bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUSTAINABILITY OF BLOOD PRESSURE REDUCTIONS AT INTERVENTIONS LED AT BARBERSHOPS: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS
Authors: Muruganathan A. , Rader Florian , Blyler Ciantel , Vijayaraghavan Krishnaswami , Maheshwari Anuj , Verma Narsingh , Mubarak Mr , Das Mk , Mohanan Pp , Mishra Sundeep , Mehta Ashwani 
Published: April 2021

Objective:
Novel approaches are required in order to detect and manage hypertension in low and middle-income countries. One model is by using barbershops as a contact platform to engage with patients on a regular basis. We explored the evidence for the contemporary role of barbershop led interventions to manage hypertension in community setting, by only including randomized controlled clinical trials (RCCTs)

Design and method:
We searched Cochrane Library, pubmed- MEDLINE, IndMED online databases to conduct a systematic review of the published RCCTs. Studies with non-barbershop led, generalised community-based setting approaches were excluded by using the Boolean operators. Graphpad was utilised for statistical analysis

Results:
The results yielded four clinical trials of which three met inclusion criteria, published in last 10 years (2011 to 2019). The parameters were analysed for the study design, patient characteristics, impact factor of the journals, duration, and outcomes. Cumulatively, 1826 subjects (mean 609 subjects, SD ± 367, SEM ± 212, minimum 319, maximum 1022, range 703, 95% CI -304 to 1521, p = 0.103 NS) have been evaluated across three RCCTs. The cumulative duration of the trials was 32 months (mean 11 months, SD ± 1.2, SEM ± 0.67, minimum 10, maximum 12, range 2, 95% CI 7.8 to 13.5, p = 0.0039). The baseline systolic BP of upto 140 mm Hg has been the uniform enrolment criteria. Based on the impact factor of the journals (mean 31, SD ± 35, SEM ± 20, minimum 2.8, maximum 71, range 68, 95% CI -56 to 119; p = 0.26 NS), we formulated an indexed weightage score (mean 100, minimum 9, maximum 225, SD ± 112, SEM ± 65, range 216, 95% CI -178 to 378, p = 0.26 NS). The patients who were treated with specialists, received more BP medication and different classes of medication than those treated by primary care physicians and BP reduction was 21 mmHg (p < 0.0001)

Conclusions:
Barber based intervention model have demonstrated to be a feasible connect between the patients and healthcare providers resulting in sustained BP reductions in the community, especially when care linkage to hypertension specialists can be achieved
LONGITUDINAL CHANGE IN RENAL DYSFUNCTION BIOMARKERS PREDICT OUTCOME DIFFERENTLY IN HYPERTENSIVE AND NORMOTENSIVE PERSONS FROM THE GENERAL POPULATION. THE TROMSØ STUDY
Authors: Solbu Marit Dahl , Melsom Toralf , Norvik Jon Viljar , Eriksen Bjørn Odvar , Eggen Anne Elise , Løchen Maja -Lisa , Zykova Svetlana N. , Jenssen Trond Geir 
Published: April 2021

Objective:
Serum uric acid (SUA), urinary albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) are associated with hypertension and adverse cardiovascular (CV) outcome. Little is known about outcome after longitudinal changes in these biomarkers. We aimed to assess the associations between seven years’ change in these renal biomarkers and the incidence of CV disease and mortality in hypertensive and normotensive individuals from the general population.

Design and method:
We included all participants with measurements of SUA, eGFR and ACR in survey 4 (1994/95) and 5 (2001/02) of the Tromsø Study. Hypertension at baseline (1994/95) was defined as systolic blood pressure (BP) >  = 140 mmHg, diastolic BP > = 90 mmHg and/or antihypertensive drug use. We used Cox regression to examine the associations between seven years’ > = 25% increase in SUA and/or ACR, and/or annual eGFR decline of > = 3 mL/min/1.73 m2, and myocardial infarction (MI), ischaemic stroke (IS) and all-cause mortality. Multivariable models adjusted for baseline CV risk factors, changes in systolic BP and body mass index were run separately in hypertensive and normotensive subjects

Results:
Of the 4663 participants included, 59% had hypertension. At baseline, mean age was 58.3 (9.8) years, eGFR 94 (13) mL/min/1.73 m2, SUA 310 (89) μmol/L and median ACR 0.53 (0.36, 0.87) mg/mmol. Between the 2001/02 visit and 31.12.2013, 479 persons suffered from MI, 394 IS and 1296 died. Increase in ACR > = 25% was associated with MI in normotensive (HR 2.09; 95% CI 1.47, 2.98), but not hypertensive subjects. Change in ACR, SUA or eGFR was not associated with IS. All three variables were associated with all-cause mortality in hypertensive, but not normotensive subjects. However, the association between SUA and death was no longer significant when adjusted for ACR and eGFR change.

Conclusions:
Increasing ACR was a risk factor for MI in normotensives, whereas increasing ACR and rapid eGFR decline predicted mortality in hypertensive individuals. Change in different biomarkers of kidney dysfunction may reflect different pathophysiological processes. Further research is needed to determine whether change in renal biomarkers may be useful in follow-up of hypertensive and normotensive persons.
REMAINING CARDIOVASCULAR RISK MARKERS IN PARTICIPANTS WITH WHITE-COAT HYPERTENSION DIAGNOSED BY HOME BLOOD PRESSURE RECORDINGS
Authors: Johansson Martina , Ström Edvin , Östgren Carl Johan , Engvall Jan , Wijkman Magnus , Nyström Fredrik 
Published: April 2021

Objective:
White coat hypertension (WCH) is defined as having hypertensive blood pressure in the office but normal ambulatory or home blood pressure (HBP) levels. The cardiovascular prognosis in WCH is controversial. Some studies have demonstrated it to be a benign condition while others have linked it to possible health complications. The objective for this study is to evaluate remaining cardiovascular risk markers in WCH patients by analyzing interactions of WCH with metabolic factors, calcium score, pulse wave velocity (PWV) and carotid plaques in a large, randomly selected population-based cohort.

Design and method:
BP was measured in both clinic and at home in 5057 middle-aged participants. HBP was measured morning and evening for 7 days except for the first day in which the morning was spent in the clinic. WCH was defined as having a systolic OBP > = 140 mmHg and/or diastolic BP > = 90 mmHg while HBP systolic BP < 135 and diastolic BP < 85 mmHg. In some calculations WCH was lowered to HBP < 125/ < 75 mmHg. Normotensive BP was defined as OBP < 140/ < 90 and HBP < 135/ < 85. Blood tests, computer tomography (CT) scanning of the abdomen, coronary arterial angiography, arterial PWV, cardio-thoracic imaging and ultrasonography of the carotid arteries was performed. In addition, all participants filled out extensive electronic lifestyle questionnaires and this information was also accounted for. Independent t-tests were used for all calculations and to compare normotensives (NT) and WCH with the two different cut-offs, against known risk factors.

Results:
All tests showed significant signs of more metabolic and cardiovascular damage for WCH patients compared to normotensives, even with the stricter WCH definition (see table 1 and 2). Calculations from questionnaire data showed that normotensive women scored lower on a scale designed to measure nervousness than women with WCH (p = 0.022) and men with WCH reported a higher alcohol consumption than men with normal BP (0.012)

Conclusions:
Available data suggests that excessive BP reactivity limited to the doctor's office with stricter than usual definitions pose as a cardiovascular risk marker and that these patients probably could benefit from dedicated treatment.
SERUM CHLORIDE AND ADVERSE CARDIOVASCULAR RISK IN THE WEST OF SCOTLAND GENERAL POPULATION
Authors: McCallum Linsay , Lip Stefanie , Padmanabhan Sandosh 
Published: April 2021

Objective:
To examine the association between serum Cl- and cardiovascular and non-cardiovascular morbidity and mortality outcomes in the West of Scotland general population.

Design and method:
Patients aged > 18 years resident in NHS Greater Glasgow and Clyde who had serum Cl- measured at baseline were included in the study. The study was approved by NHSGGC Local Privacy Advisory Committee (LPAC) (GSH/16/CA/012). Baseline defined as: first serum Cl- taken outwith one-month of an acute hospital admission or one-month post discharge and in the absence of prescription for diuretic therapy in the previous 3 months or serum sodium < =125 or > = 150 mmol/L; serum creatinine > 125 micromol/L. ICD-10 codes were used to characterise diagnosis and cause of death. Primary outcomes were a composite of fatal/non-fatal events for each specified outcome: all CV events, MI, IHD, heart failure, all stroke, stroke subtypes, PVD, cardiac dysrhythmia, COPD, asthma pneumonia/influenza, chronic liver disease, diabetes, kidney disease. The study population were divided into ten groups based on serum Cl- (< = 99,100–101.9,102–102.9,103–103.9,104–104.9,105–105.9,106–106.9,107–107.9,108–110.9 > = 111mmol/L). Outcomes assessed using Cox-PH models. Model 1 was adjusted for age and sex. Model 2–6 for age, sex, and variables including prevalent cardiovascular disease, prevalent diabetes, Scottish Indices of Multiple Deprivation (SIMD), serum Na+, serum bicarbonate, total cholesterol.

Results:
The study population contained 519,957 patients with serum Cl- measured at baseline. The population were 50.6 (17.7) years old; 43.5% were male; 9% had diabetes at baseline and 3.8% had a history of cardiovascular disease. One third (33.4%) of the population resided in an area within the SIMD quintile 1. There was a ’U’-shaped non-linear association between serum Cl- and risk of fatal/non-fatal events. The results from Model 1 are presented in Figure 1. The greatest risk was seen in groups 1–3 (Cl- < 103mmol/L) and groups 8–10 (Cl- > 106mmol/L) compared with group 6 (Cl- 104–105mmol/L) for all CV events, MI, heart failure, PVD, all stroke, ischaemic stroke, COPD, pneumonia/influenza, liver disease and kidney disease.

Conclusions:
In a large general population from the West of Scotland, there was a ’U’-shaped non-linear association between serum Cl- and risk of fatal/non-fatal CV and non-CV events.
NOX5 AND VASCULAR SIGNALLING IN HUMAN HYPERTENSION
Authors: Camargo Livia , Montezano Augusto , Hussain Misbah , Wang Yu , Zou Zhiguo , Rios Francisco , Awan Fazli , Touyz Rhian 
Published: April 2021

Objective:
Nox5, a key ROS-generating oxidase in human vessels, regulates vascular contraction and is implicated in vascular damage. However molecular mechanisms regulating vascular Nox5 are elusive. We questioned the role of Nox5 in vascular smooth muscle cell signalling in hypertension.

Design and method:
Intact small arteries and vascular smooth muscle cells (VSMC) isolated from small arteries from normotensive (NT) and hypertensive (HT) subjects were studied. Nox5 expression and phosphorylation (western blot, immunoprecipitation); ROS generation (chemiluminescence); protein oxidation (oxidised peroxiredoxin/DJ-1), activation of signalling pathways (Src, PKC, MLC phosphorylation; immunoblotting), and actin cytoskeletal organization (phalloidin staining) were assessed in the absence and presence of Nox5 inhibition (mellitin, 100 nM). To exclude Nox1–4 effects, we used p22phox silenced VSMCs (siRNA).

Results:
Nox5 expression was increased in intact arteries from HT subjects (70 + 26.79% vs NT, p < 0.05). In VSMC, ROS levels (139 ± 27% vs NT, p < 0.05), and oxidation of peroxiredoxin (201.8 + 40.34% vs NT, p < 0.05) and DJ-1 (71.7 + 16.51% vs NT, p < 0.05) were increased in HT. Nox5 expression (103 ± 23% vs NT, p < 0.05) and phosphorylation (77 + 17.93% vs NT, p < 0.05) were increased in the HT group. Nox5 inhibition reduced Ang II-induced ROS generation in both groups (p < 0.05 vs Ctl). In contrast, p22phox silencing increased ROS in both groups, an effect blocked by mellitin (p < 0.05 vs Ctl). Nox5 associates with c-Src. Treatment with a Src inhibitor (PP2, 10 μM) did not reduce Nox5 phosphorylation. Furthermore, PP2 failed to reduce AngII-induced ROS generation in p22phox-silenced VSMCs. Nox5 inhibition reduced Ang II-induced c-Src activation (p < 0.05 vs Ctl), suggesting that Nox5 is upstream of c-Src. Next, we investigated the role of Nox5 in vascular signaling. In cells from hypertensive subjects, p22phox silencing was associated with sustained Ang II-induced PKC and MLC20 phosphorylation, an effect blocked by mellitin and PP2 (p < 0.05 vs Ctl). VSMC from hypertensive subjects had an increased number of stress fibres, which was attenuated by mellitin and PP2.

Conclusions:
Our findings demonstrate that in human hypertension Nox5 is upregulated. This is associated with activation of c-Src, increased redox-sensitive signalling and VSMC cytoskeletal reorganisation. We define a novel Nox5-ROS-c-Src signalling pathway that may play a role in vascular remodelling in hypertension.
ROLE OF INHIBITION OF CGMP-DEPENDENT PROTEIN KINASE (PKG) SIGNALLING ON ANTICONTRACTILE FUNCTION OF PERIVASCULAR ADIPOSE TISSUE
Authors: Rosei Claudia Agabiti , Rossini Claudia , De Ciuceis Carolina , Porteri Enzo , Brami Valeria , Nardin Matteo , Chiarini Giulia , Petelca Alina , Coschignano Maria Antonietta , Tiberio Guido Alberto , Muiesan Maria Lorenza , Rizzoni Damiano 
Published: April 2021

Objective:
Perivascular adipose tissue (PVAT) has an anticontractile effect.This capacity is lost in obesity (Circulation 2009) through adipocyte hypertrophy, leading to hypoxia, inflammation and oxidative stress. It has been previously demonstrated that cGMP-dependent protein kinase (PKG) plays a key role in regulating normal PVAT function (Cardiovasc Res. 2014). Aim of the study was to investigate functional responses of small resistance arteries with and without PVAT in normotensive subjects and obese patients, testing the effects of DT-2,(a peptidic highly selective inhibitor of PKG) on contractile response

Design and method:
We have investigated 9 normotensive severely obese patients (Obese) and 6 hypertensive severely obese patients (Obese-Hyper) undergoing bariatric surgery, as well as 7 normotensive lean subjects (CTRL) undergoing an election surgical intervention.No sign of local or systemic inflammation was present in any subject or patient. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph. A concentration-response curve to noradrenaline (NA, from 10–9 to 10–5Mol/l) was evaluated in vessels with intact prerivascular fat tissue (WF)and in vessels in which perivascular fat tissue was removed (NoF). Concentration response to NA was repeated in small arteries WF and NoF in the presence of DT-2 (125 nM) in both normoxic and hypoxic (95% N2/5%CO2 for 30’)conditions

Results:
In normoxic conditions the presence of PVAT reduced contractile response to NA in small arteries from CTRL (ANOVA p = 0.04 vs. NoF). The anticontractile effect of PVAT completely disappeared in Obese and Obese-Hyper patients. In CTRL preincubation with DT-2 lead to increase contractile responses to NA in arteries WF (ANOVA p = 0,04 WF+DT-2 vs WF). This effect was more evident during hypoxic conditions after incubation with DT-2 in all groups. No significant effect was observed on contractile response to NA in arteries WF and NoF from Obese and Obese-Hyper patients after incubation of DT-2, in normoxic conditions

Conclusions:
The anticontractile effect of PVAT is present in normotensive subjects and it is lost after inhibition of PKG signalling. The absence of effect after preincubation of DT-2 on arteries WF from Obese and Obese-Hyper patients suggests a dysregulation of PKG signalling pathways in these groups, which seems essential for its downstream dilator function in small resistance arteries
ROSTAFUROXIN RESTORES THE INCREASED PERIVASCULAR INNERVATION IN RESISTANCE ARTERIES OF HYPERTENSIVE RATS
Authors: de Paula Ricardo Bernardino , Rossoni Luciana Venturini 
Published: April 2021

Objective:
Ouabain (OUA) inhibiting Na+, K+-ATPase (NKA) activity modulates neurotransmitter release from perivascular innervation (PVI). However, the role of OUA on PVI through NKA/cSRC signalosome pathway is unknown. Thus, we investigated the role of rostafuroxin (ROSTA) treatment, an OUA signalosome pathway antagonist, on PVI of mesenteric resistance arteries (MRAs) from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats, mainly on sympathetic and nitrergic PVI participation.

Design and method:
Five-week after DOCA-salt treatment, rats were allocated into two groups: DOCA-salt treated with ROSTA (1 mg/kg per day gavage, 3 weeks) or vehicle. Male, Wistar rats uninephrectomized were used as normal control (NC). Systolic blood pressure (SBP) was measured weekly by tail-cuff method. Electric field stimulation (EFS), noradrenaline (NA) and sodium nitroprusside (SNP) response-curves were evaluated in isolated MRA without endothelium.

Results:
ROSTA treatment decreased SBP (42%) compared to DOCA-salt. EFS induced contractile response in MRAs of all groups, while this response was higher in DOCA-salt compared to NC or ROSTA group. EFS-induced contraction was reduced in the presence of alfa-adrenoceptor antagonist (phentolamine, PNT) in all groups, whereas this contractile response was blocked by the association between PNT and suramin (P2-purinergic receptor antagonist) only in NC and ROSTA groups. L-NAME enhanced the contraction induced by EFS; however, this effect was smaller in DOCA-salt rings compared to NC and ROSTA. EFS-induced contraction was abolished in MRAs preincubated with tetrodotoxin (voltage-dependent sodium channel blocker). On the other hand, concentration–response curves to exogenous NA and SNP were unmodified among groups.

Conclusions:
ROSTA treatment was able to reduce perivascular sympathetic innervation and to increase nitrergic innervation on the contractile response to EFS in MRAs of DOCA-salt rats. These modifications might contribute to the beneficial effects of OUA/NKA/cSRC pathway antagonism on volume-dependent hypertension.
HYPERTENSION, AUTONOMIC DYSFUNCTION AND SUDDEN DEATH RISK IN CADASIL DISEASE: NOVEL DATA
Authors: Kotliar Carol , Obregon Sebastian 
Published: April 2021

Objective:
Sudden death (SD) is the first cause of mortality in CADASIL disease (CD)(Cerebral Autosomic Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). An early development of cardiac autonomic neuropathy (CAN) in the pathogenesis of CD was demonstrated by others. As we detected hypertension in members of 4 families of this rare condition we decided to explore the imbalance of the autonomic nervous system as a potential tool for the prediction of SD risk.

Aims:
to explore the relationship between hypertension and CAN in CD.

Design and method:
We included 10 hypertensive (officce and 24 hs ABPM) patients with CD. Autonomic function was evaluated by the study of heart rate variability (HRV) and Ewing test (handgrip, inspiration/espiration, valsalva manouver and orthostatism). CAN stages were determined as as subclinical, early and advanced.

Results:
CD patients were classified as hypertensives (n:5), or normotensives. Table 1 showed hypertensives subjects characteristics and the distribution of CAN. The control group was constituted with patients with CD and arterial normotension (n:5), the study of HRV and Ewing Test being normal in them. No association was observed between the number and extent of brain lessions, location, impact of white matter with the presence of hypertension. The prevalence of CVRF was similar between both groups.

Conclusions:
Autonomous alterationwas identified in 80% of hypertensive patients with CADASIL disease in our population sample. This association would be independent of traditional CVRF, and the evolutionary characteristics of brain lesions. Although hypertension has not been reported elsewhere as associated with CD, its identification could indicate the risk of autonomic nervous system involvement in these patients. The relevance of their suspicion would reside in the risk re-stratification of cardiovascular events with a focus on the risk of sudden death, linked to the NAC. The limitation of the reduced number of subjects requires the analysis of this hypothesis in a larger population sample, the present being a proof of concept that could justify the development of a survey work in other centers that report cases of this rare disease.
NEW STROKE RISK SCORE FOR PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Minushkina Larisa , Brazhnik Victoria , Zubova Ekaterina , Chichkova Marina , Hasanov Nyaz , Kosmacheva Elena , Zateyshchikov Dmitry 
Published: April 2021

Objective:
The study aimed to analyze the possible association of clinical factors with the development of strokes in patients after acute coronary syndrome (ACS).

Design and method:
1843 ACS pts from the 4 PCI centers were included in ORACLE II (ObseRvation after Acute Coronary syndrome for deveLopment of trEatment options) observational multicenter study (NCT04068909 ClinicalTrials.gov) in 2014–2017 years. Mean age 64,9 years, 1149 (61,9%) man. The primary end-point was all-cause death. Ischemic stroke was one of the secondary end-points. We collected data about unfavorable outcomes on 25, 90, 180 and 360 days after hospital discharge. We also control blood pressure (BP) on the day of discharge and at all follow-up visits.
Visit-to-visit BP variability was expressed as the CV (%) of mean BP across all visits during the follow-up.

Results:
We fixed 42 stokes during the follow-up (2,3%). 25 strokes were fatal. Patients with stroke during the follow up were older (70,9 ± 11,88 and 64,7 ± 12,72, p = 0,01), had higher blood pressure visit to visit variability (CV 25,3 ± 4,25 and 12.7 ± 3,67%, p = 0,019). These patients more frequently had arterial hypertension (100% and 88%, p = 0,017) and lower rate of achievement target blood pressure (35,7% and 62,7%). Patients with stroke had higher rate of atrial fibrillation (38,1% and 16,9%), heart failure (83,3% and 49,6%), peripheral atherosclerosis (47,6% and 25,4%), CKD (64,3% and 36,7%), IGT (17,1% vs 7,1%). Stroke patients were less likely to receive anticoagulant therapy (2,0% vs 5,8%, p = 0,003) and were less likely to receive PCI during index hospitalization (31,1% vs 50,5%, p = 0,01). These patients also had lower level of HDL (1,00 ± 0,266 vs 1,18 ± 0,503, p = 0,039). According to results of linear regression analysis we make simple stroke risk score: BP CV low than 12% (-1), atrial fibrillation (+3), heart failure (+2), IGT (+2), CKD (+1), HDL more than 1 mmol/l (-1), PCI (-1), anticoagulants treatment (-3). Score higher than 4 is associated with high store risk. Area under the ROC curve for this risk score was 0,780.

Conclusions:
BP variability and HDL levels, GFR, PCI, heart failure, atrial fibrillation, and anticoagulant treatment were associated with the risk of ischemic stroke.