bluuebunny/crossref_metadata_2025_split huggingface dataset:
RENAL EFFECTS OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS IN PATIENTS WITH HEART FAILURE WITH REDUCED OR PRESERVED EJECTION FRACTION
Authors: Patoulias Dimitrios , Katsimardou Alexandra , Boulmpou Aristi , Siskos Fotios , Imprialos Konstantinos , Stavropoulos Konstantinos , Zografou Ioanna , Papadopoulos Christodoulos , Doumas Michael 
Published: June 2022

Objective:
SGLT-2 inhibitors confer cardiovascular protection for patients with heart failure (HF) regardless of diabetes mellitus (DM) or chronic kidney disease (CKD) status at baseline. However, it has not been extensively studied whether SGLT-2 inhibitors exert reno-protective effects in patients with heart failure (HF), either with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Declining of renal function is of utmost importance for patients with HF; thus, development of optimal treatment strategies to prevent or delay this progression to renal failure is required.

Design and method:
We sought to evaluate whether SGLT-2 inhibitors confer reno-protection in patients with HF, pooling data from relevant trials. We evaluated the following surrogate outcomes: the composite renal outcome, as defined across the 3 included trials, and the > 40% decrease in estimated glomerular filtration rate (eGFR) from baseline. Definition of composite renal endpoint is as follows: time to first occurrence of: (1) chronic dialysis; (2) renal transplantation; (3) sustained reduction of > 40% in estimated GFR; or (4) sustained estimated GFR of less than 15 ml per minute per 1.73 m2.

Results:
We pooled data from 3 randomized, controlled trials for a total of 14,462 enrolled subjects with HFrEF or HFpEF, assigned either to SGLT-2 inhibitor treatment or placebo. Overall risk of bias was evaluated as low across all trials. SGLT-2 inhibitor treatment resulted in a non-significant decrease in the risk for the primary composite outcome by 27% (RR = 0.73, 95% CI; 0.50–1.08 I2 = 66%, p = 0.11). In addition, SGLT-2 inhibitor treatment led to a non-significant decrease in the risk for > 40% decrease in eGFR from baseline, compared to placebo (RR = 0.70, 95% CI; 0.48–1.03, I2 = 54%, p = 0.07). No difference was identified between HFpEF and HFrEF enrolled subjects.

Conclusions:
SGLT-2 inhibitors provide significant cardiovascular benefits in patients with HFrEF or HFpEF; however, they do not exert significant reno-protection among patients with HF.
PR INTERVAL DURATION AS A RISK FACTOR FOR NEW-ONSET ATRIAL FIBRILLATION IN PATIENTS WITH ARTERIAL HYPERTENSION
Authors: Papakonstantinou Panteleimon , Andrikou Ioannis , Konstantinidis Dimitrios , Tsioufis Konstantinos 
Published: June 2022

Objective:
Hypertension (HTN) is one of the most important risk factors associated with atrial fibrillation (AF). Prolongation of the PR interval has been associated with an increased risk of incident AF, while PR interval is a component of the Framingham risk score for AF. However, the results regarding PR prolongation as a risk factor for AF are inconsistent. We aim to evaluate the predictive role of the PR interval for AF development in a large cohort of HTN patients.

Design and method:
Consecutive patients with essential hypertension without known AF at baseline were followed up for a mean period of 5.3 ± 3.3 years. A 12-lead ECG and an echocardiography study were performed on each patient at baseline and annually, and 24 h Holter rhythm monitoring was used in the event of arrhythmia symptoms. Routine clinical and paraclinical examinations as well as medications were implemented during the follow-up period according to the European Society of Cardiology/ European Society of Hypertension guidelines for HTN management. The PR interval and P wave duration were obtained from the baseline ECG.

Results:
We included 1807 hypertensives (mean age 57 ± 11 years; 49% males) with office systolic blood pressure (SBP)/ diastolic blood pressure (DBP) 144 ± 17/89 ± 11mmHg. During the follow-up period, 65 cases (3%) of new-onset AF were recorded. Patients with new-onset AF (n = 67) compared to those without AF (n = 1740) had greater baseline P wave duration (115 vs 110 ms) and PR internal (174 vs 157 ms). Multivariable Cox regression analysis showed that higher baseline PR internal is significantly associated with the development of AF (HR 1.01, 95% CI 1.01–1.02; p = 0.01), while there was no significant predictive value for baseline P wave duration on the incidence of new-onset AF. Baseline increased DBP was associated with a higher incidence of AF (HR 1.05, 95% 1.003–1.091; p = 0.037).

Conclusions:
Baseline PR internal is a significant predictor of new-onset AF in hypertensive patients. The PR prolongation could be considered as a marker for cardiovascular degenerative aging caused by vascular inflammation and myocardial fibrosis.
BIOMARKERS OF FIBROSIS AND INFLAMMATION IN PATIENTS WITH METABOLIC SYNDROME AND ATRIAL FIBRILLATION: WHAT ARE THE DIFFERENCES IN MOLECULAR MECHANISMS IN HYPERTENSION AND OBESITY?
Authors: Ionin Valery , Elizaveta Barashkova , Viktorya Pavlova , Georgy Borisov , Ksenya Averchenko , Elena Baranova 
Published: June 2022

Objective:
To determine the concentration of blood fibrotic and inflammatory biomarkers in patients with atrial fibrillation (AF) associated with metabolic syndrome (MS) components.

Design and method:
The study included 646 patients aged 35–65 years: patients with AF and MS (n = 142), those with AF and without MS (n = 113), those with MS and without AF (n = 175) and the control group consisted of healthy subjects without cardiovascular and metabolic diseases (n = 107). All participants underwent anthropometric and laboratory investigations. Profibrogenic (aldosterone, galectin-3, TGF-beta1, CTGF) and proinflammatory (CT-1, IL-6) factors were determined in serum and plasma by ELISA.

Results:
The highest concentrations of fibrotic and inflammatory biomarkers were found in patients with AF in combination with MS. In MS patients without AF, the concentration of aldosterone, galectin-3, TGF-beta1, CTGF, CT-1, and IL-6 was also higher than in healthy subjects. In patients with AF and hypertension (HTN), but without abdominal obesity (AO), higher values of aldosterone (108,1 ± 70,3 pg/ml and 89,3 ± 32,2 pg/ml, p = 0,003) and TGF¬beta1 (3680,1 ± 1863,3 pg/ml and 1968,1 ± 1611,5 pg/ml, p = 0,015) in serum than in AF patients without HTN and without AO. In the group of patients with AF and AO, but without HTN, higher concentrations of IL-6 (2,9 ± 0,7 pg/ml and 1,9 ± 0,6 pg/ml, p = 0,001) and CTGF (162,9 ± 92,2 pg/ml and 116,3 ± 63,4 pg/ml, p = 0,0001). Correlation analysis made it possible to establish a stronger relationship between aldosterone and TGF¬beta1 with systolic blood pressure (r = 0,493, p < 0,0001 and r = 0,530, p < 0,0001), and CT¬1, CTGF and IL¬6 in a greater degree correlated with waist circumference (r = 0,563, p < 0,0001; r = 0,626, p < 0,0001; r = 0,480, p < 0,0001).

Conclusions:
It can be assumed that hypertension through the aldosterone system and TGF-beta1, as well as abdominal obesity through the cytokine system CT-1 and IL-6 activate various mechanisms and pathways for myocardial emodelling. Integral molecules galectin-3 and CTGF mediate their interactions, in particular in patients with a combination of several MS components and contribute to a higher AF risk.
CORRELATION OF DIABETES REMISSION WITH REDUCTIONS IN BLOOD PRESSURE AND CARDIOVASCULAR RISK SCORES: RESULTS OF SIX MONTHS OF RANDOMISED TRIAL WITH DIGITAL TWIN TECHNOLOGY
Authors: Shamanna Paramesh , Joshi Shashank , Shah Lisa , Dharmalingam Mala , Vadavi Arun , Damodaran Suresh , Mohammed Jahangir , Mohamed Maluk , Poon Terrence , Keshavamurthy Ashok , Thajudeen Mohamed , Bhonsley Suchitra 
Published: June 2022

Objective:
Twin precision treatment improves metabolic parameters using a whole-body digital twin platform powered by artificial intelligence and internet of things

Design and method:
We evaluated 6 month data of RCCT (n = 128). Diabetes remission was defined as HbA1c < 6.5% for at least 3 months without Anti-Diabetic Medication (ADM)

Results:
Mean age and duration of diabetes (yrs) was 43 (±9.4, 95% CI 42 to 45) and 3.5 (±2.7, 95% CI 3 to 4). 88.3% (n = 113) achieved diabetes remission. At enrolment 76% (n = 97) were on ADM, of which 90% (n = 87) were off ADM. There was a significant change (change, % reduction) in HbA1c % (8.9 to 5.6, -38.2), SBP mmHg (128 to 118, -8.5), DBP mmHg (84 to 78, -7.8), waist circumference cm (97 to 86, -11.2), body weight kg (78 to 67, -12.7), BMI (27.2 to 23.5, -13.6), HOMA2IR (1.9 to 1.02, -48.4), Framingham Risk Score (FRS) (15.4 to 6.6, -56.4), Atherosclerotic Cardiovascular Disease (ASCVD) (7.9 to 3.1, -60.7), [p < 0.0001], QRISK3 (12.8 to 9.3, -27.3) scores, [p = 0.0027], at six months. (Table). There was a significant positive correlation between HbA1c reduction, and reductions in SBP (r 0.2, 95% CI 0.03 to 0.36, p = 0.03), HOMA2IR (r 0.23, 95% CI 0.06 to 0.39, p = 0.0074), ASCVD (r -0.17, 95% CI 0.004 to 0.34, p = 0.04), FRS (r 0.22, 95% CI 0.056 to 0.38, p = 0.0097). 57% (n = 73) were hypertensives. At 6 month, 33% (n = 6/18) were off anti-hypertensive medication

Conclusions:
Digital twin technology enables a significant reduction in BP, CV risk scores and insulin resistance which correlates with the remission of T2DM
INVESTIGATING THE QUALITY OF MACHINE LEARNING RESEARCH AND REPORTING IN HYPERTENSION
Authors: Du Toit Clea , Tran Tran , Aryal Sachin , Lip Stefanie , Manandhar Ishan , Sykes Robert , Pattnaik Harsha , Deo Neha , Alsanosi Safaa , Sionakidis Aristeidis , Ngoc Le Nhu , Mccallum Linsay , Mehta Dhruven , Kassi Maria , Rostron Maggie , Stevenson Leah , Tummala Ramakumar , Kashyap Rahul , Joe Bina , Padmanabhan Sandosh 
Published: June 2022

Objective:
Artificial intelligence and machine learning (AI/ML) are increasingly being applied to big clinical data to tackle research questions that cannot be answered with traditional statistical methods. The field is still in its nascent stages and there is a paucity of guidelines for conducting and reporting AI/ML research in hypertension. The objective was to apply the HUMANE checklist to survey the present landscape of AI/ML in hypertension to inform the development of hypertension-specific guidelines and recommendations.

Design and method:
The HUMANE checklist was developed by global clinical and AI/ML experts through the Delphi method. It assesses the quality of medical AI/ML articles based on whether they cover subjects expected in any peer-reviewed, clinical or AI/ML research publication. A cooping review was carried out to identify articles presenting original research in AI/ML and hypertension published in 2019–2021. Two independent reviewers applied the checklist to each article and in the case of discordance, the response was adjudicated by an AI/ML expert. Results were analysed to assess compliance with the survey (% of papers satisfying checklist requirements).

Results:
A total of 63 manuscripts was reviewed. A summary of results is shown in Figure 1. Highest compliance was seen for items relating to general article presentation, with compliance ranging from 68% to 98% (description of statistical analysis methods and background context, respectively). Lowest compliance was seen with checklist items relating to clinical research and AI/ML methods. 44% of reviewed articles described the demographics of their dataset and 48% stated their inclusion/exclusion criteria. Nonetheless, datasets were deemed appropriate for investigative aims in 93% of articles. 30% of manuscripts reported their calibration measures, while 73% stated their performance metrics. Internal validation was carried out in 75% of studies, but external validity was assessed in only 14% of cases. Algorithmic bias was addressed in 11% of papers.

Conclusions:
Application of AI/ML methods in hypertension research is growing, but the majority of current work has major shortfalls in reporting quality, model validation and algorithmic bias. Our study identifies areas of improvement to enable the full realisation of the potential of AI/ML in hypertension.
ASSOCIATION OF SERUM RENALASE WITH THE RISK OF HYPERTENSION IN CHINESE ADULTS WITH NORMAL KIDNEY FUNCTION
Authors: Wang Keke , Chu Chao , Wang Yang , Yu Yan , Liao Yueyuan , Ma Qiong , Wang Dan , Zheng Wenling , Hu Jiawen , Mu Jianjun 
Published: June 2022

Objective:
Renalase, a novel flavoprotein with oxidoreductase activity secreted from kidney and heart into the circulation, plays a crucial role regulating blood pressure. However, research on the relationship between serum renalase and hypertension is controversial. This cross-sectional study is to evaluate the relationship of serum renalase and the risk of hypertension in Chinese adults with normal kidney function.

Design and method:
We conducted follow-up of the long-term hypertension study cohort established in Hanzhong, Shaanxi Province from April to July 2017. Blood and urine samples were collected and blood pressure was measured. Serum renalase levels were determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Data from 2263 subjects was included and nalysed.

Results:
Serum renalase levels were higher in hypertensive subjects than in normal BP subjects with normal kidney function (2.09 ± 0.55 g/ml vs. 2.17 ± 0.52 g/ml, P < 0.01). Simple correlation analysis revealed that renalase was positively associated with SBP (r = 0.10, P < 0.01) and DBP (r = 0.11, P < 0.11). However, after adjusting confounding factors, logistic regression analysis suggested there was no significant relationship between serum renalase and the risk of hypertension.
Further investigation revealed that renalase had a significant interaction effect on hypertension for gender (P for interaction < 0.001), BMI (P for interaction < 0.001) and smoking (P for interaction < 0.001). Those with a BMI above 25 and a renalase above 2.48 g/ml had a higher risk of hypertension. In male and current smokers, subjects with 1.76–2.09 g/ml renalase were more prone to develop hypertension.

Conclusions:
Our findings suggest that the renalase level in specific populations has heterogeneous effects on blood pressure. Further clinical trials are needed to assess the potential role of renalase as a biomarker of hypertension.
THE EFFECTS OF SURGICAL AORTIC VALVE REPLACEMENT ON ARTERIAL STIFFNESS
Authors: Sigala Evangelia , Terentes-Printzios Dimitrios , Andreas Katsaros , Nikolaos Baikoussis , Nikolaos Koumallos , Vasileios Lozos , Nikolaos Giakis , Konstantinos Filis , Konstantinos Tsioufis , Vlachopoulos Charalambos 
Published: June 2022

Objective:
Assessing arterial properties in patients with aortic valve stenosis undergoing surgical aortic valve replacement (SAVR) is difficult, and the results to date have been inconclusive. We sought to investigate how SAVR affects vascular stiffness in the short and long term.

Design and method:
We included 55 patients (mean age 70 ± 8 years, 69% men) with severe symptomatic aortic stenosis who underwent SAVR. Arterial stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV). Measurements were conducted at baseline, in the acute phase, and 1 year after the operation.

Results:
Immediately after SAVR there was an increase in cfPWV (7.66 ± 1.63 m/s vs 8.27 ± 2.06 m/s, p = .010) that was sustained at 1 year (7.66 ± 1.63 m/s vs 8.98 ± 2.31 m/s, p = <.001, figure 1). Similarly, baPWV increased in the acute phase (1597 ± 455 cm/s vs 1954 ± 658 cm/s, p < .001) and persisted 1 year postoperatively (1597 ± 1833 cm/s, p < .001, figure 2).

Conclusions:
After SAVR the arterial system shows an increase of stiffness in response to the acute relief of the obstruction, which is retained in the long term.
HEMATOLOGICAL BIOMARKERS ASSOCIATED WITH INFLAMMATION AND CARDIOVASCULAR RISK IN PSORIASIS SEVERITY
Authors: Santos Ana Carolina , Gil Ângela , Ferreira Joana , Filipe Paulo , Bicho Manuel 
Published: June 2022

Objective:
Psoriasis is a chronic inflammatory disease charactered by abnormal proliferation of keratinocytes and infiltration of immune cells and is associated with increased cardiovascular risk. Psoriasis Area and Severity Index (PASI) is a clinical tool used to assess the severity of psoriasis. Circulating biomarkers, such as those of complete blood count (CBC) derived ratios such as platelet-lymphocyte (PLR) and lymphocyte-monocyte (LMR), have been shown to be associated with autoimmune diseases and have been identified as indicators of systemic inflammation surrogate biomarkers.
This study aims to evaluate the impact of CBC biomarkers on psoriasis and their clinical severity (PASI).

Design and method:
Sixty-three psoriasis patients with a mean age of 52.50 ± 12.81 years. Sociodemographic, hemodynamic and routine blood laboratory data were collected. Patients were stratified based on PASI: < 5 (Group I) and > or equal to 5 (Group II).
Biochemical parameters were determined in serum according to standardized methods.
For statistical analysis SPSS program was used and a significant value for p < 0.05.

Results:
Compared patients between the group I and II it were observed higher levels in this last group of: hemoglobin (p = 0.049), mean corpuscular hemoglobin concentration (p = 0.027), leukocytes (p = 0.012), neutrophils (p = 0.006), erythrocyte sedimentation rate (p = 0.032), Gamma-glutamyltransferase (p < 0.001), alkaline fosfatase (p = 0.046), triglicerides (p = 0.038), PLR (p = 0.012) and lower values of: ymphocytes (p = 0.010), LMR (p = 0.018), chloride (p = 0.035), cholesterol-HDL (p = 0.003) and tumour Necrosis Factor alpha (p = 0.030).

Conclusions:
Routine CBC, derived indices and biochemical parameters related to inflammation and cardiovascular risk appear to be inexpensive and easily accessible biomarkers to psoriasis severity.
MAJOR IMPACT PREDICTION CARDIOVASCULAR RISK IN YOUNG ADULTS
Authors: Da Silva Oliveira Alda Pereira , Gomes Paula , Matos Andreia , Miguel José Pereira , Freitas Graça , Bicho M. Clara , Bicho Manuel 
Published: June 2022

Objective:
Apparently healthy young adults may have risk factors associated with arterial hypertension (HBP) and atherosclerosis. The objective was to evaluate the presence of HBP, obesity and other anthropometric or metabolic cardiovascular (CV) risk parameters in young adults and their association to inflammation connected blood count parameters, as possible earlier determinants for the path of CV future disease.

Design and method:
A sample of 250 students (76 men, 174 women; aged 22.1 ± 2.79 years; 94.8% Caucasians; 82.3% eutrophic) was studied. Body Mass Index (BMI Kg/m2), waist circumference (WC cm) and blood pressure (BP mmHg) were measured according to standard methods. Blood count parameters, glucose, cholesterol, HDL and triglycerides (mmol/L) determined according to standard hospital laboratory. Statistics: t-student, ANOVA or equivalent non-parametric, Chi-square and Pearson/Spearman correlations according normality distribution.

Results:
Most subjects (91.5%) had normal BP (mean ± SD systolic 116.7 ± 14.0; diastolic 69.6 ± 9.4). HBP frequency showed no differences between gender (p = 0.154), but an association between BMI (p < 0.000) with HBP was observed, as 92.9% of hypertensive patients were also obese or overweight. In male compared to women, higher glucose values (p = 0.000), BMI (p = 0.011) and WC (p = 0.000) but lower HDL values (p = 0.000) were observed. BMI and WC were also higher (respectively p = 0.005 and p = 0.004) in hypertensive subjects. WC adjusted for BMI was a risk factor for HBP (p = 0.043; OR = 1.059; 95% CI = 1.002–1.119). Regarding BMI classes (<18.5, 18.5–25, > 25) values were higher in overweight/obese subjects for the following ratios to HDL: monocytes (p = 0.045), monocytes X LDL (p = 0.006), platelets X LDL (p = 0.002), monocytes X platelets X LDL (p = 0.005), monocytes X platelets (0.032). In hypertensive subjects, monocyte X platelet to HDL ratio was higher (p = 0.03) compared to normotensive and a correlation was also observed between glucose and the following ratios to HDL: monocytes X LDL (p = 0.033), monocytes X platelets (p = 0.045) and monocytes X platelets X LDL (p = 0.034).

Conclusions:
Even in younger age groups a major impact prediction cardiovascular risk is possible. Anthropometric, metabolic and blood count parameters and its association could be early biomarkers associated with hypertension and should be considered as indicators of present and/or future cardiovascular disease.
SERUM BIOMARKERS, SKIN AUTOFLUORESCENCE AND OTHER METHODS. WHICH PARAMETER BETTER ILLUSTRATES THE RELATIONSHIP BETWEEN ADVANCED GLYCATION END PRODUCTS AND ARTERIAL STIFFNESS
Authors: Gelzinský Július , Filipovský Jan , Mayer Otto , Mlíková-Seidlerová Jitka , Mares Stepan 
Published: June 2022

Objective:
Impaired glucose metabolism plays an important role in the stiffening of large arteries. Advanced glycation end-products (AGEs) are responsible for the onset of specific complications in diabetic subjects; however, they may exert harmful effects on cardiovascular system also in non-diabetics.
AGEs bind to specific receptor (RAGE) expressed in various cells. The AGEs-RAGE complex participates in various stages of atherosclerosis and arterial stiffening. Circulating soluble isoform of RAGE (sRAGE) captures circulating AGEs, thus preventing their patophysiological consequences.
We aimed to investigate the associaton between aortic pulse wave velocity and multiple paramaters of glucose metabolism.

Design and method:
1061 subjects were examined in the Pilsen subsample of Czech Post-MONICA study (= 1% random sample of general population aged 25–74 years). Pulse wave velocity (PWV) was measured using the Sphygmocor device (AtCor Medical Ltd., Australia). Following markers of glucose metabolism were assessed: fasting glucose level, glycated hemoglobin, carboxy-methyl lysine (marker of circulating AGEs), sRAGE (circulating soluble isoform of RAGE), skin AGEs (autofluorescence method). Since ratios may better describe the balance between harmful and protective factors, following risk factors ratios were calculated: CML/sRAGE, skin AGEs/sRAGE.

Results:
Aortic PWV was strongly associated with fasting glucose, sRAGE, skin AGEs and the skin AGEs / sRAGE ratio. Only weak association with HbA1c was found.
All parameters of glucose metabolism were included simultaneously in a stepwise regression of pulse wave velocity. Besides age, mean arterial pressure and male sex, fasting glucose and skin AGEs were positively associated with PWV, while there was a negative association with sRAGE (significant in non-diabetic population only). In contrast, neither CML, nor its ratio to sRAGE showed any association with arterial stiffness.

Conclusions:
Autofluorescence method allows to assess easily and quickly the contents of skin AGEs, which were associated with aortic stiffness in general population sample. sRAGE level had a negative association with PWV, thus reflecting its protectivity against arterial stiffening. These two parameters influence aortic stiffness over and above fasting glucose level which is per se a strong determinant of aortic PWV even in non-diabetic population.