bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppressive therapy and humoral response to third mRNA COVID-19 vaccination with a six-month interval in rheumatic disease patients
Authors: Kashiwado Yusuke , Kimoto Yasutaka , Ohshima Shiro , Sawabe Takuya , Irino Kensuke , Nakano Shota , Hiura Junki , Yonekawa Akiko , Wang Qiaolei , Doi Goro , Ayano Masahiro , Mitoma Hiroki , Ono Nobuyuki , Arinobu Yojiro , Niiro Hiroaki , Hotta Taeko , Kang Dongchon , Shimono Nobuyuki , Akashi Koichi , Takeuchi Tsutomu , Horiuchi Takahiko
Published: June 2023

Objectives

To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination.

Methods

This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay.

Results

The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3–6 weeks after the second vaccination and 3–6 weeks after the third vaccination. Seroconversion rates were <90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. Antibody levels after the third vaccination were significantly lower in the groups prescribed TNF inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs in a multivariate analysis adjusting for age, sex, and glucocorticoid dosage. The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus.

Conclusions

Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution.
A possible contribution of the locus coeruleus to arousal enhancement with mild exercise: evidence from pupillometry and neuromelanin imaging
Authors: Yamazaki Yudai , Suwabe Kazuya , Nagano-Saito Atsuko , Saotome Kousaku , Kuwamizu Ryuta , Hiraga Taichi , Torma Ferenc , Suzuki Kenji , Sankai Yoshiyuki , Yassa Michael A , Soya Hideaki
Published: June 2023

Acute mild exercise has been observed to facilitate executive function and memory. A possible underlying mechanism of this is the upregulation of the ascending arousal system, including the catecholaminergic system originating from the locus coeruleus (LC). Prior work indicates that pupil diameter, as an indirect marker of the ascending arousal system, including the LC, increases even with very light-intensity exercise. However, it remains unclear whether the LC directly contributes to exercise-induced pupil-linked arousal. Here, we examined the involvement of the LC in the change in pupil dilation induced by very light-intensity exercise using pupillometry and neuromelanin imaging to assess the LC integrity. A sample of 21 young males performed 10 min of very light-intensity exercise, and we measured changes in the pupil diameters and psychological arousal levels induced by the exercise. Neuromelanin-weighted magnetic resonance imaging scans were also obtained. We observed that pupil diameter and psychological arousal levels increased during very light-intensity exercise, which is consistent with previous findings. Notably, the LC contrast, a marker of LC integrity, predicted the magnitude of pupil dilation and psychological arousal enhancement with exercise. These relationships suggest that the LC-catecholaminergic system is a potential a mechanism for pupil-linked arousal induced by very light-intensity exercise.
Long-Term Effects of an Education Stipend Program on Domestic Violence: Evidence from Bangladesh
Authors: Sara Raisa , Priyanka Sadia
Published: June 2023

Intimate partner violence (IPV) remains a widespread global phenomenon. Among various factors, a low level of education is considered a significant risk factor for experiencing IPV. This paper evaluates whether a secondary school stipend program introduced in 1994 for rural girls affected the long-term prevalence of IPV in Bangladesh. The study exploits two sources of variation in the intensity of program exposure and geographic eligibility and finds that cohorts of rural women eligible for the program experienced significant declines in IPV. Evidence on mechanisms suggests that the program delayed marriage formation and changed partner quality, namely their education and employment, consistent with positive assortative matching resulting from women's improved educational attainment. There are no significant changes in labor market outcomes, decision making within the household, or women's attitude toward the acceptability of domestic violence. Marital matches present a plausible channel through which the program reduces the risk of IPV.
Assessing Acinetobacter baumannii virulence and treatment with a bacteriophage using zebrafish embryos
Authors: Neto Sofia , Vieira Ana , Oliveira Hugo , Espiña Begoña
Published: June 2023

Acinetobacter baumannii is the leading bacteria causative of nosocomial infections, with high fatality rates, mostly due to their multi‐resistance to antibiotics. The capsular polysaccharide (k‐type) is a major virulence factor. Bacteriophages are viruses that specifically infect bacteria and have been used to control drug‐resistant bacterial pathogens. In particular, A. baumannii phages can recognize specific capsules, from a diversity of >125 that exist. This high specificity demands the in vivo identification of the most virulent A. baumannii k‐types that need to be targeted by phage therapy. Currently, the zebrafish embryo has particularly attained interest for in vivo infection modeling. In this study, an A. baumannii infection was successfully established, through the bath immersion of tail‐injured zebrafish embryos, to study the virulence of eight capsule types (K1, K2, K9, K32, K38, K44, K45, and K67). The model revealed itself as capable of discerning the most virulent (K2, K9, K32, and K45), middle (K1, K38, and K67), and the less virulent (K44) strains. Additionally, the infection of the most virulent strains was controlled in vivo resorting to the same technique, with previously identified phages (K2, K9, K32, and K45 phages). Phage treatments were able to increase the average survival from 35.2% to up to 74.1% (K32 strain). All the phages performed equally well. Collectively, the results show the potential of the model to not only evaluate virulence of bacteria such as A. baumannii but also assess novel treatments' effectiveness.
FEATURE-BASED CLUSTERING OF LEFT VENTRICULAR STRAIN CURVE FOR RISK STRATIFICATION IN GENERAL POPULATION
Authors: Ntalianis Evangelos , Sabovcik Frantisek , Cauwenberghs Nicholas , Kuznetsova Tatiana
Published: June 2023

Objective:

Global left ventricular (LV) strain has been identified as an important predictor of adverse cardiovascular (CV) events. However, currently only the peak strain is used from the LV deformation curve, neglecting the temporal information hidden in all phases of heart cycle. Therefore, we employed unsupervised machine learning methods on time-series-derived features from LV strain to identify distinct clinical phenogroups associated with the risk of developing adverse events in the general population.

Design and method:

We prospectively studied 1185 community-dwelling individuals (mean age, 53.2 years; 51.3% women), in whom we acquired clinical and echocardiographic data including LV strain traces at baseline and collected CV events (n = 94) on average 5.2 years later. We utilised Gaussian Mixture Model (GMM) on different features derived from LV strain curve, including slope during systole and diastole, peak strain, slope during late diastole and the duration and height of diastasis (Figure, left panel). We evaluated the clinical significance of the clusters (k) by comparing the clinical characteristics and CV adverse outcome.

Results:

Based on inertia and BIC scores the optimal number of clusters (k) was 4. The first two clusters had differences in heart rate, but had similar low CV risk profiles. Cluster 4 had the worst CV risk factors combination, and higher prevalence of LV remodelling and diastolic dysfunction (i.e. lowest e ‘velocity and highest E/e’) compared to other clusters. Kaplan–Meier showed an increased cumulative incidence risk for all CV events across clusters (Figure, right panel). After adjustment for traditional risk factors, the risk was significantly higher in clusters 3 (HR: 1.35; 95% CI: 1.01-1.82; P = 0.043) and 4 (HR: 1.32; 95% CI: 1.05-1.67; P = 0.017) than in cluster 1, while the risk of adverse events did not reach the significant level in subjects with an abnormal peak LV strain (<17%) (HR 1.12; P = 0.66).

Conclusions:

Unsupervised machine learning algorithm employed on features derived from time series LV strain curves identifies clinically meaningful clusters, and provides important prognostic information over the peak LV strain.
THE EFFECT OF SEMAGLUTIDE ON BLOOD PRESSURE IN PATIENTS WITHOUT DIABETES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kennedy Cormac , Hayes Peter , Salama Sulafa , Hennessy Martina , Fogacci Federica
Published: June 2023

Objective:

The interplay of hypertension and obesity is well described. Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). The aim of this review is to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes.

Design and method:

This systematic review was performed in line with the 2020 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science. Studies were screened to include randomised controlled trials of semaglutide versus a placebo in adults without diabetes. Continuation of anti-hypertensive treatment was a secondary outcome. Pooled and sensitivity analyses were performed and risk of bias was assessed.

Results:

611 potential studies were found by the search and 6 RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in SBP was -4.83 mmHg (95% CI -5.65 to -4.02) while that for DBP was -2.45 mmHg (95% CI -3.65 to -1.24). Only two studies (STEP 1, 4) reported change in anti-hypertensive medications. In STEP 1, 34.3% of those on anti-hypertensive medications, and receiving the intervention, either decreased or stopped these drugs, versus 16% in the placebo group. Equivalent figures were 25.5% and 11.9% for STEP 4. Critical appraisal revealed all included studies to be of a high methodological quality.

Conclusions:

The magnitude of BP reduction evident following semaglutide treatment in normotensive populations with obesity and without diabetes is clinically significant. The effect of semaglutide in those with obesity and hypertension is yet to be determined. Targeting excess body weight may be a novel therapeutic strategy for patients with difficult to control hypertension.
ANTIHYPERTENSIVE TREATMENT EVALUATION IN A MULTIMORBIDITY AND POLYPHARMACY TRIAL (ATEMPT): A RANDOMISED CONTROLLED TRIAL
Authors: Rahimi Kazem , Majert Jeannette , Nazarzadeh Milad , Ramakrishnan Rema , Bidel Zeinab , Hedgecott Debbie , Perez-Crespillo Abel , Turpie Wendy , Akhtar Naseem , Allison Moira , Court Christine A. , Billot Laurent , Kotecha Dipak , Potter John
Published: June 2023

Objective:

Older patients with multimorbidity and polypharmacy have been underrepresented in previous clinical trials of antihypertensive treatment. Thus, it is unclear how to best manage blood pressure (BP) in this patient group.

Figure. Mean systolic pressure in the two treatment groups over the course of the trial.

Design and method:

ATEMPT was a home-based, two-armed, parallel-group, partially blinded randomised controlled clinical trial. Individuals aged 65 years or over with multimorbidity (three or more chronic conditions) or polypharmacy (5 or more types of medications) with a systolic BP of 115 - 165 mmHg were recruited. Participants were randomised to up to two more versus up to two fewer classes of antihypertensive medications, depending on their baseline systolic BP and any pre-existing antihypertensive treatments. The primary outcome of the trial was change in home-measured BP. Secondary outcomes included cognitive function and health-related quality of life measured with validated instruments.

Results:

230 participants aged 76.0 years (SD 6.1) were recruited. Participants were taking 5.7 (2.4) non-antihypertensive medications at baseline and had four comorbid conditions. Using a dynamic randomisation algorithm, 126 participants were assigned to more and 104 to fewer antihypertensives. After a median of 10.3 months follow-up (IQR 4.2), the average number of antihypertensives per participant was 3.0 (SD 1.4) and 1.9 (SD 1.5), in the more vs fewer antihypertensive arms, respectively (p = 0.001). Mean systolic BP was 133 mmHg (SD 14.4) and 134 mmHg (16.5) at baseline and changed to 122 mmHg (SD 10.5) and 133 mmHg (15.3), in the more vs fewer antihypertensive arms, respectively (p = 0.002) (Figure). There was no meaningful difference in cognitive function, health-related quality of life, frailty score or the occurrence of serious adverse events between treatment arms. Dizziness and fatigue were more commonly reported among participants assigned to more antihypertensives.

Conclusions:

The decentralised design of ATEMPT enabled the participation of older mostly non-hypertensive individuals with multimorbidity and polypharmacy from home. The remote intervention led to a meaningful reduction in systolic BP with no effect on the quality of life or cognitive function.
THE ASSOCIATION OF TRIGLYCERIDE-GLUCOSE INDEX AND RELATED PARAMETERS WITH HYPERTENSION AND CARDIOVASCULAR RISK
Authors: Miao Huanhuan , Yang Shijie , Zhou Zhanyang , Zhang Yuqing
Published: June 2023

Objective:

Triglyceride-glucose index (TyG) was initially proposed as a reliable surrogate indicator for insulin resistance, which was later demonstrated to be associated with hypertension and CVD. The new parameters, TyG-BMI, TyG-WC, TyG-WHR and TyG-WHtR, which combine TyG and anthropometric indicators, were also reported to be related to hypertension and CVD. The study was designed to explore the association of TyG and related parameters with hypertension and cardiovascular risk.

Design and method:

A total of 16834 participants were enrolled in this study. Binary logistic regression analysis was used to explore the association between each parameter and the risk of hypertension and CVD across quartiles of TyG and related parameters. The receiver operating characteristic curve (ROC) was used to compare the diagnostic ability of TyG and its related parameters to identify people with hypertension and high cardiovascular risk.

Results:

The mean age of participants was 56.9 years, and 5776 (36.4%) were male. Compared with the lowest quartile groups of TyG and related parameters, the corresponding risks of hypertension in the highest quartile groups were significantly increased after adjustment. TyG-WC showed the highest diagnostic efficacy for hypertension (AUC: 0.665, 95% CI: 0.656 - 0.673) followed by TyG-WHtR (AUC: 0.664, 95% CI: 0.656 - 0.672), TyG-BMI (AUC: 0.658, 95% CI: 0.650 - 0.666), TyG-WHR (AUC: 0.655, 95% CI: 0.647 - 0.663) and TyG (AUC: 0.614, 95% CI: 0.605 - 0.622). Similarly, compared with the lowest quartile groups of TyG and related parameters, the corresponding risks of high cardiovascular risk in the highest quartile groups were also significantly increased. TyG-WC exhibited the strongest association with cardiovascular risk (OR: 8.167, 95% CI: 6.559 - 10.170). Furthermore, TyG-WHR showed the highest efficacy in distinguishing participants with high cardiovascular risk (AUC: 0.718, 95% CI: 0.710 - 0.726) followed by TyG-WC (AUC: 0.704, 95% CI: 0.695 - 0.712), TyG-WHtR (AUC: 0.674, 95% CI: 0.665 - 0.683), TyG-BMI (AUC: 0.639, 95% CI: 0.630 - 0.648) and TyG (AUC: 0.638, 95% CI: 0.629 - 0.647).

Conclusions:

The new parameters that combine TyG and anthropometric indicators have close and independent associations with hypertension and cardiovascular risk. Among them, TyG-WHR shows the highest efficacy in distinguishing participants with high cardiovascular risk, which may be helpful for the primary prevention of CVD.
THE PREDICTION OF CARDIOVASCULAR EVENTS BY PHENOTYPE OF CENTRAL AND PERIPHERAL BLOOD PRESSURE IN SUBJECTS WITHOUT HYPERTENSION
Authors: Kim Gee -Hee , Kim Min -Sik
Published: June 2023

Objective:

Hypertension (HBP) is a common disease with aging, but the rate of recognition or poor control is still high. Until now, most guidelines related to HBP consisted of only peripheral blood pressure (BP) measurement. However, according to many studies, it is known that central BP (CBP) has a clearer relationship than peripheral BP, which can more clearly express an individual's BP status with the prediction of cardiovascular (CV) events. Therefore, we aimed to evaluate the effect of CBP on the prediction of CV events and to investigate the prediction of CV events by phenotype of central and peripheral BP in subjects without hypertension.

Design and method:

A total of 2910 patients were enrolled from June 2011 to December 2016, and were followed up through October 2022. CBP was measured using radial tonometry. The primary endpoints were composite outcome.

Results:

The median follow-up period for enrolled patients was 7.5 years. Out of a total of 722 patients (mean age of 52.5 ± 13.7 years) without HBP, 21 patients (2.9%) had events of primary end points during the follow up period. Systolic BP averaged 126 mmHg (±15 mmHg) in the event-free group and 136 mmHg (±15 mmHg) in the CV event group, while CBP measured 115 mmHg (±16 mmHg) in the event-free group and 126 mmHg (±16 mmHg) in the CV event group. In Cox proportional hazards model, CBP and systolic BP, every 10 mmHg increase, showed an increase in risk of 30% and 40% respectively. Isolated central systolic hypertension and both central and peripheral systolic hypertension showed 4.9 % and 6% of the CV event rate, respectively (p = 0.897).

Conclusions:

Irrespective of the brachial BP status, isolated central hypertension increased CV events. Therefore, to prevent CV events is an essential control not peripheral BP but also CBP.
MULTIPLE RENAL ARTERIES AS A RISK FACTOR FOR SEVERE HYPERTENSION IN YOUNG ADULTS?
Authors: Josipovic Josipa , Crnojevic Ivana , Moric Bernardica Valent , Jelakovic Ana , Bulj Nikola , Ivanko Iva , Krpan Tomislav , Jelakovic Bojan
Published: June 2023

Objective:

The significance of multiple renal arteries (MRAs) in arterial hypertension (AH) is not fully understood. Lower perfusion pressure due to longer length and narrower caliber of MRAs could cause segmental hyperreninemia sufficient to result in renin-dependent systemic hypertension. Sympathetic renal nerve activity might be affected by hyperreninema as well.

The aim of the study was to examine the characteristics of young adult hypertensives in relation to the existence of MRAs that were diagnosed during evaluation for secondary arterial hypertension.

Design and method:

32 patients underwent routine evaluation for secondary hypertension and target organ damage. Patients were divided into two groups, one with MRAs and the other without MRAs. Data were presented as mean +standard deviation and compared by the Indipendent-Sample t-test.

Results:

The mean age was 38 years, and 13 patients were diagnosed with MRAs. There were more men in the MRAs group, otherwise, there were no significant differences in baseline characteristics between the groups (BMI, smoking, family history). None of them were diagnosed with secondary endocrine hypertension or renal artery stenosis. MRAs group showed significantly higher values of office SBP/DBP (p < 0,012) and 24-hour SBP/DBP (p < 0,001), and nonsignificantly higher values of heart rate. Although nonsignificant, direct renin concentrations were slightly higher in the MRAs group, while insulin levels were higher in the non-MRAs group. Dyslipidemia was diagnosed in most patients, without significant differences between groups.

Electrocardiographic and echocardiographic changes suggesting hypertensive heart remodeling were found in 55% of patients in MRAs compared to 32% in non-MRAs, there were no significant differences in NTproBNP levels. A nonsignificant reduction in glomerular filtration rate was noticed in the MRAs group, while there were no significant differences in 24-hour albuminuria (p 0,308; p 0,614).

Conclusions:

The significance of MRAs in arterial hypertension is a matter of debate. In our study of young patients with arterial hypertension and MRAs, we observed features of more severe hypertension with already existing hypertensive target organ damages. Proper medical treatment with antihypertensive agents is crucial. Future studies will answer the question about interventional therapeutic procedures’ role in preventing cardiovascular complications.
COGNITIVE FUNCTION IS ASSOCIATED WITH LONG-TERM BENEFITS OF BLOOD PRESSURE MANAGEMENT PROGRAMME: A 4-YEAR PROSPECTIVE COHORT OF 1,151 PARTICIPANTS FROM ELDERLY CENTRES IN HONG KONG
Authors: Tsoi Kelvin , Chen Yize , Hao Ziyu , Yiu Karen
Published: June 2023

Objective:

The blood pressure (BP) trend is shown to have seasonally fluctuated, and is affected by both personal physical and cognitive conditions. This study aimed to investigate the long-term benefits of a BP management programme with adjustment for year-round BP fluctuations among the elderly in Hong Kong.

Design and method:

Elderly participants with ages above 55 years were recruited from 76 elderly centres and were prospectively followed up between September 2016 and January 2020. Personal interviews were conducted to assess personal health conditions. Nursing calls and social worker engagement were offered for those with suboptimal BP readings. The inclusion criteria were the participants who reported more than 80% of weekly BP records in at least 2 years of follow-up. The seasonal BP fluctuations were adjusted by time series models and the overall BP treads were tested by the Mann-Kendall test. The logistic regression models were used to investigate both the physical and cognitive conditions for good BP management.

Results:

A total of 1,151 elderly participants with a mean age of 79 years were included in the study. Based on the trend testing by Mann-Kendall test, 553 (48%) participants were classified as improved BP trend, i.e. downward trends of BP records, and 598 (52%) were classified as having stable or deteriorated BP levels. The multivariate model showed that improved BP trends were associated with baseline systolic BP levels, (OR 1.03, 95% CI 1.02 - 1.04), cholesterol problems, and subjective memory complaints (OR 0.64, 95% CI 0.47 - 0.85) (Table 1). Compared with eating junk food every day, eating less than once a week were good for BP management.

Conclusions:

Seasonal blood pressure fluctuations always influence the performance of blood pressure management programmes. Time-series modelling is possible to figure out the real trend of personal blood pressure records after adjustment for seasonal effects. This study demonstrates that the long-term benefits of our blood pressure management programme were limited by the elderly with memory complaints. When we are offering blood pressure management programme, special arrangement is required for the participants with mild cognitive impairment or even dementia.
DISCREPANCIES IN THE OUTCOME OF PLASMA ALDOSTERONE LEVELS ASSESSED BY IMMUNOASSAY AND MASS SPECTROMETRY - CLINICAL RELEVANCE FOR THE DIAGNOSIS OF PRIMARY HYPERALDOSTERONISM
Authors: Bacmaga Gilbert , Dabrowska Natalia , Was Joanna , Sokolowska Dorota , Kolodziejczyk-Kruk Sylwia , Matsko Pavlo , Talarowska Paulina , Pregowska-Chwala Barbara , Peczkowska Mariola , Kabat Marek , Cendrowska-Demkow Iwona , Lutynska Anna , Januszewicz Andrzej , Dobrowolski Piotr , Prejbisz Aleksander
Published: June 2023

Objective:

To assess potential discrepancies in the clinical interpretation of the salt loading test (SLT) resulting from the assessment of aldosterone concentrations by two different methods - immunoassay and mass spectrometry.

Design and method:

Eighty-one patients (47F, 34M, mean age 47.7 ± 14.1 years) with suspected primary hyperaldosteronism (PA) who underwent an SLT were included in the ongoing study. Patients had their treatment modified according to current guidelines prior to the test. The SLT was performed in the sitting position and blood samples were taken before and after 4 hours of administration of 2 litres of saline. An aldosterone concentration higher than 61 ng/dL (170 pmol/L) was considered indicative of a diagnosis of PA. Plasma aldosterone concentrations from the same samples were assessed by: (1) chemiluminescence-based immunoassay (CLIA), LIAISON® by DiaSorin, and (2) liquid chromatography-mass spectrometry (LC-MS), MassChrom Chromsystems kit, UHPLC technique using a QTRAP 6500+ instrument (Sciex). Renin concentration was assessed by CLIA.

Results:

Median plasma aldosterone concentrations after saline administration assessed by CLIA were significantly higher than those assessed by LC-MS (64.4 vs 44.0 ng/dL; p < 0.001). The correlation coefficients for plasma aldosterone concentration after saline administration was 0.69 (p < 0.001). PA was diagnosed by one of the methods in 22 of patients and by both methods in 16 patients. Conflicting results were obtained in 6 patients (7.4%): in 5 patients CLIA was suggestive of PA but LC-MS not and in one patient LC-MS was suggestive of PA but CLIA not. In four cases, plasma aldosterone concentrations were slightly above or below the cut-off values (CLIA vs LC-MS: 62.9 vs 53; 61.9 vs 50; 97.8 vs 61 and 112 vs 58 ng/dL) in at least one of the methods. In the other two cases, the discrepancies were more pronounced (50 vs 80 ng/dL and 126 vs 24 ng/dL).

Conclusions:

Discrepant results of aldosterone assessment by CLIA and LC-MS methods were obtained in 7.4% of patients. Discrepancies were generally related to borderline results. If a plasma aldosterone concentration value close to the cut-off values is obtained, a repeat determination using another method should be considered.
ORAL SODIUM BUTYRATE INCREASES DAYTIME SYSTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL
Authors: Verhaar Barbara , Wijdeveld Madelief , Wortelboer Koen , Rampanelli Elena , Levels Johannes. H.M. , Collard Didier , Cammenga Marianne , Berg-Garrelds Ingrid M. van den , Danser A.H. Jan , Born Bert-Jan H. van den , Nieuwdorp Max , Muller Majon
Published: June 2023

Objective:

The microbiota-derived short chain fatty acid (SCFA) butyrate has been shown to modulate blood pressure (BP) in rodent studies, while in humans, plasma butyrate levels have been associated with BP. Nonetheless the net effect of butyrate on hypertension in humans remains uncovered. In this study, we aimed to determine the effect of oral butyrate on BP in hypertensive patients.

Design and method:

We performed a double-blind randomized placebo-controlled trial including 23 patients with grade I hypertension. Antihypertensive medication was discontinued for the duration of the study with a wash-out period of four weeks before starting the intervention. Participants received either oral sodium butyrate capsules 4 g per day or placebo capsules with an equivalent amount of sodium chloride for four weeks. The primary outcome was daytime 24-hours systolic BP. We also collected data on short-term heart rate variability (HRV) using finger photoplethysmography, and extracellular water percentage using body impedance analyses. We measured plasma renin, aldosterone, and fecal SCFA levels. Gut microbiota composition was determined using 16S rRNA sequencing. Differences between groups over time were assessed using linear mixed models (group*time interaction).

Results:

Study participants had a mean age of 59.0 ± 3.7 years, 56.5% female and an average baseline office systolic BP of 143.5 ± 14.6 mmHg and diastolic BP of 93.0 ± 8.3 mmHg. Daytime 24-hours systolic and diastolic BP significantly increased over the intervention period in the butyrate compared to the -placebo group, with an effect size of 9.65 (95%CI 3.88 - 17.15) mmHg in daytime 24-hours systolic BP and 5.08 (95%CI 1.89 - 8.76) mmHg in diastolic BP in the linear mixed model. Heart rate and extracellular water percentage changes were not significantly different between the groups. There was a trend towards increasing HRV in the butyrate group (group*time p = 0.078), but no significant changes in renin and aldosterone levels, nor in fecal SCFA levels. Butyrate did not impact gut microbiota composition substantially.

Conclusions:

Four weeks of oral butyrate treatment increased daytime systolic and diastolic BP in hypertensive subjects. Our findings implicate that not all SCFA have beneficial effects on human cardiovascular health which warrants caution in future prebiotic and butyrate intervention studies.
COMPARATIVE EFFICACY AND ACCEPTABILITY OF ANTIHYPERTENSIVE DRUG CLASS COMBINATIONS FOR CARDIOVASCULAR DISEASE PREVENTION: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Brunström Mattias , Brunström Anton , Jussil Heidi , Panagiotopoulou Kanella , Chaimani Anna , Carlberg Bo
Published: June 2023

Objective:

European guidelines recommend combination therapy for most hypertensive patients, but direct comparisons between major drug class combinations are lacking. Our aim was to compare the efficacy and acceptability of different drug class combinations.

Design and method:

We performed a systematic review and network meta-analysis guided by the recommendations from the Cochrane collaboration. We included all trials assessing any antihypertensive drug combination against another combination, single agent or placebo, with at least 1000 patient-years of follow-up in each treatment arm. Risk of bias was assessed using Cochrane Collaborations RoB2 tool, excluding trials at high risk of bias from the analysis. Odds ratios from individual trials were pooled using random-effects network meta-analysis, with composite major cardiovascular events as the primary outcome for efficacy, and treatment discontinuation as the primary outcome for acceptability.

Results:

85 trials, including 406 067 participants followed for an average of 4.0 years, were included in the analysis. Mean age was 64.0 years and 41% percent were women. Overall, 15 different drug classes, drug class combinations and placebo were included in the network. Direct comparisons between dug class combinations were sparse, and there were signs of inconsistency between direct and indirect comparisons, particularly for acceptability. The main results are presented in figure 1. Combination therapy using renin-angiotensin system inhibitors (RASi) and calcium channel blockers (CCB) appeared most effective in preventing major cardiovascular events, followed by a combination of thiazide and potassium-sparring diuretics. The combination of RASi and diuretics appeared least effective among combinations studied. For acceptability, no combination differed significantly compared to placebo, although combinations including an angiotensin receptor blocker (ARB) trended towards being more acceptable, and combinations including and angiotensin-converting enzyme inhibitor trended towards being less acceptable, compared to placebo.

Conclusions:

In this first network meta-analysis of antihypertensive drug combinations, RASi + CCB appears most effective in preventing major cardiovascular events. Based on a more beneficial acceptability profile, combinations including ARB may be preferred over combinations including ACEi, although these findings should be interpreted with caution due to lack of direct comparisons.
COMPARATIVE EFFICACY AND ACCEPTABILITY OF DIFFERENT ANTIHYPERTENSIVE DRUG CLASSES FOR CARDIOVASCULAR DISEASE PREVENTION: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Brunström Mattias , Brunström Anton , Jussil Heidi , Panagiotopoulou Kanella , Chaimani Anna , Carlberg Bo
Published: June 2023

Objective:

No single trial has compared all major antihypertensive drug classes head-to-head and current guidelines give different recommendations for first-line agents. Our aim was to assess the efficacy for cardiovascular disease prevention as well as acceptability across all antihypertensive drug classes.

Design and method:

We performed a systematic review and network meta-analysis guided by the recommendations from the Cochrane collaboration. We included all trials assessing any antihypertensive agent against another agent or placebo with at least 1000 patient-years of follow-up in each treatment arm. Risk of bias was assessed using Cochrane Collaborations RoB2 tool, and trials at high risk of bias were excluded from the analysis. Odds ratios from individual trials were pooled using random-effects network meta-analysis, with composite major cardiovascular events as the primary outcome for efficacy, and treatment discontinuation as the primary outcome from acceptability.

Results:

85 trials, including 406 067 participants followed for an average of 4.0 years, were included in the analysis. Mean age was 64.0 years and 41% percent were women. Overall, 15 different drug classes, drug class combinations and placebo were included in the network. There were some signs of inconsistency between direct and indirect comparisons, particularly for acceptability. The main results are presented in figure 1. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARB), and calcium channel blockers (CCB) all reduced the risk of major cardiovascular events compared to placebo. Diuretics showed a similar trend, whereas beta-blockers (BB) and renin inhibitors did not. For acceptability, ARB and CCB were comparable to placebo, diuretics showed a non-significant trend towards more discontinuations, whereas ACEi, BB and alpha-blockers were significant more prone to treatment discontinuation compared to placebo and other agents.

Conclusions:

This is the most comprehensive network meta-analysis of antihypertensive agents to date. Our findings indicate that ACEi, ARB and CCB are the most effective agents in preventing major cardiovascular events. Based on a more beneficial acceptability profile, ARB and CCB may be considered most appropriate as first-line agents, although these findings should be interpreted with caution due inconsistency.
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.