bluuebunny/crossref_metadata_2025_split huggingface dataset:
TREATMENT STRATEGIES AND ADHERENCE TO THE TRIPLE COMBINATION OF AN ANGIOTENSIN-CONVERTING ENZYME INHIBITOR, A CALCIUM-CHANNEL BLOCKER, AND A DIURETIC
Authors: Rea Federico , Morabito Gabriella , Savaré Laura , Pathak Atul , Corrao Giovanni , Mancia Giuseppe 
Published: June 2023

Objective:
To compare adherence to antihypertensive treatment between patients prescribed the perindopril/amlodipine/indapamide single-pill combination (SPC) vs the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a SPC of two drugs plus the third drug separately.

Design and method:
Patients aged > = 40 years who received a prescription of perindopril/amlodipine/indapamide SPC during 2015-2018 were identified and the date of the first prescription was defined as the index date. For each patient prescribed the SPC, a subject who started ACEI/CCB/D treatment as a two-drug SPC plus a third drug separately (i.e. 2 pills) at the index date was identified. Adherence to the triple combination was assessed over the year after the index date as the proportion of the follow-up days covered (PDC) by prescription. The primary aim was to compare the odds of being highly adherent to the drug therapy (PDC>75%) between groups. Secondary aims were to compare (i) the risk of cardiovascular hospitalizations and (ii) the costs of cardiovascular health services (hospitalizations, drugs, and outpatient services).
Log-binomial regression models were fitted to estimate the risk ratio, and its 95% confidence interval, of treatment adherence in relation to the drug strategy. A Cox model and a linear regression model were fitted to compare the risk of cardiovascular hospitalizations and mean of healthcare costs, respectively, between groups.

Results:
28,210 patients prescribed the perindopril/amlodipine/indapamide SPC were identified and matched to 28,210 patients prescribed ACEI/CCB/D in two pills.
Compared with patients under two-pill combination, those who were treated with the SPC had a higher propensity to be highly adherent to the triple combination (2.38, 2.32 – 2.44).
Three-drug SPC users had a 13% lower risk of cardiovascular hospitalizations and a € 64 lower costs for cardiovascular healthcare services (p < 0.001) due to reduced hospitalization costs (€ 59).

Conclusions:
In a real-life setting, patients who were prescribed the perindopril/amlodipine/indapamide SPC exhibited more frequently a good adherence to antihypertensive treatment than those prescribed a combination of ACEI/CCB/D as a two drugs SPC plus a third drug separately.
PREVALENCE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) USE IN PATIENTS WITH HYPERTENSIVE CRISIS
Authors: Soodeh Jahangiri , Mousavi Seyed Hamidreza , Reza Hatamnejad Mohammad , Salimi Maryam , Bazrafshan Hamed 
Published: June 2023

Objective:
One of the known risk factors for hypertensive crisis (HTN-C) is non-steroidal anti-inflammatory drugs (NSAIDs) which their adverse effects can lead to end-organ damage such as gastrointestinal and cardiovascular issues.
Data on the correlation between NSAIDs and HTN-C are limited. In this study, we determined the prevalence of NSAID use among patients with HTN-C.

Design and method:
This cross-sectional study was conducted among patients primarily diagnosed with HTN-C referred to Alzahra hospital, Shiraz, Iran from April 2015 to April 2020. Demographic data, as well as information regarding the past medical and drug history and laboratory findings, were gathered -retrospectively. The history of NSAID use was also asked specifically. The collected data were analyzed by SPSS and the P-value less than .05 was considered significant.

Results:
A total of 257 patients with a mean age of 59.73 were enrolled in the study. Among them 62.6% were female and 137 patients (53.33%) used NSAIDs. Of all the patients 197 (76.7%), 71 (27.6%), and 46 (17.9%) suffered from concomitant hypertension (HTN), diabetes mellitus (DM), and ischemic heart disease (IHD) respectively. A significant relation was found between having each of the comorbidities and NSAIDs use among HTN-C patients (P-value <.0001). NSAIDs use was also significantly higher in older age (P-value <.0001) and female gender (P-value <.02). A high rate of NSAID use was seen among HTN-C patients with a positive significant correlation to concomitant diseases, older age, and female gender.

Conclusions:
The Results of our study indicate that NSAIDs are frequently used among those with HTN-C and considering the adverse effects of these medication our results further highlight the importance of monitoring and limiting NSAID use.
THE ASSOCIATION BETWEEN ANTIHYPERTENSIVE TREATMENT AND SERIOUS ADVERSE EVENTS BY PREVIOUS HISTORY OF ADVERSE EVENTS: AN OBSERVATIONAL COHORT STUDY
Authors: Sheppard James , Koshiaris Constantinos , Stevens Richard , Lay-Flurrie Sarah , Banerjee Amitava , Bellows Brandon , Clegg Andrew , Hobbs Richard , Payne Rupert , Swain Subhashsia , Usher-Smith Juliet , McManus Richard 
Published: June 2023

Objective:
Antihypertensives are effective at reducing the risk of cardiovascular disease, but are also associated with an increased risk of serious adverse events (SAEs), particularly in older people. Since these patients may also be at increased risk of cardiovascular disease, guidelines recommend deprescribing medications only in those with a previous history of adverse events. This study examined whether the association between antihypertensive treatment and adverse events is greater in this population.

Design and method:
This was an observational cohort study, using data from the Clinical Practice Research Datalink in England (Aurum and Gold databases combined). Patients were eligible if they were aged 40 years or older, with a systolic blood pressure reading between 130-179 mmHg and not previously prescribed antihypertensive treatment. Outcomes were defined as hospitalisation or death within 10 years due to hypotension, syncope, falls, fractures, acute kidney injury (AKI), electrolyte abnormalities and primary care consultations for gout. The association between treatment and SAEs was examined by Cox regression, using propensity score adjustment, sub-grouped by whether or not individuals had a history of adverse events.

Results:
A total of 3,834,056 patients, aged 57±12 years, were eligible for the study. Of these, 484,187 (12.6%) were prescribed antihypertensive medication in the 12 months prior to the index date. A total of 902,100 patients (23.5%) had a history of previous adverse events. Over 7.1 years, antihypertensives were associated with an increased risk of hypotension, syncope, falls, AKI, electrolyte abnormalities and gout but not fractures. For those with no history of adverse events, the absolute risk of SAEs with treatment small, ranging from 6 (falls) to 16 (AKI) events per 10,000 patients treated per year. However, in those with a previous history of these adverse events, the risk was notably higher, ranging from 19 (falls) to 80 (AKI) events per 10,000 patients treated per year.

Conclusions:
Antihypertensive treatment is associated with an increased risk of SAEs particularly in those with a history of serious adverse events. Clinical guidelines should continue to recommend that patients with a history of serious adverse events are recommended as candidates for deprescribing interventions.
PREVALENCE AND CLINICAL CORRELATES OF HYPOTENSIVE EPISODES AMONG OLDER HYPERTENSIVE ADULTS UNDERGOING 24-H AMBULATORY BLOOD PRESSURE MONITORING
Authors: Rivasi Giulia , Capacci Marco , Ceolin Ludovica , Turrin Giada , Rossi Lorenza , Liccardo Alessandra , Bisignano Maria Francesca , Testa Giuseppe Dario , Mossello Enrico , Ungar Andrea 
Published: June 2023

Objective:
Older adults have increased susceptibility to hypotension. Hypotensive episodes have a negative prognostic impact at old age, being associated with adverse events such as syncope, falls and injuries, which impair quality of life and functional autonomy. 24-hour ambulatory blood pressure monitoring (ABPM) is a useful diagnostic tool to detect hypotension, although it is rarely used for this purpose.
The present study aimed at assessing the prevalence and the clinical variables associated with hypotensive episodes on ABPM among older hypertensive adults.

Design and method:
prospective observational study involving hypertensive patients aged 75 or older evaluated at two outpatient clinics of Careggi Hospital, Florence, Italy. All participants underwent a comprehensive geriatric assessment, office blood pressure measurement and ABPM. Hypotensive episodes were defined as single daytime systolic blood pressure (SBP) measures <90 mmHg. Clinical variables associated with hypotensive episodes were investigated using multivariable logistic regression.

Results:
Among 123 participants (mean age 81 years, 59% female), the 16% showed hypotensive episodes on ABPM. Patients with hypotensive episodes were older (84±5 vs 81±4 years, p = 0.002), had a higher prevalence of dementia (50% vs 26%, p = 0.034) and received a higher number of daily medications (8[6-10] vs 6 [5-9], p = 0.036). Moreover, they showed lower 24h-SBP (139±15 vs 149±15, p = 0.008), daytime SBP (141±15 vs 151±15, p = 0.005) and night-time SBP (129±18 vs 140±20, p = 0.005) and a higher prevalence of white coat effect (30% vs 12%, p = 0.034). At multivariable analysis, hypotensive episodes were associated with use of angiotensin-receptor blockers (ARBs, OR 24.325, p = 0.002), independently of age, sex, dementia, 24h-SBP and number of medications. By contrast, use of ACE-inhibitors (OR 0.719, p = 0.013) and thiazide diuretics (OR 0.978, p = 0.048) were inversely associated with hypotension on ABPM.

Conclusions:
Hypotensive episodes are a common finding in older adults undergoing ABPM. Hypotensive episodes more frequently occur in patients with lower SBP and white coat effect and are independently associated with ARBs use. ACE-inhibitors and thiazides are inversely associated with hypotensive episodes on ABPM.
PREDICTIVE VALUE OF PROTEIN-BOUND UREMIC TOXINS FOR HEART FAILURE EVENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Zwaenepoel Bert , Backer Tine de , Biesen Wim Van , Glorieux Griet , Verbeke Francis 
Published: June 2023

Objective:
Evaluate whether the plasma free fraction of four important protein-bound uremic toxins (PBUTs), indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG) and hippuric acid (HA), are independently associated with new heart failure (HF) events in patients with chronic kidney disease (CKD), not on dialysis.

Design and method:
Retrospective, single center analysis. 526 patients with CKD stages G1-G5 (not on dialysis), were included between January 2011 and January 2014. Outcome parameters were monitored until June 2017. Exclusion criteria were pregnancy, age <18 years, active infection, active malignancy, history of transplantation or a cardiovascular event within the past three months. Free fractions of uremic toxins were quantified by ultrahigh-performance liquid chromatography. Kaplan-Meier survival curves were constructed to investigate the univariate association between PBUTs and the composite endpoint of hospitalization or death due to HF. Multivariate Cox regression models were used to study the independent association of PBUTs with outcome.

Results:
The study population (57.8% male) had a median age of 66 years and varying degrees of CKD: stage G1 (12.2%), 2 (16.3%), 3A (21.1%), 3B (27.8%), 4 (19.2%) and 5 (3.4%). After a median follow up of 5.4 years 43 patients (8.4%) developed the primary endpoint, 18.6% (8/43) were fatal. In Cox regression analysis with adjustment for age, gender, body mass index, diabetes and systolic blood pressure, the free fractions of all four PBUTs remained independent predictors of new heart failure events [IxS: HR 1.46 (95% CI: 1.06 – 2.01; P = 0.019); pCS: HR 1.75 (95% CI: 1.21 - 2.54; P = 0.003); pCG: HR 1.65 (95% CI: 1.17 - 2.32; P = 0.004); HA: HR 1.43 (95% CI: 1.05 - 1.95; P = 0.022)]. Univariate survival analyses are shown in Figure 1.

Conclusions:
Free fraction of the PBUTs indoxyl sulfate, p-cresyl sulfate, p-cresyl glucuronide and hippuric acid were independently associated with hospitalization and mortality due to HF in patients with CKD. The pathophysiological pathways by which these toxins may contribute to heart failure remain to be elucidated.
THE SPECIFICS OF POSTCOVID ATRIAL FIBRILLATION IN ELDERLY AND LATE-LIFE PATIENTS WITH ARTERIAL HYPERTENSION AND ISCHEMIC HEART DISEASE
Authors: Wang Zheming , Talibov Faiz , Zbyshevskaya Elizaveta , Mayer Mark , Makeeva Tatiana 
Published: June 2023

Objective:
To study the frequency and conditions for the emergence of atrial fibrillation paroxysms (AFP) in elderly and late-life patients in the postcovid period on the background of comorbid pathology.

Design and method:
2 months after SARS-Cov-2-pneumonia, 124 people were examined, 66 of them (41 men and 25 women) aged 68±5.9 years (group 1) and 58 (33 men and 25 women) aged 81±4.3 years (group 2). According to computed tomography (CT) performed during SARS-CoV-2-pneumonia, in group 1, 12 patients (18.2%) had lung lesion volume < 25% (CT1); 34 patients (51.5%) 25-49% (CT2); 18 patients (27.3%) 50-74% (CT3); 2 patients (3%) > 75% (CT4). In group 2, 14 patients (24.1%) had CT1; 18 patients (31.1%) CT2; 21 patients (36.2%) CT3; 5 patients (8.6%) CT4. All patients had arterial hypertension (AH) and coronary heart disease (CHD) on the background of atherogenic dyslipidemia; 59 had type 2 diabetes mellitus (DM), 13 had chronic kidney disease (CKD). Holter monitoring (HM) was performed for all. The content of ferritin, D-dimer, and CRP in the blood plasma was measured for all.

Results:
According to the HM, in 13 of 66 (19.7%) group 1 patients, AFP were registered, of which 7 patients had 30-40 minutes seizures, 3 patients – about 2 minutes seizures. 3 patients were hospitalized, their sinus rhythm was restored by cardioversion. In 16 of 58 (27.6%) group 2 patients, HM revealed AFP, 2 of them were hospitalized due to the deterioration of their condition, the sinus rhythm was restored by cardioversion. In 7 patients, AFP did not exceed 30 minutes; in another 7 patients, AFP were short, no more than 2-3 minutes. Blood ferritin in group 1 was 175±66.2 ng/ml; in group 2 212±40.2 ng/ml (p = 0.012); D-dimer 501±50.3 ng/ml and 835±53.8 ng/ml, respectively (p = 0.0002); CRP 4.3±2.1 mg/l and 8±3.3 mg/l, respectively (p = 0.0009).

Conclusions:
2 months after SARS-CoV-2-pneumonia with a large area of lung damage, elderly and late-life patients with a very high cardiovascular risk have signs of inflammation, and a tendency to increased thrombosis, which probably causes the AFP emergence.
ARTERIAL HYPERTENSION AS A PREDICTOR OF THROMBOEMBOLIC EVENTS IN PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH DIRECT ORAL ANTICOAGULANTS
Authors: Sinigoj Petra , Kabaklic Amela , Hitij Jana Brguljan , Mavri Alenka 
Published: June 2023

Objective:
The aim of the study was to assess predictors of thromboembolic events in patients with atrial fibrillation treated with direct oral anticoagulants (DOAC).

Design and method:
From our single-centre prospective registry we enrolled 2792 consecutive atrial fibrillation patients that were started on dabigatran, rivaroxaban or apixaban. The mean duration of treatment exposure was 724 days. The primary outcome was the incidence of thromboembolic events. The incidence of bleeding events and death were also assessed. Potential risk factors for thromboembolic events were evaluated using Cox regression analysis.

Results:
During the follow-up, 94 patients experienced a thromboembolic event (1.9%/year). Twelve patients experienced two and one patient experienced three thromboembolic events. Considering only the first thromboembolic event, 39 patients experienced a stroke, 14 patients a transient ischaemic attack (TIA), 12 patients a systemic thromboembolism (SE), 19 patients myocardial infarction (MI) and 10 patients a venous thromboembolic event. Twelve thromboembolic events were fatal (0.2%/year). According to a multivariate Cox regression analysis (Table 1), significant predictors for a composite endpoint of stroke, TIA, SE and MI were age group (HR 1.27, 95% CI 1.04–1.56, p = 0.022), arterial hypertension (HR 2.86, 95% CI 1.15–7.12, p = 0.024) and history of stroke, TIA or SE (HR 2.6, 95% CI 1.66–4.05, p < 0.001). The incidence of major bleeding was 2.3%/year.

Conclusions:
In this prospective clinical study we have shown that age, arterial hypertension and history of stroke, TIA or SE were strong predictors of arterial thromboembolic events in patients with atrial fibrillation treated with DOAC. Among those, arterial hypertension had the highest hazard ratio. Since arterial hypertension presents a potentially modifiable predictor, it can be assumed that its treatment was not adequate.
EFFECT OF LOW BLOOD PRESSURE ON ACUTE HEART FAILURE PROGNOSIS ACCORDING TO HEART FAILURE CLASSIFICATION
Authors: Kim Hyun-Jin , Jo Sang-Ho 
Published: June 2023

Objective:
Blood pressure (BP) management is complex in patients with heart failure (HF), but is important with respect to HF progression and clinical prognosis. We evaluated the actual prescribing patterns of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) and beta-blockers (BB) in patients with HF at discharge and clinical prognosis according to initial BP level in patients with acute HF.

Design and method:
Study data were obtained from a multicenter cohort that included patients hospitalized for acute HF. Patients who had available data regarding initial BP and left ventricular ejection fraction were included in this analysis. The patients were classified into two groups: heart failure reduced ejection fraction (HFrEF) group versus. HF mildly reduced ejection fraction (HFmrEF) and HF preserved ejection fraction (HFpEF) group. Initial systolic blood pressure (SBP) was classified into <100, 100-119, 120-139, 140-159, and > = 160mmHg, and diastolic blood pressure (DBP) into <50, 50-69, 70-89, 90-109, > = 110mmHg.

Results:
Among 2,778 patients, HFrEF patients used ACEi, ARB, or BB at discharge even if their SBP was as low as less than 100mmHg, and there was no significant difference in frequency of medication use by BP level. However, HFmrEF and HFpEF patients showed a tendency to significantly decrease the frequency of medication use as BP decreased. In HFrEF, the lower the initial BP, the higher the incidence of all-cause death and composite clinical events including HF readmission or all-cause death (Table). However, in HFpEF and HFmrEF, there was no significant difference in clinical outcome according to BP. In addition, initial SBP (<120mmHg) was independently associated with 1.81-fold increased risk of long-term mortality [Odds ratio (OR) 1.81, 95% confidence interval (CI) 1.349-2.417, p < 0.001], and initial DBP (<80mmHg) was also 2.24-fold increased risk [OR 2.24, 95% CI 1.645-3.053, p < 0.001].

Conclusions:
Poor clinical prognosis is expected if the initial BP low in patients with HFrEF, and low BP (<120/80mmHg) affects increased mortality independently of HF medication use. Clinicians should be aware of the effect of low BP in patients with acute HF and provide delicate BP control.
DAPAGLIFLOZIN MODULATES ADROPIN SERUM LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CHRONIC HEART FAILURE
Authors: Berezin Alexander , Fushtey Ivan M. , Berezin Alexander A. 
Published: June 2023

Objective:
To investigate an effect of sodium glucose linked transporter 2 (SGLT2) inhibitor dapagliflosin on the levels of adropin in patients with type 2 diabetes mellitus (T2DM) with chronic heart failure (HF).

Design and method:
The study is open label multicenter (private hospital Vita-Centre, Zaporozhye, Ukraine, EliteMedService, Zaporozhye, Ukraine and City Hospital #7, Zaporozhye, Ukraine) non-randomized cohort investigation. We prospectively enrolled 417 patients with T2DM and HF from entire cohort of 612 T2DM pa-tients. The eligible patients were treated with guided-recommended HF therapy de-pending on HF phenotypes, which included SGLT2 inhibitor dapagliflozin in a dose of 10 mg OD orally along with angiotensin receptor-neprilysin inhibitor (ARNI) / ACE inhibitors / angiotensin-II receptor blockers (ARBs), mineralocorticoid receptor antag-onist (MRA), beta-blockers. Anthropometrics, clinical data, Echocardiography / Doppler examinations and biomarkers assessments were performed at the baseline and over 6-month interval.

Results:
Over 6-month period after initial prescription of SGLT2 inhibitor dapagliflozin the levels of adropin in entire group demonstrated a significant growth up to 26.6% (from 237.4 [25%-75% IQR = 190.50–275.30] ng/mL to 300.2 [25%-75% IQR = 267.80–335.70] ng/mL, P = 0.04). In female subgroup, an increase in circulating level of adropin was sufficiently higher (from 269.5 [25%-75% IQR = 231.20–299.20] ng/mL to 365.2 [25%-75% IQR = 340.10–388.60] ng/mL, P = 0.01), when com-pared with male subgroup (from 211.2 [25%-75% IQR = 190.40–237.50] ng/mL to 259.6 [25%-75% IQR = 206.50–321.40] ng/mL, P = 0.16). Multivariate logistic regression analysis of entire group showed that relative changes of left ventricular (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and E/e` were significantly associated with increased adropin levels. In fe-male subgroup, but not in male subgroup, relative changes of LVEF (P = 0.046), LAVI (P = 0.001) and E/e` (P = 0.001) exhibited their independent predictive values for adropin changes.

Conclusions:
The levels of adropin seem to be a predictor for favorable modification of hemodynamic perfor-mances that is independent from N-terminal brain natriuretic pro-peptide.
INFLAMMATION MARKERS AS POTENTIAL MEDIATORS FOR THE ASSOCIATION BETWEEN ARTERIAL STIFFNESS AND OBESITY
Authors: Trouvé Ryan , Wei Dongmei , Vanassche Thomas , Aelst Lucas Van , Verhamme Peter , Janssens Stafen , Zhang Zhen -Yu 
Published: June 2023

Objective:
Arterial stiffness is a strong independent predictor of cardiovascular diseases. Obesity was closely associated with arterial stiffness. This study hypothesised that inflammatory markers mediated the association between obesity and arterial stiffness.

Design and method:
We performed a cross-sectional study in 965 Flemish individuals (mean age 49.4 ± 15.6 years, 51 % female). Carotid-femoral pulse wave velocity (PWV) was measured as indicator of arterial stiffness via application tonometry. Obesity was defined as BMI > = 30 kg/m2. Fourteen plasma inflammatory cytokines were determined, using an ELISA-based assay and composite inflammation scores were calculated using Crohnbach's alpha as an indicator of internal consistency reliability for measurement of inflammatory burden. Insulin resistance (IR) was calculated via the homeostasis model assessment (HOMA), and resistance was defined as HOMA > = 1.9.

Results:
An increased PWV was found in individuals with obesity, compared to those without obesity (8.1 vs. 7.4 m/s, p < 0.001). After adjusting for sex and age, the association between, PWV and obesity remained (0.35, 95% CI: 0.08 – 0.63, p = 0.011). Obesity was positively associated (p < 0.001) with CRP (0.059, 95% CI: 0.037 – 0.081), IL-6 (0.046, 95% CI: 0.023 – 0.068), leptin (0.147, 95% CI: 0.122 – 0.172) and PAI-1 (0.036, 95% CI: 0.015 – 0.058). Mediation analysis showed that the association between PWV and obesity was partially mediated by inflammatory burden scores (18.70 %, p < 0.05) and was borderline mediated by leptin (28.70 %, p = 0.060) and insulin resistance (15.44 %, p = 0.054).

Conclusions:
Our findings confirm the role of inflammation as major mediator in obesity associated arterial stiffness. Leptin and insulin resistance might also involve in arterial stiffness in obesity, which may provide potential treatment targets.