bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE RELATIONSHIP BETWEEN LUNG MIBG UPTAKE AND CLINICAL RESPONSE TO RENAL DENERVATION
Authors: Leo Andrea , Piludu Sara , Ubaldini Giulia Mori , Dalpiaz Hermann , Sciarrone Paolo , Buralli Simona , De Carlo Marco , Taddei Stefano , Masi Stefano , Gimelli Alessia , Bacca Alessandra 
Published: May 2024

Objective:
Renal denervation (RDN) attenuates the sympathetic nervous system overactivity that characterizes patients with elevated blood pressure (BP). Given that accurate predictors of BP response to RDN remain to be identified and that metaiodobenzylguanidine (MIBG) scintigraphy allows non-invasive assessment of sympathetic nerve activity, we explored if the kidney, heart and lung MIBG uptake predict BP response to RDN.

Design and method:
Thirteen patients with difficult-to-treat hypertension underwent radiofrequency-based RDN. Before the procedure, clinical and pharmacological history, office and ambulatory BP values and cardiovascular risk factors were recorded. Patients also underwent preprocedural rest echocardiography and MIBG scintigraphy. After RDN, a follow-up visit was performed at 3 months, with registration of office and ambulatory BP values. We considered as responders (R) those patients showing a reduction of office BP values on unchanged BP-lowering treatment and those who reduced the number and/or dosage of BP-lowering medications while maintaining optimal control of office BP.

Results:
Seven patients were classified as R (1 woman, mean age 48±11 years), while 6 were non-responders (NR) (2 women, mean age 50±8 years). The reduction in office systolic and diastolic BP values from baseline to 3 months was significantly larger in R vs NR (p=0.01). Furthermore, the burden of BP-lowering medications after the procedure was reduced more significantly in R (-44%) than NR (-16%), p<0.01. Baseline heart rate was the only clinical parameter significantly different between R (median 82, IQR [67-98]) bpm vs NR (median 62, IQR [60-72]) bpm, p<0.05. In early MIBG acquisitions, the lung/mediastinum ratio on both sides showed higher MIBG uptake in R vs NR (p<0.05). In late acquisitions, only the left side showed a significant difference between R and NR (p<0.05). There was a higher MIBG uptake in the right vs. left lung in the whole population and in R vs NR. All other MIBG scintigraphy parameters were similar between groups.

Conclusions:
Among patients with difficult-to-treat hypertension, those responding to RDN showed a higher lung/mediastinum ratio at MIBG scintigraphy and a higher heart rate before the procedure. Further studies are needed to confirm these preliminary results.
MORIN ATTENUATES INFLAMMASOME-DEPENDENT MYOCARDIAL INJURY IN DIABETIC RATS: MODULATION OF THE SIGNALING PATHWAY
Authors: Arya Dharamvir , Verma Vipin Kumar , Bhatia Jagriti 
Published: May 2024

Objective:
Diabetes is a risk factor that predisposes to atherosclerotic cardiovascular diseases. The risk of myocardial infarction in diabetes is higher and this warrants investigation into exploring new drugs that can attenuate myocardial injury. In diabetes, high blood glucose levels lead to vascular inflammation which accelerates atherosclerosis. Morin, a plant flavonoid, was found effective for septic shock, cancer, cardiovascular, and renal complications and acts as an agonist for insulin secretion. This study aims to evaluate the mechanism involved in the cardioprotective action of Morin in diabetic rats.

Design and method:
In male Wistar rats, streptozotocin (70 mg/kg; i.p.) was administered to induce diabetes. Diabetes-confirmed rats (blood glucose >400mg/dl) were divided into 4 groups (n=8), i.e., Diabetic-control; Diabetes+Isoproterenol (ISO); Diabetes+ISO+Morin and Diabetes+Morin, in addition to this, one control group was also included in the study. Morin was orally administered at the dose of 40 mg/kg for 28 days and on the 27th and 28th day of morin administration, ISO was administered to designate groups at the dose of 85mg/kg s.c., to induce myocardial injury. After 24 hours of the second dose of ISO administration, the rat was sacrificed after collection of blood, and heart was excised to do the biochemical, histopathological and molecular investigations.

Results:
ROS rush following ISO administration leads to the activation of the intrinsic and extrinsic pathways of apoptosis. Morin significantly reduced oxidative stress, cardiac injury markers levels, inflammation, and apoptosis. In addition, it also reduced serum insulin and blood glucose levels. Histopathology showed cardio-protection with morin. Akt/eNOS, Nrf2/HO-1, MAPK signaling pathways, and Insulin signal transduction pathways were positively modulated by Morin pre-treatment. It also significantly modulated NLRP3 inflammasome formation.

Conclusions:
Morin attenuated oxidative stress and inflammation and also modified the activity of various molecular pathways to mitigate cardiomyocyte damage during ISO-induced MI in diabetic rats.
THE REDUCTION OF MONACOLIN K DOSAGE FROM 10 TO 2.9 MG RESULTS IN A LOSS OF EFFECTIVENESS OF THE LIPID-LOWERING THERAPY
Authors: Napolitano Brunella , Trenta Eva Azzurra Li , Napolitano Valentina , Pulicanò Martina , Ruffolo Andrea Domenico , Vena Evelina , Balsano Mario , Spagnuolo Vitaliano 
Published: May 2024

Objective:
Nutraceuticals can be a valid therapeutic alternative in certain classes of patients. Since June 2023, European Union has mandated a reduction in the dosage of monacolin (<3 mg/day). There is currently no literature data regarding maintenance of therapeutic effectiveness on LDL levels with this dosage.

Design and method:
We evaluated efficacy [percentage reduction in LDL and percentage of achieving the therapeutic goal (<100 mg/dl) of a nutraceutical containing 2.9 mg of monacolin K (MK) in patients with moderate cardiovascular risk (SCORE >0.9 <5% at 10 years)], who were unwilling to take statins, compared to treatment with nutraceutical containing 10 mg. We evaluated 55 patients (35 females) consecutively attending outpatient clinic for dyslipidemia. All patients had been under treatment, for at least nine months (average 14.4±4.8 months), with a nutraceutical containing 10 mg of MK (Colenorm Plus®) and, since June 2022, they started taking nutraceutical containing 2.9 mg of MK. Before any lipid-lowering treatment, the values were: mean age 62.2±8.5 years, BMI 25.5±0.7, TC 202.6±29.3, HDL 53.2±10.7, LDL 125.4±31.7, TG 123±39.2.

Results:
At baseline: BMI 26.7±3.7, TC 167.5±37.2, HDL 50.9±13.4, LDL 92.4±37.5 (-26% compared to no therapy), TG 120.3±59.7. The 63.64% of patients reached target <100 mg/dl. Six weeks after starting new therapy: BMI 26.9±3.5, TC 185.5±43.4, HDL 52.4±10.1, LDL 111.5±33.8, TG 126.5±31.8. LDL values decreased by 11.2% compared to no therapy but increased by 20.7% compared to 10 mg. Patients reaching the goal decreased to 27.27%.

Conclusions:
Reduction of MK to 2.9 mg results in a significant lost in the efficacy on LDL levels and the achievement of the therapeutic goal compared to 10 mg. A new strategy for lipid-lowering nutraceuticals, based on the combination of 2.9 mg of MK with other lipid-lowering molecules, is necessary to achieve a good therapeutic response.
ANTIPLATELET THERAPY IN PRIMARY PREVENTION. OBSERVATIONAL STUDY AND SURVIVAL ANALYSIS IN HIGH CARDIOVASCULAR RISK PATIENTS.
Authors: Meireles-brandao Joaquim , Meireles-brandao Lucia , Coelho Rui , Rocha-goncalves Francisco 
Published: May 2024

Objective:
Cardiovascular diseases are the leading cause of morbidity and mortality in industrialized countries.
This was a retrospective observational study, evaluating clinical outcomes, metabolic consequences and survival rate resulting from prolonged antiplatelet therapy for primary prevention in patients with high CVR.

Design and method:
Overall, 516 patients were randomly selected from cardiovascular risk and metabolism consultations in a single center in Porto (Portugal). Sociodemographic, lifestyle and clinical characteristics were collected at baseline, including biochemical parameters, vascular risk scores and tests for heart and cardiovascular evaluation. In this follow-up with a median of 11 years, 287 patients received adjuvant antiplatelet therapy in primary prevention. Association between sex, observation time and treatments with LDLc and HDLc variations were assessed. Multiple linear regression was performed to evaluate which factors could explain the differences in HDLc and LDLc levels. Kaplan-Meier survival analysis was also conducted.

Results:
Therapy with statins was initiated early for metabolic compensation of dyslipidemia, according to clinical practice. Statistically significant reductions were found for almost all biochemical parameters, mean carotid intima-media thickness and lipid metabolism parameters, including triglycerides, total cholesterol and the respective fractions. Patients taking statins showed greater increased HDLc values and reduced LDLc values than those who were not. Additionally, women showed a more favorable evolution regarding HDLc increase compared to men.
Survival rate was estimated at 77.5% with 22 years as the maximum observed time. The median time of survival was not computed, since more than half of the patients (77.5%) were alive after 22 years. No bleeding episodes were recorded during this long period of observation.In fact, 99.0% of patients were alive after 10 years and the percentage of patients alive remained over 90% at 17 years. After 18 years of observation, 88.6% of patients were alive, and at 20 years 77.5% were alive without major cardiovascular events (MACE).

Conclusions:
Antiplatelet therapy should always be considered in primary prevention in patients with high CVR.
There were no cases of hemorrhage or MACE. The survival rate estimated for the study population was 77.5% over 22 years.
MULTIDRUG RESISTANT DYSLIPIDEMIA: A CASE REPORT
Authors: Maloberti Alessandro , Daus Francesca , Pavanello Chiara , Toscani Giorgio , Riccio Alfonso , Fabbri Saverio , Ciampi Claudio Mario , Caccia Andrea , Tognola Chiara , Algeri Michela , Intravaia Rita Cristina My , Merlini Piera , Mosca Lorena , Cavallari Ugo , Giannattasio Cristina , Morelli Marco 
Published: May 2024

Objective:
Recently introduced lipid-lowering agents (PCSK9-i, bempedoic acid) can efficiently treat statin-intolerant patients, who couldn’t reach LDL target before. Nonetheless, there are still cases where the pharmacological management may have strong limitations.

Design and method:
A 71 year-old woman, with multiple cardiovascular risk factors (diabetes, hypertension and familial dylipidemia, LDL-C 276) underwent heart transplantation for a hypertrophic cardiomyopathy with an evolution towards a dilated phenotype in 2005. Before the transplant, she was on low-dose statin treatment (pravastatin 10 mg/die) that was suspended years later owing to hyper-CKemia (600 U/L), despite her being totally asymptomatic.
A second attempt with simvastatin/ezetimibe 40/10 mg resulted again in elevation of CK levels, associated with significant muscular pain. Thus, just ezetimibe was continued.
In 2020, 15 years after the transplant, the patient underwent a coronary angiography showing a moderate coronary allograft vasculopathy (ISHLT CAV2). Specifically, a sub occlusive ostial left main coronary artery lesion was treated by percutaneous angioplasty and stent implantation.
Since a lower LDL target was needed (LDL-C 55 mg/dL),

Results:
Alirocumab was introduced. However, 6 months later, no significant LDL levels reduction had been observed. The shift to evolocumab led to the same result, although the patient reported full therapeutic compliance.
In the suspicion of anti-drug antibodies development, we opted for Inclisiran without achieving a significant decrease in LDL-C levels.
In parallel with the search for genetic mutations in the PCSK9 gene and other genes involved in cholesterol metabolism (including LDLR, APOB, and LDLRAP1 and resulting positive only for common variants in LDLR receptor), therapy with bempedoic acid was initiated, again without substantial benefit (LDL-C 118 mg/dL).

Conclusions:
Despite cholesterol management has been simplified by the introduction of new drugs, it may still be complex in patients requiring very low LDL-C levels in some specific cases. Drugs with a LDL receptor-independent mechanism of action (e.g., evinacumab) may allow the achievement of therapeutic goals suggested by clinical guidelines.
HEART RATE REDUCTION WITH BETA-BLOCKERS REDUCED LEFT ATRIAL FUNCTION IN HYPERTENSIVE PATIENTS WITH RECURRENT ATRIAL FIBRILLATION
Authors: Kokhan Elizaveta , Kiyakbaev Gayrat , Kobalava Zhanna 
Published: May 2024

Objective:
Higher resting heart rate (HR) has been shown to be an independent cardiovascular risk factor. However, some retrospective studies suggest that beta-blockers (BBs)-associated reduction in HR worsens left atrial (LA) function and increases the risk of stroke in hypertensive patients.
Purpose: to assess the impact of HR reduction with BBs on LA function in hypertensive patients with paroxysmal or persistent mild symptomatic atrial fibrillation.

Design and method:
In this open prospective trial, we randomly assigned 91 patients with hypertension, elevated HR (>70 bpm, sinus rhythm) and recurrent atrial fibrillation with rare paroxysms to receive BBs with a target HR (sinus rhythm) of less or greater than 70 bpm.
All patients underwent an echocardiogram at baseline and at the end of the study. Conventional echo measures and extended LA measures, including the minimal and maximal LA volumes (LAVmin and LAVmax) and LA emptying fraction (LAEF), were performed. The primary endpoint was the median LAEF measurement at the end of the study.

Results:
47 patients were randomized to group with a target HR of =<70 bpm and 44 patients to >70 bmp. Among them, 44 and 41 patients completed the study. The mean follow-up was 4.4 months.
At the end of the study, median HR was 62 bmp in =<70 group and 73 bpm in >70 group (p<0.001). Both groups received similar antihypertensive therapy and there were no intergroup differences in systolic (129 vs 130; p=0.32) and diastolic (78 vs 78; p=0.53) blood pressure.
Patients in =<70 group had significantly lower LAEF compared with >70 group (37 vs 42%; p=0.02). Both groups had similar indices of LAVmin (22 vs 19ml/m2; p=0.66) and LAVmax (38 vs 37ml/m2). E/E’ and left ventricle mass index did not differ between study groups at the end of the study, but E’ was significantly lower in the =<70 group.

Conclusions:
Beta-blockers treatment with strict HR reduction (=<70 bpm) significantly reduced LA function as compared to lenient target HR (>70 bpm). Although higher HR is a risk factor for hypertensive patients, its excess reduction with BBs could be harmful in this group.
RETROSPECTIVE, OBSERVATIONAL, LONGITUDINAL STUDY OF DRUG UTILIZATION FOR THE TREATMENT OF UNCOMPLICATED ESSENTIAL HYPERTENSION IN BULGARIA
Authors: Gruev Ivan , Stoyanova Sefka , Hristov Emil , Yordanov Emanuil , Parvova Iva 
Published: May 2024

Objective:
To evaluate drug utilization and assess rational drug use in the treatment of patients with uncomplicated essential hypertension in Bulgaria, using quantitative and qualitative measures at national level.

Design and method:
Retrospective, observational, longitudinal study of data from the public registers of the National Health Insurance Fund for the period 2017-2021 using the WHO ATS/DDD methodology and descriptive statistical methods.

Results:
The analyzed population included 129 312 patients with uncomplicated essential hypertension /I10/ - 11.09% of all hypertensive patients in Bulgaria. The average cost per year was 8 229 567.10 BGN (1 Euro=1.95583 BGN) - respectively the cost per patient per year was 63.64 BGN, the monthly cost was 5.30 BGN and the cost per day was 0.17 BGN. The amount of 8 229 567.10 BGN was divided into two groups - costs for mono-products (67.73%) and costs for combined products (32.27%).
The analysis of the actual therapeutic practice in Bulgaria showed that the most prescribed products for this indication were beta-blockers Nebivolol and Bisoprolol, calcium channel blocker Lercanidipine and centrally acting anti-adrenergic agents Moxonidine and Rilmenidine. Sartans were represent predominantly by Telmisartan. In all cross-sectional analyses, the significant use of Lercanidipine was very prominent.
Regarding the fixed-dose combinations, medicinal products, containing AT1-blocker and thiazide diuretic were preferred choice for treatment - the most prescribed combination was Valsartan with Hydrochlorothiazide (15.93% of the reimbursement costs for fixed-dose combinations).

Conclusions:
Despite of the clear recommendation in the guidelines, monotherapy was still preferred treatment for uncomplicated essential hypertension /I10/ in Bulgaria, during the studied period /2017-2021/. We must persist with the continuous education of the GPs, in order to improve the therapy and control of the arterial hypertension in Bulgaria.
IMPACT OF THIAZIDES AND DIHYDROPYRIDINES ON HEART FAILURE AMONG HYPERTENSIVE PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS
Authors: Alsanosi Safaa Mohammed , Alshanberi Asim M , Alhindi Yosra Z , Mccallum Linsay , Padmanabhan Sandosh 
Published: May 2024

Objective:
Background: Hypertension (HTN) can lead to heart failure (HF) if left uncontrolled or poorly managed over time. Thiazide diuretics have a more significant antihypertensive effect than loop diuretics and are commonly prescribed for managing fluid retention in HTN. In contrast, dihydropyridine calcium channel blockers predominantly have peripheral vasodilatory actions that primarily target blood vessels to control HTN. However, there is a lack of sufficient data when it comes to evaluating the cardiovascular clinical outlook (including HF) for hypertensive patients treated with calcium channel blockers and diuretics.
Objective To review the literature systematically and perform meta-analyses on impact of thiazides and dihydropyridines on HF incidents among hypertensive patients.

Design and method:
We searched the four major databases of MEDLINE, EMBASE, Web of Science and Cochrane (from 1993 – October 2023) for randomised controlled trials (RCTs) of thiazides or dihydropyridines. We included RCTs with at least 100 hypertensive participants and a minimum follow-up period of one year. Two authors independently selected the included RCTs, assessed the risk of bias, and collected data on HF. Meta-analyses were performed to summarise the pooled risk ratios (RRs) of HF between treatment arms.

Results:
The initial literature search identified 1896 records. After duplicates were removed, 1653 records were left, and a full-text review of the 403 eligible studies led to the exclusion of 396 RCTs. In the end, seven RCTs with a total of 49,409 participants were included in our meta-analysis. As to the effect of thiazides and dihydropyridines on HF, the point estimate for statins was less than 1, but it did not reach statistical significance in the overall analysis (the pooled RR in the fixed-effect model was 0.77 [95% CI: 0.70,0.84; I2=53%; X2 p < 0.00001]).

Conclusions:
There is a statistically significant difference between thiazides and dihydropyridines in terms of HF incidents among hypertensive patients, but there are positive implications for clinical guidance. Further research and analytical investigations are necessary to corroborate and reinforce the findings gathered from various studies.
LONG-TERM EFFECTS OF CPAP THERAPY FOR SUPPRESSING CAROTID ATHEROSCLEROSIS IN HYPERTENSIVE PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME
Authors: Sawayama Yasunori 
Published: May 2024

Objective:
To examine the long-term effect of CPAP on carotid artery intima-media thickness (IMT) in hypertensive patients with Obstructive Sleep Apnea Syndrome (OSA).

Design and method:
This study conducted over three years at a teaching hospital included 54 patients newly diagnosed with OSA who received either CPAP or conservative treatment(CT). In total, 24 patients received CPAP, while 30 received conservative treatment, with no significant differences observed in age, BMI, ESS, AHI, arousal index, or minimum SaO2. CPAP usage averaged 4.6±0.3 hours per night over the three years. Carotid IMT was assessed with B-mode Doppler ultrasound from both carotid arteries, using images of the far wall of the distal 10 mm of the common carotid arteries at baseline and after 3 years.

Results:
During the 3-year follow-up, there was a more significant decrease in blood pressure in the CPAP group compared to the CT group. Mean blood pressure at 36 months was 120/71 mm Hg in the CPAP group and 131/82 mm Hg in the CT group. The IMTs at 36 months were 1.13±0.31 mm (-14.5% vs. baseline, p=0.0034) and 1.27±0.36 mm (+1.1% vs. baseline, p=0.05) in the CPAP and CT groups, respectively. There was a significantly greater decrease in the CPAP group compared to the CT group (p=0.0014).
RESISTANT HYPERTENSION: WHEN DRUG THERAPY IS THE CULPRIT
Authors: Ambrosino Ilaria , Rivasi Giulia , Capacci Marco , Ceolin Ludovica , Rossi Lorenza , Bisignano Francesca , Liccardo Alessandra , D’Ambrosio Giuseppe , Ceccarelli Greta , Ungar Andrea 
Published: May 2024

Objective:
Resistant Hypertension is not uncommon in clinical practice. The causal role of medical therapy is often underestimated.

Design and method:
We describe a case of (pseudo)Resistant Hypertension where medications contributed to (pseudo)resistance.

Results:
An 83-year-old male patient was referred to our Hypertension Clinic in July 2020 for poor blood pressure (BP) control despite polytherapy (Valsartan 320 mg/die, Nebivolol 5 mg/die, Doxazosin 4 mg/die, Clonidine patch 5 mg/die, Lercanidipine 20 mg). Medical history included recent stroke (June 2020), hypercholesterolemia, hyperuricemia, hypothyroidism, and previous right nephrectomy for renal carcinoma (2010), on treatment with the Tyr-kinase receptor inhibitor Sunitinib (2 weeks/month) at the time of assessment.
He reported a recent Emergency Department visit for high BP (210/105 mmHg), with no target organ damage. Mean home BP was 160/70 mmHg.
Lercanidipine was stopped due to poor tolerability (ankle swelling) and Canrenone 50 mg/die was introduced. A month later, 24-hours Ambulatory Blood Pressure Monitoring (ABPM) showed persistence of inadequate BP control (mean 24h BP 151/68 mmHg, mean daytime BP 152/70 mmHg).
As Doxazosin (α1-receptors antagonist) and Clonidine (α2-receptors agonist) both act on alfa-adrenergic receptors, but in opposite way, Doxazosin was progressively reduced and then withdrawn, with subsequent improvement of BP control.
However, high BP variability persisted. Home BP diary showed higher values while on Sunitinib treatment and lower BP during washout periods (Figure 1).
Indeed, Sunitinib is associated with a 15-25% incidence of hypertension. Moreover, some studies demonstrate a correlation between Sunitinib treatment and marked BP increases. Therefore, patient's treatment was modulated increasing BP medications during Sunitinib cycles and reducing antihypertensive treatment intensity during washout periods.

Conclusions:
The present case report highlights the clinical relevance of iatrogenic resistant hypertension, that is often overlooked in clinical practice, particularly if related to non-routine medications, e.g. antiangiogenic agents.
Moreover, this case report draws attention to pseudoresistant hypertension caused by inappropriate antihypertensive associations such as Doxazosin and Clonidine. Indeed, these drugs are highly specific for α1 and α2-receptors, respectively, but they can also bind other receptor subclasses, thus potentially interfering each other due to competitive binding.