bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac function in patients with Paget disease of bone: standard and advanced echocardiographic study
Authors: Giaquinto A , Abate V , Muscariello R , Pirrotta F , Merlotti D , Gennari L , Esposito R , Rendina D 
Published: November 2023

Abstract

Background/Introduction
Paget’s disease of bone (PDB) is a common metabolic bone disorder and cardiovascular diseases are considered a possible PDB metabolic complication. Heart complications have only been described anecdotally as high-output heart failure due to high blood flow when skeletal involvement is extensive.

Purpose
Scientific studies that compare the structural and functional characteristics of the heart in this population are few and dated. The aims of this study were to evaluate echocardiographic parameters in PDB patients.

Methods
60 PDB patients and 115 control subjects, matched by age, weight, height and history of arterial hypertension were enrolled. All subjects underwent to standard and advanced echocardiography examination.

Results
PBD patients showed a lower values of left ventricular ejection fraction (LVEF) (60,86 ± 4,51 vs 62,79 ± 4,30%, p 0,007), global longitudinal strain (GLS) (21,42 ± 2,20 vs 22,35 ± 2,21%, p 0,021) and myocardial work efficiency (MWE) (94,1 ± 2,0 vs 95,4 ± 2,9%, p 0,021), and higher values of interventricular septum thickness (IVSd) (9,9 ± 1,4 vs 9,1 ± 1,4 mm; p 0,003), and relative wall thickness (RWT) (0,38 ± 0,07 vs 0,35 ± 0,07, p 0,031) compared to controls, while there were no significant difference between the other parameters analyzed (Table 1). Calcification and/or sclerosis of aortic valve was detected in 26 PDB patients (43,3%) compared to 27 subjects (23,5%) in control group (Fisher’s exact test p-value = 0,006). Calcification and/or sclerosis of mitral annulus was detected in 14 PDB patients (23,3%) compared to 12 controls (11,6%) (Fisher’s exact test p-value = 0,022) (Table 2).

Conclusion
The study results support the hypothesis that PDB is a systemic condition, influencing cardiac function and structure, associated with increased cardiovascular risk. Our data showed that myocardial function in PDB patients is impaired. The lower resting values of LVEF, GLS and MWE represent an early subclinical myocardial damage.Table 1Table 2
Gout is associated with increased cardiovascular risk: results from analysis of the CPRD dataset
Authors: Ferguson L , Mcinnes I B , Sattar N , Conrad N 
Published: November 2023

Abstract

Background
Gout, a common crystal arthropathy, has been associated with higher cardiovascular risk. However, the degree to which this risk is potentially mediated by traditional risk factors, and whether this risk differs across individual cardiovascular disorders (CVD), inclusive of heart failure, is unclear.

Purpose
We aimed to determine the risk of incident cardiovascular disease in patients with newly diagnosed gout, whether this varied across a range of cardiovascular disorders, and the potential impact of traditional risk factors.

Methods
We used linked primary and secondary electronic health records from 22 million individuals in the Clinical Practice Research Datalink (CPRD) to assemble a cohort of individuals newly diagnosed with gout between 01/01/2000 and 31/12/2017 and free of cardiovascular disorders (CVD) up to 12 months after diagnosis, and up to five individuals matched on age, sex, socioeconomic status and region, with follow-up until 30/06/2019. We investigated the incidence of twelve cardiovascular outcomes and used Cox-proportional hazards models to examine differences in patients with and without gout. In sensitivity analyses, models were further adjusted for known cardiovascular risk factors (blood pressure, BMI, smoking, cholesterol, and type 2 diabetes).

Results
We identified 153 645 individuals with Gout and 714 192 matched controls. Of these, 31479 people with and 106 520 without gout developed incident CVD during a median of 6.5 years of follow-up. Patients with gout had a higher risk of cardiovascular outcomes than controls: hazard ratio (HR) [95% confidence interval (CI)] 1.57 [1.52, 1.63]. Excess cardiovascular risk disproportionally affected women (HR in women: 1.88 [1.75, 2.02], HR in men: 1.50 [1.40, 1.62]), and was highest in the very young (HR in people aged 45 years or less: 2.20 [1.91, 2.54]) (Figure 1). Excess risk was visible across all 12 cardiovascular diseases investigated, and was particularly pronounced for heart failure, arrhythmias, and valve disease (HR for heart failure: 1.84 [1.73, 1.96], HR for atrial fibrillation and flutter: 1.81 [1.72, 1.91], HR for valve diseases: 1.83 [1.71, 1.97]). Patients with gout presented with on average 3 units higher body mass index than matched controls, and had higher prevalence of chronic kidney disease, dyslipidaemia, and hypertension. In sensitivity analyses, adjusting for known cardiovascular risk factors attenuated the strength of the associations by around half, although gout remained an independent CVD risk factor.

Conclusion
Patients with gout present a higher risk of developing a range of cardiovascular outcomes, in particular heart failure, arrhythmias, and valve disease. These findings suggest patients with gout should have formal CV risk assessment, and stronger attention to lifestyle interventions to mitigate future atherosclerotic and cardiorenal risks.Fig1 CVD rates & HRs in gout vs controls
Impact of pemafibrate on lipid profile and insulin resistance in patients with statin-treated coronary artery disease with metabolic syndrome
Authors: Nakamura A , Kagaya Y , Saito H , Kanazawa M , Sato K , Miura M , Kondo M , Endo H 
Published: November 2023

Abstract

Background
Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor α, a vital modulator of lipid and glucose metabolism. We examined the effects of this drug on lipid markers and insulin resistance in patients with metabolic syndrome (MetS).

Methods
In the randomized, crossover PEBE study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks, followed by crossover of another 24-weeks. Forty-six of 60 patients (77%) enrolled in the PEBE study were founded to have MetS. In the present subanalysis, we compared patients with MetS (MetS group, n = 46) and those without MetS (Non-MetS group, n =14). The primary endpoints were changes from baseline in serum TG, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (Apo A-I) levels, while the secondary endpoint was change in the homeostasis model assessment of insulin resistance (HOMA-IR).

Results
There was a significant decrease in serum TG levels (from 266.6 mg/dL to 148.0 mg/dL in MetS group, p &lt; 0.001; from 203.9 mg/dL to 97.6 mg/dL in Non-MetS group, p &lt; 0.001), but %Change was not significantly different between the two groups (−44.1% vs. −51.6%, p = 0.099). Serum HDL-C and Apo A-I levels significantly increased in both groups, but no significant differences in %Change were found between the two groups (p = 0.591 in HDL-C; p = 0.432 in Apo A-I). HOMA-IR significantly decreased in MetS group (from 4.3 ± 4.0 to 3.1 ± 2.2, p = 0.011) but not in Non-MetS group (from 1.7 ± 1.0 to 1.5 ± 1.0, p = 0.553). %Change in liver enzyme levels was markedly decreased in MetS group than in Non-MetS group (alanine aminotransferase, −25.1% vs. −11.3%, p = 0.027; gamma-glutamyl transferase, −45.8% vs. −36.2%, p = 0.020). Although serum adiponectin levels did not change significantly in both groups, leptin levels significantly decreased in MetS group (from 18.5 ng/mL to 16.6 ng/mL, p = 0.004), but not in Non-MetS group (from 9.2 ng/mL to 9.0 ng/mL, p = 0.917).

Conclusion
Pemafibrate is as efficient in patients with MetS as in patients without MetS in improving the lipid and glucose metabolism. In addition, the use in MetS patients may be more effective in improving liver function and insulin resistance.
Improving statins effectiveness by targeting baseline LDL cholesterol in type 2 diabetes mellitus, a systematic review and meta-analysis
Authors: Soroush N , Nekouei Shahraki M , Mohammadi Jouabadi S , Amiri M , Aribas E , Stricker B , Ahmadizar F 
Published: November 2023

Abstract

Background
Although the guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D), it remains controversial whether their cardiovascular effectiveness depends on baseline LDL-Cholesterol (LDL-C) levels at the start of statin use.

Purpose
To determine whether the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality differ according to baseline LDL-C categories.

Methods
This study was registered in the PROSPERO database (CRD42022374004); and was performed according to the PRISMA statement. Through January 2022, Medline, Embase, and Web of science were systematically searched from inception. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to study if the association between statin use and the risk of all-cause mortality and MACE (a composite of myocardial infarction, hospitalization due to heart failure, stroke, and revascularization events) modified by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) &lt;100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) ≥130 mg/dl (3.37 mmol/l) categories.

Results
A total of 11 cohort studies (n= 408,937 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.67 [95% CI 0.57 to 0.79]) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79]), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels of 130 mg/dl or higher had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29, 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and &lt;100 mg/dl categories were respectively (0.66 [95% CI 0.53 to 0.82]) and (0.83 [95% CI [0.68, 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44, 1.02]). Statin use was associated with reductions in HRs of MACE (0.99 [95%CI, 0.98 to 1.00]; P = 0.11) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses.

Conclusion
The results of this study suggest that the greatest cardiovascular protective effects of statin therapy in patients with T2D are attributable to patients with baseline LDL-C levels of 130 mg/dl or higher in real-life settings of observational studies.
Oral anticoagulant therapy and risk of admission to long-term care in patients with atrial fibrillation: a nationwide cohort study
Authors: Teppo K , Airaksinen K E J , Halminen O , Linna M , Jaakkola J , Haukka J , Putaala J , Mustonen P , Langen V L , Kinnunen J , Hartikainen J , Lehto M 
Published: November 2023

Abstract

Background
The impact of oral anticoagulants (OACs) on outcomes in patients with atrial fibrillation (AF) has been a focus of extensive research in the past decades, but there is a complete paucity of information about their effect on the need of long-term care (LTC) in this aging and multimorbid patient group.

Purpose
To assess the hypothesis that OAC therapy is associated with lower need of LTC in patients with AF.

Methods
The registry-based FinACAF cohort study covers all patients with incident AF from all levels of care in Finland from 2007 to 2018, as well as all their OAC purchases, LTC admissions, and information on previous home care acuity. Incidence rate ratios (IRRs) for admission to any type of LTC were estimated with Poisson regression using Lexis-type data structure based on three time scales: follow-up time from AF diagnosis, calendar year, and age. OAC use was treated as a time-varying variable from first OAC purchase onwards.

Results
We identified 188 752 patients (49.0% female; mean age 71.4 years; mean follow-up 3.6 years) with incident AF without prior LTC, of whom 143 534 (76.0%) initiated OAC therapy and 11 775 (6.2%) were admitted to LTC. OAC therapy was associated with a lower rate of LTC admission (adjusted IRR with 95% CI: 0.79 (0.76-0.82)). The association was most evident among patients over 70 years (Kaplan-Meier curve of survival without LTC in Figure). Warfarin and direct oral anticoagulants (DOACs) were both associated with lower need of LTC. Furthermore, when compared to warfarin, DOACs were associated with a lower LTC admission rate (adjusted IRR with 95% CI: 0.69 (0.61-0.79)). No significant disparities were observed between different DOACs. High age and previous need of home care, as well as dementia, psychiatric disorders, and ischemic stroke were the strongest factors associated with the need of LTC.

Conclusions
In this nationwide cohort of patients with incident AF, OAC therapy, particularly with DOACs, was associated with a substantially lower risk of admission to LTC.Survival without LTC. Age over 70 years.
Effectiveness and safety of bempedoic acid in routine clinical practice: 1-year follow-up snapshot of the MILOS German cohort
Authors: Gouni-Berthold I , Koskinas K , Averna M , Stulnig T , Vanassche T , Blackburn C , Smolnik R , Soronen J , Wenz-Poschl K , Pinto X , Parhofer K 
Published: November 2023

Abstract

Background
Low-density lipoprotein cholesterol (LDL-C) has an established role in the development of atherosclerotic cardiovascular disease. The 2019 ESC/EAS dyslipidaemia guidelines recommended more intensive treatment goals, however, many patients do not reach them. Bempedoic acid (BA) is a first-in-class ATP citrate lyase inhibitor that lowers LDL-C levels. There is limited data on the use of BA and BA + ezetimibe (EZE) fixed-dose combination (FDC) in clinical practice.

Purpose
The purpose of this snapshot of 1-year follow-up data from the MILOS study is to evaluate the effectiveness and safety of BA and its FDC in routine clinical practice in Germany.

Methods
MILOS is a European, prospective, observational, non-interventional study in adult patients with primary hypercholesterolaemia or mixed dyslipidaemia. Patients were recruited from 126 sites in Germany between January 2021 and January 2022, and are followed up for 1–2 years after baseline measurements. Here, we summarise 1-year follow-up data from a snapshot taken on January 13th, 2023.

Results
Of 992 patients enrolled in Germany, 714 had either completed their 1-year follow-up or discontinued the study prematurely, and 524 of these 714 patients attended their 1-year follow-up visit. For this snapshot, 714 patients are used when determining cardiovascular (CV) outcomes and safety endpoints, and 524 patients are used when reporting efficacy data. The overall mean (SD) age of the population (n=524) was 64.7 (10.0) years, and 60.7% were male.
Patients treated with BA/BA+EZE FDC had an overall mean LDL-C level of 2.18 mmol/L (84.1 mg/dL) at 1 year compared with 3.20 mmol/L (123.6 mg/dL) pre-treatment, representing a mean relative LDL-C reduction of 27.3%. Overall, 25.8% (135/524) of patients had reached their LDL-C goal after 1 year of treatment compared with 4.0% (21/524) pre-treatment (Figure 1A and 1B). The overall incidence rate of the composite endpoint of major adverse cardiovascular event (4-component MACE) including CV death, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularisation (n=714) was 3.36%. At 1-year follow-up, 19% (136/714) of patients had an adverse drug reaction (ADR) suspected to be related to BA/BA+EZE FDC, and 0.8% (6/714) had serious ADRs, as deemed by the investigator.

Conclusion
This snapshot analysis of 1-year follow-up data suggests that the addition of BA to other lipid-lowering therapies increases the proportion of patients at LDL-C goal by ∼6-fold in the observed cohort. The safety and tolerability profile of bempedoic acid are in line with data from randomised controlled trials.
The renal outcome post contrast exposure in patient with diabetes and SGLT2 inhibitor
Authors: Chen C , Yi-Cheng Lin Y C L , Chih-Chin Kao C C K , Chun-Yao Huang C Y H 
Published: November 2023

Abstract

Introduction
Contrast-induced nephropathy (CIN) is increasingly prevalent as the increased age and comorbidities. Though most CIN can be reversible, some may progress to acute kidney disease (AKD) and subsequent chronic kidney disease (CKD)1-3. Sodium–glucose cotransporter-2 (2SGLT) inhibitor has been known to bring better renal outcomes 4-7. However, whether it affect contrast-induced kidney injury is not known well. we

Purpose
We aimed to investigate the renal outcomes post-contrast exposure in patients with diabetes and SGLT2 inhibitor.

Materials and methods
We used the Taipei Medical University Clinical Research Database (TMUCRD), composed of clinical data from 3 teaching hospitals. which stores electronic health data of 3 million patients. Patients with diabetes and exposure to contrast in CT-imaging studies or catheter-based angiography from 2016 to 2020 were included. The primary outcome was major kidney adverse event (MAKE), which included acute kidney disease (AKD), chronic kidney disease (CKD), renal replacement therapy (RRT), new onset of urinary albumin-creatinine ratio (uACR), eGFR decline ≥ 40% and all-cause mortality. We used overlap weighting to reduce confounding factors, as in observational studies.

Results
A total of 12,421 patients were included in this study, of them, 920 and 11501 patients were categorized to SGLT2 inhibitor users and non SGLT2 inhibitor users, respectively. SGLT2 inhibitor user had lower MAKE risk as compared with non-SGLT2 inhibitor i user (incidence rate: 37.9 v.s. 53.4 per 1,000 person months, P value = 0.0002) after exposure to contrast media. The incidence rate of AKD, CKD, and eGFR decline ≥ 40% were significantly lower in SGLT2 inhibitor user. However, there were no significantly different in the risk of RRT, new onset of uACR or all-cause mortality.

Conclusions
In this retrospective cohort study, we found that SGLT2 inhibitor user was associated with lower MAKE comparing with non-SGLT2 inhibitor user after contrast exposure in patients with diabetes.Outcomes of DM patients with PCI or contKaplan-Meier plot of major adverse kidne
Empagliflozin suppresses the differentiation/maturation of human epicardial preadipocytes and improves paracrine secretome profile
Authors: Kondo H , Takano M , Miyamoto S , Takahashi N 
Published: November 2023

Abstract

Aims
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the epicardial adipose tissue (EAT) in human, which could enhance the cardioprotective effect in heart failure and atrial fibrillation. However, the precise mechanism of EAT reduction remains unclear. We investigated the direct effect of SGLT2 inhibitor, empagliflozin, on human primary epicardial adipocyte and preadipocyte.

Methods and Results
In Arm1, human EAT biopsies obtained during surgery and isolated preadipocyte/adipocytes were used for evaluating SGLT2 expression. In Arm2 and Arm3, we investigated the direct effect of empagliflozin on the differentiation/maturation and secretome profile of human preadipocyte/adipocyte. We validated the effect of empagliflozin on paracrine effect of EAT using co-culture with human iPS-derived atrial cardiomyocytes and empagliflozin-treated human epicardial adipocyte in Arm4. The validity of findings obtained from Arm1-4 were verified in view of clinical perspective in Arm5 and Arm6. SGLT2 was mainly expressed in the human pre-adipocyte in EAT. The expression levels of SGLT2 significantly diminished when the pre-adipocyte terminally differentiated. The formation of lipid droplets and fatty acid binding protein 4 (FABP4) expression in adipocyte were attenuated by empagliflozin treatment without affecting cell proliferation. mRNA levels of IL1α, IL1β, IL6, TGFβ and MCP1 in empagliflozin-treated adipocyte were significantly decreased. Of these, secreted protein levels of IL6 and MCP1 were significantly downregulated in supernatant of empagliflozin-treated cells. Co-culture of human iPS-derived atrial cardiomyocytes and adipocyte pre-treated with or without empagliflozin revealed that empagliflozin had striking suppressive effects on myocardial oxidative stress. Only IL6 mRNA expression in human EAT showed the clinically relevant association in terms of the difference of AF prevalence, anti-diabetic drug and N-terminal pro-brain natriuretic peptide.

Conclusions
We demonstrated that empagliflozin suppresses human epicardial pre-adipocyte differentiation/maturation, possibly leading to the reduction of EAT volume, and improves paracrine secretome profile of EAT. IL6 might be a key adipokine regulated by SGLT2 inhibitors.
Factor XI inhibitors in early clinical trials: a meta-analysis
Authors: Galli M , Laborante R , Ortega-Paz L , Franchi F , Rollini F , D'amario D , Capodanno D , Tremoli E , Gibson C M , Mehran R , Angiolillo D J 
Published: November 2023

Abstract

Background
Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes.

Methods
We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy.

Results
Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included. Compared with enoxaparin, FXI inhibitors were associated with reduced any-bleeding (RR 0.49, 95% CI 0.31-0.77), no difference in major bleeding (RR 0.96, 95% CI 0.41-2.28) and reduced trial-defined efficacy endpoint (RR 0.62, 95% CI 0.49-0.79), the latter driven by the high dose regimens. Compared with DOACs, FXI inhibitors were associated with a trend towards reduced any-bleeding (RR 0.66, 95% CI 0.31-1.38) and no difference in major bleeding (RR 1.03, 95% CI 0.22-4.78) or in trial-defined efficacy endpoint (RR 1.23, 95% CI 0.88-1.70). Compared with placebo, FXI inhibitors were associated with increased any-bleeding (RR 1.25, 95% CI 1.08-1.43) and a trend towards increased major bleeding (RR 1.21, 95% CI 0.75-1.93), both driven by high dose regimens, with no difference in trial-defined efficacy endpoint (RR 1.02, 95% CI 0.92-1.13).

Conclusions
Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy.