bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROSPECTIVE OBSERVATIONAL STUDY ASSESSING AMBULATORY BLOOD PRESSURE IN PRIMARY ALDOSTERONISM AFTER SURGICAL AND MEDICAL TREATMENT
Authors: Puar Troy , Zhang Meifen , Khoo Joan , Chai Siang Chew 
Published: April 2021

Objective:
Primary aldosteronism (PA) affects 5–10% of all patients with hypertension. Patients with PA can be treated with mineralocorticoid antagonists (medications), or curative adrenalectomy (surgery) if they have unilateral PA. Some studies have shown that surgery leads to greater improvement in blood pressure (BP) compared with medications.

Design and method:
We conducted a prospective study from 2016 - 2019 in patients with PA to assess for BP changes after both surgical and medical treatment. All patients had a 24hr ambulatory BP measurement done before treatment, and 12 months after. Daytime ambulatory systolic BP, diastolic BP, number of hypertension medications, and WHO defined daily dose (DDD) of hypertension medications were compared at baseline versus 12 months post-treatment.

Results:
32 patients with PA, mean age 56.0 ± 10.5 yr, 7 females (21.9%) completed both baseline and 12 months post-treatment ambulatory blood pressure. 13 patients (40.6%) were treated with surgery, and the remaining 19 patients were treated with medications. In the entire cohort, daytime systolic BP improved from 144.0 to 135.8 mmHg, P < 0.05, and diastolic BP from 87.3 to 84.8 mmHg, P = 0.18. In patients post-surgery, there was a trend towards improvement in systolic BP from 148.8 to 137.6 mmHg, P = 0.13, and diastolic BP from 92.1 to 85.7 mmHg, P = 0.09. In addition, there was a significant decrease in use of hypertension medications, from 2.1 to 0.7 medications, P < 0.01, and DDD from 3.6 to 0.8, P < 0.01. In patients post-medical treatment, systolic BP improved from 140.8 to 134.5, P = 0.035, diastolic BP did not change from 84.1 to 84.2, P = 0.93. There was an increase in number of hypertension medications from 1.9 to 2.7, P < 0.01, and DDD from 3.1 to 3.5, P = 0.24.

Conclusions:
Treatment of PA leads to improvement of blood pressure. In patients with unilateral PA who undergo surgery, this is also accompanied with a significant reduction in use of antihypertensive medications.
INFLAMMATION AND SALT IN YOUNG ADULTS: THE AFRICAN-PREDICT STUDY
Authors: Crouch Simone , Roux Shani Botha-Le , Delles Christian , Graham Lesley A. , Schutte Aletta E. 
Published: April 2021

Objective:
Low-grade inflammation and a diet high in salt (sodium) are both established risk factors for cardiovascular disease. High potassium intake attenuates increases in blood pressure in response to high salt intake and may have a similar protective effect on the modulation of inflammation. To better understand these interactions under normal physiological conditions, we investigated the relationships between 22 inflammatory mediators with 24hr urinary potassium in young healthy adults stratified by low, middle and high salt intake (sodium tertiles). We additionally stratified by ethnicity due to salt-sensitivity seen in black populations.

Design and method:
We included 991 healthy black (N = 457) and white (N = 534) adults, aged 20–30 years with complete data for 24hr urinary sodium and potassium. Blood samples were analysed for 22 inflammatory mediators.

Results:
Differences between plasma concentrations of inflammatory mediators between the low, middle and high sodium tertiles were not seen in either the black or white groups. In multivariable-adjusted regression analyses in white adults, we found only in the lowest sodium tertile that potassium associated negatively with the pro-inflammatory mediators interferon gamma, interleukin-7, interleukin -12, interleukin -17A, interleukin -23 and tumor necrosis factor alpha (all p greater than or equal to 0.046). In the black population, we found no independent associations between potassium and any inflammatory mediator were found.

Conclusions:
In young white adults 24 h potassium associated independently and negatively with specific pro-inflammatory mediators, but only in those with a daily salt intake less than 6.31 grams, suggesting potassium to play a protective, anti-inflammatory role in a low-sodium environment. No similar associations were found in young healthy black adults.
LONG-TERM ADHERENCE TO ANTIHYPERTENSIVE TREATMENT BY URINARY/PLASMA DETECTION IN PATIENTS WITH RESISTANT HYPERTENSION IN THE RENAL DENERVATION FOR HYPERTENSION (DENERHTN) TRIAL
Authors: Kably Benjamin , Fouassier David , Lorthioir Aurélien , Gosse Philippe , Delsart Pascal , Courand Pierre-Yves , Denolle Thierry , Pereira Helena , Billaud Eliane , Azizi Michel 
Published: April 2021

Objective:
The DENERHTN trial reported the BP–lowering efficacy of renal denervation (RD) in addition to a standardized stepped-care antihypertensive treatment (SSAHT) in patients with resistant hypertension (RHTN) vs. SSAHT alone at 6 months despite a similar (around 50%) prevalence of partial+complete nonadherence (NA) to antihypertensive drugs (AHD). We report here adherence to AHD at 12 months.

Design and method:
106 patients with RHTN to indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to RD+SSAHT or SSAHT alone. For SSAHT, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added from 2 to 5 months if home BP was greater than or equal to 135/85 mmHg. From 6 to 12 months, patients received AHD at physician's discretion. At 6 and 12 months, urine/plasma AHD screening with ultrahigh performance LC-MS/MS was performed on available samples.

Results:
From 6 to 12 months, 25/44 (56.8%) RD+SSAHT patients and 26/53 (49.1%) SSAHT patients had a change in their antihypertensive treatment by their physician (p = 0.446). The percentage of NA decreased between 6 and 12 months from 50.0% (n = 20/40) to 42.9% (n = 15/35) in the RD+SSAHT group and from 53.3% (n = 24/45; p = 0.759) to 41.7% (n = 15/36; p = 0.919) in the SSAHT group. Among patients with samples at both 6 and 12 months, 10/33 (30.3%) RD+SSAHT patients and 7/33 (21.2%) SSAHT patients had a change in adherence (p = 0.398). A total of 5/18 (27.7%) RD+SSAHT and 0/13 (0/0%) SSAHT patients who were adherent at 6 months became NA at 12 months (p = 0.0580). Conversely, the same proportion of patients who were NA at 6 months became adherent at 12 (RD+SSAHT: n = 5/15, 33.3% vs. SSAHT: n = 7/20, 35%).

Conclusions:
In patients with RHTN of the DENERHTN trial, the prevalence of NA to AHD drugs at 12 months remained high >40% but not different in the RD+SSAHT and SSAHT groups. About 1/3 of the patients became adherent at 12 months in both groups. However, numerically more patients became NA in the RD+SSAHT group than in the SSAHT group, which may impact the BP response to RD.
GROWTH DIFFERENTIATION FACTOR-15 IS AN INDEPENDENT PREDICTOR OF CARDIOVASCULAR DISEASE IN JAPANESE PATIENTS WITH CARDIOVASCULAR RISK FACTORS: THE J-HOP STUDY
Authors: Negishi Keita , Hoshide Satoshi , Ishiyama Yusuke , Shimizu Hayato , Shinpo Masahisa , Kario Kazuomi 
Published: April 2021

Objective:
Growth differentiation factor-15 (GDF-15) is emerged as a novel biomarker to predict adverse outcomes in community-dwelling individuals and patients with cardiovascular (CV) disease. However, there is a paucity of information on the association between blood GDF-15 levels and adverse outcomes in outpatients with CV risk factors. In this study, we evaluated the prognostic value of GDF-15 in outpatients with CV risk factors and compared with those of other prognostic biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT).

Design and method:
We collected blood samples from 3,562 patients with CV risk factors in the J-HOP (Japan Morning Surge-Home Blood Pressure) study. Blood GDF-15 levels were determined by immunoassay analysis. During a mean follow-up period of 6.6 years, we recorded the incidence of adverse outcomes as follows: 1) cardiac events defined as ischemic heart disease and heart failure, 2) stroke events defined as ischemic stroke and cerebral hemorrhage, 3) all-cause death, and 4) cancer death. Patients were stratified according to tertiles of GDF-15. The association between GDF-15 and each outcome was evaluated by Cox-proportional hazard models adjusting for established risk factors and other biomarkers (hs-TnT and NT-proBNP).

Results:
We observed 141 (4.0%) cardiac events, 81 (2.3%) stroke events, and 155 (4.4%) death including 63 (1.8%) cancer death. Multivariate Cox regression model showed that patients in highest tertile of GDF-15 were independently and significantly associated with increased risk of stroke and death except for cardiac events [stroke events, hazard ratio (HR) 2.87, p = 0.008; all-cause death, HR 2.38, p = 0.007; cancer death, HR 2.48, p = 0.049; cardiac events; HR 1.07, p = 0.805, respectively] compared with lowest tertile after adjustment for established risk factors and other biomarkers. Furthermore, adding GDF-15 to the predictive models for stroke and death improved discrimination and reclassification more than adding other biomarkers to the models.

Conclusions:
In this study, GDF-15 predicts death and stroke except for cardiac events. Information of GDF-15 might be helpful when assessing the risk of death and stroke events in Japanese patients with CV risk factors.
PLASMA FATTY ACIDS AND THE RISK OF VASCULAR AND MORTALITY OUTCOMES IN INDIVIDUALS WITH TYPE 2 DIABETES: RESULTS FROM THE ADVANCE STUDY
Authors: Harris Katie , Oshima Megumi , Sattar Naveed , Wurtz Peter , Jun Min , Welsh Paul , Chalmers John , Woodward Mark 
Published: April 2021

Objective:
This study aimed to quantify the association of essential and other plasma fatty acids biomarkers with macrovascular disease, microvascular disease and death in individuals with type 2 diabetes.

Design and method:
A case cohort study (N = 3,576), including 654 macrovascular events, 341 microvascular events and 631 deaths during 5 years of median follow-up was undertaken in participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study.
The fatty acids measured from baseline plasma samples, by proton nuclear magnetic resonance (NMR) analysis, were omega-3, docosahexaenoic acid (DHA), omega-6, linoleic acid (LA), polyunsaturated (PUFA), monounsaturated (MUFA) and saturated fatty acids (SFA). Hazard ratios (HRs) were modelled per standard deviation higher percentage fatty acid. C-statistics and net reclassification improvement were used to test the added value of fatty acids for risk prediction.

Results:
After adjustment for traditional cardiovascular risk factors, an inverse association was observed for omega-3 fatty acids and DHA (HR [95%CI]: 0.87 [0.80, 0.95] and 0.88 [0.81, 0.96], respectively per 1SD higher percentage) with the risk of macrovascular events, and for omega-3 fatty acids (HR [95%CI]: 0.91 [0.84, 0.99] per 1SD higher percentage) with death. Such associations were also evident when investigating absolute levels of fatty acids. There were no statistically significant associations between any fatty acids and microvascular disease after adjustment. However, there was limited improvement in predictive ability of models when any fatty acid was added.

Conclusions:
Plasma omega-3 fatty acids and DHA were found to be inversely associated with macrovascular disease, whilst omega-3 fatty acids was also inversely associated with death. These results provide additional support for regular consumption of food rich in omega-3 fatty acids in type 2 diabetes.
IDENTIFICATION OF CANDIDATE BIOMARKERS FOR SALT SENSITIVITY OF BLOOD PRESSURE BY INTEGRATED BIOINFORMATICS ANALYSIS
Authors: Chen Chen , Liu Guanzhi , Chu Chao , Zheng Wenling , Hu Jiawen , Wang Yang , Ma Qiong , Yan Yu , Yuan Yue , Liao Yueyuan , Mu Jianjun 
Published: April 2021

Objective:
In the current study, we aimed to identify potential biomarkers for salt sensitivity of blood pressure (SSBP), which may provide a novel insight into the pathogenic mechanisms of salt-sensitive hypertension. Firstly, we conducted weighted gene coexpression network analysis (WGCNA) and selected a gene module and 60 hub genes significantly correlated to SSBP. Then, GO function and KEGG signaling pathway enrichment analysis and protein-protein interaction (PPI) network analysis were performed. Furthermore, we identified a five-gene signature with high connectivity degree in the PPI network and high AUC of ROC curves, which may have high diagnosis value for SSBP. Moreover, through combining two gene screening methods, we identified 23 differentially expressed circRNAs and selected the top 5% circRNAs (1 circRNA) with the highest connectivity degree in the coexpression network as hub circRNA highly associated with SSBP. Finally, we carried out RT-qPCR to validate the expression of five hub genes, and our results showed that the expression of HECTD1 (P = 0.017), SRSF5 (P = 0.003), SRSF1 (P = 0.006), HERC2 (P = 0.004), and TNPO1 (P = 0.002) was significantly upregulated in the renal tissue in salt-sensitive rats compared to salt-resistant rats, indicating that these five hub genes can serve as potential biomarkers for SSBP.
ASSESSMENT OF URODYNAMICS AND CONCENTRATION FUNCTION OF PARENCHYMA IN PATIENTS WITH ARTERIAL HYPERTENSION AND GOUT
Authors: Gromova Margarita , Kislyak Oxana , Tsurko Vladimir , Kashkadayeva Anna , Averinova Svetlana , Aliokhin Andrei 
Published: April 2021

Objective:
To assess the urodynamics and concentration function of the parenchyma in patients with arterial hypertension and gout.

Design and method:
We examined 87 patients with arterial hypertension and gout. 83% were men (mean age 55.4 ± 12.3 years). Grade 1 of arterial hypertension was detected in 43.7%, grade 2 - in 36.9%, grade 3 - in 19.3%. All the patients had chronic gouty arthritis, 30% of the patients had tophi. Markers for kidney damage, urine sediment, GFR calculation were evaluated in all the patients. All the patients were given a systemic examination of their nephro-urological condition based on complex renal scintigraphy (SENS-CRS) with the in-depth differential analysis of the impaired renal parenchyma function, upper and lower urinary tract (fig.1).

Results:
According to the standard method of GFR calculation using the CKD-EPI formula, we found that 10 patients (11.3%) had no CKD symptoms; stage I-II CKD was observed in 56 patients (64.5%), stage III-IV in 21 patients (24.2%). 16 patients with arterial hypertension and serum creatinin level >125 μmol/l were allocated to a subgroup of patients in the category of increased risk of developing high stages of CKD. According to the CKD-EPI formula, those 16 patients had CKD stage I-II and one patient had stage III CKD with a high risk of transition it to stage IV. The reliable difference (p < 0.05) was established only by the D (%) indicator that is by the radiopharmaceutical removal rate from the renal parenchyma when we compared the analyses of complex renal scintigraphy data in the 16 specified patients and in the remaining 71 patients with arterial hypertension (tab.1).

Conclusions:
Patients with arterial hypertension from the time of gout diagnosis must be included in the nephro-urological control system. It is important to control the risk factors related to the probability of CKD progression. The renocortical parameter D (%) used in the SENS-CRS technology is a prognostically important preclinical marker of intrarenal congestion when the latent development of serious morphological and functional disorders in the renal parenchyma occurs that leads to the CKD development or aggravation of the existing CKD stage.
CORRELATION OF ANKLE-BRACHIAL INDEX WITH SEVERITY OF CORONARY ARTERY DISEASE IN PATIENTS HOSPITALIZED FOR ACUTE MYOCARDIAL INFARCTION
Authors: Koumelli A. , Tsioufis K. , Konstantinou K. , Mantzouranis E. , Kasiakogias A. , Dimitriadis K. , Milk A. , Konstantinidis D. , Leontsinis I. , Tousoulis D. 
Published: April 2021

Objective:
Ankle-brachial index (ABI) is an stablished predictor of cardiovascular events in different clinical setting including hypertension

Purpose:
To assess the usefulness of ABI evaluation for identifying multivessel CAD in patients with acute myocardial infraction (AMI).

Design and method:
We studied 101 patients [77.2% male; mean age 60.9 years; 63.4% hypertensives; 24.8% with diabetes mellitus (DM)] who were hospitalized because of ST-elevation MI (STEMI, 51.5%) and Non-ST–elevation MI (NSTEMI). All patients underwent baseline estimation of clinical and laboratory parameters during their hospitalization. The ABI was measured according to established methodology using a certified automated device and abnormal ABI was defined as a value <0.9. Severity of CAD was estimated by the number of affected main vessels.

Results:
In the entire population, mean ABI was 1.11 ± 0.17, while 15.8% of patients had abnormal ABI. NSTEMI patients compared to those with STEMI demonstrated a trend forlower ABI (1.07 ± 0.18 vs 1.12 ± 0.16; p = 0.144) and more often abnormal ABI (22.4% vs 9.6%; p = 0.103). Using univariate analysis in the entire population, severity of CAD was correlated with age (r = 0.133; p = 0.053), history of DM (r = 0.225; p = 0.01), ABI value (r = 0.214; p = 0.029) and abnormal ABI (r = 0.242; p = 0.015). In multivariate regression models, both ABI value (b = 0.258; p = 0.014) and abnormal ABI (b = 0.218; p = 0.036) remained significant predictors of CAD severity independently of gender, age, DM, smoking, low density lipoprotein (LDL-C), 24-h systolic blood pressure and the type of MI.

Conclusions:
An impaired ABI is associated with greater risk of multivessel CAD in patients with AMI. This finding in patients with acute coronary syndromes may thusraise the suspicion of advanced disease, alerting to the need for moreaggressive diagnostic and therapeutic strategies.
ROLE OF ATYPICAL CHEMOKINE RECEPTOR 2 IN PERIVASCULAR ADIPOSE TISSUE INFLAMMATION IN ANGIOTENSIN II DEPENDENT HYPERTENSION
Authors: Mikolajczyk Tomasz , Skiba Dominik , Vidler Francesca , Love Samantha , Justo-Junior Amauri , Nosalski Ryszard , Graham Delyth , Maffia Pasquale , Graham Gerard , Guzik Tomasz 
Published: April 2021

Objective:
Hypertension (HT) is associated with perivascular adipose tissue (PVAT) inflammation in which chemokines play a crucial role. Atypical chemokine receptor 2 (ACKR2) is essential for CC-chemokine ligand binding and their degradation resulting in regulation of inflammation. We hypothesized that ACKR2 is important for immune cell recruitment into PVAT.

Design and method:
Using flow cytometry we analysed the numbers of leukocytes infiltrating PVAT in ACKR2-/- mice and WT (wild-type, C57BL/6J) infused for 14 days with Ang II (angiotensin II, 490ng/min/kg).

Results:
Chronic infusion of Ang II caused increased of leukocyte (CD45+) content in PVAT in both WT and ACKR2-/- mice. This increase was particularly evident for T cell subsets in WT but not in ACKR2-/-. However the number of macrophages (F4/80+CD11b+) was increased in both groups. Interestingly, ACKR2-/- revealed decreased T cell number infiltrating PVAT upon Ang II infusion in comparison to WT. Hypertension was associated with increased CCR1, CCR2 and CCR3 expression in PVAT in both WT and ACKR2-/-. However, ACKR2-/- revealed higher expression of CCR1 and CCR2 but not CCR3 in comparison to WT. Interestingly, increased expression of CCR5 in PVAT upon Ang II infusion in WT was not observed in ACKR2-/-. Hypertension resulted in increased RANTES level in aorta and PVAT to the same extent in both WT and ACKR2-/-. However, MCP-1, MIP-1 alpha and MIP-1 beta level was higher in ACKR2-/- aorta than in WT aorta upon Ang II infusion. ACKR2 expression was lower in PVAT than in aorta. Interestingly, Ang II administration decreased the expression of ACKR2 in aorta but increased ACKR2 level in thoracic PVAT. RNAscope analysis revealed ACKR2 expression in vascular smooth muscle cells (VSMC). Vessels isolated from ACKR2-/- were protected from vascular dysfunction and revealed reduced ROS production in comparison to WT upon Ang II administration. ACKR2-/- mice developed similar extent of blood pressure increase as WT in hypertension.

Conclusions:
In hypertension, ACKR2-/- is associated with decreased T cell content and reduced CCR5 expression in PVAT. This is accompanied by improved vascular function and diminished ROS production, independently of blood pressure regulation.
TRPM7 IS PROTECTIVE AGAINST CARDIOVASCULAR DAMAGE INDUCED BY ALDOSTERONE AND SALT
Authors: Rios Francisco J. , Zou Zhi -Guo , Harvey Adam P. , Harvey Katie Y. , Neves Karla B. , Alves-Lopes Rheure , Nichol Sarah Ef , Camargo Livia L. , Chubanov Vladimir , Gudermann Thomas , Montezano Augusto C. , Touyz Rhian M. 
Published: April 2021

Objective:
TRPM7 is a channel-kinase that regulates cellular signaling and Mg2+ homeostasis. We demonstrated that TRPM7 is protective against cardiac inflammation and dysfunction. Since hyperaldosteronism causes hypertension and Mg2+ wasting, we questioned whether TRPM7 plays a role in aldosterone-induced hypertension and fibrosis.

Design and method:
Wild-type (WT) and TRPM7-deficient (M7+/δ) mice were treated with aldosterone (600 μg/Kg/day) and/or 1% NaCl (drinking water) (aldo, salt or aldo/salt) for 4 weeks. Blood pressure (BP) was evaluated by tail-cuff. Vascular function was investigated by wire myography. Inflammatory infiltrate was investigated by flow cytometry. Molecular mechanisms of fibrosis and inflammation were investigated in cardiac fibroblasts (CF) isolated from WT and M7+/δ mice. Protein expression was assessed by western-blot and histology.

Results
: Aldo/salt reduced TRPM7-phosphorylation (62%) and expression (30%) in WT, similarly to reduced levels observed in M7+/δ-veh. M7+/δ exhibited increased BP by aldo (140mmHg), salt (135mmHg) and aldo/salt (137mmHg) vs M7+/δ-veh (117mmHg) (p < 0.05), whereas in WT, BP was increased only by aldo/salt (134mmHg). All treatments induced endothelial dysfunction in M7+/δ as observed in acetylcholine-relaxation curves [Emax% M7+/δ: aldo (81±4), salt (69 ± 4) and aldo/salt (75 ± 3.0), p < 0.05], whereas in WT, Emax% was reduced after aldo (68 ± 4) and aldo/salt (80 ± 3). Phenylephrine-contraction and SNP-relaxation curves were similar among groups. In kidneys from WT, aldo/salt increased numbers of macrophages (47% vs 32% WT-veh) and CD4+T cells (33% vs 22% WT-veh) (p < 0.05), effects observed in M7+/δ-veh (macrophages: 42%, CD4+T cells: 34%). Aldosterone increased CD8+T cells in kidneys from M7+/δ (16% vs M7+/δ-veh 9%). Collagen was increased only in aortas from M7+/δ-aldo (31%) and M7+/δ-aldo/salt (45%). Aldo/salt induced higher collagen deposition in hearts (68%) and kidneys (126%) from vs WT. Hearts from M7+/δ-veh exhibited increased p-Stat1 and p-Smad3 (1.5-fold), whereas tissues from WT exhibited 3-fold increase only after treatments. CF from M7+/δ showed increased activation of Stat1 (2-fold), Smad3 (9-fold), ERK1/2 (8-fold) and reduced pStat3 (70%) vs WT. These effects were ameliorated by Mg2+ supplementation (p < 0.05).

Conclusions:
We define a novel protective role of TRPM7 in aldosterone-salt induced cardiovascular damage, which when downregulated, facilitates hypertension, vascular remodeling and cardiac fibrosis through Mg2+-dependent mechanisms.