bluuebunny/crossref_metadata_2025_split huggingface dataset:
USE OF ANTIHYPERTENSIVE COMBINATION THERAPY DURING THE COVID-19 PANDEMIC - A CROSS-SECTIONAL, NATION-WIDE STUDY 2019-2021
Authors: Dobrowolski Piotr , Prejbisz Aleksander , Bozek Gabriel , Kon Beata , Machnio Aneta , Urbanski Filip , Madry Roman Topor , Kreutz Reinhold , Januszewicz Andrzej , Milkowski Maciej 
Published: June 2023

Objective:
To assess changes in the use of antihypertensive drug combinations during the COVID-19 pandemic and the degree of adherence to the recommendations of more frequent use of combination therapy by ESC/ESH 2018 guidelines, data of all patients who filled a prescription for an antihypertensive drug in Poland were analyzed.

Design and method:
Patients who filled at least one prescription from ATC groups C02, C03, C07-10, C10BX in each of the years 2019, 2020 and 2021 were extracted from the obligatory prescription database of the National Health Service in Poland. This database covers all filled prescriptions in Poland. We have excluded from the analysis patients with diagnosis of heart failure. Combination therapy was assumed if prescriptions of two drugs overlapped for at least 40 days. In the case of the use of single pill combinations (SPC), the combined use of the individual substances included in the SPC was automatically recognized by the database. The frequencies were analyzed for the years 2019, 2020 and 2021 respectively.

Results:
In years 2019, 2020 and 2021 – 10,328,341, 9,478,949 and 9,637,595 patients fulfilled the inclusion criteria. One antihypertensive drug was used by 28.5, 28.0 and 28.3% of patients. The remaining patients used two antihypertensive drugs 27.4, 28.1 and 28.0%, three antihypertensive drugs 21.6, 22.2 and 22.1%, four antihypertensive drugs 12.7, 12.8 and 12.7% and 5 or more antihypertensive drugs 9.8, 9.0 and 9.0%. There was a modest increase in two drug SPC, which were used by 28.0, 28.7 and 29.8% of patients. There was an increase in the use of three drug SPC – 2.6%, 2.9% and 3.4% of patients.

Conclusions:
Although a modest, significant increase in the frequency of SPC use, both based on two and three antihypertensive drugs, was found, the COVID-19 pandemic and the ESC/ESH 2018 recommendations supporting the use of combination treatments, have had little impact on the prevalence of combination treatment in Poland.
GUIDELINES-BASED THERAPEUTIC STRATEGIES FOR CONTROLLING HYPERTENSION IN NON-CONTROLLED HYPERTENSIVE PATIENTS FOLLOWED BY FAMILY PHYSICIANS IN PRIMARY HEALTH CARE. THE GPHT-PT STUDY
Authors: Polonia Jorge , Pereira Raul 
Published: June 2023

Objective:
In a prospective open study conducted in Primary Care by GPs, we evaluated the efficacy of a single pill of candesartan + amlodipine as the only anti-HT medication in patients (18 - 80 years) with uncontrolled hypertension (HT) (BP > 140/or > 90 mm Hg, either treated with anti-HT monotherapies (Group I), or combinations with hydrochlorothiazide (HCTZ) (Group II), or not receiving medication at all (Group III).

Design and method:
Each of 100 GPs recruited the first 25 patients without CV events and with uncontrolled HT. Three groups were defined in the first (v0) clinical evaluation and evaluated in 2 more moments (v6 and v12 weeks) in which office blood pressure (BP, mean of 2 of 3 records) was evaluated as in guidelines. Control of HT = BP< 140/90 mmHg. ANOVA repeated measurements controlling as covariant the age (X = 61.95; ± 9.69).

Results:
Of 1234 patients recruited, 762 (age 61 + 10 years, 52% women) completed the 12 weeks of study: (Group I, n = 332, 58% women; Group II, n = 77, 42% women; Group III, n = 343, 51% women). According to severity, patients were medicated with one of 3 (morning) fixed combination candesartan/amlodipine dosage: 8/5 or 16/5 or 16/10 mg/day. SBP/DBP values (mm Hg). In Group I BP = 156/91 + 12/11 (v0); v12 : SBP/DBP -25/-14 mm Hg <0.01 and 85% pts controlled with 8/5 (67%), 16/5 (17%), 16/10 (16%). In Group II BP = 161/93 + 16/13 (v0); v12 SBP/DBP -29/-14 mm Hg <0.01 and 91% pts controlled with 8/5 (44%), 16/5 (17%), 16/10 (39%). In Group III BP = 167/95 + 15/10 (v0); v2 : SBP/DBP -34/-17 mm Hg <0.01 and 76% controlled patients with 8/5 (54%), 16/5 (29%), 16/10 (17%). There was no weight variation during the study. From v6 and v12 BP falled but without statistical significance.

Conclusions:
In patients with uncontrolled HT (under monotherapy, combinations with HCTZ or non-medicated) followed by GPs, therapeutic measures in accordance with guidelines with a fixed combination ARB/amlodipine allowed to achieve HT control at 12 weeks in 76 - 91% of previously uncontrolled patients, reinforcing the advantages of implementing these strategies in primary clinical practice.
REAL-WORLD ANALYSIS ON DRUG UTILIZATION, CARDIOVASCULAR HOSPITALIZATION AND HEALTHCARE COSTS OF PATIENTS ON SINGLE PILL VS FREE COMBINATION OF PERINDOPRIL/BISOPROLOL IN ITALY
Authors: Masi Stefano , Kobalava Zhanna , Veronesi Chiara , Giacomini Elisa , Esposti Luca Degli , Tsioufis Konstantinos 
Published: June 2023

Objective:
The present real-world analysis aims to compare the drug utilization, CV hospitalizations and healthcare direct costs related to the use of single-pill combination (SPC) or free-combination of perindopril/bisoprolol (PER/BIS) in a large Italian population.

Design and method:
This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or free combination between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as free-combination ( ± 1 month) or SPC. Before comparing the SPC and free-combination cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Adherence was defined by proportion of days covered (PDC) and time to treatment discontinuation (evaluated by Kaplan-Meier curves). Given that the SPC PER/BIS can be taken as half a tablet a day, the PDC was calculated assuming the prescription of one tablet/day or half tablet/day. Mean annual healthcare direct costs were analyzed as overall drugs, hospitalizations and outpatient services costs during follow-up.

Results:
The original cohort included 11,440 and 6,521 patients taking the SPC and free PER/BIS combination, respectively. After PSM, two balanced SPC and free-combination cohorts of 4,688 patients were obtained (mean age 70 years, approximately 50% male). Proportion of adherent patients (PDC > = 80%) was higher for those on SPC (45.5% and 76.3% assuming one SPC/day or half SPC/day, respectively) than those on free-combination (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% in SPC cohort and 41.7% of patients in the free-combination cohort (p < 0.001, Figure 1A). The SPC cohort had less cardiovascular (CV) hospitalizations (5.3%) and shorter CV hospital admissions (0.4 ± 2.3 days) than the free-combination cohort (7.4% and 0.6 ± 2.9 days), p < 0.001 for both comparisons (Figure 1B). Mean annual total healthcare costs were lower in the SPC (1,999€) than in the free-combination (2,359€) cohort (details on cost items are presented in Figure 1B).

Conclusions:
Patients treated with PER/BIS SPC have higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on free-combination.
IMPACT OF RAMIPRIL/AMLODIPINE DOSE COMBINATIONS OF SINGLE-PILL VERSUS FREE EQUIVALENT COMBINATIONS ON PERSISTENCE AND MAJOR ADVERSE CARDIOVASCULAR EVENTS: A REAL-WORLD ANALYSIS
Authors: Farsang Csaba , Burnier Michel , Narkiewicz Krzysztof , Rokszin György , Abonyi-Tóth Zsolt , Kovács Gábor , Potukuchi Praveen Kumar , Abdel-Moneim Mohamed , Simonyi Gabor 
Published: June 2023

Objective:
Guidelines recommend use of single-pill combination (SPC) for management of hypertensive patients. Very few studies compared SPCs and free equivalent combinations (FEC) focusing on short-term persistence and major adverse cardiovascular events (MACE) outcomes. This study assessed the impact of different dose combinations of ramipril/amlodipine (R/A) SPC versus FEC on treatment persistence and MACE in patients with hypertension over a 5-year period.

Design and method:
This real-world, retrospective, observational cohort study was performed using National Health Insurance Fund of Hungary database. The study included hypertensive patients aged > = 18 years who initiated on R/A SPC or FEC, of different dose combinations: R/A 5/5 mg, 5/10 mg, 10/5 mg and 10/10 mg, between 01 April 2012 and 31 December 2018. Primary endpoint was the long-term persistence rate, applying 90-days grace period, between R/A SPC and FEC. Secondary endpoint was the rate of MACE (composite of non-fatal myocardial infarction, stroke, hospitalization for heart failure and all-cause death). Analyses were performed using Cox-proportional hazard model and propensity score sub-classification method to adjust the imbalances in baseline characteristics.

Results:
Overall, 173,206 patients with hypertension were included (SPC group, N = 104,882 [61%], and FEC group, N = 68,324 [39%]); R/A 5/5 mg representing the largest proportion (N = 107,992 [62%]). In SPC and FEC groups, mean (SD) age was 61.31 (13.75) and 66.08 (13.10) years and proportion of male was 45.4% and 43.1%, respectively. As shown in Table 1, the rate of non-persistence was significantly lower with all R/A SPCs compared to FECs from Month 1 to Month 24 (P < 0.001). Thereafter, the rate of non-persistence remained significantly lower in the SPC groups except in the R/A 5/5 mg dose. MACE was significantly reduced with all R/A SPCs compared to FECs (HR 0.68–0.73; P < = 0.002). There was no impact of age and gender on the association between the treatment and persistence rate or MACE outcomes.

Conclusions:
Our results confirm the beneficial effects of SPCs compared to FECs in achieving long-term improvement on persistence rate and MACE outcomes in patients with hypertension and support current guidelines recommending a widespread use of SPCs.
THE INFLUENCE OF DEPRESSION IN HYPERTENSIVE ELDERLY PATIENTS
Authors: Munteanu Alice Elena , Ispas Irina , Ionita Iulia Teodora , Casian Mihnea 
Published: June 2023

Objective:
Depression and cardiovascular diseases are two common pathological entities in the elderly, their incidence increasing with advancing age. Clinicians have empirically observed that depression is an independent risk factor for hypertension, thus showing the need to demonstrate this hypothesis through clinical trials and also the correlation of depression with the occurrence of other cardiovascular diseases.

Design and method:
The study was carried out on 127 patients in the Emergency County Hospital dr. Pompei Samarian Calarasi, with cardiovascular disease, including hypertension, and/or depression. The presented study is observational, analytical, retrospective. The study group was randomized according to inclusion and exclusion criteria established prior to patient selection.

Results:
Hypertension is very common in the elderly. We observe a significant increase in blood pressure values with age.
Patients at low, moderate, and high cardiovascular risk tend to have mild or moderate depression, and those at very high risk tend to have moderate or severe depression.
Depression influences cardiovascular risk factors, favoring the increase of serum cholesterol and triglyceride values and favoring the decrease of serum HDL-cholesterol values, the influence of depression being statistically significant.
The proportion of patients with hypertension who associate depression increases with increasing blood pressure values. To emphasize the importance of depression in hypertension, we excluded patients with metabolic syndrome. It has been observed that in these patients the association between depression and hypertension increases, emphasizing the fact that depression represents a cardiovascular risk factor.
Studying the relationship between the severity of depression and the degree of arterial hypertension, it was observed that in patients with high blood pressure, the degree of depression is high.

Conclusions:
Considering all these aspects, we emphasize the importance of the correct and early diagnosis of depression in elderly patients, this being an important risk factor for cardiovascular diseases, including hypertension, often ignored in medical practice.
A SIGNIFICANT INCREMENT IN LEFT ATRIAL PRESSURE AFTER CRYOBALLOON ABLATION INDICATE WORSE ATRIAL FUNCTION: EVIDENCE FROM APPEARANCE-AF TRIAL
Authors: Zhongyuan Ren , Wu Jiayu , Xu Yawei , Zhao Dongdong , Zhao Yifan , Maimaitiaili Rusitanmujiang 
Published: June 2023

Objective:
Left atrial pressure (LAP) is a direct reflection of left atrial function, while LAP could fluctuate following left atrial procedure. The pattern of LAP change in response to pulmonary vein isolation (PVI) and its significance remain to be explored. This study aimed to investigate the pattern of LAP change before and after PVI, and its correlation with other clinical profiles.

Design and method:
28 patients underwent PVI using cryoballoon ablation were included (from APPEARANCE-AF trial). Pre-ablation and post-ablation LAP were directly measured via catheter. The correlation of LAP change with demographics, biochemical measurements, and speckle traced echocardiographic indexes of left atrium (LA) were investigated.

Results:
The included cohort has a mean age of 73.8±8.4 years old, with 12 male (42.9%). Instant PVI was achieved in all patients without complications. The average mean LAP (mLAP) measured before and after PVI was 8.2±4.5 mmHg (pre mLAP) and 14.0±6.5 mmHg (post mLAP), with a significant increment (↗mLAP: 5.8±4.5 mmHg, P<0.001). The change in LAP significantly correlated with LA strain rate in reservoir (LASr, r = -0.58, P = 0.001) and conduit phase (LAScd, r = 0.63, P<0.001) and LA ejection fraction (r = -0.48, P = 0.014). Correspondingly, patients with larger LAP increment (inc-mLAP, increment of mLAP>5 mmHg, n = 14) presented significant worse atrial function indicated by LASr (17.3%±5.6% ninc-mLAP vs 11.5%±7.3% inc-mLAP, P = 0.030), LAScd (-9.6%±2.2% ninc-mLAP vs -5.7%±3.6% inc-mLAP, P = 0.003).

Conclusions:
PVI could significantly increase LAP, and a higher change of LAP might indicate worse atrial function. The prognostic value of LAP change necessitates further follow-up evaluation.
RISK STRATIFICATION OF STAGE B HEART FAILURE USING HOME BLOOD PRESSURE MONITORING AND EFFECT ON THE INCIDENCE OF HEART FAILURE
Authors: Wachi Sumika , Narita Keisuke , Hoshide Satoshi , Kario Kazuomi 
Published: June 2023

Objective:
Recently, the international guideline recommends use of the universal definition of Stage B heart failure (HF) based on cardiac biomarkers for risk stratification of asymptomatic HF. There is a few study reporting the association between home blood pressure (BP) and the stage B of HF. We thus assessed this issue by using the dataset of the nationwide prospective study regarding home BP monitoring, the Japan Morning Surge Home BP (J-HOP) study.

Design and method:
In the J-HOP study, 4,310 outpatients with cardiovascular risk were enrolled and underwent a consecutive 14-days home BP monitoring in morning and evening. In the present study, we assessed 3,218 participants after excluding participants with pre-history of HF and other cardiovascular diseases and lack of data in biomarkers. NT-proBNP 125pg/ml or Hs-cTnT >0.014ng/ml in women, >0.022ng/ml in men were defined as the Stage B of HF based on the guideline (n = 604).

Results:
In the multivariable logistic model, increase of morning home systolic BP was significantly associated with the risk of the stage B of HF (adjusted OR per 10mmHg, 1.25; 95%CI, 1.16–1.33). After followed-up of median 6 years, 19 patients were hospitalized for HF. The stage B of HF was at greater risk of developing heart failure than the stage A patients (adjusted HR, 3.76; 95% CI, 1.40–10.06) in the multivariable Cox model.

Conclusions:
From our findings, morning home BP might be useful for risk stratification of early stage of HF.
A COMMERCIAL-OFF-THE-SHELF FREQUENCY MODULATED CONTINUOUS WAVE RADAR FOR VITAL SIGN MONITORING
Authors: D’Elia Massimo Emiliano , Zarudniev Mykhailo , Bonnet Stephane 
Published: June 2023

Objective:
Radar systems are capable of retrieving remotely micro-movements with very high precision. Millimeter-wave radars are already used in several medical applications (e.g. sleep disorders, heart beat rate, patient monitoring) and have shown promising results towards a remote Doppler cardiogram or arterial pulse wave measurements techniques. In this work, we tested a 122 GHz commercial-off-the-shelf (COTS) Frequency Modulated Continuous Wave (FMCW) radar for vital (respiratory and cardiac) signals monitoring. This required the setting up of a very precise experimental bench and the investigation of a robust data processing procedure.

Design and method:
An experimental bench (see Figure 1-a) has been set up with a high precision Newport linear actuator: a small target can be then displaced with less than 3 μm accuracy. Such system can replicate the thorax displacements due to the respiratory and cardiac activity. Two different motions were simulated: a ‘large’ 8 mm displacement at 0.15 Hz (a.k.a. respiratory) and a ‘small’ 0.5 mm at 1 Hz (a.k.a. cardiac). Furthermore, a shaker system can be used to reproduce completely arbitrary movements, even from real acquired Electrocardiogram (ECG) data. In this case, however, a reference measurement system would be necessary to determine the accuracy.

Results:
A first measurement set was dedicated to evaluate the accuracy of the radar system: around 50 acquisitions for each type of displacements were carried out. The accuracy of the radar measurements results in the order of ∼10 μm (see Figure 2). A second measurement set tested the dynamic resolution: in this case, a 0.4 Hz sinusoidal signal and a 0.8 Hz pulsation mix were fed to the shaker system. The radar is capable of retrieving both signal signatures (see Figure 3), with errors due to the combination of sharp pulse rise and low radar sampling frequency

Conclusions:
We show that a COST radar is able to retrieve vital signs chest displacements with a good accuracy in both amplitude and dynamics, thus representing a valid option for a remotely continuous cardiovascular monitoring. Next objectives are In Vivo measurements with an in-house radar system and measurements of blood pulse waves.
RADIAL ARTERY PHENOTYPING IN SYSTEMIC SCLEROSIS THROUGH ULTRA-HIGH FREQUENCY ULTRASOUND: A RADIOMIC APPROACH
Authors: Poli Federica , Boleto Goncalo , Khettab Hakim , Boutouyrie Pierre , Allanore Yannick , Bruno Rosa Maria 
Published: June 2023

Objective:
Systemic sclerosis (SSc) is a disorder characterized by a massive vascular involvement. Imaging biomarkers of vascular involvement in SSc may have potential clinical implications for prediction of the pathogenesis of vascular complications. This study is aimed at identifying possible patterns of vascular wall disarray and remodeling in radial arteries of SSc patients, by means of ultrahigh frequency ultrasound (UHFUS).

Design and method:
5 end-diastolic frames of the right radial arteries of 41 patients with SSc and 41 healthy controls were obtained by VevoMD (70 MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). 74 radiomic features and 4 engineered parameters were extracted: inner and outer layer thickness, and presence of adjunctive acoustic interfaces (triple signal). A feature selection algorithm was applied to reduce the number of features. The selected features were used to train classification model, using Linear Support Vector Machine (SVM).

Results:
The SVM classification model showed good performance (sensitivity = 0.63, specificity = 0.88, accuracy = 0.75, AUC = 0.75) to discriminate SSc patients from controls using fifteen selected features. Inner layer (208±61 vs 179±47 μm, p = 0.04) and outer layer thickness (104±22 vs 120±36 μm, p = 0.03) were significantly higher in SSc than in controls, triple signal pattern more frequent in patients (p = 0.002).

Conclusions:
Wall ultrastructure of radial arteries of SSc patients is altered: inner and outer layer thickened, showing frequently a triple signal pattern. Radiomic approach allow to distinguish between radial images from SSc patients and controls with a 75% accuracy.
IDENTIFYING HYPOKALEMIA RISK IN HYPERTENSIVE PEOPLE: USING MACHINE LEARNING IN THE UNITED STATES NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 1999-2018
Authors: Lin Ziying , Cheng Yuen Ting , Cheung Bernard Man Yung 
Published: June 2023

Objective:
Hypokalemia is a side-effect of diuretics. We aimed to use machine learning to identify features predicting hypokalemia risk in hypertensive patients.

Design and method:
Participants with hypertension in the United States National Health and Nutrition Examination Survey 1999-2018 were included for analysis. To choose the optimal algorithm, we tested five machine learning algorithms (Logistic Regression, k-Nearest Neighbor, Random Forest, Recursive Partitioning and Regression Trees, and eXtreme Gradient Boosting) with 38 screened features. We selected the most appropriate model according to the area under the receiver operating characteristic curve (AUROC). We then selected the key hypokalemia-associated features in the hypertension group and their cardiovascular diseases (CVD) subgroup using the SHapley Additive exPlanations (SHAP) values. Using SHAP values, the key features and their impact pattern on hypokalemia risk were determined.

Results:
21,096 hypertensive participants, of whom 3,540 had known CVD, were included for analysis. The Random Forest algorithm had the highest AUROC (hypertension dataset: 0.73 [95%CI, 0.70-0.75], P<0.001; CVD subgroup: 0.76 [95%CI, 0.70-0.82], P<0.001) and sensitivity (hypertension dataset: 0.62; CVD subgroup: 0.72) based on 38 features screened. Moreover, the nomogram based on the top fifteen key features screened by random forest retained good performance (hypertension dataset: 0.73 [95%CI, 0.70-0.75], P<0.001; CVD subgroup: 0.74 [95%CI, 0.68-0.81], P<0.001): gender, race, age, poverty income ratio, smoking status, body mass index, systolic and diastolic blood pressure, non-potassium-sparing diuretics use and duration, duration of renin-angiotensin blockers, potassium-sparing diuretics use, polypharmacy, and comorbid arthritis and diabetes in hypertension dataset; while in CVD subgroup, renin-angiotensin blockers use replaced potassium-sparing diuretics use.

Conclusions:
Our predictive model shows good performance, and hypokalemia-associated key features have been identified in hypertensive patients and the subgroup with CVD. These findings from machine learning facilitate the development of artificial intelligence to highlight hypokalemia risk in hypertension patients.