bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P077: Hypertension And Ischemic Stroke; The Effect Of A Combined Anti-hypertension Medications And Thrombolytic Therapy
Authors: Poupore Nicolas , Allen Bridgette , Nathaniel Thomas I
Published: September 2020

Background:
The aim of this study is to identify clinical risk factors in acute ischemic stroke ( AIS) pretreated with anti-hypertensive (anti-HTN) medications with a subsequent thrombolytic therapy that are associated with potential worsening or improving neurological functions.

Methods:
We analyzed retrospectively collected data from consecutive AIS patients with a combined anti-HTN medications and recombinant tissue plasminogen activator (rtPA) therapy for AIS. We used logistic regression model to identify demographic and clinical risk factors that are associated with improving or worsening neurologic functions in AIS patients with a combined anti-HTN and thrombolytic therapy. The overall correct classification of the logistic regression models was determined using the Hosmer-Lemeshow test, while the area under the receiver operating characteristic curve was used to test the sensitivity of the model. The variance inflation factor was used to check for multicollinearity.

Results:
In the adjusted analysis, patients with increasing age (Odd ratio (OR)=1.035, 95% CI, 1.022-1.049,
P
<0.001), female AIS patients (OR = 1.630, 95% CI, 1.182-2.248,
P
=0.002) with a history of substance abuse (OR = 2.315, 95% CI, 1.107-4.842,
P
= 0.026) were associated with worsening neurologic functions. However, Caucasians (OR = 0.535, 95% CI, 0.361-0.793,
P
= 0.002) with dyslipidemia (OR = 0.655, 95% CI, 0.479-0.897, P = 0.008), obesity (OR = 0.642, 95% CI, 0.472-0.873,
P
= 0.005), high-density lipoproteins (HDL; OR = 0.988, 95% CI, 0.976-1.000,
P
= 0.045), and with a direct admission (OR = 0.509, 95% CI, 0.341-0.761,
P
= 0.001) were associated with improving neurologic function in AIS patients with a combined anti-HTN medications and rtPA therapy.

Conclusion:
Our findings reveal specific demographic and clinical risk factors that are associated with worsening or improving neurological functions in AIS pretreated anti-HTN medications with a subsequent thrombolytic therapy. This finding suggests the development of management strategies to manage identified clinical risk factors in AIS patients pretreated with anti-HTN medications prior to thrombolytic therapy.
Abstract P078: Sex Differences In Aortic Stiffness Following Simulated Microgravity In Middle Aged Rats
Authors: Yamaleyeva Liliya M , Elsangeedy Ebrahim , Willey Jeffrey S , Pulgar Victor M
Published: September 2020

Men and women have different cardiovascular responses to spaceflight. We determined sex differences in arterial stiffness, an independent risk factor for cardiovascular dysfunction, in rats after the exposure to 14-days of simulated weightlessness via hindlimb unloading (HLU). Male and female Sprague-Dawley rats at 20 weeks of age were either tail suspended via HLU or remained full-weight bearing in similar cages. Female control rats had lower body weight compared with males. There was no significant effect of HLU on body weight in either male or female rats. Our data demonstrate that HLU increased aortic pulse wave velocity, an index of arterial stiffness, in female rats (2.7 fold vs. control female- adjusted for body weight, n=5-6), but not in males. HLU had no effect on the levels of structural proteins (alpha smooth muscle actin or myosin) in either female or male rats. The levels of G-protein-coupled estrogen receptor 1 (GPER) were lower in the thoracic aorta of female rats exposed to HLU compared with female controls (0.3±0.02 vs. 0.39±0.01 relative density, p<0.05, n=6-7); lower aortic GPER levels were associated with greater aortic media thickness (110.5±4.2 vs. 97.1±3.1 μm, p<0.05, n=5) and lower COX-2 protein levels (0.47±0.04 vs. 0.61±0.02 relative density, p<0.05, n=3-4). However, no differences in GPER, aortic media thickness, or COX-2 were observed in the aortas of male rats after HLU versus male controls. The administration of GPER agonist, G1 (400 ug/kg/day) prevented the increase in aortic pulse wave velocity in the intact females following HLU (2.2±0.2 vs. 9.7±1.8, p<0.05, n=4). Our data demonstrate sex differences in aortic stiffness in response to simulated microgravity. Since GPER has many protective actions in the cardiovascular system, a dysregulation of estrogen signaling may attenuate the protection of females from cardiovascular dysfunction following the exposure to spaceflight stressors.
Abstract P089: Assessment Of Sensorimotor Function To Establish A Clinically Relevant Animal Model Of Intracerebral Hemorrhage (ICH) Using The Hypertensive Transgenic Rat (mRen2)27
Authors: Contillo Nicholas J , Anzalone Anthony , McMullen Nathan , Peterson Keyan , Tschoe Christine , xiang zhidan , DIZ Debra I , Wolfe Stacey
Published: September 2020

Uncontrolled hypertension is the leading cause of spontaneous ICH and elevated SBP is a strong predictor of poor outcomes in ICH patients. An animal model of the chronically hypertensive, metabolically dysfunctional and pro-inflammatory state of the ICH patient population is needed to advance clinically-relevant ICH research. Transgenic (mRen2)27 rats overexpress the murine Ren2 gene and develop hypertension and metabolic syndrome by 12-14 weeks of age. Indices of diastolic and systolic cardiac function are in decline in (mRen2)27 males by 30 weeks of age, but are preserved in females at this age. To establish whether (mRen2)27 rats exhibit sensorimotor dysfunction as compared with control Sprague Dawley (SD) rats, male and female (mRen2)27 rats underwent corner turn (CT), vibrissae evoked forelimb placing (VEF), cage wire hang (CWH), and open-field (OF) testing for five consecutive weeks starting at 20-weeks of age (n=16; female=8; each strain). Despite the significant between-strain difference in SBP [189 ± 3 mmHg in (mRen2)27 and 119 ± 3 mmHg in SD; p<0.001], there were no significant between-strain differences in sensorimotor testing at weeks 20, 22, 23, and 24 (Table 1). At week 21, a significant between-strain difference was identified isolated to the VEF test (p<0.01). As sensorimotor testing is critical to assess the effect of experimentally-induced ICH in rodent models, the lack of strain differences supports the viability of (mRen2)27 rats as a clinically relevant model for the comparison of ICH superimposition in the two strains at this age without consistent baseline sensorimotor deficits.

(Cardiovascular Sci. and Hypertension & Vasc. Res. Ctrs; Neurosurgery)
Abstract P108: The Cause and Treatment of Paroxysmal Hypertension
Authors: Mann Samuel , Solanki Kaushal
Published: September 2020

Introduction:
The cause and treatment of paroxysmal hypertension (PH) (“pseudopheochromocytoma”) in the 98-99% of patients who do not have a pheochromocytoma has long been a mystery. It has been linked to a psychosomatic origin based on the finding in nearly all patients of repression of emotions associated with either a past history of overwhelming stress or trauma or a repressive coping style. The purpose of this study is to convey further experience in understanding and treating PH.

Methods:
We reviewed the medical records of patients with a diagnosis of PH. Patients were considered to have PH if episodes were sudden in onset, were unprovoked (not precipitated by stress or anxiety) and were symptomatic (e.g., headache, flushing, tachycardia and/or others). Patient characteristics, psychosocial history and response to treatment were assessed. Based on the previous study, the psychosocial characteristics examined most closely were the presence of a past history of trauma or overwhelming stress, the emotional response to that trauma, the presence or absence of a history of depression or anxiety, and the presence or absence of a repressive coping style.

Results:
Sixty-eight percent of patients (24 of 35) reported a history of trauma with repression of related emotions; a repressive coping style was evident in 26% (9 of 35). Neither characteristic was evident in only 2 patients (6%). Most patients were prescribed clonidine and/or alprazolam for acute management of paroxysms; this intervention was considered sufficient by 10 (28%). Twenty-three of the remaining 25 were offered treatment with an antidepressant. Two refused and two could not tolerate an effective dose. Of the remaining 19, 17 (89%) responded, including 10 (53%) with complete cessation and 7 (37%) with reduction in frequency of paroxysms. The disorder resolved promptly without medication in 2 patients who gained awareness of emotions long held from awareness.

Conclusions:
The psychosocial history, the marked efficacy of antidepressant agents, and the rapid cure associated with gaining of awareness of previously repressed emotions strongly support the origin of PH in repressed emotions. To date, no other cause or effective treatment has been reported.
Abstract P111: Systemic TLR4 Blockade Ameliorates Neuroinflammation & Blood-Brain Barrier Disruption In Hypertensive Rats
Authors: Mowry Francesca E , Biancardi Vinicia C
Published: September 2020

Hypertension is linked to blood-brain barrier (BBB) disruption and neuroinflammation in areas such as the hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM). We have shown that Angiotensin II (AngII) induces BBB breakdown via type 1 receptors (AT1r) and activates hypothalamic microglia
ex vivo
through AT1r and Toll-like receptor 4 (TLR4). We hypothesized that TLR4 activation is a key contributor to AngII-mediated BBB disruption, neuroinflammation, and autonomic dysfunction. Spontaneously hypertensive rats (SHR) were treated with Losartan (AT1r blocker; 20 mg/kg; oral; 4 weeks; SHR-Los) or TAK-242 (TLR4 blocker; 2 mg/kg;
i.p.
; 2 weeks; SHR-TAK), and age-matched to control SHR and Wistar Kyoto rats (WKY). Indirect tail-cuff mean arterial pressure (MAP) was normalized in SHR-Los (104 vs 100 mmHg in WKY) and reduced in SHR-TAK (129 vs 154 mmHg in SHR). During conscious baroreflex assessment, TAK-242 rescued the responsiveness of SHR baroreflex gain (ΔHR/ΔMAP;
phenylephrine:
WKY: -2.56; SHR: -1.47; SHR-TAK: -2.20;
nitroprusside:
WKY: -2.39; SHR: -0.91; SHR-TAK: -2.06). Sympathetic nervous system activity (indirect; hexamethonium) was elevated in SHR (-65 ΔMAP) versus WKY (-47 ΔMAP) and SHR-TAK (-43 ΔMAP). Microglial activation, indexed by morphological analysis of IBA1 immunofluorescence (IF), was enhanced in SHR (
PVN:
end-points [EP]: -36.1%, branch length [BL]: -26.8%;
RVLM:
EP: -41.6%, BL: -33.4% vs WKY) and normalized in SHR-Los and SHR-TAK. Elevated TNF-α IF densities in SHR (PVN: +57.9; RVLM: +58.0% vs WKY) were abolished with AT1r or TLR4 blockade. Both treatments normalized PVN IL-6 IF (SHR: +46.6% vs WKY) and reduced RVLM IL-6 (SHR: +77.4%; SHR-Los: +32.4%; SHR-TAK: +33.9% vs WKY). Increased BBB permeability in SHR, quantified by leakage of a low MW dextran-conjugated dye, was apparent in the PVN (3.619% area), RVLM (3.700% area), and nucleus tractus solitarius (NTS; 3.588% area) compared to WKY (PVN: 1.558%, RVLM: 1.572%, NTS: 1.800% area), while TAK-242 restored the barrier’s integrity in each region. Taken together, these data support a significant contribution of TLR4 activation to AngII-driven autonomic dysfunction, neuroinflammation, and BBB disruption in hypertension.
Abstract P123: Accuracy Of Hypertensive Emergency Diagnosis Code In Administrative Database: Insights From National Inpatient Sample 2017
Authors: Ansari Mohammed , Mohammed Moghniuddin , Ranka Sagar , Noheria Amit , Sheldon Seth , Reddy Madhu
Published: September 2020

Background:
Hypertensive emergency (HTNE) diagnostic code was introduced, in the US, in October 2016 to improve identification of patients with end-organ damage due to high blood pressure but its impact is unclear.

Objective:
To assess the accuracy of HTNE code using administrative data.

Methods:
We used National Inpatient Sample 2017 to identify adult patients, age ≥18 years, with International Classification of Disease-10th Clinical modification (ICD-10-CM) code of I16.1. We used the presence of end-organ damage diagnostic codes to identify true HTNE.

Results:
A total of 194,495 patients had a diagnosis of HTNE. Of these only 144,070 (74.1%) had a concomitant diagnosis of end-organ damage. Baseline characteristics of entire cohort stratified by presence of target organ damage (Table 1A) and frequency of end-organ damage in true HTNE patients (Table 1B) are shown. Patients with true HTNE were likely to be older and male with higher co-morbidity burden. There was also significant difference in outcomes between two groups with a higher proportion of true HTNE patients experiencing longer length of stay and increased mortality which is in-line with previous studies.

Conclusions:
The accuracy of hypertensive emergency diagnosis code is low with positive predictive value of 74.1% and caution is advised when using with administrative data. Further studies, using individual patient discharge records, are required to validate HTNE code.
Abstract P124: Blood Pressure Characterization In
Btg2
Mutant Rat
Authors: Hoffman Matthew , Takizawa Akiko , Jensen Eric , Schilling Rebecca , Grzybowski Michael , Geurts Aron M , Dwinell Melinda R
Published: September 2020

Hypertension (HTN) is a complex disease influenced by heritable genetic elements and environmental interactions. Dietary salt is among the most influential modifiable factors contributing to increased blood pressure (BP). It is well established that men and women develop BP impairment in different patterns and a recent emphasis has been placed on identifying mechanisms leading to the differences observed between the sexes in HTN development. The current work reported here builds on an extensive genetic mapping experiment which sought to identify genetic determinants of salt sensitive (SS) HTN using the Dahl SS rat. BTG anti-proliferation factor 2 (
Btg2
) was previously isolated by our group using congenic breeding experiments which identified it as a female causative SS HTN candidate gene. In the current study,
Btg2
was mutated using TALEN targeted gene disruption on the SSBN congenic rat background. The
Btg2
mutated rats exhibited impaired BP and proteinuria responses to a high salt diet compared to wild type littermates. Differences in body weight, mutant pup viability, skeletal morphology, and adult nephron density suggest a potential role for
Btg2
in developmental signaling pathways. Subsequent cell cycle gene expression assessment provides several additional signaling pathways that
Btg2
may function through during salt handling in the kidney. The expression analysis also indicates several upstream targets that can be explored to further isolate therapeutic approaches for SS HTN.
Abstract P125: Genes And Pathways Associated With Apparent Treatment-resistant Hypertension In Patients With Chronic Kidney Disease: An Analysis Of The Cric Study
Authors: Wang Ling , Ma Shuangtao , Cui Yuehua , Yang Yufan , Wang Donna
Published: September 2020

Patients with chronic kidney disease (CKD) have a 4-fold increased risk of developing apparent treatment-resistant hypertension (aTRH) compared with the general population. This study aimed to identify key genes and pathways associated with aTRH based on data from the Chronic Renal Insufficiency Cohort (CRIC) study. In this study, 823,094 whole-genome single-nucleotide polymorphisms (SNPs) of 3,024 patients (1,215 with aTRH defined by 2018 American Heart Association Scientific Statements and 1,809 without aTRH) were used for the analysis. First, we identified 997 significant (p<0.05) genes associated with aTRH using the SNP-set kernel association test (SKAT) analysis after controlling for race, gender, body mass index, and diabetes. The top 5 significant genes identified were NMNAT3 (p=1.2х10-4, coding for an enzyme that catalyzes nicotinamide adenine dinucleotide synthesis), SLC2A13 (p=1.4х10-4, coding for a glucose transporter), PTBP1 (p=1.7х10-4, coding for an RNA-binding protein that controls alternative splicing), IZUMO4 (p=1.9х10-4, coding for a protein that facilitates fertilization), and CCDC9 (p=1.9х10-4, coding for coiled-coil domain-containing protein 9). Next, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses based on significant genes obtained from SKAT analysis. The identified top 5 GO pathways were “Metaphase plate congression” (p=1.3х10-4), “Histone deacetylase binding” (p=1.3х10-4), “Transcription regulatory region DNA binding” (p=1.7х10-4), “Cytokine-mediated signaling pathway” (p=1.8х10-4), and “Phosphotyrosine residue binding” (p=6.6х10-4). The top 5 KEGG pathways identified were “RNA degradation” (p=1.1х10-4), “Viral carcinogenesis” (p=1.5х10-4), “PD-L1 expression and PD-1 checkpoint pathway in cancer” (p=5.2х10-4), “NF-kappa B signaling pathway” (p=6.5х10-4) and “Bacterial invasion of epithelial cells” (p=9.6х10-4). Thus, these findings may provide new insights into molecular mechanisms underlying aTRH in patients with chronic kidney disease, e.g., the NF-kappa B signaling pathway may contribute to the development of aTRH through enhanced inflammatory responses.
Abstract P135: Covid-19 And Hypertension: Pooled Analysis Of Observational Studies
Authors: Samala Venkata Vikramaditya Reddy , Gupta Rahul , Aedma Surya Kiran
Published: September 2020

Introduction:
The pandemic of COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 infection. Although clinical data is limited, studies published so far raise concerns about an association between hypertension and worse clinical outcomes in COVID-19. Our aim was to assess the association between hypertension and mortality in COVID-19 patients.

Methods:
A systematic electronic search was performed in PubMed, Embase, and Google Scholar. Retrospective studies with original COVID-19 hospitalized patient data and reporting prevalence of hypertension was included in our study. Pooled analysis using a random-effects model was performed to look at the association between hypertension and mortality.

Results:
22 studies from 8 countries with over 11,000 patients were included in our analysis. Hypertension was the most prevalent comorbidity in hospitalized COVID-19 patients (42%), followed by diabetes mellitus (23%)(Figure 1). Hypertension by itself was associated with higher rates of mortality (Figure 2). Other less prevalent comorbidities include non-hypertensive cardiovascular disease (11%), CKD (6%), CVA (5%), COPD (4.3%).

Conclusion:
Hypertension is the most prevalent comorbidity in hospitalized COVID-19 patients, followed by diabetes mellitus and was found to be significantly associated with higher rates of mortality. Surprisingly, hypertension is significantly more common than COPD in this population. The reason for this is unclear, there is no evidence currently that hypertension is directly related to mortality in this population. More randomized studies are needed to assess the effect of hypertension on mortality in COVID-19 patients.
Abstract P139: The Relationship Between Tissue Sodium Storage, Immune Cell Activation And Salt-sensitive Hypertension
Authors: Sahinoz Melis , Elijovich Fernando , Laffer Cheryl L , Pitzer Ashley , Stewart Thomas G , Ikizler Talat A , Kirabo Annet
Published: September 2020

Introduction:
Salt Sensitivity (SS) of blood pressure (BP) is an independent predictor of death due to cardiovascular disease, but its pathogenesis is poorly understood. Sodium (Na
+
) is stored in the skin and muscle interstitium. This hyperosmolar Na
+
activates monocytes
in vitro
via oxidative stress with generation of isolevuglandin (isoLG) protein adducts that are immunogenic and activate the adaptive immune system.

Methods:
Five subjects with essential hypertension discontinued all anti-hypertensive therapy for two weeks before the study. SS was assessed by an inpatient protocol of salt loading (460 mmoL/24h) and salt depletion (10 mmoL/24h, plus furosemide 40 mg x 3). Muscle and skin Na
+
contents were measured at baseline (BA) by
23
Sodium magnetic resonance imaging (
23
NaMRI). Urine and serum electrolytes, glomerular filtration rate and the % CD14
+
monocytes containing isoLG adducts using flow cytometry were obtained at BA, after salt-loading (HI) and after salt-depletion (LO). All continuous data are displayed as median (interquartile range). Spearman’s correlation was used to test associations.

Results:
Median age was 54 years (44-55), 60% of subjects were female, screening systolic BP (SBP) was 140 mmHg (134-148), diastolic BP was 88 mmHg (84-99) and BMI was 35 kg/m
2
(30-39). SBP response to salt-depletion (salt-sensitivity index, SSI) varied from -13.8 to +1.8 mmHg. %isoLG
+
CD14
+
cells were 48 (27-65) at BA, 55 (31-56) at HI, and 70 (33-72) at LO (p=0.594, by the Kruskal-Wallis test). The correlation between SSI and delta (Δ) %isoLG
LO minus HI,
was 0.86, [95% confidence interval (CI), -0.07-0.99] which may suggest conclusively as we gather more data that the greater the SSI, the larger the decrease in isoLGs by salt depletion. Muscle Na
+
content correlated with 24h urine Na
+
(BA) (r=0.90, 95% CI, 0.11-0.99), however, the correlation with BP, SSI or isoLGs was inconclusive, potentially due to the small sample size. Skin Na
+
content correlated with baseline %CD14IsoLG
+
(r=0.91; 95% CI, 0.12-0.99).

Conclusions:
Na
+
intake is a component of the determinants of muscle Na
+
. Skin Na
+
is associated with increased isoLGs in monocytes, a marker of immune cell activation. Variability in ΔCD14isoLG may serve as a biomarker for SS of BP in humans.
Abstract P142: Sex-differences In M1-like Macrophage Counts In Aortic Perivascular Adipose Tissue Precedes High Fat Diet-induced Hypertension In Dahl S Rats
Authors: Kalyana Kumar Ramya , Garver Hannah , Liamon-Thompson Erinn , Fink Gregory D , Watts Stephanie W , Rockwell Cheryl
Published: September 2020

Perivascular adipose tissue (PVAT) may connect adiposity to hypertension because of its functions and proximity to blood vessels. Immune cells in adipose tissue are proposed to couple adiposity to hypertension development in a sex-specific fashion. It is unknown if sex-differences exist in PVAT’s immune community during the onset of adiposity-induced hypertension. Both sexes of the Dahl S rat strain become equally hypertensive (table) when fed a high fat (HFD) diet. We hypothesized that both sexes have similar immune cell composition in PVAT with the development and progression of HFD-induced hypertension. Male and female Dahl S rats were fed a regular (10% calories from fat; CD) diet or a HFD (60%) from weaning. Thoracic aorta PVAT (APVAT) was harvested at 10 (pre-hypertension), 17 (onset) or 24 (chronic) weeks (w) of diet. Macrophages (subtypes), neutrophils, mast, T (subtypes), B, NK cells were measured by flow cytometry. At 10 w, HFD females had 5X the number of M1-like macrophages
vs
HFD males. At 17 w, CD females had 10X the number of M2-like macrophages
vs
CD males. At 17 w and 24 w, males had greater number of CD4 (2X) and CD8 (1.5X) memory T cells
vs
females, independent of the diet (table). In summary, sex-differences in M1-like macrophage counts in APVAT precedes the development of HFD-induced hypertension in Dahl S rats. The progression of hypertension is associated with memory T cells in males and M2-like macrophages in females. This study is foundational to understand the sex-specific roles of these immune cells in regulating vascular tone in HFD-induced hypertension, underscoring the need for novel sex-specific anti-hypertensive immune modulators.
Abstract P145: Blood Pressure De-regulation And Renal Function Are Main Determinants Of Covid-19 Mortality
Authors: Lanzani Chiara Livia , Simonini Marco , Messaggio Elisabetta , Arcidiacono Teresa , Bucci Romina , Betti Paolo , Rovere Querini Patrizia , Conte Caterina , Vezzoli Giuseppe , Manunta Paolo
Published: September 2020

Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease causing a Severe Acute Respiratory distress syndrome. In 392 consecutive COVID-19 patients hospitalized in IRCCS San Raffaele in Milan (age 67 years range 28-94, Sex M, 74,7%) from march 2 until 25 April 2020, renal function was monitored. History of Hypertension (HYP) was the main comorbidity factors (58 %) under drug medications in 86.1% (ACEi/ARB 56,5).

AKI (any stage) was detected in 6.2% of patients at emergency department (ED) admission. Baseline kidney function and HYP were the main determinants of ED-AKI (ED-AKI in HYP 89.5% vs 56.4 % in non-HYP; p=0.004) with an increased risk of 4.98 (95% CI 1.04-23.80; p=0.044) after adjustment by independent covariates, including age and respiratory distress.Moreover, MBP levels at presentation were inversely related with increased risk of ED-AKI. A stand-alone level of MBP < 86 mmHg (i.e.< 120/70 mmHg) or <65 mmHg at presentation were independently associated with increased risk of AD-AKI of 3.95 (95% CI 1.41-11.04, p=0.009) or 9.13 (95% CI 1.40-59.77; p=0.021), respectively. Nevertheless, no relationship between MBP and severity of respiratory distress was observed. No effect of any specific chronically used antihypertensive pharmacologic treatment was observed. During hospitalization AKI (H-AKI) occurred in 34.7% of patients; the median time to AKI development was 7 days (IQR 3-12 days). The incidence of H-AKI was significantly higher in elderly patients (age > 65 yrs; 42.5% vs 24.3 %, X
2
16.62; p<0.0001) or with HYP (43.4% vs 20.6 %, X
2
21.57; p<0.0001). Survival analysis showed that age over 65 years, HYP and severity of respiratory distress were main determinant of H-AKI. However, in a model of univariate Cox regression, only age above 65 years, COPD, CKD stage 3-5, HYP, MPB<86 mmHg at ED admission, and severity of illness were independently associated with twice increase of overall in-hospital mortality.In conclusion, we observed that history of Hypertension, CKD and hypotension at the presentation are important risk factor for ED-AKI and mortality in patients with COVID-19 infection. Early reduction of antihypertensive therapy if blood pressure is lower than 120/70 may decrease AKI development and mortality in COVID19.
Abstract P150: Concerted Diurnal Rhythms Of Gut Microbiota With Salt-sensitive Hypertension And Renal Damage
Authors: Mandal Juthika , Chakraborty Saroj , Cheng Xi , Galla Sarah , Hindupur Anay , Saha Piu , Yeoh Beng San , Mell Blair , Yeo Jiyoun , Kumar Matam Vijay , Yang Tao , Joe Bina
Published: September 2020

Circadian, diurnal rhythm is a vital physiological feature of life forms, which enables holobionts to adapt to the day and night cycles. Evidence suggests that both factions of the holobiont, i.e, the host and its microbiota demonstrate physiological circadian rhythms. Blood pressure is a good example of a host physiological feature with a well-defined diurnal rhythm. In a healthy human, blood pressure (BP) rises to its peak during awakening morning hours and declines to the lowest level during night. In salt-sensitive hypertension, aberrant diurnal rhythms of BP and gut dysbiosis have been demonstrated. Given the critical role of gut microbiota in BP regulation, our current objective was to investigate whether there are synchronous rhythms of holobiont in rodents on low salt and high salt diets and if inflammation pattern also changes diurnally. We examined Dahl Salt-Sensitive (S) rats on low (0.3%) and high (2%) salt diets and BP and inflammation pattern was checked. As hypothesized, both microbiota and kidney inflammation showed diurnal rhythm in response to low salt and high salt diet. Major shifts in diurnal patterns of specific groups of microbiota were observed between the dark (active) and light (rest) phases, which correlated with the diurnal rhythmicity of BP. Diurnal rhythms of Firmicutes, Bacteroidetes and Actinobacteria were independently associated with BP. Discrete bacterial taxa were observed to correlate independently or interactively with one or more of the following 3 factors- 1) BP rhythm, 2) dietary salt, 3) amplitude of BP. PICRUSt analysis revealed diurnal rhythmicity of microbial pathways, characterized by microbiota upregulated biosynthetic processes during active phase and upregulated degradation pathways of metabolites in resting phase. These diurnal changes in microbiota, their functional pathways and BP amplitude were associated with concerted rhythmicity of renal Lipocalin 2 and Kim1 expression and circulating β-hydroxybutyrate in high salt S rats. Such concerted rhythmicity of holobiont with peak of changes at active phase of salt hypertension suggests that targeting this timepoint to reshape microbiota and/or intervene with medication could efficiently benefit the hypertensives
Abstract P153: Initial Non-adherence To Antihypertensive Medications: A Systematic Literature Review
Authors: Cooke Catherine E , Xing Shan , Gale Stormi , Peters Sadie
Published: September 2020

Introduction:
An important component of hypertension management is the initiation and continuation of antihypertensive medications. Ongoing medication non-adherence is well studied. However, there is a paucity of research about the frequency and clinical consequences of failing to take the first dose of the prescribed medication, a treatment challenge known as initial medication non-adherence (IMN).

Objective:
To summarize the published evidence on the prevalence, associated factors, consequences, and solutions for IMN to antihypertensive medications in the United States (US).

Methods:
A systematic literature search was performed in Medline (PubMed) to capture publications on IMN from 2010-2019. To be included, studies must have reported results of IMN to antihypertensive medications. Studies that solely evaluated non-adult populations, employed weaker study designs (i.e., case reports/series), were not written in English, or were conducted outside of the US were excluded.

Results:
The search identified 2289 unique articles from which 15 studies were included. Estimates of the prevalence of IMN to new antihypertensive medications ranged from 5-34% (331/6393 to 269/791) of patients, and 1-48% (7160/642,376 to 10,987*/23,033) of prescriptions (n=9 studies). Results varied due to differences in study populations, data sources and whether new was defined as no prior history of the specific medication, the class or any antihypertensive. Associated with IMN were new hypertension diagnosis, lower blood pressure values, higher medication cost, non-white non-Hispanic race/ethnicity, fewer healthcare visits after prescribing, and higher co-morbid disease burden (n=3 studies). Patient-reported reasons for IMN included cost and side effect concerns (n=2 studies). One of the four intervention studies found lower IMN with a live phone call from the pharmacy compared to usual care (-6.9%, [29,106/82,373 - 841/1993], p<0.0001). No studies examined the clinical, economic, or humanistic consequences of IMN.

Conclusion:
Up to one-third of patients fail to obtain a newly prescribed antihypertensive medication. Future research is needed to document the clinical consequences and determine cost-effective approaches to address IMN.

*calculated
Abstract P161: Randomized Trial Of Magnesium Glycinate Supplementation And Blood Pressure In Middle-aged Adults
Authors: Sesso Howard D , Copeland Trisha , Coates Jennifer L , Solano Olubunmi A , Clar Allison , Roche Elise C , Chandler Paulette D , Manson JoAnn E , Rist Pamela M
Published: September 2020

Introduction:
Magnesium (Mg) intake is inversely associated with BP and hypertension risk in observational studies. However, short-term randomized trials on seated BP have been inconsistent, with few studies measuring 24-h ambulatory BP (ABP). In addition, Mg glycinate, a more easily absorbed form of supplemental Mg, has been largely untested in randomized trials and may serve as a first-line approach for BP reduction among those with elevated, untreated, BP.

Methods:
We conducted a randomized, double-blind, placebo-controlled trial (NCT03688503) testing 480 mg/d of elemental Mg glycinate versus placebo for 12 weeks among 59 otherwise healthy participants aged 30-74 y with elevated seated BP (systolic BP (SBP) 120-149 mmHg and/or diastolic BP (DBP) 80-94 mmHg) and no history of anti-hypertensive medication use. At baseline, 6 weeks, and 12 weeks, we measured seated BP, monitored 24-h ABP, and collected blood samples. Our primary aim tested Mg glycinate on 12-week changes in seated BP and 24-h ABP, and subgroup analyses considered if sex, age, or baseline BP modified the effect of Mg on BP.

Results:
Baseline characteristics were equally distributed at randomization (mean age, 57.2 y; 58% men) with mean seated BP of 133.4/82.6 mmHg. Compliance was high (Mg, 87%; placebo, 96%). After 12 weeks, there was no significant effect of Mg glycinate versus placebo on seated SBP (-4.5 vs -1.6 mmHg from baseline; p=0.38) and DBP (-1.9 vs -0.9 mmHg from baseline; p=0.64), nor was there any significant effect on overall, daytime, or nighttime 24-h ambulatory SBP and DBP (all p>0.05). In subgroup analyses, the effect of Mg glycinate on seated SBP was suggestively, but non-significantly, stronger among those with baseline seated SBP ≥130 mmHg (-9.3 vs -2.7 mmHg; p=0.12; p, interaction=0.24) and among women (-9.7 vs -3.1 mmHg; p=0.26; p, interaction=0.29). Age, seated DBP, and mean 24-h ambulatory SBP and DBP did not modify the effects of Mg supplementation.

Conclusions:
A Mg glycinate supplement did not significantly reduce seated or 24-h BP in adults with elevated, untreated BP. Forthcoming analyses will expand on the role of serum and dietary Mg levels. Larger trials are warranted to elucidate possible effects of Mg glycinate on seated SBP among those with elevated BP and among women.
Abstract P163: Blood Pressure Checks And Diagnosing Hypertension: Provider Knowledge, Beliefs, And Practices
Authors: Green Beverly , Anderson Melissa L , Cook Andrea J , Ehrlich Kelly , Hall Yoshio N , Hansell Laurel D , Hsu Clarissa , Joseph Dwayne , Margolis Karen L , McClure Jennifer B , Munson Sean A , Thompson Matthew J
Published: September 2020

Context:
The US Preventive Services Task Force recommends out-of-office blood pressure (BP) measurement before making a new diagnosis of hypertension, using 24-hour ambulatory (ABPM) or home BP monitoring. However, this approach is not common in routine practice.

Objective:
To evaluate provider knowledge, beliefs, and practices about BP diagnostic tests

Methods:
The setting was 10 primary care medical centers in a single health care system. E-mails with a link to a survey were sent to 420 providers, with 282 (67%) responding, including 102 medical assistants (MA), 28 licensed practical nurses (LPN), 33 registered nurses (RN), 86 primary care physicians (physician), and 33 advanced practitioners (AP). Outcomes were a descriptive analysis of provider BP measurement and hypertension diagnosis knowledge, beliefs, and practices.

Results:
Most providers (78.8%) believed that BP measured manually with a stethoscope and ABPM as very or highly accurate way to measure BP when making a new diagnosis of hypertension. In contrast, most providers did not believe that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate. Almost all providers reported that they always or almost always relied on clinic BP measurements in making a new diagnosis of hypertension (95.7%), but the majority of physician/APs would prefer using ABPM (60.5%) if it was readily available. Providers were mixed as to whether patients received home BP training and whether home BP monitors were checked for accuracy. Physician/APs reported varying home BP schedules with no schedule the most common response (37.3%), followed by 14 days (19.1%), and 7 days (10.9%). Almost all physicians/APs reported using a clinic BP threshold of 140/90 mmHg for making a new diagnosis of, but a few reported 130/80 mmHg. Very few physician/APs reported guideline concordant home or ABPM diagnostic thresholds, with 140/90 mmHg the most common response.

Conclusion:
In our study providers did not report following evidence-based guidelines for making a new diagnosis of hypertension, and appeared to have substantial gaps in knowledge, beliefs, and use of recommended practices. Interventions to increase use of evidence-based practices for diagnosing hypertension are needed.
Abstract P166: Sex And Age Differences In Ambulatory Blood Pressure Monitoring Tolerability
Authors: Khaddage Sarah , Patterson Julie , Dixon Dave L
Published: September 2020

Background:
Recent guidelines endorse the use of ambulatory blood pressure monitoring (ABPM) for out-of-office BP measurement and HTN management. Past literature has described patient perceptions of ABPM tolerability but differences between sex and age have not previously been determined. The objective of this study was to evaluate sex and age differences in such patient perceptions.

Methods:
This was a prospective, single-arm trial (NCT03920956) of a community pharmacy-driven ABPM service that enrolled 52 patients at least 18 years of age who were suspected of having white coat, masked, or sustained HTN, have symptoms of hypotension, or require confirmation of an initial diagnosis of HTN. We evaluated the tolerability of the ABPM device (Oscar 2; SunTech Medical, Morrisville, NC) as a secondary outcome with a previously published 8-question survey using a 0-10 scale (0=not at all, 5=somewhat, 10=extremely). The responses were dichotomized as either favorable (0-4) or unfavorable (5-10) with reverse coding for positively-worded questions. Descriptive statistics and Chi-square analyses were used to describe sex and age differences.

Results:
A total of 50 surveys (96%) were completed and returned. Respondents were 50% female (n=25) with a mean (SD) age of 57.5 (15.8), and 58% (n=29) were at least 55 years of age. Female respondents were more likely to find the monitor cumbersome to wear at times other than at home, work, or driving (16/21, 76.2% vs. 10/25, 40%, p = 0.014). Although nonsignificant, male respondents were more likely to find the monitor embarrassing to wear (7/25, 28.0% vs. 2/24, 8.3%, p = 0.076). In comparisons of tolerability by age, subjects less than 55 years of age were more likely to report being disturbed by the pump during driving (8/21, 38.1% vs. 1/24, 4.2%, p = 0.005), at other times (7/20, 35.0% vs. 2/24, 8.3%, p = 0.029), and found the monitor embarrassing to wear (7/21, 33.3% vs. 2/28, 7.1%, p = 0.019).

Conclusions:
Previous studies suggest that ABPM is generally well-tolerated by patients but may cause some discomfort or disturbed sleep. Differences in tolerability appear to become more evident across age groups and sex. These data suggest select patients may require additional counseling and education to ensure adherence to ABPM.
Abstract P167: Leveraging The Electronic Health Records System And Home Blood Pressure Monitoring To Optimize Blood Pressure Control
Authors: Kim Elizabeth H , Luong Eric , Nguyen Trevor Trung , Castillo Sandy , Ebinger Joseph E , Cheng Susan
Published: September 2020

Background:
Home blood pressure monitoring (HBPM) devices can now be linked to electronic health records (EHR) systems in ways that could be used to facilitate blood pressure (BP) management; however, their potential feasibility and utility remain unclear.

Methods:
For our pilot study, we identified N=5 outpatients with uncontrolled hypertension and implemented use of a HBPM device with frequent monitoring and direct linkage to the EHR, whereby real-time data was made available to treating providers. We matched our intervention patients by age and sex with N=50 patients who also had uncontrolled hypertension and underwent standard-of-care treatment. We assessed change over time in BP measures for the intervention and standard-of-care groups.

Results:
In analyses accounting for differences in the timing and frequency of BP measurements, we observed that the intervention compared to the standard-of-care group had an average systolic BP at 8 weeks that was lower in percent change from baseline (β=-22 mm Hg, P=0.008). We also found a difference between baseline and 8-week systolic BP within the intervention group (mean difference -25.9 mm Hg, P=0.024).

Conclusions:
In our pilot, intensive remote HBPM appeared to improve BP levels over the short term. While unblinded and not controlled for factors beyond age and sex, this pilot demonstrates feasibility of an EHR-linked HBPM intervention and potential efficacy that may be related to increased patient as well as provider awareness translating to greater patient-provider engagement around hypertension management. More studies are needed to validate and expand from our findings.
Abstract P171: The Intermediate Korotkoff Sounds: Variation In Sound Proportions In Different Age Groups Of Men And Women In A Healthy Adult Population
Authors: OBrien Jim , Mohammedzein Assad , caples norma , Cronin Edel , Walshe Martin , Walsh Philip , Owens Patrick
Published: September 2020

There are 5 known Korotkoff sounds which occur during a standard blood pressure (BP) measurement cycle, the first 4 (K1 to K4) having specific acoustic signatures, and the fifth (K5) occurring where sound first becomes absent. The different Korotkoff sound proportions (KSPs) are not well understood. Using bespoke acoustic analysis technology, we compared KSPs (K1P, K2P, K3P, K4P) in normotensive men and women at different ages and described the effect of normalising the cuff deflation rate (CDR) to allow 60 heart beats (CDR
60
) versus a standard 3mmHg/s (CDR
3mmHg
). At a CDR
3mmHg
, men had a higher K2P (36% vs 26%, p=0.006) and lower K3P (27% vs 38%, p=0.002) than women. K3P significantly increased with age in both men (p<0.001) and women (p<0.004). CDR
60
caused a significant drop in K2P (p<0.001) and rise in K3P (p=0.019). These differences may reflect changes in vascular stiffness which may vary with gender, age and CDR. To our knowledge, this phenomenon has never been described before and requires further investigation.
Abstract P174: Value Of Six Minute Walk Test In The Evaluation Of Children With Elevated Blood Pressures
Authors: Pearson Kelsey , Hanevold Coral , Carlin Kristen , Baker Amanda , Flynn Joseph T , Halbach Susan
Published: September 2020

Lifestyle modifications, a mainstay of hypertension (HTN) therapy, include recommendations for regular physical activity. However, fitness is not typically assessed. In the HTN clinic at Seattle Children’s, we conduct the 6-minute walk test (6MWT) in children
>
6 yrs referred for HTN. We sought to assess whether children referred for HTN underperform on the 6MWT.

Methods:
We performed a retrospective chart review of patients seen from 9/1/18 - 9/30/19 who completed an ambulatory blood pressure monitor (ABPM) and 6MWT. Chart review included ABPM results, age, sex, BMI z-score, self-reported physical activity (RepPA) levels, rating of perceived exertion (RPE) and comorbid conditions. Exclusion criteria included lack of ABPM, 6MWT or compromised exercise capacity. ABPM was classified according to the 2014 AHA guidelines and 6MWT was compared to normative datasets. Fisher’s Exact test was used to compare the distributions of distance from mean values for the 6MWT and ANOVA was used to compare mean BMI z-score and RPE among groups. Linear regression assessed 6MWT with HTN status, adjusted for age, sex, and BMI z-score.

Results:
Demographics and clinical measures are summarized in Table 1. RepPA, 6MWT and RPE did not differ significantly. Most children underachieved regardless of group; the distance walked was
>
2 SD
below
mean in 31 of 52 (60%). BMI z-score was significantly higher in the abnormal ABPM group. Linear regression showed no effect of HTN status.

Conclusion:
Most children underperformed on the 6MWT and results did not differ based on HTN status. This study suggests the 6MWT is useful to assess fitness in this population and serves as baseline for comparison.
Abstract P179: The Magnitude, And Not Direction, Of Blood Pressure Change Influences The Risk Of Serious Adverse Events In SPRINT
Authors: Buhnerkempe Michael , Prakash Vivek , Botchway Albert , Adekola Oritsegbubemi , Flack John M
Published: September 2020

Background:
The landmark Systolic Blood Pressure Intervention Trial (SPRINT) showed that more intensive systolic blood pressure treatment (SBP < 120 mm Hg) was associated with lower risk for cardiovascular events and mortality but higher risk for serious adverse events (SAEs). However, it is unclear if the magnitude and/or the direction of the BP change determines SAE risk. In this study, we aim to determine how the magnitude and direction of BP change impacts SAE risk.

Methods:
This is a secondary analysis of 7922 participants in SPRINT. Time-varying Cox proportional hazards models were used to explore the relationship between visit-to-visit BP change and SAE risk. BP change was categorized using five intervals: 1) decreases ≥30 mm Hg, 2) decreases 10-29 mm Hg, 3) increases or decreases <10 mm Hg (reference category), 4) increases 10-29 mm Hg, and 5) increases ≥30 mm Hg. Additional variables adjusted for in the model included: age, gender, race, estimated glomerular filtration rate, treatment group, and baseline atherosclerotic cardiovascular disease (ASCVD) risk. Hypotension was excluded as an SAE to prevent bias in SAE risk in the large BP decrease category.

Results:
The hazard ratio (HR) for SAEs compared to the minimal BP change category was greatest for BP increases above 30 mm Hg (HR = 1.62, 95% confidence interval [1.30, 2.01]). However, the HR was similar for sharp BP decreases over 30 mm Hg (HR = 1.52 [1.23, 1.87]). Milder BP increases and decreases were associated with lower SAE risk (HR = 1.18 [1.06, 1.32] and HR = 1.10 [0.98, 1.22] for BP changes 10 to 30 mm Hg and -30 to -10 mm Hg, respectively). There were no significant interactions between BP change, intensive treatment, and baseline ASCVD risk.

Conclusions:
SAE risk was similar for similarly sized increases and decreases in BP between visits, with higher magnitude changes associated with higher SAE risk. When accounting for the magnitude of BP change, no significant effect of intensive treatment or baseline ASCVD risk was found.
Abstract P189: Long-term Blood Pressure Variability And Risk Of Cardiovascular Disease Events Among Community-dwelling Elderly
Authors: Ernst Michael E , Chowdhury Enayet K , Beilin Lawrie , Margolis Karen L , Nelson Mark R , Wolfe Rory , Tonkin Andrew , Woods Robyn L , McNeil John J , Reid Christopher M
Published: September 2020

Greater blood pressure variability (BPV) in midlife increases risk of future cardiovascular disease (CVD) events, but the impact of BPV in adults who have reached older ages while remaining free of CVD is unknown. We examined risk of overall incident CVD, ischemic stroke subgroup, and all-cause mortality associated with long-term, visit-to-visit BPV in participants of the ASPirin in Reducing Events in the Elderly study, a randomized primary prevention trial of daily low-dose aspirin in community-dwelling adults in Australia and the United States (US) aged 70 and older (65 if US minority) without evidence of CVD. The mean of three blood pressures (BP) using an automated cuff was recorded at baseline and annually. CVD was a prespecified composite secondary endpoint of ASPREE, and included fatal coronary heart disease, nonfatal MI, fatal or nonfatal stroke, or hospitalization for heart failure. All CVD events were adjudicated as part of the main trial. This analysis included participants who survived without CVD to the second annual visit and had BP recorded at baseline, years 1 and 2 (n=16,482). BPV was defined as within-individual standard deviation of mean systolic BP across these visits. Cox proportional hazards regression adjusting for confounders was used to calculate hazard ratios (HR) according to tertile of estimated BPV, with year 2 as time zero to minimize immortal time bias. Our results (Table) show that higher visit-to-visit BPV in older adults without previous CVD is associated with increased risk of future CVD events, ischemic stroke, and all-cause mortality, suggesting that BPV in older ages should be considered a potential therapeutic target for CVD risk-lowering.