bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP57: Chronic Inhibition Of Brain Rhomboid-like Protein 2 (irhom2) Activity Decreases Arterial Blood Pressure In Salt-sensitive Hypertension In Mice
Authors: Mohammed Mazher , Elgazzaz Mona , Berdasco Clara , Lazartigues Eric D
Published: August 2021

We previously reported that ADAM17 (aka tumor necrosis factor-α convertase) is critical for the development of hypertension in experimental models and patients. Recent studies highlighted that ADAM17’s formation of TNF-α relies on prior maturation of this sheddase, controlled by the rhomboid-like protein 2 (iRhom2) specifically in microglia. Genetic deletion of iRhom2 in mice shows significant attenuation of TNF-α and ADAM17 activity in a tissue specific manner. Here, we hypothesized that silencing iRhom2 activity specifically in the brain would decrease blood pressure (BP) in the DOCA-salt model of hypertension, in mice. Uninephrectomized mice were implanted subcutaneously (sc) with DOCA-pellets (50 mg) and provided with 1% saline in drinking water. In addition, mice were chronically implanted with an icv cannula connected to a sc osmotic minipump for delivery of: (1) iRhom2-siRNA (9.6 μg/kg/day), (2) scrambled siRNA (SCR 0.2 μg/kg/day), (3) ADAM17 antibody (ADAM17-Ab; 23.8 μg/kg/day) or (4) artificial cerebrospinal fluid (aCSF) for 2 weeks while BP was recorded by telemetry. DOCA-salt treatment led to a significant increase in BP in the control groups (SCR: 156 ±3 mmHg and aCSF: 161 ±1 mmHg; n=3/group; p<0.001) compared to baseline values (122 ±2 mmHg; n=12). ICV infusion of iRhom2-siRNA or ADAM17 neutralizing antibody for 2-weeks in DOCA-salt-treated mice resulted in a significant attenuation of BP (iRhom2-siRNA: 152 ±2 mmHg and ADAM17-Ab: 151 ±2 mmHg n=3/group, p<0.001). These data suggest that: 1) Selective silencing of iRhom2 from microglia is as potent as ADAM17 neutralization throughout the brain in lowering BP and 2) iRhom2 is a potential new therapeutic target for the treatment of salt-sensitive hypertension.
Abstract MP61: Sex Difference In The Response Of Human Renal Proximal Tubule Cells To A Nephrotoxic Agent.
Authors: Moore Shaun , Kumar Megha , Yaqub Daniel , Gildea John J , Felder Robin , Jose Pedro A , Armando Ines
Published: August 2021

Our previous work indicated that the renal dopamine D2 receptor (D2R) has a significant role in regulating renal inflammation and injury, as well as in blood pressure control. In mice, D2R has protective effects in the kidney by limiting the inflammatory and fibrotic reaction; impaired D2R function results in renal inflammation and damage. Some common single nucleotide polymorphisms (SNPs; rs 6276 and 6277) in the human
DRD2
gene are associated with decreased D
2
R expression and function and high blood pressure. To determine the effects of the presence of SNPs in the response to the nephrotoxic aristolochic acid (AA, 5μg/ml, 24 h), we studied immortalized human renal proximal tubule cells isolated from normal tissue of nephrectomies and genotyped for
DRD2
SNPs and
DRD2
wild-type (WT). We also determined whether this response is sex dependent. D2R protein was higher in male than in female WT (135±5 vs 100±4%; n=3/group; P<0.04) and lower in males with SNPs (43±2%, P<0.05) and females with SNPs (23±2%,P<0.05), compared with their respective WT counterparts. In both male groups (WT and SNPs), AA increased D2R protein by 80-100% but had no effect in WT females and increased ~50% in females with SNPs. The TNFα mRNA was higher in males with WT and SNPs which was increased by AA 9-10-fold in WT males and females but only 2-3-fold in those with SNPs. The TGFβ mRNA was similar in WT males and females and increased to the same extent in both groups with SNPs and was not affected by AA in all groups. Col1a1 mRNA was higher (30%) in WT males and females than those with SNPs; AA decreased Col1a1 mRNA in all groups. FN1 mRNA was higher (30-40%) in males and females with SNPs than WT; AA increased FN1 mRNA only in males and females with SNPs. The mRNA expression of the cell proliferation marker Ki-67 was higher in WT females than WT males (1.5-2-fold) and higher with SNPs than WT in both groups; AA increased Ki-67 mRNA in both groups and to a greater extent in males than in females. Taken together our data indicate that the presence of
DRD2
SNPs affects the baseline expression of inflammatory and fibrotic factors and the response to AA is dependent on both sex and the presence of
DRD2
SNPs. These data may have potential clinical translation since rs6276/6277 is commonly expressed (42%/23%) in the human population.
Abstract MP63: Cytochrome P450 1B1 Mediated Inhibition Of Group IV Cytosolic Phospholipase A
2
α In Paraventricular Nucleus Protects Female Mice From Angiotensin II-Induced Hypertension, Increased Renal Sympathetic Activity And Proteinuria
Authors: Singh Purnima , Dutta Shubha Ranjan , Song ChiYoung , Malik Kafait U
Published: August 2021

Recently we showed that 2-methoxyestradiol (2-ME), an estrogen (E2) metabolite generated by CYP1B1 (cytochrome P450 1B1) in the paraventricular nucleus (PVN), protects female mice from Ang (angiotensin) II-induced hypertension and increased renal sympathetic activity. We also demonstrated that group IV cPLA
2
α (cytosolic phospholipase A
2
α) in the brain contributes to Ang II-induced hypertension in male mice. This study was conducted to determine the contribution of central cPLA
2
α and its relationship to CYP1B1 in Ang II-induced hypertension in female mice. cPLA
2
α knockdown in the PVN by transduction with adenovirus (Ad)-cPLA
2
α-short hairpin (sh)RNA (200 nL, bilaterally, 1.0х10
12
pfu/mL) but not its control Ad-scrambled (Scr)-shRNA (2.5х10
11
pfu/mL) in ovariectomized (OVX) wild-type (

cPLA
2
α

+/+
/
Cyp1b1
+/+
, n=8/group) and intact

cPLA
2
α

+/+
/

Cyp1b1
-/-

(n=12/group) female mice attenuated the effect of Ang II (700 ng/kg/min, subcutaneous, osmotic pump, 2 weeks) to increase the systolic blood pressure (SBP, mmHg) as measured by tail-cuff (Day 12: 129±3 vs 168±7 and 119±3 vs 172±5, respectively, P<0.05). Moreover, reconstitution of cPLA
2
α in the PVN by transduction with Ad-cPLA
2
α-DNA (1.1х10
12
pfu/mL) but not its control Ad-GFP-DNA (1.0х10
11
pfu/mL) in OVX-

cPLA
2
α
-/-

/
Cyp1b1
+/+
mice (n=4/group) restored the effect of Ang II to increase SBP (Day 12: 163±7 vs 124±4, P<0.05). Furthermore, Ad-cPLA
2
α-shRNA but not Ad-Scr-shRNA transduction in the PVN in OVX-

cPLA
2
α

+/+
/
Cyp1b1
+/+
and intact

cPLA
2
α

+/+
/

Cyp1b1
-/-

mice reduced and Ad-cPLA
2
α-DNA but not Ad-GFP-DNA transduction in the PVN in OVX-

cPLA
2
α
-/-

/
Cyp1b1
+/+
mice restored the effect of Ang II to increase the renal sympathetic activity as indicated by urinary norepinephrine level (ng/mL, 324±36 vs 707±94, 359±49 vs 979±70, 690±44 vs 421±43, respectively, n=4/group, P<0.05) and proteinuria (mg/24 hour, 4±1 vs 10±0.4, 3±0.4 vs 7±1, 9±0.8 vs 3±0.7, respectively, n=4/group, P<0.05). These data suggest that E2-CYP1B1 derived metabolite 2-ME protects against Ang II-induced hypertension, renal sympathetic activity, and proteinuria by inhibiting cPLA
2
α activity in the PVN. Thus, 2-ME and/or agents inhibiting cPLA
2
α activity could be useful for treating hypertension and its pathogenesis in females.
Abstract MP65: Increased Sedentary Time Is Associated With Greater Postpartum Blood Pressure In Women With A History Of Preeclampsia
Authors: Nuckols Virginia R , Stroud Amy , Gruber Kelsey , Ngonyama Rumbidzai , Brandt Debra , Santillan Donna A , Santillan Mark K , Pierce Gary L
Published: August 2021

Introduction:
Women with a history of preeclampsia (hxPE) are at a four-fold increased risk for chronic hypertension and have elevated aortic stiffness compared withhealthy pregnancy (HP). Higher sedentary time (ST) is related to higher odds of hypertension in clinic among young women regardless of the amount of moderate-to-vigorous physical activity (MVPA). As pregnancy and postpartum are uniquely vulnerable times of increased sedentary behavior, the objectives of this study were to determine whether ST is associated with higher blood pressure (BP) and aortic stiffness in women with hxPE compared with HP 1-3 years postpartum, and if change in ST from late pregnancy to postpartum is related to change in BP or aortic stiffness.

Methods:
Women with hxPE (N=33) and HP (N=46) completed the Pregnancy Physical Activity Questionnaire (PPAQ) 18±6 months postpartum. BP was assessed in triplicate in clinic and by 24-hour ambulatory blood pressure monitoring and aortic stiffness by carotid-femoral pulse wave velocity (CFPWV). In a subset of women (N=20), clinic BP, CFPWV and the PPAQ were previously evaluated in the third trimester.

Results:
Women with hxPE reported more leisure-time ST compared with HP (18 [7-19] vs 7 [5-7] MET-hr/wk, P<0.001), whereas MVPA did not differ (77 [39-106] vs 56 [35-88] MET-hr/wk, P=0.13). 24-hour ambulatory BP was higher in women with hxPE (120 [114-126] vs 114 [109-120] mmHg, P=0.049; 78 [72-82] vs 74 [70-77] mmHg, P=0.056), but CFPWV did not differ independently of BP (6.1 vs 5.5 m/s, P=0.33). Postpartum ST, but not MVPA, was associated with higher 24-hr systolic (ρ=0.24, P=0.04) and diastolic BP (ρ=0.27, P=0.02) and higher CFPWV (ρ=0.31, P=0.008) independent of body mass index. Increases in ST from late pregnancy to postpartum (0 [-3-2] ΔMET-hr/wk, P=0.22) was related to increased BP (systolic ρ=0.42, P=0.06; diastolic ρ=0.44, P=0.050) and increases in CFPWV (ρ=0.54, P=0.02) despite a reported increase in MVPA (21.5 [-0.5-63] ΔMET-hr/wk, P=0.04).

Conclusions:
Greater ST is related to higher BP and aortic stiffness 1-3 years postpartum, and women with hxPE report greater leisure-time ST compared with HP controls. Reduction in ST may represent an achievable interventional strategy to improve cardiovascular health in women with hxPE.
Abstract MP66: Social Determinants And Co-morbid Conditions In Women Of Child-bearing Age With Hypertension From 2001-2018
Authors: Kovell Lara C , Meyerovitz Claire , Ayturk Didem , Juraschek Stephen P , Moore Simas Tiffany A , PERSON Sharina D , Lemon Stephenie C , McManus David D
Published: August 2021

Introduction:
Hypertension (HTN) is the most important modifiable risk factor of serious maternal mortality and morbidity. Social determinants, including economic stability and access to healthcare, influence HTN outcomes and are critical to understanding and addressing racial and ethnic differences in HTN control.

Objective:
To assess social determinants and co-morbidities in US women of child-bearing age with HTN by race/ethnicity

Methods:
We studied women (age 20-50) with HTN in the National Health and Nutrition Examination Surveys 2001-2018. Social determinants and co-morbid conditions were examined in groups categorized by race/ethnicity - Non-Hispanic White (White), Non-Hispanic Black (Black), and Hispanic. Demographics, anthropometric measures, and co-morbid conditions were compared with White women as reference.

Results:
In all women with HTN, the mean (SE) age was 36.0 (0.3) years and 63% were on BP medication. Compared to white women, Black and Hispanic women had lower food security, poverty income ratio, smoking use, and private insurance (all p<0.0001,
Table
). Black women had higher BP medication use, BMI, and BP compared to White women (all p<0.0001). Hispanic women had higher rates of diabetes (p=0.009) and no place to go for healthcare (p=0.005) compared to White women. Food insecurity was present in 34% of Hispanic women.

Conclusions:
Despite effective diagnostics and therapy, health inequity is common in women of child-bearing age with HTN, with differences by race/ethnicity in social determinants and co-morbid conditions. Each racial/ethnic group with HTN brings social determinants and comorbid conditions important for providers to recognize.
Abstract MP67: Differential Effects Of Selective Renal Denervation On Intrarenal Neurohormone System Involved In Blood Pressure Regulation
Authors: Zhou Hao , Lai Yinchuan , Chen Weijie , Xu Yanping , Liu Hang , Li Yidan , Yin Yuehui
Published: August 2021

Aims:
To investigate alterations of intrarenal neurohormonal system involved in BP regulation after renal nerve stimulation (RNS)-guided renal denervation (RDN), and compare the significance of ablation on different BP-elevated magnitude sites.

Methods and Results:
Twenty-one dogs that met inclusion criteria were randomized to receive RDN at strong (SRA group, n=7) or weak (WRA group, n=7) BP-elevation response sites guided by RNS, or underwent RNS only (RNS-control, RSC, n=7), and fully recovered from the acute experiments. After 4 weeks, renal sympathetic and renin angiotensin system activity parameters, and major transporter expression were assessed by immunology and histochemistry. Compared with RSC group, RDN therapy significantly attenuated renal norepinephrine and tyrosine hydroxylase levels, alleviated renin release, and inhibited onsite generation of angiotensinogen. Meanwhile, the expression of exciting axis components, including angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II type-1 receptor, were down-regulated, while the protective axis components such as ACE2 and Mas receptors, were up-regulated in both WRA and SRA group. Moreover, RDN reduced the abundance of aquaporin-1 and aquaporin-2 in kidneys. Although RDN had a minimal effect on overall NKCC2 expression, its activation (p-NKCC2) and directional enrichment in the apical membrane (mNKCC2) were dramatically blunted. Further analysis showed that all these changes were more significant in SRA group than WRA group.

Conclusions:
RDN effectively reduced systemic BP by affecting renal neurohormone-receptor axis, as well as expression and/or activation of major transporters. Selective RDN at strong BP-response sites presented a more superior beneficial effect, reconfirmed the feasibility of RNS-guided RDN.
Abstract MP70: Aldosterone And Inverse Salt Sensitivity Of Blood Pressure
Authors: Xu Peng , Gildea John J , Akhter Mahabuba , Carey Robert M , Yue Wei , Felder Robin A
Published: August 2021

Salt sensitivity affects approximately 20% of adults worldwide and has similar mortality and morbidity sequalae as hypertension. Research has focused on the harmful effects of a high salt diet but have not focused on the harmful effects of a low salt diet. Inverse salt sensitive (ISS) individuals require high salt intake in order to maintain a normal blood pressure. Aldosterone increases ENaC and sodium reabsorption via the mineralocorticoid receptor (MR). We previously reported that αENaC was significantly lower in ISS renal tubule cells isolated from urine (uRTC), while these cells showed higher ENaC like activities under trypsin stimulation. We hypothesized that aldosterone may act as a stimulus and play a role in ISS high blood pressure on a low salt diet (LSD). Plasma aldosterone was significantly increased on LSD in all salt study participants, and ISS individuals showed the highest aldosterone level (ISS HS 3.8±0.38, n=26; ISS LS 35±3.38, n=22; SR HS 4.34±0.18, n=180; SR LS 32.62±1.6, n=152; SS HS 4.65±0.35, n=43; SS LS 26.08±2.18, n=38; HS Vs LS, p<0.001, two-way ANOVA). Moreover, both aldosterone and plasma renin activity (PRA) were significantly lower in salt sensitive (SS) individuals on LSD (PRA LS: ISS 6.05±0.87, n=17; SR 5.94±0.36, n=108; SS 4.43±0.57, n=34; p<0.05, one-way ANOVA), indicating LSD was protective to SS individuals. Treatment of uRTCs with 1 μM aldosterone increased MR and αENaC expression in ISS but not in SR (salt resistant) cells (MR: SR VEH 12164±213; SR Aldosterone 12327±128; ISS VEH 12128±40 vs ISS Aldosterone 13506±128, n=3, p<0.001, two-way ANOVA; αENaC: SR VEH 5023±46; SR Aldosterone 4895±55; ISS VEH 4270±21 vs ISS Aldosterone 5013±113, n=3, p<0.001, two-way ANOVA). High salt treatment further decreased MR in ISS but not in SR cells (ISS: 142mM 11066±188 vs 192mM 10425±74; p<0.05, n=3 two-way ANOVA). These results are consistent with the hypothesis that ISS individuals retain excess Na
+
and exhibit decreased BP when compared to SR or SS individuals under high salt diet, but reabsorb more sodium and exhibit elevated blood pressure under low salt diet. Higher circulating aldosterone and ex-vivo urine derived renal cell aldosterone sensitivity under low salt conditions may be a novel diagnostic test to identify ISS individuals.
Abstract P101: Primary Aldosteronism Screening In At-risk Populations
Authors: Nhan Winnie , Urban Caitlin , Chen Yuxuan , Zhao Lili , Holevinski Lynn , Turcu Adina F
Published: August 2021

Background:
Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is associated with higher rates of cardiovascular, metabolic, and renal comorbidities as compared to equivalent primary hypertension (HTN).

Objective:
To evaluate the rates and patterns of PA screening across various at-risk populations.

Methods:
We performed a retrospective review of adult patients seen in a university-based outpatient setting between 1/1/17-6/30/20, who had HTN plus at least one of the following criteria: 1) taking ≥3 antihypertensive agents (resistant HTN); 2) age <35; 3) obstructive sleep apnea (OSA); 4) hypokalemia; or 5) an adrenal mass. We excluded patients with adrenal insufficiency, congenital adrenal hyperplasia, severe renal disease, and end stage heart failure.

Results:
We identified 93,362 patients (54.6% men, mean age 64±16 y, 82.3% white, 12.8% black, 2.3% Asian) meeting at least one PA screening criterion. Of these, 3.4% were screened for PA. Screening occurred in 2.7% (1,813/66,185) of patients with resistant HTN; 4.2% of those with HTN and OSA (1,297/29,322) or hypokalemia (599/5,387); 5.1% of those <35 y (461/8,573); and 46.5% (452/972) of patients with HTN and an adrenal mass. Multiple logistic regression showed that the odds of screening were highest in patients with hypokalemia: OR: 3.4 (3.2-3.7), and were independent of having atrial fibrillation or myocardial infarction. Among patients with resistant HTN and those with HTN and OSA, women vs. men (OR: 1.2-1.4) and blacks vs. all other races (OR: 2-2.6,
p
<0.0001 for all) were more likely to be screened. Conversely, among patients <35 y and those with adrenal masses, there were no race or sex differences. Although ~8 years younger, patients with resistant HTN and HTN+OSA screened had higher prevalence of chronic kidney disease, cerebrovascular accidents, dyslipidemia, and diabetes than those not screened.

Conclusions:
PA remains vastly under-recognized, even in large academic settings. Consideration for PA is given more often after comorbidities have developed. Enhancing awareness and screening rates for PA are critical for preventing cardio-renal and metabolic complications in many patients with HTN.
Abstract P103: A PATIENT'S 45

YEAR STORY AFTER 1 3/4 ADRENALECTOMY FOR PRIMARY ALDOSTERONISM DUE TO ADRENAL HYPERPLASIA: IMPROVED CONTOL WITH LO NA DASH DIET.
Authors: Grim Clarence E , Kabrna Paul
Published: August 2021

This report relies on detailed hospital/clinic records from the UK provided by the patient(PK) and his physicians for review and synthesis. In 1976 an asymptomatic, 24 y/o college lad had a routine health screening BP of 245/125. He was admitted. HPI was negative for symptoms or prior history of HBP. FH was - for low K or HBP, + for CAD in men <50. PE: ? increased heart size, Fundi Grade II. Hypokalemic alkalosis was noted, a renal arteriogram was normal. Adrenal (Ad) CT showed a normal L Ad but the R was not visualized, plasma aldosterone (PALDO) was elevated but 24 hr urine ALDO was not. PRA was not available at this time. Ad venography was negative, but the R Ad could not be cannulated. The DX was bilateral disease. Spironolactone (S) was started at 300 mg/d. He was readmitted for surgery 2 months later. BP = 160/100 and K was normal. At surgery, L Ad was said to be 2x normal and it and 3/4 of the R Ad were excised. Oral cortisol coverage was needed for 2 months, then ACTH gel for 2 months. BP was lowered for about 2 months off medications but then returned to 200/110. S was restarted at 400 mg/d with good control but gynecomastia developed. BP control was attempted with S and hydralazine for several years but despite being normal at home was always high in the office. Age 33 noted to have K of 3.2 and muscle “fasciculations”. S was increased. AFIB developed at 51. He converted to NSR with Amiodarone. BP continued to be difficult to control till age 56 when he began to move to the DASH diet recommended by my (CEG) patient online support Group which I have managed now for 19+ years. At 58, he retired from teaching early to care for his wife. At 62, PALDO was 1300 and Renin was 10 on S+DASH diet (ENa 55, EK 139 mM/d). Then 600/1 off S + on high salt intake (ENa 125, EK 100 mM/d). At 60, MRI showed “adenoma R” Ad. Rx with S/enalapril continued with home BPs 122/84. At 65, non-ST MI diagnosed, PTA/stenting was performed. BP has been stable for last 3 years with home BP 120/80 on DASH Diet, Spiro 100/enalapril 20 mg/d. Statin myalgia prevented statins. Lipids and BP have improved on DASH. HBP returns when he deviates from DASH. This case shows that long-term survival after 1 3/4 adrenalectomy for Conn’s (due to hyperplasia) is possible and suggests moving to the DASH diet improves BP control (last 3 year AVE 112/73).
Abstract P109: A Promising Novel Hypertension Drug Candidate
Authors: Gavras Haralambos , Neutel Joel , Elin Ronald J , Rosanoff Andrea , Costello Rebecca B , Mani Jayashree , Jaffe Russell
Published: August 2021

This study tests the hypothesis that RMJH-111b, a novel drug candidate, can improve blood pressure (BP) in hypertensive adults without the gastrointestinal distress that is often experienced with oral magnesium (Mg) treatment. A Phase 1 / 2 study tested the clinical tolerability, safety and efficacy as well as pharmacokinetics of RMJH-111b softgels. Each softgel contains 110 mg elemental Mg as inverted micellar nanodroplets designed to enhance intestinal uptake and cell delivery of active constituents. Forty-one hypertensive people were screened, twenty-two qualified to be enrolled and twenty-one completed the 10 day inpatient trial. In the study, after a 7 day washout period, participants were admitted and had a 3 day run in on only placebo followed by a 7 day double blind treatment period. Fifteen people received active treatment with 440 mg of elemental Mg BID (a total of 880 mg daily) and six received placebo. Data collected include daily seated blood pressure as well as 24h ambulatory blood pressure (ABPM) measurements. In addition, ECG, routine laboratory tests including serum Mg levels and 24h urinary Mg excretion were performed on days 3 and 10.ABPM 24h mean blood pressure changes day, night and 24° are as follows:

SBP
day
:-6.2, DBP
day
:-2.3, SBP
night
:-4.9
,
DBP
night
:-1.3
,
SBP
24°
:-6.6
,
DBP
24°
:-2.8
,
SBP+DBP
24°
:-9.4.

One individual was excluded because her SBP decreased from 155 to 108 mm Hg after five days on protocol, below the 110 mm SBP protocol exclusion criteria. No symptoms of hypotension were observed. A correlation was noted between 24h levels of urinary Mg excretion and the 24h ABPM BP reduction. There were no adverse effects in the study group. A trend correlating serum Mg levels increase and BP decrease across the study population was noted. Based on retroactive statistical analysis of data presented, if 100 people had been studied using the same protocol, a statistical significance with a p value.
Abstract P116: VARIATION IN MEAN ARTERIAL PRESSURE (MAP) AND ITS HEMODYNAMIC COMPONENTS DURING 24-HOUR AMBULATORY PULSE WAVE ANALYSIS: IMPACT OF AGE, RACE, GENDER AND BODY SIZE
Authors: Nagpal Sagar , Mukhopadhyay Debduti , Osmond Peter , Schwartz Joseph E , Izzo Joseph L
Published: August 2021

BP is highly variable within and between individuals but the impact of variation in underlying hemodynamic components is unknown. We tested the feasibility and clinical associations of quantitated variances in MAP and its hemodynamic components [heart rate (HR), stroke volume (SV) and total vascular resistance (TVR)] obtained by 24-hr ambulatory pulse wave analysis (PWA, Mobil-O-Graph, IEM, Stolzberg, DE). BP and PWA were measured every 20 min for 24 hrs. Indexed to body surface area, MAP = HR*[SV index (SVI)]*[TVR index (TVRI)]; ln(MAP) = ln(HR) + ln(SVI) + ln(TVRI); and total MAP variability = var [ln(MAP)] = covariance (cov)[ln(HR), ln(MAP)] + cov[ln(SVI), ln(MAP)] + cov[ln(TVRI), ln(MAP)]. Relative contributions to var[ln(MAP)] for each hemodynamic component (as %) were calculated and associations with demographic characteristics were analyzed by correlations and t-tests. We studied 152 people (49% women, 23% black); mean(SD): # readings 57(11), age 59(16) yr, BMI 29.9(6.5) kg/m
2
, systolic BP 135(18) and MAP 106(14) mmHg. Mean(SD) 24-hr values were: ln(MAP) 4.64 (0.13), ln(HR) 4.20 (0.15), ln(SVI) -3.32 (0.15), and ln(TVRI) 3.75 (0.18). Relative contributions of hemodynamic components to total 24-hr ln(MAP) variation were: TVRI 54(36)%, HR 33(38)%, and SVI 13(40)%. The large SDs of these relative contributions led to analysis of potential contributing factors: TVRI contribution was correlated with 24-hr mean MAP (r=0.24, p=0.003) and was higher (>54%) in males (p=0.03) and blacks (p=0.04); HR contribution was inversely related to MAP (r=-0.26, p=0.001), age (r=-0.29, p=0.0003) and BMI (r=-0.173 p=0.05) and was lower (<33%) in blacks (p=0.008); SVI contribution was correlated with age (r=0.31, p<0.0001) and BMI (r=0.23, p=0.005) and was higher (>13%) in women (p=0.03). We conclude that 24-hr ambulatory PWA can identify components of MAP variation within individuals and their associations with demographic factors. The relative contributions of hemodynamic components (HR, SV, TVR) to 24-hr variability in ln(MAP) varies systematically with 24-hr mean MAP, age, race, gender, and BMI. Theoretical clinical implications may include therapeutic adjustments for extremes of variation in HR (beta-blockers), TVR (vasodilators) or SV (diuretics).
Abstract P118: Angiotensin Ii Hypertension-dependent Decrease In Circadian Rhythms Of Cardiovascular Parameters: Role Of Peroxisome Proliferator Activated Receptor-α
Authors: Lee Dexter L , Johnson Sheree M , Stukes Ian , Williams Nia , Ananaba Ugoeze C , Reece Takisha , Khundmiri Syed J
Published: August 2021

Decreases in circadian rhythms of cardiovascular parameters, such as day to night changes in mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), systolic (SP) and diastolic pressure (DP) are an index of cardiovascular disease. Peroxisome proliferator activated receptor - alpha (PPAR-α) has been shown to decrease inflammatory markers and hypertension a slow pressor dose of Angiotensin II (Ang II); however, the role of PPAR-α on cardiovascular parameters during the initial stages of Ang II infusion is unknown. We hypothesize that the absence of PPAR-α will cause a reduction in the day to night changes in MAP, HR, PP, SP and DP during the initial stages of a slow pressor dose of Ang II. Male (10 - 12 weeks old) PPAR-αknockout (KO) and wild-type (WT) mice were infused with Ang II (400 ng/kg/min) for three days. Radiotelemetry was used to measure the cardiovascular parameters. The baseline MAP values were: 100
+
10 mmHg (WT) and 108
+
9 mmHg for KO. The baseline HR values were: 530
+
10 bpm (WT) and 526
+
6 bpm (KO). The baseline PPs were 17
+
0.2 mmHg (WT) and 18
+
0.3 mmHg (KO). The baseline SBPs were 108
+
9 mmHg (WT) and 116
+
10 mmHg (KO). The baseline DBPs were 91
+
9 mmHg (WT) and 98
+
10 mmHg (KO). During the first three days of Ang II infusion, the change in day to night MAP was 20 ± 2 mmHg and 10 ± 2 mmHg in Ang II treated WT and KO mice, respectively. Changes in day to night HR were 25 ± 4 bpm and 46 ± 7 bpm for WT and KO mice, respectively. The day to night changes in PP were 8 ± 1 mmHg for WT and 2 ± 2 mmHg for KO mice. The day to night changes in SBPs were 20 ± 2 mmHg and 12 ± 3 mmHg for WT and KO mice, respectively. Changes in day to night DBPs were 18 ± 2 mmHg for WT and 9 ± 2 mmHg for KO mice. TBARS and Interleukin-17 were increased in heart homogenates of KO + Ang II (15 ± 2 μM) and (1.5 ± 0.3 ng/mL) vs WT + Ang II (11 ± 3 μM) and (1.0 ± 0.2 ng/mL). Nitrite/Nitrate was decreased in KO + Ang II (1.0 ± 0.1 nM) vs WT + Ang II (1.5 ± 0.5 nM). In summary, the absence of PPAR-α decreases the day to night changes in MAP, SBP, DBP and PP during the initial three days of a slow pressor dose of Ang II. In the absence of PPAR-α, increases in oxidative stress and inflammation are mechanisms that may contribute to the changes in the cardiovascular parameters and suggest the occurrence of cardiovascular diseases during a slow pressor dose of Ang II-infusion.
Abstract P119: Cardiovascular Risk And Subclinical Target Organ Damage In A Young Adult Population Provided By A Primary Healthcare Center In Brazil (Laparc Study)
Authors: Deberaldini Marinho Beatriz , Santos Deisianny , Borges Rodrigo , de Souza Mello Tomás , Ushijima Natalia , Fernandes Ana Cristina , Pecly Inah , Muxfeldt Elizabeth
Published: August 2021

Background:
In this young and apparently healthy population, it is important to identify early CV risk factors and subclinical target organ damage (TOD) with low complexity procedures, aiming regression, control and primary prevention with future reduction of CV morbidity and mortality.

Objectives:
To evaluate subclinical TOD using Ankle-Brachial Index (ABI), Office and Home Pulse Pressure (PP), identifying arterial stiffness.

Methods:
A cross-sectional population study for CV risk assessment in adults aged 20-50 years old provided by a Primary Healthcare Center in Brazil. A total of 632 individuals were evaluated (40% male; mean age 36 ± 9 years). Socio-demographic, anthropometric data, and lifestyle evaluation were recorded. All underwent Office Blood Pressure (OBP) measurements in the 4 limbs to calculate the ABI and office PP. All received the Home Blood Pressure Monitoring (HBPM) device (7 days protocol) and the mean of the general BP and the calculation of the PP were evaluated. They also performed an ECG to calculate Sokolow-Lyon Index (SLI) and Cornell Voltage Index (CVI).

Results:
The prevalence of hypertension according to OBP was 16% and 18% according to HBPM, but with a low agreement between diagnoses (kappa = 0.385). HBPM identified 4 phenotypes: normotension (74%), sustained hypertension (8%), masked hypertension (10%), and white coat hypertension (8%). The median of office PP was 46 [39-52] mmHg and of Home PP was 45 [41-50] mmHg. Elevated Office PP and Home PP (> 60 mmHg) were identified in 64 and 28 participants, respectively. High office PP was more frequent in men, obese, with increased neck circumference and lower ABI. It was also associated with higher SLI and CVI. High Home PP was also more frequent in men, obese, with increased neck circumference and higher CVI. The median of the ABI was 1.14 [1.08-1.22], which is the cutoff point we used to define early changes in the ABI. Individuals with decreased ABI are more obese, with smaller neck circumference and lower OBP control. They also had higher systolic BP values and office PP (49 vs 43 mmHg, p<0.001).

Conclusion:
In this young population, early changes in subclinical TOD already identify a higher CV risk profile, indicating the importance of implementing prevention measures to reduce this risk.
Abstract P122: The Identification Of New Serum Uric Acid Levels Cut-off Point To Prevent Prehypertension And Hypertension Based On Jnc 7 And Acc/aha 2017 Classification: A Cross-sectional Study
Authors: Sja'bani Mochammad , Aziza Bawazier Lucky , Irijanto Fredie , Zulaela Zulaela , Widiatmoko Agus , Kholiq Abdul , Tomino Yasuhiko
Published: August 2021

Background:
Serum uric acid levels have been reported to be associated with elevated blood pressure and hypertension events. It is needed to determine the prognostic serum uric acid (SUA) cut-off point to prevent the incidents of prehypertension and hypertension.

Methods:
This was a cross-sectional study involving a total of 733 participants who a had history of prehypertension in 2007. These participants were selected from “Mlati Study Database” in 2007 by simple random sampling using statistical software. Participants underwent both physical and laboratorical examination. Data were analyzed based on JNC 7 and ACC/AHA 2017 guideline.

Results:
Based on JNC 7 classification, the analysis using ROC curve showed that the prognostic SUA cut-off point of 4.85 mg/dL was able to indicate the incidents of prehypertension or hypertension in the database (95% confidence interval, CI, 0.532-0.629, p=0.001). Additional analysis using ACC/AHA 2017 guideline as the blood pressure classification was also performed for comparison. Based on ACC/AHA 2017 classification, the ROC curved showed a slightly higher SUA cut-off points than the previous analysis using JNC 7. The prognostic SUA cut-off point of 4.95 mg/dL was able to indicate the events of hypertension stage 1 and stage 2 in the database (95% confidence interval, CI, 0.532-0.615, p=0.001). These results were parallel with the previous study which reported that SUA cut-off points of 5-7 mg/dL (high-normal SUA) and ≥7 mg/dL (high SUA) were associated with the incidents of prehypertension and hypertension.

Conclusion:
The new SUA cut-off points may be used as an early warning for the development of prehypertension and hypertension in the future.
Abstract P125: Hypertension, Awareness, Treatment, And Control In Nepal: Results From May Measurement Month 2020 Blood Pressure Screening
Authors: Acharya Pawan , Koirala Sweta , Soti Pabitra Babu , Sharma Sneha , Sapkota Abhishek , Kafle Simrin , Paudel Kiran , Poudel Santosh , Neupane Dinesh
Published: August 2021

Background:
May Measurement Month (MMM) 2020 was not officially executed globally due to the COVID-19 pandemic. But in Nepal, the MMM 2020 was conducted by following COVID-19 safety measures.

Methods:
We used an opportunistic screening campaign for blood pressure measurement among individuals ≥18 years in Nepal. Of the three measurements, the second and third measurements were used to estimate the mean systolic and diastolic blood pressure(BP). We defined hypertension as the systolic BP ≥ 120 or diastolic BP≥90 mmHg and or currently taking antihypertensive medicine.

Results:
Among the total 11,486 participants, 57%(6568/11486) were females. The mean age of the screenees was 45years(SD=17.0). The mean systolic and diastolic BP were 125.8(SD= 18.0) and 81.6(SD=10.5) respectively. About 31.3%(3592/11481) participants had hypertension. Among the hypertensive persons, 40.2%(1444/3592) were aware of their hypertension status. Among these who were aware, 79.4%(1146/1444) were taking antihypertensive medicine. However, the overall proportion of hypertensive patients taking medicine was 32.0%(1146/3592). The BP was controlled among 46% ( 527/1444) of participants who were under medication. Logistic regression analysis adjusting age, sex, body mass index(BMI), and smoking status found males, higher age groups, higher BMI, and smokers had higher odds of being hypertensive. (Figure 1)

Conclusion:
The results suggest a need to address the gap in awareness, diagnosis, and treatment of hypertension in Nepal. The results are limited due to the non-random participation of screenees. Figure 1. Odds ratio plot
Abstract P126: Self-management Program And Black Women With Hypertension
Authors: Abel Willie M
Published: August 2021

Introduction:
Prevalence rates of hypertension (HTN) among Black adults (males 58.3% and females 57.6%) in the United States is among the highest in the world. Black females (46%) experience a higher incidence of Stage 2 HTN than Black males (42%) contributing to a greater risk of heart failure, stroke, and kidney disease. Levels of awareness, treatment, and control of HTN among Black women are decreasing. Effective strategies to combat these trends are imperative. Lifestyle changes and medication adherence are proven strategies to facilitate blood pressure (BP) control. Getting individuals with HTN to incorporate these strategies into the context of their everyday physical and social environments where they can be performed independently requires active individual engagement in healthcare behaviors and self-care activities.

Aim:
This study examined the effects of the Chronic Disease Self-Management Program (CDSMP) on self-care (maintenance, management, and confidence) and BP control in Black women with HTN at baseline and then 3-, 6-, and 9-months post CDSMP.

Methods:
The current study used data from the Interactive Technology Enhanced Coaching Intervention RCT for Black Women with HTN study. All participants completed a 6-week CDSMP at the beginning of the study. Self-care data were collected using the Self-Care of HTN Inventory along with manual BP readings at baseline, and repeated measures at 3-, 6-, and 9-months.

Results:
Of the 90 community-dwelling Black women enrolled in the study, 83 completed the CDSMP and 69 completed the study. The mean age was 53.57 (
SD
= 10.07) years and the average number of years diagnosed with HTN was 11.06 (
SD
= 8.47). All participants had BP readings greater than 130/80 mmHg at baseline and 44.92% (31 of 69) moved to less than 130/80 mmHg at 9-months. A weak negative correlation occurred at 9-months between systolic BP and self-care management,
r
(67) = -.26,
p
= .029, and confidence,
r
(67) = -.25,
p
= .035; and diastolic BP and self-care management,
r
(67) = -.31,
p
= .009, and confidence,
r
(67) = -.28,
p
= .018.

Conclusion:
The CDSMP was feasible, successfully delivered, and well-received by those enrolled in the study. Future studies should evaluate effective interventions for self-care strategies to improve long-term BP control.
Abstract P133: Prevalence Of Medication Non-adherence Via Therapeutic Drug Monitoring In Patients With Uncontrolled Hypertension Treated At A Safety Net Hospital
Authors: Osula David , Wu Bryan A , Schesing Kevin , Das Sandeep R , Brown Nancy , Moss Elizabeth , Vongpatanasin Wanpen
Published: August 2021

Background:
Medication nonadherence presents one of the greatest challenges to hypertension management. Previous studies from our group have shown therapeutic drug monitoring (TDM), biochemical monitoring of drug levels, is more accurate than self-report, detailed questionnaires, or prescription fill rate in detecting nonadherence. Prior studies have also shown a prevalence of nonadherence from 45% to 80% among insured patients with uncontrolled hypertension despite having been prescribed a multi-drug regimen. Previous studies have not assessed adherence to antihypertensive drugs in a safety net population by TDM.

Methods:
We performed a cross-sectional study in patients with uncontrolled hypertension in the primary care Internal Medicine and Cardiology Clinics at Parkland Health& Hospital System (PHHS). Patients with BP of 130/80 mmHg, prescribed ≥2 antihypertensive medications, and self-reporting medication adherence were enrolled after informed consent. Plasma samples were obtained for measurement of 44 cardiovascular drugs using liquid chromatography mass spectrometry.

Results:
Among 77 patients with uncontrolled hypertension (57% female, 65% Black, 12% Hispanic), 13 (17%) were nonadherent to at least one anti-hypertensive drug by TDM. There was no difference in baseline characteristics between the two groups. The adherent and nonadherent groups had similar systolic (146±13 vs 148±18, p=0.67) and diastolic (83±9 vs 88±10 mmHg, p=0.13) BP. All patients had either medical insurance or some form of prescription financial assistance. 15 patients had prescription financial assistance, while 62 patients had medical insurance. Nonadherence rates for patients on financial assistance programs did not significantly differ from patients with medical insurance (13% vs 18%, p>0.999).

Conclusions:
We found a surprisingly low prevalence of anti-hypertensive medication nonadherence in this uncontrolled hypertension population despite many barriers to treatment. Our study suggests a lesser role of medication nonadherence in uncontrolled hypertension in the safety net population.
Abstract P137: Nonspecific ST-T Change In Electrocardiogram Was Associated With A Reduced Constructive Myocardial Work In Hypertensive Patients With Preserved Ejection Fraction
Authors: Ishikawa Joji , Nakamura Saori , Toba Ayumi , Miyawaki Masashi , Shimizu Ruri , Yamamoto Aya , Aoyama Rie , Harada Kazumasa
Published: August 2021

Background:
Nonspecific ST-T change in electrocardiogram can be observed in hypertensive heart disease with preserved left ventricular ejection fraction (LVEF); however, the relationship between nonspecific ST-T change and global myocardial work in echocardiography was unclear.

Methods:
We evaluated global longitudinal strain (GLS), GWI (global work index), GCW (global constructive work), GWW (global wasted work), GWE (global work efficiency), using offline analyzing system (View Pal, GE) in 196 hypertensive patients with preserved LVEF (>50%). Nonspecific ST-T change and major ST-T change (depression of ST in V5 lead >1mV) was also evaluated in electrocardiogram.

Results:
Mean age was 79.3±8.2 years (men 37.8%). Compared with patients with no ST-T change, those with nonspecific and major ST-change had a smaller absolute value of GLS (-20±3, -18±4, -14±5%, P<0.001) and had smaller constructive work load [GWI (2140±488, 1915±472, 1523±776 mmHg%, P<0.001), GCW (2410±514, 2165±471, 1694±784 mmHg%, P<0.01)]. Additionally, those with nonspecific and major ST-T change had an increased wasted myocardial work [GWW (87±61, 109±58, 138±71 mmHg%, P<0.001)], and this resulted in reduction of myocardial work efficiency [GWE (95±4,93±3,87±12%,P<0.001)]. Even after adjustment for age, sex, diabetes, dyslipidemia, EF, LV mass index, relative wall thickness, parameters of diastolic function (E/A, E/e’, left atrial volume index, tricuspid valve regurgitant flow velocity), and electrocardiogram LVH of Cornell product and Sokolow-Lyon voltage, the patients with nonspecific ST-T change had a significantly smaller LV global constructive work. [GWI (2243±41 vs. 1998±96 mmHg%, P=0.025), GCW (2501±45 vs. 2210±105 mmHg%, P=0.015)].

Conclusion:
In hypertensive patients with preserved LVEF, nonspecific ST-T change in electrocardiogram was associated with a reduced constructive work in LV.
Abstract P140: Mutant Mice Carrying Global Loss Of
Npr1
Exhibit Cardiac Fibrosis, Hypertrophy, And Congestive Heart Failure: Implication Of TGF-Beta/SMAD Signaling Pathway
Authors: Ramasamy Chandramohan , Subramanian Umadevi , Pandey Kailash N
Published: August 2021

The cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP) bind to natriuretic peptide receptor-A (NPRA), which synthesizes the second messenger cGMP. The objective of this study was to determine the underlying mechanisms that regulate the development of cardiac hypertrophy, fibrosis, and congestive heart failure (CHF) in
Npr1
(encoding NPRA) gene-knockout mice. The
Npr1
null mutant (

Npr1
-/-

, 0-copy), heterozygous (

Npr1
+/-

, 1-copy), and wild-type (

Npr1
+/+

, 2-copy) mice were orally administered with transforming growth factor-β1 receptor I (TGF-β1R1) antagonist, GW788388 (2 mg/kg/day) by oral gavage for 28 days. The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVEDS), posterior wall thickness (PWT), and percent fractional shortening (FS) were analyzed by echocardiography. The heart was isolated and used for the analysis of fibrotic markers using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot methods. The heart weight-to-body weight (HW/BW) ratio, LVEDD, LVEDS and PWT were significantly (p<0.005) increased in

Npr1
-/-

and

Npr1
+/-

mice than wild-type

Npr1
+/+

mice. The FS was greatly reduced in

Npr1
-/-

and

Npr1
+/-

mice compared with

Npr1
+/+

mice. The

Npr1
-/-

null mutant (0-copy) mice showed 52% increase in HW/BW ratio and 6-fold induction of cardiac fibrosis as compared with 2-copy control mice. The cardiac expression of fibrotic markers including collagen-1a (COL-1a; 3.5-fold), connective tissue growth factor (CTGF; 5-fold), α-smooth muscle actin (α-SMA; 4-fold), TGF-β1RI (4-fold), TGF-β1RII (3.5-fold), and SMAD-2/3 proteins (3-to-5 fold) were significantly increased in

Npr1
-/-

and

Npr1
+/-

mutant mice compared with age-matched

Npr1
+/+

animals. The treatment with TGF-β1R1 antagonist, significantly (p<0.001) prevented the cardiac hypertrophy, fibrosis, CHF, and down-regulated the expression of fibrotic markers and SMAD proteins in mutant mice. The LVEDD, LVEDS, and FS were significantly (p<0.001) improved in the drug treated

Npr1
-/-

mice. The present results indicate that the cardiac hypertrophy, fibrosis, and CHF in
Npr1
mutant mice is regulated through the TGF-β1-mediated SMAD-dependent signaling pathway.
Abstract P143: Assessment Of Biventricular And Aortic Function In Arterial Systemic Hypertension By Speckle Tracking Echocardiography
Authors: Capotosto Lidia , Germanò Giuseppe , Giordano Marcello , Lorenzano Marianna , Germanò Rosanna , Lorenzano Svetlana , Muscaritoli Maurizio , Vitarelli Antonio
Published: August 2021

Background:
The purpose of the present study was to assess whether systemic arterial hypertension is associated with abnormal right ventricular (RV) structure and function as assessed by three-dimensional speckle tracking echocardiography and how those changes are related to left ventricular (LV) strain, left ventricular hypertrophy (LVH) and aortic (Ao) function.

Methods:
We examined 115 hypertensive (mean age, 65±16 years; 52% male) and 115 healthy adults (mean age, 68±13 years; 54% male). Patients were divided into two groups: patients with LVH (Group I, LVMI>115g/m
2
men, LVMI>95g/m
2
women) and patients without LVH (group II). LV longitudinal (LS), circumferential, radial and area (GAS) strains were calculated by three-dimensional speckle tracking echocardiography (3DSTE). RV free-wall longitudinal strain (LS) was determined by 3DSTE. Aortic (Ao) distensibility and stiffness index (SI) were calculated using accepted formulae. The corrected aortic strain (Ao-S) by two-dimensional speckle tracking echocardiography was calculated as the global aortic strain /pulse pressure. Data analysis was performed offline (GE EchoPAC).

Results:
Overall, Ao-SI was increased (r=0.74, p=0.003) and Ao-S was decreased (r=0.79, p=0.002) in hypertensive patients compared with controls. Ao-SI had a negative correlation with Ao-S (r=-0.76, p<0.001). Ao-S correlated with LV and RV longitudinal strain (r=0.62,p=0.02, and r=0.58,p<0.05, respectively) and LV and RV area strain (r=0.66,p=<0.01, and r=0.53,p<0.05, respectively). RV-LS and LV-GAS were lower in Group 1 patients compared to Group 2 (r=0.81, p<0.001), and lower in Group 2 patients compared to controls (r=0.59, p=0.02). There was a positive correlation between LV and RV LS (r=0.52, p<0.05). RV-LS was independently associated with Ao-S (β=0.37, p=0.01), LV-GAS (β=0.32, p=0.027) and LV-LS (β=0.26, p=0.034) in the whole hypertensive population.

Conclusions:
In systemic hypertension there is a complex interaction between LV strain, RV strain and Ao strain. Reduced RV strain can occur even in the absence of LV hypertrophy.