bluuebunny/crossref_metadata_2025 huggingface dataset:
LV reverse remodeling after SAVR in patients with severe symptomatic aortic stenosis: impact on the clinical outcome
Authors: Lima M R L , Abecasis J A , Reis Santos R R S , Maltes S M , Guerreiro S G , Freitas P F , Ferreira A F , Ribeiras R R , Andrade M J A , Madeira M M , Ramos S R , Sousa Uva M S U , Adragao P A
Published: October 2024

Introduction

Surgical aortic valve replacement (SAVR) is the treatment of choice for young patients with severe aortic stenosis (AS) and low surgical risk. Left ventricular (LV) reverse remodeling (RR) after surgery is expected to occur. However, this is not always the case following afterload relief, and this may impact the prognosis. We aimed to assess the prognostic effect of distinct definitions of LV RR after SAVR in the long-term outcome of patients with severe AS.

Methods

Single-centre prospective study including patients referred for SAVR due to severe symptomatic AS, with no previous history of ischemic cardiomyopathy. Both pre- and post-operative transthoracic echocardiographic (TTE) and cardiac magnetic resonance (CMR) study (at the 3rd to 6th month after SAVR) were performed. LV RR was defined when in presence of at least one of the imaging criteria: >15% decrease in end-diastolic volume (EDV) by CMR; >15% decrease in LV indexed mass (LVM) by CMR; >10% decrease in geometric remodeling (LV mass/EDV ratio) by CMR; >10% increase in LV ejection fraction (LVEF) by CMR; >50% increase on global longitudinal strain (GLS) by TTE. We assess the prognostic value of RR definitions for the outcome after SAVR using Cox regression and Kaplan-Meier analysis. The primary endpoint was defined as all-cause mortality, heart failure (HF) hospitalization or worsening HF.

Results

We enrolled 140 patients – mean age 71±9 years-old, 49% male, predominantly high-gradient-normal flow AS (mean gradient 65±18mmHg, aortic valve area 0.7±0.2cm2, index stroke volume 47±11mL/m2) submitted to SAVR. At a mean follow-up (FUP) of 34±12 months, 23 (16%) patients met the primary endpoint: 4% (5 patients) died immediately after surgery; three patients died at the FUP (overall mortality rate of 6%). 12 patients (9%) were admitted for HF and 7 (5%) had at least one episode of worsening HF. 118 patients had complete pre and post-surgery imaging study (mean FUP: 36±10 months): 103 patients (87%) had at least one RR parameter (Table 1). Post-operative RR was not independently associated with the clinical outcome (Figure 1A). LVM was the sole independent predictor of the outcome at univariate analysis (Figure 1B–F).

Conclusions

LV RR after SAVR is highly prevalent in a cohort of patients with classical severe symptomatic AS. However, only LVM regression independently predicts the clinical outcome after surgery. This may stand the greater importance of structural reverse remodeling, rather than LV functional improvement, after pressure overload relief.
Association of hypertension and the risk of cancer: a study based on the UK Biobank
Authors: Wu H , Li Z H , Ou Y Q
Published: October 2024

Introduction

With the increasing incidence rate of hypertension and carcinoma, there is a growing interest in investigating the potential link between these two diseases. The subdiscipline of hypertension, Onco-hypertension, has been proposed and attracted much attention. However, there are still few researches on this subdiscipline.

Purpose

This study aims to investigate the relationship between hypertension and the occurrence of cancer. Additionally, we explore whether anti-hypertensive treatment has any impact on the incidence of cancer.

Methods

This study involved 244,496 participants recruited between 2006-2010 from the UK Biobank, with 21,765 participants were diagnosed with the hypertension according to the ICD10 coding. The Cox regression was used to analyse the the risk of cancer associated with hypertension. The effect of anti-hypertensive treatment on the occur of cancer was also verified according to the Cox regression and the Drug target Mendelian randomization.

Results

Compared to those participants without hypertension, those people with hypertension have higher risk of the occur of cancer(adjusted hazard ratio(aHR) 1.35, 95% confidence interval(CI)1.3-1.4), especially in breast cancer(aHR 1.43, 95% CI 1.27-1.61), prostate cancer(aHR 1.85, 95% CI 1.7-2.02), lung cancer(aHR 2.15, 95% CI 1.86-2.48), renal cancer(aHR 1.91, 95% CI 1.46-2.49), pancreas cancer(aHR 1.55, 95% CI 1.2-2). Compared to those people with hypertension but without anti-hypertensive treatment, the anti-hypertensive treatment increase the cancer risk(aHR 1.19, 95% CI 1.06-1.33). However, thiazide diuretic have protect effect for hypertension patients on occur of the prostate cancer (aHR 0.74, 95% CI 0.61-0.89) and beta-receptor blocker have protect effect for hypertension patients on occur of the lung cancer (aHR 0.71, 95% CI 0.54-0.93). The result of Drug target Mendelian randomization shows the anti-hypertensive treatment have no significant effect on the risk of cancer.

Conclusion

The onset of high blood pressure is linked to an elevated risk of several cancers. However, it cannot be conclusively determined whether the use of medications for high blood pressure increases or decreases the overall risk of cancer. This study provides instructive evidences for the further study of Onco-hypertension.The result of main analyseThe analyse of the antihypertensive drug
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

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

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<0.001), thrombospondin-2 (THBS2, βobservational=0.05, SE=0.009, PFDR<0.001), paraoxonase-2 (PON2, βobservational=-0.03, SE=0.008, PFDR<0.001), and sclerostin (SOST, βobservational=-0.03, SE=0.009, PFDR<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

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 >210mmHg in men and >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=<0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p<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=<0.0001), MSNA levels (36vs28 bursts, p=<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

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 >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

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

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

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 <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

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, >85% of patient achieved BP control (<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

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 < 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.
Efficacy comparison of transcatheter aorticorenal ganglion ablation and renal denervation in a hypertensive canine model
Authors: Long Y X , Lai Y C , Li D , Ren Y W , Ma X M , Zhou H , Yi X , Chen L Y , Yin Y H
Published: October 2024

Background

Transcatheter renal sympathetic denervation (RDN) has been proposed to be an adjunctive treatment in uncontrolled hypertension. However, non-responders to RDN were not rare. Considering the lack of a procedure endpoint and the limitation of anatomic-based ablation strategy, incomplete or futile denervation may contribute to non-responsiveness. Aorticorenal ganglion (ARG) is a purely sympathetic ganglion that projects to the proximal and distal renal artery, forming the peri-arterial nerve network. Ablation of this ganglion results in significant renal denervation. However, it remains unknown whether ARG ablation has a superior effect in lowering blood pressure (BP) compared to RDN.

Purpose

The aim of the study was to determine whether ARG ablation improved the BP-lowering effect compared to RDN in a hypertensive canine model.

Methods

A total of 21 male Chinese Kunming dogs were included and randomized into three groups: ARG ablation group (n=7), RDN group (n=7) and control group (n=7). In the ARG ablation group, anatomically based high-frequency stimulation (HFS) was performed in the aorta and inferior vena cava (IVC) under the guidance of 3D anatomical construction (Figure 1A). ARG ablation sites were identified by HFS-induced BP elevation response (>10mmHg) and renal artery vasoconstriction (Figure 1B). In the RDN group, HFS-guided ablation was conducted at the positive site (BP elevation response >5mmHg) from the distal to proximal renal artery. Endpoint of the procedure was defined as the elimination or attenuation of BP elevation induced by HFS. BP was assessed at baseline and 4 weeks after the procedure.

Results

The left ARG ablations were performed at the inferior aspect of superior mesenteric artery (4/7), the abdominal aorta (2/7) and the proximal renal artery (1/7), while the right ARG ablations were performed at the posterior aspect of the IVC (6/7) and the ostium of the left renal vein (1/7). The gross anatomy of bilateral ARGs was shown in Figure 1C. The hemodynamic response to ARG stimulation was significantly greater than that of renal artery stimulation (40.0±13.4 vs 13.3±3.7 mmHg, Figure 2A, B); meanwhile, ARG ablation is more effective in blunting the BP elevation response compared to RDN (30.7±11.7 vs 9.6±2.6, P=0.001, Figure 2A, C). With a 4-week follow-up, ARG ablation demonstrated a greater systolic BP-lowering effect than RDN (-29.6±12.0 vs -15.3±6.9 mmHg, P=0.018, Figure 2D). No complications were found during the procedure or follow-up.

Conclusion

Our study suggests that ARG ablation could lead to a more efficient BP-lowering effect compared to RDN, which provides a novel paradigm for autonomic modulation in the treatment of hypertension.Figure 1Figure 2
Cumulative effect of lifetime smoking history on arterial stiffness and subclinical atherosclerosis in patients with arterial hypertension
Authors: Ioakeimidis N , Kouroutzoglou A , Terentes-Printzios D , Dima I , Laina A , Angelis A , Lazarou E , Papadatos S , Kalfountzos D , Tsioufis K , Vlachopoulos C
Published: October 2024

Introduction

Although the effect of smoking status on blood pressure (BP) changes is well known an adverse association between cumulative smoke exposure (by pack-years) and functional and structural changes in arteries of patients with high BP has not been consistently demonstrated. Aim of the study was to explore the contributions of cumulative smoke exposure to the vascular consequences of arterial hypertension.

Methods

Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), augmentation index (AIx) and carotid intima media thickness (cIMT) were measured in 485 adults aged less than 60 years old without a history of cardiovascular disease. The cohort was divided into three groups according to office systolic BP (SBP) and diastolic BP (DBP): normal (SBP <130 and DBP <85 mmHg, n=242), high normal (130≤SBP<140 or DBP 85≤DBP<90mmHg, n=96), and hypertension (SBP≥140 or DBP≥90mmHg, n=147). The cohort was subdivided according to pack-years of smoking history as never smokers (0.0 pack-years), light smokers (<20 pack-years), moderate smokers (20-40 pack-years), and heavy smokers (> 40 pack-years).

Results

The three BP groups had similar age and metabolic parameters (body mass index, fasting blood glucose and LDL-C). Figure shows PWV, AIx and carotid IMT by smoking exposure, stratified by BP level. The lowest PWV level was observed in never smokers with normal BP; whereas heavy smokers with hypertension exhibited the highest PWV. Also of note, heavy smokers with normal BP exhibited comparable PWV to light and never smokers with hypertension. Furthermore, in smokers with more than 20 pack-years tobacco exposure, PWV was higher among patients with high normal BP compared to subjects with normal BP (all P<0.01). In contrast to the monotonic increases in PWV and AIx by BP and pack-years smoking history, carotid IMT was generally similar among BP groups on the basis of cumulative exposure category. This finding may indicate a plateau in subclinical atherosclerotic burden over cumulative tobacco exposure for all BP categories.

Conclusion

Tobacco cumulative exposure adversely modify the effect of BP on arterial stiffness. Given that most adults who smoke start before the age 18 years, efforts to promote smoking cessation should continue to target younger adults with high BP.BP, tobacco exposure-vascular changes
Remnant cholesterol and cardiovascular and all-cause mortality in Korean adults
Authors: Kim B J , Kang J G
Published: October 2024

Background

Although previous studies have reported that remnant cholesterol (RC) is associated with cardiovascular disease, studies on RC and various mortality related outcomes including cardiovascular mortality in the general population are scarce and most of them are limited to Western populations.

Purpose

This study aims to evaluate the effect of RC on mortality related outcomes in a relatively young and middle-aged Korean population.

Methods

This cohort study included 268,219 subjects (mean age, 38 years and 50.6% men) who were enrolled in the Kangbuk Samsung Health Study between 2003 and 2016. Fasting RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDLC).

Results

The median RC was 0.47 mmol/L (18 mg/dL) and the prevalence of ≥ 1 mmol/L RC was 11.4%. During the median FU of 6.7 years, high RC (RC ≥ 0.47 mmol/L) significantly increased the risk of multivariable-adjusted cardiovascular mortality compared with low RC (HR[95% CI], 1.43[1.07, 1/93]). Compared with the lowest quintile (RC <0.31 mmol/L), the HRs for cardiovascular mortality were 1.95[0.78, 4.84], 2.47[1.03, 5.91], 2.39[1.00, 5.72], and 2.84[1.19, 6.78] in the second, third, fourth, and highest quintiles, respectively. The HRs for all-cause mortality in the 3rd, 4th, and highest quintiles remained significant (1.24[0.97, 1.59], 1.38[1.08, 1.76], 1.34[1.05, 1/71], and 1.32[1.03, 1.69] in the 2nd, 3rd, 4th, and highest quintiles, respectively). However, there was no significant risk for cancer mortality between RC quintiles. Notably, subgroup analysis showed that individuals with high RC and high hsCRP and high RC and high lipoprotein(a) had a more than twofold and threefold increased risk of cardiovascular mortality, respectively, compared with low RC and low hsCRP and low RC and low lipoprotein(a).

Conclusions

High RC was significantly associated with increased risk of cardiovascular and all-cause mortality, but not with cancer mortality. In particular, high hsCRP and high lipoprotein(a) weighted the risk association between high RC and cardiovascular mortality.
The projected global burden of modifiable risk factors on cardiovascular disease from 2025 to 2100
Authors: Chong B , Jayabaskaran J , Kueh M , Goh R , Li H , Foo R , Chan M , Chew N
Published: October 2024

Background

Cardiovascular diseases (CVDs) are the primary cause of global mortality and morbidity. Controlling modifiable risk factors driving the CVD epidemic is a vital focus of primary prevention efforts worldwide. Understanding the epidemiological trends in these risk factors is therefore essential in designing effective countermeasures against CVDs for the years to come.

Purpose

This study aims to forecast the disability-adjusted life years (DALYs) associated with CVDs attributable to high systolic blood pressure (SBP), high body-mass index (BMI), high fasting plasma glucose (FPG), high low-density lipoprotein (LDL) and tobacco use from 2025 to 2100, stratified by GBD super-regions, sex, sociodemographic index (SDI), and age-groups.

Methods

Historical data on DALYs from 1990 to 2019 from the Global Burden of Disease (GBD) study was used to project DALYs associated with modifiable risk factors of CVDs from 2025 to 2100. Trends across GBD super-regions, sex, SDI, and age-groups were also examined.

Results

Between 2025 and 2100, age-standardised DALY rates (ASDR) per 100,000 population are forecasted to fall across all modifiable risk factors, with the greatest decline seen in tobacco use (-76.0%) and high LDL (-66.9%). Globally, high SBP and high BMI expect the greatest ASDR in 2100 (both 891 per 100,000 population), while tobacco use expects the least (213 per 100,000 population). High BMI is expected to rise 623.0% in South Asia and 221.5% in South-east Asia, East Asia and Oceania from 2025 to 2100, while high FPG is expected to rise 114.2% in North Africa and the Middle-east and 110.6% in South Asia. Females are expected to have lower overall and greater reductions in ASDR across all modifiable risk factors when compared to males from 2025 to 2100. Notably, males expect a 11.0% rise in high BMI worldwide across this period. The age-prevalence of modifiable risk factors is expected to be bimodal in 2100, highest in those aged 50-59 as well as 75-84 years old, possibly suggesting improvements in global screening efforts or the earlier development of metabolic dysfunction. All modifiable risk factors are predicted to fall in high and high-middle SDI regions from 2025 to 2100. In contrast, low, low-middle, and middle SDI regions expect a rise in high FPG and high BMI across this same time frame. The burden of modifiable CVD risk factors is expected to be highest in low-middle SDI regions in 2100, as compared to high-middle SDI regions in 2025.

Conclusion

While the global decline in ASDR of modifiable risk factors suggests overall improvements in the primary prevention of CVDs, regional spikes in high BMI and FPG calls for the implementation of timely, targeted interventions accounting for local trends in CVD. Moreover, the disproportionate metabolic burden expected in lower SDI regions in the coming decades requires concerted, international support to alleviate the global burden of CVDs.
Systolic blood pressure time in target range and cardiovascular disease and premature death
Authors: Han X , Yang Q , Zhou X , Wu S
Published: October 2024

Background

Time-in-target range (TTR) for systolic blood pressure (SBP) independently predicts cardiovascular outcomes. However, there are limited research based on real-world data.

Purpose

To estimate SBP-TTR associated with cardiovascular disease (CVD) and premature death among the employed individuals with hypertension.

Methods

This study is based on the Kailuan cohort. As part of the Kailuan study, a workplace-based hypertension management programme was initiated in 2009 for employed people with hypertension. The TTR was defined as 120 to 140 mmHg according to the current guidelines, and in the sensitivity analyses it was further defined as 110 to 130 mmHg. TTR was estimated over the first 6 months of follow-up using linear interpolation. The association between SBP-TTR with CVD, premature CVD and premature death was estimated using adjusted Cox proportional hazards regression models to adjust for multiple confounders.

Results

A total of 9552 hypertensive participants were included. A one standard deviation increase in SBP-TTR is associated with a 19% reduction in the risk of CVD (HR:0.81; 95%CI: 0.74 to 0.88), a 24% reduction in the risk of premature CVD (HR:0.76; 95%CI: 0.67 to 0.86), and a 17% reduction in the risk of premature death (HR:0.83; 95%CI: 0.74 to 0.92). When SBP-TTR is redefined as 110-130 mmHg, a one standard deviation increase in SBP-TTR is associated with a 23% reduction in the risk of CVD (HR:0.77; 95%CI: 0.70 to 0.84), a 30% reduction in the risk of premature CVD (HR:0.70; 95%CI: 0.60 to 0.81), and a 27% reduction in the risk of premature death (HR:0.73; 95%CI: 0.66 to 0.80). These associations were independent of SBP-mean and SBP-SD. Subgroup analysis results indicate that SBP-TTR contributes to a reduction in the risk of premature death in individuals with a high cardiovascular risk score.

Conclusions

SBP-TTR was statistically associated with a decreased risk of CVD, premature CVD and premature death. Intensifying blood pressure control measures can further increase cardiovascular benefits.
Associations of omega-3 fatty acid subclasses with cardiovascular diseases in 500,000 individuals
Authors: Kerminen S , Jostins-Dean L , Schut K , Wurtz P , Barrett J C
Published: October 2024

Increased blood levels of omega-3 fatty acids have consistently been shown to be associated with reduced risk of cardiovascular diseases (CVD). However, large scale placebo-controlled trials of omega-3 supplementation have had discordant results: in 2018 REDUCE-IT reported a 25% risk reduction, whereas in 2020 STRENGTH reported no risk reduction. The two trials had both different placebos (mineral vs corn oil) and omega-3 formulations (EPA vs DHA+EPA). There is not yet a consensus on what explains these results.

Here we describe the profiling of omega-3 fatty acid subclasses, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) with nuclear magnetic resonance (NMR), and test their associations with incident CVD in 500,000 individuals from UK Biobank.

We utilized 500 MHz NMR spectrometers to analyze total omega-3 and its subclasses in EDTA plasma samples and employed biomarker-specific quantification algorithms to measure their absolute concentrations. In this study, we developed a novel algorithm to quantify EPA, complementing previously described algorithms for omega-3 and DHA. Correlation (r^2) of this novel NMR-based quantification and gas chromatography-based measurements was 0.77 for EPA. On average, DHA comprised 44.5% of the total omega-3 concentration, EPA accounted for 22.2%, and other subclasses constituted 34.3% in the cohort.

We computed age and sex adjusted associations of omega-3, DHA, and EPA with 10-year risk of CVD among individuals who were not taking cholesterol lowering medication. We discovered protective associations: for DHA a hazard ratio of 0.85 (0.86-0.89, 95% confidence interval) per standard deviation versus 0.96 (0.95-0.98) for EPA, and 0.95 (0.93-0.97) for total omega-3 (Figure).

Since DHA (used in the STRENGTH trial with a null result) has a significantly stronger epidemiological association than EPA, these results from a large-scale observational study do not support the hypothesis that the differential use of DHA and EPA in the REDUCE-IT and STRENGTH trials explains their divergent results.Figure
Study design of the CARDIO-TTRansform cardiac magnetic resonance imaging substudy
Authors: Fontana M , Masri A , Garcia-Pavia P , Cuddy S , Cappelli F , Cipriani A , Gillmore J D , Razvi Y , Moon J C , Reicher B , Chen J , Viney N , Duran J M , Tsimikas S
Published: October 2024

Background

Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping can track treatment response in patients with cardiac amyloidosis by assessing changes in cardiac amyloid burden along with associated changes in structure and function. The CARDIO-TTRansform trial is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial designed to assess the efficacy and safety of eplontersen in transthyretin amyloid cardiomyopathy (ATTR-CM). Eplontersen is a ligand-conjugated antisense oligonucleotide designed to reduce hepatic production of transthyretin protein, the amyloid fibril precursor protein in ATTR-CM. Patients with hereditary or wild-type ATTR-CM on available standard of care were randomized 1:1 to receive 45 mg of eplontersen or placebo via subcutaneous injection every 4 weeks. Patients in the main study with no contraindication to CMR were invited to participate in this sub-study.

Purpose

The primary objective is to measure the change in amyloid burden (defined as % change in ECV from baseline) over time in patients receiving eplontersen versus placebo.

Methods

Participants will undergo CMR with ECV mapping at baseline, 25, 49, 97 and 140 weeks (Figure 1). Images will be acquired under a standardized protocol comprising cine imaging with steady state free precession sequence, late gadolinium enhancement imaging (LGE) and T1 mapping. T1 mapping will be performed before the administration of contrast and will be repeated 15 minutes post-contrast using the same slice locations, to produce ECV maps.

Results

In the main study, 1432 patients were randomized from 120 sites across 20 countries. Of these patients, 157 patients were enrolled in the CMR sub-study, from 6 centers across 4 countries. Images will be read centrally at the end of the study. All participants in the study will also receive serial transthoracic echocardiography with strain analysis to correlate findings with conventional imaging techniques, and a subset of patients from the CMR substudy will be co-enrolled in a scintigraphy substudy for further characterization of amyloid deposition in their heart.

Conclusion

The CARDIO-TTRansform CMR substudy represents the largest CMR study of ATTR-CM. The CMR sub-study has enrolled a broad global population of patients with hereditary and wild-type ATTR-CM and will provide key information on the impact of eplontersen on the cardiac amyloid load and the associated change in structure and function.