bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Copenhagen chronic kidney disease echo study (COInCYDE)
Authors: Landler N , Bro S , Feldt-Rasmussen B , Hansen D , Kamper A.L , Freese E , Soerensen I.M.H , Seidelin E , Olsen N.T , Olsen F.J , Gislason G , Biering-Soerensen T 
Published: November 2020

Abstract

Background
The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population.

Purpose
To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD.

Method
Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines.

Results
63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese.
Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls.
Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group.

Conclusion
In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD.
Figure 1. Estimated GFR vs. GLS & histogram of GLS

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark
Exposure to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the association with neurocognitive side effects: a meta-analysis and meta-regression
Authors: Hirsh-Raccah B , Yanovsky A , Rotshild V , Danenberg H , Eliaz R , Matok I 
Published: November 2020

Abstract

Background
Lipid lowering therapy may be associated with impaired cognitive function. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse effects remains unclear.

Purpose
To assess the neurocognitive safety of PCSK9 inhibitors using meta-analysis and meta-regression of randomized controlled trials (RCTs).

Methods
PubMed (MEDLINE), Embase and Cochrane library were searched. RCTs that reported assessments of neurocognitive outcomes of participants using PCSK9 inhibitors, with a duration of follow up of at least six months were included. The results of the search were screened by two independent reviewers. Any disagreements were resolved by consensus. The research was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for meta-analyses. Results were pooled using random-effects models. The primary safety outcome of this analysis was defined as the reported incidence of neurocognitive adverse effects.

Results
Results of 21 trials were included in the analysis. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. No significant difference in the incidence of neurocognitive side effects between the treatment and control groups was identified (RR=1.01, 95% CI: 0.86–1.19, I2=3%). Same results were seen in separate analysis for each of the medicines (Alirocumab- RR=0.88, 95% CI: 0.72–1.08, I2=0%, Evolocumab- RR=1.42, 95% CI: 0.74–2.73, I2=55%). In a meta-regression analysis there was no statistically significant association between the assessed and the risk for neurocognitive side effects.

Conclusions
Pooled results of our meta-analysis and meta-regression clearly show that the exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse events. Due to the increasing proportion of patients using lipid-lowering therapy these results are positively reassuring. However, more data from long-term outcomes studies is needed to further evaluate the effect of longer exposure to PCSK9 inhibitors

Funding Acknowledgement
Type of funding source: None
The effect of elevated triglycerides and purified eicosapentaenoic acid ethyl ester (EPA) for cardiovascular risk reduction in the UK Biobank population
Authors: Radenkovic D , Vakili D , Botta G , Boli A , Banach M , Bhatt D.L 
Published: November 2020

Abstract

Elevated plasma triglycerides (TG) are associated with insulin resistance, metabolic syndrome and major adverse cardiovascular events (MACE). Elevated plasma TG (&gt;150 and 200–499 mg/dL) were recently reported to be a predictor of heart failure in patients with coronary heart disease on statin therapy with a respective 19% and 24% risk increase compared to normal TG levels. REDUCE-IT was a major double-blind randomised controlled trial that tested a novel formulation of highly purified eicosapentaenoic acid ethyl ester (EPA) in 8179 patients with elevated TG on statin therapy. In the trial, daily 4g of EPA lowered MACE by an absolute rate of 4.8% compared to a placebo over a median 4.9-year follow-up. This reflected a 25% risk reduction in MACE and a number needed to treat of 21. EPA recently received significant public attention in late 2019 as the FDA has approved it for secondary prevention and high-risk primary prevention of cardiovascular disease (CVD) in patients with elevated TG that match the trial criteria in the USA. We aimed to investigate the risk reduction in MACE from using EPA in the UK population.
We used the UK BioBank, a panomic resource following 500,000 participants over &gt;10 years, with similar age and sex adjusted rates of CVD as the UK population. We first calculated the hazard ratios and Kaplan-Meier survival curves by deciles of increasing TG for incidence of combined CV outcomes: stroke, coronary heart disease, and atherosclerosis. Non-linear CoxPH and DeepSurvival models were trained using different variables from &gt;200,000 UK BioBank participants' data. C-index with standard error and confidence interval estimated with bootstrap sampling ensured quality control. We then matched the UK Biobank population with the REDUCE-IT inclusion criteria and estimated the reduction of combined cardiovascular outcomes if EPA was approved in this population.
Hazard ratios increased for TG levels to 5.44 between the 10th decile, and the 1st decile TG level, which was used as baseline. 3563 UK Biobank participants matched with the REDUCE-IT criteria. With the assumption that EPA would have the same effect on the UK Biobank population, we estimate that if the participants were taking EPA, only 29% of the risk group versus actual 37% would have suffered an outcome within the UK Biobank follow-up period. This means that 289 less individuals would have suffered an event instead of the recorded 1318, for a total of 1037. That means according to the number needed to treat analysis, 13 patients would need to be treated to prevent 1 patient from experiencing an event.
Elevated TG increase risk for CV events in the UK Biobank population. Purified EPA might become an important tool in our arsenal for CVD secondary and primary prevention.
Survival Curves & CI of TG for CVD

Funding Acknowledgement
Type of funding source: None
Higher responsiveness to rosuvastatin in polygenic versus monogenic hypercholesterolaemia: a propensity score analysis
Authors: Mickiewicz A , Futema M , Cwiklinska A , Kuchta A , Kaszubowski M , Chmara M , Jankowski M , Wasag B , Fijalkowski M , Jaguszewski M , Humphries S.E , Gruchala M 
Published: November 2020

Abstract

Background
The underlying monogenic defect in familial hypercholesterolemia (FH) can be detected in ∼40% of cases. The majority of mutation-negative patients have a polygenic cause of high LDL-cholesterol (LDL-C) due to having inherited a greater than average number of common LDL-C raising single nucleotide polymorphisms (SNPs).

Purpose
We sought to investigate, whether the monogenic or polygenic defect in FH is associated with the response to rosuvastatin.

Methods
Individuals with a clinical diagnosis of FH were tested for mutations in LDLR and APOB genes. A previously established LDL-C-specific polygenic risk score (PRS) was used to examine the possibility of polygenic hypercholesterolemia in mutation negative patients. The propensity score analysis was performed to evaluate the variables associated with the response to rosuvastatin. The type of hypercholesterolemia (polygenic or monogenic) and following variables: age, gender, LDL-baseline, statin intolerance, ezetimibe use, rosuvastatin dose, diabetes and cardiovascular disease (CVD), were examined to minimize the bias of this observational study.

Results
LDLR/APOB mutation was found in 47 (42%) patients, whereas polygenic hypercholesterolemia was diagnosed in 65 (58%) of patients. Mean age was comparable in both groups (54±13 vs 51±13, p=0.134). CVD was diagnosed in ≈26% of individuals in both cohorts (p=0.343). There was no difference in the distribution of CV risk factors, such as arterial hypertension, smoking, diabetes, body mass index and in rate of statin intolerance. Monogenic subjects had higher baseline LDL-C compared to polygenic (Table 1). Adjusted model showed a lower percentage of change in LDL-C after rosuvastatin treatment in monogenic vs. polygenic subjects (46% vs 55%, p&lt;0.001) (Figure 1). The probability of achieving LDL-C targets in monogenic FH was lower than in polygenic subjects (0.075 vs. 0.245, p=0.004). Polygenic patients were more likely to achieve LDL-C goals, compared to mutation-positive patients (OR 3.28; 95% CI:1.23–8.72).

Conclusion
Our findings indicate an essentially higher responsiveness to rosuvastatin in patients with a polygenic cause, as compared to those carrying monogenic mutations.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): 1. Polish Ministry of Science and Higher Education European Regional Development Fund under the Programme Innovative Economy 2007–2013 (POIG.01.01.02-22-079/09). 2. British Heart Foundation (PG 08/008). 3. The National Institute for Health Research, University College London Hospitals, Biomedical Research Centre. 4. The Foundation Leducq Transatlantic Networks of Excellence Program grant (no. 14 CVD03)
Changes in markers of subclinical atherosclerosis in patients with familial hypercholesterolemia treated with evolocumab: a prospective cohort study
Authors: Calcaterra I , Di Minno A , Gentile M , Tripaldella M , Buonaiuto A , Forte F , Di Taranto M.D , Giacobbe C , Iannuzzo G , Rubba P.O.F , Di Minno M.N.D 
Published: November 2020

Abstract

Background
PCSK-9-i demonstrated efficacy in cholesterol reduction and prevention of cardiovascular events.

Purpose
Changes in lipid-profile, oxidative stress and subclinical atherosclerosis markers in patients with familial hypercholesterolemia (FH) during 12 weeks of treatment with PCSK-9-i.

Methods
Patients with FH starting a treatment with Evolocumab® were included. TC, LDL-C, Lp(a), small dense LDL (assessed byLDL score), 11-dehydro-thromboxane (11-TXB2), 8-iso-prostaglandin-2alpha (8-iso-PGF2α),FMD, RHI and carotid stiffness were evaluated at baseline and after 12weeks of treatment.

Results
25 subjects were enrolled (52% males, mean age 51.5 years). At the 12-week, the median reduction was 38% for TC, 52% for LDL-C, 7% for Lp(a) and 46% for LDL score; 11-TXB2 and 8-iso-PGF2α were reduced of 18% and 17%, respectively. FMD changed from4.78%±2.27 to10.6%±5.89 (p&lt;0.001), with RHI changing from 2.37±1.23 to 3.76±1.36 (p&lt;0.001). Carotid stiffness changed from 8.8 (IQR: 7.0–10.4)m/sec to 6.6 m/sec (IQR: 5.4–7.5), p&lt;0.001). At a multivariate analysis, changes in LDL score predicted changes in FMD (β=−0.846, p=0.015) in carotid stiffness (β=0.429, p=0.041), and in 8-iso-PGF2α (β=0.778, p=0.012).

Conclusions
Small dense LDL reduction is related to changes in oxidative stress and in subclinical atherosclerosis markers in FH patients treated with Evolocumab®.
Changes in endothelial function

Funding Acknowledgement
Type of funding source: None
Empagliflozin significantly attenuates QTc prolongation in rats due to sotalol
Authors: Baris V.O , Dincsoy B , Gedikli E , Erdem A 
Published: November 2020

Abstract

Introduction
Sotalol (SOT) is a Class 3 antiarrhythmic drug and commonly used for various arrhythmia treatments. However; it can prolong QT interval and lead to malignant arrhythmias. Empagliflozin is a selective SGLT-2 inhibitor used in the treatment of Type 2 diabetes and has been shown to have positive effects on cardiovascular outcomes. Since the effect of empagliflozin (EMPA) on potassium channel activation is not yet known, there is no recommendation for the concomitant use of these drugs.

Purpose
In this study, we aimed to evaluate possible protective effects of empagliflozin in sotalol induced QT prolongation.

Materials and methods
Twenty-four male Wistar Alba rats were randomized into four groups. The first (control) group (n: 6) received only serum physiologic (1ml) via orogastric gavage (OG). The second (EMPA) group (n: 6) received EMPA (10 mg/kg) via OG. The third (SOT) group (n: 6) received SOT (80 mg/kg) via OG. The fourth (EMPA+SOT) group (n: 6) received EMPA (10 mg/kg) and SOT (80 mg/kg) via OG. Under anesthesia; PR, QT intervals and heart rate (HR) were measured and QTc value was also calculated at second hour on lead II using electrocardiogram (ECG).

Results
In the SOT group; QT intervals, T wave durations and QTc values were found to be statistically longer than the control group, whereas HR was found to be lower than the control group (p&lt;0.01). In the EMPA+SOT group; QT intervals, T wave durations and QTc values were significantly lower and HR was significantly higher compared to the SOT group (p&lt;0.001, p&lt;0.01, p&lt;0.001, p&lt;0.001 respectively) (Table)

Conclusion
In the present study, we detected that EMPA significantly ameliorates SOT induced QT prolongation. In addition to this, we have also shown that EMPA can be used safely with SOT in clinical practice. With more clinical trials, the routine use of EMPA may be suggested to prevent QTc prolongation in diabetic patients receiving SOT. Finally; our study indicates that EMPA can effect on potassium channels.

Funding Acknowledgement
Type of funding source: None
Cardiovascular outcomes in patients with type 2 diabetes and reduced eGFR and albuminuria: a REWIND post hoc subgroup analysis
Authors: Colhoun H , Malik R , Botros F , Atisso C , Gerstein H 
Published: November 2020

Abstract

Background/Introduction
Diabetic kidney disease affects up to 40% of people with diabetes and is associated with higher cardiovascular (CV) risk. REWIND was a multicentre, randomised, double-blind, placebo-controlled trial with a primary outcome of first occurrence of the composite endpoint of CV death, nonfatal myocardial infarction, or nonfatal stroke (Major Adverse Cardiovascular Event [MACE]-3). Dulaglutide treatment reduced the incidence of MACE-3 in patients with type 2 diabetes (T2D) with or without established CV disease.

Purpose
This REWIND post hoc subgroup analysis evaluated the effect of dulaglutide on MACE-3 in patients with an eGFR&lt;60 and ≥60 mL/min/1.73m2 and patients with micro-/macro-albuminuria (UACR ≥30 mg/g) or normoalbuminuria (UACR &lt;30 mg/g).

Methods
Eligible patients were those ≥50 years old with T2D who had either a previous CV event or CV risk factors. Patients were randomised (1:1) to dulaglutide 1.5 mg or placebo, both in addition to standard of care. A Cox proportional hazards model with treatment, eGFR subgroup (&lt;60 and ≥60 mL/min/1.73 m2), and treatment by eGFR subgroup interaction was used to analyse time to the first occurrence of MACE-3. These analyses were also conducted for albuminuria subgroups (micro-/macro-albuminuria or normoalbuminuria). Estimates of hazard ratios (HR) with 95% confidence intervals (CI) were calculated for each subgroup.

Results
At baseline, 2,199 of 9,901 patients (22.2%) had an eGFR &lt;60 mL/min/1.73 m2, 2,676 (27.0%) had microalbuminuria, and 791 (8.0%) had macroalbuminuria. This post hoc subgroup analysis showed that dulaglutide treatment was consistently associated with MACE-3 risk reduction in patients with eGFR &lt;60 and ≥60 mL/min/1.73 m2 (HR [95% CI]: 0.93 [0.76–1.13] and 0.86 [0.75–0.99], respectively; interaction p=0.545). Similarly, MACE-3 risk reduction was consistent in patients with micro-/macro-albuminuria or normoalbuminuria (HR [95% CI]: 0.84 [0.72–0.99] and 0.93 [0.79–1.10], respectively; interaction p=0.374).

Conclusions
Regardless of baseline eGFR or albuminuria status, dulaglutide reduces MACE-3 outcomes in patients with T2D and established CV disease or multiple CV risk factors.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Eli Lilly and Company
Effects of antiarrhythmic drugs on atrioventricular conduction in patients with preexisting bundle branch block
Authors: Kochav S , Chen R.C , Dizon J.M.D , Reiffel J.A.R 
Published: November 2020

Abstract

Background
Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown.

Purpose
To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB.

Methods
We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time.

Results
Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]).

Conclusion
Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected.

Funding Acknowledgement
Type of funding source: None
Prevalence of drug-drug interactions for oral anticoagulant drugs in patients with atrial fibrillation and relationship with outcomes: a population-based cohort study
Authors: Proietti M , Cortesi L , Spagnoli F , Nobili A , Marengoni A 
Published: November 2020

Abstract

Introduction
The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) changed the treatment of atrial fibrillation (AF) patients, promising a better safety profile and a lower chance of interaction with drugs than vitamin K antagoniste (VKA).

Aim
To evaluate the prevalence of possible drug-drug interactions (DDIs) in a cohort of newly anticoagulated AF patients, their impact on outcomes and possible differences between VKA and NOACs users.

Methods
We performed an analysis derived from administrative databases in Lombardy Italian region. All patients ≥40 years admitted from 01/06/2013 to 30/06/2018 with an AF diagnosis that were VKA or NOACs new users were included in this analysis. Possible DDIs were evaluated according to the prescription of OAC therapy, on the basis of current available evidence. Stroke, intracerebral hemorrhage (ICH), any bleeding and all-cause death were the study outcomes.

Results
Among the 122816 patients included in the analysis, mean (SD) age 76.3 (9.6) with 47.3% females, a mean (SD) CHA2DS2-VASc of 3.5 (1.4) was found. A total of 70180 (57.1%) patients were prescribed with VKA and 52636 (42.9%) with NOACs. A possible DDI was recorded in 63273 (51.5%). Patients exposed to DDIs were older and less likely female (both p&lt;0.0001) and with a higher mean (SD) CHA2DS2-VASc (p&lt;0.0001). Rate of stroke, ICH, any bleeding and all-cause death were higher in those patients exposed to DDIs (all p&lt;0.001). After full adjustment, exposure to possible DDIs was associated with an increased risk for any bleeding (HR: 1.08, 95% CI: 1.05–1.12) and all-cause death (HR: 1.10, 95% CI: 1.07–1.13), with no differences for stroke and ICH. Comparing VKA and NOACs patients exposed to possible DDIs, we found that VKA users exposed to possible DDIs, after adjustments, were at higher risk for all the outcomes (Table).

Conclusions
In a large cohort of AF patients newly prescribed with OAC, possible DDIs were largely prevalent, in particular in VKA users. Presence of a possible DDI is associated with an increased risk of any bleeding and all-cause death. VKA users exposed to a possible DDI were at higher risk for any outcome than NOACs users exposed to a possible DDI.

Funding Acknowledgement
Type of funding source: None