT).

Methods:
Hypertensive patients (≥ 140/90 mm Hg, n=90) taking ARB or CCB anti-hypertensive drugs were recruited and randomized into 3 study groups: 1) usual care; 2) retail pharmacy in-store care which was offered as a walk-in service and provided by pharmacists who were equipped with the CareLinker solution consisting of blue-tooth BP monitor, an App and a cloud database to display history BP data, personalized meal plans and health coaching contents; or 3) home-based tele-medical care by which patients used GSM-embedded BP monitor to auto-send BP data to the pharmacists who then resorted to the CareLinker Decision Support Solution, a cloud-based backend engine, to consult patients over phone on a biweekly basis. This was a 12-month real-world research and the two primary end points were the anti-hypertensive medication adherence measured by Proportion of Days Covered (PDC) and changes of SBP.

Results:
PDC of the 3 study groups at baseline was 84.0% (group-1, control), 85.4% (group-2, pharmacy in-store intervention) and 87.6% (group-3, home-based tele-medical care), p > 0.05 between the 3 groups. At the end of the 12-month study, PDC was reduced to the annual average of 31.9% (group-1), 49.5% (group-2) and 61.2% (group-3), with p<0.05 between group-1 and the 2 intervention groups (group-2 and -3). Reduction of SBP was 3.4±2.4 mm Hg (p=0.166, group-1), 11.7±3.2 mm Hg (p=0.001, group-2), and 15.5±2.6 mm Hg (p=2.26*10
-6
, group-3), with p= 0.014 (group-1 vs group-2) and p= 0.002 (group-1 vs group-3). DBP was reduced by 3.2±1.5 mm Hg (p=0.043, group-1), 6.8±2.4 mm Hg (p=0.008, group-2), and 6.8±2.8 mm Hg (p=0.004, group-3). Plotting PDC with BP reduction found a strong positive correlation for SBP: r= 0.692, p<0.001, and a weaker correlation for DBP: r= 0.301, P=0.004.

Conclusion:
Pharmacist-led digital healthcare can improve adherence of anti-hypertensive medication by as much as 84% (group-3 vs group-1), leading to enhanced community BP control.
Abstract P386: The Paraventricular Nucleus in Control of Blood Pressure and Its Role in Hypertension
Authors: Basting Tyler M , Lazartigues Eric , Murkerjee Snigdha , Xu Jiaxi
Published: March 2022

Rationale and objectives:
In conscious mammals the importance of neural control over sympathetic tone in relation to cardiovascular (CV) function is well established. Neuro-CV dysregulation leads to increased sympathetic activity and neurogenic hypertension. The paraventricular nucleus (PVN) of the hypothalamus and both the rostral ventrolateral medulla (RVLM) and nucleus of the tractus solitarius (nTS) in the brainstem are currently viewed as key hubs for BP control and are implicated in producing or relaying the increased sympathetic tone in hypertension. We propose increased activity in the PVN, potentially through an upregulation of the renin angiotensin system, causes an increase in blood pressure. We test this theory by examining how stimulation or lesioning of the excitatory PVN neurons in conscious mice affects blood pressure and sympathetic activity.

Methods:
PVN and nearby glutamatergic neurons were unilaterally transduced with channelrhodopsin using an adeno-associated virus (CamKII-ChR2-eYFP-AAV) in wildtype mice. We then measured the effect of acute stimulation of excitatory PVN neurons on resting blood pressure (telemetry) and baroreflex in conscious mice. Additionally, in vGlut-cre mice glutamatergic neurons of the PVN were bilaterally lesioned utilizing a cre-dependent caspase (Dio-Caspase-AAV). We then recorded baseline resting blood pressure and baroreflex in conscious mice before and after DOCA-Salt hypertension. Finally, we measured nor-epinephrine levels as a quantification of sympathetic activity.

Results and conclusions:
Unilateral PVN excitation increased blood pressure from baseline by ~10 mmHg. Glutamatergic lesions of the PVN resulted in a blunted rise in BP when animals went through the DOCA-Salt protocol. These experiments demonstrate that the autonomic dysfunction seen in hypertension could be due to changes in the PVN. Overactivation of the PVN in hypertension is probably one of multiple factors that increase sympathetic drive resulting in an increased blood pressure.
Abstract P387: Depletion of Perivascular Macrophages in the Brain Delays Blood Pressure Elevation in Angiotensin II-salt Hypertensive Rats
Authors: Yamazato Masanobu , Ishida Akio , Yamazato Yoriko , Nakamura Takuto , Ohya Yusuke
Published: March 2022

Objectives:
Perivascular macrophages in the cerebrospinal fluid (CSF) are immune surveillance cells in the brain. Increase in angiotensin II (Ang II) in the periphery gradually produces neurogenic hypertension which is associated with brain inflammation. However, little is known on the role of perivascular macrophages in the CSF on neurogenic hypertension. We hypothesized that perivascular macrophages in the CSF have an important role in the development of neurogenic hypertension by relaying and amplifying excess peripheral Ang II signals to brain parenchyma.

Methods:
Sprague-Dawley rats had surgery to instrument radio telemetric pressure transducers to abdominal aorta. Following a one-week recovery period, the rats had surgery to implant either saline or Ang II filled osmotic minipump subcutaneously and received intracerebroventricular (icv) injection of either control liposome or clodronate liposome. The clodronate liposome is a drug that selectively induces apoptosis to macrophages which have liposome phagocytic activity. After the surgery, all rats were provided high-salt diet (2.0% NaCl). Blood pressure of rats was recorded three times a week for 2 weeks. Different set of rats had hexamethonium challenge test to evaluate sympathetic tone in 7 or 9 day after initiation of the infusions.

Results:
Rats that received Ang II infusion with control icv (n=7) gradually increased mean arterial pressure (MAP) compared with rats that received saline infusion (n=5) and reached significant increase in 6 days after the initiation of infusions. Rats that received Ang II infusion with clodronate icv (n=6) had delayed increase in MAP and reached significant increase in 10 days and had significantly lower MAP (91±4 mmHg) compared with rats that received Ang II infusion with control icv (111±4 mmHg) in day 8. Peak depressor response to hexamethonium was increased only in rats that received Ang II infusion with control icv when compared with saline infused rats examined in 7 or 9 days after initiation of the infusions.

Conclusion:
Perivascular macrophages in the CSF may have important role in the development of angiotensin II-salt neurogenic hypertension.
Abstract P408: Waist-to-height Ratio Index For Predicting The Incidence Of Hypertension
Authors: Choi Jung Ran
Published: March 2022

Background:
Several anthropometric indices such as body mass index (BMI) and waist circumference (WC) have been examined as indicators of cardiovascular diseases in both adults and children. Waist-to-height ratio (WHtR) has been considered a superior predictor for detecting cardiovascular risk factors than BMI. We investigated the association between WHtR and incident hypertension in prospective study.

Methods:
A total of 1,718 subjects aged 39-72 years in a longitudinal study were recruited. Participants were divided into two groups according to development of hypertension during 2005-2008 (baseline) and 2008-2011 (follow-up). Logistic regression models were used to evaluate WHtR as a significant predictor of the hypertension.

Results:
During 2.8 years of follow-up, 185 new cases of hypertension (10.8%) were diagnosed with an incidence rate of approximately four percent per year. The WHtR was significantly higher in the subjects who had developed hypertension than in those who had not (0.54±0.05 vs. 0.51±0.05,
p
<0.001). After adjusted for baseline age, gender, smoking status, alcohol intake, regular exercise, total cholesterol (LDL), and systolic blood pressure (SBP), logistic regression analysis indicated participants with the highest quartile of WHtR (WHtR≥0.54) were 4.51 times more likely to have hypertension than those with the lowest quartile (OR 4.51; 95% CI 2.41-8.43; p<.0001). The area under the curve (AUC) for WHtR in identifying hypertension risk was significantly greater than BMI (p=0.0233).

Conclusion:
A positive association between WHtR and the incidence of hypertension was found in Korean adults. We assumed the WHtR may be a better predictor of incident hypertension in a community-based prospective study.
Abstract P412: Genetically Increased Angiotensin I-converting Enzyme and Peripheral and Renal Vascular Reactivity in Mice
Authors: Chollet Catherine , Placier Sandrine , Chatziantoniou Christos , Hus-Citharel Annette , Caron Nathalie , Roussel Ronan , Alhenc-Gelas Francois , Bouby Nadine
Published: March 2022

Angiotensin 1-converting enzyme (ACE) levels in man are under strong genetic influence. Genetic variation in ACE has been linked to risk for and progression of cardiovascular and renal diseases. Causality has been documented in genetically modified mice but mechanisms underlying causality may remain incompletely documented. To further document the vascular and renal consequences of a moderate genetic increase in ACE we studied mice carrying three copies of the ACE gene (ACE3) and littermate wild type 2-copy animals (WT). We studied peripheral and renal vascular reactivity to angiotensin II and bradykinin, by measuring blood pressure and renal blood flow (RBF) after intravenous administration, and also reactivity of isolated glomerular arterioles, by following intracellular calcium mobilisation. Vasoconstrictor responses to angiotensin II were significantly enhanced in ACE3 compared to WT over the whole range of doses tested (0.25, 0.5, 1 and 2 ng, n=5/6 per group, ANOVA, genotype effect, MAP p<0.01, RBF p<0.05). The lowest dose of Ang II increased MAP by 5.3±1.3 and 16.7±4.0 mm Hg in WT and ACE3, respectively and decreased RBF by 0.136±0.035 and 0.486 ±0.097 ml/min. ACE gene copy-number had no influence on the response to intravenous norepinephrine (2, 4 and 10 ng) or bradykinin (25, 50 and 100 ng). In isolated glomerular afferent arterioles, maximal calcium response to angiotensin II (10
–12
to 10
–7
mol/L) was increased in ACE3, consistent with the hemodynamic study. Δ [Ca
2+
]
i
max (nmol/l) was 239 ± 22 in ACE3 versus 189 ± 16 in WT (n=9, p<0.01). Duplication of ACE gene also altered the signalling pathways triggered by endothelial activation by bradykinin or carbachol in pre-constricted muscular efferent arterioles. While in WT the NOS-NO pathway was not functional in these arterioles, with lack of NOS mRNAs and lack of effect of L-NAME, in ACE3 NOS3 gene expression was induced and NO mediated the effect of bradykinin or carbachol, which was inhibited by L-NAME. These data document new, unexpected vascular consequences of a genetic increase in ACE synthesis. Enhanced vasoconstrictor effect of angiotensin II, probably due to loss of counter-regulatory mechanisms, may contribute to the risk for cardiovascular and renal diseases linked to genetically high ACE.
Abstract P414: Blockade of Sodium Glucose Cotransporter 2 by Canagliflozin Suppresses High Glucose-induced Angiotensinogen Augmentation in Renal Proximal Tubular Cells
Authors: Satou Ryousuke , Woods T. Cooper , Miyata Kayoko , Cypress Michael W , Katsurada Akemi , Dugas Courtney M , Lightell Daniel , Navar L. Gabriel
Published: March 2022

Intrarenal angiotensinogen (AGT) is mainly expressed in proximal tubular cells (PTC). AGT is increased by hyperglycemia (HG) in type 1 and 2 diabetes mellitus, which causes elevated intrarenal angiotensin formation contributing to the development of hypertension and kidney injury. Sodium glucose co-transporter 2 (SGLT2) is abundantly expressed in early PTC and may promote increased intrarenal AGT by increasing intracellular glucose levels. This study tested the effects of canagliflozin (CANA), an SGLT2 inhibitor, on HG-induced AGT elevation in cultured PTC. Mouse PTC were treated with 5, 10 or 25 mM glucose. 0-10 μM CANA was applied one hour before glucose treatment. AGT mRNA and protein levels were measured by digital PCR and western blot analysis. Levels of intracellular reactive oxygen species (ROS) were determined with H
2
DCF-DA. Tempol, an antioxidant, was used to test if elevated ROS is involved in HG-induced AGT upregulation. 10 mM glucose increased AGT protein levels at 12 hours (3.06±0.48-fold compared with 5 mM glucose) and treatment with 10 μM CANA attenuated the AGT augmentation (1.68±0.05-fold). AGT protein levels were also increased by 25 mM glucose; but CANA did not suppress the AGT levels caused by this glucose concentration. In PTC treated with 10 mM glucose for 12 hours, the suppressing effect on AGT upregulation was observed with 1 and 10 μM CANA. Lower concentrations of CANA (0.01 and 0.1 μM) did not lower AGT protein levels significantly. Elevated AGT mRNA expression by glucose was also attenuated by CANA. Treatment of PTC with 1 mM pyruvate also increased AGT expression levels, indicating that glycolysis is involved in HG-induced AGT upregulation. After incubation of PTC with 10 mM glucose for 12 hours, intracellular ROS levels were elevated compared to baseline (4.24±0.23-fold) and these were also inhibited by CANA (0.2±0.08-fold). Furthermore, tempol attenuated AGT upregulation in HG-treated PTC. These results indicate that enhanced glucose entry via SGLT2 into PTC elevates intracellular ROS generation by stimulation of glycolysis and consequent AGT augmentation. Thus, SGLT2 inhibition by CANA may limit HG-induced AGT stimulation which suppress intrarenal angiotensin formation and reduce kidney injury in diabetes mellitus.