bluuebunny/crossref_metadata_2025 huggingface dataset:
Is chronic kidney disease predictive of coronary artery bypass grafting after acute coronary syndrome? A systematic review and meta-analysis
Authors: Scott J , Letts M , Hajee-Adam W , Chau C , Bailey P , Johnson T , Caskey F J , Selman L E , Ben-Shlomo Y
Published: October 2024

Background

Coronary artery bypass grafting (CABG) provides superior long-term outcomes to percutaneous coronary intervention (PCI) for multi-vessel coronary artery disease. People with chronic kidney disease (CKD) are at increased risk of multi-vessel coronary artery disease, and experience greater morbidity and mortality following acute coronary syndrome (ACS).

Purpose

To determine whether CKD affects choice of revascularisation strategy after ACS.

Methods

We searched EMBASE, MEDLINE, SCOPUS, CENTRAL and the NIHR’s website of funded studies to identify articles referring to ACS and invasive coronary management in high-income countries over the past 12 years until 29th September 2023. Full text articles were included if data on rates of CABG were reported in people with and without CKD who were revascularised following ACS. CKD was defined as one or more recording of an estimated glomerular filtration rate (eGFR) <60mls/min/1.73m2, however proxies for this were accepted. Risk of bias was assessed via ROBINS-E. Random effect meta-analyses estimated the odds ratios for CKD and CABG, stratified by ACS type and receipt of dialysis. Certainty of evidence was assessed according to GRADE.

Results

Initial searches generated 15,138 articles, of which 13 observational studies were included in this review (8,021,743 participants). Amongst people revascularised following ACS, those with CKD were more likely to receive CABG than those without kidney disease (OR for the average exposure effect 1.47 (95% CI 1.30-1.66)). The likelihood of CABG in people with CKD receiving dialysis and those with CKD not receiving dialysis were similar as the 95% confidence intervals demonstrate (ORs 1.25 (95% CI 1.00-1.57) and 1.41 (1.19-1.67) respectively). The effect of CKD on increased likelihood of CABG appeared greater following ST-elevation myocardial infarction (STEMI) than non-ST elevation ACS (NSTE-ACS) (OR 1.53 (95% CI 1.27-1.83) versus 1.10 (0.98-1.25) respectively, p=0.003). Certainty of the evidence was low for receipt of CABG in people with CKD not receiving dialysis, and moderate for all other outcomes.

Conclusion

In high-income countries, CKD is associated with increased receipt of CABG amongst people revascularised following ACS. This finding is likely explained by the greater prevalence of multi-vessel coronary artery disease in this population. It is however unclear why the association between CKD and receipt of CABG is stronger in those with STEMI compared to NSTE-ACS, and whether this accurately reflects differential need between the two groups.Figure 1Figure 2
Effect of renal dialysis session on novel echocardiographic parameters of left and right ventricle in patients with end-stage renal disease
Authors: Afendoulis D , Sitaras P , Moutafi M , Voutas P , Ampeliotis M , Didagelos M , Kartalis A
Published: October 2024

Introduction

Chronic heart disease is among the leading causes of end-stage renal disease (ESR). On the other hand, patients with ESR undergoing dialysis demonstrate often subclinically impaired left and/or right ventricular function according to small studies, and higher prevalence of chronic heart disease. However, data regarding the effect of renal dialysis on novel echocardiographic parameters among renal dialysis patients remain limited.The purpose of our study, was to study the effect of renal dialysis on novel echocardiographic parameters of left and right ventricle.

Methods

All 50 patients (14 females) of mean age 62.9 years undergoing renal dialysis in our kidney unit regularly were included in our study. Blood pressure, heart rate and weight measurements and heart echocardiogram with measurement of LV GLS, RV GLS, RV FWS, LA ResS, E/e’ ratio, Right Ventricular Systolic pressure (PASP) and inferior vena cava (IVC) diameter, before and after renal dialysis session, were carried out.

Results

Mean values of body weight (79,9 vs 77,6 kg), heart rate (74,2 vs 73,5 bpm) and blood pressure (131,5/80,6 vs 123,5/76,9 mmHg) were as expected statistically significant reduced after renal dialysis (p<0,001). Values of PASP (36,1 vs 27,8 mmHg), E/e’ ratio (14 vs 12,5) and IVC diameter (1,6 vs 1,3 cm), were statistically significant reduced after renal dialysis (p<0,001). Furthermore, values of RV GLS (-19,3 vs -20,3 %), RV FWS (-21,2 vs -22,6 %) and LA ResS (29,6 vs 30,7%), were statistically significant improved after renal dialysis session (p <0,001), while LV GLS depicted a minor improvement (-17,9% vs 18,2%) not statistically significant.

Conclusion

In conclusion, renal dialysis session had a beneficial effect on novel echocardiographic parameters of left and right ventricle (RV GLS, RV FWS, LA ResS) due to improvement of hemodynamic parameters (blood pressure, heart rate, PASP and IVC diameter) and intravascular volume reduction. Larger clinical studies should be organized to further investigate the effect of renal dialysis on those parameters and the underlying mechanisms in the chronic setting of hemodialysis.
Correlation between postdialysis blood pressure assessed at different time points and home blood pressure monitoring
Authors: Nadruz W , Bezerra R , Teles F , Franco C M M A , Vieira L M S F , Sposito A C , Feitosa A D M
Published: October 2024

Background

Hemodialysis patients undergo blood pressure (BP) measurements during the predialysis, intradialytic and postdialysis (POSBP) periods at the dialysis sessions. However, there is no consensus regarding the time point when POSBP measurement should be performed.

Purpose

This study investigated the relationship of POSBP measurements performed at different time points with home blood pressure monitoring (HBPM).

Methods

This prospective study included 98 long-term dialysis patients (67% men; age=59.4 ±17.7 years; 79% using antihypertensive medications). During one week, POSBP measurements were obtained in sitting patients by trained health staff using oscillometric BP monitors lodged in the dialysis machines at all dialysis sessions in three different periods: 1) immediately after the dialysis period ended (POSBP1); 2) after returning the patient's blood (POSBP2) and 3) after hemostasis of the fistula or catheter sealing (POSBP3). In the same week, HBPM was performed using validated devices and was calculated as the mean of BP measurements obtained on six consecutive days, comprising three readings in the morning and in the evening after at least 3 min of rest, before antihypertensive medications were taken, with the patients seated. Abnormal BP was defined as HBPM≥135/85 mmHg. Based on the optimal cut-point values derived from ROC curves analysis, we built cutoffs for POSBP1 (143/79 mmHg), POSBP2 (153/78 mmHg) and POSBP3 (151/80 mmHg) corresponding to HBPM values of 135/85 mmHg.

Results

The values of POSBP1, POSBP2, POSBP3 and HBPM were 138±21/72±13, 143±24/73±13, 142±22/72±13 and 128±19/76±13 mmHg, respectively. Systolic HBPM showed greater correlation with systolic POSBP3 (r=0.71), followed by POSBP1 (r=0.68), POSBP2 (r=0.67), while diastolic HBPM showed greater correlation with diastolic POSBP2 and POSBP3 (both r=0.56), followed by POSBP1 (r=0.49) (all p<0.05). The POSBP3 cutoff showed the highest association (odds ratio [95% CI]= 8.06 [3.21, 20.27]), accuracy (area under the curve [95% CI]= 0.74 [0.65, 0.83]) and concordance (kappa coefficient=0.47) to identify elevated BP at HBPM in comparison with the POSBP1 and POSBP2 cutoffs (Figure).

Conclusion(s)

POSBP3 exhibited the strongest correlation with HBPM and had the highest accuracy to detect elevated HBPM in dialysis patients and may be a potentially preferable POSBP measurement in clinical practice.
Guideline-directed medical therapy and in-hospital mortality in acute coronary syndrome patients with advanced renal dysfunction
Authors: Jin Z , Zhou X , Yang Q
Published: October 2024

Background

It is unclear whether early (initiated within 24 hours of admission) guideline-directed medical therapy [GDMT, i.e., the combined use of β-blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, dual antiplatelet drugs and statin] could benefit acute coronary syndrome (ACS) patients with advanced renal dysfunction [estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2].

Objectives

The purpose of this study was to verify whether GDMT could improve in-hospital mortality in ACS patients with advanced renal dysfunction.

Methods

This study included 3,288 and 3,520 ACS patients with admission with advanced renal dysfunction from the CNEDSSP and CCC-ACS cohorts, respectively. Multivariable-adjusted analysis and propensity score matching (PSM) were employed to assess the impact of GDMT on in-hospital mortality.

Results

In a pooled analysis of the CNEDSSP and CCC-ACS cohorts, early GDMT was associated with significantly lower in-hospital mortality (relative ratio [RR]: 0.62, 95% CI: 0.47 to 0.81). PSM revealed an attenuation of the association of in-hospital mortality with early GDMT in ACS patients, with statistically significant associated reductions observed only in myocardial infarction (MI) patients (hazard ratio [HR]: 0.45, 95% CI: 0.27 to 0.75 in CNEDSSP cohort; HR: 0.48, 95% CI: 0.27 to 0.84 in CCC-ACS cohort). A random-effect pooled analysis for MI patients with admission advanced renal dysfunction demonstrated a 56% lower in-hospital mortality among GDMT users (RR: 0.44, 95% CI: 0.31 to 0.65).

Conclusions

This nationwide study highlights that early GDMT is associated with a reduced risk of in-hospital mortality in ACS patients (particularly in MI patients) with advanced renal dysfunction.
Much ado about nothing: the impact of coronary angiography on kidney function in individuals with chronic kidney disease
Authors: Dirir O , Johnson J , Khwaja A
Published: October 2024

Background and Objectives

Chronic kidney disease (CKD) is associated with premature coronary artery disease and an increased risk of cardiovascular morbidity and mortality (1). Historically, there has been a tendency to delay or even avoid coronary angiography (CA) in those with CKD due to an increased risk of contrast-induced nephropathy or concern over precipitating the need for chronic dialysis. Such "renal nihilism" may account for the poorer outcomes observed in CKD patients who present with acute coronary syndromes (2). The role of this retrospective analysis was to evaluate the impact of CA on the temporal trend in kidney function in individuals with CKD over a 24-month period.

Methods

The clinical details of 120 individuals under long-term local follow-up by various Nephrology clinics (CKD clinic, low creatine clearance, polycystic kidney disease, transplant and immunosuppression clinics) was collected. All underwent CA locally. Kidney function was observed at set intervals of 12-, 9-, 6- and 3-months prior to CA, immediately post-CA, and at 3-, 6-, 9- and 12-months post-CA. Only results obtained after the desired time point but within 28 days were included. All CAs regardless of either their indication (elective or urgent) or whether percutaneous intervention (PCI) was performed, were included. Patients already on dialysis at the time of the CA were excluded. Statistical analysis was performed via one-way ANOVA.

Results

Patient characteristics are summarised in table 1. The average age of patients was 67, with a male preponderance (72%). 22% had CKD 3, 24% had CKD 4 and 12% had CKD 5. 9% were kidney transplant recipients. 37% underwent urgent CA whilst a total of 22% had PCI. 27% progressed to requiring renal replacement therapy (RRT). The mean length to RRT was 2.8 years.

The rate of decline in kidney function in the last 12 months prior to CA was 7.7% and 6.3% in the year after CA (figure 1). There was no statistically significant difference in kidney function after CA (p = 0.395). This was replicated in analyses focussing on CKD classes 3, 4 and 5 individually, within stable kidney transplant recipients, and within analysis comparing PCI vs non-intervention CAs.

Conclusion

The results demonstrate CA does not accelerate the decline in kidney function in those with known CKD over a 12-month period, and suggests where appropriate, an invasive treatment strategy should be consider and utilised more often in this population.Table 1:Patient characteristicsFigure 1:Trend in eGFR relative to CA
Electronic nudges to increase influenza vaccination in patients with chronic kidney disease: a prespecified analysis of NUDGE-FLU-CHRONIC
Authors: Grundtvig Skaarup K G , Johansen N D , Vaduganathan M , Bhatt A , Modin D , Chatur S , Claggett B L , Janstrup K H , Kober L , Solomon S D , Sivapalan P , Jensen J U S , Martel C , Krause T G , Biering-Sorensen T
Published: October 2024

Background

Annual influenza vaccination is recommended for individuals with chronic kidney disease (CKD); however, guideline adherence is suboptimal potentially related to lack of awareness of vaccine availability and effectiveness.

Purpose

This prespecified analysis of the NUDGE-FLU-CHRONIC trial investigated the effectiveness of digital behavioral nudges on influenza vaccine uptake based on the presence or absence of CKD.

Methods

NUDGE-FLU-CHRONIC was a randomized, nationwide trial, conducted during the 2023/2024 influenza season including younger and middle-aged (18-64 years) Danish citizens with chronic illnesses (making them eligible for the free Danish vaccine program). Participants were randomized in a ratio of 2.45:1:1:1:1:1:1 to receive either usual care (no letter) or one of six different letter-based nudges, delivered via the governmental electronic letter system on September 26, 2023. Baseline and outcome data were obtained with the Danish nationwide registers. Primary endpoint was receipt of an influenza vaccine no later than January 1, 2024.

Results

A total of 299,881 individuals were randomized in NUDGE-FLU-CHRONIC trial, among them, 15,208 (5.1%) had a history of CKD. Participants with CKD had a median age was 53.1 years (IQR, 42.2-59.6) and 46.0% were female. During follow-up, 43.7% of participants with CKD were vaccinated compared with 35.8% of participants without CKD (p<0.001). Any letter was highly effective in increasing influenza vaccination in the overall population but was slightly less effective in those with a history of CKD (p for interaction = 0.005). In participants with CKD, any letter increased vaccination by 25% versus no letter (46.3% vs. 37.1%; difference, 9.3 percentage points; 99.29%CI, 6.9-11.6; RR, 1.25; 99.29%CI, 1.18-1.33). In participants without CKD, any letter increased vaccination by 43% (39.2% vs. 27.4%; difference, 11.8 percentage points; 99.29%CI, 11.3-12.3; RR, 1.43; 99.29%CI, 1.41-1.45). Similar patterns were observed when assessing each intervention letter individually (Figure 1). Effectiveness of any letter vs. usual care was consistent across CKD subgroups, except for concomitant diabetes vs no diabetes (Figure 2). There was no observed effect modification by CKD duration (p for interaction = 0.78) or by estimated glomerular filtration rate (p for interaction = 0.78) modelled continuously for any letter vs. usual care.

Conclusion

In this prespecified analysis from the nationwide NUDGE-FLU-CHRONIC trial, only approximately 1 in 3 younger and middle-aged adults with CKD received influenza vaccination. Digital nudge letters emphasizing the importance of annual influenza vaccination significantly boosted rates of vaccination across a broad range of individuals with CKD.Figure 1Figure 2
Association between estimated glomerular filtration rate and prognosis in patients with cardiovascular disease with and without sarcopenia
Authors: Sugawara N , Kamiya K , Hotta K , Hamazaki N , Nozaki K , Ichikawa T , Ueno K , Uchida S , Noda T , Ogura K , Miki T , Maekawa E , Yamaoka-Tojo M , Matsunaga A , Ako J
Published: October 2024

Background/Introduction

A low estimated glomerular filtration rate (eGFR) has been identified as a poor prognostic factor in patients with cardiovascular diseases (CVD). Since serum creatinine, which defines eGFR, is a metabolite of skeletal muscle, low skeletal muscle mass can result in reduced creatinine production and potentially overestimate renal function. This raises concerns about the reliability of eGFR as a prognostic indicator in patients with both CVD and sarcopenia. The impact of this relationship, however, remains uncertain.

Purpose

This study aimed to explore the association between eGFR and prognosis in patients with CVD, both with and without sarcopenia.

Methods

We included 2,444 CVD patients (mean age 69.0 ± 13.7 years) who had assessments of eGFR and sarcopenia at discharge. Sarcopenia was diagnosed according to the 2019 Asian Sarcopenia Working Group Diagnostic Criteria. Patients were categorized into sarcopenia and non-sarcopenia groups, each further divided into high eGFR (eGFR ≥60 mL/min/1.73 m²) and low eGFR (eGFR <60 mL/min/1.73 m²) subgroups. Kaplan-Meier curves, log-rank tests, and multivariate Cox regression analyses were employed to compare prognoses between these groups, adjusting for age, sex, BMI, left ventricular ejection fraction (LVEF), history of myocardial infarction (MI), acute coronary syndrome (ACS), heart failure (HF), hypertension (HT), dyslipidaemia (DL), diabetes mellitus (DM), and smoking history. The primary endpoint was a composite of all-cause mortality and rehospitalization.

Results

Median follow-up was 1.11 (interquartile range [IQR], 0.43–2.32) years for the non-sarcopenia group and 0.94 (IQR, 0.30–2.15) years for the sarcopenia group. Event rates were 24.2% in the non-sarcopenia group and 30.8% in the sarcopenia group. Both Kaplan-Meier and log-rank tests indicated that a low eGFR, regardless of sarcopenia status, was associated with a higher incidence of composite events (p < 0.001). Multivariate Cox regression analysis revealed a significant association between low eGFR and increased risk of composite events in both the non-sarcopenia [hazard ratio (HR): 1.55, 95% confidence interval (CI): 1.44–1.67; p < 0.001] and sarcopenia groups [HR: 1.36, 95% CI: 1.25–1.48; p < 0.001].

Conclusion

Low eGFR is associated with poor prognosis in patients with CVD, irrespective of sarcopenia status.
Mapping renal impairment and cardiac structure and function: observation and genetic insights from 30,000 cardiac magnetic resonance images
Authors: Liu J , Huang H , Lu X , He Y , Tang N , Chen J , Liu Y
Published: October 2024

Background

The elevated risk of heart failure in kidney dysfunction is well-identified. However, the early alteration of renal impairment on cardiac structure and function, as well as genetic susceptibility associations have not been well reported. We sought to map the early effects of kidney dysfunction on cardiac remodeling with the cardiac magnetic resonance images (MRI) and identify share genetic correlation in community population.

Methods

Of 29,592 subjects underwent MRI test were recruited from the population-based UK Biobank study from 2006-2010. Renal function was assessed by historical identified chronic kidney disease (CKD), log-transfrom estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRCysC) or serum creatine (eGFRSCr) and urine albumin-to-creatinine ratio (uACR). Multivariable generalized linear regression was used to analyse the association of 4 different kidney function indexes with six cardiac MRI-derived traits: left atria and ventricle, right atria and ventricle, and ascending and descending aortas. Genetic correlation between renal function decline and cardiac traits were evaluated by Mendelian randomization (MR).

Results

The mean (SD) age of subjects was 54.9 (7.5) years, and 51.1% were women. Observational and MR analysis showed a reliable relationship of lower level of eGFRCysC with reduced biventricular end systolic volume, biventricular ventricular end diastolic volume and left ventricular mass, and lower level of eGFRSCr with reduced left ventricular cardiac output.

Conclusions

Our study indicates the observational and genetic correlation between kidney function decline and cardiac measurements. These findings provide insights into the potential mechanisms behind their comorbidity and the future development of therapeutics.Renal function decline & Cardiac Imaging
Inhibition of ceramide de novo synthesis mitigates atherosclerosis
Authors: Chong S Y , Louise R A , Huang C , Ting H J , Seah F , Qi X , Pastorin G , Storm G , Wang J W
Published: October 2024

Background

Atherosclerosis is the primary underlying cause of cardiovascular disease. Plasma ceramides are positively correlated with an increased risk of major adverse cardiovascular events and serve as an alternative biomarker for cardiovascular disease. Importantly, ceramide levels are notably higher within atherosclerotic plaques. Therefore, inhibiting the ceramide de novo synthesis pathway in the plaques may serve as a potential therapeutic intervention for atherosclerosis.

Purpose

We aim to assess the therapeutic efficacy of a nano-formulation of myriocin, a targeted inhibitor of serine-palmitoyl transferase, the key enzyme in ceramide de novo synthesis, in treating atherosclerosis.

Methods

Myriocin was encapsulated within the hydrophobic core of lipid-based nanoparticles specifically designed for this study. Male and female ApoE-/- mice, subjected to an 8-week high-fat diet regimen, received either myriocin nanoparticles (treatment group) or empty nanoparticles (control group) intravenously once a week for 4 weeks at a dose of 1.3 mg/kg body weight while still on the high-fat diet. At the study endpoint, whole aortas were harvested and subjected to Oil Red O staining to quantify the total lesion area. Histological staining was performed on serial sections of the aortic root to analyze the cellular composition within the plaques. Plasma samples were collected for total cholesterol measurement and lipidomic analysis.

Results

Upon intravenous administration, myriocin nanoparticles exhibited preferential accumulation in atherosclerotic plaques. Compared to control mice, those treated with myriocin nanoparticles exhibited a 58.7% reduction in total lesion area in male ApoE-/- mice and a 64.6% reduction in female ApoE-/- mice (p<0.0001). Consistently, the lesion areas in the aortic root were also reduced in the treated mice. Notably, myriocin nanoparticles enhanced collagen and alpha-smooth muscle content, while reducing macrophages and neutral lipids within the plaques, leading to a reduced plaque vulnerability index and preventing rupture events. TUNEL staining revealed reduced cellular apoptosis in the atherosclerotic plaques, resulting in a smaller necrotic area in the treated mice. In vitro experiments demonstrated that myriocin nanoparticles effectively inhibited lipopolysaccharide-induced inflammatory response and oxidative stress in bone marrow-derived macrophages. Furthermore, myriocin nanoparticles restored the gene expression of enzymes involved in the fatty acid beta-oxidation pathway, such as ACOX1 and CPT1A, in foam cells.

Conclusion

Using myriocin nanoparticles to inhibit excessive ceramide production due to inflammation reduces inflammation, and ROS production, while restoring fatty acid beta-oxidation in macrophages. This approach emerges as an effective strategy for targeting ceramide de novo synthesis within atherosclerotic plaques, thereby mitigating atherosclerosis progression and improving plaque stability.
Association between genetic predisposition of AF and the risk of ischemic stroke and thromboembolism
Authors: Lai Y , Li S , Li M , Jiang C , Sang C , Du X , Dong J , Ma C
Published: October 2024

Background

Ischemic stroke and thromboembolism are the major complications of atrial fibrillation (AF), however, its association with genetic background of AF remains unclear.

To investigate the association between genetic predisposition of AF underlying common variants and the risk of ischemic stroke and thromboembolism.

Methods

We included unrelated individuals with non-valvular AF from UK biobank. The polygenic risk scores of AF (PRSAF) was calculated for each individual using the effect weight from a previous study which has been validated in both European and mixed-ancestry population[1, 2]. The SNPs from the original score were lifted over to GRCh38 and 6514708 of 6730541 were available in the UK biobank genotype data. The clinical data was defined by ICD-10 code. The primary endpoint is ischemic stroke or thromboembolism resulting in hospitalization after first AF diagnosis.

Results

A total of 28810 unrelated patients were included in the study. Among them, 4064 had PRSAF over 90th percentile of the general population, and were considered having high genetic risk. The rest 18746 with per SD increase in PRSAF lower than 90th percentile of the general population were considered having lower genetic risk. Generally, age and sex adjusted model demonstrated that per standard deviation change in PRSAF is associated with 9% increase in the risk of stroke or thromboembolism (HR=1.09, 95%CI: 1.03-1.14), and patients with high genetic risk was associated with 15% increase in the risk of stroke or thromboembolism (HR=1.15, 95%CI: 1.02-1.31).The result remained stable when further adjusted for clinical risk factors (1.09, 95%CI: 1.04-1.15 per SD increase in PRSAF) and competing risk of death (1.10, 95%CI: 1.05-1.16 per SD increase in PRSAF). There was no interaction between CHA2DS2-VASc score risk stratification and the per SD increase in PRSAF (P interaction = 0.751, Figure 1A). However, the association between per SD increase in PRSAF and the event tended to be affected by age at AF onset (HR = 1.02 95%CI: 0.94, 1.11 for early onset AF; HR = 1.12 95%CI: 1.05, 1.19 for non-early onset AF, P for interaction = 0.062, Figure 1B). Multi-variate COX regression including PRSAF, components of CHA2DS2-VASc score, and other AF risk factors revealed that history of stroke/thromboembolism, age over 65 years, hypertension, diabetes and high AF genetic risk were significantly associated with the outcome (Figure 1C). To evaluate the importance of these risk factors, average population attributable fraction for 10-year risk of stroke/thromboembolism in the study population was calculated, indicating that genetic risk of AF is responsible for 3.26% (0.89%-5.63%) of the events (Figure 1D).

Conclusion

Genetic predisposition of AF underlying common variants is associated with ischemic stroke and thromboembolism independent of clinical risk factors. But its role in different AF populations, like early onset AF, remains further investigation.Figure 1
Direct oral anticoagulants exhibit lower risks of mortality and bleeding compared to vitamin-k antagonists in atrial fibrillation patients on chronic hemodialysis: a meta-analysis
Authors: Goyal A , Jain H , Maheshwari S , Fatima L , Javed B , Shrestha A B , Mahalwar G
Published: October 2024

Background

Atrial fibrillation (AF) is a common arrhythmia in patients with chronic kidney disease (CKD). Although direct oral anticoagulants (DOACs) are equally or more effective than vitamin K antagonists (VKAs) in patients with moderate CKD, evidence claiming the benefits of DOACs over VKAs in patients on hemodialysis (HD) is scarce.

Purpose

This meta-analysis aimed to assess the outcomes of patients with AF on chronic HD by comparing the clinical outcomes of DOACs versus VKAs.

Methods

A systematic literature search was conducted across various databases to retrieve studies focusing on efficacy and safety outcomes in patients with AF on chronic hemodialysis comparing DOACs and VKAs. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel random-effects model in Review Manager 5.4. Statistical significance was set at p <0.05.

Results

Nine studies with 39, 831 patients were included. The risk of all-cause mortality [RR: 0.73; 95% CI: 0.60, 0.88; p=0.001], major bleeding [RR: 0.63; 95% CI: 0.52, 0.76; p<0.00001], gastrointestinal bleeding [RR: 0.67; 95% CI: 0.53, 0.85; p=0.0009], intracranial hemorrhage [RR: 0.57; 95% CI: 0.38, 0.84; p=0.004], all-cause stroke [RR: 0.64; 95% CI: 0.51, 0.81; p=0.0001], and ischemic stroke [RR: 0.53; 95% CI: 0.29, 0.96; p=0.04] were lower in the DOAC group than in the VKA group. The risk of cardiovascular-related death [RR: 1.34; 95% CI: 0.69, 2.60; p=0.39], and clinically relevant non-major bleeding [RR: 0.90; 95% CI: 0.75, 1.08; p=0.26] showed no significant differences.

Conclusion

The risks of all-cause stroke, ischemic stroke, all-cause mortality, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage in the patients with AF undergoing chronic HD were lower in the DOAC group than in the VKA group. Further large-scale RCTs are needed to generate more robust evidence through adequately powered studies, leading to conclusive results that are applicable to real-world scenarios.
The high-dose statin treatment reduces neutrophil extracellular traps formation in patients with coronary artery disease
Authors: Stepien K , Natorska J , Zabczyk M , Zalewski J , Jawien J , Undas A
Published: October 2024

Background

Neutrophil extracellular traps formation (NETosis) is currently considered as an important mediator in atherosclerosis and atherothrombosis. However, the impact of high-dose statin treatment, as potent cholesterol-lowering agents with pleiotropic effects, on NETosis in coronary artery disease (CAD) has been poorly described.

Purpose

We sought to assess whether in CAD patients the recommended statin treatment intensification is associated with changes in NETs-related markers and if such changes can alter fibrin clot properties.

Methods

130 patients with advanced CAD, who did not achieve the target low-density lipoprotein cholesterol (LDL-C) were included. Before and at least 6 months after initiation of high-dose statin therapy (rosuvastatin 40 mg/d or atorvastatin 80 mg/d) citrullinated histone H3 (H3cit), myeloperoxidase (MPO) and neutrophil elastase (NE) as markers associated with NETosis were assessed in relation to C-reactive protein (CRP), thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins.

Results

At baseline, NETosis did not differ depending on gender and cardiovascular risk factors but H3cit correlated with MPO (R=0.543, P<0.001) and CRP (R=0.540, P<0.001). All NETosis markers were inversely correlated with Ks. Median LDL-C reduction by 25% (P<0.001) on high-dose statin treatment was independent from H3cit reduction by 30.4%, MPO by 28.1%, and NE by 25.5% (in all P<0.001, Figure 1). The ΔH3cit and ΔMPO, but not ΔNE were associated with ΔCRP (R=0.855, P<0.001; R=0.250, P=0.004, respectively), Δthrombin activatable fibrinolysis inhibitor (TAFI) (R=0.385, P<0.001; R=0.245, P=0.005), and inversely with ΔKs (R=-0.315, P<0.001; R=-0.395, P=0.001). In multivariable analysis the H3cit decrease was independently associated with ΔCRP (β=0.771, P<0.001), ΔTAFI (β=0.125, P=0.013) and Δfibrinogen (β=0.106, P=0.034) but not with ΔLDL-C.

Conclusions

As has been shown for the first time high-dose statin treatment reduces levels of NETs-related markers, regardless of lipid-lowering effect in CAD patients.
Long-term administration of atorvastatin had no effect on the occurrence and progression of spontaneous hypertensive intracerebral hemorrhage in mice
Authors: Bian X , Guo Y , Chen J , Song W , Dou K
Published: October 2024

Background

Intracerebral hemorrhage (ICH) is a catastrophic disease with limited treatment options. Statins and low low-density lipoprotein cholesterol (LDL-C) levels have been reported to be associated with increased risk of ICH. Safety concerns of statins were raised as statins become the cornerstone of anti-atherosclerosis therapy. To date, the effect of statins on the incidence of ICH still remains a controversial topic.

Purpose

The aim of this study was to investigate the effect of atorvastatin on the occurrence and progression of hypertensive ICH in mice.

Methods

Male wild-type C57BL/6J mice, 13 months old, were randomly divided into atorvastatin (Ato, n=20) group and vehicle (Veh, n=20) group. The atorvastatin group and vehicle group were given atorvastatin (20 mg/kg) and same volume of 0.5% sodium carboxymethylcellulose by oral gavage for 8 weeks, separately. Angiotensin II (Ang II) and L-NAME were then used to induce hypertensive ICH. The time of stroke symptom onset was documented. Hemorrhage volumes were measured by spectrophotometric hemoglobin assay.

Results

After 8 weeks of atorvastatin or vehicle administration, serum LDL-C levels were significantly lower in the mice treated with atorvastatin than vehicle controls (0.705 vs. 1.008 mmol/L, P<0.001). The administration of atorvastatin did not show significant effects on the systolic blood pressure (SBP) levels when compared with the vehicle group (164 vs. 166 mmHg, P=0.497) after the induction of Ang II and L-NAME. Hemorrhage was observed in brain morphology, and was further verified by hematoxylin and eosin staining or MRI scans in mice that showed signs of stroke. During the 28-day experimental period, 75% (15/20) of mice in the atorvastatin group developed signs of ICH, and 70% (14/20) of mice in the vehicle group developed in the similar time window. The incidence of hypertensive ICH had no significant difference between atorvastatin and vehicle groups (Log-rank P=0.761). Hemorrhage volumes were also comparable between the two groups (1.462 vs. 1.392 uL, P=0.788).

Conclusion

Reducing serum LDL-C levels by long-term administration of atorvastatin had no effect on the occurrence and progression of spontaneous hypertensive ICH in middle-aged mice.
Ezetimibe use and mortality after myocardial infarction: a nationwide cohort study
Authors: Kyto V , Tornio A
Published: October 2024

Background

Inhibition of intestinal cholesterol absorption by ezetimibe improves outcomes after myocardial infarction (MI), yet real-world data on ezetimibe is lacking.

Purpose

To study usage and outcome impact of ezetimibe after MI.

Methods

Consecutive MI patients in Finland (2010-2018) were retrospectively studied (N=57,505; 65% men; mean age 69 years). Study data were combined from national registries. The median follow-up was 4.5 (IQR 2.8-7.1) years. Differences between groups were adjusted with multivariable regression. Ezetimibe use was studied with competing risk analyses. Median follow-up was 4.5 (IQR 2.8-7.1) years.

Results

The cumulative incidence of ezetimibe use was 3.7% at 90-days, 13.4% at 5-years and 19.8% at 10-years. Younger age was the strongest predictor for ezetimibe use (adj. sHR 6.67; CI 5.88-7.69 for patients aged <60 vs. ≥80 years). Women were more likely to use ezetimibe during follow-up than men. The average proportion of patients using ezetimibe during follow-up was 6.8%. (11.7% at 10-years). Ezetimibe was discontinued by 43.6% of patients during the follow-up. Patients with early ezetimibe after MI had lower all-cause mortality during follow-up (33.6% vs. 45.1%; adj. HR 0.77; CI 0.69-0.86; p<0.0001). Early ezetimibe use was associated with lower mortality irrespective of sex, age, atrial fibrillation, diabetes, heart failure, malignancy, revascularization, or statin use. Ongoing ezetimibe therapy during follow-up was associated with lower mortality in time-dependent analysis (adj. HR 0.53; CI 0.48-0.59; p<0.0001).

Conclusion

Ezetimibe is associated with lower risk of death after MI, but therapy use is limited and discontinuity is frequent.
SHR-1918, a monoclonal antibody against angiopoietin-like 3, in healthy subjects: a randomized, double-blind, placebo-controlled, phase 1 study
Authors: Xie Z , Ye L , Hu W , Lv C , Zhu M
Published: October 2024

Background

Low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) are important risk factors for atherosclerotic cardiovascular disease. Angiopoietin-like 3 (ANGPTL3) is involved in the regulation of lipid metabolism and can increase serum TG and LDL-C levels by reducing their clearance. SHR-1918 is an ANGPTL3 monoclonal antibody developed to inhibit ANGPTL3 activity, thereby reducing the level of TG and LDL-C.

Purpose

This phase 1 single ascending dose study aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1918 in healthy subjects.

Methods

Six dose cohorts were planned, including 100, 300, 450, 750, 900 (optional), and 1200 (optional) mg. For each cohort, 12 healthy subjects were enrolled and randomized (9:3) to receive single subcutaneous SHR-1918 or placebo. Subjects were observed for seven days post-dose and followed up to Day 148 for the 100 mg cohort and Day 190 for the other dose cohorts. The primary endpoints were safety and tolerability.

Results

A total of 72 subjects were enrolled in the six dose cohorts from 100 to 1200 mg (SHR-1918, n = 54; placebo, n = 18). SHR-1918 was well-tolerated at tested doses. Treatment-emergent adverse events (TEAEs) were reported in 49 (90.7%) subjects in the SHR-1918 group and 17 (94.4%) subjects in the placebo group. The most common TEAEs were upper respiratory tract infection (25.9% with SHR-1918 vs. 27.8% with placebo), protein urine present (22.2% vs. 22.2%), and blood uric acid increased (16.7% vs. 16.7%). All TEAEs were mild or moderate in severity. There were no serious adverse events or TEAEs leading to death. Serum concentration of SHR-1918 generally increased with increasing doses. Maximum serum concentration was reached 8.0 to 10.0 days after injection, and mean t½ was 29.4 to 53.3 days across the dose range. SHR-1918 exposure exhibited in a slightly greater-than-dose-proportional manner from 100 to 1200 mg. Serum LDL-C and TG levels markedly and rapidly decreased in all SHR-1918 dose cohorts and remained under the baseline value up to the end of follow-up period for the higher doses, whereas those in the placebo group were above baseline at most follow-up visits (Figure 1 and 2). In the 750 to 1200 mg cohorts, the largest decline in LDL-C from baseline ranged from -46.5% to -49.1%, and the maximum decrease in TG ranged from -67.4% to -82.8%. On Day 85, there remained to be 36.9% to 39.0% reduction in LDL-C and 59.9% to 79.1% reduction in TG for the higher doses. Anti-drug antibody was not detected in SHR-1918-treated subjects.

Conclusions

SHR-1918 was well-tolerated and showed promising efficacy in healthy subjects. A phase 2 study has initiated to evaluate SHR-1918 in hyperlipidemic patients (NCT06109831).Serum LDL-C after SHR-1918 injectionSerum TG after SHR-1918 injection
Impact of SGLT2 inhibitor dapagliflozin on myocardial protein profile in rats with long-standing Type 1 diabetes mellitus
Authors: Rodrigues E A , Dionizio A , Rosa C M , Campos D H S , Damatto F C , Borim P A , Pagan L U , Oliveira J P G , Souza L M , Gatto M , Araujo T T , Buzalaf M A , Cunha T M , Okoshi K , Okoshi M P
Published: October 2024

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. However, as most trials have focused on Type 2 DM, the impact of SGLT2 inhibitors on Type 1 DM remains unclear.

Objective

To investigate the effects of long-term treatment with SGLT2 inhibitor dapagliflozin on the left ventricular (LV) proteome in Type 1 DM rats.

Methods

Male Wistar rats were divided into three groups: Control (C, n=7); Diabetes (DM, n=6); and Diabetes treated with Dapagliflozin (DM+DAPA, n=8) for 30 weeks. Diabetes was induced by streptozotocin (40 mg/kg). Dapagliflozin was added to chow at 5 mg/kg/day. Label-free mass spectrometry was used to assess LV proteome using a nanoAcquity UPLC-Xevo QTof MS system and ProteinLynx Global Server (PLGS) software. Cytoscape software, Cluster Marker, and Cluego plugins were used for bioinformatic analysis. Statistical analysis: ANOVA and Tukey or Kruskal-Wallis and Dunn.

Results

Dapagliflozin increased body weight (C 574±43; DM 339±31*; DM+DAPA 413±30*# g; p<0.05: * vs C; # vs DM) and reduced glycemia [C 108 (101–111); DM 554 (529–562)*; DM+DAPA 343 (237–416)*# mg/dL; p<0.05: * vs C; # vs DM]. One rat died in C and two in DM+DAPA. A total of 252 differentially expressed proteins were identified. Most proteins identified in the networks were downregulated in DM vs C and upregulated in DM+DAPA vs DM. Six proteins related to energy metabolism (Atp5j, P21571; CKm, P00564; Ak1, P39069; Atp5h, P31399; Mdh1, O88989; and Idh2, P56574), four involved in myocyte excitation-contraction (Act1, P68065; Casq2, P51868; SERCA1, Q64578; and SERCA2a, P11507), and two associated with oxidative stress (Sod1, P07632; and Sod2, P07895) were upregulated in DM+DAPA x DM. Comparing DM with C, the KEEG Pathway with the highest percentage of gene associations for upregulated proteins was related to gap junction (25.6%), necroptosis (25.6%), and fatty acid degradation (25.6%), and for downregulated proteins was related to Alzheimer disease (27.3%), cardiac muscle contraction (25%) and glycolysis/gluconeogenesis (13.6%). Comparing DM+DAPA with DM, the KEEG Pathway with the highest percentage of gene associations for upregulated proteins was related to Parkinson disease (18.3%), cardiac muscle contraction (14.2%), citrate acid cycle (9.47%), necroptosis (8.88%), and cGMP-PKG signaling (7.10 %), and for downregulated proteins was related to ketone bodies synthesis and degradation (100%).

Conclusion

Dapagliflozin is safe and prevents changes in the expression of proteins related to energy metabolism, cardiac muscle contraction, and oxidative stress in Type 1 diabetes mellitus rats. These results offer new insights into the cardioprotective mechanisms of dapagliflozin in Type 1 diabetes mellitus.
Implantable loop recorders in children and adolescents with Brugada syndrome: the YoungBruLoop study
Authors: Conte G , Ciconte G , Bergonti M , Crotti L , Tondo C , Rossi A , De Asmundis C , Caputo M L , Casella M , Saenen J , Pappone C , Schwartz P , Auricchio A , Brugada P , Sarquella Brugada G
Published: October 2024

Background

Young (<18 years of age) patients with Brugada syndrome (BrS) are often underrepresented in BrS studies and their management, especially related to syncopal episodes, remains unclear.

Purpose

To describe the arrhythmia prevalence and clinical implication derived from continuous rhythm monitoring by implantable loop recorder (ILR) among patients younger than 18 years of age, and to assess the etiology behind syncope of undetermined origin.

Methods

A total of 147 BrS patients with ILR were enrolled in 12 international centers and divided into pediatric (age <12 years; n=77, 52%) and adolescents (age 13 to 18 years; n=70, 48%).

Results

Mean age was 11.3 years (36.1% females, 21.1% spontaneous type I ECG). Forty-six patients (31.2%) underwent ILR implant due to syncope. Over a median follow-up of 3.6 years, an arrhythmic event was recorded in 22.4% of patients and in the vast majority of cases it was of non-ventricular origin (44% atrial, 47% bradyarrhythmias). Predictors of arrhythmias at univariate Cox Regression analysis were spontaneous type I ECG (HR 2.1 - 95%C.I. 1.1-4.1), history of syncope (HR 3.1 - 95%CI 1.5-6.3) and age >12 years (HR 2.0 - 95%C.I. 1.0-3.3). Ventricular arrhythmias occurred in 4 patients, all with spontaneous BrS, and were related to fever in half of cases. In patients with recurrent syncope, the prevalence of truly arrhythmic syncope was 17.8%, and it was due to brady-, atrial- and ventricular arrhythmias in 40%, 20% and 40% of cases, respectively.

Conclusions

Continuous rhythm monitoring with ILRs in BrS pediatric patients detects a broad range of heart rhythm disturbances including life-threatening arrhythmias. Ventricular arrhythmias occur predominantly in patients with spontaneous type I ECG and in half of cases are fever-related. Despite the young age, brady- and atrial arrhythmias are overall frequent and represent the cause of arrhythmic syncope in 60% of patients. Young BrS patients with syncope of undetermined origin may benefit from ILR implant.
Impact of SGLT2 inhibitors on liver-related outcomes in patients with heart failure - a population-based study in HK
Authors: Yang H Y , Yang R Q , Yiu K H
Published: October 2024

Background

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now recommended for heart failure with preserved ejection fraction (HFpEf). While their side effects on respiratory and renal outcomes in patients with type 2 diabetes have been studied, the impact on liver-related diseases within HF patients is not well-established.

Purpose

This study aims to evaluate the association between SGLT2 inhibitor use and the risks of adverse liver events among HF patients.

Methods

We conducted a retrospective cohort study using the Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify 80,248 HF patients (mean age 73.37 ± 12.88 years; 49.2% male) between 2013 and 2022. Propensity score matching was applied to achieve a 1:3 ratio of SGLT2 users to non-users, ensuring balanced baseline characteristics. Competing risk regression within Cox proportional hazards frameworks quantified the risks for cirrhosis, hepatocellular carcinoma, liver-related death, and significant elevations in liver enzymes (ALT or AST >3x normal and bilirubin >2x normal).

Results

During a median follow-up of 6.02 years (interquartile range: 3.48–9.25 years), there were 12,103 liver-related deaths. SGLT2 was associated with a 52% reduced risk of cirrhosis (adjusted subdistribution hazard ratio [SHR]: 0.48; 95% confidence interval [CI]: 0.36-0.65), a 61% lower risk of hepatocellular carcinoma (SHR: 0.39; 95% CI: 0.26-0.42), a 13% decreased risk of liver-related death (SHR: 0.87; 95% CI: 0.77-0.98), and a 19% risk reduction in elevated liver enzymes (SHR: 0.81; 95% CI: 0.68-0.96). 5-year cumulative incidences were 1.7%, 0.62%, 13%, and 5.4%, respectively, for SGLT2 users compared to 3.7%, 1.9%, 16%, and 7.0% for SGLT2 nonusers.

Conclusion

SGLT2 use is associated with a decreased risk of adverse liver outcomes in HF patients. This suggests a potential protective role for SGLT2 in liver health within this population.