bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.