bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fenofibrate modulates cardiac energy metabolism in moderate-severe aortic stenosis: a mechanistic double-blinded randomised controlled MR trial
Authors: Monga S , Valkovic L , Myerson S G , Neubauer S , Rider O J , Mahmod M 
Published: October 2024

Abstract

Background
Aortic stenosis (AS) is associated with impaired cardiac metabolism and high-energy phosphate production which can further exacerbate the progression to HF. Myocardial lipid accumulation and reduced production of high-energy phosphates have important implications for both systolic and diastolic heart function in AS. Peroxisome proliferator-activated receptor alpha (PPAR-alpha agonist, has the potential to optimise cardiac substrate metabolism, thereby, may be effective in improving cardiac dysfunction and functional capacity in AS.

Methods
In this prospective, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe asymptomatic AS (n=72) were randomly assigned to Fenofibrate 200 mg daily or matching placebo for 6 months in 4:1 fashion. Of the total 72 participants, 59 received Fenofibrate and 13 received placebo. All subjects underwent cardiac magnetic resonance (CMR) and exercise testing at 0 and 6 months, with follow-up data available in 47 patients. The primary end point was change in myocardial triglyceride content (MTG) determined by proton magnetic resonance spectroscopy (1H-MRS). Secondary outcome measures included change in cardiac energetics (PCr/ATP) determined by phosphorus magnetic resonance spectroscopy (31P-MRS), left ventricular strain determined by myocardial tagging and exercise capacity i.e. peak VO2 assessment via cardiopulmonary exercise testing.

Results
Cardiac energetics (PCr/ATP) showed statistically significant improvement in the Fenofibrate group (0.14 ± 0.48; CI: - 0.03, 0.30; p=0.05) vs placebo group (0.11 ± 0.75; CI -0.42, 0.65; p=0.64). There was also significant reduction in MTG in the Fenofibrate group (mean change -0.40 ± 0.97; 95% CI -0.74, -0.06; p=0.02). MTG content also reduced in the placebo group (mean change -0.41 ± 0.26, 95% CI -1.10, 0.18, p 0.13), but the reduction was not statistically significant. Though no significant changes were seen in the systolic function parameters, there was a significant improvement in diastolic function in the fenofibrate group only (peak diastolic longitudinal strain rate 9.6, 95% CI: 1.13, 18.1; p = 0.02). Peak VO2 did not show any significant improvement in either group.

Conclusions
Fenofibrate works as a metabolic modulator upregulating fatty acid metabolism in pressure overload AS hearts. Such modulation is associated with an improvement in cardiac energetics and diastolic function in moderate-severe AS.Main results from baseline to 6 monthsBaseline demographic and CMR parameters
Proteome-wide associations of pulse pressure in the UK Biobank
Authors: Dib M , Meena D , Azzo J D , Salman O , Beeche C , Chirinos J A 
Published: October 2024

Abstract

Introduction
Large artery stiffness (LAS) significantly contributes to the burden of cardiovascular morbidity and mortality, and is marked by an increased pulse pressure (PP)(1). Therapeutically targeting LAS may help in mitigating cardiovascular disease and other comorbidities.

Purpose
We aimed to investigate the proteomic associations of PP, and their putative causal role using Mendelian randomization (MR).

Methods
We first investigated associations between baseline circulating protein levels for 2,941 protein analytes measured using Olink technology, and PP in the UK Biobank (N=54,219). Regression analyses were adjusted for age, sex, mean arterial pressure, body mass index and stroke volume. Next, we conducted two-sample MR analyses to evaluate associations between genetically-predicted plasma protein levels and PP, for 1,820 proteins with available genetic instruments. We conducted inverse-variance weighted MR as our main analysis, and genetic colocalization analyses as sensitivity. We used a 5% false discovery rate (FDR) threshold to account for multiple comparisons.

Results
After correction for multiple comparisons, measured levels of 61 out of 2,923 proteins were significantly associated with PP (Figure 1). Genetically-predicted levels for 58 proteins were significantly associated with PP after FDR correction (Figure 2). At nominal significance, 31 proteins were concordantly associated with PP in both analyses, and 19 had consistent directions of effect, including natriuretic peptide B (NPPB, βobservational=0.04, Standard Error (SE)=0.009, PFDR&lt;0.001), thrombospondin-2 (THBS2, βobservational=0.05, SE=0.009, PFDR&lt;0.001), paraoxonase-2 (PON2, βobservational=-0.03, SE=0.008, PFDR&lt;0.001), and sclerostin (SOST, βobservational=-0.03, SE=0.009, PFDR&lt;0.001). NPPB was concordant in direction of effect and met an FDR-corrected significance threshold.

Conclusions
Our study identifies multiple novel proteins with a putative causal effect on PP. Our findings identify NPPB with a high level of statistical confidence, which could have important implications given the current availability of FDA-approved medications to boost NPPB effects. Our findings will lead to further investigations regarding the biology and clinical role of the identified candidate therapeutic targets.
Treadmill exercise test as a screening tool in the development of hypertension
Authors: Kalos T , Dimitriadis K , Manta H , Fragoulis C , Konstantinidis D , Drogaris S , Tatakis F , Kakouri N , Tsioufis P A , Andrikou I , Kouremeti M , Mantzouranis E , Leontsinis I , Tsioufis C 
Published: October 2024

Abstract

Background
Guidelines promote screening people with high normal BP for the presence of end-organ damage because their presence is associated with a 2- to 3-fold increase in the risk of CVD.

Purpose
Office blood pressure measurements may be unable to detect early subclinical cardiac damage of adverse prognostic significance in subjects with high normal blood pressure.

Methods
100 consecutive subjects with high normal BP [systolic BP=130-139mmHg and/or diastolic BP=85-89mmHg] were examined for early signs of hypertension-mediated organ damage (HMOD). They underwent an echocardiographic study, a negative for ischemia treadmill exercise test (Bruce protocol) where the index SBP/MET-slope [(peak SBP—resting SBP)/(peakMET-1)] was used. Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). The sympathetic drive was assessed by MSNA. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in the office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advice to lower their BP. The endpoint was the development of HTN either with Office BP or ABPM.

Results
Of 100 subjects (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg), 40 developed HTN in 3 years. 34 subjects developed Hypertensive Response to Exercise (HRE) (BP &gt;210mmHg in men and &gt;190mmHg in women) and all of them developed HTN. The SBP/MET-slope in future hypertensives was increased in all stages till peak exercise independently of sex type (stage1: 6.7vs4.9 p=0.049, stage2: 8.4vs4.8 p=0.001, peak: 6.7vs4.9, p=0.001). Their exercise capacity was reduced (10vs11.3METs, p=0.002) as well as their maximum exercise heart rate (156vs164, p=&lt;0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p&lt;0.001), Day SBP (127vs124mmHg, p=0.012) Office Pulse Pressure (51vs47mmHg, p=0.01). Additionally, they had increased PWV (8.3vs7.5m/sec, p=&lt;0.0001), MSNA levels (36vs28 bursts, p=&lt;0.0001), LVMI (38vs34 gr/m2.7, p=0.02), and a statistically significant deterioration of 2021 CKD-EPI eGFR (90 vs 97 mL/min/1.73 m², p=0.02). All of them correlated with development of hypertension (p=0.002), while they did not differ regarding their metabolic profile at the follow-up.

Conclusion
Detecting exaggerated blood pressure response and specifically an increased SBP/MET-slope in the end of second stage of Bruce protocol at treadmill exercise test is associated with increased systemic vascular resistance and early subclinical HMOD which may upgrade an individual’s cardiovascular disease (CVD) risk as they progress to HTN indicating a need for instituting a BP-lowering strategy.
Association of different timepoint and threshold of time-in-target-range and MACEs: insight from the SPRINT study
Authors: Moran L I , Zhao Y , Yi Z 
Published: October 2024

Abstract

Objective
To evaluate the prognostic value of different timepoint and threshold of systolic blood pressure (SBP) Time in Target Rang (TTR) in Major Adverse Cardiovascular Events (MACEs).

Method
This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 2-years follow-up were enrolled. Different SBP TTR indexes was calculated by different timepoint (3 month,12 month,24 month) and threshold (110-130mmHg;110-140mmHg;110-130mmHg for intensive treatment group and 120-140mmHg for standard treatment group) (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs) occurred 2 years later, defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death.

Results
A total of 7134 participants in SPIRNT were enrolled in this study. Those SBP TTR indicators with independent predictive value of MACEs were selected by a multivariable COX model adjusted for traditional cardiovascular risk factors (Fig 2). SBP TTR calculated with 110-140mmHg window in 3 months (3month SBP TTR110-140) was considered to be the best predictor of MACEs occurred 2 years later among selected SBP TTR indexes according to c statistics and relative informativeness (Table1). The restricted cubic spline plot was used to evaluate the nonlinear trend of the TTR indicator. In addition, we obtain the cut-off value by looking for the point in the RCS curve with the largest slope change. 0.65 was considered to be the best truncation for 3month SBP TTR110-140(Fig 3). Patients with 3month TTR110-140 greater than 0.65 had 23.9% lower incidence of MACEs than patients with TTR less than or equal to 0.65 (HR 0.761[0.592-0978], P=0.033).(Table 2) In addition, for patients with early SBP control (3month SBP TTR110-140 &gt;0.65), there was no significant difference in mean SBP between 110-130 mmHg and 130-140 mmHg (Fig4 Group1 Vs Group2). Lasso regression also suggests that TTR110-140 has more informatics advantages than TTR110-130 in cox model at different timepoints (Fig5).

Conclusions
3month SBP TTR110-140 was considered to be the best predictor of MACEs occurred 2 years later in different SBP TTR indexes, which indicated the importance of early SBP control. This study also proposed 0.65 as the critical value of 3-month SBP TTR110-140 for prevention of the incident of MACEs. In the future, more cohort studies are needed to expend these findings.
Intensive blood pressure lowering after endovascular thrombectomy in acute ischaemic stroke: an updated systematic review and meta-analysis of randomized controlled trials
Authors: Ayyan M , Sharma D D , Mansoor A , Nimal S R , Jain M , Nasser Z , Choudhary V , Villegas M J , Janarthanam S , Cheema H A , Ehsan M , Ahmad A , Rehman W U , Mactaggart S , Ahmed R 
Published: October 2024

Abstract

Background
Endovascular thrombectomy is an effective treatment in those with acute ischemic stroke. However, following successful reperfusion there are still many uncertainties as to the factors which influence patient outcome. Effective blood pressure management in this cohort has been elicited as one of these factors, with worse outcomes seen at both the high and low extremes.

Purpose
Pinpointing an optimal systolic blood pressure target after this procedure is still uncertain. We aimed to perform an updated meta-analysis of randomised controlled trials (RCTs) to evaluate the safety and efficacy of intensive blood pressure management as compared to conventional blood pressure management in this patient population.

Methods
We searched various electronic databases, including Embase, MEDLINE (via PubMed), and CENTRAL, to retrieve relevant RCTs evaluating a strategy of intensive blood pressure management after endovascular thrombectomy compared to conventional management. We pooled risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes, using RevMan 5.4.

Results
The meta-analysis included 4 RCTs with a total of 1560 patients. According to the analysis, intensive blood pressure management was associated with a statistically significant decrease in the number of patients showing functional independence (modified Rankin scale mRS score=0-2) at 90 days (RR 0.81; CI = 0.72-0.91; I2 = 12%). Regarding 90-day mortality, the pooled results from three RCTs showed no statistically significant difference between the intensive blood pressure management group and the conventional blood pressure management group (RR 1.17; CI = 0.90-1.52; I2 = 0%). There was no statistically significant difference between the two groups regarding the incidence of intracerebral haemorrhage (ICH) (RR 1.05; CI = 0.90-1.23; I2 = 0%) and the incidence of symptomatic intracerebral haemorrhage (sICH) (RR 1.10; CI = 0.76-1.60; I2 = 0%).

Conclusion
The meta-analysis showed no benefit of intensive lowering of blood pressure in terms of functional independence at 90 days, mortality rates, and incidence of ICH. Future large-scale trials should focus on other interventions to improve prognosis in these patients.Figure 1Figure 2
Safety, tolerability and blood pressure lowering of the innovative guanylyl cyclase a-receptor activator MANP in an ethnically diverse resistant hypertension population: a phase 1B clinical trial
Authors: Chen H , Smith D H , Neutel J M , Moroni D , Iyer S R , Crown J , Sangaralingham S J , Burnett J C 
Published: October 2024

Abstract

Background/Introduction
MANP is a novel atrial natriuretic peptide (ANP) analog bioengineered as a particulate guanylyl cyclase A receptor (GC-A) activator with superior receptor binding, resistance to neprilysin degradation, natriuretic, aldosterone suppressing and blood pressure (BP) lowering properties than native ANP. MANP is now under clinical development for resistant hypertension (RH). The rationale for its design was the fundamental role of the ANP/GC-A system in BP homeostasis through which GC-A activation with MANP leads to BP reduction through renal, vascular, and hormonal mechanisms mediated by the second messenger cGMP.

Purpose
We investigated the safety, tolerability, cGMP activation and BP reductions of MANP compared to placebo in subjects with RH.

Methods
We performed a double-blind, placebo controlled randomized trial in 36 RH patients comprised of approximately 50% non-African Americans (NAA) and 50% AA. MANP was administered in 6 cohorts receiving ascending subcutaneous (SQ) doses of MANP once daily from 3 ug/kg to a maximal dose of 7 ug/kg or placebo for 5 days and then followed for 21 days after dosing. Endpoints included safety, cGMP activation and changes in systolic BP (SBP), aldosterone (Aldo) levels and glomerular filtration rate (GFR).

Results
MANP was safe and well tolerated. One patient in the 7 ug/kg cohort was discontinued due to symptomatic hypotension. Compared to baseline, plasma cGMP increased in all MANP groups on Day 1 and Day 5 with no change in the placebo group. The maximal SBP reduction in the MANP group on Days 1 (D1) and 5 (D5) was -17.5 (D1) and -16 mmHg (D5) with 3 ug/kg (lowest dose) and -39.5 (D1) and -36.3 mmHg (D5) with 7 ug/kg (highest dose); Changes in the Placebo group were -6.3 (D1) and -16.7 mmHg (D5). Notably, the SBP reductions in AA were greater than NAA in the 4 and 7 ug/kg cohorts. After the 1-hour timepoint on both the first and fifth days, Aldo and percentage of Aldo reduction generally remained suppressed compared to baseline. Twenty-one days after MANP dosing, SBP remained lower in three groups receiving SQ MANP (4, 4.5 and 7 ug/kg) compared to placebo in association with a preservation of GFR. There were no reported drug related serious adverse events.

Conclusions
This clinical trial demonstrates that once a day SQ administration of MANP in RH subjects activates cGMP, without attenuation over 5 days, and reduces SBP and preserves GFR. At higher doses of MANP, SBP reductions were greater in AA compared to NAA. MANP also demonstrated Aldo inhibiting actions compared to placebo. Importantly, MANP was overall safe and well-tolerated. Our findings support the continued clinical development of MANP as a novel GC-A activating peptide for the treatment of RH.
Angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers vs. calcium channel blockers for 12,478 young hypertensive patients under 40 in 10-year follow-up
Authors: Jo S H , Shim H S , Hong J Y , Kim T H , Cheon D Y , Kim S A 
Published: October 2024

Abstract

Background
It is uncertain whether angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs) is superior to calcium channel blockers (CCBs) in young hypertensive patients.

Purpose
To compare ACEIs/ARBs with CCBs in hypertensive patients &lt;40 years for 10years.

Methods
We enrolled adults aged 20-39 with hypertension from 2007-2010 using the Korean national Insurance. Among 409,151 hypertensive patients, we made propensity matched analysis to compare the 2 drugs.

Results
12,478 patients were enrolled, 6239 in ACEIs/ARBs and 6239 in CCBs group. Primary endpoint of a composite of myocardial infarction (MI), heart failure (HF), stroke, and total death was similar in 2 groups in young hypertensive patients in 10-year follow-up: 662 (ACEIs/ARBs) vs. 642/10000 (CCBs) with hazard ratio (HR) of 1.03 (reference, CCBs) (CI 0.90-1.18, P=0.657).
In individual event of a MI, HF, stroke and total death, there was no difference in 2 groups: 99 vs 128/10000 persons (ACEIs/ARBs and CCBs respectively) with HR 0.77 (CI 0.56-1.08, P=0.13) in MI, 114 vs. 87/10000 (HR 1.32, P=0.123) in HF, 314 vs. 306 /10000 (HR 1.03, CI 0.64-1.20, P=0.795) in stroke and 184 vs. 167/10000 (HR 1.11, CI 0.85-1.44, P=0.454) in total death.

Conclusions
In young hypertensive patients, ACEIs/ARBs did not superior to CCBs in 10year clinical follow-up in large population.
Pharmacologic treatment of hypertension guided by non-invasive haemodynamics in primary care improves blood pressure control
Authors: Romer D , Cleland J , Sobotka P , Matthews R , Kaiser R , Granov I , Froehlich J , Perez M , Colangelo F , Crossey R , Bottorff M , Hardtke C , Vered Z 
Published: October 2024

Abstract

Background
Current guidelines on hypertension (HTN) provide blood pressure (BP) targets and therapeutic algorithms but ignore the potential to treat individual patients according to their haemodynamic profile. We have shown that use of non-invasive haemodynamic information obtained by impedance cardiography (ICG) can improve BP control in the primary care setting.

Purpose
To investigate whether improved rates of BP control by matching patients’ non-invasive haemodynamics to specific pharmacologic treatments and increasing patient engagement translates into improved clinical outcome measures.

Methods
Electronic medical records (EMR) were obtained for 14,698 patients from two US primary care groups between 2014 and 2023. ICG was done when BP exceeded 140/90 mmHg. Haemodynamic measurements included mean arterial pressure (MAP), cardiac index (CI), cardiac power index (CPI), total peripheral resistance index (TPRI), stroke index (SI) and heart rate (HR) (Figure 1). Haemodynamic ICG profiles were classified as: Vasoconstriction, Hyperdynamic, or Mixed pattern. Printed clinical decision support (CDS) tools and later an EMR integrated CDS application were used to communicate recommendations to physicians. Printed reports were shared with patients to increase their engagement. Pharmacological therapy was tailored based on haemodynamic information. Rates of successful BP treatment and the occurrence of myocardial infarction (MI) or stroke were tracked through the EMR.

Results
Of 14,698 patients, 50% were women, 17% were Black and 17% were aged 18-49 years, 45% aged 50-69 years, and 38% age ≥ 70 years. A total of 21,246 ICGs were performed classifying patients as Vasoconstriction 47%, Hyperdynamic with high heart rate (HR) or high stroke index (SI) 24%, and Mixed Haemodynamic (combination of Vasoconstriction and Hyperdynamic) 29% (Figure 1). Demographic features were not strongly associated with haemodynamic classification.
Within 2-3 years of inclusion, &gt;85% of patient achieved BP control (&lt;140/90 mmHg), which was sustained during follow-up. Over a median (IQR) follow-up of 8 (2016-2023) years, there were 14 (5) MI and 34 (16) strokes. These event rates appear to be lower than those reported in other large cohorts of patients with HTN.

Conclusions
Treating patients with HTN according to their individual haemodynamic profile is associated with high rates of BP control. Further analysis will determine whether the rates of MI, stroke and death are lower than expected based on the patients baseline risk profile.Haemodynamic Status (ICG Test Results)
Assessing the efficacy of renal denervation in patients with resistant arterial hypertension: a systematic review and meta-analysis
Authors: Ribeiro Goncalves O , Guilherme Maia J , Kendi Tsuchiya Sano V , De Oliveira Macena Lobo A , Alves Kelly F , Morbach V , Cezar Aquino De Moraes F , Menegaz De Almeida A 
Published: October 2024

Abstract

Background/Introduction
Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN emerges as an alternative for patients with resistant arterial hypertension. Despite this, the clinical efficacy of RDN is still not fully understood.

Purpose
Therefore, we aimed to compare the use of renal denervation versus sham procedure or pharmacological treatment in patients with resistant HTN.

Methods
We performed a systematic search of PubMed, Embase, Cochrane databases for randomized controlled trials (RCTs) comparing the use of renal denervation procedures and sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2. Heterogeneity was examined with the Cochran Q test I² statistics. Mean difference (MD) with 95% CI were pooled across trials. P values of &lt; 0.05 were considered statistically significant. The primary continuous outcomes of interest were change from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP) and serum creatinine.

Results
Twenty-one RCTs reporting data on 3345 patients were included in this meta-analysis. Among them, 2004 (59,91%) received renal denervation and 1341 (40,09%) received pharmacological treament or sham procedure. Follow-up ranged from 2 to 48 months. The mean age of patients between studies ranged from 50.7 to 65 years. Compared to control group, RDN significantly reduced Systolic Blood Pressure (SBP) (MD -3.53 mmHg; 95% CI -5.94 to -1.12; I2 = 74%) and Diastolic Blood Pressure (DBP) (MD -1.48 mmHg; 95% CI -2.56 to -0.40; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; I2 = 40%) there was no significant difference between RDN and control groups.

Conclusion
In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.